The Plot Against Asthma and Allergy Patients

THE PLOTAGAINST ASTHMA

AND ALLERGYPATIENTS

Asthma, Allergies, Migraine, and ChronicFatigue Syndrome are Curable,but the Cure Is Hidden

from the Patients

Felix Ravikovich, M.D.

As featured on CBC’s fifth estate

PublishingKOS

BOOKS ON MEDICINE THAT WORKS

Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page i

ACKNOWLEDGMENTS

This book is my first and only literary child. It took nine long years to carry

it, and I would not have been able to deliver it without the support of several

people.

I want to pay tribute to the late Drs. Bayard Horton and Kenneth Melmon

for their fascination with histamine, their devotion to it, their research and

their belief that one day histamine will serve patients.

This book would not be possible without my wife Galina who is, actually,

my co-author. She conceived the idea and for two years, while I was fighting

in the courts, she worked on it alone, researched the medical sources collected

by me and began to put my ideas on paper. When I joined her, she became my

sounding board, the only knowledgeable person with whom I could share my

astonishing, at times dramatic discoveries made during my detective search of

medical literature. The situation forced her to immerse herself so deeply into

some of the most serious fields of medicine and science that by the end, she

became, albeit unofficially, the equivalent of a professional in clinical

immunology. Her background as a university professor enabled her to work

out how to present the most complicated material in the way digestible not

only for those who have a medical or biological education, but also for intel-

lectuals with little or no such experience.

I express my love to my son Alex who was a comforting friend, whose

advice I sought in many critical situations during the process, and who

patiently corrected my imperfect English.

I would like to express my special thanks to Klemmens Fass, my unofficial

lawyer, who remained faithful to me when my other lawyers betrayed me. He

Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page ii

refused outright to be paid for the long hours of discussions during the years

of my prosecution by the College. He also became my behind-the-stages law

teacher, and his advice helped me to go through all the stages of the legal

proceedings as well as the writing of this book.

I am grateful to Denise Crawford for her willingness to help with the

numerous technical and linguistic problems that I encountered through the

years of writing.

I appreciate the enormous work done by Isidor Zelinkovsky at the early

stages of my prosecution by the College of Physicians and Surgeons of

Ontario. He managed to get the Canadian Broadcasting Corporation inter-

ested in the histamine affair and persuaded them to give the opportunity to

my patients to tell their stories of their almost miraculous improvement and

outright recoveries with histamine therapy and the despair over losing it. The

program aired in Canada and in parts of U.S. created the necessary publicity,

which, in my opinion, contributed to my having not lost my license outright;

I was given a reprimand and forbidden to use histamine.

I am thankful to Ed Sprague, a patient who has become a close friend and

as such accompanied me to all of my meetings with the lawyers and through

the many stages of my trial as a silent witness. The numerous improprieties

he saw have changed his views on our justice system forever. Later on, he was

the most active organizer of press releases sent to the medical institutions,

media and government bodies of Ontario.

I cannot overestimate the tremendous support of Elizabeth and Daniel

Gamper that enabled me to go on with my work and book writing.

My gratitude goes to Tom Hirsch, my first literary agent, who became a

passionate advocate of histamine therapy and was willing to give up his fees

just to see this book published.

Last, but not the least, I thank Helke Ferrie who has dared to publish this

book. The people of Ontario should be grateful to her for the courage to fight

the medical regulatory authorities and for regularly publishing the facts about

the crimes committed by them against patients and doctors.

I am thankful to those of my patients who organized PRET (Patients’

Rights for Effective Treatment), a group that arranged the meeting at CBC’s fifth

estate television studio, demonstrated in front of the building which houses

the College of Physicians and Surgeons of Ontario, published and distributed

information on histamine therapy, attended the legal proceedings and kept

writing letters of support.

Acknowledgments iii

Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page iii

Copyright © 2003 by Felix Ravikovich

All Rights reserved. No part of this book may be reproduced in any manner whatsoeverwithout prior written permission from the publisher except in the case of brief quotationsembodied in review.

National Library of Canada Cataloguing in Publication

Ravikovich, Felix, 1938–The plot against asthma and allergy patients: asthma, allergies, migraine, chronic

fatigue syndrome are curable, but the cure is hidden from patients / Felix Ravikovich.

Includes bibliographical references and index.ISBN 0-9731945-1-0

1. Allergy—Treatment. 2. Asthma—Treatment. 3. Medicine—Research. I. Title.

RC584.R39 2003 616.97'06 C2003-906757-2

Cover and text design/layout: Heidy Lawrance Associates

Printed in Canada on recycled paper

Published and distributed by

KOS Publishing Inc.

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Tel: (519) 927-1049

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Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page iv

TABLE OF CONTENTS

Acknowledgements ii

Introduction by Helke Ferrie vii

PART 1 Immune Mechanisms 1

PART 2 Causes and Triggers in Allergy 69

PART 3 Allergic Inflammation 98

PART 4 “Histaminegate” 106

PART 5 Medications 173

PART 6 Allergy Skin Testing and Immunotherapy 203

PART 7 Bronchial Asthma 238

PART 8 Diseases of Hypersensitivity 318A. Chronic RhinitisB. Skin AllergiesC. Hay Fever

PART 9 Functional Encephalopathies 344A. Vascular HeadacheB. Chronic Fatigue and Immune Dysfunction

SyndromeC. DepressionD. Attention Deficit and Hyperactivity DisorderE. Irritable Bowel SyndromeF. Other Histamine-Related Encephalopathies

Epilogue “Eppur Si Mouve!” 387

Bibliography 390

Appendix 396• Abstracts presented by Dr. F. Ravikovich at

international conferences and his article• Letter by Dr. K. Melmon to Dr. F. Ravikovich• Press release by the patients’ committee, PRET• Notice to the reader

Index 408

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Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page vi

Introduction: Renovating Medicine

“Practicing medicine without knowledge of biochemistry and

physiology is merely pop-gun pharmacy.”

Sir William Osler, 18901

“Far too large a section of the treatment of disease is today

controlled by the big manufacturing pharmacists, who have

enslaved us in a plausible pseudo-science.”

Sir William Osler, 1909

As the publisher and editor of this book it is an exceptional pleasure to be

asked to write an introduction to this most unusual work. Many readers who

know me from my regular articles on the politics of medicine published in

Vitality Magazine, Alive and others, share my conviction that the greatest

problem modern medicine faces in our time is the perverting influence of

political and corporate power on good medical practice and medical research.

To make medicine once again patient-centered, not patent-centered, and to

free medical research from corporate priorities, is the task of our time as

surely as it was the task in the 18th century to remove political power from

kings and put it into the hands of the people.

Indeed, the most profound insight I have experienced first as a medical

science writer, and now as a publisher of “Books on Medicine that Works,” is

the discovery that in virtually all areas of medicine the basic scientific break-

throughs achieved in the leading research institutions are rarely communi-

cated to people, are very often not even taught to medical students, and are not

readily available to practicing doctors.

Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page vii

What IS readily available to everybody is information on yet another

supposedly miraculous drug which promises to alleviate the symptoms of any

known disease. Pick up any recent edition of Macleans Magazine, for example,

and attached to its outside you will find, courtesy of GlaxoSmithKline, in

dramatically colored red, white, and black a folder stating: “IMPORTANT

INFORMATION FOR PEOPLE WITH ASTHMA ENCLOSED.” A handy

little quiz inside allows the reader to be sure in seconds that he or she may

suffer from asthma more seriously than previously thought and that their

“asthma is not under control.” This message comes to you courtesy of

GlaxoSmithKline, the world’s largest producer of steroid puffers.

You are holding in your hands a book that, unlike the above advertisement,

really does contain important information for people suffering from asthma.

Dr. Ravikovich is fully familiar with the world-wide basic science research on

allergic diseases, successfully used a cure and reported on his results at inter-

national conferences. He also tells you why that cure is not generally known or

available. Here is the story of a doctor who fought for his patients.

This book provides the reader with a political revelation, a medical tour

de force, and a scientific detective story. It will take you into the world of the

immune system and its biochemistry and you will become thoroughly

familiar with the world’s leading medical journals and the medical research

into the bio-chemistry of the causes of asthma and allergic disease.

But this is also a shocking detective story: you will learn how those very

same medical researchers, who to this day are celebrated leaders in the

community of immunologists, mysteriously disavowed their own findings

and effectively betrayed patients worldwide as they bowed to corporate

agendas—for reasons best known to themselves. Although this seems unbe-

lievable at first, it is not without precedent.

The same developments have been published with regard to cancer and

psychiatric illnesses. There, too, some of the leading researchers who had

discovered the underlying mechanisms of both areas of illness with the

potential cures for both, and had published their findings in the world’s most

prestigious science journals, What is significant here is to understand clearly,

that none of that research in allergy, cancer and psychiatry was superceded by

new findings, or in any way proven incorrect, or found to be a dead end for

scientific research. The astonishing revelations contained in this book are

supported by what happened in cancer and psychiatric research because in

those areas, the revival of all that useful medical research is beginning to

viii THE PLOT AGAINST ALLERGY PATIENTS

Plot/Allergies•i-xii•1-317 11/21/03 2:19 PM Page viii

Introduction ix

happen now. It is my fervent hope that this outstanding book will start the

same process of revival for asthma and allergy.

Today, the sell-out of medical practice to agendas that have nothing to do

with curing the sick, is nearly total. Patients are now referred to as

“consumers” who are encouraged to believe that they have “choices” of treat-

ment offered in that enormous market of modern medicine run as a business.

It is as if illness has become an accepted life-style choice—right after the car

industry. After all, Pfizer is not only the world’s largest pharmaceutical corpo-

ration, but also the world’s second largest corporation. The representatives of

the drug companies are accepted as “stake-holders” in medicine to the point

where they are part of determining standards of practice, sit on the councils

of the medical licensing authorities, virtually control all medical research in

the absence of publicly funded research (but not in most of continental

Europe), and act as policy and fundraising staff for our political leaders.2

As for the business mantra of “consumer choice,” for the asthma and

allergy patient it’s basically steroids or steroids or steroids: mint flavored

syrups for kids, or laced with antibiotics (to cover all bases), or as shots, as

creams, and usually as the ever present puffer shaped as a toy for kids, handy

and pretty like a lipstick for the ladies. As for the cure, “profits can only be

harvested from chronic disease” a CEO of a pharmaceutical giant observed in

a recent shareholder’s meeting.3

But whose responsibility is it to fix this situation? Consider this then: The

world’s most prestigious science journal, Nature (March 28, 2002), ran an

article entitled “Can you believe what you read?” showing how the editors of

the most respected medical journals have begun to do some radical house-

cleaning when it became overwhelmingly apparent that published research

too often reflects corporate interests to the point of distorting the observed

facts. On June 27th 2002 Nature reported that even medical bio-ethicists are

now “being offered stock board positions, consulting contracts, research grants,

and even stock options” by pharmaceutical companies—and they accept

these goodies! Two international conferences were held in 2002 on conflicts

of interest in medicine (Atlanta and Warsaw). The former editor of the New

England Journal of Medicine, Marcia Angell, justly famous for her fearless

scrutiny of corruption in medicine, now works closely with the Center for

Science in the Public Interest (www.csip.org), a watchdog exposing unethical

behavior of doctors selling out to industry and industry’s false or self-servingly

incomplete product claims.

Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page ix

x THE PLOT AGAINST ALLERGY PATIENTS

Just how bad things have become can be measured by the fact that on

February 5 2002 the prestigious journal, Annals of Internal Medicine (vol. 136,

no. 3) and the UK’s famous Lancet simultaneously published the “Physicians

Charter” as a new manifesto to guide medicine (www.professionalism.org).

The charter asserts that it is time doctors get back to the basics. The Charter

reads like the Hippocratic Oath of 2,500 years ago translated in modern

English. The message is simple and blunt: don’t abuse your patients finan-

cially or sexually, don’t hurt them, let them chose among available treatments,

and treat them properly even if they are black, Jews, poor, retarded, dying, just

plain old, or don’t have any money, and don’t blab about them to others

without their consent. Central among all these ancient basics of medical

ethics was the admonishment that a doctor must not lie when you do research

because somebody offers to pay you for it. (The immunologists whose work is

discussed in this book would do well to read this Charter.) Wow! This docu-

ment was prepared by an international team of medical ethicists for the inter-

national effort called the “Medical Professionalism Project.” It states at the

outset: “We share the view that medicine’s commitment to the patient is being

challenged by external forces of change” which “tempt physicians to forsake their

traditional commitment to the primacy of patients’ interests.”

So, that is what the international medical community admits, Dr. Raviko-

vich provides in this book evidence in support of this urgent need for a major

renovation of the House of Medicine and why that renovation must start with

doctors, after which the pharmaceutical industry is easily tamed.

This book is not simple. But neither is living with asthma, hives, irritable

bowel syndrome, chronic fatigue, constantly itchy skin, the annual round of

hay fever, or potentially fatal food allergies. The information in it is not “alter-

native”—the research is entirely mainstream. Here you will learn why you are

sick, why your standard treatments don’t work very well and make you sicker

through so-called side effects, how you could become healthy, or at the very

least greatly improved and get off drugs, and what you can do to help make

this healing treatment available.

This is no ordinary self-help book—indeed I wish it was. This book is a

crash course in asthma and allergy medicine designed to empower you with

knowledge and hopefully inspire you with a holy rage and the determination

to help bring out these facts so they become generally known to doctors and

patients alike.

Plot/Allergies•i-xii•1-317 11/24/03 11:20 AM Page x

A good book like this does not need my recommendation, but a quick

guided tour might help the reader who is new to this material. Thus, Part 1

provides the technical detail of how the immune system works, as is generally

agreed upon by scientists in this field. For the beginner Part 2 may serve as a

useful beginning; Part 5 will help patients understand why they are not

improving and what is known in mainstream pharmacology about these

drugs and their serious limitations and dangers. Part 4 has the provocative

title “Histaminegate” which refers intentionally to the Watergate scandal of

the 1970s. This chapter deserves the reader’s closest attention and is worth

reading with the greatest attention to detail. The remaining chapters provide

information on the various allergic diseases which will be of special interest

to different readers.

The Epilogue is something of a bombshell because it describes the most

recent publication on allergy research that came out only two weeks before

this book was submitted in its manuscript form to me. This research paper

fully validates everything you read in this book and returns to the research

that was more and more successfully hidden over the past two decades. The

politically significant fact of this development is that this was published by

the Swiss government’s research institution funded by tax money, not drug

companies. The equally important medical historical facts are that now “the

truth which was denied entrance through the door has forced its way in by the

window”—as the Russian proverb puts it and as Dr. Ravikovich is fond of

reminding us.

The Appendix contains documentation on the terrible struggle Dr.

Ravikovich became involved in when his life-saving treatment was attacked

by the medical licensing authorities, and suggestions are included on what

you, as the reader or friend of an asthma and allergy patient, can do to change

the current situation.

Treating asthma, allergy and related diseases successfully, at a fraction of

the current cost of mere limited symptom control, is an art and a science easily

learned by any interested doctor. There is currently a great deal of interest in

therapies that cure and are not merely symptom control methods generally

employed by the majority of physicians. What suffering patients often don’t

realize is how terrible the frustration of doctors is who wish to help but often

are prevented by the regulatory systems from employing new methods.

Introduction xi

Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page xi

If doctors want this scientifically validated treatment approach to use, it

could be learned within a week or two. It is founded on basic science and as a

treatment validated through experience. However, here in Ontario the use of

histamine to treat asthma is literally forbidden since 1996 even though

blocking medical innovation and overruling patient choice is contrary to the

Medicine Act of Ontario and the Helsinki Accord on Human Rights which

Canada signed in 1988. This ban was ordered without a single item of

supporting scientific evidence and bypassed all mandatory debate required for

the formulation of medical standards of practice. You can change that. Read

this book and consider the information given in the Appendix and exercise

your rights as a citizen and as a patient.

Helke Ferrie

1. Michael Bliss, William Osler: A Life in Medicine, University of Toronto Press 19992. See The Olivieri Report, published by the Canadian Association of University

teachers, Lorimer, 2002. For cancer see S. Epstein, The Politics of Cancer Revisited,1998, East Ridge Press. Epstein is one of the world’s leading oncologists known espe-cially for his success in getting DDT banned and refocusing cancer research onto thescience of carcinogens. He is responsible for laws protecting workers from asbestos,pesticides, radiation etc. throughout North America and the European Union. Forpsychiatry see the new book by the world-renowned pharmacology scientists andcorporate whistleblower David Healey, Let Them Eat Prozac, Lorimer 2003,published by the Canadian Association of University Teachers.

3. J. Robinson, Prescription Games: Money, Ego and Power Inside the GlobalPharmaceutical Industry, McClelland & Stewart, 2001.

xii THE PLOT AGAINST ALLERGY PATIENTS

Plot/Allergies•i-xii•1-317 11/21/03 2:06 PM Page xii

PART ONE

IMMUNE MECHANISMS

CELLSAlmost a century and a half ago, a German scientist, Rudolf Virchow, made a

revolutionary discovery: the body is actually a “state” consisting of “citi-

zens”—live cells, each of which is a perfectly balanced unit. A deviation from

the cellular balance is a disease, that is, lack of ease. Cells are our invisible

natural workforce and best health guardians. Therefore it is important to

understand what can go wrong with their complicated functioning, how to

help them restore their rhythmical work, and how to achieve this with

minimal introduction of suppressive medications.

What is a cell? It is a tiny basic operative unit of a live body. If we accept

Virchow’s view of our body as a “state,” then it is populated with over 100 tril-

lion “citizens” working in coordination with each other. Our health and quality

of life depend totally on how our cells function. Cells have different colours,

sizes, and shapes and can be stationary or in motion. Under the membrane of

each cell, there is a chemical lab, and the chemicals it generates determine the

cellular function. Similar cells unite in teams to form tissues and organs.

Cellular teams work in unison, no matter where in the body they reside, and

produce the same chemicals at any given moment. A cell contains over a billion

molecules, and each carries specific chemical messages. Cells communicate

with each other in a cell-to-cell talk through these chemicals, just as we

communicate with words, spoken or written. The more chemicals a cell is able

to manufacture, the more “verbal” it is. Some cells perform limited local func-

tions only, and their inner labs are fairly simple. Others are complex pharma-

Plot/Allergies•i-xii•1-317 11/21/03 12:38 PM Page 1

ceuticals able to produce as many as 300,000 different

proteins: these cells perform numerous complex func-

tions. The possibility of cloning an animal from just one

cell makes it clear how intricate its lab can be.

Cells are very “friendly” with one another. They lie

in close proximity, and if something is wrong with one

group, and it changes its chemistry, the neighbors

express their “sympathy” by changing their chemistry

as well. You definitely experienced it many times: your

boss yells at you, and your legs give way, your pulse

accelerates, your stomach turns into a knot, and you

are ready to rush to the washroom. All this happens

because the cells in your nerves, muscles, intestines,

vascular wall and endocrine glands identify with your

hurt feelings regulated by the brain cells. The opposite

happens when your satisfied or elated brain cells start

to release endorphins, natural narcotics, and the cells

all over the body respond by participating in the joy. You feel as if you can fly,

able to lift heavy objects and solve most difficult problems. This is what the

unity of the different departments of the body means.

GENESAll cells comprise the same set of over 30,000 minuscule particles within its

nucleus. They are called genes. A gene is a biological unit of heredity that

passes certain physical characteristics from parents to their children. Genes

determine everything from such evident things as the eye colour, the voice

timbre or the height, to such imperceptible minutiae as actual operations of a

cellular lab. Every cellular chemical has its gene that governs its function.

Genes are behind each cellular operation and secretion. In their chemical

language, they instruct the cells what proteins and in what amount to produce

in particular situations. A cell’s performance depends on the performance of

the genes. The same genes work synchronically in all cells and send the

messages from within, and the genetic instructions influence the lab’s activity

qualitatively and quantitatively. If there is no genetic error or mutation

affecting the functioning of our cells, our health is good.

Nature is not faultless. Our dissatisfaction with something in our appear-

ance is actually a reflection of how we perceive our visible genetic imperfec-

2 THE PLOT AGAINST ALLERGY PATIENTS

Our body consists of

cells, which are tiny

chemical labs of various

complexities. The chemi-

cals released by cells

are the language of

their communication.

They listen attentively

to each other’s talk, and

therefore, the work of

different groups of cells

is interrelated. This

makes the functioning

of the organs comprised

of these cells also

interrelated.


tions. Health problems often reveal genetic imperfections hidden from the

eye. We may be born with genetic errors or may acquire them inexplicably in

the course of life or through exposure to a harmful factor—such as radiation,

toxic environment, etc. The term for genetic changes—mutation—comes

from the Latin mutare—to change. Defective genes send flawed messages to

the cellular lab, leading to the inappropriate production of the corresponding

chemicals. The resulting imbalanced chemistry means a disease in the organ

or system comprised of cells that produce this substance. Several genes or

even a group of them may be responsible for each

disease. Changes in DNA, the nucleic acid which is the

carrier or genetic code, can be structural and func-

tional. The latter means that the genes are, in prin-

ciple, structurally normal, but have some “variations”

in their activity. This is of key importance for clinical

medicine, since if only the genes’ functioning is

impaired, attempts to correct it can be successful. Not

by deleting and replacing them, as is planned in the

current trend towards potentially dangerous genetic

engineering, but by tuning them up instead.

Once initiated, a genetic change is potentially

transmissible, and may be passed by parents to their

children, grandchildren, etc. Genetic errors leading to

health problems may be so subtle that their existence

remains unnoticed for years until time and/or strong

effect deepen the hidden flaw. Doctors often see

parents that are taken aback when their child is diag-

nosed with asthma or other allergic disease that

neither of them seems to have; it is the combination of

parents’ genes that has amplified their own non-

apparent genetic errors in their offspring.

THE INTERRELATED FUNCTIONING OF GENES AND CELLSEach gene performs the same operation again and again. It is like a tiny

perpetual motor operating in a sophisticated machinery that includes the

interdependent work between the genes and the cells. The relationship of the

chemical lab and the genes that lie at the heart of each cell is not unilateral, as

Immune Mechanisms 3

Tiny particles inside

cells called genes are

carriers of our heredity.

The genes govern

cellular functioning, and

hence, chronic diseases

are mainly the result of

incorrect messages sent

to the cellular lab by

faulty genes. Genetic

changes occur sponta-

neously or through the

impact of external

factors and may be

passed to future

generations. If the

genetic faults are of a

functional, rather than

structural nature, medi-

cine has a chance to

attempt a correction.


it may seem. It is not simply a matter of the genes governing and the lab

obeying. Genes need “fuel” or “feedback” for their functioning, and certain

chemicals generated by the cellular lab itself play this role as do some chemi-

cals coming from outside. Some activate the genes’ functioning, others inhibit

it. Genes can give proper instructions to the cells only when they get an

adequate “fuel supply.” Indeed, as Dr. Craig Venter, one of the two leaders of the

Genome Project, said on April 23, 2002 at the Gairdner Foundation International

Awards event, “proteins are the building structure of life, not genes.”

The understanding of the reciprocity in the functioning of the genes and

cells may turn the dream of medicine—safe and efficient genetic engineering

—into reality. Use of proper substances may gently correct the functioning of

the genes and hence, rectify their messages to the cells. These substances would

be genomodulators, and their effect upon the genes

would be genomodulation. To modulate means to adjust.

The Latin root modulare means to bring out characteris-

tics peculiar to a definite region; thus, genomodulation

would mean a repair of genetic functioning to the

normal level. Such type of “genetic engineering” would

be non-invasive and safe. Since medicine does not use

this sort of genomodulation, one would think that such

proteins-modulators are not known or are commer-

cially unavailable. Wrong. This book will discuss later

two powerful genomodulators that work in harmony

with each other like a unit.

1. One is a chemical generated by the cells and

released into extracellular space, also existing

in a form of a drug.

2. The other is an intracellular enzyme.

Both have been known for decades as messengers

informing the cellular lab. If their harmonious work is

impaired, we may use a synthetic version of the first in

injections, and it will naturally engage the other.

Numerous chronic conditions can improve or be cured

by this. The improvement means that the genetic func-

tioning in the patients treated this way was corrected

temporarily or for good.


The activity of the

cellular lab and the

functioning of the genes

are interdependent.

Moreover, cellular

production at large can

affect the genes’

activity. Medicine can

use this fact as the key

to access the genes if

their defects are only

functional, not struc-

tural, and thus realize

safe “genetic engi-

neering.” The use of a

well known synthetic

version of a body’s

chemical triggers the

response of an intracel-

lular enzyme and

enables the latter to

restore the functioning

of impaired genes.


IMMUNITYEverybody knows that immunity is the body’s defence

against disease, but, among laymen, few are aware that

it is, actually, a defence realized by cells called immuno-

competent. These cells are competent in recognizing the

enemy and producing the chemistry that protects the

host. We are born only with the seeds of immunity. The

fighting ability of immunocompetent cells is dormant

for the first several months of life. Exposure to an

enemy “wakes them up.” Each exposure provides a chal-

lenge for them to specialize—to become competent in

fighting a particular enemy. Some cells neutralize viruses

and bacteria, some fight cancer, others react to allergens

in those who are prone to allergic reactions. Each category of the specialized

cells performs its specific function. Thus, many groups of cells are united under

the concept of immunocompetence. Their coordinated work can be compared

to a well-rehearsed orchestra, and the released chemistry is the music.

Immunocompetent cells are located throughout the body. Certain genes

govern all aspects of their functioning. As was recognized a century ago,

immune diseases are the result of changes of the genes that govern all the

activity of the immune cells. The instructions of defective genes are, naturally,

defective, so are the kinds and the amounts of the chemicals liberated by these

cells. An error may turn the cellular music into a cacophony the way a poorly

tuned piano key can turn a concerto into a disaster. The uncoordinated music

of the immunocompetent orchestra means a poor defence against diseases,

no defence at all, or a distorted defence/reaction.

ENEMIES OF THE IMMUNE SYSTEMWe live in a world full of microorganisms that try to invade the body mainly

through our respiratory and gastrointestinal tracts and skin. These organisms

may cause a disease, but may also play a positive role in challenging our

immune system, causing the cells to produce defensive proteins and thus,

couching them how to defend us. We also have our inner “enemies” such as

excessive stress, hormonal changes due to puberty, pregnancy, menstrual

period, extreme temperature swings, etc., which require extra effort for the

body to adjust. When not in excess, an adjustment strengthens our immune

system, since the cells learn in the process what substances to produce and in

Immune Mechanisms 5

Our immunity consists

of highly complex

groups of cells called

immunocompetent cells.

They work in coordina-

tion with each other and

specialise to fight

different diseases. These

cells start to malfunc-

tion if the genes

governing the immune

response are mutated.


what amounts to deliver them. For example, the longer life span among

women compared to men is considered to be due to the frequent hormonal

challenges that strengthen their immune system.

However, our society has created numerous challenges that exceed the ability

of our immune system to resist them with success. Our food is full of colorants

and preservatives, some indicated on labels, others hidden. We breathe toxic

fumes and drink contaminated water. We feed the cattle and chicken with

antibiotics and hormones that speed their growth. We

even legalize the hazardous effects of these drugs by

allowing their “permissible” amount in meat and

poultry. Cattle are fed grass and grain treated with fertil-

izers, and we allow a certain amount of these poisons in

canned goods that use dairy and meat products. To

compound our problems, we often take medications

because we do not want to tolerate a slight discomfort,

even for a short period of time, and easily find a doctor

willing to write out a prescription. The respect of the

society to drugs is so high that we write them with capital

letters. We are forced into vaccinating our children

although the generally accepted “hygiene” theory by S.

Romagnani recognizes that the increased exposure to

vaccinations is among the factors contributing to the

spread of allergies and asthma.1

Social pressures in our competitive society are also

important health hazards. Our biological evolution has

not caught up with the fast pace of “civilization” and its stressful and

sustained emotional factors that contribute to the destruction of our great

defender—the immune system. This destruction starts with the genes that

govern the “pharmaceutical lab” of immunocompetent cells. Apart from

accumulating unfavourable external conditions that affect our genes, their

malfunctioning and/or mutation may occur spontaneously in the course of

life, without any obvious reason.

ALLERGY AS A CELLULAR OVERREACTIONThe very term allergy indicates that a patient’s body functions differently

from a normal body: Greek allos means other, while ergon means work. Like

an abused child who snaps at suspects an enemy even in a friendly stranger,


Genes malfunction

due to inborn errors

or those acquired in the

processes of life. Their

functioning may also

change under the influ-

ence of extreme envi-

ronmental factors.

Genetic changes are

called mutations.

Mutations create a

predisposition to cellular

malfunctioning, since

flawed genes send

wrong signals to the

cells they govern.


an immune system governed by impaired genes sees enemies not only in

viruses, bacteria or cancer cells but in the things and events which would leave

a healthy immune system undisturbed. It may “snap”

at a pollen particle, fur/dander of a pet, a favorite

food, the texture of fancy underwear, a pleasant

scent of a perfume, a weather change, a mood fluctu-

ation or a natural rise or fall in one’s own hormonal

levels. The cells may also “overreact” without any

challenge, that is, spontaneously, which means that

they start releasing certain chemicals in disproportional

amounts. Such chemical overreaction of immuno-

competent cells is called hypersensitivity or hyper-

releasability.

Allergies are genetically predetermined. They start

with the malfunctioning of the regulatory genes

responsible for the balanced work of the allergy depart-

ment of the immune system. Genetic predisposition is

the primary dominant factor in the production of

allergic diseases, while the environment may become a

complimentary factor. In the absence of genetic muta-

tion, the effect of the environment is mostly temporary

and leads to acute reactions and temporary symptoms,

not to chronic allergic diseases. This explains why

some people develop lasting allergy symptoms upon

a certain exposure, while others get away with an

acute episode.

A slight genetic defect, mostly inherited, occasionally acquired, may remain

unnoticed for years. However, time itself and/or cumulative effects of the

hazards may “break the back of the camel.” In other words, the initial small

defect in the genes may become magnified, and as a result, the operation guided

by these genes may cause the cells to respond with a pathological reaction to

what they would have perceived as harmless before. Since the language of the

cells is their dynamic chemistry, the malfunctioning immunocompetent cells

speak in chemically improper syntax and thus produce the signs of disease.

Conventional allergy dwells on the environment as allergy cause and

rarely spells out the fact that a trigger may provoke a recurrent allergic disease

only in people with the underlying genetic defects or predisposition. Allergic

Immune Mechanisms 7

Immunocompetent

cells genetically

predisposed to malfunc-

tioning are hypersensi-

tive and may overreact

spontaneously without

a trigger, or react to a

friendly environment by

releasing wrong chem-

istry. This brings on

allergy symptoms. Only

those people whose

genes are mutated have

chronic allergic

diseases. Exposure to a

harmful environment

may only augment the

genetic defect and

through this lead to

hyperreleasability of the



reactions without any trigger are also left unexplained. This deflects attention

from primary errors to secondary events.

IS TREATMENT OF ALLERGIES ON THE GENETIC LEVEL FEASIBLE?Knowledge of the alphabet is not sufficient to enable one to combine the

letters into words, and words into sentences. In a similar way, we cannot say

that the current listing of about 30,000 genes gives us the knowledge of their

functions and, most importantly, their interrelations, not to mention, the

patterns of their manipulations. The understanding that genetic malfunc-

tioning lies at the core of allergies means that its correction would be the best

possible treatment for diseases of hypersensitivities. The interrelationship of

genes responsible for one single disease, as well as their interrelationship with

the rest of the genome, are extremely complex processes and may never be

fully understood. Besides, the procedure of correcting or replacing flawed

genes is technically very complicated, and is, therefore, as the leading geneti-

cists say, many years away. Francis Collins, head of the Human Genome

Project of the National Institutes of Health, predicts, that by 2010, we may

have about 25 tests for genetic predisposition to about 25 major causes of

diseases and death. Diagnostic tests, not therapies! One ought to think also

about the many possible physiological, moral, and ethical issues involved in

such therapies.

There is another obstacle. Rationing of knowledge is common in modern

medicine, and drug companies have already started battling over patenting

the genome discoveries. Drugs or new methods of genetic therapy can rightly

be considered discoveries, but the industry wants to patent that knowledge!

Imagine what would have happened if the inventors of alphabets had decided

to patent the letters. If the industry finds support for this plan from our

corrupt governments, the possibility of genetic cures will be moved to still

further into the future. Another problem is related to the enormous amount

of money needed to fund the development of procedures for the intricate

process of penetrating genes. Thus, as an every day treatment, genetic engi-

neering is not feasible, even theoretically, in the near future. Fortunately, aller-

gies and asthma, although multigenic and multifactorial diseases, arise mostly

not from structurally defective genes but from deviations in the genes’ func-

tioning. This means that in order to reverse an allergic disease, we need only

to “tune up” these genes. The fact that in allergies, the performance of the



governing genes is correctable should make medicine happy. More so because

the prevalence of allergy and asthma grows rapidly.

HOMEOSTASISTo understand how medicine can “tune up” the body and help it to reverse

allergies on its own, we must understand a basic law of nature—homeostasis.

The word consists of two roots: home(o)—sameness and stasis—standing, and

thus, the term denotes the tendency to preserve a balance. Nature strives for

harmony and endowed us with delicate self-regulatory systems. Whenever

unfavourable forces affect our body, these systems are challenged and, without our

awareness, adjust to the changes, thus protecting us. For

example, exposure to cold causes shivering, which is

the body’s way of warming up, while exposure to hot

weather automatically causes profuse sweating that

prevents overheating. Both the warming and the

cooling are achieved through spontaneous changes in

the cellular chemistry.

Look how clever the body deals with dieting: after

an initial weight loss, the metabolism slows down to

make better use of the smaller amount of food the

dieter consumes. In fact, weight loss may practically

stop despite the reduced food intake. While this may

upset dieters, our metabolism is “computerized” to

help the body to survive during food-deficient times.

Another example: if you eat a lot of sweets, the

high level of blood sugar mimics the condition of

diabetes and may lead to metabolic changes. To

prevent complications, the body has a mechanism to cope with the dangerous

excess: the insulin-producing gland gets the instruction to increase its output

to metabolize the sugar.

Any deviation from the norm, be it a deficit or a surplus, may be equally

harmful, and these examples show that a healthy body self-rectifies such

changes through its protective autoregulatory switches governing all func-

tions. The tendency towards maintaining equilibrium, no matter whether it is

body temperature, blood pressure or hormone production or, in fact, produc-

tion of any chemical, is an inborn feature that keeps the body alive and is a part

of the universal law of homeostasis.

Immune Mechanisms 9

The body functions

normally when all the

cellular substances are

produced in balanced

amounts. A healthy body

possesses regulatory

tools through which it

corrects imbalances.

The main condition

under which the immune

system functions

normally is a homeo-

static production of all

chemicals by the



Homeostasis is the core of immune system functioning. Health is balanced

cellular production of all chemicals, or harmonious cellular functioning. Each

time our immune system fights an invader, its only task is to restore the

balanced production of chemicals by immunocompetent cells. Unlike other

immune-related chronic diseases, allergies and asthma are much more easily

reversible because permanent changes in the tissues’ interior occur only in the

very advanced stages. The spontaneity of relapses and remissions in allergies

and asthma indicates that it is possible to restore the functioning of the

immunocompetent cells involved in them because the mutation of the under-

lying genes is only functional.

CELLULAR RECEPTORSWhat are the tools through which a healthy body regu-

lates the production of all of its substances? Knowing

them in general, we could probably find the ailing regu-

latory tools in allergy patients, repair them and help

these people. The instruments through which the body

establishes homeostatic amounts of cellular secretions

are cellular receptors, which all cells have either on the

surface of the cell membrane, or inside the cell itself.

Receptors are molecules of protein that work like

antenna, each very selective in their response to the

surrounding environment. Each type of receptor is

tuned to a certain signal. Some discern a signal of pain,

others of temperature, sound, color, a specific chemical

substance, etc. Signals come in the form of chemicals,

the language of the cells. Each receptor selectively binds

to a specific substance, or picks up the information

contained in a physical stimulus, and then dispatches

the obtained information to the cellular lab. The received signals affect the

manufacturing process in the inner cellular lab. The information travels with

a lightning-like speed. The more complex the cellular lab, the more varied its

receptors are. Different groups of cells may have the same type of receptors

and hence, respond to the same signal by changing their chemistry in tandem.

Intracellular signaling followed by chemical effects is called signal transduc-

tion, while cell-to-cell talk is signal transmission. The development and

activity of all cellular receptors are determined by genes.


Cells have various

receptors, and each

kind senses specific

stimuli and/or chemical

messages. The receptors

then change chemically

in response to the stim-

ulus or bind to the

substances that carry

these messages and

pass the “digested”

information to the inner

lab for production of

certain chemicals and

hence, physiological

effects.


A cell with its receptors can be compared to an insect whose antenna detect

signals from its peers or the environment. In response to a stimulus, a signal,

the insect’s body produces certain chemicals, and that changed chemistry

conveys a message for action. The signal may prompt the insect’s body to

exude venom to repel/kill an enemy or to secrete pheromones specific to the

situation: to alert its peers of a danger, to attract an insect of the opposite sex,

to call for help. Similarly, receptors are conductors of such cellular messages.

Imagine an insect with its antennas severed: all its communication with the peer

community and the environment are is cut off, and the insect is doomed to die.

Similarly, the cell’s ability to synthesize and release chemicals depends on its

receptor functioning and our health depends on proper receptor functioning.

RECEPTORS AS SWITCHESA cell is a generator of chemicals, and like any gener-

ator, it is supposed to have switches to turn the

processes on or off. An immunocompetent cell

synthesizes numerous chemicals and has switches for

each of the chemicals it generates. Cellular receptors

play the roles of switches that intensify or temper the

cellular production process. To make sure that the

cell produces just the right amount of a particular

substance, there are receptors that switch on its

release and other receptors that switch it off. Each

cellular switch works within a range. The regulation

is implemented the same way the temperature of an

iron is increased or reduced by turning the lever,

depending on the type of the fabric being pressed.

Proper control over the synthesis and release of

chemicals is vital because both excess and deficit can

lead to disease, as is, for instance, the case of a coma

resulting from blood sugar excess or its shortage.

Each receptor type is tuned to a certain chemical. Cells “measure” the

amount of this chemical in the surrounding space with their receptors in the

same way that an insect’s antenna senses the environment for specific signals

and then passes its message to the inner lab. The lab responds accordingly

either with intensification or inhibition of the release. This receptor-mediated

process goes on incessantly.

Immune Mechanisms 11

The body corrects any

unbalanced cellular

production through

receptors that work like

turn-on and turn-off

switches. Every cellular

chemical is regulated by

its specific receptors,

and like switches, they

adjust production to

cellular norm. Only prop-

erly working on/off

switches provide the

correct release of each

cellular chemical.


If a certain receptor type, say an off switch, is inef-

ficient, its counterpart, the on switch, works unop-

posed. This can make the cell generate so much of a

chemical that it inundates the tissues and leads to

disease. Only efficient on/off receptors can provide

balanced output.

RECEPTOR EFFICIENCY DETERMINS PROPERCELLULAR WORKIn the same way a high grade TV antenna determines

the number of stations and the quality of the image,

cellular receptors provide a proper message transmis-

sion. For adequate cellular functioning, both the quan-

tity and the quality of receptors are important: the cells

should have enough cellular receptors, and these

should be well developed. Scarce, underdeveloped or

inefficient receptors cannot adequately discern signals,

nor can they transmit coherent information to the

interior of the cellular lab.

As was said, the operation of any on-switch must be

counterbalanced by the off-switch. An example is a

warm shower: only functional taps can provide one.

Otherwise, we would have either cold or hot water

only. In every-day life, nobody tries to resolve the

problem of a broken cold water tap by reducing the

flow from the hot tap. It is the broken tap that needs to

be repaired. Every-day logic that prompts us to fix the

broken tap, fails when it comes to fixing our health.

Here is proof.

The immune system is designed as a self-regulatory machinery, and aller-

gies are among self-regulatory diseases. This knowledge allows us to develop

medications that will stimulate or block receptors depending on the purpose.

Medications can relieve the symptoms either by blocking the active healthy

receptors or by stimulating the inactive ones. Activation of the inefficient tool

is preferable since it not only rectifies the primary defect but also preserves

the integrity of the rest of functioning system. Strangely, drugs designed to

stimulate deficient responses are a rarity in medicine in general and are


Only well developed

receptors are able

to sense and correct the

release of cellular chem-

icals by increasing or

decreasing their produc-

tion. If one kind of

receptor is inefficient,

the cells release the

chemicals according to

the signals of its oppo-

site. Thus, the ineffi-

ciency of a turn-off

receptor type leads to

the predominance of the

chemistry generated

by its rival turn-on

receptor. None of the

current allergy medica-

tions repairs the prime

defect—inefficient

receptors—they do not

restore the protective

ability of the immune

system. Instead, all of

them block the activity

of the efficient receptors.


absent in allergy, but allergy therapy concentrates primarily on blocking the

active, normal (!) responses. Logically, help should come in the form of facil-

itating the repair of the primary defect. But conventional allergy practice

completely disregards this simple logic and uses only suppressors.

CONVENTIONAL TREATMENT OF ALLERGIESEach organ with unhealthy immunocompetent cells expresses its malfunc-

tioning through the symptoms typical of its specific nature. Thus, the lower

respiratory tract expresses its disease through cough and bronchial obstruction;

a runny/stuffy nose is a sign of the affliction of the nasal lining, while itch and

rash indicate the involvement of the skin. Two kinds of medications are used to

treat allergies. The purpose of both is symptomatic relief, not cure. These are

symptomatic drugs that target the end organ—bronchi, nasal passages, skin,

etc. They are supposed to block the release of the “bad” chemistry that causes

the symptoms and thus to relieve bronchial obstruction, an itch or a nasal

congestion. Actually, the “bad” chemistry is secondary to the primary cause

which is the deficient turn-off receptors, but unfortunately the restoration of

their activity with proper stimulants never becomes the treatment target. Given

the fact of the mutated genes causing the harmful functioning of the flawed recep-

tors, allergy patients are doomed to perpetual medicalization and regular visits to

medical offices. Moreover, the suppression of the excessive release fails too often,

and then other drugs are prescribed. These not only attempt to reduce the effect

of the “bad” chemistry, but suppress all the processes in the cellular lab, bad and

good, and that is why they are called immunosuppressants. Worse yet, even at

the cost of cellular suppression, these medications provide only temporary

relief, because they do not eliminate the cause of the malfunction in the cells,

but merely suppress all the work of the cellular lab. This suppression covers all

immunocompetent cells, and their protective functions are also shut down.

These medications suppress the functioning of the cells far beyond the immune

system, and thus, these side effects greatly overshadow even their apparent short-

term benefits once taken for a long period. Of course, allergy is a chronic disease,

and so these medications are often taken daily, which undermines the body’s

entire immunity in addition to all those side effects. The immunocompetent

cells, already compromised by the pre-existing genetic malfunctioning, lose

their innate ability to produce their protective chemistry. This deprives the

patient consuming the drug of most immune defences and, hence, severely

affects the course of the allergic illness for which the drugs are prescribed.



In general, we often learn about drugs’ side effects

only when the fatalities from their consumption rise too

high to be ignored. Such drugs are taken off pharmacy

shelves, replaced by others, allegedly safer products, and

only time exposes the adverse effects of those newer

products. In allergies and especially in asthma, immuno-

suppressive medications are, however, the only effective

ones, and allergists try to reduce the side effects of these

widely prescribed drugs. Adverse effects are rarely

discussed in medical sources and are usually missing

from medical textbooks as well. No wonder, that in the

long run, the course of the disease, for which these

medications are prescribed, becomes worse.

Napoleon Bonaparte is said to have remarked:

“Doctors will have more lives to answer for in the next

world than even we generals.”

T-CELLSAny discussion of a self-regulatory disease should start

with the commanders of the immune cells. They are

the T-cells or T-lymphocytes. These cells are a nature’s

masterpiece. The verbs used to define the T-cells’ role

in immune response and function affirm that they

initiate, propagate and orchestrate all immune reac-

tions. T-cells mainly direct the battles by telling other

immunocompetent cells what chemicals to generate

and in what amounts. They also most actively partici-

pate in all processes where their subordinates are

involved, and immediately respond to the messages

coming from other cells. Various chemicals signal these

commands and responses.

T-cells possess a unique ability to learn how to

participate in immune reactions and govern them. At

first, these cells are “naïve.” In a medical context this

word is used to describe the fact that an immune cell

has not yet been exposed to invaders and, therefore, has not yet had a chance

to express its fighting potential. Exposure to a virus, microbe, or any other


Modern allergy the-

rapy focuses on the

end organ by blocking

the natural on-receptors

responsible for the over-

production of those

substances which, in

excess, cause the symp-

toms. Most commonly,

and especially in

asthma, it uses immuno-

suppressive medications

that allegedly target the

“bad” chemistry, but in

reality suppress the

work of all immunocom-

petent cells. Blocking is

too often inefficient.

Suppression destroys

the cellular ability to

produce protective

chemistry, which results

in the generally under-

mined immunity, and, in

the long run, worsening

of the primary disease

and/or other side

effects of various kinds

and severity. Neither

approach aims to

restore the functioning

of the immune system

and by that, resolve the

allergy problem.


intruder provides the cell with information that causes it to become “educated.”

This activation signifies the beginning of their specialization in the corre-

sponding field. The process continues with repeated exposure to the trigger

in a way similar to muscle training when exercise results in a corresponding

muscle development.

Allergy is a deviation from the norm. T-cells are supposed to be our

protectors, but in the allergic patient they lack their regulatory ability. This

creates the background for an exaggerated activity of

the subordinate immune cells, now promoting disease.

In allergy-prone people, any foreign substance or any

unspecified event may become a trigger of a disease-

promoting immune response. T-cells called

T-helpers (TH1 and TH2) now unfortunately “help” to

produce chemicals promoting the allergic response.

The only other subdivision of T-cells that never

fails us and stays in the disease fighting mode are the

T-suppressors. T-suppressors get activated simulta-

neously and in response to the activity of all other

helper cells. In the ’70s, the term was introduced that

labeled suppressors as T-suppressor regulatory cells

denoting that they regulate all responses, especially in

allergies.2 Suppressors moderate not only the host-

hostile activity of helpers, but also the disease-

promoting activity of other immunocompetent cells.

In the process of maturation, all T-cells, T-suppressors

and both kinds of T helpers, become memory T-cells.

This means, that like the brain, they remember how to

participate in the fight by releasing certain chemicals

characteristic for their and activities in promoting or

suppressing disease.

T-SUPPRESSORST-suppressors are our protectors in the immune

system’s war we call allergy. Their overall activity

determines whether allergy will or will not take place.

The conclusion is that if one has allergy symptoms, T-suppressors are for some

reason insufficient. Interestingly, since 1991, discussion of these cells, central for


T-cells are central to

immunity. They

specialize in fighting

different diseases. After

an encounter with an

invader, which they

perceive as an enemy,

they retain memory of

what chemicals to

produce for any future

fight. In allergy, there

are two natural opposing

subdivisions of T-cells—

helpers that are mainly

on the disease-

promoting side, and

suppressors that func-

tion to promote health

and also control the

work of T-helpers. Both

kinds of cells, once

specialised, become

memory cells and

remember how to fight

for or against the

disease.


allergic processes, has disappeared from medical sources

on allergy, even though, of course, these cells are still

present and doing their work as they always have done.

At the same time, the same publications describe in

detail helpers, TH1 and TH2, which are subordinate to

T-suppressors. A legitimate question is: why?

There can be only one logical explanation for this:

by removing the protectors, T-suppressors, from the

stage, the discussion now centers only on the disease-

promoting T-helpers. By not discussing the role of

T-suppressors, which restore the body’s disease-fighting

ability, the unlimited use of various medications is justi-

fied. By acting as if T-suppressors are not significant,

the human body is portrayed by medical science as if it

was unable to regain its disease-fighting ability. This,

view justifies the unlimited use of various medications,

including very potent ones. The most frightening fact

is that, along with controlling the disease-promoting

activity of the immune cells, these drugs collaterally

also crush the activity of our saviours, T-suppressors.

While the symptoms may temporarily be controlled,

the price for this temporary relief may be the oblitera-

tion of our T-suppressors and thus also their ability to

fight for us against disease. The fact that T-suppressors

are ignored in medical discussion is, from a scientific point of view, incom-

prehensible; it was science that discovered them and elucidated their activity.

Ignoring T-suppressors also contradicts the laws of homeostasis upon which

a functioning immune system depends, namely that disease-promoting action

always also stimulates the disease-fighting forces, in order to defend the host.

MAST CELLSAmong the closest subordinates of T-cells, two kinds play a special part in

allergic reactions. They are sister cells—stationary mast cells and mobile

basophils. Mast cells reside in tissues, while basophils flow with blood. Due

to the similarity of their functions, when speaking about mast cells, we imply

basophils as well, even though they enter an allergic reaction at different

stages.


T-suppressors are

controllers of all

allergy-related immune

responses, and their

activity and memory are

the keys to the normal

functioning of all partici-

pating cells. Inability of

T-suppressors to control

T-helpers and organize

the defence against

them explains allergy

symptoms. Inexplicably,

during the ’90s, these

cells have practically

disappeared from all

allergy-related scientific

publications, which

creates the false view

of our immunity as a

system ruled and oper-

ated totally by negative

forces.


If T-cells are the conductors of the orchestra of allergy-participating cells,

mast cells are the lead instrument. Their leading role indicates that all the

properties of mast cells and basophils are realized in allergy as in no other

disease. They start and maintain allergic reactions. Mast cells are major gener-

ators of chemicals in allergic reactions. The word mast comes from the

German verb to feed, thereby indicating that these cells “feed” the immune

processes with their abundant chemistry, which then provides for the various

immune reactions.

The most important and prolific chemical among them is histamine.

Although histamine has been known for almost a century as a cellular chem-

ical, in 1952, it was discovered to be a product of the mast cells. Since then, it

has always been emphasized in all textbooks and medical dictionaries as the

most distinctive feature of these cells and allergic diseases. Each mast cell

contains 50–200 histamine granules densely packed under the cellular

membrane. Mast cells are very “touchy” in general, but especially in allergy

patients: upon certain chemical changes in the surrounding space, the gran-

ules crack like fragile egg shells and leak out histamine. This act is called

degranulation. Histamine leaks abundantly in many diseases where there is

an infectious or immune-related inflammation, or an injury. However, in

allergies, mast cell release of histamine is especially profuse, and, therefore,

histamine release is accepted as the start and the hallmark of allergic reac-

tions. In humans, histamine is the only pre-stored mediator that participates in

allergic reactions; it causes initial activation of all immune cells participating

in allergy, and it changes their chemistry. Because mast cells concentrate in

the skin, air passages, brain, gastrointestinal tract, histamine spill occurs

predominantly in these areas. Mast cells initiate allergic reactions by over-

spilling histamine, while their sister cells, basophils, take over at a delayed

stage and maintain the process. Their histamine production constitutes about

90% of all histamine released. While mast cells can produce numerous medi-

ators of allergy, apart from histamine, basophils produce mainly histamine.

The hyperresponsiveness of mast cells and basophils, and their exaggerated

release of histamine, as the major driving force, allows us to call allergies

diseases of hypersensitivity. The mast cells’ hyperactivity in releasing histamine

is a sign of the person’s inborn predisposition to allergy, which means that

certain genes governing the function of these cells are faulty.

In his work on mast cells and basophils, Dr. L. Lichtenstein, the pioneer of

histamine research, and the 1994 president of the American Academy of



Allergy and Immunology (AAAI), reaffirmed this idea

in his presidential address published in the most pres-

tigious immunological periodical.3 To the present day,

this concept has not been rejected or even questioned.

However, in the latest medical sources histamine

leakage at early and late stages of allergic reaction is

described solely under the unrevealing mast cell

releasability or mast cell degranulation, activation, or

recruitment, with the word histamine always omitted.

At the same time, the names of other, qualitatively and

quantitatively inferior mediators of allergy are empha-

sized. In this way, the impression is created that mast

cells are disconnected from their central product,

histamine, and, thereby, their role in allergic reactions

appears as seemingly insignificant. Instead, what is put

forward as significant are other cells that neither

initiate allergic reactions nor keep the allergic response

going, or/and enter the game only in response to a

histamine spill at much later stages. This conceals the

inseparability of mast cells and basophils from hista-

mine granules as their most characteristic feature, and

deflects attention from the fact that a massive hista-

mine spill signals the onset of allergic symptoms and

maintains these at later stages.

DENDRITIC CELLSThe third type of cells important in allergies is the

dendritic cell. The name dendritic comes from the Greek

tree. Indeed, threadlike extensions of dendritic cells

resemble a branched tree—the image that inspired their

name. These cells’ “secretory products are more diverse

than those known for any other cells of the immune system,” states the leading

medical textbook on internal medicine.4 There are several types of dendritic

cells, and they densely populate the skin, the lungs, the lymph nodes, and the

nasal mucosa. One kind is of particular interest for us because of its regulatory

activity in immune processes, its ability to affect the performance of T-cells, and

its cardinal role in skin allergies and related skin conditions. These are Langer-


Mast cells and

basophils are the

cells that unleash and

maintain allergic reac-

tions. Their central

feature is the presence of

histamine granules under

the membrane. In allergy

patients, these cells are

abnormally sensitive and

may release excessive

amounts of histamine in

response to virtually any

trigger and do so sponta-

neously. The histamine

spill ignites allergic reac-

tions. Uncontrollable

release of histamine from

these cells is a genetically

predetermined feature

and is a major indicator

that the host has aller-

gies. The exaggerated

histamine release from

mast cells and basophils is

the key event in allergy,

which clinical and even

theoretical allergy medi-

cine now basically ignores.


hans cells, or simply LCs. These cells are a repository of numerous chemicals,

histamine among them. They bind to the intruder and present it to T-cells for

identification and action. LCs also possess the unique migratory ability of trav-

eling from the skin to the regional lymph nodes and inform T-cells of the pres-

ence of intruders encountered on the skin or in the air passages. In addition, the

changing chemistry of LCs following their encounter

with an intruder, can directly involve other immuno-

competent cells. LCs have another unique feature—

affinity with nerve cells, which also belong to the family

of dendrites. The extensions from LCs stretch to the

dendrites of nerve cells, thus forming their continua-

tion. These connections, as well as the cells’ reciprocal

chemistry, become the bridges for their communica-

tion. The involvement of LCs on the skin inevitably

leads to the involvement of the nerve cells and vice versa.

Skin diseases of neurological origin, such as psoriasis or

neurodermatitis, are the best examples of the ties and

interdependent functioning of the immune and

nervous systems in the body.

HISTAMINESince all allergic reactions start and continue with a

histamine spill, histamine will become central to this

book. Practically speaking, allergies and asthma are

diseases of one substance—histamine. When a person

does not have allergies, histamine release in that

person’s immunocompetent cells is balanced. That is

why it is so important to clarify what histamine is.

The word histamine is made up of two Greek

roots: histios meaning pertaining to tissue and amino denoting a chem-

ical group, an integral constituent of all proteins. Histamine is a compound

found in different concentrations in all body tissues. It is an active participant

in all health-promoting as well as all disease-promoting processes. Its

precursor is histidine, one of the nine essential amino acids. The term essen-

tial in regard to amino acids denotes that it is one of the nine compounds

without which there is no life. Being similar to all essential amino acids, histi-

dine cannot be synthesized by humans and is obtained only from food. In the


Among immunocom-

petent cells, there is

the family of dendritic

cells. One type,

Langerhans cell or LCs,

are especially important

in allergy. They densely

populate the skin, while

other members of the

dendrite family reside

all over the body. Upon

an encounter with an

enemy, LCs bind to it

and present it to T-cells,

thus activating them.

Dendritic cells have a

special affinity to nerve

cells, which are also

dendrites, hence the

easy involvement of

both in each other’s

activities.


body, it naturally transforms into histamine. Numerous food proteins contain

a different inherent amount of this histamine’s predecessor. Especially rich are

seafood, certain fish and meats (mackerel, sole, pork), cheeses, red wines,

chocolate, citrus fruits, nuts, beer. Consumption of such foods leads to

increased formation of histamine, and therefore, hypersensitive people often

have an allergic reaction after eating them.

Like everything in the body, the innate histamine concentration in tissues

is genetically predetermined. This is highly individual and also fluctuates

depending on the physiologic state of the body at any given moment. The

increasing histamine concentration in tissues may occur due to the overreac-

tion of its main repository—the mast cells—to their internal environment.

That is why allergy symptoms may instantaneously flare up upon the slightest

change in the body’s chemistry. Such changes may occur when a person sleeps

less or more than usual, gets warm or cold, or even when a sudden mood

change takes place. Sometimes, histamine overspill may occur without any

trigger at all, simply spontaneously.

WHAT HISTAMINE DOES IN THE BODYIn normal body functioning, although pre-stored mainly in mast cells and

basophils, all immunocompetent cells contain histamine. Moreover, they start

to synthesize it de novo upon activation, and this makes histamine the most

important messenger in immune processes or, as science calls it, a mediator,

in all aspects of immune function. Nerve cells and endocrine cells also synthe-

size histamine. In the nervous system, where it passes on its most important

messages, histamine is called a neurotransmitter. Each cell in the body is

connected to nerve cells; therefore histamine messages reach each cell and

affect its functioning.

Every substance in the body carries its own specific information. For

instance, adrenalin mobilizes defensive mechanisms of the body, while insulin

is responsible for the carbohydrate metabolism. Histamine’s scope of activity

is inconceivably wide. Indeed, histamine “regulates (!) various activities of the

brain, such as the arousal state, brain energy metabolism, locomotor activity,

neuro-endocrine, autonomic and vestibular functions, feeding, drinking, sexual

behaviour and analgesia (pain).”5 This means that when we sleep or wake up,

move, think, feel pain, eat, make love, etc. histamine is active passing its

messages, which will vary depending on the organ’s or tissue’s function.



Another theoretical work that covers the multiple areas of histamine

activity emphasizes that “histamine proved to be important for the immune

homeostasis.”6 Since balanced immunity signifies health, this knowledge from

the basic sciences confirms that not only the allergy-related functions of the

immune system depend on histamine, but also its general functioning. It logi-

cally follows, that an imbalanced production of histamine must inevitably

affect the above-named functions, and such symptoms as insomnia, or exces-

sive fatigue, joint and muscle pains, poor vascular tone, low libido, and even

general weakening of the immunity are a possibility.

Basic science teaches that histamine not only participates in numerous

functions, but regulates many of them. If we develop this idea further, it logi-

cally follows that by blocking its activity with medications such as the antihista-

mines or the highly popular antacids (which are antihistamines for gastrointestinal

disorders), we inevitably disrupt all the above-listed functions. Did you know

that? I bet you didn’t even though you may have consumed some of these

drugs and possibly also experienced their side effects. Your doctor may not

know about the regulatory properties of histamine because he or she was not

taught about the scope of histamine activity, but was taught simply to

prescribe antihistamines and antacids. Doctors generally know histamine

only as an “evil” mediator of allergy, which, being spilled from mast cells,

initiates and conducts pro-disease messages among the cells participating in

allergic reactions. They also know that histamine excess leads to excessive

secretion of gastric acid. Therefore, for doctors who are taught this limited

view, histamine suppression seems the right thing to do.

HISTAMINE IS AN AUTACOIDThe word autacoid comes from the Greek autos—self and akos—remedy or

medicine. There are several autacoids, such as adrenalin, a powerful hormone

that increases blood pressure, accelerates the heart rate, etc. Then there is

serotonin, familiar to migraine and depression sufferers, since its imbalance

leads to these conditions. Too much adrenalin can be fatal; at the same time,

synthetic adrenalin saves lives in critical situations. Autacoids are substances

of bifocal activity: too much can be harmful, as can be too little. Not all

medical dictionaries list the word autacoid, but if you are lucky to find it, you

will read that histamine is an autacoid as well. Strangely, in the same diction-

aries, the entry for the word histamine will not mention its remedial properties.



In a few old textbooks this positive aspect of histamine is mentioned. Today,

most textbooks emphasize only its disease-promoting activity in allergies,

migraine headaches or production of gastric acidity

and the need to suppress this activity. This is so despite

the fact that histamine is a substance of dual effect,

as is, for instance, adrenalin also.

Something is wrong: Why does standard medicine

fight histamine’s excessive activity with drugs? Why

does it pretend that the only role for histamine is a

negative one when, in fact, it belongs to the family of

autacoids? How can the substance contained in all cells

of healthy (!) people be considered so hazardous to the

body? What is wrong with Mother Natures’ design?

HISTAMINE HOMEOSTASISAllergy and related diseases are conditions caused by

the initiation of inappropriate histamine release and

activity. This does not make histamine a harmful

chemical, since it is an inherent part of life and organ

functioning. It is the imbalanced release and uncon-

trolled activity of this substance that become harmful.

The overspill means that the switches that control

histamine release are inefficient.

The existence of such switches is evident from the

way a healthy body extinguishes an acute allergic reac-

tion. Here is an example of how it happens. Exposure to

an allergenic food or a strong smell may occasionally

provokes mast cells’ degranulation in a healthy host.

The tissues full of these cells are the first to respond

with symptoms—hives, itchy eyes, a congested nose,

etc. This signals that the impact was too strong even for

the healthy self-regulatory switches, and they were

unable to turn off the histamine leakage. However, the disruption of their

otherwise normal functioning is brief, the body’s chemistry shifts to a disease-

contributing mode only for a short period. If the patient does not want to

put up with these temporary symptoms, he may take an antihistamine. At

some point, the receptors regain their ability to turn off the flood, and the


Histamine is a

substance produced

by all of the body’s cells.

It participates in

numerous functions and

regulates many.

Histamine transmits

numerous vital messages,

without which our body

would not be able to

function. It is crucial for

the proper work of the

immune and nervous

systems that regulate the

functioning of the rest of

the body. Despite this

fact, medical textbooks

mostly avoid mentioning

histamine, and when they

do present it, they dwell

solely on its allergy-

contributing properties.

This justifies the use of

numerous medications

that block its activity

which results in the

disruption of numerous

vital functions.


symptoms stop. The body was able to reverse the

disease on its own.

Things are different in a hypersensitive patient.

There is no effective turn-off, therefore the reaction

lingers and may progress due to a shift towards

pro-disease chemistry. Something is permanently

wrong with the protective regulatory mechanisms

in the immune system, and this defect maintains the

symptoms. Now the patient may be forced to turn

to a never-ending, pill-swallowing regime.

It is clear that in allergy patients, histamine turn-

off receptors need help to be able to establish homeo-

static production. Only the restoration of receptor

functioning may end allergy symptoms and save the

patient from daily medications. Despite the fact that

receptor repair would be of much more benefit,

allergy medicine recognizes only the blocking

approach: it either inhibits the functioning of the

healthy receptors, or suppresses the activity of the cells

totally. In either case, the effect is temporary, since it

does not correct the prime defect.

HISTAMINE RECEPTORSHistamine-synthesizing cells have not one but several

kinds of histamine receptors that regulate its synthesis

and release. They are marked by the letter H that stands

for histamine and numbers that denote their type. We

will speak mostly about three kinds of histamine recep-

tors and just mention the forth, although science has

identified more. All four receptors—H1, H2, H3, H4—

are important in passing numerous histamine

messages. Since H receptors operate with the substance that participates and

regulates numerous immune and neurological functions, these functions

depend on the efficiency of these receptors. In allergy, H1 receptors are turn-on

switches for histamine synthesis and release. H2 and H3 receptors are off

switches. Only when H2/3 receptors are deficient, the normal H1 receptors

become disease-promoting tools because they contribute to the histamine


Histamine is a

substance of dual

activity. It does cause

allergy as well as some

other disorders, but only

when it is released

excessively. More

important is the fact

that histamine is

responsible for

messages of health

among the cells. By

originally including

histamine into the group

of autacoids, science

recognized its healing

properties. By excluding

it now, the medical

profession has distorted

scientific fact. Silence

about the vital role of

histamine for the func-

tioning of the whole

body and its curative

ability is of special

concern in clinical

immunology and allergy

where histamine is

of overwhelming

importance.


release. In the areas other than allergies, the application

of these receptors is different and is not discussed in this

book. H4 receptor generates and activates immunocom-

petent cells in allergy and other diseases.

The H1 receptor type was discovered over half a

century ago. The role of these receptors in the excessive

production of histamine has been studied thoroughly

and described in all textbooks.

H2 receptors were discovered by James Black, a

Nobel Prize winner. These receptors are fairly well

described by basic science, but practicing physicians

are only taught their role in excessive gastric acid

production, while their central immunoregulatory role

in allergies, asthma and other immune-related diseases

is almost always excluded from the program.

H3 receptors were discovered on nerve cells in 1983

by the French neurophysiologist J. Arrang and a team

of European scientists. Later on, these receptors were

identified on other cells, including immunocompen-

tent cells. I doubt that the neuro- and immunoregula-

tory role of these receptors is known to most practicing

physicians.

The H4 receptor was first described by D. G. Raible

and his colleagues in 1994. This receptor plays a major

role in bone marrow activity. The H4 receptor is vital

for the production of immunocompetent cells and

hence, the functioning of the immune system. Standard

medical textbooks generally do not contain any infor-

mation on this receptor.

A Canadian research team working in the Winnipeg

cancer institute discovered another class, namely the

intracellular receptor H1C that delivers histamine

messages to the heart of each cell’s genetic material.7

From a paper sent to me by a renowned American immunologist, I learned

about the existence of yet another type, Hx receptor. With time, still more

histamine receptors may be identified. The existence of multiple histamine

receptors, each of which mediates different cellular functions, indicates the


Like any substance,

histamine overpro-

duction is controlled in a

healthy body by certain

turn-off receptors. If

these receptors are

inefficient, the exagger-

ated histamine release

leads to the prevalence

of histamine-induced

disease-promoting

chemistry, and hence,

allergy symptoms char-

acteristic for the tissues

and organs in which the

flood occurs. The two

options an allergy

patient has are: a)

medications that either

inactivate the work of

the healthy turn-on

receptors or suppress

all the activity of the

cellular lab; b) repair of

the inefficient turn-off

receptors in order to

enable them to control

the leakage. Conventional

allergy medicine prefers

the blocking approach

with its temporary

effect.


importance of the substance whose messages they

conduct.

All immunocompetent and nerve cells, those of the

vascular walls and the endocrine glands, indeed, the

cells of all regulatory systems, synthesize histamine,

and thus they have histamine receptors. The distribu-

tion and functional activity of all H receptors are the

central factor that determines the release of histamine

by different cells. This release affects the work of

numerous organs and systems, and when impaired,

manifests in various physiological and clinical effects.

H1-SWITCH VS. H2/3 SWITCHAll H receptors are meant to respond primarily to

histamine. In allergy, H1-receptors are responsible for

the symptoms. They are activated by the histamine

present in the extracellular space and signal the

cellular lab to generate histamine. The body moder-

ates histamine release through H2/3 receptors. Their

messages are opposite to the H1-receptor messages.

When the messages of H1 receptors are counterbal-

anced by the messages of H2/3 receptors, histamine is

produced in the amount needed for the normal func-

tioning of the tissues, such as cellular growth, wound

healing, muscular and vascular tone, pain reduction,

proper hormone production, etc. If H2 and H3 receptors are inefficient, as it

is in allergy, histamine liberation becomes excessive. This results in the preva-

lence of disease-promoting chemistry, and the areas especially rich in mast

cells—the lungs, skin, gut and brain—respond with symptoms specific to

them. Histamine overactivity involves all cells possessing histamine receptors.

The more histamine receptors the cell has, the greater its involvement.

Histamine surplus has a negative effect on neighboring cells, and they start to

generate disease-oriented chemistry. This amplifies the pathological process,

and creates a situation where the strong H1-receptor messages prevail, and

thereby maintain allergy symptoms.

The inactivity of H2/3 receptors turns normal H1 receptors into the target

for the main allergy medications, antihistamines. Substances that inactivate


Histamine production

and activity are

regulated by stimulatory

and inhibitory receptors

marked with the letter

H. By now, several kinds

of H receptors have

been discovered and

their mode of action

established as different

in different organs. The

fact is that clinical text-

books tend only to

contain information that

leads to the production

of medications that

block stimulatory H1

receptors; they do not

contain information on

the healthy regulatory

effects on the nervous

and immune systems

through the role of the

H2/3 receptors.


receptor response are called antagonists, and antihistamines are H1-receptor

antagonists. Antihistamines immobilize H1 receptors for the period they

circulate in the body; that is, until excreted, and then, another dose of the

drug is needed to keep H1 receptors under control. A negative side of antihis-

tamines is that, while they circulate in the bloodstream, all the health-promoting

histamine messages are inhibited: wound healing slows down, vascular tone

weakens, the brain loses its clarity, etc.

Two questions arise: 1. Why are H2/3 receptors weak and unable to provide

the balanced release of histamine? 2. Is it possible to boost the efficiency of

these receptors? I will try to answer both.

TWO WAYS TO CONTROL ALLERGYNature programmed the body, and especially the

immune system, to function in such a way that any nega-

tive effect could be easily counteracted. In relation to

histamine balance, this is so unless there is an inherited

or acquired error in the genes responsible for the forma-

tion and/or activity of H2/3 receptors. Due to an error,

these receptors may be underdeveloped, inefficient

and/or scarce. If the error is minor, histamine release will

be slightly in excess, and the bearers of the deficient

receptors may experience negligible symptoms. At some

point, a seemingly irrelevant event or simply a time

factor may reinforce the genetic defect and make it

obvious through a full-blown allergic condition.

Medicine knows that the blocking effect of H1-antihistamines is, at best

short-lived and that they are required on a regular basis. Medicine also knows

that suppression of any cellular functioning for extended periods of time is

highly undesirable because of the potential health hazards. Logic tells us that the

only effective and safe way to control histamine release is to activate the H2/3 recep-

tors, and enable them to perform their natural function. Moreover, basic science

provides us with the additional knowledge that the H1 receptor, proclaimed as

“bad” in allergy, is not solely allergy-oriented, but is also protective: it assists the

H2 receptor in its protective activity. This confirms the opinion of a number of

research teams who found that H1-antihistamines, designed to block the

receptor’s activity, “might not be ideal therapeutic strategy” since they also

inhibit normal histamine metabolism.8


Histamine release is

induced through H1

receptors, while H2 and

H3 receptors inhibit its

release. Thus, in allergy,

H1 are on-switches, and

H2/3 are off-switches.

Allergy symptoms occur

when the off-switches

are unable to turn off

the histamine release,

and the leakage

continues unabated.


Can we correct the receptor functioning with the

presence of the faulty genes that govern it? Can we do

this without invasive genetic interference? Yes, we can.

Let us see how it can be done.

CELLULAR AND SYNTHETIC HISTAMINEExercise develops muscles, and similarly, activation

strengthens receptors. The scientific term for substance

that activates receptors is agonist. In nature, strength-

ening of the inefficient H2/3 receptors occurs through

histamine. Its synthetic version has been available for

almost a century. Can it be used for activation? Yes, it

can. In this connection, questions arise:

■ If extracellular histamine keeps H1 receptors active

all the time, why can’t it activate H2/3 receptors?

■ If synthetic histamine can activate the inefficient

H2/3 receptors, what is the difference between

synthetic histamine and our body’s histamine?

Let us start by looking at the difference between

histamine found in our cells and the one in the

commercially available form. To establish the potency

of a drug, one measures its level in the blood and

tissues. All substances in the body start to break down

and are metabolized after a certain amount of time.

The time it takes for half of the drug to be metabolized

is known as its half-life. So, the half-life of an anti-

histamine determines how many hours apart a tablet

should be taken. The difference between the half-life of

natural histamine in our cells and its drug version is

the most important distinguishing fact between them.

Unfortunately, medical textbooks almost never

explain the difference between the two. In fact, although

both are called histamine, they are far from being iden-

tical in terms of their action in the body. Intracellular histamine is stored in the

granules of mast cells and basophils for about three weeks. Being released into

extracellular space, it disintegrates within few minutes. In a healthy body,

histamine release is smooth, and its much-needed messages spread all over the


When the off recep-

tors, H2 and H3, are

genetically defective

and/or scarce, there is

little or no opposition to

the normal H1 receptors,

and histamine release

turns into a flood.

Histamine excess causes

the production of pro-

disease chemistry by

the participating cells.

The tissues full of

histamine-induced

chemistry respond with

corresponding allergy

symptoms. The two ways

to treat patients are:

1) temporarily control

histamine release by

blocking H1 receptors

and provide sympto-

matic relief; 2) activate

H2 and H3 receptors and

fix the problem.

Continual blocking

disrupts normal func-

tioning of the tissues

with H1-receptor-bearing

cells, and this makes

activation of the weak

receptor more logical.


body. In a sick person, it leaks excessively, which leads to an allergic reaction.

Although the spilled histamine is metabolized within minutes, the constantly

cracking granules of mast cells and basophils maintain its high levels in the

tissues. Moreover, this exaggerated leakage provokes the manufacture, or

synthesis, of additional histamine, particularly by other

immunocompetent cells, T-cells which begin to make

more and more of it as well. This increases the amount

of histamine in the extracellular space and thereby

causes a whole cascade of illness-contributing chem-

istry. This is like gasoline being poured over a smol-

dering fire—it “inflames” the affected tissues. Indeed,

the term that describes the process is inflammation.

Such inflammation has nothing to do with an infection;

it is a tissue reaction to the cascade of pro-disease

chemicals.

Synthetic histamine differs from its natural cellular

chemical counterpart in several aspects. First, man-

made histamine is usually employed in a diluted form

and can, therefore, be much less concentrated than the

natural substance. Second, injected histamine is an

“uncombined” isolated substance, which means it is a foreigner in the chem-

ical soup simmering in the tissues. It is like a new log thrown into a fire, and

time is required for it to start burning. But, actually, there is no time for that:

although the half-life of both cellular and synthetic histamine is only a few

minutes the injected drug breaks down completely, whereas the immensely

exaggerated liberation of cellular histamine goes on due to the continuous

degranulation. Just compare the impact of a few minutes of man-made low-

dose histamine with the incessant oozing of histamine from mast

cells/basophils. These qualitative and quantitative aspects explain why the

synthetic chemical cannot lead to a disease the way the body’s histamine can.

H1- AND H2/3 -RECEPTOR RESPONSE TO CELLULAR AND SYNTHETIC HISTAMINESynthetic histamine cannot lead to disease, but can it lead to recovery? Yes.

Receptors respond differently to cellular and injected histamine. Theoretically,

both kinds should activate all histamine receptors—H1, H2 and H3, but this is

not the case. When H2/3 receptors are deficient, the pro-inflammatory chemistry


Synthetic histamine

differs fundamentally

from the cellular chem-

ical. It has a short half-

life, its concentration is

very low, and it is inde-

pendent of the disease-

promoting chemistry.

Injected histamine

cannot produce and

maintain the state of

disease the way cellular

histamine can.


is too overwhelming for them. However, they discern the isolated mild signal of

the injected histamine amid the frenzy of the pro-disease signals and respond to

it by getting more active. A signal enables them to turn off the H1-tap. We may

compare the weak H2/3 receptors with a child who passes by a huge rock that

looks like a mountain for him, but picks up a small stone. The healthy H1 recep-

tors “feel comfortable” within the milieu full of histamine and histamine-

triggered pro-inflammatory mediators; a small dose of the injected histamine

will not be strong enough to incite them to adverse activity. This is why we

achieve the H2/3 effect by injecting small doses of histamine.

To see how both kinds of histamine work, let us take asthma as an example.

The lung tissue, if spread out, would occupy an area the size of a tennis court.

The lungs have the largest number of mast cells and basophils, the main

producers of histamine. Add to this the disease-promoting chemistry induced

by the initial spill. Now, compare this “ocean” with a small amount of histamine

in a syringe. Not only the small dose of diluted synthetic histamine is too mild

to activate H1

receptors, but its half-life is only a few minutes—time not suffi-

cient to unleash, not to say sustain, a disease process. However, the time and the

dose are enough to activate H2/3 receptors and hence, lead to the production of

pro-health chemistry by all participating cells. The protective H2/3 effect

opposes the H1 effect exactly in the way a healthy body does. Even though

medicine operates mostly by measuring and crunching numbers to establish

what is less than normal, and what is beyond the range of the normal, qualita-

tive effects may be more important in regulatory diseases than mere measured

quantities. In allergy, it is not so much the amount of the opposing chemistry that

reverses the disease process, but the regulatory potency of the newly introduced

mediators. For an asthma patient, it means relief of the symptoms.

The degree of the improvement varies and depends on the functional

resilience of these receptors and the degree of their original deficiency. The

exact concentrations of histamine which activate only H2 receptors and

control H1-receptor activation (from 10–9 M to l0–4M) have been scientifi-

cally established.9 The H2/3 receptors react synergistically, which means they

are more effective when working together, and the H3 receptors are sensitive

to even lower doses of synthetic histamine.

Within a few minutes, the injected histamine starts breaking down and leaves

behind only its stimulatory effect. Like a pendulum that swings for some time

after it is released, the weak receptors temporarily continue their natural function

of turning off histamine leakage. The length and degree of their activation



cannot be determined by any test; they become clearly

evident through observation of the patient during the

course of treatment. The judgment is clinical, which

means it is based on observed and reported improve-

ment. Through careful observation, a doctor quickly

gains experience on how to gauge the dose that would

provide further stimuli to keep the H2/3 receptors

active. Since histamine injections involve all the H2/3-

receptor-bearing cells, the tissues containing these cells

improve their functioning. The change of the symp-

toms after each injection is the indicator what organs

are involved in the disease. Similar to an exercise

program, repeated histamine injections strengthen the

receptors and enable them to oppose the negative H1-

receptor effect.

THE BIAS AGAINST HISTAMINE RECEPTORS INALLERGY MEDICINEBias in the description of the H1 and H2/3 receptors in

allergy and related diseases is obvious: while H1

receptor is described in detail, the role of H2 and H3

receptors in allergy is virtually absent from medical

sources of the ’90s. Most of the commercially available

allergy medications are designed to block the activity of

the H1 receptors. All antihistamines are such medica-

tions. Description of the H2 receptors is also drug-

oriented and limited to their role in blocking excessive

gastric secretions, which promote the use of the H2-

receptor blockers. Yet, the knowledge exists that H2-

receptor activation may enable the immune system to

control allergy without medications. Similarly, the self-

inhibiting features of histamine could also help in

certain gastrointestinal disorders, and this will be discussed later in the book.

But making this scientific data widely known would go against the interests of the

drug industry. It is no secret that the medical elite is closely connected with

drug developers and depends on them for most of their research funding.10

This explains why the curative H2-receptor effect in allergy is not common


Continuous and

excessive histamine

spillage from the cells

that have inefficient

H2/3 receptors (“off

switches”) produces

mostly unopposed H1

effect, and this main-

tains histamine leakage

and the disease state.

Synthetic histamine,

with its short half-life,

much lower concentra-

tions and independence

of the pro-disease

chemistry, produces

only a mild signal, which

leaves H1 receptors

unresponsive, but stimu-

lates the weak receptors

which are sensitive to

H2 and H3 receptors.

Activation of H2/3 recep-

tors counterbalances or

reduces the disease-

promoting H1-receptor

effect. Repeated stimu-

lation strengthens H2/3

receptors and enables

them to balance the

cellular production.


knowledge. The H3-receptor effect is also kept in the theoretical domain even

though both animal testing and trials on humans are very promising.

HISTAMINE: THEORY AND PRACTICEHistamine was first synthesized by two German chemists, A. Windhause

and W. Vogt in 1907, and its physiological activity was discovered by Sir

Henry Dale and P. Laidlaw in 1910. Shortly after-

wards it was empirically used as a drug for asthma

and allergies. Over all these years, histamine has

fascinated physicians as a naturally occurring chem-

ical and as a medication. During Sir Henry Dale’s

time, a Histamine Club was formed to unite those

scientists and doctors who studied and/or used

histamine. In the ’60s, with the establishment of

allergy as a medical branch, interest was channeled in

three directions:

a) allergists were busy with presenting histamine in its

negative light only, developing antihistamines to

suppress it and advertising their drugs;

b) researchers, using animal and human tissues, were

accumulating

information on the multiple functions of histamine in the body.

c) practitioners, dissatisfied with conventional methods, used it “in treating

various allergic manifestations, for desensitization in cases of hypersensi-

tivity, and in the treatment of peripheral vascular diseases, Meniere’s

disease, and headache.”11 Below are a few of the examples of how

histamine was researched and employed.

There is no precedent in the history of medicine for the establishment of

an international research society that studies the activity of one (!) substance

only. There are societies that focus on a disease or group of substances, but

none that researches one substance. In this connection, the existence the

European Histamine Research Society (EHRS) with members also from North

America becomes even more surprising in light histamine has been down-

played in the contemporary medical community. The EHRS was founded in

1972 on the basis of the Histamine Club, and as its Home Page on the internet

states, it unites the medical professionals who “have a common love: hista-

mine.” The society’s annual meetings take place in different countries, and the


The histamine-

inhibiting ability of

the H2/3 receptors is

obscured in the allergy

literature and virtually

never applied in prac-

tice, primarily because

of the financial interests

involved in the wide-

spread sales of numerous

medications designed

only to block histamine

activity.


speakers at the meetings include internationally renowned allergists and

immunologists. EHRS even has an “anthem,” every line of which ends with the

word histamine. Leaving out the literary significance of this song, we can state

that an anthem devoted to a body’s substance is yet another unprecedented

phenomenon. In 1995, EHRS was incorporated into the Inflammation Society,

and its publication, Agents & Actions, changed its title to Inflammation

Research. This can only make one wonder if the importance of histamine for

the body’s functioning has plummeted, and if so, why this has not been

reflected in basic science. The other explanation would be that somebody

wanted to eliminate the very name of histamine. Thus, although the society

still exists, conducts its forums, continues to study histamine (mostly theoret-

ically), it has formally disappeared. This is a real mystery—one of many—

surrounding this substance.

Further evidence of histamine’s uniqueness is the unprecedented number

of antagonists, antihistamines and antacids, developed to suppress its activity.

No other chemical in the body has so many versions of antidotes. The power

of histamine is such that it continues to inspire the drug industry to manufac-

ture its antagonists, which constitute the world’s largest group of medications.

One of the most prolific researchers of the physiological and pathological

roles of histamine was J. Parrot, the world-famous French physiologist, editor

of the journal de Physiologie, and the founder of the Histamine Club. His

chapter, Etiologie generale des affections allergiques, in the medical textbook, J.

Charpin: Traite’ des maladies allergiques 1980, predicts the great success of

histamine in clinical medicine. J. Parrot made a presentation before European

physicians in 1980, which is only available in English as a short Summary and

in a rather poor translation. Parrot said: “it is possible to decrease in vivo (in a

live body –F.R.) the activity of (cellular histamine –F.R.) or to protect the

patient… by injecting in him a mixture in adequate ratio of serum gamma-

globulin and histamine.” The mixture of histamine and gammaglobulin (a class

of body protein) is called histaglobulin or histaglobin. The dose of gamma-

globulin in the compound is so small that it acts rather like a solvent instead of

being a biologically active, while the fixed dose of histamine is within of high

therapeutic activity. Since 1959, histaglobulin has been used in Europe in hay

fever, rhinitis, allergic dermatitis, and asthma, and has shown in practice and

studies much better results than other medications. The proof of biological

neutrality of gammaglobin in the mixture is the fact that, in the control groups,

it was usually used against histaglobulin as a placebo, an inert substance.



Through the thirties and fifties, Bayard Horton, a world-renowned Ameri-

can neurologist, employed histamine in diseases such as vascular headaches,

multiple sclerosis, Alzheimer’s, Meniere’s disease. Horton’s name is assigned

to two medical conditions. One of them, Horton’s syndrome, has another

name—histamine cephalgia (headache). So great were the achievements of

this scientist that in 1988, seminars were held by American neurologists in

honour of his work. Although the doses of histamine used by Horton were

not homeopathic, he abided by the principal of homeopathy—like treats like.

He fought the excessive histamine release by injections of synthetic histamine:

big fire is best extinguished by another big fire. As often happens with

geniuses, Horton received posthumous acknowledgement, while during his

life, he had often been ridiculed for his “obsession” with histamine and his

belief that “nature heals but histamine cures.” Patients were coming to him

“from Texas, from Oregon and Washington, and from the mid-west to mobile

home sites near the hospital,” and were “rolling in with their campers to

receive histamine treatment.”12 Yet, his 1,402 medical charts have not yet been

evaluated.

Horton’s treatment was later revived by S. Diamond who is now world

leader in vascular headaches and director of the Diamond Headache Clinic in

Chicago. In the past, his team used histamine for cluster headaches in addi-

tion to other therapeutic measures and had a 40% success rate.13 Around 1989

or 1990, I saw a documentary on TV that showed the use of histamine in that

clinic and wrote a letter to Dr. Diamond. Responding on August 10, 1990 Dr.

Diamond and his colleague Dr. F. Freitag stated that, like myself, they had

“achieved excellent results in selected patients with intractable cluster

headache” and regretted that in the past “this excellent technique” was inap-

propriately used, which led to its falling into disfavor in the medical commu-

nity. The professors wrote that they were interested in my research and would

want more information on my own method of selecting patients for hista-

mine therapy. I wrote to them that the method was described in my published

article that had accompanied my first letter, and that clinical implementation

of my method would require meeting personally. I received no further reply.

From the flyers now advertising annual seminars conducted by the Diamond

Headache Clinic for practitioners, I know that these no longer include hista-

mine therapy.

As a more recent example of the never-dying interest in histamine is the

Web site of the American Council for Headache Education that in Headache



News refers to successful trials of histamine injections for migraines, which

had proven resistant to other therapies (http://www.achenet.org/news/

older/101999.php).

In the ’60s and ’70s, histamine was extensively studied all over the world on

animals and people, described in articles and entered in textbooks. For instance,

U. Serafini wrote in the Handbook of Experimental Pharmacology 1971 of

successful histamine therapy in various allergies, including bronchial

asthma.14 Extensive research laid the foundation for theoretical allergy in the

late ’60s and ’70s in USA. This research described the roles of the cells in

allergic reactions; the dual action, negative and positive, of the processes; clas-

sification of the two already discovered histamine receptors; the key role of the

H2 receptor in strengthening of the protective part of immunity; the positive

effect of histamine on gene expression; the indicators for the prime genetic

defects that distinguish allergy patients from normal subjects. The researchers

synthesized histamine congeners (analogues) and used them in patients. All

this research we will discuss in detail in a later chapter entitled Histaminegate.

Spectacular results of histamine testing led to assumptions that its “thera-

peutic efficiency could surpass the efficiency of the treatment with hormones

of exogenous origin” (corticosteroid drugs–F.R.).15 As knowledge of histamine-

inhibitory receptors was only in its infancy then, different hypotheses were

formulated to explain its curative effect. One of them suggested that the body

increases its tolerance to injected or inhaled histamine, as it does to any drug,

and repeated doses can enable the patient to tolerate an exaggerated histamine

release by the cells. Another hypothesis speculated that histamine stimulates the

body production of internal corticosteroids, and this removes the need of their

synthetic form prescribed in allergies and asthma, which are especially resistant

to treatment. As it turns out, each of these ideas contains some truth.

In the ’70s and ’80s, injectable histaglobulin was successfully employed in

Europe and Japan for allergies and asthma in numerous open clinical trials

and also in several double-blind studies in Japan. These significant trials are

ignored because they were published in Japanese and have not been easily

available. I accidentally found them among references to an article.16 Thanks

to a patient of mine who was of the Japanese origin I was able to read these

articles. On my request, she located them in the local library during her visit

to Tokyo and translated them into English for my benefit.

J-P. Girard, Chief of the Allergy Clinic in Geneva, conducted similarly

successful open clinical studies as well as a double-blind trial on allergy and



asthma patients using histaglobulin.17 As in the majority of the studies

involving histaglobulin, the control group received gammaglobulin as a

placebo, which proves it is histamine that is the active ingredient in the

combination. Since the work did not exist in English, I had it officially trans-

lated and then, submitted to Dr. R. B. Haynes, a recognized expert in epidemi-

ology and biostatistics, professor at the McMaster University in Hamilton,

Ontario, for assessment of the reliability of the data. Professor Haynes,

provided a written confirmation that Girard’s trial had been conducted prop-

erly, which means it provided a reliable basis for therapy. Up to now, Girard’s

clinical employment of histamine is unknown to physicians in North

America, and the numerous open clinical studies carried out in a number of

European countries are equally unknown.

By the mid-90s, the information on histamine trials was already so well

hidden that the authors of the monograph entitled Allergens and Allergen

Immunotherapy18 actually asserted that histamine desensitization introduced

in 1932 had been “initially encouraging” and “designed to modulate immune

functions,” but its benefits “could not be determined without controlled clin-

ical trials.” If the leaders in the field (Dr. R. Lockey, the author of this mono-

graph, is an ex-president of the American Academy of Allergy, Asthma and

Immunology, AAAAI) are unaware of successful trials, it is only natural that

practising physicians not known about histamine desensitization and its value

for patients.

Ergot is known as the fungus growing on cereals and containing high

amounts of histamine. It is of interest that conventional medicine uses drugs

which have ergot in their name. Among them, there are cafergot and ergota-

mine often prescribed for migraine headaches. Studies show that if cafergot is

taken long enough, the results are better than with other medications

prescribed for migraine headaches. A relatively new nasal spray (dihydroer-

gotamine mesylate) is credited with safety and efficiency for migraine. The

drug is actually decades old, although not in the form of a nasal spray.

Medical sources indicate histamine’s connection with ergot, and this makes it

easy to trace the role of histamine in these medications. My reference library

contains several works that indicate the importance of histamine in autoim-

mune disease such as rheumatoid arthritis. One of them is a chapter in

Therapeutic Immunology 1996, in which a Stanford team confirms the cura-

tive role of histamine in various immune-related diseases, including arthritis.

The professor of Immunopharmacology and Internal Medicine at Stanford,



K. Melmon, the developer of histamine congeners, headed the research.

Although arthritis is a debilitating chronic disease of high incidence, and the

situation is crying for help, nobody suggests the use of histamine therapy, and

probably nobody ever will. It is astounding but true, that the second edition

of Therapeutic Immunology published in 2001 no longer contains the chapter

written by the Stanford scientists. Has immunology become disinterested in

curing rheumatoid arthritis?

Recently, interest in the combination of histamine and caffeine has been

revived, and a patented drug was approved by the FDA and advertised for use

in multiple sclerosis. Considering the overwhelming potency of histamine

and its diverse activity in the body, one can assume it is not caffeine but hista-

mine that produces most of the effect.

Equally remarkable are the articles that document tumor shrinkage

following histamine use. They describe how the physical condition improves

within 5–7 weeks even in terminally ill cancer patients.19 Unfortunately, the

authors did not make any theoretical observations to support their encour-

aging findings, although older information exists describing the immune

mechanisms that cause the tumor-reducing effect. The lack of connection

between theory and practice shows in another publication written a year later.

This time, it is a purely theoretical article on the destructive effect of hista-

mine on cancer cells.20 This work does not contain any references to earlier

trials, nor does it make suggestions for future clinical trials. The positive effect

of histamine on tumour regression is not that unexpected. Some conforma-

tion is already found n the findings of the Manitoba Institute of Cell Biology,

Canada. Several articles of that institute’s researchers state that a lasting use of

antihistamines might lead to cancer. This concern is shared by the FDA.21

Strangely, physicians often learn about the concerns expressed on the highest

levels of regulatory agencies only due to accidental revelations by journalists. The

facts on the connection between commercial antihistamines and cancer made

it into the mainstream media in the mid-nineties. However, information

regarding the potentially beneficial effect of histamine on cancer is virtually

inaccessible for journalists.

The implication of histamine’s cancer-promoting role comes from yet

another recent example. A drug manufacturer in San Diego developed a

medication that combines histamine with a cellular chemical (interleukine

Il-2). Resistance to cancer is proportional to the killer cells’ efficiency, and this

drug, when taken in a certain kind of cancer, produced a 62-fold (!) increase



in the number of killer cells. Interestingly, it produced only a 5-fold increase

with the interleukine alone. Make your own judgment as to which is, in fact,

the active ingredient. Since I do not have personal experience of treating

cancer, I can only speculate on the success of this combination and its poten-

tially far-reaching implications.

Some of the most compelling information can be found in the works of

the world’s leading geneticists from the Harvard Medical School. They

acknowledge the curative role of histamine and the protective role of mast

cells by saying that “histamine release from mast cells may paradoxically limit

the extent of inflammatory and immune reactions” via the H2 receptor.22

Moreover, on page 284 of this same article, whose research was supported by

the National Institutes of Health, the writers state that “histamine modulates

gene expression” and thus corrects the imperfect functioning of the genes!

The authors specifically name allergies and rheumatoid arthritis among the

diseases that may be positively affected by such a correction of gene expres-

sion. Up until now, researchers refer to this work for support. One of the most

recent being a paper titled Histamine alters gene expression… .”23 This should

not come as a surprise, since for 3 decades, it has been known that for the

immune cells, histamine is the most potent stimulant of a vitally important

enzyme called cAMP. This enzyme stops inflammation in the immune

system. One can only wonder why no author has so far suggested the use of

this simple biochemical pathway to be investigated through clinical trials.

But allergists do know about the pivotal role of cAMP in allergy. We know

this because the world’s leading allergists, L. Lichtenstein and S. Holgate, use

this knowledge in the development of asthma medications that achieve a

similar effect in a roundabout way. The drugs’ first trials showed low efficacy,

but I am sure they will appear in the pharmacies. At the same time, the

straightforward method of elevating the enzyme cAMP levels with histamine

injections appears to be unacceptable to the industry—most likely because it

works “too” effectively.

Perhaps the best example of the central importance of histamine for the

functioning of our body comes from the proceedings of the international

conference Histamine and Disease conducted in California in 1989. Here we

had yet another unprecedented event—an international event devoted to one

substance only. This event resulted in a special issue of the world’s most cited

medical periodical in the field—Journal of Allergy and Clinical and

Immunology—JACI.24 High profile scientists made declarations about hista-



mine’s cardinal role in various chronic conditions, especially in allergies. No

practical applications were suggested. (We will tell you more about this

conference later in the chapter Histaminegate.)

The interest in histamine did not die in the nineties, but the tendency was

becoming more and more obvious to stress its negative effects and at the same time

to silence its immunomodulatory and neuroregulatory ability and ignore the tools

that realize it. This obvious bias did not go unnoticed by some scientists who

were evidently unaware of this organized plot. Here is an example from the

international journal that presents pharmacological agents, medications, and

their application—Pharmacology & Therapeutics.25 The authors speak on the

one hand, about histamine antagonists, which we know as the H1-antihista-

mines and certain antacids or H2-antihistamines, and on the other, about

agonists, which, in fact, are various versions of synthetic histamine: “In this

article, we review the recent developments in the field of histamine research,”

they say. The article states that H2-receptor antagonists get the approval for

their efficiency, whereas “…potential uses of H2 agonists… so far have not led

to clinical application.” At this point, the authors refer to the 1982 work

written, among others, by a former president of AAAI, L. Lichtenstein, who

thirty years before (!) had thoroughly described the immunomodulatory H2-

receptor activity. On page 450, the text continues: “An attractive application of

H3 agonists seems to be in asthma (!). H3 agonists would reduce ….the release

of histamine from mast cells.” This time, the reference is given to another

world’s leading scientist, P. Barnes. In addition, the authors indicate that hista-

mine H3 receptors play an important role in the homeostasis of several neuro-

transmitters, such as histamine itself, adrenaline and serotonin.

Even one such statement makes it clear that science does know that by acti-

vating H3 receptors, histamine is able to establish not only its own balance but

also the vital for health balance of other neurotransmitters. But “so far, no useful

applications of H3 agonists have been found,” the article concludes with regret.

As all these numerous theoretical works on histamine make clear that hista-

mine, due to its bifocal property and its centrally important regulatory role in the

functioning of various systems of the body, obeys the Law of Nature. According to

the Oxford English Dictionary, a law of nature is “correct statement of invariable

sequence between specified conditions and specified phenomenon.” The immense

amount of available knowledge on histamine’s dual function and its regulatory

activities is uncontested because it is based on molecular biology, physiology and

pathophysiology (physiology of disordered functioning)—sciences that may



change sometimes in the interpretation of the events, but rarely on the events

repeatedly seen under the microscope or even with just the naked eye.

Furthermore, documented clinical trials have repeatedly confirmed theory. Still,

since the early ’90s, allergy medicine has continuously ignored this immense

body of knowledge by disregarding, silencing and actively distorting the facts

that could lead to the restoration of health in millions of people. This fact is

observed so frequently (as we discussed above), appears to be so well orches-

trated, and is so clearly visible in the works of different authors that it is hard not

to suspect what I would call a plot against histamine.

The finishing touch, as it were, of this obvious conspiracy is the silent and

inexplicable removal of all the material on histamine’s immunomodulatory

properties from the recent editions of several textbooks on allergy and clinical

immunology. This removal did not occur because of new findings which discredit

everything known so far about histamine, but was undertaken without scientific

debate—quietly. Here are several examples:

■ In 1985, the chapter written by R. Rocklin in the textbook Allergy spelled

out all histamine-centered and related mechanisms of allergy. The 1997

edition of this same textbook, still used in universities, is now “updated”:

this specific chapter has been eliminated; no revision of the discarded

scientific data is reported.

■ The 1982 textbook Immunopharmacology contained a chapter with a

detailed analysis of histamine and its role in immunity; the textbook has

not been reprinted.

■ The second edition of Therapeutic Immunology excluded the only chapter

contained in its first edition on the immunomodulatory effects of hista-

mine in chronic immune diseases, including rheumatoid arthritis.

■ In 1990, S. Hill, a renowned immunopharmacologist who specialized in

histamine research, wrote the chapter Classification of Histamine

Receptors in the 1990 edition of Pharmacological Reviews. In the 1997

edition, this chapter became 12 pages shorter and much less informative.

The vital fact that histamine works “as a modulator of the immune

response,” as Hill had called it in 1990, was taken out seven years later.

Also gone is the idea of “the possibility to use H2 agonists as immune

suppressant agents,” as is the fact that “a number of histamine congeners

(agonists) have now been produced.”

Stephen Holgate is one of the world’s most respected contemporary

immunopharmacologists and one of the most prolific authors in this field.



Recently, he acknowledged the significance of histamine in medicine by

saying that “The discovery of histamine by Dale and Laidlaw in 1911 created

a new science—immunopharmacology.” This science studies the nature,

chemistry, effects and uses of drugs and their effect on immunity. Histamine,

according to Holgate, “has stimulated the development of antagonists”26 This

means histamine gave a huge boost to the drug industry and doctors in drug

research, and both continue to thrive on it. This also means that histamine

launched Holgate’s career as an immunologist. For this, allergists and the

drug industry thanked histamine in a perverted way: today, everything related

to histamine is avoided, and its remedial features are thoroughly and purpose-

fully obliterated. Allergology and immunopharmacology have been effectively

hijacked by commercial interests—much to the detriment of the patients.

Still, histamine is such an amazing substance that theoreticians continue

to research it. In April 2002, the editors of JACI summarized “the articles of

interest.”27 They say that “histamine might have a chronic antiallergic effect,”

and that it “it is known that histamine might exert modulatory effects on

some immune and inflammatory responses.” They point to the H2 receptor as

the tool that causes a “negative feedback effect on histamine release,” which

means it inhibits its own destructive over-release. The editors’ reference is also

to the most recent publication.28 These quotes are yet another example of the

fact that the knowledge on the curative properties of histamine is available,

but it is prevented from entering clinical practice.

CYTOKINESHistamine is the primary mediator of allergic reactions. Among other partici-

pants, there are also cytokines. This term has recently become an inherent part

of immunology. The word comes from the Greek, where cyto means cell, and

kinesis—movement. Cytokines are products of the immune system; they are

proteins released by immunocompetent cells. They provide kinesis, the

dynamics in the cells and among cellular mediators. In a broad sense, the

words mediators and cytokines are interchangeable: both denote cellular chem-

icals taking part in immune reactions. The difference is that cytokines are

regulatory chemicals, choreographers rather than the actual dancers in the

ballet called allergy. In different immune diseases, there are different choreog-

raphers, but they always preserve their guiding role.

Cytokines can be roughly divided into two groups: disease-promoting and

disease-inhibiting, or, as science calls them, pro-inflammatory and anti-



inflammatory. When they are released into the extracellular space, their pres-

ence works as a command telling cells what to do—to carry on with the state

of illness or to undo that process. The amount, kind and activity of cytokines

determine which way the course of the disease will turn.

HISTAMINE-INDUCED CYTOKINESCellular production of chemicals is an interdependent

process. Profuse histamine release announces the

beginning of an allergic reaction and induces various

chemical events. Like all mediators, pro- and anti-

inflammatory cytokines are brought to life by the

original excessive histamine spill. Allergy medicine

even named the two central groups of cytokines hista-

mine-induced suppressor (or inhibiting) factors (HSF)

and histamine releasing factors (HRF), with the word

factor as the substitute for cytokine. These two groups

provide opposite effects during allergic reactions. An

allergic reaction is maintained through the prevalence

of histamine releasing factors. As the term indicates,

they increase histamine release and hence, the cascade

of disease-promoting chemistry. Histamine releasing

cytokines are produced by various immunocompetent

cells when their H1 receptors are activated by histamine.

Histamine-induced suppression works in the opposite direction: it

reverses the disease process by inhibiting the liberation of histamine and

histamine-related pro-disease chemistry. By calling these cytokines hista-

mine-induced factors, science acknowledges that their formation is secondary

to the histamine effect. Regrettably, the word induced is mostly omitted,

which changes the meaning and correspondingly, the understanding of the

notion. The use of the word induced indicates that those factors activated by

histamine cause the suppression of histamine in its harmful function. By not

using this terminology, one hides the original induction and also subsequent

remedial role of histamine. The production of suppressing factors is induced

when histamine activates the H2 receptors. The prime generators of

suppressor factors are, as the name tells us, T-suppressors. T-suppressors

possess “a major regulatory influence” in allergy, wrote R. Rocklin who discov-

ered the first suppressor factor in 1977.29,31 His chapter in Allergy 1985 indi-


Cellular products

carry certain

messages and are called

mediators. Those

mediators that direct

reactions are called

cytokines. The origin

of chronic immune

diseases lies in the defi-

ciency of antiinflamma-

tory cytokines. The

course of the disease

depends on how

prevalent the pro-

inflammatory cytokines

are over the anti-

inflammatory ones.


cated on page 176 the overwhelming importance of these cells as well as their

product, the suppressor factors, for controlling allergic processes. On page

182, the author emphasized the fact that histamine is the originator and regu-

lator of both pro- and anti-inflammatory effects. I referred to this chapter as

being central to understanding allergies, and speculated that its elimination

from the 1997 edition of the textbook was probably intentional for reasons

totally unrelated to good medicine.

As the law of homeostasis dictates, the ratio of histamine-induced pro-

inflammatory to anti-inflammatory cytokines determines health. The univer-

sally known medical textbook, Harrison’s Principles of Internal Medicine,

which is published in new and updated editions every two years, stated the

following already back in the 1987 edition: “…complex cellular… interac-

tions involve a delicate balance among positive and negative influences and

ultimately result in expression of an appropriate immune response. The

slightest imbalance in these immunoregulatory circuits may result in aberrant

immune function leading to clinically apparent immune-mediated disease”

(p. 334). If the consequences of the slightest imbalance are that serious, the

damage caused by disregarding a major imbalance of the pro- and anti-

inflammatory cytokines can hardly be overestimated. Once the topic was

considered so important that an award-winning work covering the cytokines

as “the missing link” in understanding allergies was presented at the AAAI-

sponsored lectures for post-graduate courses.30 We do not hear about this

anymore.

The interrelationship of histamine and the cytokines is further proof of

nature’s wholeness: not only does the histamine spill lead to their release, but,

in turn, the release of cytokines affects the further leakage of histamine. Thus,

pro-inflammatory cytokines contribute to further histamine release, while

anti-inflammatory ones inhibit it. A simplistic comparison of the interde-

pendence would be a can of sardines in oil: sardines acquire the taste of the oil,

while the liquid tastes of the fish.

HISTAMINE-INDUCED SUPPRESSOR FACTORSIn allergy, there can be no recovery without histamine-induced suppressor

factors. The first such factors were described in the 1970s by R. Rocklin and K.

Melmon, then the world’s leading immunologists specializing in histamine.

The ability of these cytokines to control allergic reactions proves the self-reme-

dial effect of histamine, and the fact that they are primarily the products of



T-suppressors, proves the protective role of these cells in allergy. The central

role of the histamine-induced cytokines in reversing allergic disease and bronchial

asthma was confirmed by a number of eminent authors, and Dr. A. Kaplan, the

editor of the two editions of the textbook Allergy and the 2003 President of World

Allergy Organization, is one of them.

In 1991, Dr. Kaplan was a member of the team that

made a presentation at the 47th annual meeting of the

American Academy of Allergy and Immunology on

histamine-induced cytokines. In that presentation it

was observed that: “an imbalance of these factors may

play a role in the pathogenesis (mechanisms) of

disease in which histamine is an important mediator,”

and these factors are “an important regulatory mecha-

nism in the releasability of histamine.”32 Four years

later, this same team of authors again covered hista-

mine-induced cytokines as important participants in

the chemical war in allergy. The views expressed in

that article are consistent with the views on any war:

victory is achieved only when the less powerful party

succumbs to the more powerful one. The article

admits that the ratio of histamine releasing factors to

suppressor factors “may be critical to pathogenesis of

a wide variety of allergic and rheumatic diseases,”

and that it “may determine the level of inflammation observed in allergic

disease.”32,33 Since histamine induces the production of both the pro-and

anti-inflammatory chemistry, it controls the border between health and

disease. This puts histamine into the very centre of allergic reactions. Equally

important is also the fact that histamine plays a “critical” role in another

group of immune-related diseases, namely the rheumatoid kind.

Logically speaking, allergy should look at the two viable ways of preventing

or aborting an allergic reaction, namely curb the activity of the disease medi-

ators or increase the production of the protective factors. But it seems that the

logic of allergy has become the servant of the drug manufacturers. At present,

the protective regulatory cytokines that inhibit the pro-inflammatory activity

without medications are hardly ever mentioned even in theoretical textbooks.

Clinical allergy focuses totally on restraining the pro-disease chemistry,

choosing to develop suppressors to each mediator and cytokine. As there are


Histamine, being a

substance of dual

activity, produces both

pro-inflammatory and

anti-inflammatory chem-

istry. The proportion

of histamine-induced

protective and hista-

mine-induced disease-

promoting chemistry

determines control or

progression of allergic

reactions. The produc-

tion of histamine and

histamine-induced

cytokines is interde-

pendent.


legions of pro-inflammatory mediators, there may well be the opportunity to

develop legions of suppressive medications.

Strange things started to happen since the early ’90s. T-suppressors that

synthesize histamine-induced suppressive factors have disappeared from text-

books on allergy as well as from reports presented at international symposia. With

the only remaining view of histamine as a villain and the health promoting

abilities simply ignored, one cannot expect that there will be any discussion on

how to increase the release of the protective cytokines. In The Cytokine

Handbook of 1998, which has over 1000 pages, histamine induced suppressor

factors are mentioned only in the abbreviated form—HSF. This makes no

sense at all because the text contains no indication what this abbreviation

means. Its role and connection with histamine are also not mentioned.

In 2001 an international workshop claiming to be “state of the art” was

conducted in collaboration with the World Health Organization and spon-

sored by the AAAAI. This event serves as additional proof of the biased atti-

tude of the medical establishment towards the cytokines in allergy.34 It stated

(page S182) that “for didactic reasons,” only pro-inflammatory cytokines are

discussed. No explanation is given what the “didactic” reasons for the exclu-

sion of the suppressive factors are. To conceal the protective abilities of the

immune system merely serves to make the cure for allergy and asthma ever

more elusive.

T-SUPPRESSORS AS THE PRIMARY DEFENCE AGAINST ALLERGY T-suppressors work solely through the stimulation of the H2-receptors;

defending us, unlike other immunocompentent cells that work depending on

the circumstance.35 The scarcity of the H2-receptors or their inactivity cause

suppressors to be deficient in their function. Only when these receptors are

prolific and active, T-suppressors can be considered useful and only then are

they able to actively participate in immune reactions and regulate the homeo-

static activities of the participants. Like the hard drive of a computer, they

retain the memory of how to reverse allergic reactions and guide subordinate

functions. The size of this memory is highly individual and may last for up to

20 years. Can you imagine having a chance to live for 20 years without allergic

symptoms? Can you imagine the financial losses of such a development for the

drug manufacturers?

Lately, allergy medicine has become a most puzzling field: well established

knowledge disappears from debate—and strangely, it seems to be mainly the



one which is most critical for recovery. Thus, recent textbooks and periodi-

cals avoid the word histamine, and only occasionally, one may find out that

there is a mediator called histamine. The fact that it is an autacoid, or a

healing substance, can only be discovered if one is curious enough to under-

take a purposeful, detective-style investigation through

the older literature on allergy. The protective function

of histamine H2 receptors in allergy is found in sources

on molecular biology or genetics. On the contrary, the

negative effect of H2 receptors on the production of

gastric secretions is emphasized in textbooks, periodi-

cals and pharmaceutical compendia, obviously to

support the need for the overwhelmingly popular

receptor-suppressive medications (zantac and pepcid).

This development is taking place in spite of the

fact that medical science has shown that the

T-suppressor cell is “a unique cell with a unique func-

tion”; that these cells are “the key clues to the regula-

tion of function in the immune system,” and provide

“a functional cadre of T cells that act to downregulate

the immune response.”36 In the past, allergists also

admitted that “The suppressor cells abnormalities

observed in allergic subjects may reflect a primary

defect inherent to the atopic diathesis (allergy)

(Allergy ed. by A. Kaplan 1985: 190). As was said, the

chapter that stated this is gone from the second edition

of this textbook. With the disappearance of all these

histamine-connected phenomena, gone is the under-

standing of what allergies and asthma are, and what

should become the target for therapy. This explains why

the conventional therapies are not successful.

Interestingly, all allergy-related articles that simply

cannot avoid references to T-suppressors usually call them CD8+ cells, but

never identify them as suppressors. Calling them CD8+ effectively hides their

protective role, since this term comprises two kinds of T-cells, not just

T-suppressors. The “abolishment” of suppressors urgently needs a scien-

tific justification—especially so because on the cellular level, the regulatory

role of T-suppressors’ can be compared to that of the heart or brain.


Since clinical

immunology (or

allergology) conceals

the anti-inflammatory

properties of histamine,

it is only natural that it

would also conceal the

existence of histamine-

induced anti-inflamma-

tory cytokines and their

primary producers, T-

suppressors. Thus aller-

gists totally disregard

the body’s own ability

to produce regulatory

disease-fighting

cytokines and never

seem to even think of

activating their produc-

tion. Instead, they work

on the development of

numerous medications

that could suppress the

multitude of pro-disease

cytokines.


H2 AND H3-RECEPTOR EFFECTThe growth and efficiency of H2-receptors are due to

histamine stimulation, and there is a quantitative and

qualitative aspect to both. The increase in the number

of those H2 receptors indicates that more underdevel-

oped cells turn into efficient suppressors and thus

multiply the defending army that promotes health.37

Histamine injections intensify the activity of these

receptors by providing repeated signals. Science teaches

that “the presence of the H3 or H2 receptors might alter

susceptibility to H1 effects.”38 In other words, histamine

hyperreleasability (the H1 effect) can be inhibited by

causing the H2 and H3 receptors to work together

synergistically, for together they are even more

powerful; this is the H2/3 effect. So far, no H3 receptors

have been found on T-suppressor cells. However, mast

cells and neurons have both H2 and H3 receptors. As

was said before, H1 receptors need strong signals,

whereas H2 and H3 receptors respond to low concen-

trations of histamine. So, through gentle stimulation

with injected histamine, the number of H3 receptors on

immunocompetent cells and neurons grows, and the

combined H2/3-receptor efforts amplify the disease-

fighting activity. These facts and the potential for gene

modulation through the activation of the H2-receptors

offer great promise for those chronically ill allergy

patients who do not benefit from conventional thera-

pies whose numbers are growing at an alarming rate.

Very few doctors are aware of these scientific facts. Even in the ’70s and

’80s, when the functions of the H2 and (later) H3 receptors were first

described, their protective effect was never made known for therapeutic

application. In 2001, at an international workshop covered by the Journal of

Allergy and Immunology39 the H2 and H3 receptors were casually mentioned,

but again, their protective functions in the immune and nervous systems

being omitted.


On the molecular

level, the primary

defect in allergy

patients is their under-

developed H2 receptors,

while on the cellular, it

is inactive T-suppressor

cells. Active molecules

of the H2 receptor

promote the develop-

ment of suppressors and

enable them to reverse

allergic reactions.

T-suppressors mature

only with activation of

H2 receptors, and this

makes these cells insep-

arable from histamine.

The secrecy surrounding

the remedial properties

of histamine has resulted

in the disappearance of

T-suppressors and H2

receptors from scientific

sources on allergy.


Of course, it is difficult to involve all scientist into

the this concealment of important knowledge.

Occasionally one stumbles upon revelations such as

this one where the truth, once again, peeks out unex-

pectedly: “Interestingly, in the 1980s, R. Rocklin and

co-workers published several studies showing (that)

histamine-induced suppressor-cells activity and

suppressor factor… We can speculate that this factor

might have been IL-10 (interleukin–10, the recog-

nized key anti-inflammatory cytokine in allergy

–F.R.). In summary, our data, considered in the

context of these and other studies, strongly suggest

that histamine, apart from exerting potent effector

functions in inflammation and allergy, mainly via H1

receptors, may have important immunoregulatory

functions via H2 receptors expressed on immune

cells.”40 Contemporary allergy keeps the following

facts secret, namely that

■ there are histamine-induced suppressor factors;

■ the mysterious Il-10, the central cellular cytokine in

controlling allergic reactions, is such a factor;

■ T-suppressors are the main producers of these factors.

Allergists have buried the curative mechanisms of the allergic part of our

immune system, turned it into an enemy, and made it a convenient target for

countless drugs which are only inhibitors.

H1 SUPPRESSION VS. H2/3 ACTIVATION You may ask why we should care what we use to treat a patient, antihistamines

for blocking one kind of receptors, or histamine to stimulate two others, since

the result is the same—suppression of an allergic reaction. Let us compare

these approaches:


H2and H3 receptors

perform a hista-

mine-inhibiting and anti-

inflammatory role. The

combined H2/3 effect

could oppose H1-

receptor activity, stop

histamine spill and the

subsequent chemical

reaction, and by that,

relieve allergy symp-

toms. Basic science

has provided all the

supporting data, but

clinical medicine does

not teach them. It

appears to conceal this

knowledge purposefully.


H1-receptor blocking H2/3-receptor stimulation

Disrupts histamine messages and, as Restores normal functioning of all cells

a consequence, reduces its activity not that have these receptors without

only in the allergy-participating cells, disrupting H1-receptor messages.

but also in all parts of the body, thus

preventing their normal functioning.

Requires regular drug replenishment Allows the body to function normally for

due to its brief effect. a long time and eliminates the need for

regular drugs.

Does not eliminate the main cause of Rectifies the source of the problems—

the symptoms—H2/3-receptor inactivity. strengthens the inactive H2/3-receptors.

If blocking is successful, it creates the Alleviates the symptoms due to the

illusion of good health while allowing restored ability of the cells to function

the defect to deepen. properly.

Just looking at the table, one can clearly see the advantage of the stimula-

tory effect over suppression. Why is it that modern medicine does not intro-

duce the simple, biologically preferable approach of H2/3-receptor activation

into clinical practice? Why, instead, would medicine insist on suppressing the

activity of the H1 receptors and disrupt their needed messages throughout the

body? The reason is simple: the slightest possibility of permanent or lasting

correction of the functional genetic error endangers the profits of the drug

market.

THE INTRACELLULAR ENZYME CYCLIC AMPReceptors are conductors relaying the messages of the substances that activate

them. To be transformed into an action, these messages need fuel, and intra-

cellular enzymes are this fuel. Enzymes are protein molecules that catalyze or

inhibit chemical reactions. They are responsible for the energy of the cellular

lab, its production and operation. One enzyme is of special importance for

the whole body functioning and especially on behalf of the immune system.

It is called cyclic AMP (cyclic adenosine monophosphate), or simply, cAMP.



It plays the key role in the activity of many hormones.

The general perception is that the notion of hormone

is applied solely to the products of endocrine glands,

and originally, medicine did use this word in a limited

meaning. Over time, the scientific term hormone has

expanded to cover any chemical able to produce wide-

spread, regulatory effects on particular cells, both

locally and anatomically remote. When the effect is

systemic we consider it to be a systemic effect.

Histamine, for instance, is a local hormone that invokes

local as well as systemic effects. Hormones are the most

potent substances, which determine the work of all

organs and systems. The fact that the effectiveness of

so many hormones depends on the levels of cAMP

makes this enzyme so vitally important. Over 90% (!)

of the immune system’s work depends on cAMP,

therefore lower than normal quantities of this

enzyme predispose a person to certain immune

diseases. As might be expected, it is only natural for

medicine to research what body chemicals can effec-

tively increase cAMP, and for the drug industry to

develop medications that would reproduce the effect

of these chemicals.

There is special relationship between histamine

and cAMP. Histamine is not just another local

hormone whose activity depends on cAMP. There is a

reciprocal interdependence between the enzyme and

histamine. Histamine is recognized to be the most

potent stimulant among the substances able to raise the levels of cAMP. Its

signal sent via H2 receptors activates cAMP, and the enzyme, in turn, starts a

chain of chemical reactions that engage the genetic material. The messages

from the genes facilitate generation of defensive chemistry. Most authorita-

tive sources affirm the histamine/cAMP interdependency and call for using

this feature in the development of therapies. The best reference in this regard

would be the universally used textbook Harrison’s Principals of Internal

Medicine. Already in the 1980s, it emphasized “the real importance of cyclic

AMP for medicine as a tool in understanding normal and pathologic regulation


The primary defect in

allergy is H2/3-

receptor inefficiency.

Blocking the efficient H1

receptors by antihista-

mines and other conven-

tional medications is

much less effective than

stimulating the ineffi-

cient H2/3 receptors due

to the brevity of the

symptom relief and the

disruptive effect of

these drugs upon the

cellular network. Only

activation of H2/3 recep-

tors allows us to achieve

a lasting relief or cure.

Allergists prefer the

strategy of blocking the

H1 effect rather than

stimulating the H2/3

effect. Coincidentally,

this strategy provides

great and reliable

revenues for the phar-

maceuticals.


and in developing new drugs” (p. 374) and pointed to

the H2 receptors as the route for elevating this

enzyme’s levels.

Excerpts from an international periodical devoted

to drug research may serve as another example:

“…stimulation of the H2 receptor leads …to a massive

production of cAMP.” “The H2 receptor is primarily

coupled to the …production of cAMP.” “Numerous

reports have shown that histamine increases the levels

of cAMP.” The same ideas are developed in the earlier

quoted work by a world-renowned geneticists who also

point to the H2 receptor as a conductor of histamine

messages that stimulate the enzyme and through it,

regulate gene functioning: “…the activation of hista-

mine H2 receptors results in generation of cAMP”41,42

And as a final example, I will refer to the most recent

work with the self-explanatory title—Histamine regu-

lates cytokine production—which indicates that nothing

has changed in basic sciences within the past three

decades since the discovery of cAMP/histamine inter-

dependent “friendship.” The article compares hista-

mine with other activators of cAMP and states: “none

of the mediators of allergy has any comparable anti-

inflammatory cAMP-mediated effect.”51

ALLERGY AND THE cAMP/HISTAMINE TEAMFirst, allergies are immune diseases, and cAMP is the

central enzyme responsible for the proper functioning

of the immune system. Second, allergies are caused by

the excessive production of histamine. Therefore, the

histamine/cAMP team and H2 receptor—which is the

connecting “wire” between the two—acquire extraordinary importance when

we want to control allergic inflammation. The first evidence implicating

cyclic AMP in control of leukocyte function goes as far back as 1968 when it

was presented by two authors, one of whom is a former president of AAAI, L.

Lichtenstein, the scientist who studied the cAMP/histamine interrelationship

most extensively. There it is stated that the basic biochemical defect in allergy


Protein molecules

called enzymes form

the intracellular fuel

that transmits messages

relayed by different

substances via their

receptors. One such

enzyme, cyclic AMP,

is vital for the normal

functioning of the cells

in numerous organs and

systems, and especially

for the immune system.

Science recognizes

histamine as the primary

activator of cAMP in


Histamine uses H2

receptor for communica-

tion. In theory, medicine

recognizes the hista-

mine/cAMP relationship

as the key mechanism

for reversal of immune-

related inflammation.

However, these scien-

tific facts have not had

any effect on drug

production.


patients is lower than normal levels of cAMP: “if leukocytes or mast cells of

asthmatics accumulate lesser amount of cyclic AMP … than do the same cells

in normal subjects, physiologic control of the release of inflammatory medi-

ators might be deranged.”43 All of this shows

■ the lower than normal level of cAMP in allergy patients;

■ the need to elevate it in order to diminish the intensity of allergic inflam-

mation;

■ the agent that increases the level of cAMP—histamine;

■ the route through which histamine conducts the message—H2 receptor;

■ the result of the implementation of the histamine-sent message—reduction

of the immune inflammation;

■ the cause of allergic inflammation eliminated by H2-receptor messages—exaggerated histamine release.

We must admire the authors who did this intensive

research and wonder why none of this has been trans-

ferred to clinical allergy practice over the past three

decades. Practical use of this information could rid

millions of allergy and asthma patients of needless

suffering.

CORRECTING GENETIC FUNCTIONING WITHCELLULAR HISTAMINELet us see how the messages of intracellular histamine

reach the nucleus of the cell. Genetic functioning

occurs in DNA (deoxyribonucleic acid). Today,

everyone knows that DNA is the carrier of the hered-

itary biological material in all organisms, the major

constituent of genes. RNA, another acid (riboxynu-

cleic), is at the service of DNA, and both constitute

genes. RNA creates templates for protein synthesis.

The part of RNA called messenger RNA instructs the

cell what proteins to produce and in what amounts,

which places messenger RNA at the centre of the

genetic performance. Now, it so happens that cAMP is

the principal enzyme that regulates the synthesis of

messenger RNA, and through it maintains the opera-

tion of a large number of families of genes. These


Research of leading

allergists concludes

that histamine messages

delivered by its H2

receptor intensify the

activity of cAMP, the

enzyme needed for the

normal functioning of

the immune system. The

primary biochemical

defect in allergy

patients is low levels of

cAMP, therefore hista-

mine messages become

vital in raising these

levels. Accumulation of

cAMP results in the

production of protective

chemistry by the

immunocompetent cells,

inhibition of excessive

histamine release and

hence, reversal of

allergic reaction.


include the genes responsible for the function of the immune system, the

brain, the lungs, the skin, the skeletal muscles, the heart, the endocrine glands,

etc.

Mother Nature never fails to surprise us, and cAMP is one of her greatest

surprises. Not only does this enzyme always protect the body, but it is also

flexible in its performance; therefore, depending upon the body’s need, cAMP

may suppress the disease-promoting activity or activate the production of the

disease-suppressing chemistry. Activity of this enzyme determines the fighting

ability of the immune system.

Nature combined the two miracles—cAMP and histamine—into one unit

to work for us. It really is a marvellously simple scheme: histamine, via H2

receptor generates cAMP, which in turn regulates the performance of the

genes, and that results in a wide range of anti-inflammatory chemistry and

disease-fighting effects. Working together as a pump that provides genetic

fuel, histamine and cAMP form the backbone for signal transduction, cellular

production and the subsequent cell-to-cell talk. The fact that histamine can

change the functioning of immunocompetent cells and neurons permitted

science to call histamine an immuno- and neur-omodulator. However, there

is more to histamine’s miraculous features.

All operations in the body are genetically driven, and this gene activity

together with its subsequent effects has a name: gene expression. Histamine is

capable of reaching the heart of the cell, and influence genetic functioning. In

order to do its healing work, histamine needs as a prerequisite functionally

adequate H2 receptors which provide the natural pathway for histamine

messages to reach the genetic material. As we know, allergy symptoms are the

result of the weakness of this very receptor.

THE PRIME DEFECTS IN ALLERGYWe named several important defects known to exist in allergies: H2-receptor

inefficiency, mast cells/basophil hyperreleasability, T-suppressor scarcity/

inefficiency and low levels of cAMP. How can it be that so many defects are of

central importance? The explanation is: they are found on three different

levels, but they stem from the same root. All three are the links of the same

chain, and all three can be restored simultaneously if the target is properly

selected. Here is a summary of what makes allergy patients different from

healthy individuals, and how the deviations can be corrected.



All the defects are of GENETIC origin—malfunc-

tioning of the genes affects the protective aspects of

immunity, such as the allergy-participating cells, their

receptors and products. In the absence of genetic

flaws, most of the effects of the environment on the

production of symptoms are brief. This fact makes the

inner causes that require correction primary in impor-

tance, and the outer triggers secondary.

■ The first level is BIOCHEMICAL–pre-existing low

levels of the enzyme cAMP, which provides fuel

for the operation of the defensive forces of our

immune system. Without this enzyme’s induction,

the balance shifts, and the overreacting immune

forces prevail.

■ The second level is MOLECULAR–here we may

find deficient, synergistically working molecules

called H2 and H3 receptors. This may cause an

inactivation of the enzyme cAMP, because this

enzyme becomes activated only by healthy hista-

mine messages via the H2 receptor.

■ The third level is CELLULAR–here a defect manifests,

first of all, in the mast cells/basophile high hista-

mine releasability and T-suppressor inefficiency,

both resulting from the H2/3-receptor inefficiency.

To correct the defects at all the levels, one should acti-

vate H2 and H3 receptors with injections of hista-

mine. Their synergistic operation will raise the levels

of cAMP, inhibit histamine release from mast cells and basophils, and

generate and activate T-suppressors. The understanding of the prime defects

in allergy and asthma can then lead to a proper management of these diseases.

Treating allergy and asthma is relatively easy when these principles are applied.

This is not useful to the pharmaceutical corporations.

SYNTHETIC HISTAMINE IS A NATURAL GENE MODULATOR The most effective way to treat chronic diseases would be to change the func-

tioning of the faulty genes. Today’s genetic engineering is a technical proce-

dure, in which undesirable parts of the genetic material are substituted with


Histamine messages

via the H2 receptors

activate the enzyme

cAMP. This enzyme

ignites a chain of intra-

cellular chemical events

that reach the genetic

material and change the

functioning of the genes

known as gene expres-

sion. Successful correc-

tion of gene expression

results in those

corrected messages to

be transmitted to the

cellular lab. This brings

about normalized

cellular production, and

the end of allergy symp-

toms. To be able to

deliver stimulatory

messages, these recep-

tors must be efficient

and functional.


the ones that are supposed to function better. The

process is complicated and contains numerous ethical

and legal problems. If medicine could duplicate nature’s

methods by non-intrusive correction of functional

defects, it would achieve the desired results in harmony

with nature. Correction of gene expression is ultimately

an attempt to imitate Nature. One can also call this gene

modulation, a kind of genetic engineering. Imple-

mented via histamine injections, it would be much safer

than the invasive, unpredictable and technologically

complex manipulation. It has already been tested clini-

cally. Simplified, the scheme of allergic and other hista-

mine-based diseases looks like this: the H2 receptor,

genetically underdeveloped, is unable to

1) turn off the histamine spill by mast cells and

basophils;

2) generate active T-suppressors for efficient defence;

3) accumulate cAMP.

Gene modulation should come as repeated activation of

the inefficient H2 receptors by histamine injections. This

would lead to an accumulation of cAMP in all H-

receptor-bearing cells as they form a histaminergic

system that transmits the histamine effects all over the

body, including the genes. The team work of histamine

and cAMP is especially beneficial for the tissues that

have the most dense distribution of cells with the

highest histamine production—such as the lungs, the

skin, the nasal passages, the brain and the gastroin-

testinal tract. Lasting remissions in allergies, asthma,

vascular headaches, irritable bowel syndrome, etc.,

following histamine therapy suggest that the relevant

genes are functioning properly again.

In my practice, I saw every day how gene modula-

tion through histamine injections worked. I can attest

to the truth of the statement made by Bayard Horton,

also convinced of the efficacy of histamine therapy. He

observed that histamine “can make the lame walk, the


The lasting correction of

the gene expression

through histamine injec-

tions can be called gene

modulation or natural

genetic engineering. Unlike

the more controversial and

incomparably more compli-

cated technical proce-

dures, this is safe and

efficient. Modulation of

allergy-governing genes

restores the functioning of

the relevant cells with the

subsequent control over

the release of histamine

and histamine-induced

chemistry in a sustained

way. Although many

diseases, in which cAMP

plays a role can be treated

this way, allergies and a

number of related condi-

tions could gain maximum

benefit, as their cause is

excessive histamine

release, and control over

that release ends the

disease. Three things make

histamine a gene modu-

lator of choice in immune-

related diseases: 1) its

unique ability to activate

cAMP; 2) its availability in

synthetic versions; 3) its

safety and low cost for

society and for the patient.


deaf hear, and the blind see. I know. I have seen it happen. More ‘miracles’ in

my experience have been wrought with histamine than with all other thera-

peutic procedures combined.”44

Gene modulation in allergies and related diseases could be standard practice

if only clinical immunologists employed the findings of their own research.

However, they withhold the theoretical knowledge of all curative properties of

histamine to prevent the use of its synthetic analogues in a clinical setting.

Allergy medicine bears full responsibility for sabotaging the main task its

professional status requires—help its patients.

THE STIMULATORY APPROACH Medicine in general and clinical allergy specifically are based on symptom-

suppressive medications. However, it would be wrong to say that medicine is

completely devoid of drugs that stimulate protective cellular activity. Imitrex,

a drug used to alleviate migraine headaches, is one example of highly praised

family of medications able to relieve headaches that do not respond to the

strongest pain blockers. How do Imitrex and similar drugs work?

According to the law of homeostasis, when the level of any substance in

the body rises, its further production is inhibited by the control mechanisms.

As the existing theory states, migraine headaches occur due to an excessive

release of the brain chemical serotonin. All migraine medications are, actu-

ally, painkillers. They block receptors passing messages of pain. Imitrex is a

type of a serotonin analogue. It stimulates serotonin-inhibiting receptors,

and the inhibition temporarily relieves the headache. The synthetic analogue

pushes the button which the cellular serotonin, though in excess, could not

push. There is an analogy in the performance of histamine and serotonin.

Compare:

Histamine Serotonin

Excess of histamine causes allergy Excess of serotonin causes migraine

and related symptoms (including headaches

migraine headache)

Injections of synthetic histamine Injections of imitrex (a serotonin

restore the balance of internal analogue) restore the balance of the

histamine. internal serotonin



Imitrex been universally accepted and has also received the highest phar-

maceutical award as the best medication of the year. By contrast, histamine,

even though it has many similar properties, has been resisted by the highest.

This attitude to medications has deep social roots.

MEDICINE AS PART OF THE ECONOMYOur socio-economic philosophy provides the answers to all the questions

surrounding histamine. Medicine is a major sector of our economy. Treat-

ment of patients makes medicine a consumer product. Our society has come

to expect ever-increasing profits from all businesses regardless of the field of

endeavour. The health sector must be profitable too. Like any other sector,

medicine has its producers and consumers. Leading medical professionals are

involved in drug research, development and testing, and are, thus, interested

in expanding the drug market. The rising incidence of allergy, asthma and

related diseases creates the most favourable conditions for that, since the

existing remedies are, at best, only temporarily helpful and therefore become

products of daily use. The trend towards an increase in drug consumption

provides the basis for skyrocketing revenues. Your interests, as a customer, are

in conflict with the interests of the producers because you want to get an inex-

pensive, and, even more important, long-lasting or possibly even a curative

product. Yet, such products reduce the market demand. From the standpoint

of market economy, histamine is not a profitable drug. There are several

reasons why synthetic histamine, unlike Imitrex, is doomed.

First, Imitrex regulates serotonin production but leaves histamine, which

is superior to serotonin, unregulated. Therefore, Imitrex and the newer

Imitrex-like drugs are able to relieve ONE migraine attack. The duration of

relief is different in different migraineurs. Another attack may start hours

after and necessitate another dose. Cost of an Imitrex injection is about $50

Canadian dollars.

Histamine may provide lasting regulation of its own production and lead

to the regulation of the synthesis and release of the dependent serotonin.

Histamine therapy rectifies the core chemical imbalance and thus allows the

patient a long, medication-free period, while Imitrex tackles the secondary

events. If the regulatory switches for histamine, the H2/3 receptors, are

resilient by nature, it is possible that the patient may never again have

migraine attacks. The present cost of a full course of histamine therapy would

be somewhere between $20 and $100 Canadian dollars, depending solely on

its availability as controlled by the drug companies.



Second, Imitrex and similar medications for

migraine have been patented by FDA as new drugs,

and this provides a great future for the producer in

terms of revenues. Histamine, on the other hand, has

been on the market for almost a century, and there-

fore, no patent is needed to start producing it. No

patent means no profit for the producer.

Third, the use of Imitrex is limited to migraines,

whereas histamine is highly effective for all sorts of

vascular headaches, plus allergies, asthma and a

number of immune-related diseases. This universality

may eliminate the need of numerous medications

after a treatment course with histamine injections and

basically ruin the drug industry.

Histamine as a conventional drug? “Never,” say the drug producers that

provide sprays, pills and ointments for allergies and asthma, and painkillers

for headaches. The drug developers have formidable power because they can

pay for the best minds.

DUALITY IN NATUREAn observation that may be worth exploring at this point is the logic of nature’s

laws and the logic of histamine therapy that goes along with it. Let us speculate

on duality. Everything in life is dual: life and death, love and hatred, health and

disease. This has been depicted through the centuries in the two-faced god

Janus, or Yin /Yang symbols, and in the eternal fight of Good and Evil.

Opposing chemical processes co-exist in the body at any given moment,

and the state of health vs. disease is determined by the prevalence of one over

the other. For example, as long as the formation of new cells exceeds their

degeneration, the body grows and develops. When degeneration takes over,

ageing starts. Take another example. If the body’s consumption of food is well

regulated by metabolism, we keep our weight under control. As we age, we

become prone to gaining weight even with the same food intake. This

happens because age wears out the mechanisms that regulate our metabo-

lism, and it slows down. To stay in good shape, we should either reduce our

food consumption, or boost the body’s chemical processes by exercise, or,

better, do both. Balance is the answer to all problems.

In a healthy body, balance is achieved through its innate autoregulatory

mechanisms and systems. However, whenever damage does occur, relief


While drug developers

successfully use

stimulation of inefficient

receptors to temporarily

regulate other body

chemicals, they never do

it with histamine. The

wide range of immuno-

logical and neuroregula-

tory effects produced by

histamine injections is

not employed by clinical

allergy.


should come from fixing the processes, rather than using artificial, unreliable,

or collateral means. Therefore a change in exercise level and diet is a better

response to weight gain than the consumption of appetite-suppressing pills

or radical stomach stapling.

However, anything bad that does not exceed the body’s ability to over-

come it, presents a challenge to the protective forces and keeps them active.

For instance, the fight against a virus teaches the immune system how to

defend the host if the virus repeats its attack. The virus expands the protec-

tive memory of the immunocompetent cells. In the same manner, any good

possesses seeds of the bad. The body’s processes are never unilateral, more-

over, “bad” and “good” ones go on simultaneously. Here is an example of a

natural duality: a small sliver gets under the skin. To destroy it, immuno-

competent cells specialised in fighting foreign bodies rush to the site, gobble

it up and turn it into pus in the process. On the one hand, pus is the product

of this protective activity, on the other, its potential release into the blood

and lymph flow harbours danger such as a secondary generalized infection

or sepsis.

With the genes, this pattern of duality is also found in the actions of effec-

tors and repressors. While the first kind gives instructions to the cells what

chemicals to produce, the second type moderates the effector’s activity. In

many chronic illnesses, genetic changes are functional and therefore poten-

tially correctable. The effector gene messages depend on the messages of the

repressor. The H1-receptor effect implemented by T-helpers becomes over-

whelming only if the counterbalancing H2 effect is inefficient. The duality of

allergic reactions can be easily proven: allergy patients suffer but rarely die

because the power of the pro-disease forces in the body is not absolute, and

the defensive forces, though weakened tends to carry the day.

The inborn ability of cellular histamine to stimulate both positive and

negative forces is yet another confirmation of duality in allergy. “Some effects

of histamine are pro-inflammatory… whereas others are anti-inflammatory,”

said a pioneer of histamine research, R. Rocklin.45 Thus, although histamine

spill from mast cells initiates an allergic reaction, “histamine release from

mast cells may paradoxically limit the extent of inflammatory and immune

reactions,” and reduce the levels of pro-inflammatory cytokines.46

Duality is a law of nature especially applicable to such self-regulatory

systems as the immune system. To ignore this is to defy nature itself. By

presenting immune mechanisms in allergy as a unilateral process, allergy justi-



fies the one-sided approach—suppression of the evil forces. Modern allergy

disregards the ability of the same immune cells to fight for us.

DUALITY AS A TOOL OF ALLERGY TREATMENTAllergic diseases are different from other immune diseases, in which we deal

with physical obstacles. For example, in cancer, we deal with a tumor that must

be shrunk; in rheumatoid arthritis, degeneration of tissues must be reversed,

etc. Allergy, in contrast, is a purely chemical imbalance that can be changed,

often in seconds or minutes. Spontaneous relief from a bout of sneezing or an

asthma attack is achieved. Unless allergy has advanced so far that secondary

degenerative changes in the lung tissue take place, asthma is the most

reversible immunologic disease. Lasting drug-free remissions in asthma or

other allergic diseases are proof. It is hard to overestimate the harm of the

latest tendency to present allergies, and especially asthma, as a disease of struc-

tural changes in the tissues, similar to wound-repair processes. It is tragic, that

today, we have diseases that can in many cases be reversed or greatly improved

presented to the public as being conditions with irreversible organic changes.

Since the body is erroneously thought of as lacking its own remedial tools, we

are offered only harsh suppressive methods and even surgical procedures.

Allergic diseases are diseases of hypersensitivity, and histamine duality is

their essence. They can be compared to balancing scales with one pan full of

disease-promoting mediators and the other, with disease inhibitors. In order to

balance the scales, we can reduce the over-weighted scale H1 or increase the load

on the under-weighted scale H2/3. The overloaded scale H1 would require

constant support because of the seething histamine-induced chemistry main-

tained by the continuous release from the immunocompetent cells. This is

exactly what conventional medicine dictates—constant interference. This

approach disregards the broken regulatory tools of the immune system and

allows the damage to spread. Besides, although the aim of these drugs is to

suppress allergy symptoms, they block histamine activity everywhere, even

though other tissues need it for their normal functioning. Blocking is espe-

cially harmful in view of the chronic nature of the disease and hence, the

chronic requirement for drug consumption. “Make not thy stomach an

apothecary’s shop,” a proverb warns. Yet, we do.

The second way to balance the scales is to load the pan with disease-

inhibiting mediators. Stimulation of pro-health forces is called immunomod-

ulation or immunotherapy. Immunotherapy strengthens the inefficient



receptors, and they establish lasting, balanced production of the “good” medi-

ators. This approach helps avoid creation of additional health problems, so

common in patients on daily drugs.

Allergology medicine does not generally acknowledge the duality of

allergic processes; therefore it cannot recognize the legitimacy of two

opposing approaches in the management of allergic diseases. Allergy employs

only the one that suits it—suppression of natural chemistry. Its creed is—the

more suppression, the better.

DUALITY AND THE MEDICAL PROFESSIONIn a living body, all reactions are interrelated. Our society is a live organism, and

its processes are inevitably interdependent. As a part of our economy, medicine

is doomed to be market-oriented, with vested interests politicizing it. Medicine

provides numerous jobs to many sectors of the economy and hence, income to

a large number of people. In doing so, it creates its financial and political dicta-

tors. Unfortunately, we tend to overlook how heavily medicine is interlaced

with politics and the market economy until we ourselves are affected by it.

Doctors are both the supporters and the victims of the existing system.

The sheer number of allergy/asthma patients turns allergy into a field of

extreme interest for a medical practitioner. Any doctor treating an allergy

patient faces the dilemma—to cure or not to cure? In the case of a successful

treatment, the patient stops visiting his doctor. Of course, by word-of-mouth,

other patients will come leaving their former doctors who were unable to help

them. However, this may bring their original doctors’ wrath upon the healer,

especially if he is on a lower level of the hierarchical structure. Besides, imagine

what the consequences would be if the successful treatment spread widely in this

lucrative field of medicine. Would there be enough allergy patients for this sector

of the medical profession to survive? Patients’ improvement versus doctors’ loss of

profit—this duality is created by our over-doctored society.

Another problem for the doctors is that to access true knowledge, they

will have to dig it out of mountains of irrelevant and confusing information

that conceals and/or misinterprets the facts. Not too many doctors are ready

to replace their shiny stethoscopes with spades. Digging is tiring and unpaid.

Moreover, “the mind once stretched, never regains its original dimensions,” as

Oliver Wendell Holmes, a 19th century physician and writer said. Such a

“stretching” is dangerous for “the fathers” of the field, since nobody should

dare to know more than they do. Hence, in the confrontation of knowledge

vs. peace of mind, the latter wins.



Doctors face yet another dilemma. Let us assume a doctor chooses to

repair the immune system. Because of the individual sensitivity of the

immune responses, dosage is a factor to be seriously considered. The inborn

concentrations of histamine in the tissues are highly individualized and

depend on the number of the histamine-releasing cells involved in the given

area. This, together with the highly specific responsiveness of all the H recep-

tors in different individuals, influences the dose of the synthetic version.

Both T-cells and mast cells are extremely sensitive to histamine, but no test

can accurately measure this sensitivity. Dose selection rests entirely upon the

clinical judgment of each individual doctor, aided by his theoretical knowl-

edge, his personal experience and intuition as well as the time spent with

each patient. The dose should be sufficient to incite H2/3-receptor activity

and to provide improvement, but at the same time, to avoid an aggravation,

it should not activate the H1 receptors. Although transitory, any worsening

of the condition would be especially undesirable in asthmatics and small

children. Who needs all these troubles? It is much easier to prescribe a conven-

tional pill or spray to be taken once or twice each day, with no personal respon-

sibility. If a patient on a conventional therapy has a severe adverse reaction or

even dies, the doctor is not guilty as long as everything was strictly according to

the guidelines.

Standards of practice in medicine serve two major purposes: doctors are

held in tight reign, but the restrictions create lack of individual accountability

and liability. The situation relieves the doctor of the need to make decisions

and at the same time, it removes any personal responsibility. If a doctor does

not challenge the medical authorities with daring innovations, they will

defend him. In this way, they defend the rules established by them. Those who

have tried to sue a doctor probably have first-hand experience of how

unwilling the medical profession is to go against one of its own. At the same

time, a practitioner who may have cured hundreds or thousands is still liable

if his method does not fit the mould. Another case of duality: what is good

for a patient is fraught with dire consequences for his doctor.

My personal story is just one of probably many. For helping about 2,500

patients to live normal, medication-free life, I was punished. In a properly

functioning society, a physician should, at least, be encouraged to continue

with his therapy, even it goes beyond the so-called standards. Such “hand-

cuffing” of ideas and good intentions are the best illustration of the real

values of our society.



PATIENTS AND DUALITYPatients face a dilemma too. Many of those who have mild and moderate

allergies do not realize the danger of medications because they do not abuse

them. The side effects may not be evident for years. Besides, not only in

allergy, but also in disease in general, people are tempted to seek out quick

relief. A pill to alleviate a headache saves them time and effort they would

otherwise need to learn to relax, to give up coffee or chocolate, change the

regimen of sleep, etc. It is much easier to take appetite-reducing pills or go for

liposuction than to exercise till one sweats and to forgo things like fries and

mayonnaise. Human nature gravitates towards easy approaches to problems.

Most often, when patients are given the choice between a temporary but fast

fix or a lengthy corrective procedure that requires effort on their part, they

will favor the easy way.

However, nature does not like short cuts. We should follow nature and

therefore leave conventional allergy and asthma medications for acute situa-

tions or as the last resort when repair of our immune system fails. We should

use the duality of the body’s functions to its own benefit. As everything in the

body is expressed through its chemistry, we should look for ways to shift the

chemical balance in favor of health. The shift should be based on the restora-

tion of those mechanisms that the body relies upon, in contrast to symptom-

suppressing drugs that provide quick but brief relief and leave the underlying

problem unattended. Not to mention the side effects of such drugs, which

may be worse than the original disease.

Logical? Yes. Good for health? Yes. Difficult? Absolutely. Difficult for both

parties: for patients to select, and for doctors to implement. There is an excuse

for patients choosing symptomatic medications. Immunotherapy or, “allergy

shots,” would be the only known alternative to daily medications. Patients

came to me who had been treated for 10–15 years with allergy shots and told

me their stories about the adverse reactions. The textbook Allergy 1985

supported the conclusion: “…with little evidence of efficacy for the technique

as commonly practised, immunotherapy fell into disrepute in the scientific

community at large.”47 According to the consensus of the pillars of allergy,

nothing has changed over the time and 10 years later, we read “Safety, cost and

efficiency should be considered prior to initiation of immunotherapy.”48 By

saying all that, both the textbook and the journal reveal that conventional

allergy shots are potentially unsafe, obviously costly and inefficient. Knowing

this, can we blame patients who are unwilling to undergo such immunotherapy?

In fact, the most recent article points to “the marked drop in immunotherapy.”49



BASIC SCIENCES AND PRACTICAL MEDICINE—THE DIFFERENCETo understand how access to thoroughly researched data can be blocked, one

should understand the course of discoveries in medicine. Here is a general

example to illustrate the process of a discovery.

Step One. An unfamiliar molecule is found on (or in) a cell. To prove that

it is a receptor, it is challenged pharmacologically with different substances,

synthetic versions or analogues of the body’s chemicals. The challenge reveals,

which of them activate or inactivate the receptor and in what concentrations.

The activating chemicals are agonists, the blocking ones are antagonists. The

challenge also shows the physiological role of this receptor or, as science calls

it, the receptor’s expression. The response of the receptor to the challenge—

with inhibition or increase of the cellular production of a particular

substance—determines its role of a turn-off or turn-on switch. Other cells are

searched for the same receptor type because the efficiency of the given

receptor will affect the functioning of all cells possessing it. Naturally, the

work of the organs comprised of these cells also depends on the tiny receptor,

as underproduction or overproduction of the given chemical may result in a

state of disease. This receptor underdevelopment, inefficiency or scarcity, may

become the cause of a chronic disease affecting the whole body. All this neces-

sitates a thorough investigation of the “geographical” location of the receptor

and its functions in different cells and organs.

Step Two. The development of pharmacological agonists or antagonists

for the given receptor is considered. They are viewed as the basis for potential

medications. When developed, these chemicals are tube- and tissue-tested,

and then tried on animals. Limited studies on humans may be conducted.

Step Three. To manufacture the drug or not will depend not so much on its

effectiveness in the studies, but mainly on the thoroughly calculated potential

profits for the pharmaceutical industry in general. From the point of view of

any business, it is senseless to invest in a project known from the start to be a

financial failure. The drug’s effect is usually inversely proportional to the

profit. Moreover, any drug that could restore the functioning of a defunct

receptor may financially ruin not only its producer but undermine the industry

on the whole, since it eliminates the need of daily symptom suppressors. There-

fore, the most successful clinical trials may have limited, if any, publicity and

may never reach the human testing stage.



LIFE BEFORE PROFITFor those of you who may believe in the goodness of the pharmaceutical

industry, I will relate a fable written by Felix Krivin, a writer well known in

the former Soviet Union. The fable is about Paris, a character from Greek

mythology. Paris acquired an apple, the proverbial Apple of Discord, which he

was supposed to give to the most beautiful goddess. Three of the goddesses

were vying for the apple and were promising Paris rewards in return. One

promised to make him rich; the second offered him power; the third would

give him the love of the most beautiful woman. Paris hesitated. He loved

wealth, power and women, but most of all, Paris loved… apples. Our drug

industry is like Paris. It loves its patients. It loves its reputation of being their

benefactor. It loves doctors whom it constantly “educates” about its products

and uses as promoters of those. But most of all, it loves its profits. Just

remember the three-year court fight of the 25 million African AIDS patients

with 39 drug companies for the right to have cheaper generic drugs. In 2001,

the industry gave in only due to the strongest public opposition.

Basic sciences are relatively less politicized. Looking into their microscopes,

researchers do not yet know about the future fiscal implications of their find-

ings. This permits the publication of the initial theoretical information. It is

different with clinical medicine directly tied to revenues and thus dependent on

and strictly controlled by pharmaceuticals. Any access to the information that

may reduce profits is solidly blocked. Drugs with a wide scope of action and

curative properties contradict the essence of the drug market. The failure of

contemporary medicine in chronic disease forces the medical profession to find

who is to be blamed for this, and the industry becomes the target. Thus, three

editors of JACI, D. Leung, H. Nelson and S. Szefler making their comments on

state of the art in allergic rhinitis and asthma, say: “…the pharmaceutical

industry has failed to appreciate the magnitude of the suffering experienced by

these patients and has not risen to the challenge of finding an effective and safe

treatment for their affliction.”50 However, a major detail appears to slips the

attention of these respectable scientists: industry alone cannot do all the deci-

sion-making. The blame falls, first of all, on the scientists and doctors working

for it and supporting it in its anti-patient policy.

HISTAMINE AND THE DRUG INDUSTRYThe story of histamine is the best illustration of how scientific developments

are stonewalled. Histamine research and its empirical use for almost a century



provided prolific data, including the discovery of the H1 receptor in the early

thirties. Medicine universally embraced histamine as the central allergy medi-

ator that initiates and maintains allergic reactions. The development of H1-

receptor blockers known as antihistamines was consistent with the theoretical

data existing at that time, and more than satisfactory from the standpoint of

profit. Antihistamines met all the requirements needed by the drug manufac-

turers: they did not cure, were considered (at that stage) safe, and were to be

taken on a daily basis (up to several times a day). On today’s drug market,

there are no drugs that can compete with H1-antihistamines for profitability.

From the moment of its discovery, fascination with histamine prompted

worldwide research, and new findings of its role in the body accrued through

the years. The discovery of the H2 receptor signified another phase, during

which outstanding discoveries were made. The first extensive descriptions

were made in the sixties, and in the early seventies. L. Lichtenstein and M.

Melmon found that the H2 receptor possessed an opposite function to the H1

type, allowing it to play the protective role in allergies. Moreover, H2 receptor

possessed the unique ability to transform histamine messages into accumula-

tion of the intracellular enzyme cAMP. H2-receptor stimulation enabled the

body to reverse immune inflammations and allergic reactions, by turning off

the histamine flood. This permitted science to classify histamine as an auta-

coid, a self-remedy of unprecedented importance in immunology. The cura-

tive properties of histamine and its synthetic analogues were thoroughly

studied. In the ’50s, Parrot developed histaglobulin, and in the ’70s, K.

Melmon and his team synthesized histamine congeners. Both proved to be

safe and effective in allergic diseases and could thus become successful rivals

to antihistamines and other conventional therapies.

Up until now, histaglobulin is quietly employed here and there, while the

congeners have remained unknown to clinical medicine. Also remaining

concealed is the theoretical substantiation of the potential benefits of hista-

mine therapy in other chronic immune disorders. The efficiency of histamine

in allergy would be in inverse proportion to their marketability. Along with

the stimulatory effect of the H2 receptor, the possibility of blocking it was also

researched, and here, the results were different: a new drug category—the H2-

receptor antagonists or H2 antihistamines—were developed to be used for

excessive stomach acidity. They were welcomed by the drug industry, and

together with H1 antihistamines, have become one of the most profitable

pharmaceutical products.



In the early eighties, H3 receptors were found in nerve cells, and their

histamine-inhibiting effect, which is similar to H2 effect, was described. Some

time later, this receptor was found on immunocompetent cells as well.

Further research showed that H3-receptor stimulation could regulate not only

histamine release but also the release of other neurotransmitters, mediators of

nerve cells. H3-receptor agonists were created and proved effective for neuro-

logical symptoms as well as certain immune-related conditions. Actually, H3

receptor could become the key to the new therapy—neuromodulation. It

could correct the imbalance of neurotransmitters and rid patients of a wide

number of neurological symptoms, including such common ones as vascular

headaches. Moreover, the synergism of the H3-receptor and H2-receptor

functioning steps up the remedial effect in allergies as well. But, the improve-

ment would be lasting or permanent, and this appears to have doomed H3-

receptor agonists.

Still, nothing exposes the close ties between allergists and the drug industry

more than developing a certain drug group for asthma, which I mentioned

earlier. They target the enzyme cAMP, the levels of which are lower than

normal in allergy patients. The simplest solution would be imitation of

Nature which would mean H2-receptor stimulation. However, this avenue is

closed, since it would lead to the unwelcome revelations about the demoted

histamine. The drug developers choose a circuitous approach: through

another enzyme, they try to inhibit the natural degradation of cAMP. This

method is doomed from the start because with the pre-existent low level of

this enzyme, the effect of the new medications will be limited. The inhibition

may, at best, maintain the existing levels. This is contrary to the potentially

successful straightforward increase through histamine.

These allegedly novel drugs are, in fact, very old as they mimic the effect

of the half-a-century-old theophyllines. The best illustration of the efficiency

of theophyllines is given in the work supported by a research grant from the

Agency for Healthcare Research and Quality. It says that theophyllines,

“which once dominated asthma therapy (63% of visits in 1978), were used in

only 2% of visits in 2002.”49

By looking towards the increase of the enzyme cAMP in the development

of an asthma medication, allergists acknowledge its prime role in allergic

inflammation. Of most peculiar interest is that the development of these

drugs is headed by L. Lichtenstein, who had described in the late ’60s and in

the ’70s the pathway that leads to cAMP activation—H2-receptor activation.



The logical conclusion is: the choice of less efficient ways of asthma manage-

ment is intentional.

Somebody thoroughly calculated the potential fiscal loss from the use of

histamine and its synthetic versions. The theoretical data on histamine’s

possessing immune-, neuro- and gene modulation properties had “impru-

dently” been entered in theoretical sources through the unsuspecting ’60s,

’70s and ’80s. It provided the solid basis for the clinical employment of hista-

mine in chronic immune and neurological diseases. Open and double-blind

clinical trials confirmed histamine’s efficiency in patients with allergy,

asthma, and certain neurological disorders. Perversely, these trials spelled out

histamine’s potential negative effect on the drug market. By the nineties, this

“blunder” and its possible financial repercussions were fully realized. This

explains how the information on histamine has been kept virtually out of the

reach of doctors and patients.

ENDNOTES 1. S. Romagnani. The role of lymphocytes in allergic disease. JACI 2000;105:399-4082. A. Kaplan, ed. Allergy, 1985, pages 8 and 1763. JACI 1995;95:7874. Harrison’s Principles of Internal Medicine, 1987, p. 3315. H. Wada et al. Is the histaminergic neuron system a regulatory centre for the whole-brain

activity? Trends in neuroscience 1991;14:415-8.6. L.Stunciu. Immunomodulation by histamine. Ann.Biol.Clin. 1990;48:623-57. Brondes et al. Histamine as an intracellular messenger. Biochemical Pharmacology 1990;40:1677-81.8. L. Yan et al. Histamine… Pharmacogenetics 2000;10:261-6,9. R. Rocklin et al. Characterization of the human blood lymphocytes that produce a histamine-

induced suppressor factor (HSF) Cellular Immunology 1980;51:226-23710. See for example The Olivieri Report published by the Canadian Association of University

Teachers, Lorimer, 2001, in which it is urged that the government pass legislation protectingresearch integrity, and thereby patients.

11. Dorland’s Illustrated Medical Dictionary, 27th edition, p. 768.12. D. Goldblast True Believer Bayard Taylor Horton. Seminars in Neurology 1988;8:339-34213. S. Diamond et al. Treatment of Intractable Cluster, Headache 1986;26:42.14. M. Rocha e Silva. Handbook of Experimental Pharmacology 1966;18/1:89915. M. Cirstea. On the mechanism of desensitization by histamine. Rev. Roum. Physiol. 1971;

8:253-25816. JACI December 1997 p. 81617. J-P Girard. A double-blind study of triplex-histaglobin in the treatment of grass pollenosis.

Praxis 1989;78:62-518. R. Lockey et al. Allergies and Allergen Immunotheraphy, 1999, second edition19. L. Stanciu. Immunomodulation by Histamine, Ann. Biol. 1990, 48, 623-25); and see also C.

Burtin et al.. The New England Journal of Medicine, Letters to the Editor, March 1983, 591-220. F.L. Pearce. Editorial: Biological effects of histamine: An overview, Agents and Actions

1991;33,1/2:4-6.21. FDA reviews antihistamine mouse study. FDA Talk Paper 1994; May 17:2



22. E. Vannier et al. Histamine Suppresses Gene Expression and Synthesis…. J.Exp.Med.1991;174:281-284.

23. D. Takeuchi et al. Histamine alters gene expression… JACI 2001;107:310-424. JACI, 1990;86:589-68625. R. Leurs et al. Molecular pharmacological aspects of … Pharmacology & Therapeutics

1995;66:413-46326. S. Holgate. The epidemic of allergy and asthma. Nature 1999;402:Suppl:B2-B427. B. Zweiman, M. Rothenberg. Beyond Our Pages. JACI 2002;109:72828. J Clin Invest 2001;108:1865-7329. Allergy 1985, p. 18430. J.A.Grant et al. Histamine-releasing factors and inhibitors: historical perspectives and possible

implications in human illness. JACI 1991;88:683-93 31. R. E. Rocklin, D. K. Greineder, K. L. Melmon. Histamine-induced suppressor factor… Cell

Immunol 1979;44:40432. P. Kuna et al. IL-8 inhibits histamine release induced by histamine releasing factors…JACI

1991;87:20733. P.Kuna et al. Chemokines of the alfa, beta-subclass inhibit human basophil’s responsiveness to

MCAF/ MCP. JACI 1995;95:574-834. JACI 2001:108:S147-33635. Allergy 1985 p.183-536. E. Sercarz, & U. Krzych. The distinctive specificity of antigen-specific suppressor T cells.

Immunology Today 1991;12:110-11737. R. Rocklin et al. Generation of antigen-specific suppressor cells… N.Engl.J. Med,1980;302:1213.38. M. White The role of histamine in allergic diseases, JACI 1990;86:605.39. JACI 2001;108:S17840. I. Elenkov et al. Histamine potently suppresses human IL-12 and stimulates IL-10 production

via H2 receptors. The Journal of Immunology, 1998, 161:2586-259341. R. Leurs et al. Molecular pharmacological aspects of histamine receptors. Pharmacology and

Therapeutics. 1995;66:413-42. E. Vanier et al. Histamine suppresses gene expression and synthesis of tumor necrosis factor via

histamine H2 receptors. J.Exp. Med. 1991;174:281-443. H. Bourne, L. Lichtenstein, K. Melmon et al. Modulation of inflammation and immunity by

cyclic AMP. Science 1974;19-2844. B. Horton. Chronic progressive retrobulbar neuritis… Boswell Hosp Proc 1979;5:4-2045. Allergy 1985:18846. E. Vannier et al.. Histamine Suppresses Gene Expression and … J.Exp.Med 1991;174:281-28447. A. Kaplan, ed. Allergy 1985. p. 679.48. Focus On The Literature 1996;15:949. R. Stafford et al. National trends in asthma visits and asthma pharmacotherapy, 1978-2002. JACI

2003;111:729-3550. The Editor’s Choice. JACI 2002;109:58051. A Mazzoni et al. Histamine regulates cytokine production… J Clin Invest 2001;108:1865-73



PART TWO

CAUSES AND TRIGGERS IN ALLERGY

CAUSE VS. TRIGGERSDifferentiation between causes and triggers in allergy is of prime importance.

Triggers vary from patient to patient, while causes create the background for

triggers to ignite chemical changes. Without the underlying failure of the

immunocompentent cells, which is the cause, triggers are harmless. Proof is

found in the fact that exposure to the same allergens produces symptoms only

in some of us. Thus, even during the worst allergy season in North

America—ragweed time—there are many people who do not experience a

single sneeze or itch.

The true causes of allergies were described, although vaguely, in the ’70s

and ’80s in a few theoretical textbooks and periodicals, and they were the

subject of occasional reports at symposia. Causes of allergy were even taught

at educational courses for medical postgraduates. Although the material was

never presented systematically, it was responsible for progress in the field of

allergy research. Sadly, these discoveries about causes were not further devel-

oped or applied clinically. Today, medical students are not generally taught

what cellular defects are the basis of allergy symptoms. Through the nineties,

the descriptions of causative mechanisms were reduced to a mere trickle and

finally stopped. This means, that even though the known causes of allergy


were not in any way scientifically disproved, there was no factual reason to

ignore this information and no new findings that rendered the known causes

obsolete—the most important information for a student of allergy was

simply left out of the new textbooks, and excluded from all publications and

gatherings of allergists.

In the absence of true knowledge false claims become inevitable. Today’s

allergy medicine exclusively connects allergic diseases to allergens, that is, the

triggers, whereas the cellular defects, without which no allergen could provoke a

chronic allergic condition, are never named as the key

factors. Textbooks present allergies as reactions to

harmless substances, or a hypersensitive state acquired

through exposure to a particular allergen, or a disorder

in which the body becomes hypersensitive to particular

allergens. Such descriptions distort the fact known to

the majority of allergy sufferers: allergy symptoms may

arise in the absence of allergens. As a result of the

distortion, medicine fights triggers and tries to control

the secondary hypersensitivity processes provoked by

them. It never considers re-activation of the originally

hypoactive immune mechanisms in order to correct

the condition.

THE REACTION OF THE NORMAL IMMUNE SYSTEM TO AN ENEMYTo understand a deviation from the norm, one should be familiar with the

norm. Therefore, to understand how the immune system of an allergic person

responds in an exaggerated way to a non-offensive surrounding, one should

know the basis of how a healthy body responds to external triggers.

Every day, numerous proteins, viruses, microbes and various foreign

substances penetrate the body through the airways, the digestive tube and the

skin. All of them are a part of the flora and fauna that surround us. The scien-

tific term for a stranger is antigen. The Greek root gennan means to produce:

antigens are able to produce an immune response against them. The immune

system organizes its chemical defense against those antigens, which it regards

as potentially dangerous. This is how it happens:

Antigen-presenting dendritic cells bind to the intruder and physically

deliver it to T-cells and at the same time, transmit their chemical messages.


The true cause of

allergy is the geneti-

cally preconditioned

hypoactive functioning

of the protective part of

the immune system.

Environmental factors

are triggers that may

only provoke or accel-

erate the pre-existing

cellular malfunctioning.


The name of T-cells comes from thymus, the gland

from which they are derived upon maturation, the

T-cells start to release cytokines—their chemical

orders to other participants. T-helper cells immedi-

ately launch the defensive operation by dispatching

their own chemical instructions to B-cells, the

“factory” of defensive proteins, which arise out of

bone marrow (hence the name B-cells). B-cells go

through a transformation stage and generate protec-

tive proteins called antibodies or immunoglobulins.

The medical sign for Immunoglobulin is Ig, and it is

followed by one of the four letters denoting its kind—

IgA, IgD, IgG, IgM. Actually, antibodies are cellular

receptors for antigens, and like all receptors, they

interact with the antigens—bind to them. Thus, the

primary function of immunoglobulin molecules is to

bind to the antigen and inactivate it. Each antibody

interacts with one specific antigen. For instance, an

antibody to the virus causing measles is different from

the antibody to the chickenpox virus. An antibody fits

its antigen in the way a leather glove fits the hand.

In medical language, we use the metaphor of the lock

and the key: an antigen and its antibody match each

other like a key fits in its specific lock. In other words,

antigens are specific material triggers in response to

which the body forms specific antibodies.

It takes 3 to 14 days after the first exposure for the

antibody to fully develop and be able to neutralize the

antigen. As a rule, if another encounter with the same

antigen happens before the formation of the anti-

bodies is complete, the host is still defenceless. This

maturation process makes it clear why we fall ill with

infections upon our first exposure to a microor-

ganism, whereas during its second intrusion, the

antigen is inactivated. The presence of those specific

antibodies left from the first encounter and/or the

memory of the immunocompetent cells, which know

Causes and Triggers in Allergy 71

Antigen is a substance

able to trigger an

immune response. A healthy

body defends itself from

dangerous antigens by

forming two major cate-

gories of specific proteins—

cytokines and antibodies.

Cytokines are chemical

instructions of T-cells to

other cells: what chemicals

to produce and in what

amount. An instruction to

produce antibodies is one of

the many messages of

T-helpers to the antibody-

producing B-cells.

Antibodies need 3–14 days

to develop after the first

encounter of the host with

the antigen, after which

they are ready to inactivate

those antigens in subse-

quent encounters. Proteins

acting as antibodies are

called immunoglobulins, and

the sign for them is Ig. The

chemistry of each antibody

is compatible with the

chemistry of the challenging

antigen. Antibody formation

is a protective act of a

healthy immune system, and

like any immune process, it

is supervised by T-cells.

T-helpers “help” in cytokine

and antibody production,

while T-suppressors imple-

ment control over the whole

process. Antibody formation

is a process secondary to

the original T-cell activation.


how to organize a defence, also explains why certain infections do not occur

twice.

In the normally functioning immune system, during the course of anti-

body formation, different T-cells perform different functions, but all of them

are protective. Thus, the role of T-helpers is to render “help” in the produc-

tion of antibodies and cytokines, while T-suppressors implement the qualita-

tive and quantitative control of the whole process, mainly by secreting their

own cytokines.

THE REACTION OF THE IMMUNE SYSTEM TO ANTIGENS IN ALLERGYPATIENTSAll textbooks describe the details of how the immune system of an allergy

patient responds to specific triggers. We will do this too, but will emphasize

the roles of the participating cells. Our task is to see what happens when a

substance, harmless for a healthy immune system, becomes an instigator of

an unnecessary immune response and allergic symptoms.

The important point is that genetically compromised immune cells in an

allergy patient are unable to tell a harmless stranger from a dangerous one,

and thus the number of specific triggers becomes limitless. Because of the

primary T-suppressor hypoactivity, the poorly controlled T-helpers become

disease-promoting. They generate pro-disease chemistry and become

internal enemies by facilitating the formation of unnecessary IgE antibodies

by B-cells. IgE antibodies are formed to benign strangers and therefore

behave differently than the protective antibodies would have done.

T-suppressors still preserve their commanding role, but because they are

compromised to begin with, their innate weakness prevents them from

adequately controlling the reactions.

The stages of antibody formation are similar in health and in allergy:

■ antigen presentation to T-cells by their specialized subordinates named

antigen-presenting cells;

■ activation of T-cells and their production of cytokines to conduct the

immune response;

■ messages from T-cells to B-cells to produce matching antibodies and to

other cells to induce certain cytokines.

The differences from the norm are:

■ the enemy could be anything;

■ the unusual IgE antibodies are not protective.



Similar to protective antibodies, IgE antibodies need

time to develop. Upon that, they settle down on mast

cells and basophils and wait to ambush the trigger.

When the antigen shows up again, the Y-shaped IgE

antibodies stick to it and form an inseparable antigen/

antibody complex. To immobilize the offender, the

adjacent complexes start to clump together. As we

learned earlier, each mast cell contains up to 200 hista-

mine granules. These cells are very sensitive even in

health. In allergy patients, their sensitivity is exagger-

ated and is one of the most determining factors of these

diseases. The chemical events that take place on the

outer membrane of the mast cells lead to perforation

of the granules, a process medicine calls degranula-

tion. Histamine, which is the only pre-stored allergy

mediator, leaks through the pores of the cell

membrane and starts the allergic reaction. Any itch,

sneeze or cough is a manifestation of a local spill.

The synthesis of inappropriate chemistry and anti-

bodies by T-helpers means that they have abandoned

their role as immune protectors; thus we are left with

T-suppressors as our only defenders in allergy. Even

being weak, they try as much as they can, to control

the processes of improper chemical release and anti-

body production. If an allergy patient does not die it

is only due to the efforts of the weakened but faithful

suppressors which do not stop in their work to restore

the original balance. Therefore, the disappearance of

T-suppressors from all medical sources on allergies is

as odd as talking about the solar system without

mentioning the sun.

WHY DOES AN ALLERGEN-TRIGGERED REACTIONLAST EVEN IN THE ABSENCE OF THE TRIGGER?The half-life of IgE antibodies is 2–3 days, after which

they start to degrade. Knowing this, it is logical to

assume that once the originally triggering antigen is


Genetically malfunc-

tioning T-cells may

mistake any harmless

substance for an enemy

and order the formation

of inappropriate chem-

istry that includes anti-

bodies of the IgE type.

Antibody formation in

allergy patients is similar

to the process in healthy

people. However, unlike

protective antibodies,

IgE antibodies do not

neutralize the trigger but

lock with the antigens on

the surface of mast cells

and basophils. These

cells are hypersensitive

in allergy patients, and

the presence of the

unusual antigen/antibody

complexes leads to an

exaggerated release of

histamine and the subse-

quent disease-promoting

chemistry. The sites of

the highest spill cause

allergy symptoms.

However, IgE antibody

formation is the event

secondary to the activa-

tion of the malfunctioning

immunocompetent cells

and therefore cannot be

considered the cause of

allergic diseases.


gone, the allergic reaction unleashed by it would abate after 2–3 days. This is

exactly what happens, for instance, with hay fever patients: the end of the

pollen season means the end of their allergy symptoms. This, however, is not

so in too many instances. A reaction ignited by a certain trigger continues and

may even intensify in its absence. In other words, the

antigen plays the role of the car starter, and after that,

the motor runs on its own. What keeps the motor

running becomes most important in view of the fact

that allergy medicine focuses on allergens and IgE anti-

bodies. The explanation is found in the excessive

leakage of the disease-promoting chemistry orches-

trated by T-cells. In chronically ill allergy patients,

liberation of histamine is continual because the weak

H2/3 receptors are unable to control it. It is accurate to

say that histamine is the central event that opens

Pandora’s box containing numerous disease-

promoting chemicals. This chemistry is the biological

marker of immune dysfunction, while IgE antibodies

are merely a part of this chemistry and the conse-

quence of the dysfunction. The severity of the symptoms

depends not on the IgE count but on the degree of the

H2/3-receptor weakness and the resultant pro-disease

chemistry. This explains why the disease may continue

even when the IgE antibodies have degraded.

NONSPECIFIC TRIGGERS IN ALLERGYSo, an allergic reaction, provoked by specific allergens, may continue in their

absence, moreover, it may even start without any allergen! A paradox: how can

a disease which starts and/or without an allergen be called allergic? The

human mind tends to choose the easiest way in its comprehension of events

and their causes, therefore we easily accept as symptom-causing those triggers

that can be seen, touched or at least imagined—specific triggers. Still, a lot of

triggers are not proteins, and it is more difficult to comprehend that allergy

symptoms may result from sunlight, weather changes, emotional upheaval, phys-

ical exertion, electromagnetic fields, or physiological body changes such as sleep

or awakening, pregnancy, menstrual cycle, etc. The reactions to the same event

vary in different people. For instance, some may feel better after exercising or


Allergens only trigger

symptoms in those

who have cellular

defects related to H2-

receptor deficiency and

T-suppressor weakness.

These inner immune

defects allow the disease

to continue even when

the triggering antigens

are no longer present,

and the IgE antibodies

have degraded. This

supports the view that

cellular malfunctioning

is primary, and that

IgE antibodies are

secondary in allergies.


making love, while in others, these may provoke or

aggravate symptoms. Such triggers are called nonspe-

cific. Some of them may be determined or suspected

due to the cause-and-effect connection and the

commonality of allergy symptoms in certain circum-

stances. Sometimes, just understanding what provokes

the symptoms may help patients overcome the

temporary suffering because they may be able to avoid

or reduce the occurrence of certain situations.

However, in many allergy patients, symptoms may be

the result of nonspecific phenomena that cannot be

pinpointed and, therefore, cannot be controlled in

view of their inexplicable spontaneity and lasting

nature. Practically any patient may experience aggra-

vation without any evident reason. This may occur at

any time of the day, season, or life period and differ

from patient to patient. Nonspecific influences are

unpredictable, erratic, highly individual and mostly

unavoidable even if one understands that they

provoke allergy symptoms. They do not lead to the

production of specific IgE antibodies but only activate

T-cells and induce the release of pro-disease cytokines and mediators that

involve other immune cells.

It is vital to recognize the existence of both specific and nonspecific trig-

gers, as well as to understand that allergy symptoms may arise without any

identifiable antigen or phenomenon. You may wonder why it is so important.

The answer is: as long as specific material triggers are not the only ones

causing allergic symptoms, focusing on them alone should not be the sole

objective in the management of allergy patients—as is now the case.

THE ROUTES OF NONSPECIFIC REACTIONS Reactions in response to immaterial nonspecific triggers—temperature

changes, vibration, stress or the body’s hormonal changes—are not all related

to an allergen. Although medical textbooks mention the existence of allergic

reactions to nonspecific triggers, when it comes to the explanation of the

processes that underlie allergic reactions, the descriptions are limited to

IgE-related mechanisms. However, what is known about the physiology of


An ailing immune

system may over-

react to nonspecific

triggers, which can be

equally responsible in

provoking allergic symp-

toms as IgE-producing

identifiable triggers.

Both make T-cells

generate disease-

promoting cytokines and

mediators. The very

fact that a nonspecific

trigger may produce

symptoms proves that

the core of the problem

lies not with the trigger

but with the inherent

defects in the immune

system.


cells provides a clear explanation of reactions that are not related to specific

allergens. This is what happens during nonspecific reactions.

It so happens, that the immune and nervous systems are interrelated.

Nothing in the body acts in total isolation. T-cells, mast cells, dendritic cells,

and neurons all live and work in tissues close to one another. They are washed

by each others’ secretions and often have similar receptors responding to the

same stimuli. All four groups of cells possess histamine receptors and, there-

fore, respond to its overspill. Any of the four may unleash that reaction.

For instance, something as simple and common as an environmental

change from warm to cold may affect sensory nerve endings in the skin,

causing their chemistry to change, and in doing so involves mast cells that

start to leak with histamine. The reactions that follow are similar to the ones

provoked by allergens like ragweed. A local skin exposure to a low tempera-

ture may increase a systemic reaction, especially in the areas of the highest

histamine spill. So, the patient may have a skin itch or get the hives, have a

stuffy nose, or an asthmatic attack, with no allergen in the picture. Cold may

directly activate mast cells, which are in abundance in the skin and airways,

and their profuse spill of histamine will start a reaction. Dendritic cells in the

skin may also react to cold, and their changing chemistry will also activate T-

cells, followed by the engagement of the main histamine producers, mast

cells. Finally, T-cells may become directly activated, as they are also found in

large numbers in the skin and respiratory tract. The compromised T-helpers

respond by producing disease-promoting cytokines and mediators similar to

those observed in classical, allergen-provoked reactions. Histamine produced

de novo by the participating cells, amplifies the disease process started by the

leaking mast cells and basophils. The participating cells become the source of

numerous diseases-promoting cytokines and mediators, which, in turn,

contribute to further liberation of histamine and histamine-induced chem-

istry. This all leads to allergic symptoms characteristic of that organ or tissue,

in which the reaction takes place. Thus, an asthma attack or a stuffy nose,

upon exposure to low temperatures, is rather common even though often

misdiagnosed as a cold.

Also analogous are the processes that underlie allergy symptoms

provoked by the body’s physiological changes. Here is an example. Awakening

in the morning is accompanied by the activation of certain departments of

the central nervous system dormant at night. That involves those brain areas

that regulate the production of hormones needed by the body for its adapta-



tion to the working day after a night’s sleep. The variety of hormones involved,

as well as their levels in the blood, change according to those demands. The

T- and mast cells found in large numbers are able to respond because they

accept communications coming from this changing chemistry. If, however,

these cells are faulty by nature, they overreact to the chemical messages with

a histamine overspill and make matters worse by transmitting their alarm

reaction to the peripheral structures via the histaminergic system. This

explains why some patients have early-morning sneezing attacks or difficulty

breathing upon awakening. These changes are, by the way, unpredictable in

each individual.

The T-cells, mast cells, dendritic cells and nerve cells, all become engaged in

the same reaction, regardless of which one of the group initiated it. They work

together as a well-trained army. Their activation by any non-specific stimulus,

be it external or internal, provokes a histamine overspill. Its continuous leakage

maintains the process and chemically involves all of them. While a nonspecific

reaction bypasses the stage of specific IgE antibody formation, the final

outcome of events remains very similar to a reaction triggered by an allergen.

Although reactions to nonspecific trigger show that the presence of IgE anti-

bodies is not a reliable indicator of allergies in a person, contemporary allergy

medicine insists on focusing on IgE antibodies and, therefore, fails to explain all

those commonly observed deviations from the “standard.” Sometimes these are

even fatal reactions to peanuts, for example, in babies who have never been

exposed to peanuts and, therefore, cannot have IgE antibodies to these nuts. The

immune system supposedly only responds to a repeated exposure, once

specific IgE antibodies have formed. The fact that babies may die during such

a very first exposure does not fit the accepted concept, and leads to the

unfounded search for the mother’s consumption of peanuts during her preg-

nancy or breastfeeding, even though we know that IgE antibodies do not pass

through the umbilical cord and have not been found in breast milk.

There is an even more impressive example: the very first bee sting received

in life can be fatal. The IgE-based concept cannot explain this phenomenon.

Also vague are the explanations of the processes that underlie reactions due

to such nonspecific factors as cold, sun light, physical exertion, etc., although

the ability of these phenomena to provoke symptoms has forced allergists to

recognize their existence and they even have a name for them, namely phys-

ical allergy. In all such cases, the cause is genetically predetermined-readi-

ness of mast cells/basophils to release histamine.



The inability to explain what processes underlie the

symptoms induced by nonspecific triggers created

their artificial classification as nonimmunologic, in

contrast to the immunologic processes induced by

specific triggers. The gross inaccuracy of this division

is obvious—all reactions with the participation of

major immune cells cannot be anything but immuno-

logic.

THE GREY ZONEPoor comprehension of the mechanisms of diseases of

hypersensitivity by the medical profession is especially

evident in the area that remains a grey zone today. Not

only does the subject create heated discussions, it even

leads to litigation initiated (and often lost) by patients.

Let us consider this important and confusing area.

The grey zone is represented by substances that, on

one hand, have a chemical formula and thus materially

exist, on the other, no antibodies to them have been

detected. The prejudices ruling orthodox allergy do

not permit recognition of these triggers because no IgE

antibodies are found in such instances. Among these

triggers are impurities, unwanted substances in the

environment that may provoke negative responses.

They include not only unpleasant fumes but also the

gentle aromas of perfumes and other products. All

these triggers are classified by allergy as air pollutants

or irritants.

Having created the new term—irritant—allergists

fail to explain the mode of action of irritants. What

do they irritate? Don’t they irritate the same receptors

on the same cells that allergens do, since there is no

other way to change the cellular chemistry than

through receptors? You may accuse me of splitting

hairs and ask: Does it matter what terminology allergists use, if the only

thing that matters is that patients suffer and should get treatment? It does

matter. Such misclassification harms allergy sufferers. I will show you why.


Nonspecific triggers

stemming from body

chemistry or an environ-

mental physical factor

may cause a response of

hypersensitive immunity

similar to the one

caused by specific trig-

gers. The response

always starts with an

excessive histamine

release from mast cells.

The similarity of recep-

tors, the cellular ability

to produce and respond

to the same chemicals—

histamine in particular—

and the shared

chemical-electric

“language” of communi-

cation explain the simul-

taneous engagement of

nerve cells and immuno-

competent cells in

allergic processes. No

matter what triggers

these reactions, and

what cells get activated

first, the reactions are

immunologic, since

major immune cells and

their products take part

in them.


Modern allergy medicine recognizes only specific IgE antibodies as the

unarguable proof of allergy. Its position is that when the diagnosis is needed for

legal purposes, the presence of IgE antibodies must be documented. Therefore,

those who initiate litigation claiming that their sickness resulted, for instance,

from staying in a certain polluted building will not be considered sick if IgE

antibodies to suspected pollutants are not found. The conclusion will be: there

is no evidence that these patients have an allergic disease. Nothing in the sealed

building where they work could produce their symptoms. Especially so, if the

symptoms are not something as unquestionable as asthma, but are of a less

demonstrative, nonspecific nature, such as headaches, dizziness or fatigue.

There is now good news for those who are sensitive to cigarette smoke: finally,

the IgE antibodies to tobacco have been isolated and may thus become

irrefutable proof of allergic illness being triggered by tobacco smoke. However,

the remaining sufferers may still find themselves labeled as hypochondriacs

because the existing standard consensus is: those symptoms are just a state of

mind only. The complaints are viewed as purely psychological. The fact that the

constant contact with the irritant could have damaged the inherently suscep-

tible immune and nervous systems is not accepted, and no certificate will be

provided even to those who become outright incapacitated.

The absence of laboratory evidence of specific IgE antibodies provides a

loophole for the patient’s employer, supervisor, or building owner. It relieves

them of liability for the conditions in which the sufferer works or lives. For

instance, it is easier to prove an allergy to cockroaches than to the pesticide used

against them in your apartment, since the cockroach antibodies are identified in the

traditional manner. The search for specific IgE antibodies remains the guiding

criterion when providing patients suffering from diseases of hypersensitivity

with certificates confirming their illness. Allergists are adamant in naming

diseases of hypersensitivity allergies. Had lawyers known medicine, they could

have easily exposed this concept. The best argument of the groundlessness and

hypocrisy of the position taken by standard allergists is their ready recognition

of the existence of occupational asthma and allergies which they agree result

from exposure to pollutants, with no specific IgE antibodies found on testing.

THE ARTIFICIALITY OF CONVENTIONAL CLASSIFICATIONThe division of allergic diseases into the so-called “immunologic” (allergen-

related) and “nonimmunologic” (provoked by physical phenomena and irri-

tants) is unscientific. I will give two examples. The already mentioned



cigarette smoke used to belong to the group of nonspecific irritants. Then IgE

antibodies were identified, and this permitted re-classification of smoke into

an allergen. Another example is latex. Opinions about latex as an allergen

have recently been challenged. Latex allergy used to be limited to latex gloves,

and medical professionals who wore them were considered to be a risk group.

Not long ago, it was found that hypersensitivity to latex was also common in

other groups of the population that never wore latex gloves. Toys, pacifiers,

tires and other products of rubber are among the many sources of latex. Latex

particles are found everywhere, and lately, latex has been relabeled by aller-

gists as a pollutant. Has there been an observed physical change of the routes

through which latex causes an allergic reaction? No. Will it change anything

in the treatment? Absolutely not, since it has always been limited to avoid-

ance. So, why is the strict classification so badly needed? This game-playing

with real, biological events merely served to conceal the allergists’ inability to

explain and treat allergies in general, specially when it comes to irritants.

The cellular processes that lead to symptoms are never clarified in text-

books and only occasionally touched upon in periodicals. The focus is on

triggers. Moreover, true science is further distorted when the symptoms to

nonspecific triggers or irritants are presented as nonimmunologic even though

allergy symptoms are the result of the involvement of immunocompetent

cells. Strangely, allergists fiercely fight to keep patients with such “nonim-

munologic” diseases in their purely immunologic practice.

The truth is that in allergy, irritants or pollutants work through the same

mechanisms as specific and nonspecific triggers. Upon inhalation or touch,

irritants may:

■ produce a direct effect upon T-cells, and these start to generate disease-

promoting chemistry;

■ directly affect dendritic or mast cells and make them leak with histamine

and histamine-induced disease-maintaining mediators;

■ affect sensory nerve endings, and the changing chemistry of nerve cells may

involve immune cells.

The subsequent reactions are more or less similar: activation of mast cells/

basophils with their exaggerated release of histamine and histamine-induced

chemistry. This is exactly what a combined team of scientists from England and

Turkey said in an article on asthma: “…air pollutants... may modulate airway

disease, such as asthma, by increasing the release of pro-inflammatory mediators.”1



ALLERGY AND BORDERLINE DISEASES The common origin of allergies with neurological

symptoms is proven by their frequent coexistence. A

certain food can provoke a headache and itchy skin, so

does stress, while hay fever sufferers often experience

fatigue and headaches. Even those allergists whose

minds are made up on allergens being the only trig-

gers, have no choice but to recognize that migraine, a

neurological symptom, is common in allergy patients.

The prevalence of symptoms related to the nervous

system and the absence of allergy symptoms not

necessarily indicate the purely neurological or

immune origin of the disease. It may result from the

chemical imbalance in either type of these cells. The

nature of these cells to depend on each other’s chem-

icals rests on the logic of the unity of the body as a

whole mechanism, in which the malfunctioning even

of a small part affects the work of the whole structure.

Histamine is not only the key mediator of allergies but

also a major neurotransmitter. Therefore, in the

absence of organic diseases, a great number of symp-

toms such as headaches, dizziness, fatigue, anxiety

or depression, vague arthritic-like joint or muscular

pains (e.g. fibromyalgia), abdominal cramps, bloating,

diarrhea, constipation (e.g. irritable bowel syndrome),

frequent urge to urinate, etc., may well be signs of a

condition related to histamine dysregulation. Even if

only allergic symptoms exist at a given time, the

involvement of the neighboring neurons is possible at

any stage. These histamine-provoked symptoms are

manifestations of allergy-like processes in the central nervous system. At

present, each symptom that accompanies allergies is often diagnosed and

treated as a separate disease. The name of a disease that has become so

common—chronic fatigue and immune dysfunction syndrome (CFIDS or

CFS)—comprises the symptoms of both nervous and immune systems, and

may serve as an example of their interrelation.


There are triggers,

reactions to which

are not classified by

conventional allergy as

immune-related because

no IgE antibodies to

them are found. The

term used for such trig-

gers is air pollutants or

irritants. Poor under-

standing of the under-

lying cellular processes

prevents modern allergy

from explaining the

immune processes

invoked by “pollutants.”

Allergists call the

reactions provoked

by pollutants as “non-

immunologic” in

contrast to “immuno-

logic” IgE-mediated

allergies. The accepted

IgE-based dogma is

simply incorrect because

all reactions, in which

immune cells and their

products are engaged,

are immunologic.


HISTORIC EXPLANATION OF WHY ALLERGY PRACTICE IS BASED ON ALLERGENSLet us trace how it happened that allergens, just one

group of numerous triggers, have inappropriately been

proclaimed as the cause of allergic diseases. The word

allergy was first introduced in 1906 by the Austrian

pediatrician Clemens von Pirquet whose name is

connected in medicine with the diagnostic skin test for

tuberculosis. The term comes from two Greek roots:

allos—different, that is, a condition differing from the

norm, and ergon—work. Thus, allergy simply means an

abnormal body reaction. Pirquet called foreign

substances capable of producing a reaction different

from norm allergen. Both in allergen and antigen, the

Greek root gennan means to produce. These words are

roughly synonyms in the context of allergic diseases.

Lay persons use the word allergen, while the scientific

term is antigen.

More than half a century passed before allergy took

roots as a branch of medicine. Its practitioners were

unsuccessfully fighting for scientific recognition until

the ’60s. The reasons for their rejection had to do with

the way medicine changed since the time of Pirquet—a change that was not

the best. Pirquet, who unknowingly started allergy as a discipline, had made

his greatest discoveries mostly due to clinical observations, which he consid-

ered to be the most important part of medicine. Traditional medicine removed

itself from Pirquet’s principles and started to rely on laboratory proof more

and more exclusively. At present, phenomena that cannot be proved by testing

are treated as if they were nonexistent. Therefore, even though abnormal or

allergic reactions were undeniable, scientists who studied them, searched for

material proof of their existence. Without laboratory proof, allergy did not

have a chance to be established as a legitimate part of internal medicine. The

unpredictability of allergy symptoms was not helpful in recognizing the exis-

tence of this disease. In 1966, the brilliant guess made by Pirquet and his

colleague Bela Schick of “collision of antigen and antibody” got confirmation:


Immunocompetent

cells and nerve cells

share certain receptors

and respond to and

release the same chemi-

cals. They become

inevitably involved in

the reactions started by

either kind. This explains

why allergy symptoms

are often accompanied

by neurological symp-

toms. Histamine, as the

central mediator in

allergy and a governing

neurotransmitter, can

become the cause of

both allergy and neuro-

logical symptoms if

produced in exaggerated

amount.


unusual specific antibodies, IgE, were found in the host’s body and declared to

be the hallmark of allergic diseases. Following this discovery, medicine

proclaimed that only the presence of IgE antibodies confirms allergies.

At that time, the scarcity of knowledge in this field justified such a decla-

ration. Since then, accumulating information made it clear that the notion of

allergy was much wider than the original, solely allergen-dependent theory,

and that non-specific factors could also provoke allergy symptoms. This

simply meant recognizing that patients might have allergy symptoms without

showing the antigen/IgE antibody complex on mast cells. Their symptoms

could equally well be the result of activation of their hyper-responsive

immune mechanisms. At this point, allergy should have embraced the new

data and reconsidered the stance that only IgE antibodies can be the single

indicator of allergies. It did not happen. As history teaches us, the moral and

ethical standards of those who have already come to power often become

entrenched, and the bearers of new knowledge always seem to endanger those

in power. To preserve their positions of authority, the supporters of the

allergen/IgE antibody-based concept turned it into a cult, they started to

conceal the existing findings and created a new hypotheses, which are not in

agreement with observed facts.

Proof that this concealment and distortion are intentional can be found in

the entries on the word allergy in medical dictionaries: “the original meaning,

now obsolete, includes all states of altered immunological reactivity, immunity

as well as hypersensitivity,” allergic reactions to cold, heat, light, etc. are named

physical allergy.2 Occasionally, the most renowned scientists dare publicly to

recognize that the term allergy “has become corrupted and is now frequently

used synonymously with IgE-mediated allergic disease,” whereas “some

allergic diseases… develop through Ig-E-independent mechanisms”3

However, these very scientists still continue to disseminate the IgE-based

doctrine. Today, this dogma has become the Procrustean bed that all mecha-

nisms of allergy must fit into, and the true causes are simply cut off because

they do not fit—as the legs were cut off from people who did not fit the bed

created by the ogre Procrustos in the Greek myth. The best proof of the power

of the allergen-based concept is the universal acceptance that allergies are

caused by cats, mites, pollens, etc., and that by eliminating, avoiding or

destroying these, one gets rid of the disease.



ELIMINATION AS THE MAIN TREATMENTIf you are an allergy patient, your doctor has definitely instructed you to thor-

oughly vacuum your bedroom, strip carpets off the floors, seal your mattress

with a plastic cover and regularly wash your pet with special soaps. You prob-

ably also received a list of no-no food products. You may have stopped

wearing perfumes and lotions, got rid of your dog/cat, started buying foods

only from Health Food stores and studying the labels on food packages for

preservatives. Has it worked? Most probably not. It may even be that, despite

all these measures, the symptoms are growing worse. The reasons are simple:

the overwhelming majority of allergy patients present with a mixture of

antigen-specific and non-specific symptoms. Washing and vacuuming may

reduce the effect of potential allergens and, at best, somewhat mitigate the

course of the disease but never mend the damage in the immune cells that

bring on the symptoms. Being unchecked, the defect tends to worsen.

The elimination procedure itself is often difficult to implement. For

example, one cannot achieve complete sterility in the bedroom and make it

free of dust mites. Or if you do not wear lotions or perfumes, those who

work with you may not conform to your request not to use them. Your

neighbor in the movie theatre may be a pet owner, and your hypersensitive

airways feel the pet’s dander on his jacket. Few tiny particles of pollen that

percolate through doors or windows may be enough to produce itchy eyes or

an asthmatic cough. Even in the absence of smoke, an allergy patient may

develop a reaction to the clothes that carry a faint tobacco smell. We do not

live in a vacuum, and potentially dangerous encounters with triggers are

unavoidable.

In addition to the difficulty of eliminating the triggers, the expediency of

it is questionable. Many authors suggest it may even do more harm than

good. For instance, a study conducted on nursing mothers on an elimination

diet as compared to those on a regular diet indicated that the babies breastfed

by the mothers of the first group had an increased “prevalence of eczema and

allergy,” and that “infant food allergen exposure via maternal intake produces

tolerance rather than sensitization”4 In this respect, it would be interesting to

know the opinion of allergists on the Indian and Thai cuisines with their high

use of nuts, especially peanuts, and absence of anaphylactic reactions to nuts

among that population. More and more popular is the advice to expose

babies to potential allergens, pets in particular, for the purpose of preventing

allergies in the future. In a similar way, microorganisms that have become a



normal part of the environment do not affect us but can be fatal only to the

people with no previous exposure to them.

Although allergy medicine has not been able to solve its version of

Hamlet’s dilemma: to eliminate or not to eliminate, allergen elimination

remains central in the management of allergies.

HOUSE DUST MITE—ENEMY No 1Mite is a four-letter word in allergy medicine. House dust mites are attacked

with the utmost ferocity. Although it is an organism seen only through a

microscope, it is usually portrayed as a huge, monstrous, spider-like creature.

No wonder such pictures make patients shudder and then declare war against

the enemy, which is, in fact, the innocent fauna inhabiting the flora of all our

rooms, especially bedrooms. Scientific papers devote numerous pages to the

use of sprays developed for killing mites and cockroaches. The complex

names of the ingredients of these aerosol preparations resemble a page from

a chemistry textbook for university students. The authors often admit that

extended studies are necessary to determine the safety of these chemicals and

their efficacy in reducing allergic symptoms. Reading such articles, one can

never be sure what the recommendations are: to use or not to use the aerosol

that “can denature the mite allergen and reduce levels from carpets and

mattresses but does not kill the dust mites,”5 or “although effective... is not yet

proven to be safe for long-term usage.” Some of these sprays can probably do

more harm to health than the allergens they intend to destroy.

In The Toronto Star, on March 11, 1995:L17, I came across a remarkable

piece of advice given by a Southampton pediatrician, Dr. Jill Warner: teddy

bears and other stuffed toys should be put into a freezer during the day, so

that asthmatic children could take them at night to bed. Low temperatures

supposedly kill the mite and prevent attacks. The doctor did not say a word

about the bedding that is also full of house dust mites. Should it also be kept

in a freezer? What size of a freezer should a family with two or three asthmatic

children have?

A large article in the most recent issue of the most important immunolog-

ical publication states: “Few studies have investigated live house dust mite and

mite allergen removal …by washing machines.” This particular research

(supported by The Clorox Company exporting their product to over 100 coun-

tries) was studying the methods and percentage of mite removal during

washing, which detergents and bleaches might do a better job, and what fibers



responded best.6 Of course, the higher percentage of the removed mites upon

repeated washing with the given detergents is likely to expand the market for

Clorox, but will it help allergy patients? The article does not provide the answer.

In March 1996, the participants of the 52nd annual meeting of the AAAAI

heard a report later published by the flagship journal on allergy.”7 The study

was designed to assess the clinical efficacy of special bedding covers in house

dust mite respiratory allergy” and was staged in a highly scientific setting with

the use of “placebo mattresses” as opposed to mattresses with Intervent

covers. The conclusion sounds like a scientific joke: “allergen avoidance by

Intervent covers is effective. However, in this group of moderate asthmatic

patients, it did not improve allergic asthma.” The question is what WAS effec-

tive, if the patients did not improve?

It is not uncommon to read articles written by allergists on what types of

air filters and vacuum cleaners to buy, how many minutes are needed to

achieve the best results, what water temperature to use for washing the

bedding to destroy the mites, and what sort of mattress pads to purchase so

that body moisture does not contribute to the spread of the mites. Are these

measures more effective than the “effective” Intervent mattresses that suppos-

edly control the mites but do not relieve asthma?

Many pseudoscientific arguments regarding dust mites can be easily

rebuffed. For instance, nocturnal asthmatic attacks may well be related not to

the spooky mites but to the low levels of activity of our hormones during the

night, especially, natural corticosteroids and adrenalin. During the day, they

are produced in higher amounts, and this diminishes the number and severity

of the attacks. This explains the lesser need of medications in the day time by

the majority of asthmatics. Additional proof of the insignificance or absence

of an external effect is that there are those who soundly sleep in the same

bedrooms full of mites. Yet further proof is that an allergy patient whose asth-

matic attacks occur only at night can sleep in a tent with no mites around and

still cough and wheeze. Should he look for these tiny culprits hiding in or

behind the tent?

ALLERGY TO ANIMAL DANDERAs a rule, allergists assert that pets should be removed from the house even if

there is no direct indication that a member of the household develops symp-

toms upon contact with them. Literature contains protracted explanations on

where the allergens come from (hair, saliva and glands with complicated



names), how an animal’s fur is contaminated during its self-grooming, and

how public places may be full of this evil, readily airborne allergen. But one

cannot escape from pets even if one removes them from one’s own home.

Many scientific papers seriously discuss whether “non-allergenic” dogs

exist. Some suggest that the amount of dander produced by dogs is of impor-

tance, therefore shorthaired dogs are preferable. At the international confer-

ence on chest diseases in Toronto in 2000, cat dander was deemed by an

asthma specialist from Toronto’s Mount Sinai Hospital to be the biggest

culprit in causing asthma. He even blamed the dramatic rise in pet ownership

for the rising hospitalization and mortality and joked that the same gene that

predisposes people to asthma also makes them love their cats. It is a pity, this

allergist did not consider more serious issues in his report, such as the

extremely important point that only some people are victims of allergies.

In general, cats are of special interest to allergists, and research is

conducted on mind-boggling aspects of this supposed hazards. I fail to

understand how researchers manage to make highly accurate calculations

such as this one: males are more health-threatening than females, for they,

allegedly, shed more dander. Once, I came across this: an adult cat allegedly

sheds 1.5g of dander. To conduct such precise measurements, cats must have

been closed in tiny cages to prevent the loss of the danger into the atmosphere

or must have been wearing specially designed body-tight suits for dander

collection.

The Long Island College Hospital in Brooklyn, New York studied the

effects of a cat’s color on the owner’s symptoms, and the results were

presented in 2000 in San Diego, at the international conference for North

American allergists, at their annual meeting. This report said that owners of

dark-haired cats had allergies 6.1 more frequently than owners of light-haired

cats. What accuracy! This phenomenon seems to support the centuries-old

superstitions about black cats bringing bad luck. No explanation was offered

as to how pigment could contribute to allergies.

Paradoxically, a report made at the same conference by researchers from

Detroit emphasized the protective effect of exposure to cats and dogs in early

childhood. They found that infants exposed to pet dander during their first

year of life were less likely to develop allergies, not only to these animals, but

had overall less reactions to pollens and house dust mite. The team speculated

that the harmful effect ascribed to pets should be reconsidered and referred

to earlier European studies that had drawn similar conclusions. The titles of



some articles also speak in favor of pets. For instance: Does early exposure to

cat or dog protect against later allergy development?8 So, before parting with

your favorite pet, wait until science makes a final decision on whether they are

dangerous or curative.

An amazing study was once conducted at the Henry Ford Hospital in

Detroit. It revealed that despite weekly bathing of cats with distilled water or

their spraying with a preparation, which could reduce shedding, there was little

improvement in the allergic patients. Although cats are not exactly animals that

love bathing, distilled water cannot harm them. As for the spray, as a person

who loves cats, I only hope the cats survived the chemical exposure.

Water temperatures for washing pets and the frequency of the washing

procedure are among highly debatable topics professionals carry out on the

pages of their periodicals, at symposia and share with the lay sources. Will dry

cleaning be the next issue for scientific research? Pets are so notorious among

allergists that the 2000 issue Canadian guidelines on asthma specifically point

to them: “Have a non-allergic person bathe the pet weekly.”9

Here, I want to refer to the official statistics on allergies. Although, they

vary in different sources, I am inclined to believe those provided by the

world’s leading immunologist, the editor of the European journal Clinical

and Experimental Allergy, professor S. Holgate who said that 50% of the

population suffer from allergies and asthma.10 In this connection, I feel sorry

for pet owners: try to find a non-allergic nanny to bathe a cat in the society

where every second person has some hypersensitivity! A formidable task.

Despite the conflicting results of numerous studies, the guidelines worked

out by the American allergists, and published in the March 2001 supplemen-

tary issue of The Journal of Allergy and Clinical Immunology have, among

cockroaches and dust mites, a picture of a kitten as the most common indoor

threat to be avoided or eliminated. Unexplained remains the fact that pets, as

a part of the human household for hundreds of thousands of years, have never

been considered so notorious in the production of diseases, even though exposure

to animals must have been even higher in the past. Also unexplained is the fact

that many pet owners remain symptom-free.

In life, tragedy and farce often go hand in hand. The tragedy is that allergy

has made the intentional decision to go off the right road and thus, leaves

patients in a lurch. The farce is that phony science has been substituted and

silly arguments about dogs and cats have been elevated to the level of the

cause of the most common diseases of the century. The readily available unre-



stricted grants for research into irrelevant or insignificant areas contribute to

their proliferation.

FOOD ALLERGYAllergists agree that allergy skin testing is unreliable for diagnostics, and this

will be discussed in detail in the section on this topic. Still, despite their general

agreement, skin testing for foods is often performed, and to the surprise of

many, they are diagnosed with allergies to the foods they were consuming all

their life without any reaction. These patients often end up with giving up on

a product—naturally, without any relief in their allergy symptoms.

Dieticians or doctors specializing in alternative medicine often suggest

elimination diets to pinpoint the allergenic products. As a rule, patients know

what foods cause severe reactions, and therefore those do not need analysis

and challenge. Elimination of less allergenic products starts with keeping a

journal on reactions that may occur when eating regular foods. The analysis

of the notes may help to eliminate one or several foods that trigger mild to

moderate reactions. Few comply with this lengthy and tiresome procedure.

Besides, it is too often unsuccessful because allergy is mostly not limited to

one or two food products; besides, traces of the allergenic substance may turn

up in unexpected products, sometimes, even in allergy medications.

According to the existing regulations, manufacturers must indicate on labels

only those ingredients that exceed a specified amount, whereas a patient with

a hypersensitive disease may overreact to a substance in minute quantities.

Moreover, by excluding one or two allergenic foods, the patient may still

develop allergic reactions to something he cannot pinpoint. These people are

doomed to eating only at home and cooking from absolutely known ingredi-

ents—quite a difficult task.

Misdiagnosis of lactose intolerance is especially common. Many patients

came to me with such a diagnosis, but almost none of them had had the test

necessary to establish that the particular hypoactive enzyme was missing. The

diagnosis had been made solely on the basis of the medical history, or simply

because dairy products, milk in particular, are among no-no products in the

opinion of their doctor. They had given up on all dairy products, often with

minimal or no success at all. A no-milk diet is especially difficult for children

who are tempted with ice cream, milk chocolate and pastry, which their peers

consume in their presence. Unable to resist temptation, these kids often eat

the forbidden product and pay the price—suffer from an itchy rash, a



stomach ache or discomfort, nausea, diarrhea, even an asthma attack. In most

cases, however, the symptoms result from irritable bowel syndrome or an

allergy to dairy products and not lactose intolerance.

Although food allergy is considered to be an untreatable condition, like other

allergies, it is readily treatable, in the majority of cases, with histamine injections

because the causes and mechanisms underlying food allergies are the same as

with other diseases of hypersensitivity. This explains why the symptoms disap-

peared or greatly diminished in my patients upon a short course of histamine

therapy. This is different, however, with patients who have severe allergic

reactions to certain identified foods, when a clear cause-effect relationship is

evident. Histamine, successfully used for their other allergies, may not cover

these foods, and they must be thoroughly avoided. Especially dangerous are

anaphylactic reactions to nuts, and the patients prone to them should carry a

special emergency kit and wear a bracelet that indicates the “killer” food.

These cases require attention not only of the patient’s doctor but also of those

who come into contact with the patient.

I want to finish this topic with an unusual food allergen—cockroaches.

According to the researchers from the University of South Florida, cockroach

pieces are commonly found in different brands of flour. Dr. R. Lockey, an ex-

president of AAAAI and a member of the Editorial Board of JACI, the

immunological journal, reported at the annual meeting of the Academy in

San Diego in 2000 that the average person consumes two pounds of insect

debris per year. The author suggested that many cases of allergy, including

anaphylaxis, in which no known trigger is revealed, might be the result of the

contamination with cockroaches.

Now consider the following important fact: Cockroaches have existed

almost as long as life on Earth, and thus, people have been involuntarily

consuming them throughout their 6 million-year evolution. Now, it is clear

that the standards of living, especially in the Western world, are improving,

and regulations regarding the “permissible” amounts of bug debris are getting

stricter. In fact, no other insect is fought with the ferocity that is used against

cockroaches. I speculate that the amount of pesticides in our bread should be of

more concern than the amount of the insects. Due to these chemicals, there

should be fewer cockroaches in general and, hence, in flower, and this should

decrease the allergy and asthma statistics at least in the cleanest countries.

However, the opposite is happening: asthma incidence and morbidity are on

the rise, especially in the industrialized world, and strangely, in relatively



unspoiled New Zealand. Paradoxically, the official statistics say that the coun-

tries without proper regulations on hygienic standards and, therefore, I assume,

with the highest cockroach counts, such as India, have the lowest rates of aller-

gies and asthma. Something must be wrong with the suggested concept, as

there is evident discrepancy between the scientific declarations on allergy

causes and the statistical figures existing in allergy theory.

SCIENCE LAUGHS OR A LAUGHABLE SCIENCESuggestions regarding elimination are at times so confusing that they might

sound humorous, were they not related to a serious medical problem. I will

give several illustrations. Allergists often advise that patients with hay fever

should keep the windows and doors closed so that less pollen gets into the

house. Conversely, those patients whose allergies are allegedly triggered by

dust mites, cockroaches and pet dander should always keep their windows

open to prevent allergens piling up. What should those allergy patients do

who have symptoms all year round: keep the windows closed or open? How

can one enter or exit one’s own home and not let pollen in? Can hay fever

sufferers survive the long period from early spring until first frost with the

doors and windows sealed against pollen infiltration? The answer can be

found in a short story by the world-famous Canadian writer Steven Leacock.

The author speculated on how to keep air fresh at home and made a sugges-

tion: one should let in as much fresh air as possible, then close the windows

and doors and never let this air out. Perhaps, this is the best way to get rid of

allergies. Remarkably, Leacock gave his scientific advice without having a

degree in allergy medicine.

A serious medical source gives advice to those asthma patients who suffer

most during ragweed growth: they should spend August and September in a

ragweed-free parts of Europe or the west coast of North America. Should the

same approach be taken by those who are sensitive to various pollens and

suffer from April till the first frost? What if several family members have a

similar problem? Will their bank account meet the need to change climates?

In 1992, a Toronto allergist demonstrated a sense of humor when he told

a journalist that “avoidance of asthmatic triggers, such as pets and smoking,

is preferable to the use of medications. If there is a cat, you have to get rid of

the cat. If there is a father who smokes, you have to get rid of the father who

smokes. It’s that simple.” In the year 2000, eight years after the interview and

now in the role of the Vice President of the Canadian Allergy Society, this



immunologist repeated the same advice about cats and fathers, this time, in a

medical periodical. A sense of humor is a commendable quality in a doctor,

but in a medical publication, one would also expect a serious recommenda-

tion. There was none.

Bernard Shaw once compared good advice to castor oil, which is easier to

give than to take. Allergy patients are too often given “castor-oil-advice.”

Moreover, if all these recommendations were given solely to patients, this could

be considered part of their education on elimination of the offenders. Whether

the patients followed the advice or not would be a matter of their choosing,

savings in the bank and love for their pets and fathers. However, these aston-

ishing masterpieces of medical thought are delivered by the experts in the field

to an audience of fellow immunologists and become a part of established

science. Look at the covers of Journal of Allergy and Clinical Immunology, and

you will mostly see pictures of cats, mites and cockroaches. Although the work

of allergists often incorporates things that do not exactly belong to immunology,

they do such investigations as their professional (well-paid) mission.

THE CONFUSION OF TRIGGERS WITH CAUSESThe confusion of triggers with causes reigns in this field of medicine; a scientific

article in Contemporary Allergies (June 1993), can be considered the apotheosis

of the confusion. It contains suggestions by the Allergy/Asthma Information

Association as directed by the Canadian allergists. The association lists four

factors as causes of childhood asthma and asserts that asthma develops when

1. the tendency for asthma or allergy is genetically inherited;

2. the baby is exposed to allergens;

3. he baby is exposed to pollutants;

4. the baby catches a viral infection.

The conclusion follows that “if these four factors can be controlled during the

first year of life, it is unlikely a baby will develop asthma.” The author’s name

and title were not given, but in a scientific periodical on allergy such as this

one, all articles are written or, at least, edited by an allergist. In science, to say

that heredity and pollutants or infections can be controlled during the first year

of a baby’s life sounds not like a scientific statement, but like a joke. The causes

of allergy and asthma symptoms are within, not outside the body. The proof

is that the most cared for babies who live in the cleanest environment may

show symptoms of allergy and asthma.



Even among those representing the highest authorities in allergy, we can

find these kind of incompatible notions. This is what a former president of

the Canadian Association of Allergy and Asthma, wrote on page 67 in his

article Asthma in Kids published in the Parkhurst Exchange in June 1996:

“Early viral infections, exposure to cigarette smoke and atopy seem to be the

main causes.” Viruses and smoke are triggers, while atopy is defined in

medical dictionaries as some form of inherited predisposition to allergies. An

evident discord.

Unless triggers are differentiated from the real inner cause, we will read in

scientific sources statements like: “To explain the increasing prevalence of

asthma in developed countries since the 1970s, experts have pointed to

increases in indoor allergens because of better insulation of buildings.”11

Although the author recognizes in passing that there are hereditary factors in

the origin of asthma, he points his finger at insulation. Upon reading the

article, patients may consider moving to a country where insulation is not

needed. A perfect remedy to get rid of asthma! But then, why are there so

many asthmatics in Arizona with its famous hot climate, which makes any

insulation absolutely redundant?

Do you know that, according to statistics, the world’s least polluted areas,

Cunha Island in the Atlantic, the Western Caroline in the Pacific and Shetland

Islands near Scotland have the highest asthma incidence? So does the close to

sterile-clean New Zealand. At the same time, highly polluted India, as official

statistics in allergy assure us, has one of the lowest asthma rates in the world.

Another paradox.

WHAT’S IN A NAME?If allergies can start without an allergen, or, being started by one, can

continue in the absence of this allergen, what is the legitimacy of the term—

allergic diseases? The conventional term allergy narrows and distorts the meaning

of the diseases and unjustifiably pins them to allergens and thus, to IgE anti-

bodies. It permits the medical profession to continue costly allergy testing to

allegedly identify the offensive allergens but, strangely, almost never adjusts the

treatment. It makes the search for triggers the centre of diagnostics and turns

trigger elimination into the main, though ineffective, treatment method.

Current concept of allergic diseases is confusing not only for laymen but for

doctors as well. Furthermore, the absence of detectable allergens may be

harmful to patients when a necessary medical certificate is denied because of



the prevailing orthodoxy and humiliates them by denying the reality of their

physical disease, dismissing it as the condition of an unstable mind. This situ-

ation leads to absurdities such as the one in April 1998 when chronic fatigue

syndrome was recognized as a physical disease by a Canadian court. Since

when does medicine need judges to establish a diagnosis in medicine?

In the majority of cases, symptoms are provoked by both identifiable

specific and less easily identifiable nonspecific triggers; therefore strict cate-

gorization in this field of medicine only confuses the understanding of the

immune processes; a change is urgently required. The idea of revising the

term allergy is not new in science. In 1999, I came across an article unusual in

its criticism.12 There I read that: “There is probably no term more misused in

medicine, both by physicians and medicine, than the term ‘allergy’.”

According to the author, restricting the disease “to the IgE/mast cell mecha-

nism is anachronistic,” and there is a “need to redefine all those terms

invented decades ago.” Will it be done? The change in terminology requires a

change in understanding what underlies diseases of hypersensitivity.

“Expunging the word ‘allergy’ from the medical vernacular would be a good

start to better understand the pathophysiology of diseases,” states the same

source. In my opinion, expunging of the term now is difficult because it has

become deeply rooted. Of course, the term hypersensitivity would be more

appropriate as it points to the true cause of the symptoms, but then, what do

you call the specialists that treat diseases of hypersensitivity? The more prac-

tical decision would be to leave the term as it is, but agree upon the real nature

and meaning of hypersensitivity and to tell the truth about what is currently

concealed. Namely that there is this duality of histamine and its chemistry,

which lie at the heart of allergies. It is not the change of the term that is

needed, but the change of these admittedly anachronistic views.

Allergists do not consider it urgent, despite their every-day failure in the

treatment. Allergen/IgE-based religion has become even stronger in the new

millennium. Thus, in 2001, Harvard Medical School reaffirmed, in a study

supported by a National Institutes of Health “the concept that IgE plays a crit-

ical role in asthma pathogenesis (underlying mechanisms)”13 The cover of

the journal that published this article depicted the usual, most notorious

allergens—dust mites, pets, cockroaches, while nonspecific triggers have

completely been excluded from the contents of this supplementary issue.

Interestingly, just a decade ago, the data presented at the XIV Congress of the

European Academy of Allergy and Clinical Immunology stated that only 15%



of asthma had allergic origin, 41% are non-allergic, and 44% were mixed.14

Have the diseases of hypersensitivity changed their origin, or has allergy

medicine inexplicably changed its views within the decade that separates

these works?

TO SIMPLIFY THE MATTERThe suggestion below does not claim to be original, since all notions exist in

this area of research. Still, they have never been acknowledged. For laymen,

the term allergy is simpler than hypersensitivity, and both may co-exist in lay

sources. However, science should operate with the terminology that reflects

the real knowledge. Changing the name in scientific sources to diseases of

hypersensitivity would immediately remove the limits erected by the narrow

notions of allergen and allergies. Further, diseases of hypersensitivity could be

divided into LATENT and ACTIVE. The term latent means hidden. The

genetic defect is there, but the disease is dormant because the immune system

is still strong enough to maintain equilibrium and withstand various stimuli.

A person hit “out of the blue” by allergy symptoms will understand that he

might have had the disease in a latent form, but in the absence of symptoms,

considered himself healthy. The healthy parents of a sick child will realize that

they might be the carriers of a minor genetic defect, which in combination,

has become visible in their son or daughter. Specific IgE antibodies may be

found in the absence of symptoms, which means that sensitization to certain

allergens has already taken place, but the immune system of the host is (was)

strong enough to withstand the assault. This explains why patients may, for

example, not have symptoms in the pollen season, but tests reveal IgE anti-

bodies to these pollens. With time, however, the cellular defects become

stronger, and the disease may become active.

An active hypersensitivity could further be usefully subdivided into

several groups.

■ Allergenic hypersensitivity as a term, should be limited strictly to the

symptoms triggered by allergens. Hay fever, the condition due to pollens,

may serve as an example. This form is practically always characterized by

the presence of specific IgE antibodies and, more important, symptoms

arising in the presence of the trigger(s).

■ Physical hypersensitivity includes symptoms started by environmental

events such as low or high temperatures, sunlight, vibration, pressure,

electromagnetic waves, etc. These can be identified by a thorough



medical history and are often unavoidable. Naturally, no specific IgE

antibodies are formed to physical factors.

■ Physiologic hypersensitivity is the one in which the symptoms are

provoked by natural chemical changes in the host’s body. These changes

occur seemingly without any trigger, due to daily (called circadian

rhythm), monthly or seasonal cyclic fluctuations, psychological stress,

physical activity, etc. Moreover, the symptoms may seem to arise without

a challenge, spontaneously, and may disappear in the same spontaneous

manner. Physiologic factors are difficult to trace and even more difficult

to avoid. Naturally, we cannot expect specific IgE antibodies in this sort

of hypersensitivity.

■ Chemical hypersensitivity, such as in cases of exposure to various occu-

pational agents, pollutants, impurities and fumes may occur both in the

absence and presence of the corresponding IgE antibodies.

■ Mixed type is a combination of any of the above kinds of hypersensi-

tivity and is most common.

Unlike the outdated IgE-based concept that fails to clarify the scope of the

disease and appearance or escalation of symptoms in the absence of any

evident allergen, this simple classification would remedy the situation. It

would also save the often useless and painstaking efforts to find the offender

and eliminate it. Such classification unites all five categories in the similarity

of the underlying cellular processes, all of which are obviously immunologic

and differ in details only. The main point, however, is that the re-classification

would focus on the cause of the disease—improperly functioning cells and

initial histamine hyperreleasability—and thus lead to the potential for their

repair.



ENDNOTES 1. H. Bayram et al. Effect of ozone and nitrogen dioxide on the release of proinflamamtory

mediators… JACI 2001;107:287-94 2. Dorland’s Illustrated Medical Dictionary 1988:493. Kay. Allergy and Allergic Diseases. New England Journal of Medicine. 2001;344:30-374. C.Pollard, Influence of maternal diet during lactation… JACI 1996;97:2405. Breathing Space 1993;l:3-56. L. Arlean et al. Mite and mite allergen removal. JACI 2003;111:1269-737. J. Birnbaum et al. Clinical study of bedding covers in mite-allergic asthmatic patients. JACI

1996;97:2238. Hesselmar et al. Clin Exp Allergy 1999;29:611-7 9. Bowie & L-P. Boulet What’s new in asthma? Parkhurst Exchange. April 2000:121

10. J. Gleick Gasping for Breath. Time. September 1, 1991:36-43 11. A. Desjardins. Allergy Focus 1993;3:6-712. V. Beltrani. Point-Counterpoint. Journal of Cutaneous Medicine and Surgery. 1999;3:198-20013. H. Oettgen, R. Geha IgE regulation and roles in asthma pathogenesis. JACI 2001;107:429-4014. P. Plashke et al. Summary Service Review, 1989, p. 36.



PART THREE

ALLERGIC INFLAMMATION

THE TERM INFLAMMATIONWhereas the term allergic inflammation is not new in relation to allergies and

asthma, it has lately become especially accentuated. The classification of these

diseases as inflammatory creates the impression that inflammation forms the

basis for the symptoms, and that anti-inflammatory remedies for its suppres-

sion are justified. This concept has become so commonplace that often,

medical sources do not even bother to name the inflammation as allergic, nor

do doctors who prescribe anti-inflammatory medications explain to their

patients what kind of inflammation it is. It is just “inflammation.”

How well documented is the notion of allergies and asthma as inflamma-

tory diseases? Allergy medicine provides only half-truths, probably to make it

difficult to dethrone the declarations of the high efficacy of anti-inflammatory

drugs in allergies and asthma. To reach the truth, we need to deal with the

notion of inflammation.

Dorland’s Illustrative Medical Dictionary defines the word inflammation as

a “localized protective response elicited by injury or destruction of tissues”

(1988:835). Inflammation can be of different kinds. Tissue destruction that

occurs due to bacteria or viruses is an infectious inflammation. Soft tissue

injury due to laceration, contusion or burn may lead to a post-traumatic non-

infectious inflammation or have a superimposed infection. At the site of

inflammation, there can also be loss of normal tissue functioning. Irrespective

of the origin, the inflamed area is red, swollen and painful due to tissue

response to a microorganism, or due to damage and an increased number of

various cells at the site. These cells destroy or neutralize the microor-


ganism and also participate in the healing process of

the tissues. Depending on the severity of inflamma-

tion, there may be systemic symptoms—high fever

and distress. The common features of all inflamma-

tions are their external cause and gradual develop-

ment and resolution: the symptoms accumulate,

reach their peak and slowly subside.

ALLERGIC INFLAMMATION—A PROPER TERM?The standard textbook of internal medicine, Harrison’s

Principles of Internal Medicine describes another

inflammation and characterizes it as immunologically

mediated. Such inflammation arises from excessive

release of mediators and cytokines from mast cells,

basophils and T-cells. As a deviation from the norm,

this excess can become the basis for a disease. This

kind of inflammation may not have a known external

cause, and this makes it less understandable than the

infectious or post-traumatic forms. Immune-related

inflammation is the response or reaction of tissues to pro-inflammatory media-

tors. This implies the existence of events that precede it. Unlike other inflam-

mations, in which the cause is external, in immune-related inflammations,

the cause is internal—an excessive mediator release. As in other inflamma-

tions, a local allergic event may grow into a systemic one by involving

different organs through the transmission of signals from the cells in the

affected area to those that are far away. Allergic inflammation fits perfectly

well into the definition of reactive (to mediators) inflammation: it is a reac-

tion of tissues and organs to the mediator/cytokine overspill by immune cells

occurring as a result of deficient immune regulation.

THE DIFFERENCES BETWEEN ALLERGY AND INFECTION Differences between allergic inflammation and other kinds of inflammations

arise from its different nature. Indeed, the term allergic comes from the Greek

different from ordinary.

The first difference is that the originally dysregulated immune cells

respond to an imaginary enemy, or there is no enemy at all. Therefore their

response does not produce truly defensive chemistry.

Allergic Inflammation 99

Allergic inflammation

is a chemical,

inflammation-like local

and/or systemic reac-

tion, secondary to

dysregulated functioning

of the immune cells.

Unlike the external

cause in other inflamma-

tions, immune-related

inflammations arise

from the internal cause—

deficient immunoregula-

tory forces responsible

for excessive release of

pro-disease mediators,

of which histamine is

the most important.


The second difference is the speed of progression of allergic inflammation

compared to other types. An instantaneous, often unpredictable start and end

are almost the norm in allergic inflammation, while it is the opposite with

infections. Compare an abscess and hives. Have you ever seen an abscess form

or disappear in front of your eyes—redness, swelling, pain, pus? Never. It will

go through predetermined stages: it will suppurate, rupture when ripe, and

only then will the tissues start healing. Time is required for the invasion of

bacteria, their conquest of the territory, the attraction of the numerous cells

to the battlefield, and the pus production, which means, actually, that certain

cells sacrificed their lives in the fight. The bacteria are gradually killed, either

naturally by the cells or with the help of antibiotics. Only after the destruc-

tion of the enemy do the affected tissues start to restore their normal func-

tioning—a lengthy process as well. We see similar features in the case of

injury or burn: all the hot or cold packs in the world applied to the area will

not make the swelling disappear instantaneously. On the contrary, you may

watch hives develop within minutes and fade in the same manner.

Comparison of pneumonia and asthma is also helpful. You will never find

a description of a miraculous instantaneous recovery from pneumonia such as:

one minute a patient has a high fever, general weakness, productive cough, and

in a twinkling of an eye, all is gone. In contrast, an asthma patient may experi-

ence a sudden attack, which seems to come from nowhere and total sponta-

neous relief in an instant, often with just one inhalation of a bronchodilator.

This is how dynamic, volatile and erratic allergic inflammation can be.

How volatile and dynamic allergic inflammation can be becomes obvious

when considering the following typical situation. Imagine that it is ragweed

season, and your asthma bothers you a lot. You board a plane, and as soon as

it takes off, your symptoms disappear for the period you stay in the ragweed-

free zone. However, no sooner does your plane land, your disease is back in

full swing. If a common inflammatory process caused your symptoms, how

could it immediately disappear when the trigger was gone? How could it

develop again within seconds amid complete remission? If it was a flu or a

tissue injury, the symptoms would not change on or off the plane. The speed

with which your inflammation developed and resolved contradicts all the

natural laws of the gradual development and resolution of an inflammatory

process in tissues.

The explanation is simple. On the plane, with the offender eliminated, the

release of histamine slowed down, the cellular chemistry quieted down, and the



tissues immediately restored their normal functioning. So the symptoms

disappeared. Having returned to the ragweed-saturated airport, your mast cells

and basophils, hypersensitive to the offensive allergen, again exploded with

histamine, and the shift of the chemistry followed. Your lungs and bronchi, the

depots of mast cells and basophils, responded with a cough and constriction. If

at that moment, we could watch the events in the bronchial area, we would see

the signs similar to a true inflammatory process—redness and swelling. Still,

there was no time for a true inflammation to develop. In reality, the signs and

symptoms were the result of the fluctuating cellular chemistry.

The third essential distinction between infectious and allergic inflamma-

tions is in the number and specificity of inflammatory cells, which accumu-

late at the site. The degree of inflammation should correlate with the rising

number of the cells ready to fight. The more severe the infection, the more

cells participate. Their amassing manifests through the amount of secretions

at the site—phlegm and pus. Logically speaking, in developed asthma, we

should expect a high number of inflammatory cells in the bronchial tree

mostly mast cells and T-cells (In trivial inflammation, we deal with different

cells). Paradoxically, scientists often do not see the increase in the number of

inflammatory cells at the site of apparent allergic reaction.1 This fact puzzles

some authors, but it should not. It is not so much the number of the cells that

determines the development of this inflammation, but the intensity of the

pro-disease mediators secreted by them. Swift chemical fluctuations may

trigger the most severe symptoms, with no time or need for many immune

cells to accumulate. This dynamic pattern, however, carries a positive aspect:

the quickly developed allergic reaction may resolve fast and easily, and this

ease and speed are the proof of the reversibility of allergic inflammation. Of

course, this is true only as long as the disease has not advanced to the point

where the tissues involved have not structurally changed.

ANTIBIOTICS FOR ALLERGIES AND ASTHMA?Regrettably, the term inflammation used now both for infectious and allergic

forms not only fudges over the facts in the perception of laypersons, but also

for many doctors. The confusion of the terminology seriously affects thera-

peutic management. As a result, antibiotics, which are meant to target bacteria,

are often used for allergies. Even during the height of the ragweed season or the

warm months of tree pollination, congested and wheezy patients consume

antibiotics for “bronchitis” in the absence of an identified bacterium. Sadly, the



patient’s condition depends on whether his doctor is capable (or willing) to

differentiate these two processes and their causes. Causes of allergic and infec-

tious inflammations are worlds apart, and so should treatment targets.

In infections, it is eradication of the causative agent, while, in allergies, it

should be restoration of the regulatory forces responsible for the balanced

production of immune cells. Judging by textbooks and publications in the

leading journal of immunology even in the new millennium, professorial staff

of medical schools is often unaware of what underlies allergic inflammation:

“There is an increasing number of studies suggest that chronic asthma is asso-

ciated with chronic infection,” and that certain bacteria “play an important

role in the pathophysiology of asthma,” states the leading periodical.2 The

article continues: “this opens another dimension for asthma pathophysiology

and eventually for new treatment options,” and then, the authors suggest

antibiotics as a “new” option. The trend to present allergies and asthma as

direct consequence of infections grows in parallel to the growing resistance

and inability of the medical profession to help their patients. If this continues,

medicine will never be able to treat allergies and asthma effectively. Proof of

the irrelevance of antibiotics in allergies comes from a simple comparison: the

majority of infectious conditions are cured by antibiotics, while statistics in

allergies and asthma are getting bleaker with each day despite the frequent

prescriptions of this drug group. Of course, it is also well known that uncon-

trolled and inappropriate use of antibiotics contributes to resistant bacteria—

exactly what we are seeing now.

ANOTHER GROUP OF ALLERGY MEDICATIONSThe word anti-inflammatory in relation to drugs sounds innocent due to the

unfortunate fact that antibiotics as an anti-inflammatory medication against

bacteria, have become almost the norm in the treatment of even minor colds

(usually viral in nature for which antibiotics do not work) and are perceived by

the general population as safe. In relation to allergies, this inconspicuous term

proposes that we should deal with the cellular chemistry in the same way

bacteria are dealt with: kill the cells releasing pro-inflammatory chemistry.

Antibiotics are unable to kill the disease-promoting chemistry, and so another

group of medications called anti-inflammatory takes the stage. They are corti-

costeroids. These drugs have been in use for over half a century, and were first

cautiously prescribed because of their side effects, but their use has recently

been revived. The identity of the term anti-inflammatory applied both to



antibiotics and steroids strengthens the false impression of the analogy between

infectious and allergic inflammations, and creates a sense of safety—also false.

With less and less hesitation, under the pressure of increasingly treatment-

resistant allergies and asthma, and under the even worse pressure brought to

bear upon doctors by those who formulate therapeutic guidelines, doctors

prescribe and patients take steroids. What doctors rarely, if ever, reveal, and their

patients are not informed of is that steroids belong to immunosuppressive reme-

dies. The consequences? Read the word again. Can the already dysfunctional

immune system of an allergy/asthma patient improve with a drug given to

suppress the functioning of the immune system in general? Besides, all too

often, consumption of steroids becomes as chronic as is the disease itself.

Continuous suppression of the already weakened immunity—not a very

encouraging prospect. Suppressed is the ability of the cells to produce not

only the targeted “bad” mediators and cytokines , but the “good” ones as well,

and in time, steroids disable the cellular lab. Not that doctors do this inten-

tionally. Their textbooks keep them blissfully unaware of the origin of allergic

inflammation, and the leaders in the field, as well as the manufacturers, assure

them of the safety of steroids. With the primary cellular defects remaining

unattended, the chances to arrest the resulting events are slim. The aggra-

vating fact is that these immunosuppressive medications do not have any effec-

tive alternative—at least not as generally taught in medical school—and this

justifies their aggressive prescription.

The height of misunderstanding of what an allergic inflammation is, can

be gauged by the fact that the notion of asthma being “a chronic injury and

repair response, with classic wound-repair factors… participating in the

disease” is gaining popularity.3 There is an obvious conflict here. First, the

nature of a wound is inapplicable to allergic processes. Second, a wound is a

lasting condition incompatible with the reversibility of processes in allergies

and asthma. Third, steroids impede wound healing, and therefore their

imperative prescription for “wound repair” in allergies and asthma is more

than contradictory; it is false.

WHAT UNDERLIES ALLERGIC INFLAMMATIONNo disease can be understood, classified or treated without the physician’s

comprehension of two notions—etiology and pathogenesis, therefore both

acquire special importance. Etiology is the origin of a disease, the specific

factors that cause it, while pathogenesis is the specific chemical and cellular



processes that occur in its development. The etiology of allergies has never been

spelled out, and as a result, their pathogenesis is inconsistent. Inflammation is

a nonspecific term of wide scope. Allergists have proclaimed inflammation as

the cause of asthma and allergic diseases, therefore speaking of their etiology,

we speak about the etiology of allergic inflammation.

The etiology of allergies is the primary deficiency of the genes responsible

for the protective regulatory immune tools, with the resulting low perform-

ance of the protective arm of the immune system that comprises T-suppres-

sors, the histamine H2 receptors and cyclic AMP system. These etiological

factors logically determine the pathogenesis of allergic inflammation.

The Pathogenesis of allergies stems from the inability of the immune

system to perform its autoregulatory role as nature designed it, namely to

temper any negative response of the immune cells through their own energetic

positive counteraction. The pathogenetic mechanisms include the primary

excessive release of histamine and histamine-induced pro-inflammation

cytokines and mediators, that is, prevalence of H1 negative effect over H2/3 posi-

tive effect. The response of the surrounding tissues mediated by this predomi-

nantly inflammatory chemistry is what science calls allergic inflammation.

These definitions of the etiology and pathogenesis correlate with the text-

book description of those in chronic diseases in general. As we have already

quoted from the main medical textbook, the cell/mediator interactions

“involve a delicate balance among positive and negative influences and ulti-

mately result in expression of an appropriate immune response. The slightest

imbalance in these immunoregulatory circuits may result in aberrant

immune function leading to clinically apparent immune-mediated disease.”4

This is exactly what we see in allergies.

WHAT DETERMINES DRUG PRESCRIPTIONS? Knowing what underlies allergic inflammation, it is easy to understand what

underlies the decisions regarding research, interpretation of the data and

management of patients in today’s allergy therapy. It is peculiar that with

histamine being the core of all allergy processes, bad and good, at present,

only from the name of the highly consumed anti-histamines can one guess

this. All histamine-related positive forces of the immunity are apparently

generally unknown. The person whose immune system has become an

assailant needs to be defended from it, and the generous drug industry offers



its most powerful weapons. The main reason why allergists present allergic

inflammation as the cause of allergies is to support the intention to expand the

use of “anti-inflammatory” steroids. The unfortunate fact that physiological

dependence develops over the time is also handy, for consumption grows with it.

Although allergists insistently propagate the concept of allergic inflam-

mation, they are evasive as to what causes it. Ask a doctor the same question

about other inflammations, and you will get a clear answer: viruses, bacteria

or injury. In relation to allergic inflammation, you will, most probably, hear

about dogs, cats, dust mites and pollens as causes. Only medically uneducated

patient can accept this idea, and a doctor must be equally illiterate to believe

it. If you are lucky to find a doctor who mentions an exaggerated histamine

release as the cause of your symptoms, ask him what makes you different

from your neighbor who does not have this defect. Then, with the knowledge

you have by now about histamine, ask this doctor what prevents medicine from

using its self-remedial qualities. I doubt you will find a physician who will know

what you are talking about. Do not blame him. Illiteracy in the field of allergy

is a carefully nurtured fact, true knowledge is rejected, and research is

supported in any area but the one that could help resolve the problem—hista-

mine and related events and mechanisms. Instead of rejoicing in the

reversibility that distinguishes allergy from other immune areas dealing with

more resistant or therapeutically irreversible diseases, the leading allergists

stonewall the spread of the existing true and relevant knowledge.

The drug market has become the main source of medical information. It

determines the value of drugs not from the standpoint of patient’s wellbeing

but from the economic perspective. The drug market has become the under-

lying mechanism in the promotion of the secondary event—allergic inflamma-

tion—as the origin of allergies. The etiology of this process is the sickness of our

society in general and the sickness of medicine as its inseparable and the most

lucrative field. These forces maintain the marriage of poor medicine and the

rich drug industry.

ENDNOTES 1. Editorial, The Lancet, 1991; 337:82-32. R. Martin et al. A link between chronic asthma and chronic infection. JACI 2001;107:595-6013. Wenzel S. et al. Subepithelial basement membrane… JACI 2003; 111:13454. Harrison’s Principles of Internal Medicine, 1987 p. 334



PART FOUR

“HISTAMINEGATE”

“If liberty means anything at all, it means the right to tell people what

they do not want to hear.” —George Orwell

“Read not to contradict, nor to believe, but to weigh and consider”

—Francis Bacon, The Essays

This chapter is for those whose educational background is in biology or

medicine, and who are professionally interested in more specific details and

references. It is also for patients who, out of need and/or despair, were forced

to self-educate themselves scientifically in the field. The text includes the data

covered in the part Immune Mechanisms but presents them on a deeper level.

It also investigates the “Watergate”-type activities due to which allergy is

losing its scientific credibility .

The information in this chapter is based on the work of the pioneers in

histamine research, researchers who are known to be the greatest authorities

in modern clinical immunology. In medicine, unlike many other areas, “the

discoveries of basic and population science have no practical value unless

they have clinical significance.”1 Unfortunately, the research of these pioneers

has not been applied. Had their discoveries been developed further and intro-

duced into clinical practice, they would have helped save the world from the

most common diseases of our time—allergies, asthma and numerous related

conditions.


First of all, although the researchers knew the mechanisms that underlie

allergies in detail, they failed as clinicians because they were unable to observe

clinical findings in patients and interpret them on the basis of their own theo-

retical discoveries. Second, when allergists realized how damaging these

discoveries could be for the drug market, they used this lack of clinical

substantiation to silence the well-researched theoretical findings many of

which came from the labs of these allergy gurus. At present, this fundamen-

tally significant material is virtually unknown, and the researchers themselves

never mention their discoveries that form the foundation of allergy as a

science. Astonishingly, some pioneers of histamine research have never actu-

ally declared a change in their position, they have gradually disappeared from

public view during the ’90s. Others, strangely propagate their newly acquired

views on the immune processes in allergy and avoid the very name of the

substance that launched their careers—histamine.

You may be curious to know if I believe that the scientists, whose works I

am going to discuss and quote, are among the participants of the plot against

histamine. My answer is: I do not know whether they have changed their

stand voluntarily or under duress—but it is highly improbable that they are

unaware of the vacuum that started to form around histamine in the early

’90s, and which is now virtually complete. Their high status in medicine and

their profound knowledge make it improbable for them not to have noticed

the concealment of all the data pertaining to histamine, including their own

earlier research. Conspicuous is also the absence of explanations of what

necessitated the dramatic shift in their scientific views. Only time will reveal

who was an involuntary witness, and who became a complicit participant in

the plot.

This chapter is a critical review of certain textbooks and numerous papers

published in peer-reviewed journals. The authors are often the editors or

board members of these journals, chairs of international conferences, writers

and editors of textbooks, and they are thus, trend-setters in clinical

immunology. By definition, a critical review is scholarship performed with

the purpose to correct or improve. The concept of a critical review suggests

analysis of the material with exposure of errors, misstatements and contra-

dictions within a given text as well as comparison with other existing views.

As any critical review, mine is not directed at the scientists, but at their works.

Its purpose is to improve the existing bleak situation with regard to allergies

and asthma. The emphasis is on the inexplicable turn in contemporary

“Histaminegate” 107


allergology, on the active effort to silence and misinterpret those well-

researched notions and ideas that could preserve allergy as a science. Unlike

most critical statements, books, and articles in the area of allergic diseases,

this book offers a fairly easy concrete solution. I realize I am inviting the rage

of allergists and hope that at least some of them will have the courage to

admit publicly what they already acknowledge behind closed doors: their

failure to manage patients with allergic diseases and asthma and to recognize

the urgent need for a change.

“Experts are never right or wrong; they win or lose. Right and wrong are

decided by proof; winning and losing are decided by who is doing the talking

or talks the loudest, has the last, latest or only word, and is quoted by

reporters,” says a quote from The Globe & Mail. I understand, that my voice

is a whisper compared to the loud chorus emanating from the central peri-

odicals, huge textbooks and monumental monographs. To make myself

heard, I choose to speak with their words taken from the same journals, text-

books and volumes and only point to the obvious discrepancies. Not merely

in the details, but in the most essential material.

For those who may say that being a general practitioner, I am unable to

access and scrutinize the scientific work of the allergy moguls, I can say that

my medical background does permit me to do this. I have a residency in

internal medicine and specialization in allergology. For 8 years, I worked as

an allergist in a republic of the former Soviet Union. The fact that in Canada,

I did not acquire a local certification was due to the fact that I simply could

not financially afford 4 or 5 years of residency here. For the 4 years of my

internship and preparation for exams in Canada, my wife carried the heavy

burden of being the only breadwinner in the family, and I felt I had a respon-

sibility to start working as soon as possible. I am permitted to work as an

allergist in Canada and nothing deprives me of my previous knowledge, or

diminishes my interest and ability in this field. For 30 years, I have studied

everything I could on histamine. In Canada alone, I have successfully treated

about 2,500 patients with histamine, and many more back in Russia. In 1989

and 1992, I made presentations at international conferences about my own

clinical experience and presented the supportive scientific data. These presen-

tations covered the role of H2/3-receptor effects and the stimulation of cyclic

AMP by histamine as the central regulatory mechanisms and therapeutic means.

In the late ’80s, I wanted to share my experience with others and

suggested to the Ontario allergists having a discussion on histamine



therapy. The response in Toronto was outright hostile. As Benjamin Disraeli

once said, “something unpleasant is coming when men are anxious to tell the

truth.” Indeed, on the initiative of allergists, without a single complaint from

patients, I was persecuted and prosecuted. The College of Physicians and

Surgeons of Ontario, CPSO, requested the scientific and medical proof for the

validity of histamine therapy. When I submitted the irrefutable evidence,

CPSO, instructed by its Deputy Registrar, Dr. John Carlisle, used such

methods as false allegations (the fact later explained by the prosecutor, Robert

Armstrong, as an error of a lay person in CPSO’s committee), forgery of the

signature of a court reporter, elimination of the central evidence, etc.

My patients were the living proof of the efficacy of the histamine therapy.

The scientific evidence I provided at my disciplinary hearings was so

powerful that local allergists were unable to argue it on professional grounds,

and the expert witness requested support from internationally renowned

immunologists. The support did not come in as scientific sources or argu-

ments but in the form of very short notes that rejected the therapy outright,

without giving a single reason for the rejection. The allergy elite formed a

united front in their denial of the therapy—which, I had proven, had restored

the health of hundreds of my patients. Neither the allergists, nor the College

which licenses doctors were interested in scientific fact or patients’ recovery.

During and after my legal battles with the Ontario allergy medicine estab-

lishment, I continued to gather the relevant data. There is a Russian saying,

that if the truth is not let in through the door, it flies in through a window.

Indeed, despite the concealment and distortion reigning in allergology, there

was sporadic leakage of the true findings even in the mid-90s which is the

period of the peak of the suppression of information surrounding histamine.

Today’s situation in allergy medicine provides abundant evidence of a plot. I

decided to uncover the conspiracy through disclosure of the hidden informa-

tion. Extreme circumstances have made me the messenger, and this role

obliges me to be impartial in the delivery of my message.

The majority of the references in this chapter are from major textbooks

and The Journal of Allergy and Clinical Immunology, JACI, “the most

frequently cited allergy/immunology journal in the field,” as each issue

proudly declares at its masthead. In many situations, the quotations do not

reproduce a full sentence and may therefore look as if adjusted to suit my

review. Not so. This is done out of need to simplify the text by cutting out

those details that are not the topic of this book. Moreover, scientific texts



often seem to be written in a sort of medical legalese, incomprehensible for

those who do not specialize in the field. Partially, this can be explained by the

narrowness of the topic, but lately, mostly out of the need to hide certain

elements, hence the need to talk allegorically. Besides. even the best

researchers are not always the best writers. I abbreviate long complicated

sentences to help understand the author’s ideas and emphasize in bold those

elements I consider most important.

If you follow these quotations, you will see that the drastic changes in the

views of the leaders in allergy can be traced back to 1991. That is when the key

findings suddenly began to disappear from all major sources and were substi-

tuted by insignificant, distracting data that gradually started to acquire prime

importance. The “coup” in allergy medicine was as smooth and fast as the

“velvet” revolution in Prague. The well-organized concealment and the smooth-

ness with which the changes occurred need major financial backing, and this

makes one strongly suspect the pharmaceutical industry behind the scheme. Still,

we cannot blame the sponsors as much as the performers of this “revolution,”

since, like any other, this one could not have taken place without a zealous

support of the highest medical authorities, doctors by profession.

Medicine is considered to be a blend of science and art. This chapter will

try to prove that contemporary allergology cannot be considered as either: it

has thoroughly buried its basic findings and prevented their use in clinical

practice. As a result, the incomplete and distorted data it presents as science

cannot form the basis for science or art. The frightening official statistics in

asthma and allergies are the undeniable proof of the failure of contemporary

clinical allergy practice to manage patients properly. There is hardly any field

in today’s medicine so full of discrepancies, concealed information and

misrepresentation. At the same time, there is hardly another area of basic

science so deeply studied, and so evident in its conclusions about the origin

of allergies and asthma, and what should be the target for therapy. The fact

that, by definition, allergies and asthma are reversible diseases makes the

concealment all the more scandalous.

ROSS ROCKLIN was Professor of Medicine and Chief of Allergy Division at

the New England Medical Center in Boston during the height of his hista-

mine research. He later became Senior Associate Director of Clinical Research

for Boehringer Ingelsheim and then for Astra, known then as Astra Zeneca.

Both are pharmaceutical giants that produce allergy and asthma medications.

I have not come across any publication by him in more than a decade.



R. Rocklin was privileged to be an author in fundamental textbooks. This

fact establishes him as a generally recognized scientist whose knowledge in this

field is indeed vast. Among his many publications is a chapter in Immuno-

pharmacology, a theoretical textbook published in 1982 (ed. by P. Sirois et al.)102

and another chapter was in Allergy 1985 (ed. by A. Kaplan),11 a textbook aimed

at experts in allergy and clinical immunology throughout the world. Rocklin’s

chapters are similar in both textbooks. No other textbook before or after has

provided such a complete picture of the histamine-based regulatory immune

mechanisms that underlie allergy. The author summarizes all the available

research on histamine, including his own. Both texts are unique sources of

extensive information on histamine as the principal participant of all pro- and

anti-inflammatory immune processes in allergy and on its unique role in the

functioning of the immune system. In Immunopharmacology, the title of

Rocklin’s chapter is straightforward and explains what it is about: “Immuno-

modulation of Immunity and Inflammation by Histamine.” Although the title

was later changed to “Role Of Cell-Mediated Immune Responses” in the text-

book Allergy 3 years later, its essence did not change at all.

Both chapters explain the principles involved in allergy, i.e. the genetically

predetermined primary defects, namely the original H2-receptor defect that

accounts for T-suppressor insufficiency and histamine hyperreleasability by

mast cells and basophils. The author shows that this defect can be corrected

through re-activation of these deficient receptors. Activation leads to the re-

generation of T-suppressors and the inhibition of the harmful mast

cell/basophile histamine release. Rocklin’s texts are forthright about the dual

role of histamine in the functioning of immunity. One reads under the

diagram on page 182 in Allergy 1985: “Some effects of histamine are pro-

inflammatory and enhance immune reactivity, whereas others are anti-

inflammatory and decrease immune reactivity.” On page 192, Rocklin

develops the concept that when immunotherapy with allergen extracts turns

out to be successful, one observes H2 receptor activation with resultant gener-

ation of T-suppressor cells. This idea can be logically developed further.

■ First, if active H2 receptors can end allergy symptoms, they should become

the target of any therapy.

■ Second, if well-selected allergen extracts can activate H2 receptors, histamine

can definitely do it even better, as nature itself selected histamine for this.

We may only speculate why in neither of these textbooks he consider hista-

mine therapy, which must suggests itself. It may well be that this brilliant



scientist understood, even at that early stage that, as a therapeutic means,

histamine treatment might be highly undesirable to financial sponsors of

medical research. The fact that the central findings for allergy researched and

published by Rocklin have gone into oblivion and exist only in past literature

is indicative of financial issues involved.

In 1981, a year before the publication of Immunopharmacology, in co-

authorship with another giant in immunology research, K. Melmon, Rocklin

wrote an article entitled “Autacoids as Modulators of The Inflammatory and

Immune Response.”2 The paper is primarily on histamine, and the word

modulator in the title says it all: histamine modulates immune inflammation.

The text reads as follows: “new drugs developed from mediators of inflam-

mation might be effective modifiers of the immune processes.” And further:

“As feedback control by autacoids can serve to modify immunity in a precise

and predictable way, we should probably begin devising a strategy for using

these ‘self-medications’ as alternatives to drugs that are less selective in

their actions.”

In 1984, a year before the publication of the textbook Allergy, Rocklin again

expressed the idea of the anti-inflammatory features of histamine in his lectures

at the Continuing Medical Education courses sponsored by the American

Academy of Allergy and Immunology. The AAAI (now called the AAAAI, due

to the added the word asthma to its name) is the flagship organization for all

allergy and immunology experts, and these annual lectures are, in essence, the

evolving guidelines for practicing physicians. Rocklin’s presentation that year

was later published in JACI and states that “only histamine and no other drugs

… leads to the elaboration of suppressor factor” through T-suppressor activation.

Pay attention: histamine is called drug! The title of the article, “Histamine-

induced suppressor-cells activity” does not leave any doubt about the role of

histamine in the functioning of the cells that control allergic reactions. “Ability

to activate suppressor cells... places histamine into the category of a ... physio-

logic ... autacoid,”3 that is: a self-healing bodily substance. As was said before,

autacoid is translated as self-remedy, while dictionaries define the word

‘physiologic’ as “characteristic of normal functioning, devoid of pathologic

features.” What else can one want of a medication? It can hardly be doubted

that a safe chemical normalizes the functioning of the main allergy fighters is

like “no other drugs”! This ultimately means that control of allergic inflamma-

tion is possible, and the patient has a medication-free life! The table on page

449 summarizes the regulatory effect of histamine upon the immune system,



and its title is again forthright about the role of histamine in the immune

system; it reads: “Modulation of cellular-immunity by histamine.” The article

says: “Once released, histamine presumably activates the suppressor limb of the

immune reaction and dampens the response by decreasing production or

release of inflammation-promoting lymphokines (cytokines).” “The

suppressor limb” involves mainly H2-receptor activation of T-suppressors that

inhibit allergic reaction. It is of special importance that for support, Rocklin’s

article sent the reader to an earlier work by L. Lichtenstein who is another

pioneer in the research into the modulatory properties of histamine. His works

will be discussed below.

Rocklin devoted another lecture of his to immunotherapy.4 On page 332,

the author names the therapeutic targets for immunotherapy—“induction of

… suppressor cells/factors” and “decreased reactivity of mediator-releasing

cells.” This simply means that activation by histamine enables T-suppressors to

inhibit all inflammation-promoting factors in allergy and also dampens the

hyperreleasability of the immunocompetent cells. Rocklin reinforced these

ideas two years later in the 1985 textbook Allergy by adding that not only are

T suppressors activated by histamine, but also their very existence depends on

it. On page 185, he talks about “the generation of histamine-induced

suppressor T cells” and “histamine activation of human suppressor T cells.”

There was no conspiracy around histamine at that time, and Rocklin could

easily call a spade a spade. So could others. Through the ’70s and ’80s, the

content of many articles and their titles were crystal-clear about the

immunoregulatory role of histamine. For instance, some of the titles were:

“Histamine-induced suppressor factors or autacoids as modulators of the

inflammatory and immune response”; or “Modulation of cellular-immune

responses in vitro and in vivo by histamine receptor-bearing lymphocytes”;

or “H2 receptor and the immune system,” etc. All of this was before the era

that started in the 90s when histamine became mysteriously taboo.

Textbook have stringent requirements to present either the established

information or explain that the given findings are being questioned or recon-

sidered. The requirements should be especially strict, if the presented material

is based on morphology, physiology and molecular biology—basic sciences

that do not usually change in essence but expand through new research. There

is no doubt that A. Kaplan, the editor of both editions of the textbook Allergy,

would have abided by these rules, or his position among his colleagues would

have been untenable.



Now imagine my surprise when in October 1997, at the university book-

store, I unsealed a fresh copy of the second edition of Allergy.103 My first inten-

tion was to see if there was new information on histamine, therefore I looked

up Rocklin’s name in the table of contents. By then, I had already noticed the

growing tendency to omit all histamine-related immune-modulating tools

and events. I had an inkling that, for medically unrelated reasons, the direction

of the new textbook might shift. What I saw exceeded my worst fears. The only

image I can think of here is that of a beheading. Allergy as a clinical science was

beheaded: Rocklin’s chapter, the only one on the primary underlying mecha-

nisms in allergy, had disappeared from this new edition.

The strangest thing, however, had happened to T-suppressors. The very

term T-suppressor was mentioned only in an allergy-unrelated chapter which

on page 783 questioned the very existence of these cells by asserting, without

any reasons given, that these cells had supposedly become “one of the major

controversies in immunology.” A material cell disappeared.

This raises a number of very basic and disturbing questions. How can one

explain the existence of their marker, T8 or CD8+, evidenced by the most

reputable medical textbooks and dictionaries? Are we suddenly to believe that

Gershon and his colleagues had in 1972 discovered some sort of phantom

cells, which they had capriciously named suppressors? Was this discovery a

hoax or a fantasy? Furthermore, how can one explain the discovery of the Is

(immune suppressor) genes that govern the functioning of the non-existing

T-suppressors? How can counter-suppressor cells exist if there are no

suppressors? How could the Clinical Immunology Committee of the

International Union of Immunological Societies at the World Health

Organization point to “expanded suppressor cells” as their target in the

improvement of immunotherapy if all of this was fantasy? By whom, how and

when were these cells abolished?

Mind you: T-suppressor is not just another cell. It is (was?) the key figure

in the regulation of all allergic processes of the immunity. If it was lost,

banned or re-classified, this unique fact had to be registered in all medical

sources and, above all, be explained! It had not.

With the disappearance of T-suppressors from all the chapters of Allergy

1997, H2 receptors, which are the distinctive feature of these cells, also “went

missing.” It is as if they were not discovered in the sixties by the Nobel

Laureate James Black—with the Nobel Prize seemingly being the only record

left of this discovery. If one was cynical, one might now expect, that the next



step will be the exclusion from the genome all of those already detected genes

responsible for the functioning of both T-suppressors and H2 receptors.

With Rocklin’s chapter excised, the facts and details, which substantiate

the mechanisms that underly allergy and prove the inseparability of these

mechanisms from histamine, we have a situation now in which there is no

real explanation in the current textbook, Allergy 1997, for what allergy actu-

ally is. This “disappearance” of histamine cannot be accidental: all mecha-

nisms of allergy, disease-promoting as well as protective, have an innate

dependence on histamine, and hiding its central role has led to a fundamental

misrepresentation.

The burying of this knowledge was done cautiously, so that it wouldn’t be

too obvious. On the surface, everything appeared proper: the chapters in the

revised textbook written by other authors listed all the cells (except T-

suppressors!) and their mediators and cytokines participating in allergic reac-

tions (except, of course, the histamine-induced suppressor factors). However,

listing of the cells is not enough to explain their effects, significance and inter-

relationship or show what to correct in the case of cellular malfunctioning.

Now, with everything related to histamine being omitted, the events in

allergic reactions have become hopelessly distorted. Thus, while the chapter

on mast cells and basophils provides a general description of their functions,

it does not specify that their release of histamine is the cardinal event both in

the early and late phases of allergy. Nor is there an indication that the cause

of these cells’ hyperreleasability is their deficient H2-receptors which are

unable to turn off the leakage.

Allergy 1997 is not so much a textbook, but a collection of puzzles with all

the needed clues gone. It does not answer the main questions: what cells and

what receptors control the balanced production of all cellular chemicals in

healthy people, and what goes wrong and leads to the disease. The new text-

book has created the impression that the immune system of an allergy patient

consists of cells whose chemicals work solely against the host. Naturally, only

the helping hand of the drug industry can correct this situation. Not surpris-

ingly, therefore, the second edition of Allergy 1997 has increased in the

number of pages now devoted to medication—the antihistamines.

You might object that as science develops, even some of the most solid

findings of the past may become obsolete, and this could be the reason for

changing the material in the textbook. That is a reasonable objection.

However, if this had been the case during the 12 years that separate the two



editions of the textbook Allergy, why was it not indicated, explained or

updated? Why was there not a word about such changes that would justify such

an abrupt departure from previous findings? Why were the old data simply cut

out? The fact is, the old findings have not changed. Nature has not suddenly

abolished T-suppressors and H2 receptors or changed their central regulatory role

in allergy. Rocklin’s description of the pivotal role of histamine and T-

suppressors in the immune functioning is as accurate today as it was in 1982

and 1985, when he wrote the chapters in Immunopharmacology in Allergy

1985. What is totally confusing is the fact that this new textbook, which went

through such pains to excise all reference to the existence of regulatory cells

in allergy, had no difficulty to accommodate these same regulatory cells in

allergies in a separate chapter devoted to cancer and participating T-cells!

The proof that Rocklin’s description of the immune mechanisms has

remained the basis of allergy medicine can be found in Pharmacological

Reviews, a huge collection of the most essential scientific papers and a most

reputable source of references.5 The title of the sub-chapter on page 69 is “H2

Receptors And The Immune System” and reveals the special role of these

receptors in the functioning of immunity; the author specifically refers to

Rocklin and Lichtenstein as the discoverers of the immunomodulatory role of

H2-receptors. So here, the established and unchallenged facts have snuck in by

the back door.

Up until now, Rocklin’s ideas have never been questioned or rejected as

invalid. After a decade of silence, the immune mechanisms described by him

can still be found in prestigious periodicals. Mostly, these are “silent” refer-

ences, and only in very rare situations, the text gives him the credit for the

discoveries. Earlier, we referred to the essential work sponsored by the National

Institute of Health in which it is said: “Interestingly, in the 1980s Rocklin and

co-workers published several studies showing that histamine induced

suppressor-cells activity and suppressor factor.”6 The article names this

factor, which is Il-10 (interleukine-10), and which is accepted by today’s

allergy medicine as the central tamer of allergic reactions. The authors of the

article “…strongly suggest that histamine, apart from exerting potent effector

function in inflammation and allergy (mainly via H1 receptors), may have

important immunoregulatory functions via H2 receptors expressed on

immune cells.” Actually, this is the only contemporary work I came across

among the many covering Il-10 that clarified that this central anti-inflamma-

tory chemical is a histamine-induced suppressor factor. None of the numerous



publications on Il-10 I have read related it to Rocklin’s discovery of suppressor

factors in 1977. The creations of nature, such as cells and their products, seem

to selectively disappear if they are in any way related to histamine.

In 1992, CPSO, which is the medical regulatory agency that licenses

doctors in the province of Ontario, initiated a Discipline Hearing against me

and prosecuted me for my “nontraditional” (and successful) use of histamine.

In 1993, in preparation to the hearings, my lawyer, Howard Kerbel, called

Rocklin and asked him to confirm his theory on immunomodulation via H2

receptor and the protective properties of histamine. I was present at their tele-

phone conversation. At first, Rocklin denied any research of his in the field!

Finally he realized that the lawyer he was speaking to was well informed on

the subject, and he said, “You got me, but it would be a conflict of interest for

me to speak on the subject.” At least he was honest about the situation: his

employer was now the pharmaceutical giant Boehringer, and his previous

research on H2-receptor stimulation was the opposite of the histamine-

suppressing allergy medications produced by the company. Rocklin suggested

to my lawyer that he call K. Melmon.

KENNETH MELMON was professor of Pharmacology and Medicine at

Stanford University. Starting in the ’60s, his research was primarily in hista-

mine, its immunopharmacological properties, especially the biochemical stim-

ulation of cAMP via H2 receptor. He also developed and tested histamine

derivatives. Since the ’90s, his name, like that of Rocklin, can be found mostly

in references, and even this use is waning. Melmon died in April 2002 at the age

of 67, and the central periodical for allergy, the JACI, did not even mention the

death of this giant of immunological research. If one day, clinical allergy decides

to put to clinical use his theoretical findings, or starts using his histamine

congeners, he will acquire the reputation of the savior of all allergy patients. I

say ‘if ’—because the essence of his work would be totally at odds with the

trends of contemporary therapy, which is drug and anti-histamine based.

Melmon was a frequent co-author with R. Rocklin and L. Lichtenstein. As

early as 1973, K. Melmon and L. Lichtenstein and others described how hista-

mine self-inhibits its release via the H2-receptor and thus acts as an

immunomodulator. They clearly elucidated the chain of events:

■ histamine activates the H2 receptor;

■ the receptor sends a signal to the intracellular system responsible for cAMP

enzyme production;



■ the levels of this enzyme accrue;

■ the messenger RNA governing the synthesis of anti-inflammatory chemistry

is activated;

■ the increased production of anti-inflammatory chemistry reverses allergic

reaction.

In this chain, the histamine/cAMP team becomes the core of the mechanisms

controlling allergic reaction, and the authors therefore also suggested that the

protective effect of histamine observed in vitro (in the test tube) should be

examined in trials in vivo (in living animals and people).7 Still earlier, in 1971,

the same authors thought of using the H2-receptor effect in treatment and

suggested particular concentrations (10-6M) of “exogenous histamine… to

stop the release of endogenous histamine.”8 In laymen’s language this means

that synthesized histamine inhibits production and release of body histamine.

Congeners developed by Melmon’s team are drugs specifically targeting H2

receptors, and indeed, they show impressive results in animal testing. All drugs

are first tested on animals and if they are safe and effective, they are subse-

quently subjected to human trials. In the case of histamine, it is most helpful that

almost a century after its appearance, it is probably the most researched drug on

the market, and its properties are known inside out. Being a physiologic autacoid,

it lacks toxicity—the major concern in all drug development—and its derivatives

are safe and promising for clinical use. This is what Melmon’s article said in

1985; it had a most poignant title: “Are Autacoids More Than Theoretic

Modulators of Immunity?” He wrote at that time: “The autacoids include

substances such as histamine... The hypothesis that autacoids might modulate

immunity slowly emerged... In the last 15–20 (!) years a number of investiga-

tors have proven the validity of focusing on this hypothesis.”9 I emphasized

the word focusing to show how far allergy has departed from that insight. Now,

another 20 (!) years after that suggestion was made, and almost 4 decades

having passed altogether, simply to mention histamine is equivalent to blas-

phemy, even worse, to speak of its self-remedial qualities.

That article advocated application of histamine and its derivatives. It stated

that “in vivo immune modulation now seems appropriate” and asks rhetori-

cally, “…who is applying the observations clinically?” Now read the following

carefully: “Why focus on histamine and its congeners as a prime investigative

autacoid for immune modulation? So far, it is THE ONLY autacoid shown to

have potential modulating influences on both early and late phases of

immune inflammation.”9



Melmon’s works reveal that he never changed his opinion about the cura-

tive properties of histamine. The 1996 textbook Therapeutic Immunology (ed.

by K. Austen et al.), with Melmon as an author, stated on page 192: “Histamine

appears to play an important role in limiting the inflammation processes

unlike any mechanism known for classic immune-suppressive therapeutic

agents.” The authors believe in histamine’s “potential as a therapeutic

immune-suppressive agent.”10 But, no matter how safe and good histamine

congeners may be, one should have strong reasons to doubt that they will be

used in medical offices in the near future, and this is why.

From the above-cited article, we know that “agents now are available that

stimulate one or the other receptor on selected lymphocytes,” which means

that for, at least 20 years, safe and effective drugs have existed that could selec-

tively activate the needed H2 receptor without activating its counterpart—the

H1 receptor. Allergy sufferers are definitely interested in knowing where these

agents are. So are doctors who deal with resistant allergies every day. Still, the

congeners have not been tried even for those patients with immune-related

inflammation who are not helped by any other medications. My opinion is

that Melmon’s research reached that stage in clinical medicine where even the

best minds are not free to choose the direction of their work. For example,

research grants are almost entirely controlled by the pharmaceutical industry,

and every contract contains a gag clause which provides the sponsor with the

power to disband the research effort when its results begin to contradict the

sponsor’s financial interests. These gag clauses are illegal in Canada, but they

continue to control research anyway.12 This is equivalent to a “Do not tres-

pass!” sign blocking practical application of all medical research. It seems that

Melmon’s findings were so compelling that they had to be buried. Not surpris-

ingly, the second (2001) edition of Therapeutic Immunology no longer contains

that chapter written by this great scientist and his team.

The process of research censorship appears to be systematic, because the

earlier 1997 edition of this same source, the Pharmacological Reviews, already

then excluded those parts contained in its even earlier 1990 edition, namely

the information that stressed the anti-inflammatory features of histamine

and the possibility of using histamine congeners developed by Melmon. For

example, the following passage was dropped: “These data suggest that hista-

mine-inducible suppressor cells may be important for normal immune regula-

tion and raise the possibility for the use of H2-selective and lymphocyte-selective

agonists as immunosuppressant agents. An exciting advance in this area of



research has been provided by the development of lymphocyte-specific hista-

mine derivatives. A number of histamine congeners have now been

produced.” Two references to Melmon are given at this point.13 The curative

properties of histamine did not change with time, and only the editors know

why the key elements needed for therapeutic purposes suddenly needed to be

hidden and were deemed so irrelevant as to be removed from the text. This

elimination makes even less sense in view of the regret the editor Dr. Hill

expresses over the “neglect of histamine” in the report made by his team at the

International Union of Pharmacology. This report was later included into the

1997 edition of Pharmacological Reviews.14

I can only imagine the disappointment Melmon must have felt when in

the last years of his life he realized that all his gigantic work was unclaimed

for clinical application and would not be used to help patients.

I have read all the works by Melmon on histamine I could find. Within

our correspondence, I was also privileged to view his not yet published work

on a newly discovered histamine receptor. His extensive knowledge of hista-

mine activity, and especially his desire to find a practical solution to the

problem of immune inflammations through histamine and its derivatives,

impressed me most. In 1991, I wrote Melmon a letter about my use of hista-

mine for asthma and allergies and enclosed the following abstract, already

accepted for the presentation at an international congress.

H2/3 Effect in Allergy

In acute state of allergy, the proportion of histamine to other mediators is

300:10(PGD2):1(LTC4); in pollinosis, H is the prevalent mediator. Unlike the

pathological H1-receptor action, H2/3-receptor protective effect described in

patholophysiology and pharmacology works mainly via a) activation of intracel-

lular cyclic AMP in mediator cells; b) cytokines with histamine-induced

suppressor factors determining Ig levels, perpetuation of allergic disease, its

chronicity, including non-specific bronchial hyperresponsiveness; c) autoregula-

tory H3 receptors that together with H2 receptors provide histamine and other

mediators inhibition. Thus, H2/3 effect is the key autoregulatory of humeral and

cell-mediated immunity, hence, of allergic inflammation. The existing consensus

re SUCCESSFUL hypo sensitization criteria emphasizes histamine-induced/

dependent mechanisms: decreased mediator release (basophile histamine release

test) and stimulation of suppressor T-lymphocytes with generation of H2-



receptor-bearing cells, while IgE level changes are inconsistent. This adds to the

classical theory based on antigen-antibody mechanism unable to explain certain

events in pathogenesis and suggests that the basis for allergy might be an inher-

ited or acquired receptor/enzyme deficiency to be corrected by stimulatory H2/3

effect of exogenous histamine and/or conventional hypo sensitization. The

hypothesis uniting non-specific and specific factors is supported by works of few

authors successfully using histamine and by my experience with about 2,000

patients with various allergies, over 75% of whom were treated with histamine.

The original technique for the method is described elsewhere. The preliminary

results, especially in cases of hay fever in season and bronchial asthma, are supe-

rior to those by any other treatment ”15

I asked Melmon if he was interested in the effect his research could have in

clinical practice and if he did, I would send him additional information. In

response to my letter and abstract, to prove the seriousness of his interest,

Melmon supplemented his letter of August 28, 1991 with his impressive 30-

page curriculum vitae and his articles on the (crucially significant) dual role

of histamine. He even sent me his yet then unpublished paper in which a

hand-written sign confidential crossed each page. In his letter (see Appendix)

the scientist wrote: “I am substantially interested in knowing how you came

to the conclusion, which I share, that H2/3 activity is likely to be immuno-

suppressive” (suppresses allergic inflammation through activation of “protec-

tive” immunocompetent cells). Encouraged by his interest and support, I sent

Melmon my recently published article, which had references to his work.

Melmon’s second letter of December 3, 1991 ended with “I do look

forward to further opportunities to reviewing and sharing your excellent

work.” I was happy that the great researcher was supportive of my work, but

our communication was interrupted for reasons of a nonmedical nature. In

1993, the journalists of the Canadian Broadcasting Corporation, who were

sympathetic to the plight of allergy/asthma sufferers, were preparing a

national TV program of the CPSO’s actions against my histamine therapy. In

a telephone conversation, they asked Melmon to comment on my work.

Melmon refused to do so. By that time, I had already become a medical “dissi-

dent.” Melmon had been contacted by the prosecutor, as the latter admitted

later during my discipline hearings, and, most probably, he had been told that

it would be wiser to sever our communication!16



I have the highest respect for the work done by Rocklin and Melmon. I

believe that for their contribution to allergy research, they deserve much more

credit than allergists have given them. But the very reasons for which they

should be revered are the reasons for concealing the essence of their work—

the histamine connection.

LAWRENCE LICHTENSTEIN is a former president of the AAAI and

Director of Johns Hopkins Asthma and Allergy Center, one of the world’s

most prestigious medical schools. He is a recipient of the Research Career

Development Award of the National Institute of Allergy and Infectious

disease of the US Public Health Service given for his research on the under-

lying immune mechanisms of allergy. Lichtenstein is a prolific author and

editor of papers and textbooks, key-note lecturer at international forums and

committees, and a board member of leading medical periodicals.

Lichtenstein and Melmon teamed up at the time of their most outstanding

discoveries related to histamine and produced a number of articles of such

basic importance to allergology that they continued to be referred to, even at

the peak of the censorship of works on histamine. Curiously, at the time his

own presentations began to show a dramatic change in his views on histamine.

None of his works or oral presentations has provided any scientific explanation

for these changes.

Lichtenstein started to study the H2-receptor functions soon after their

discovery by James Black and he was actually the first to show that this

receptor is an instrument through which histamine realizes its immune

modulating function. Together with Melmon, Lichtenstein specified the

concentrations at which histamine self-inhibition actually takes place, namely

at 10–6M (i.e. ten to the power of minus 6).17 Two years later, in another

article with the self-explanatory title “Inhibition of histamine release by hista-

mine controlled by H2 receptor,” they say: “…exogenous histamine could stop

the release of endogenous [histamine].” In another article, he again pointed

to mast cells and basophils as the major histamine-releasing cells and speci-

fied the concentrations at which the leakage stops.18 The article develops the

idea that “the H2 receptor located on the histamine-releasing cells, possibly

mediates an inhibitory effect on the inflammatory responses.” It is of interest

that the authors compare the histamine effect to that of antihistamines and



favor the first: “no clear effect of antihistamines on the inhibition of hista-

mine release was observed.” Moreover, they add that in high concentrations,

antihistamines “were cytotoxic,” that is, their toxicity disrupts cellular func-

tioning. (It should be of great interest to patients that today, allergists are

suspiciously silent about the self-inhibitory effect of histamine as well as

about the toxic side effects of antihistamines, but instead are very vocal about

their supposed benefits).

Four years later, Lichtenstein was still researching the H2-receptor effect and

wrote: “Our results suggest that differentiation of T-cells is accompanied by

…appearance of histamine (H2) receptors”; and again the authors specify the

protective role of these receptors in allergy.19 In another paper written with

Melmon, Lichtenstein expresses the idea of the exclusive anti-inflammatory

role of the H2 receptors in the functioning of T-cells, mast cells and basophils.

At this time of the most intensive research into histamine, the authors theorize

about the possibility of transferring the histamine H2-receptor effect into clin-

ical practice and so they wrote: “understanding of such a regulatory mecha-

nisms may open the way to new therapeutic approaches to treatment of

immunologic and inflammatory disorders in man.20 In other words, activate

the H2-receptors, and the differentiated T-“regulator-suppressor cells” will

mediate “an inhibitory effect on the inflammatory responses.” Only the scien-

tists themselves can tell why they stopped short of employing histamine clini-

cally. Was it their insufficient clinical expertise?

In the early ’90s, Lichtenstein’s stand inexplicably changed. In 1994,

Toronto allergist Dr. Allan Knight, was appointed as an expert witness by the

CPSO during my disciplinary trial in order to disprove the benefits of the ther-

apeutic use of histamine. The official transcripts contain his admission during

cross-examination that he was unfamiliar with the H2-receptor immune

modulating function described in depth by Lichtenstein 20 years before.

Knight’s lack of expertise and knowledge in histamine properties and treat-

ment prevented him from providing scientific arguments and/or sources

against the histamine immunotherapy or desensitization I was using, and so

the “expert” decided to come to the hearings with a better weapon—a personal

letter from Lichtenstein. Judge for yourself whether this letter of January 19,

1994 can be recognized as providing a scientific basis for disproving histamine

therapy:



Dear Dr. Knight:

Thank you for informing me about the physician who is quoting my

published work to defend his therapy. I have never written anything about

histamine desensitization. There is no scientific fashion in which anything

I have ever published could be used to defend histamine desensitization.

I personally believe, together with all of my colleagues, that histamine

desensitization has no role in any medical therapy.”

The high professional status of Lawrence Lichtenstein and his profound

knowledge of immunology did not require him to solicit support of “all of his

colleagues” in order to write this short note and point to the supposed

consensus in rejecting histamine desensitization. I was an unknown general

practitioner, whereas Lichtenstein was at that time the president of AAAI.

Strangely, he did not say that histamine therapy would be dangerous or inef-

fective. He seems simply to have wanted to dissociate himself formally from

his earlier histamine research by saying he had “never written about hista-

mine desensitization.” His carefully worded 5-sentence note contradicted his

own previous research: in the past, he had described histamine’s H2-receptor

activity as immune modulating, whereas now, he opposed its therapeutic use

for immune modulation. Moreover, the word immunomodulator can only

mean the wide-scope activity of the drug in a live body.

Lichtenstein’s note suggested that I had misinterpreted his ideas on

possible histamine desensitization. If so, I was not the only one. The “misin-

terpretation” of Lichtenstein’s ideas continuously occurred and still occurs

even at the highest level. Practically all authors who describe underlying

mechanisms of allergy refer to his earlier works and thus, “misunderstand”

him. Below are several examples.

■ Chapter 3 included in the textbook Allergy 1985 and titled “Biochemical

Events in Basophile/mast Cell Activation and Mediator Secretion” covers

the biochemical reactions in allergies. The text on page 44 says: “The

desensitization signal is generated in parallel to a cell activation signal.”

In other words, histamine leakage from mast cells and basophils is not a

unilaterally apro-inflammatory process, since, in parallel, it awakens the

“desensitizing” forces as well. These forces, as page 45 indicates in a table,

are the H2 receptors activated by histamine. To support this idea, the

chapter provides 7 (!) references (65–71) to Lichtenstein.



■ Two of the world’s leading immunopharmacologists stated in 1990:

“…release of histamine from human basophils is inhibited by histamine

itself. The possible mechanisms of the inhibitory effect is H2-receptor

mediated.” Three references to Lichtenstein (8, 9, 10) follow.21

■ Pharmacological Reviews is the publication of the American Society for

Pharmacology and Experimental Therapeutics.22 This publication is the

constellation of those theoretical works that form the foundation for

drug development. The included works are, actually, theories planned

for implementation in clinical medicine. The authors of a subchapter

H2-receptors and the Immune System dedicated to immunomodulation

by histamine, also seem to have misunderstood Lichtenstein. On page 69

the text says: “These data suggest that histamine-inducible suppressor cells

may be important for normal immune regulation and raise the possibility

for the use of H2 selective and lymphocyte-selective agonists as immuno-

suppressant agents.” There are 4 references to Lichtenstein. We should

disregard the oxymoron, when immune modulating histamine is called

as immunosuppressive for its ability to suppress allergic inflammation.

Otherwise, the text is clear: it is time to introduce histamine or its deriv-

atives into clinical practice, and Lichtenstein’s research endorses this.

■ The authors of another international publication devoted to drug

research regret that “potential uses of H2 agonists, such as a reduced

release of mediators of allergy, like histamine itself, from, for example

mast cells, so far have not led to a clinical application.” In the middle of

this sentence, they refer to the 1982 work co-authored by Lichtenstein

that classifies histamine receptors.23

■ The publication of the European Histamine Research Society, which

is devoted solely to histamine research, contains an article by Swedish

authors who write about nonspecific desensitization implemented by

histamine. “A current belief is that the two processes, release and desensi-

tization, proceed simultaneously. …” It is believed that desensitization

exists as a normal regulatory process during the release of histamine in

vivo.” In their description of the desensitizing ability of histamine, the

authors refer three times to Lichtenstein (ref. 5–7).24

■ Another international team wrote on the anti-inflammatory features

of histamine in a recent issue of Nature,25 and they seem to be one

more causality of “misinterpretation.” Reference 5 points to the paper



“Selective Display of Histamine Receptors on Lymphocytes”

co-authored by Lichtenstein.26 If we look into this reference (which was

also presented at my disciplinary hearings), we will read in the very first

paragraph: “…histamine mediates several anti-inflammatory effects via

histamine type 2 receptors.” The use of these receptors in therapy is

nothing but nonspecific desensitization.

The fact that so many high profile authors understood Lichtenstein in the

same way I did, means that all of us, in fact, understood him correctly: his

research proves that histamine possesses desensitizing functions. In this

connection, it is not clear why the histamine desensitization I conducted

caused an outright rejection by Lichtenstein. All I did was put it to use

successfully: I performed what the earlier award-winning research by this

allergy guru had been suggesting.

Of special interest is the dynamics of the changes in Lichtenstein’s views.

In his later works, he presented histamine as “the most infamous mediator.”27

Even in his Presidential Address, when he spoke about his career and scien-

tific achievements, Lichtenstein never mentioned histamine’s immune modu-

lating role which he had discovered and researched.28 In none of his

subsequent work does Lichtenstein any findings that would have had to have

been the cause for his radically changed position. By describing histamine as

a substance of solely disease-promoting activity and ignoring its innate self-

remedial properties, he misrepresented his own thoroughly studied scientific

data. This is regrettable, for he could be proud of his earlier work; decades

ago, he had said what the editors of JACI now present as a very important

issue: “…histamine might have a chronic antiallergic effect… .”29

Lichtenstein’s change in attitude becomes especially evident when one

looks at the difference between his views on drugs in general and towards

histamine as a potential drug. Here is an example. Along with histamine recep-

tors, Lichtenstein studied beta-adrenergic receptors, which are the target of

bronchodilators (also known as “puffers”) used in asthma. He writes in an

earlier quoted article that “asthma may be such an experiment of nature” in

which certain receptors (beta-adrenergic) are deficient. The deficiency, the text

says, leads to bronchial spasms, and this justifies the therapeutic use of beta-

stimulators called bronchodilators, which, upon inhalation, open the airways.

This article20 casts doubt on Lichtenstein’s latest position: if he thinks its

logical to activate one kind of deficient receptors (beta-adrenergic) with stim-

ulators (bronchodilators), why is he against a similar activation of another



inefficient type (H2) with histamine or its congeners? Especially so, because

Lichtenstein knows and reported repeatedly that a bronchial spasm is an event

secondary to the histamine-induced pro-inflammatory chemistry in the

airways. His own role in establishing this scientific fact becomes evident in

Chapter 10, written by Rocklin in Allergy 1985.

When Rocklin wrote that deficient histamine H2 receptors are the primary

cause of any allergy, he referred to Lichtenstein (references 55, 56).11 With this

knowledge, the stimulatory effect of histamine should look more attractive

than the use of beta-adrenergic drugs for several reasons.

■ First, the effect of bronchial inhalers on beta-receptors is short-lived since it

is applied to the secondary event;

■ Second, it is a recognized fact that bronchodilator use is dangerous in the

long run.

■ Histamine, on the contrary, produces an immune modulating effect via the

H2 receptors, and the effect can be lasting because it goes to the core of the

problem.

■ Being a physiologic autacoid, histamine is safe, as Lichtenstein once

declared.

Why, when and for what real reasons did these advantages turn into disad-

vantages in the opinion of the learned scientist?

Anti-inflammatory immunosuppressive medications may serve as

another example of the scientist’s position—now biased towards drugs in

spite of his own research. “Compounds more commonly prescribed to alle-

viate the chronic inflammation of asthma are often helpful,” writes

Lichtenstein on inhaled steroids in 1993.30 By saying that, he encourages the

use of these drugs, immunosuppressive in the generally accepted pharmaco-

logical classification, but “immune modulating” in the vocabulary of aller-

gists. What could possibly be wrong then with the use of histamine, whose

activity Lichtenstein had also called immunomodulatory ? Lichtenstein

evidently saw the therapeutic use of histamine back in 1974, when he said:

“histamine…might limit the extent or severity of an inflammatory reac-

tion”31 and also three years later when he repeated the idea: “histamine has

marked modulatory effects on… immunity”32 Isn’t modulating an inflam-

matory reaction the goal of any therapy in allergies? If so, why was histamine

excluded from the list of the core allergy mediators taught at the AAAI-spon-

sored training program for allergists and immunologists in 1994 when

Lichtenstein was its president?33



Interestingly, the material included antihistamines, and, logically speaking,

even if histamine was now supposedly the most “infamous” mediator, it

should have become the center of the lectured material in order to clarify and

successfully sell the use of these wonderful new anti-histamines. I am not

suggesting that Lichtenstein personally excluded histamine from the

program. However, for decades, he has remained an undisputed authority in

allergy, and that year, he was the spokesperson for American allergists, so he

should have known what was being put onto the program.

Just where is that line that separates research from clinical medicine? Why

do scientists abandon their own outstanding work when it comes to its poten-

tially successful application on patients? Nobody can answer this better than

Lawrence Lichtenstein who possesses the highest expertise in immunology in

general and histamine effects in particular.

The projects Lichtenstein pursues today include the development of a better

version of Claritin, and the sponsor is Schering, a drug-manufacturing giant.

He also works on modification of therapeutic allergen extracts to make them

safer and more efficient. At this point, we should go to his earlier admission that

the target of any immunotherapy is the H2-receptor activation: “In the context

of allergic or inflammatory responses… the H2 receptor, located on the hista-

mine-releasing cells, possibly mediates an inhibitory effect on the inflammatory

responses.”34 It is unclear what advantage the scientist has found in new allergen

extracts over histamine, designed by nature, to activate H2 receptors.

Lichtenstein is also involved in the development of drugs that are called

phosphodiesterase inhibitors, or shortly, PDE inhibitors. They are supposed to

delay the degradation of cyclic AMP. Lichtenstein was ahead of others in pointing

to the unique significance of this enzyme, the fact he admitted in another

article he co-authored, in which he observed that back in 1968, he and

Margolis presented in Science the first evidence implicating cyclic AMP as being

in control of leukocyte function.35 To emphasize the point, I will repeat the quote

made earlier from this same article: “If leukocytes or mast cells of asthmatics

accumulate lesser amounts of cyclic AMP … than do the same cells in normal

subjects, physiologic control of the release of inflammatory mediators might

be deranged” (p. 25). In other words, the primary biochemical defect in allergy

patients is low levels of cAMP, which, correspondingly, results in the hypoac-

tivity of certain immune cells. It is significant that Lichtenstein is also credited

with classifying histamine receptors H1 and H2, as well as the findings that the

enzyme cAMP accumulates upon the impulse delivered by the H2 receptor.



Two decades after Lichtenstein’s article in Science, doctors and researchers

are assured by Pharmacological Reviews that the ideas initiated and developed

by Lichtenstein in the ’60s and ’70s on histamine’s acceleration of the enzyme

cAMP’s accumulation have remained unchanged. This highly scientific text is

surprisingly clear and easily understood. On page 146 in Agents & Actions, the

publication of the European Histamine Research Society, we read: “Histamine

is one of the most potent stimulants of cyclic AMP accumulation in

mammalian brain slices. This increase in cyclic AMP induced by histamine

involves both H1 and H2-receptors. Stimulation of H2 receptors produces a

direct… activation of the cyclic AMP-synthesizing enzyme adenylate cyclase,

while H1 receptors act indirectly to augment the cyclic AMP response to H2-

receptor activation.” The author provides references to Lichtenstein.36 (It is of

interest that collaterally, we come to realize that H1-antihistamines interfere

with the activity of H2 receptors.)

Research in this vital area has never ceased, and the accrued data reaffirms

the importance of the earlier works of Lichtenstein. Thus, researchers from

the National Institutes of Health, Bethesda, Maryland, describe the existence

of the protective CRH/mast cell axis (CRH stands for corticotropin-releasing

hormone produced by the hypothalamus).37 This paper says: “Over the last 10

to 15 years, strong evidence has emerged that histamine may have important

immunoregulatory functions through H2 receptors that are expressed on

immune cells. We have recently found that histamine, through the stimula-

tion of H2 receptors…and the subsequent elevation of cAMP…stimulates the

production of Il-10” (central anti-inflammatory cytokine). The existence of

this axis is the recognition of the interplay of the central regulatory systems,

namely of the brain (hypothalamus is a reservoir of histaminergic neurons)

and the immune system (mast cells and basophils with their histamine gran-

ules). This scheme not only puts the histamine/cAMP unit into the center of

regulation, but also gives the direction for future therapies that can cover both

regulatory systems, namely by H2-receptor stimulation with histamine.

It is hard to overestimate the importance of the axis, which, as the text

says, participates “in the adaptation and, hence, survival of an organism.” The

existence of the axis reveals the urgent need to implement psychoneuroim-

munology in clinical setting and employ histamine as the vehicle of curative

messages in these regulatory systems.

No doubt Lichtenstein is on top of all this information; especially so, because

it relates to his previous extensive research on cAMP, and also because now, he



develops drugs for asthma that are supposed to target this enzyme cAMP. The

drugs are phosphodiesterase inhibitors, or PDE inhibitors. Strangely,

Lichtenstein, who described how exactly to reach this enzyme, chose a different,

twisted approach. The drugs he is working on will have an effect similar to the

one of theophylline. The Canadian Compendium of Pharmaceuticals and

Specialties writes in the entry on Theo-Dur: “The actions of theophylline may be

mediated through inhibition of phosphodiesterase and a resultant increase in

intracellular cyclic AMP.” The above quoted article co-authored by Lichtenstein

described as far back as 1974 the target of this drug group, and on page 20 of

that 1974 Science article, we learn that it is inhibition of histamine.Thus, it is a case of all roads leading to Rome: control over histamine release

is the unspoken but ever-desirable aim of allergy/asthma medications, and the

novel PDE inhibitors are not an exception. Now that asthma has reached

epidemic proportions, the idea of reinventing theophylline-like medications

must be very attractive for drug producers. It kills two birds with one stone.

■ First, by concentrating on retarding the metabolism of the enzyme cAMP

with PDE inhibitors, allergy diverts attention from the possibility of raising

it with histamine.

■ Second, the development of theophylline-like medications will provide

numerous scientists with work, and their gratitude will come back to the

sponsors in the form of high profits.

Will the newly synthesized inhibitors be more effective than their antiquated,

not-so-effective older cousins? I doubt it, and, indeed, the first trials of the

novel drugs are admittedly not very promising.

There is nothing wrong with improving antihistamines, perfecting allergen

extracts or creating new inhibitors. Allergy is a troubled field in clinical medi-

cine today, and anything should be researched to put the best into practice.

However, Lichtenstein who studied in depth the biochemical mechanisms that

underlie allergies and knows the most efficient ways to treat these diseases, is

now doomed to settle for ineffective ways based on false targets. He works on

antihistamines once recognized by himself as cytotoxic. He tries to make

allergen extracts safer, although at the time of his ground-breaking research on

cAMP, he thought that “understanding of such a regulatory mechanisms may

open the way to new therapeutic approaches to treatment of immunologic

and inflammatory disorders in man.” He knows how to activate H2 receptor in

order to increase the much-needed enzyme, but instead, he develops impotent

inhibitors that may, at best, maintain its levels as they are.



It is not a secret that medicine is largely controlled by the pharmaceutical

industry, and that the latter has a purely money-based approach to any

research. Today, cAMP has become one of the main focuses of attention in

allergy, for this area carries a great potential in drug creation. Lichtenstein’s

timely and actively propagated views helped to re-orient allergy. The research

he started on the enzyme cAMP and his great contributions to immunology are

now cast into relative oblivion, as is the work by Rocklin and Melmon. The

Primer on Allergic and Immunologic Disease published in JACI in 200338 does

not even reference his work anymore. Also, there is no mentioning of his work

in the two supplements of JACI that cover major symposia and yet they are full

of reports on cAMP.39 This is only natural, since reference to Lichtenstein’s arti-

cles would reveal the essence of allergic processes which is the cAMP/histamine

connection. I doubt that a scientist can be happy with situation of oblivion.

However, Lichtenstein may not share my views.

I do not have the right to condemn any researcher for the betrayal of his

work, as I know very well that the monstrous machinery of the drug industry

would crush those who dared to contradict it. The drug industry, in terms of

profit and economic principles, is justified in its opposition to histamine, but in

terms of ethical principles society ought to support those doctors whose moral

compass differs from that of drug developers. Today, doctors in research mainly

toil to serve the industry, not their patients. They have become drug promoters,

hiding the truth undesirable to research sponsors.40 Our society must help those

who are eager to introduce the most significant discoveries into practice in

the interests of patients, not the industry. At present, the role of a messenger

in allergology is fraught with great danger, and the a la Hamlet dilemma—to

tell the truth or not to tell—is solved negatively.

Before going to the next authority in the field of histamine, Allen Kaplan,

we need a preamble that will clarify the topic of his research, which is the

chemistry induced by the initial histamine spill. Unchallenged is the fact that

when the immune system of an allergy patient is activated, the easily excited

mast cells/basophils start to leak histamine and pro-inflammatory chemistry.

However, the very same immunocompetent cells, although flawed, defend the

host and respond to the challenge by secreting anti-inflammatory chemistry

such as histamine-induced suppressor (or inhibitory) factors, HSF or HRIF,

which belong to anti-inflammatory cytokines. These suppressor factors are the

primary protective weapon in the cellular fight with the inflammation

promoting chemistry.



The first histamine-induced suppressor factors brought to life by H2-

receptor activation were described by Rocklin in 1977.41 Discovery of other

histamine-induced suppressor factors soon followed. Along with that, the

pro-disease histamine releasing factors, HRF, or pro-inflammatory cytokines,

were discovered. In 1989, J. Grant and R. Alam (the latter received an award

for this research) gave lectures at the annual meeting of the AAAI. These

lectures formed the basis for their article published two years later.42 The

authors called histamine-induced factors “a missing link” in the under-

standing of the underlying mechanisms of allergy. On page 690, one reads:

“Histamine, a major mediator of allergic injury, may have an additional effect

by increasing synthesis of HRIF, a specific inhibitor of HRF, which may restore

local homeostasis.” [HRIF–histamine release-inhibitory factors, synonym of

histamine-induced suppressor factors] Moreover, “the clinical relevance of

cytokine-dependent mediator release from mast cells/basophils extends

beyond the boundary of the atopic (allergic) disease,” and that similar effect “is

observed in many chronic inflammatory disorders.” These include rheumatoid

arthritis, ulcerative colitis… and the rejection process of some tumors.” Not

only does this all point to the common roots of these chronic diseases, but

also puts histamine into the center of various immune-related inflamma-

tions. Allergic inflammation is just one of them, but it is most closely related

to histamine activity. This also means that the state of disease or health is

determined by what histamine-induced factors prevail—pro- or anti-disease.

Naturally and unavoidably, the article has references to the works by L.

Lichtenstein—and also by A. Kaplan.

At the time of this report, AAAI obviously did not realize how explosive

this “missing link” could be in understanding allergies. The very mention of

histamine-induced suppressor factors leads inevitably to considering

T-suppressors that generate them. In turn, T-suppressors lead to H2 receptors

because there are no active suppressor cells, or their protective factors without

efficient H2 receptors because: “differentiation of T-cells is accompanied by…

appearance of histamine H2 receptors,” as Lichtenstein wrote.43

The chain logically ends with the final link—histamine, as the best natural

activator of H2 receptors. Melmon’s team described, and we earlier quoted,

the reciprocal relationship of histamine and histamine-induced chemistry:

“Histamine regulates the release of lymphokines. Release of histamine is

influenced and regulated by lymphokines.”44 All this knowledge involuntarily

leads to the seditious idea of using histamine with the purpose of counter-



balancing pro-inflammation chemistry. To prevent doctors and researchers

from taking this lead, all histamine-related links of the chain have mysteri-

ously disappeared from contemporary scientific sources: histamine-gener-

ated suppressor cells, histamine-activated protective H2 receptors and

histamine-induced suppressor factors. What was once called “the missing

link” has now gone physically “missing.”

During the ’90s, allergy started to describe the chemistry in allergic reac-

tions solely as a one-sided pro-inflammatory promoting event, with the anti-

inflammatory chemistry totally ignored as if it doesn’t exist. The impression

is that the role of the immune system is not to defend but to harm, and that

the tendency to balance is not part of its nature. In reality, every action is

opposed by an appropriate counteraction, and only the net effect determines,

which way the disease goes. For instance, even the main “culprits” in allergy,

namely the mast cells that start a reaction by their exaggerated histamine spill,

“have recently been described as having other properties that could be inter-

preted anti-inflammatory.”45 Interestingly, such revelations can mostly be

found in areas of medicine other than allergy, although allergies are the most

reversible of all immune diseases, and allergic inflammation is nothing but

histamine-induced bidirectional chemistry. If the need of balanced immune

functioning is occasionally recognized by allergy as a theoretical possibility,

patient management is based solely on the suppression of one or several

disease- promoting mediators, or on the suppression of the cellular produc-

tion on the whole. The natural suppressor factors able to counterbalance the

activity of the inflammation promoting chemistry are never in the picture.

Now, the person who especially contributed to this new unilateral

approach is Dr. A. Kaplan, a former president of AAAI and the editor of both

editions of the textbook Allergy. He is the 2003 President of the World Allergy

Organization and the editor of the journal Allergy and Clinical Immunology

International.

ALLEN KAPLAN’s research always focused on histamine-induced factors. It

is interesting to follow the changes in his presentation of the mechanisms of

allergies. As mentioned earlier already, in the article “Immune Mechanisms”

co-authored with Kaplan and presented at the 47th annual meeting of AAAI,

it is stated that the ratio of histamine-induced pro- and anti-inflammatory

factors “may be critical to pathogenesis of a wide variety of allergic and rheumatic

diseases” and “may determine levels of inflammation observed in allergic



diseases as well as other chronic immune diseases.” The authors also wrote

that this ratio “may play a role in the pathogenesis of disease in which hista-

mine is an important mediator” and recognize that histamine induces the

production of bifocal chemistry, which, in turn, is “an important regulatory

mechanism in the releasability of histamine.” This echoes the above-quoted

idea expressed by Melmon the same year in Agents and Actions: “Histamine

regulates the release of lymphokines. Release of histamine is influenced and

regulated by lymphokines.” Thus, in the interpretation of Kaplan and his

team, histamine release becomes the determining factor in the development

of immune-related inflammatory diseases.

In 1995, as a co-author of another article, Kaplan still preserves the same

views on allergic reactions: “a balance between molecules of HRF or HRIF

activities exists which may determine the level of inflammation observed in

allergic diseases.”46,47

Only two years separate this article from the second edition of the text-

book Allergy edited by Kaplan (discussed above in some detail), but the

revised edition inexplicably omits these determining factors, as does the

chapter by A. Kaplan himself on cytokines. Only one sentence on page 78

reveals that the author does know that immune processes are a two way street:

“Some initial studies of asthma have examined the possibility that HRF, as

inflammatory agonist, and HRIF, as control mechanisms, are important

contributors to symptoms, and that the relative ratio of the two might deter-

mine the clinical course.” For a reader not privy to this secretive information,

the off-hand use of HRIF looks not as the determining event that could

reverse allergic reactions but as an insignificant detail undeserving of clarifi-

cation. There is no explanation that HRIF stands for histamine-induced

release-inhibitory factors, which is, actually, a synonym of HSF—histamine-

induced suppressor factors. With the absence of the required explanation, only

those who have studied these factors since this research began will understand

the meaning of the abbreviation HRIF.

However, the author does more than just hide the protective chemistry.

The pro-inflammatory factors described by Dr. Kaplan in the textbook make

allergic reaction appear as if it was a unilaterally disease-oriented phenom-

enon. One can only wonder about the reasons for his preference for such an

incorrect description of allergic reactions in the textbook, which, as Dr.

Kaplan’s website states, “is utilized in training programs throughout the

world” (www.alergycenters.salu.net/stuff/html).



The best evidence that immunocompetent cells are enabled by nature to

organize an effective defense is the existence of people who do not have aller-

gies despite the numerous surrounding triggers. It is only legitimate to ask what

cells organize such a successful defense, and indeed, the answer is basic scien-

tific knowledge: T-suppressors are our main protectors, and suppressor factors

are derived mainly from T-suppressors. But, as we have seen, T-suppressor cells

are a forbidden subject now because of the fact that “… only histamine and no

other drugs … leads to the elaboration of suppressor factor.”48 It is the unique-

ness of histamine as a remedy, both cellular and synthetic, that has become the

obstacle preventing allergists from even mentioning this substance. The fact is,

that histamine as a drug or its congeners could generate and/or activate T-

suppressors and by that, intensify the production of anti-inflammatory chem-

istry. Histamine as a drug could, become a successful competitor to the

numerous medications blocking the inflammatory chemistry. Only Dr. Kaplan

himself can prove or disprove that his changed stance is in any way related to

the dominant market concern—profits. Since Kaplan’s works once described

the bifocal histamine-induced chemistry, its presentation as being only pro-

inflammatory in the 1997 version of Allergy cannot be accidental; nor can the

disappearance of the Rocklin’s chapter from the revised edition of the textbook

edited by A. Kaplan.

As was said before, in 1994, the CPSO was using the service of Dr. A.

Knight as the expert witness in histamine therapy. Being unable to provide

any subject-matter expertise on the topic, this professor of the University of

Toronto solicited help from “heavyweights,” L. Lichtenstein and A. Kaplan, to

support him in his task to discredit my therapy. Like Lichtenstein, Kaplan

gave his opinion on the subject. His letter was to be admitted in the hearings

as evidence, therefore the author was supposed to tell the truth, only the

truth, and nothing but the truth. In my understanding, he did not. In his very

short note dated January 20, 1994, he said:

Dear Dr. Knight:

The use of histamine in vivo as an immunomodulator (i.e. histamine injec-

tions) has no validity whatsoever at any dose. Any interpretation that the

textbook entitled Allergy that I edited, recommends this therapy is a misrep-

resentation of what was described and has nothing to do with clinical disease.

Let us investigate if this is so. It is true that Dr. Kaplan never suggested

doctors use histamine as a therapy. However, contrary to what his note says,

Allergy 1985 does provide ample evidence of histamine’s immunomodulatory



effects. Thus, on page 704 in the Index we find under “histamine” that there

is the rubric “immune response modulation by (histamine).” The reference at

this point sends the readers to pages 179–189 on which Rocklin’s chapter

convincingly, and in detail, covers immunomodulation with histamine. Pages

58 and 60 of this textbook are not included in the Index under “histamine,”

which they should have been for their relevance. Page 58 says: “cells with

histamine receptors can also generate immunoregulatory substance upon

activation with histamine.” This immunoregulatory substance cannot be

anything but histamine-induced suppressor factors studied by Kaplan. The

table on page 60 names the H2-receptor function as immunomodulatory,

and the very term points to the presence of a living body with its regulatory

immune system. With all this being in the textbook, one can only wonder why

the editor insisted that I had misinterpreted the data, as I simply implemented

into practice the statements, data and ideas that A. Kaplan had accepted for

publication. I conducted successful immunomodulation with the best natural

activator of H2-receptors. Dr. Kaplan’s letter was misleading in not providing

the true facts.

The big flaw in Dr. Kaplan’s note is that it defies to the very foundation of

medicine when it says that the theories I relied on “have nothing to do with

clinical disease.” Theory and practice are inseparable in any area. As a saying

goes: theory without practice is dead, practice without theory is blind.

Theories in medicine must lead to therapies and cures, serve the sick and not be

entertained in scientific labs simply to get more funding. Regrettably, Dr. Kaplan

did not connect his own work with practice. Thus, when he stated that “a

balance between molecules of HRF or HRIF activities exists, which may

determine the level of inflammation observed in allergic diseases,”49 it was

only natural to conclude that histamine-induced inhibiting factors materi-

alize immunomodulation. This points to the duality of histamine. It was also

natural to speculate how this duality could be used to balance the chemistry

in disease and help allergy patients. Even though Dr. Kaplan’s text implies

this, he never expanded on the material.

Dr. Kaplan’s note surprised me because of the lack of concern it displayed

for the plight of my allergy patients. When he condemned histamine therapy,

which, in his opinion, “has no validity whatsoever,” he did not pay attention

to the fact that about 2,500 of my patients, the majority of whom had failed



to benefit from all conventional methods, improved or recovered due to

histamine therapy. This figure falls into the category of the mathematical Law

of Big Numbers which states that if an experiment is repeated a large number

of times under identical conditions, then the relative frequency with which a

certain event occurs and its probability should be approximately the same.

Even if the expert witness, A. Knight, had not informed Dr. A. Kaplan about

this numerical fact, the latter should have inquired what had happened to the

patients subjected by Dr. Ravikovich to his “invalid” histamine therapy. The

professor did not do that. His letter was, of course, most useful here in

Toronto, as it supported the position of the CPSO, who on several occasions,

made assertions such as that “patient outcome is irrelevant” or “not terribly

useful.”50 What then, one wonders, is relavant or useful?

The material selected by Dr. A. Kaplan for the second edition of the textbook

Allergy reflects the changes that took place in his stand and in the stand of allergy

as a science. Allergy 1997 should actually be called Allergy Revisited. The differ-

ence in presenting the information in the two books is such that one may suspect

revolutionary discoveries that dictated the change of the accepted postulates.

For instance, the second edition of the textbook has a new section called

“Immunologic Diseases” that includes AIDS, vasculitis, lupus, cancer and other

diseases that, by any standard, cannot possibly be viewed as allergy. The title of

the book—Allergy—is preserved, and one can only wonder what is behind this:

or secondary the lack of material directly related to allergic diseases, or the

desire to distract the reader from what is essential by providing information

that is irrelevant in importance. Since the common origin of allergies with the

presented immune diseases is not indicated, and as there is no deficit in the

availability of data on allergy, the last assumption seems to be most logical.

Another obvious difference between the two editions is that the first is

centered on histamine, especially Rocklin’s (dropped) chapter on the under-

lying immune processes. In contrast, the second edition, although almost 200

pages larger than its 1985 predecessor, mentions histamine only in passing, as

just another mediator. Histamine-related phenomena, H2 receptors and

T-suppressors and histamine-induced suppressor factors have disappeared. It

is only from the new chapter entitled “Antihistamines,” that one may indi-

rectly infer the key role of histamine. These inexplicable changes could have

been done only with the approval of the editor, Dr. A. Kaplan.



A. B. KAY is director of the Department of Allergy and Clinical Immunology

at the National Heart and Lung Institute in London and a co-editor of the

European journal Clinical and Experimental Allergy, the second most impor-

tant professional journal after JACI. For over a quarter of a century, the activity

of this scientist in the international arena of allergy research has steadily

grown. He has become the most prolific and authoritative author, a member

of the editorial boards of international journals and chair and key lecturer at

international symposia. Critical review of his work is rather difficult because

of the fact that he takes so many inexplicable turns back and forth in his scien-

tific interpretations. Before the analysis of Kay’s work, which is rather like a

detective operation, we should summarize the generally accepted, though

concealed, data on mechanisms that underlie allergies—the main topic of his

work. The central players of allergic reaction are

1. mast cells that launch it by their exaggerated histamine release;

2. basophils that take over this role in the late-response phase and secrete over

90% of all histamine51

3. T-cells and particularly T-suppressors that “seem to play a critical role in

immune regulation. Suppressor cells have been implicated in virtually all of

the immunological regulatory mechanisms that are presently recognized”52

All three players are inseparable from histamine although in different ways.

For mast cells and basophils, histamine is their main product. For T-cells, its

role is immeasurable: histamine determines their differentiation, and the very

existence; generation and efficiency of T-suppressors totally depend on hista-

mine. As was said before, all T-cells become producers of histamine de novo

when activated.

Numerous works recognize the pivotal role of histamine, but we will illus-

trate this by two examples. The just-quoted article with the self-explanatory

title “The regulatory effect of histamine on the immune response” is the result

of the research supported by a grant from the Medical Research Council of

Canada. It covers the roles of cells and the role of histamine in immune

responses. The text states on page 56 says: “A thorough evaluation of the role

of histamine in the immune response could lead to the understanding of

numerous clinical situations in which this hormone could be involved.” And:

“Histamine also has direct effects on a variety of lymphocyte functions and

may influence the expression of cell-mediated immune reactivity.”

The second citation comes from M. Kaliner, a top expert in histamine who

gives the key role in allergies to mast cells/basophils as histamine-releasing



cells: “The bottom line is that the mast cells initiate the process. If you inhibit

mast cells reactions, you inhibit both the immediate and late reactions.”53 Let us

trace Kay’s position on this ‘who is who’ in allergic reactions at different

times.

Mast cells/basophilsThe 1984 volume Asthma: Physiology, Immunopharmacology and Treatment is

edited by A. Kay and L. Lichtenstein. It covers the Third International

Symposium on Asthma and includes the informal discussions that take place

at this gathering. Dr. Kay is one of the participants of these discussions, and

we read on page 426: “many of the features of asthma such as … bronchial

hyperactivity, and bronchial inflammation might be secondary to the primary

mast cells defect.” Kay explains what this primary defect in mast cells is: “in

asthma, mast cells are intermittently ‘leaky’,” and “the ‘leakiness’ can be inter-

mittent (episodic asthma) or continuous (chronic asthma) … reflecting the

severity of the disease.” For support, Dr. Kay refers to his own earlier work

published in the Lancet.54 Then he goes even further when on page 427, he

points how to control asthma: “To define the triggers and drugs that inhibit

release it may be necessary to work with asthmatic mediator/mast cells.”

Another participant of the discussion, Dr. A. Kaplan, sees “abnormal hista-

mine release” as the main cause of “… stimuli that trigger asthma” (p.425).

Dr. Kay, present at the discussion, does not argue against this fact. The posi-

tion of science did not change in 1995, if we believe Dr. Kay’s co-editor, Dr. L.

Lichtenstein, who still considered mast cells and basophils as “the central

mediator-containing cells” at all stages of allergic reaction.55

In 1997, Dr. Kay’s views changed mysteriously. That year, he authored the

5-page chapter titled “Late Allergic Responses” in the second edition of the

textbook Allergy. Those five pages are, actually, the replacement of Rocklin’s

20-page chapter entitled “Role of Cell-Mediated Immunity,” which was part

of the first edition of the textbook Allergy, and which was excluded from its

1997 edition. An allergic reaction consists of two stages—immediate response

that lasts 2–4 hours and the subsequent late-response phase that may be

short, but may last much longer and even become chronic. Allergy accepts

that this late-response phase is actually ongoing allergic inflammation that,

no matter what ignites it, continues due to the malfunctioning of the partici-

pating cells. Therefore, the knowledge of what cells are primary, what makes

them malfunction, and how to correct their production becomes so essential,



both for understanding the pathogenesis, and for selecting the treatment

target. The very name of the Rocklin’s chapter says that any immune allergic

reaction depends on what cells are involved in the reaction. Rocklin did what

he was supposed to do: he named all the participating cells, indicated their

ranks in the process and specified the particular defects responsible for their

malfunctioning. His meticulous description helps one understand the

common origin of various allergic diseases and could help one find methods

of correcting the failing immune tools, irrespective of the end organ in which

the disease develops. Dr. Kay was supposed to do the same.

The drastic reduction in the number of pages compared to Rocklin—

from 20 to 5—would be irrelevant, if the problem had been presented

concisely. As the editor, A. Kaplan was to ensure that the author, A. Kay,

included this basic material into the replacement chapter. Have the author

and the editor fulfilled their obligations?

Both editions of Allergy are, actually, clinical textbooks grounded in basic

sciences, since they present the processes on the cellular and molecular levels.

Textbooks usually include those data from basic sciences that have been

accepted by medicine and specify the phenomena that require more research.

Kaplan included both Kay and Rocklin into the textbook Allergy 1985. The

inclusion meant that the material presented by both authors was verified and

solid, and that their views were compatible with the views of the editor.

Speaking about the roles of the cells in the late-phase allergic reaction,

Rocklin says on page 179: “It has been recognized that many, if not all, delayed

hypersensitivity reactions… contain sizeable infiltrates of basophils.” In fact,

any definition of mast cells and basophils, be it in a textbook or a medical

dictionary, starts with this most distinguished characteristic of theirs.

Moreover, if mast cells can release other mediators apart from histamine,

basophils release primarily histamine. Therefore the presence of a large

number of basophils at the site of allergic reaction is unequivocal in its

meaning, namely exaggerated spill of histamine.

In 1987, just two years later, Dr. Kay also recognizes the “well-documented

association between mast-cell-derived products and late-phase reactions”56

This means that covering the late phase in Allergy 1997, Dr. Kay was

supposed to emphasize the “well-documented” histamine leakage from

basophils. He was also expected at least to name the first stage launched by

histamine overspill from mast cells. He did neither of this. Kay simply

reduced mast cells and basophils to ordinary participants, but he did it skil-



fully. Nobody can rebuke him for excluding mast cells: he focused on the late

stage of reaction, and this allowed him to cut off the initial stage based solely

on histamine as an initiator.

However, even basophils that take over mast cells’ functioning in the late

stage of allergic reaction now lost their importance as did the amount of

crucial mediators and cytokines they produce, and this in spite of the uncon-

tested fact that they release more than 90% of all the secreted histamine. As

none of the works by this scientist had indicated that he started to have

doubts about the “well-established” scientific data, we may only speculate

what prompted him to turn basic immunology upside down by attaching the

central role in allergy to another group of cells, namely the eosinophils that

were never considered central. The fact that he did it in a textbook, and not

in an article, makes all this especially hard to comprehend.

EosinophilsIn 1985, in the first edition of Allergy, Kay wrote the chapter entitled

“Eosinophils” nothing in it indicated that these cells were central players, in

allergy. On the contrary, at that time, Dr. Kay described eosinophils as

dependent on mast cells and T-cells: “eosinophils appear to be recruited and

activated as a result of T-lymphocyte-…derived mediators” and at least in

part, their activation is “a result of factors derived from mast cells.” When in

1997, Kay assigns to the eosinophils a greater importance than to other

participating cells, he comes into conflict not only with science in general, but

also with logic. Given this fact Dr. Kay up to now remains a fervent supporter

of the IgE antibody hypothesis as the origin of all allergies, he should have

given the priority to mast cells and basophils, since they are the prime resi-

dence of IgE antibodies and the place for antigen/antibody reaction. This fact

alone makes eosinophils inferior, at the very least, to mast cells that ignite and

maintain the reaction.

Another change in the views of Dr. Kay concerns the protective role of

eosinophils for the immunity. In 1985, he recognized this by saying that the

eosinophils “dampen” mast cell activity, that is, slow down histamine release.

Thus, he wrote on page 96: “A role for the eosinophil in ‘deactivating’ hista-

mine has been proposed by a number of workers,” and the author does not

argue this position. How could argue this, since the fact that eosinophils

possess protective functions is common knowledge? In allergy, their activity

is implemented in the same way as with the other cells—via activation of



histamine receptors, as described on pages 176–177 by M. Kaliner in his

chapter entitled “Histamine” which is included in the huge volume

Inflammation: Basic Principles and Clinical Correlates.57

In 1997, in the revised edition of Allergy, eosinophils, without explanation,

acquire the property of being an affliction, plus they “remodel” the bronchial

wall, that is, produce structural changes (Summary, page 298). In fact, changes

in the bronchi occur as a result of the constantly seething pro-inflammatory

chemistry coming, first of all, from mast cells and basophils. Moreover, they

occur only at a far-advanced stage of asthma. Dr. Kay obviously forgot what he

knew in 1987 when he wrote: “…inflammatory cells, recruited and activated as

a result of the elaboration by mast-cells-associated chemotactic factors, lead to

the local changes in and around the bronchi.” In other words, it is not

eosinophils, but, first and foremost, the poorly opposed mast cells/basophile’s

chemistry that is responsible for the changes.

In 2001, Dr. Kay temporarily returns to his position as expressed in Allergy

1985 when he correctly denied eosinophils their prime role in allergy.58 Thus,

he says on page 112 that elimination of eosinophils in patients “had no

apparent effect on the allergen-induced late-phase asthmatic reaction or

nonspecific airway hyperresponsiveness.” In 2003, he reiterates this again; this

is his most recent presentation published as abstract No. 774: “eosinophils

…are unlikely to cause redness, swelling and induration which characterizes

the late-phase allergic response.”59

One would expect that by now Dr. Kay would have finally found the

proper role for these cells. Not so. In his latest articles, he once again declares

eosinophils as the main evil, and describes the “remodeling” of airways

supposedly performed by them, as the central event in asthma. By doing that,

Dr. Kay simply turns asthma into an irreversible disease essentially character-

ized by serious, organic, degenerative changes in the lung and bronchi.

Strangely, he makes no mention of the prerequisite pathological processes in

the immune and nervous systems, without which such gross tissue damage

cannot occur. There are always specific pathogenetic factors behind any

serious structural change, but they are left out completely.

If one accepts Dr. Kay’s views, removal of scar tissue may become the next

popular step in management of asthma, and it will be considered a condition

similar to cancer and rheumatoid arthritis, diseases that do have profound

structural formations or changes. In reality, asthma is a volatile immune

disease, the most reversible, by definition, in the majority of cases.



Regrettably, numerous authors have picked up the idea put forward by Dr.

Kay, namely that remodeling takes place through eosinophils, and that this is

the core event in asthma. This is now shaping up to become a new trend in

the perception of this disease. This is happening even though the author of

the concept has again changed his views.

In 2001, Drs. Kay and Kaplan were among the group of authors writing on

the late-phase reaction, and once again the self-contradiction is amazing.60

On page 400, the text says that eosinophils are actually only bystanders in

allergic reaction, which may go on without their active involvement: “Taken

together, these observations support the view that airways eosinophilia is not

a prerequisite to the airway narrowing associated with late asthmatic reac-

tions.” This statement coincides with Kay’s (and Kaplan’s) views of 1987 but

contradicts his (their) 1997 views.

As a specialist in eosinophils, Dr. Kay undoubtedly knows the unique

function of the recently-discovered histamine H4 receptor. Especially so,

because an article that answers the question why there are numerous

eosinophils at the site of allergic inflammation is published in the journal

edited by him. This receptor passes histamine messages to bone marrow and

stimulates production of immune cells. Therefore “H4 receptor may make it

a therapeutic target for the regulation of immune function, particularly with

respect to allergy and asthma.”61 Another authoritative pharmacological

source also states that H4 receptor gives rise to numerous immunocompetent

cells, including eosinophils, and the authors see a “potential new role for

histamine in allergy and asthma.”62

Intensified production of immune cells is a natural defensive reaction of

the body, and the fact that histamine induces such a production empha-

sizes its protective role in the functioning of the immune system. The

increased production of eosinophils indicates their protective role, not

a disease-promoting role, as ascribed to them by Dr. Kay. The specifics of

the reparative role of eosinophils are not part of this review. However,

the arguments whether their role in the production of asthma is nil or

most important should not distract from the main fact, namely that a

continuous profuse mast cell/basophile histamine release is the principal

underlying event in allergy and asthma. Histamine, any reference to

which Dr. Kay avoided, hit him unexpectedly: eosinophils, seemingly

independent of histamine, turned out to be generated and activated only

by it!



T-cellsT-cells are another element fluctuating in significance in the works of Dr. Kay.

They are universally recognized to be the leaders among the immunocompe-

tent cells participating in allergic reactions, although in a different sense than

mast cells and basophils. It has become common to describe them as the

conductors of the immune orchestra. Even if we limit the functions of

T-helper cells to their facilitation of antibody formation (negative in allergy),

an increased IgE antibody formation is an indication of excessive activity of

these cells. The only force able to restrain their disease-promoting effect is

that of the regulatory T-suppressors. They control the number and the

activity of all T-cells, IgE antibody levels, and also the chemical activity of all

immunocompetent cells engaged in the allergic reaction.

When Rocklin wrote in his now censored chapter in Allergy 1985: “The

suppressor cell abnormalities observed in allergic subjects may reflect a primary

defect inherent to the atopic diathesis” (pp. 190–191), Dr. Kay had a similar

position that found its way into his article written two years later. In this paper,

he is even clearer about his knowledge of the true leading cells in allergic reac-

tions.63 Here is a sentence from the introduction: “…successful immuno-

therapy has been associated with both an increase in the relative number of

suppressor (OKT8) T-cells as well as an abrogation of allergen-induced late-

phase responses.” Again, for support of the idea that suppressors are central in

abrogating the reaction, Dr. Kay gives in reference 11 the article by Rocklin64

which forms the basis of Rocklin’s chapter in Allergy 1985, Role of Cell-Mediated

Immunity, that centers on T-suppressors. Dr. Kay also writes: “the possibility

exists that OKT8 cells control these inflammatory events by preventing the

release of helper T-cell-derived mediators. For instance, OKT8 cells produce a

histamine-induced suppressor factor that inhibits lymphocyte proliferation

and lymphokine production.”

At this point, there is reference 27 that leads us to the 1979 paper by

Rocklin and Melmon entitled “Histamine-induced suppressor factor (HSF):

further studies on the nature of the stimulus and the cells which produce it.”

Dr. Kay’s article even specifies the underlying defect in asthma, namely a

“defect in suppressor cell function,” and he also recognizes histamine-

induced suppressor factor produced by T-suppressors as the vehicle of

controlling allergic reactions.

In 1997, the textbook Allergy does not mention of T-suppressors in Dr.

Kay’s chapter on late-phase allergic reactions. The prime defender in allergy

has inexplicably vanished.



In 2001, Kay and Kaplan are among the group of scientists writing on the

late-phase reaction. This article60 recognizes T-suppressors as the target for

therapy. On page 401, when speaking of downregulation of late response in

asthma, the authors say: “CD8+ cells have been shown to be increased after

successful immunotherapy.” As CD8 is the marker of suppressors, this phrase

is a repetition of the Rocklin’s statement in Allergy 1985: “…suppressor T cells

…bearing histamine receptors were generated during antigen desensitiza-

tion.” Rocklin was very precise in the description of allergic processes, and

saying this, pointed out that “failure to detect these cells in untreated patients

may be a reflection of the underlying defect leading to the atopic diathesis,”

that is, allergy. In other words, the prime defect of allergy, according to

Rocklin, is that the number of suppressors is too small. Now, after a decade

and a half of hesitations, Dr. Kay (and Kaplan) once again share Rocklin’s

position. Can we expect that they will publicly recognize their erred stand in

Allergy 1997 and correct it in the next edition of the textbook?

Finally, in 2003, Dr. Kay makes another indirect admission of his 1997 delu-

sion regarding the position of the cells in the late-phase allergic response when,

in co-authorship with a team of scientists, he proudly described the develop-

ment of peptides as compounds that could be used for immunotherapy in

asthma.65 And what does he now indicate is the concrete underlying mecha-

nisms in allergy and the target for immunotherapy? “Regulatory/suppressor T-

cell”! These cells, absent in his chapter on the main stage of allergic reaction, now

suddenly rise from the ashes—just when Dr. Kay is involved in the creation of

new drugs and cannot avoid showing the target for their pharmacological effect!

HistamineAs was demonstrated in the ’80s, Dr. Kay agreed with the position that it is

histamine leaking from mast cells that launches allergic reactions; that reac-

tions are over as soon as the leakage is stopped; that the defensive power of

T-suppressors determines the course of allergic reactions; that this power is

histamine-determined. The textbook Allergy 1997 mentions histamine only

in passing. This makes an article published just a year later in the journal Clinical

and Experimental Allergy, where Dr. Kay is a co-editor, especially striking.66

The very title—“Histamine—a major role in allergy?”—is amazing, and now

the approach is presented affirmatively, even though the title has a question

mark. This is what it says:

“Since its discovery in 1911, histamine has been recognized as a major

mediator in allergic reactions and diseases… Thus, findings indicate that



histamine is a crucial mediator in both the early and late-phase reactions of

an allergic response, playing important roles in cytokine release… Recent

data have added considerably to our knowledge of its role.”

However, the greatest paradox really is that this “major,” “crucial” and

“important” mediator described in the journal edited by Dr. Kay can hardly

be found in his own latest works. Which is it: an illiterate author who (with

the approval of the editor) puts an insignificant mediator ahead of all others,

or purposeful omission by the editor of histamine and histamine-related

phenomena in his own works?

The inaccuracy of Dr. Kay’s presentation of scientific facts can only be

explained by his desire to avoid all discussion of histamine. He also wrote an

extensive two-part overview under the heading Advances in Immunology,67

the in which he stated that “acute allergic reactions result from the release of

preformed granule-associated mediators when an allergen interacts with IgE

that is bound to mast cells or basophils.” Although the long-overdue acknowl-

edgement that mast cells and basophils are central for allergic reactions is a

formal great step forward since he wrote his chapter in Allergy 1997, the

plural for “mediators” is most confusing because there is only one mediator

of allergy pre-stored in the granules of these cells—and that is histamine. Dr.

Kay names histamine in the text only to deny its principal role in asthma and

uses the inefficiency of antihistamines in these diseases as the basis for the

denial. This is strange because antihistamines are not necessarily effective in

other allergies either, although the frequency with which they are prescribed

is evidence of the prevalence of histamine activity in these diseases.

This two-part paper contains statements totally contradicting the author’s

previous works, including his chapter in Allergy 1997. Moreover, it contains

contradictions within the same text. Dr. Kay commits a commonplace substi-

tution of causes with triggers by focusing on the outdated IgE-based hypoth-

esis. This gives the priority to environmental influences, which he discusses at

length. Unfortunately, the examples given by the author are not at all

supportive of his views. He points to the prevalence of allergies in Australasia,

the United States and Western Europe—countries absolutely different in their

density of population, climate, development, and industrialization; the IgE-

based concept fails to deal with this fact.

Furthermore, his speculation that allergies are more frequent in areas

where “the developing immune system is deprived of the microbial antigens”

raises yet more questions. Isn’t vaccination the analogue of “microbial anti-



gens”? If not, why do we need it? If it is equal to natural “microbial antigens,”

why is allergy/asthma incidence significantly lower in East Europe, where

vaccination was compulsory under the communist regime? Puzzling yet is

another factor he considers—“being born when pollen counts are high”—

allegedly contributes to asthma in certain areas. Do couples in some countries

have a strange preference in conceiving at a certain time of the year?

It is interesting that even though Kay recognizes the role of genetics in the

production of allergies, he does not elaborate what those prime genetic

defects are in allergy patients and labels genetic malfunctioning in allergy as

a mystery “due in part to the multiple markers.” Strangely, in the past, he

himself specified these defects as “defect in suppressor cell function.”68

Although Dr. Kay’s article intended to cover mechanisms of allergy, it left

them out. The truth is always simple. In allergy, like in any disease of dysregu-

lation, we are dealing with two forces. The disease is an evil force, and our

immunity is our savior, but in the presentation of the leading allergists,

including Dr. Kay, the disease forces are always dominant, while the protec-

tive ones are nowhere to be found. Allergy medicine today unsuccessfully fights

the evil forces with the help of the drug industry, and never gives a chance to the

weakened, but still existing natural health promoting forces. This has already

caused tremendous harm to asthma and allergy patients because of the

concealment of the true and vital information. The damage both for science

and patients will be enormously greater yet, if the latest concept of asthma as

being a disease of primary structural bronchial changes is accepted. This

concept welcomes the search for new approaches in the repair of the allegedly

irreversible changes in the affected organ, and conceals the truth, which is

that asthma is caused by a flawed, but reversible immune mechanism. Allergy

research is causing nothing less than chaos, and its leaders should make a

thorough critical review of their position.

Now you may draw your own conclusions on how allergy medicine has devel-

oped. As any medical field, it is based on morphology, biology and physi-

ology. Morphology studies the structure of the body and its parts, while

physiology studies their functions. The structure of cells and events that

underlie biological processes are studied by molecular biology. These basic

sciences are not subject to frequent fundamental changes, but mostly build

upon findings that add to what is already known. Once discovered, the cells

and their receptors do not disappear on the will of researchers or for the conven-



ience of the pharmaceutical industry. Neither do their functions change. Why

has it become so common to write on allergies without mentioning the main

participating cells and their by-products? Why is it necessary to rewrite the

events of allergic reactions and substitute the central players with those

secondary in importance? By now, you already know why. The facts are clear

and known, so let us summarize them:

■ What are the main allergy fighters? T-suppressors.

■ What makes T-suppressors efficient? Active H2 receptors.

■ What activates them? Histamine.

■ What could stop a histamine spill from mast cells and basophils? Efficient

H2 receptors.

■ What makes them efficient? Activation with histamine that does it “like no

other drug,” say the pillars of allergy.

■ Can we correct these genetic defects? Yes, we can if the needed changes in

the governing genes are functional, not structural.

■ How can it be done? By activating H2 receptor, we enable histamine

messages to increase the enzyme cAMP, the effect that increases the intracel-

lular activity and reaches the genes. Their corrected functioning results in

health promoting messages to the immunocompetent cells. The H2 receptor,

T-suppressors, at lower than normal levels of cAMP are links of the same

chain. By restoring one link, the H2 receptors, we restore the functioning of

the whole chain.

The problem in allergy medicine today is that histamine so lies at the center of

the sequence. We may not even whisper the word histamine. It is almost a mortal

sin, unfashionable, in poor taste. But really, it is the financial implications

involved in histamine that is the reason for silencing all discussion about it.

Censorship in allergy has become so entrenched in the new millennium

that the Editorial in the most prestigious immunological journal states on

page 498: “The mechanism by which immunotherapy works is unknown.”69

Editorials reflect the opinion of the world’s most renowned allergists, and this

statement indicates that even the editors of the central immunological peri-

odical are unfamiliar (are they really?) with the works of the fathers of allergy

research and are unaware of the role of T-suppressor cells as well as their

regulatory chemistry in allergy. Such opinions pronounced by high-ranking

specialists serves ultimately to close the door to the wealth of existing data

that could contribute to successful immunotherapy and, instead, open the

gates to research in numerous ineffective therapies.



This is the natural result of the substitution of the key phenomena with

numerous inferior minutia. Added to that is intermittent professional

amnesia regarding some of the events and players and their reappearance

under different names, without any clarification of their identity. The earlier

described disappearance of histamine-induced suppressor factors for a whole

decade, and then the frequent use of the term interleukin-10, without stating

that it is a histamine-induced suppressor factor, is an example.70

However, allergy research, such as it is, cannot prevent other medical areas

from publishing the data prohibited in its field, and indeed the compelling

material coming from the National Institutes of Health and the Cancer

Institute in the USA serves to expose the plot. The authors name histamine as

the best activator of the enzyme cAMP and state that “none of the other

mediators…has any effect on the production of Il-10.” They also indicate the

H2 receptor as the pathway for the induction of this interleukin.71

Another example of the determination of allergists never to call a spade a

spade is the complete removal of T-suppressors from all allergy sources and

the use of CD8+ or OKT8 cells. Without identifying these in allergy, both

terms have the same meaning, namely T-suppressors. The concealment is

such that today, the T-suppressors’ regulatory role has been attributed to

other kinds of T-cells that possess innate defensive qualities, but whose

activity is nonspecific in allergy. They have become the substitution to the

abolished specific T-suppressors, and now immunologists seriously discuss

their allegedly immunomodulatory activity in allergy.

Funny, some authors, who are most probably not informed of the plot,

inadvertently, at times, reveal the truth and declare that the newly

proposed defenders are not really controllers of allergic reactions.71 Even

the most fervent proponents of the new trend have not completely hidden

those T-suppressors under their new name, and so they write: “It is difficult

to dismiss, however, the fact that CD8+ T cells may have some function in the

control of immune response to inhaled proteins,” and that “independent

studies have identified a potential role for CD8+ cells.”72 One gets lost in this

field of medicine, even as a specialist practicing in it; it is now so full of disas-

sociated, misinterpreted, silenced or twisted theoretical events and notions,

all of which are not applicable to clinical practice. Sadly, it is ultimately the

patients who become the victims.

The tacit ban on exploring histamine and histamine-dependent immune

tools forces allergy to resort to disguising or avoiding T-suppressors and their



histamine-induced suppressor factors. T-suppressors, as was said, are

suddenly identified as CD8+ cells. The devious thing is that this is not simply

wrong—but it is a useful half-truth, which is always more convincing than a

lie. CD8+ cells comprise up to 35% of all T-cells, and they combine two

groups of cells—cytotoxic cells that have no relevance to allergy and T-

suppressors, the cells operating as the main regulatory mechanism in allergy.

Without differentiation, only those who know theoretical immunology will

understand which of these two are relevant to an allergy-related text.

To solve the problem of T-suppressors, I refer immunologists to Bernard

Shaw who prefigured their existence and their key role in immunity. In his

drama The Doctor’s Dilemma, the playwrite created a character modeled after his

friend, Sir Almroth Wright, who specialized in vaccination and inoculation.

Shaw put the words “stimulate the suppressors” into the mouth of the main

character. It is a historic fact that Dr. Wright edited the medical aspects of the

play, and thus, the words of his prototype confirm that even before

T-suppressors were discovered, experienced scientist had guessed their existence.

The main danger to truth is not so much in the complete omission of the

central events and phenomena, but in their replacement with numerous

details, some secondary in importance, some ridiculously irrelevant. These

data are then zealously disseminated within the profession and among the lay

public and acquire the status of real science. They distract from the primary

cellular defects and eliminate the possibility of correction. This explains why

the researchers of these postulates get unrestricted funds from the drug

industry. Connections of the medical profession with pharmaceuticals have

become so notorious that many doctors now try to dissociate themselves

from the industry. In response, lately, independent trusts for research have

been organized by pharmaceuticals, and one can only wonder how inde-

pendent they are.

When the cup is full, it will eventually overflow. True knowledge piles up,

and it is very difficult to completely obstruct its leakage. It happens because

research goes on in different directions including in the “do-not-trespass”

zones where intellectual censorship has taken hold, and high profile scientists

on research teams cannot be forever denied publication. Occasionally

published results reveal the true mechanisms of allergy and indirectly point

in the direction of useful therapy. Here is an example.

An international team made a presentation at the annual meeting of the

AAAAI and leaked the unwanted data: injected histamine inhibits the release of



cellular histamine! To trace the effect of histamine on T-cells, the researchers

labeled it with a fluorescent chemical and confirmed that inhibition of hista-

mine release was realized via H2-receptor effect at all the stages of allergic reac-

tions.73,74 This confirms the dual nature of histamine activity and proves that

histamine injections work because of the well recognized phenomenon of

negative feedback! Dorland’s Illustrated Medical Dictionary defines negative

feedback as “the condition of maintaining a constant output of a system by

exertion of an inhibitory control on a key step in the system by a product of

that system.” In plain words, when you push the “key step” (H2 receptor) by a

“product of the system” (histamine), you maintain the steady production of

the same substance (histamine). Simple and effective! In this connection, we

will go to another world-famous scientist who is also relevant to my personal

legal case. In the past, he wrote on the negative feedback of histamine and its

key role in allergy, but he is silent about this today. Yet, according to his own

recent admission made at the international forum of asthma specialists, his

area of interest is asthma, its origin and treatment.

STEPHEN HOLGATE is professor of Immunopharmacology Group,

Respiratory, Cell & Molecular Biology Research Division, Southampton

School of Medicine, UK. Since 1984, he and Dr. Kay are co-editors of the

journal Clinical and Experimental Allergy. Holgate is an author and editor of

numerous textbooks and monographs, chair and lecture at international

forums, including annual meetings of the European Histamine Research

Society. His work was always tied to histamine whose unprecedented signifi-

cance for medicine he has recently acknowledged: “The discovery of histamine

by Dale and Laidlaw in 1911 created a new science—Immunopharmacology.”75

This means that for Holgate, who is an immunopharmacologist, histamine is

the source and meaning of his professional career. The fact that this scientist is

one of the central designers of research projects for allergies and asthma, as

well as drug development for these diseases, makes it important to follow the

fluctuations of his scientific position.

His article entitled The Epidemic of Allergy and Asthma75 starts with a

paradoxical declaration: “The past 30 years have witnessed a spectacular

increase in our knowledge of the cellular and molecular mechanisms of

allergic diseases, which has been paralleled by the rising trends in the inci-

dence and health impacts of these diseases worldwide.” One would think

medical discoveries should help reduce the figures, otherwise, they can hardly



be called discoveries. Unfortunately, this declaration accurately reflects the

state of the art in the field, in which Holgate is a leader.

Holgate, whose career as an immunopharmacologist was launched by

histamine, knows better than anyone that all allergic processes, progression

and regression, are inseparable from histamine and related phenomena. The

book Management of Allergy in the 1990s which covers the XIII International

Congress of Allergy and Clinical Immunology 1988 includes Holgate’s article100

The Role of Histamine in Asthma (pp.14–20). There is a table on page 15 enti-

tled Biological Role of Histamine. In a succinct form, it presents the accumu-

lated knowledge on histamine’s role not only in asthma, but also in the

immune system in general as well as in the nervous system. The word biolog-

ical indicates that he describes the processes in a live body. The table shows

how histamine implements “negative feedback on histamine release.” This

biochemical mechanism means that histamine inhibits its own cellular

leakage, and the process is realized when active H2 receptors stimulate accu-

mulation of the enzyme cAMP. Holgate’s table shows that H2-receptor acti-

vation by histamine “activates suppressor cells” and “produces histamine-

induced suppressor factor.” As we see, at that not-so-distant time in 1988,

Holgate knew the true mechanisms of allergies and related diseases—the H2

receptors, and the T-suppressors and histamine-induced suppressor factors—

were obviously not yet censored. Apart from immunoregulatory properties of

histamine, the table lists its “neuroregulatory role” implemented by the H1/2/3

histamine receptors.

The story of this table is of special interest because it became of prime

importance to me personally. I presented it as a key item in my defense mate-

rial, which I submitted to the CPSO during my discipline hearings. It was an

exhibit of central importance to my defense as it provided the scientific

validity for histamine therapy in clinical practice. So important was this table

in supporting my therapy theoretically (in practice I already had proof of

thousand of patients improved or cured—which did not interest the prose-

cution) that the prosecution removed it from the article in which it was

published thus destroying the entirety of the exhibit. By that time, there had

already been so many legal improprieties committed by CPSO at my hearings

that I had expected such developments to take place, sooner or later. Indeed,

being a refugee from a totalitarian state, such as the former Soviet Union was,

prepares one very well for abuses of power wherever one is forced to

encounter them, even in Canada. I carefully observed the actions of the



CPSO’s prosecution lawyer, Robert Armstrong (who now is a provincial judge

in Ontario) and realized that the prosecution understood very well the

importance of this table as a perfect defense. I had noticed that the docu-

mentation I had submitted had been tampered with. According to legal

procedure all documentation in a trial is supposed to be identical in the hands

of both parties, the prosecution and the defense). I pointed to the removal of

the table and requested it be reinstated. It was, but then it again vanished from

the documents submitted by CPSO to all subsequent courts, including the

Supreme Court of Canada, and it was no longer possible to reinstate it at that

point. Indeed, the CPSO knew exactly what they were doing, abusive as it was

legally, for Holgate was such an authority in allergy that this table not only

provided incontrovertible and irrefutable evidence for histamine’s protective

activity, but also provided me with a total and unassailable defense defeating

the CPSO’s charge against me (i.e. practicing medicine without scientific

basis). So, the prosecution got rid of the evidence.100

I had a personal conversation with Holgate in September 1989 at an inter-

national symposium in West Berlin. I told him I had written an article about

my histamine therapy and found scientific sources, including his work, that

supported my understanding of the underlying processes. I asked him if I

could submit the article for publication to his journal, and Holgate agreed to

read the material, which I sent to him soon after. In his letter of response of

November 2, 1989, Holgate explained why my paper could not be published

in his journal. He stated that there was no “evidence of a placebo-controlled

trial.” He suggested I consider initiating such trials because “if the results are

positive as have been claimed by yourself and a number of workers that I have

met from China, then this would be quite an outstanding contribution to the

field of allergy.” The editor ended with “I look forward to hearing further

from you on this point.” At that time, I was not aware that clinical and

double-blind studies had already been conducted in Switzerland and Japan,

and it is hard for me now to speculate whether Holgate knew about them. In

any case, although Holgate formally rejected the article for publication, his

letter indicated that my hypothesis was valid enough to be tested in trials.

In 1994, the expert-witness for the prosecuting CPSO, Dr. A. Knight, was

seeking help from the allergy giants. As mentioned already, he approached

Lichtenstein and Kaplan, so now he asked Holgate to comment on my hista-

mine therapy. Dr. Knight testified at the hearings that he had actually taken

the trouble to travel to England to meet with Holgate for just this purpose,



which shows how very important it was to the CPSO to stop this therapy from

being permitted. Interestingly, I was not permitted to see Holgate’s letter

(another legally abusive turn of events), and learned about its existence only

at the hearings themselves from the prosecutor, Bob Armstrong. Holgate

allegedly wrote that his 1989 letter to me had not been the response of an

editor to an author but a personal one, and that he had never approved of

histamine therapy.

His response is very strange indeed. First, my relationship with him was

one of a purely professional kind, and such a letter of an editor to a writer

cannot be anything but his official response. Second, it is highly improbable

that this renowned scientist would suggest such a senseless project as scien-

tific trials based on an invalid idea. Third, if Holgate did not believe that

histamine therapy could be efficacious, why did he volunteer the information

about its successful application in China. Moreover, at our meeting, Holgate

suggested to me personally that should I talk to Dr. Busse whose research was

related to the histamine-related mechanisms of allergies and asthma. Why

would he needlessly burden his high profile colleague with an insignificant

topic offered by an unknown doctor? (By the way, I met with Dr. Busse during

that conference only to hear that his work was in another area. In fact, Dr.

Busse, who later became the president of AAAAI, researched and continues to

research underlying mechanisms of asthma.)

In the nineties, the protective properties of histamine and histamine-

related elements were becoming more and more obscure. However, Holgate

went further than obscurity. He, who had described T-suppressors as the key

defense tools, inexplicably turned them into hostile cells. Thus, among

immunocompetent cells that produce “pro-allergic cytokines,” he named

CD8+ T cells, the other name for suppressors. He has never given an expla-

nation as to what caused the transformation of this savoir into an evil force

within a mere decade that separates this work from the above-discussed

article, The Role of Histamine in Asthma.

Holgate’s later articles now became full of the word antihistamines and

reference to histamine is almost completely omitted. The 962-page volume

Inflammatory Mechanisms in Asthma 1998, co-edited by him goes so far as to

completely exclude all protective activities of the allergy-related immune

system, histamine included. Nature and science has been edited and is

presented in a fashion so biased as to be beyond recognition. Only once did

the editors overlook a detail that exposed their knowledge of the true mech-



anisms of allergies. They forgot to censor a reference to the 1991 article by R.

Alam and A. Grant, cited by us earlier. That article discusses the balance of

pro- and anti-inflammatory histamine-induced factors as the central missing

link in understanding and management of allergies and asthma.

With the passing years, Holgate has gone far away from his former views

and provided no scientific explanation for this change. In the year 2002, we

find him as one of the seven authors of an article discussing the interrelation

of mast cells and muscle cells.76 The text may serve as an example of how

skilful allergists have become in writing about central events without naming

them. Thus, this article presents mast cells as “predominant” players in

allergic reactions, and only if we know of the inseparability of histamine from

mast cells, do we understand that histamine is the central figure. Allergic reac-

tion in the bronchi is described properly and in detail, but in conclusion,

muscle cell abnormalities become disproportionally elevated to “a key

element in the development of asthma.” Since histamine is only mentioned in

passing, the pro-inflammatory chemistry induced by its leakage is not in the

picture either. This obscures the cause of the abnormal functioning of muscle

cells and results in putting the cart before the horse, i.e. declaring that the

secondary event is the primary one. This diverts attention from the primary

event, prevents further research into it and contributes departure from the

key elements. And this is exactly what followed.

As Holgate is one of the most powerful figures in today’s allergy research,

this publication became the subject for discussion by two editorials in the

same journal. One concludes: “both the mast cell and the muscle cell play a

part in the origin of asthma,” and “which of these has the primary role

remains to be determined.”77 Thus, the causative histamine-induced pro-

inflammatory chemistry becomes equal to the secondary damage, the muscle

cell malfunction. Moreover, the text on page 1742 says that mast cells are of

“paramount importance in the pathophysiology of asthma,” and among the

“array of mediators released from the activated mast cells,” 12 are listed, but

histamine, which is these cells’ most distinguished product, is not among

them! Either the concealment in allergy has become so total that even scien-

tists and editors have forgotten what they had studied at their medical

schools, or they are in collusion with those forces that have a vested interest

in hiding the truth.

The other editorial, This Week in the Journal, also strongly accentuates the

primary role of muscle cell functioning. It says on page 1683 that “asthma is



a chronic inflammatory disease” with unknown pathogenic mechanisms.

The suggestion follows: scientists should “shift the focus of asthma research

to abnormalities of airway smooth muscle and away from the general study

of airway inflammation.” Consider the logic of this suggestion: medicine

supposedly does not understand the essence of chronic immune-related

inflammation in asthma, but nevertheless should ignore this phenomenon

and, instead, redirect its attention to less demanding, secondary events

—abnormalities of smooth muscle cells.

Holgate’s recent concepts are conflicting in essence. Thus, in a highly

reputable journal, he presents asthma as an immune disease and IgE anti-

bodies as the pivotal element in its production: “Atopy is the single strongest

risk factor for the development of asthma.”81 Few years later, as a guest editor

at an international symposium of experts, he declares that asthma is “a conse-

quence of abnormal injury and repair responses” and agrees that “allergy does

not really cause the process of asthma.”79 At that gathering, Holgate declared

a “new paradigm for asthma pathogenesis” that, according to the specialists

present at the discussion, is “fascinating” because of the fact that it takes

allergy “out of the equation.” Sadly, such a paradigm will further obscure

asthma pathogenesis rather than clarify it.

The truth, in fact, is very simple, if properly presented. First, all structural

histological changes, “tissue destruction and remodeling,” occur only in a far-

advanced asthma, and that all of them result from the “T-lymphocyte-medi-

ated chemistry.” Second, the pro-inflammatory “T-lymphocyte-mediated

chemistry” can be offset not through its suppression but through stimulation

of the production of the disease-inhibiting chemistry. All this will inevitably

reveal the true pathogenesis of asthma that lies in the balance of histamine-

induced pro- and anti-inflammatory factors.

Holgate delivered the introductory report at this symposium and said that

he “has focused his research efforts on the cellular and molecular mechanisms

of asthma, with a special emphasis on applications to diagnosis and treat-

ment.” This self-appointed task, together with his high position, should make

Holgate especially responsible for what he says. Those below look up to him

both for theoretical support and guidance to clinical application of his ideas,

and therefore his own directions should be made absolutely clear. Regrettably,

as a shepherd, Holgate leads his flock astray. In his latest articles, Holgate

stresses the need for steroids and at the same time dreams of “treatments that

will modify the disease outcome rather than simply suppressing the inflam-



matory processes.”81 By presenting asthma as “an interplay between T-

lymphocyte-mediated airway inflammation, tissue destruction, and remod-

eling,” he plants such confusion that means his dream is not likely to come

true.

Over three decades ago, cyclic AMP was recognized as an effective mecha-

nism to control allergic reactions, and the drug industry knows this very well.

To help patients radically, one should follow nature’s way: use histamine H2

receptor as the pathway to increase that enzyme with the effect of activating

the entire anti-inflammatory chemistry. An important article in basic science

written by a group from the National Institutes of Health in Bethesda recog-

nizes that cAMP provides the central mechanism for activating the immune

system. This article also emphasizes that none of the agents stimulating cAMP

is able to induce IL-10 (the key allergy-protective histamine-induced factor)

and regulate the expression and secretion of a wide variety of cytokines

released by immunocompetent cells.82 This article provides the proof that

allergies are diseases of one predominant mediator, and recovery depends on its

proper release and activity. The way for rectification lies in the cAMP activation

via the H2 receptor. A well-read clinician can easily draw the logical conclusion

on how to transfer this knowledge into practice. Likely success, as I have

demonstrated in my practice, would be a serious problem for the pharmaceu-

tical industry. It pays the best minds to search for other less efficient ways to

reach cAMP. Such new drugs must, of course, never cure but only improve the

condition of the sufferers when taken regularly.

Like Lichtenstein, Holgate works on the development of phosphodi-

esterase inhibitors, drugs with a theophylline-like mode of action, and an

article he co-authored expresses a hope that these drugs “may emerge as a

new anti-inflammatory therapy in the treatment of allergic diseases such as

asthma.”83 While acknowledging the prime role of cAMP in cellular regula-

tion, by stating that “increases in cellular cAMP are associated with a gener-

alized downregulation of inflammatory cell activity,” the references

(especially nos 10 and 11) lead the reader to two articles that name histamine

as one of the best activators of cAMP —and Lichtenstein is the author of

both! The leaders in the field know how to treat asthma in the most effective

way. Both choose not to do it.

PETER BARNES is another leading immunopharmacologist. Like A. Kay and

S. Holgate, he presides at international gatherings, writes in prestigious



journals and is cited by many researchers. He is also a consultant to the largest

asthma drug producer GlaxoSmithKline, and is considered to be a great

authority on asthma management and medications. His research is funded by

this manufacturer as well as other multinationals.

Barnes knows what underlies allergic reactions, and how they can be

controlled. The following passage was quoted earlier in this chapter and was

written by Barnes: “…release of histamine from human basophils is inhibited

by histamine itself. The possible mechanism of the inhibitory effect is H2-

receptor mediated.” That same article emphasizes the tools needed for such

inhibition: “exogenous histamine inhibits the …release of histamine from

human basophils, acting via an H2 receptor.”84 This work also states that the

immunomodulatory role of H2 and H3 receptors “may play a potentially

important role in controlling the airway caliber of patients with asthma,” and

also “control histamine release from mast cells by means of a negative feed-

back mechanism.” Actually, that last sentence amounts to approval of hista-

mine injections that activate those H2 and H3 receptors.

A year after this publication, Barnes receives solid theoretical support for

potentially successful clinical use of histamine in asthma from the Histamine

Research Society.85 The authors write that histamine “seems to participate in

the mediation of stress-induced release of ACTH (corticotropin)” and endor-

phins. If so, this indicates a more efficient functioning of the adrenals (that

would mean no corticosteroids for asthma!) and also modulation of the

production of endorphins, which are neurotransmitters that affect both the

course of asthma and the occurrence of vascular headache, fatigue, pain

syndrome, mood swings, and irritable bowel syndrome. The article also

shows that histamine “stimulates the release of peripheral catecholamines,”

which means more release of adrenalin, and thus, eliminating or lessening the

need of bronchodilators. Together with the normalized steroid production,

this would be a huge improvement for patients suffering from asthma for

whom the combination of bronchodilator and steroids has become the norm.

Regrettably, as all theoretical works, this work does not suggest these data be

tried in clinical medicine, even though all research in medicine should be

done for this purpose. Still, these observations have provided unintentional

confirmation for the work of another scientist, J.-M. Arrang, the discoverer of

the H3 receptors, who published an article in the same 1991 volume of Agents

and Actions on pages 55–67.



With explicit reference to Barnes, Arrang and his co-authors state that “in

the respiratory field,” one observes the inhibition of inflammatory process

upon “H3-receptor stimulation in guinea pigs in vivo or in human airway

preparations in vitro.” They conclude: “These observations suggest that H3-

receptor agonists may constitute a novel approach in the treatment of asthma.”

The article also brings us the happy news that finally not only guinea pigs but

people have been found deserving of the attention of medicine: “Initial clin-

ical studies (with histamine agonists) have shown to be well tolerated in asth-

matic patients receiving the drug either via aerosols or the oral route, even in

very high dosage.” One would think that more than a decade after this initial

success in the management of such a potentially fatal disease as asthma, science

would seize upon histamine therapy and start helping asthmatics. Not at all!

Even Dr. Barnes, the chief world’s strategist of asthma therapies, disregards the

research on the theoretical aspects of asthma, successful trials on animals and

man, and his own above-quoted pro-histamine ideas.

Similarly to learned colleagues, Barnes, made an inexplicable turn in his

views. In 2000, he wrote an article in the new JACI publication called New

millennium: The conquest of allergy. There, he wrote that steroids, which “are

now first-line treatment for persistent asthma in all patients,” often do not

control the disease, produce side effects and are “not curative, and inflamma-

tion recurs when they are discontinued.”86 This would be the best time to

suggest “exogenous histamine,” previously studied by himself after all, at least

on those patients whose asthma is resistant to steroids. But he chose another

way. Weighing the pros and cons of various treatments, including

immunomodulation, which, as you know, in the language of allergists is not

immunotherapy but the euphemism for immunosuppression, he considered

the possibility of using a potent immunosuppressant as an immunomodu-

lator. He used this oxymoron although, as an immunopharmacologist, he

knows the difference between the two better than anybody. His article on the

directions of how to treat asthma ends with the pessimistic: “The possibility

of developing a cure for atopy is remote,” and the only feasible way, in his

mind, is to inhibit or suppress “components of the allergic inflammatory

response.” This of course, amounts to giving the drug industry a free hand,

for which he works, to produce countless suppressants—immune modulators

in the ambiguous vocabulary of allergy medicine.

The very word histamine is not used in the text and only once, does Barnes

reveal his true knowledge of what the precise target of asthma therapy should



be. On page 11, speaking about immunomodulation (by immunosuppres-

sors) the author writes that steroids “also inhibit suppressor T cells that may

modulate the inflammatory response.” Thus, we learn in passing that

immunomodulatory T-suppressors still exist despite the fact that clinical

allergy has done its best to ignore their existence, that steroids disable the

activity of these central protectors in allergy, and that the real meaning of the

word “modulate” is “change to the desirable,” that is, normal active level, not

to suppress below the norm.

The only hope is found in the fact that true science breaks through, no

matter how thoroughly quashed. For example, speaking about “certain

cytokines (that) have anti-inflammatory or immunomodulatory effects,”

Barnes assumes that “their secretion may be defective in patients with

asthma,” and “understanding these processes may give a better understanding

of disease. This, he suggests, may also lead to novel therapeutic approaches,

such as drugs that increase the release of endogenous inhibitors or mimic

their effects.”88 Not only does he admit that “such therapeutic approaches are

attractive since they may restore anti-inflammatory mechanisms to normal,”

but tells us that such drugs “carry a lower risk of adverse effects.”

Although histamine and histamine-induced factors are not named in the

text, the ‘defective secretion’ in asthma means that the balance is favoring inflam-

mation, and the degree of the imbalance explains the severity of the disease.

While he mentions endogenous inhibitors or products that mimic their effect,

it is strange that he does not name histamine, which, as a physiologic autacoid,

“carries a lower risk of adverse effects” compared to conventional therapies.

Histamine, its agonists and congeners are doomed to remain in the

domain of experiments. We understand this when we read in the Arrang’s

article cited above from Agents and Actions that “Ongoing studies are exploring

the activity of the drug on various models of experimentally-induced bron-

choconstriction in asthmatic volunteers.” Why do we need to induce bronchial

spasm in volunteers with so many asthmatics suffering from spontaneous

bronchial spasms? The answer is simple: the use of histamine on real asthma

patients could undermine the huge research into lucrative medications for

asthma. The Real Drug Pushers by Joel Lexchin published in 1984 states on

page 86 that the drug industry’s “focus is to develop major drugs for major

markets.” The “key influence on the direction or misdirection of pharma-

ceutical research is whether or not the product can be patented. New uses of

already existing chemicals cannot be patented, and therefore industry research



tends to ignore these substances.” Histamine is one such century old substance,

not just ignored but viciously fought by allergists because it cannot be

patented. It carries the potential for cure but not the potential favoring

industry growth.

The intention to conceal the self-regulatory forces in allergy is reflected in

an ARIA document which states that it is “intended to be state-of-the-art for

the specialist as well as for the general practitioner.”101 ARIA (see JACI 2001,

108) is the abbreviation for Allergic Rhinitis and its Impact on Asthma. This

workshop took place at an international conference that drew the leaders of

allergy medicine and was conducted under the auspices of the World Health

Organization. As the document states on page S182, “For didactic reasons,”

only pro-inflammatory chemistry is covered. For example, although the docu-

ment is on allergies, the H2 receptor is presented solely as one “responsible for

gastric acid secretion,” while its curative stimulation of the enzyme cAMP and

its therapeutic negative feedback effect are not even mentioned. What are

these “didactic” reasons that force one to conceal the defensive tools of the

immunity.

Somebody must take responsibility for the plot against histamine. The

virtual disappearance of the central chemical involved in all allergic reactions,

a major mediator and biological marker of all immune processes and a

central regulatory neurotransmitter requires an explanation. It takes great

effort to hide this immense body of research from visibility. Burning libraries

has ever been the work of those who want total control over minds, states,

people. These volumes of research are very much needed and most precious.

History teaches us what happens when pages are torn out of books, or books

are thrown into a fire. Usually authors follow, and obscurantism sets in.

My histamine story can be reduced to a sentence: a doctor, who used a

well-researched, inexpensive medication, helped or cured hundreds of

patients with undiagnosed and/or resistant diseases, and was able to explain

the underlying routes of their recovery, was not only prohibited from using

his therapy, but prosecuted and punished.99

The situation is not new in society: “What judgment shall I dread, doing

no wrong?,” asks Shakespeare in The Merchant of Venice. Medicine is just a

part of society and lives by the same rules. I should have expected “the judg-

ment.” Thinking, especially thinking differently, has always been considered

as an occupational hazard. I just happened to study basic science and theo-

retical allergy research that described the biochemical immune mechanisms



lying at the roots of my histamine therapy as central and regulatory. I inves-

tigated the chaos of fragmented details, arranged the key elements into a

logical system, introduced it into clinical practice and offered this to the

medical world without any personal gain in mind. The very scientists who

had researched and developed these fragments rejected them in their clinically

implemented form. They have never given an explanation for their rejection,

even though they have been unable to offer any alternative. This is because the

truth must have scared them and threatened other, incompatible priorities.

HISTAMINE AND DISEASE: A FORUM ON CURRENT AND FUTUREMANAGEMENTThe year 1991 appears to have been the cut off for publications on histamine.

Publications in 1991–1992 on histamine still appeared probably due to the fact

that the abstracts are usually accepted months or even years earlier. Before this

boundary date, professional meetings could readily involve discussion of hista-

mine. The title of this chapter is, in fact, the name of the conference of

American allergists and clinical immunologists that took place in the summer

of 1989. Dr. M. Kaliner was the guest editor of the supplementary issue of JACI

that covered the forum. As he said in his Introduction, “the participants were

highly respected,” the purpose for the gathering was “to foster better patient

care,” and “the topics reviewed ranged from basic science… to treatment of

common allergies.”88 This forum was the last open discussion involving hista-

mine. Probably, among the participants, there were still some researchers who

naively believed that theory in medicine should and would serve application

to patients. It might also be that a conference with this topic was possible only

because at the organizing stage, the manufacturers of allergy and asthma drugs

did not yet fully realize the “danger” of histamine, and the main sponsor,

Merrell Dow Pharmaceuticals, did not produce asthma medications and was,

therefore, indifferent.

So, what ideas were presented at the forum? The author of the first report

entitled “Mast Cell Biology” stated that “the role of mast cells is complex. Their

location at the host-environment interface suggests that they help protect (!)

the host.” And further: “…Mast cell, far from being simply a package of hista-

mine… may be an important factor in both homeostasis and disease.” These

statements indicate that histamine, as the mast cell central mediator, possesses,

apart from inflammation promoting features also anti-inflammatory ones.

The report also stated that the core of any allergic reaction lies with an exag-



gerated histamine release by the hypersensitive mast cells, and not with aller-

gens, and that in allergy, it is histamine hyperreleasability that is “a link

between non-IgE immune responses and mast cell activation.”89

Actually, this concept leaves beheaded conventional allergy, which

remains wedded to the IgE antibody dogma. The fact that histamine overspill

may ignite allergic reaction without any IgE participation renders senseless

the chase after mites, cats and cockroaches as causes. Ironically, in the new

millennium, IgE and allergen elimination are still the core management of

allergies and asthma. The presently propagated ideas imply that histamine is

just one of many mediators of allergy and therefore does not deserve prefer-

ential consideration. Moreover, if other mediators are still named, histamine

is often not even mentioned as an ordinary player.

Such views can easily be refuted, first of all, by the very name of this inter-

national conference that concentrated solely on histamine and the possibility

of its use in the management of patients. Secondly, “even though histamine is

only one of many mediators of allergic disease, it should be strongly consid-

ered when analyzing the cause and treatment of any mast cell-related disease,”

observed Dr. White, M. Kaliner’s co-author of the chapter “Histamine” in the

authoritative volume Inflammation.90 She continues in the same article: “The

presence of the H3 or H2 receptor might alter susceptibility to H1 effects” and

also: “H3 receptor is primarily responsible for turning off histamine secretion.

This receptor is found in the brain, but some data suggest that it may also be

present in the lungs and other tissues. Furthermore, the ability of the H2

receptor to turn off histamine secretion in the basophile may be mediated by

the H3 receptor.” In other words, efficient H2/3 effect wins over H1 effect (Later

research proved the existence of H3 receptors in the lungs and other tissues).

Like the discoverer of H3 receptors, J. Arrang, Dr. White emphasized the

synchronized functioning of H2 and H3 receptors. Paradoxically, the author

makes a statement that contradicts all she said before: she suggests H1 and H2

blockers be used together. Her informative report fails in its conclusions

because blocking H2 receptors would make them even less effective. One can

only ponder the logic of this suggestion.

Along with the widely used statements that histamine is important in

provoking asthma symptoms, some ideas that would today be considered

outright seditious were expressed at the symposium. For instance: “Mediators,

perhaps including histamine, are important in immunomodulation.” Or:

“Therapy directed at cells that produce these (histamine-releasing) factors



and cytokines… may prove beneficial in the treatment of asthma.”91 Unlike

Dr. White, this researcher does not spell out the anti-inflammatory function

of H2/3 receptors. As a result, the two reports, although supportive of each

other, remain disconnected.

Another conference participant, J. Hanifin, correctly presents allergy

symptoms as the result of “abnormal histamine releasing factors or,

conversely, a lack of histamine released inhibitory factors.”92 He also wrote

that “increased level of histamine releasing factors may account for

abnormal…histamine releasability” in allergies. The author outlines the two

ways of controlling histamine release and therefore its symptoms: by dimin-

ishing the amount of the disease-promoting chemistry or increasing the

amount of disease inhibiting chemistry. However, this article, as all the rest, is

limited to naming the theoretical facts and leaves unheeded the clinical impli-

cations these facts carry. There is only the ever-present rhetorical comment:

“possibilities have yet to be studied in depth.”

We quoted in the first part of the book Dr. L. Mansfield who presented a

report on the “relatedness” of asthma and allergic rhinitis to migraine—a fact

noted as far back as the early 1920s. Speaking about different neurotransmit-

ters that participate in the production of vascular headaches, this author

suggested the use of H3 agonists, which “offer promise as prophylactic agents

for people who suffer from vascular headaches.”93 Yet, again we are

confronted with the same paradox: having discussed agonists, Dr. Mansfield

speculates what antagonists (antihistamines) are more effective. One can only

assume that such a discrepancy between the description and the conclusions

from a knowledgeable scientist would be due to the limits set by some outside

force, which does not permit the scientist to speak out correctly. It is impor-

tant to note, that this conference took place at a time when the development

of serotonin-related drugs for migraine headaches was in full swing, thereby

setting a specified invisible agenda.

Not only was the relationship of allergic and neurological conditions

reported at the conference, but also another chronic condition that plagues us,

arthritis, was presented as one of a similar origin. “Mast cells and their prod-

ucts are participants in some types of synovitis (joint inflammation). Indeed,

several types of arthritis…are characterized by … mast cell degranulation and

the resulting release and generation of mast cell mediators.”94 The conclusion

of the authors is that “mast cells must be considered with other inflammatory

cells in the genesis and perpetuation of arthritis.” In the discussion that

followed, the audience suggested a change in terms and notions and the need



to “focus our attention on allergic arthritis or hypersensitivity arthritis.”

Is this not proof that the allergists recognized the common roots of

diseases of hypersensitivity and arthritis? This opinion coincides with the

views of Melmon expressed in Therapeutic Immunology 1996, when he

described histamine as the key immunomodulator in any chronic inflamma-

tion. A. Kaplan also believed at some point in the relatedness of allergies:

“mast cells degranulation (is) observed in a wide variety of immunologic

disorders including chronic urticaria, atopic dermatitis, asthma and rheuma-

toid arthritis.”95 The common roots of these disorders indicate the possibility

of similar treatments. At the forum Histamine and Disease, nobody made a

suggestion for practical implications deriving from the data presented.

The Introduction to the forum stated that it was to cover “Major

advances… made in both the understanding and treatment of allergic reac-

tions, which are the cause of man’s commonest chronic diseases.” Now, more

than a decade later, these advances remain speculative and, moreover, are

censored and concealed, removing all hope for patients to benefit from them.

MORAL AND LEGAL ASPECTS OF THE CONCEALMENT OF KNOWLEDGE The purposeful omission, distortion and misinterpretation of pivotal scientific

data, purging of textbooks, the dissemination of inaccurate theories, and the

gagging of those who do not agree with such wholesale censorship all send us

back to the Dark Ages. Every time I come across unfounded declarations of

success or revolutionary changes in the management of allergy/asthma, I

wonder whether the authors are familiar with the works that form the basis of

allergy. If not, they do not have the right to profess themselves “leaders, inno-

vators and educators” in their leading periodicals.96 For people in such a posi-

tion, knowledge is a must. Here we must look at allergists both from the legal

and moral perspective. The elite of allergy medicine are all medical doctors.

They are also official representatives of the profession since they head medical

institutes and govern research bodies as well as preside over professional

forums. This puts three kinds of legal obligations on them:

1. As doctors, they have fiduciary obligations to provide their patients with

the best available knowledge and therapies.

2. As citizens, they must not knowingly make false statements in public about

vital issues in science and therapies, and disseminate falsified information.

3. As public health officials, they do not have the right to consider the health

of individuals as a commodity or a commercial product .



The Ten Commandments are more than just religious laws. Their essence is the

code of civil and social morality on which culture is founded. Not only the

Bible, but also the collective morality of civilization demands that “Thou shalt

not give false testimony against thy neighbor.” Those who know the truth, but

give false “testimony” at their symposia or in their publications, reveal their lack

of morals, a quality unacceptable in a medical doctor. Again, not only the Bible,

but also the collective consciousness insists that “Thou shalt not kill.” They kill,

although not directly. Allergists admit that their ability “of controlling

morbidity from asthma has been rather limited,” and we all know that

mortality from asthma is on the rise. At the same time, profound research has

found ways of natural immunomodulation, and medications for this exist,

namely synthetic histamine and its congeners. They may open the way to the

creation of other modulators that will be preferable to immunosuppressive

drugs. However, “Animal models became preferred because of ease of imple-

menting experiments in animal models of human immune-based diseases, and

an unfortunate separation soon developed between human clinical immunol-

ogists and mouse immunologists,” say two allergists of the highest stature.97

Allergists regret that research is all organ-based diseases, whereas it should

concentrate on immune cells and their functioning, study “immune regula-

tion, immunotherapy, immunogenetics, and immunodiagnostics,” and look

for a “cross-disciplinary approach to understanding” of what allergic diseases

are. What the authors do not say is that the existing “mouse immunology” is

purposeful, and that any introduction of knowledge that may lead to efficient

management of patients is routinely sabotaged. Furthermore, not only

animals have undergone trials with histamine and its agonists. Double-blind

studies on humans have also been successfully conducted in Switzerland and

Japan, but they have been successfully hidden. Open clinical studies that took

place in France and Poland were published in small periodicals, and their

success has remained unknown. Only a general lack of interest and critical

opposition permits such grossly unethical concealment of vital knowledge, its

substitution with invalid contradictory hypotheses, and the diversion of

allergy medicine into the wrong direction, all to the detriment of patients.

The recently updated Hippocratic Oath and Charter on Medical Profes-

sionalism introduced in 1999 define such activity as professional and scien-

tific misconduct.98 “Indeed, one begins to believe that the fewer doctors there

are, the healthier the world might be. Far from being dedicated professionals,



we have become the abusers of people and substances, untrustworthy and

unreliable.” These words were pronounced by Dr. Ron Whelan, President of

the Canadian Medical Association at his valedictory address on August 24,

1993. Why do doctors make such declarations only upon their retirement?

Most probably, out of fear of being ostracized and severely punished by

their powerful peers.

CONCLUSIONS ON THE IMMUNE MECHANISMS IN ALLERGIES ANDRELATED DISORDERS

CONCEPT OF DISEASE

Fundamental genes’ abnormalities

↓

Dysbalanced production of the cellular chemistry

(cytokines, mediators, neurotransmitters)

↓

Malfunctioning of immune and nervous systems

with resultant inflammation

↓

Chronic diseases of dysregulation such as asthma,

allergies, vascular headaches, etc.

This concept of disease is not new; it exists in basic sciences but is not assem-

bled and spelled out as a structural notion in clinical medicine. The acknowl-

edgement and understanding of this concept would allow clinical medicine to

resolve many of today’s unsolved problems, mainly, chronic diseases.

Concept Of Histamine-Related Allergic Diseases Abnormalities of the genes responsible for the functioning

of T-suppressors and H2 and H3 receptors, levels of cAMP

↓

Inefficiency of cAMP, T-suppressors and H2/3 receptors on various cells

↓

Exaggerated release of histamine and histamine-induced

pro-disease chemistry with resultant inflammation

↓

Allergies, asthma and symptoms characteristic of the organ or tissue

with histamine hyperreleasability and/or hypersensitivity



These concepts of allergies and related diseases exist in fragmented data in

basic sciences. They also exist, although not formulated clearly and fully, in

theoretical works of leading immunologists and neurologists.

The following quote and the references used to support it are the best

proof of the ongoing censorship cursing modern allergology medicine. The

textbook Allergy 1985 contains a chapter by L. Schwartz entitled “The Mast

Cell,” which states on page 58 that the H2 receptor upon its activation with

histamine mediates “augmentation of T cells suppressor activity” and “down-

regulation of …basophile and mast cell release of histamine.” The cells with

H2 receptor “can also generate immunoregulatory substances upon activation

with histamine,” and the “levels of these are low” in allergy patients. In the

same paragraph, the text says that the very activity of immunocompetent

cells, eosinophils in particular, occurs solely through histamine-related mech-

anisms. “These findings suggest a multifaceted role for histamine in acute

allergic inflammation,” the authors conclude. They write on the same page:

“In 1953, mast cells were noted to be the major source of tissue histamine,

whereas human basophils are the major source of humoral histamine.” The

last sentence of this chapter means that allergies are diseases of one cell—

mast cell—and have one mediator—histamine. As the chapter says, the

understanding of this “can facilitate the design of new therapies for mast

cells-related disease.” Among the numerous references given after the chapter,

there are ones to L. Lichtenstein, A. Kay, S. Holgate, K. Melmon, R. Rocklin,

A. Kaplan, M. Kaliner, which means their research formed the basis for the

chapter. In fact, all those same works were the basis for my conclusions.

WHAT NEXT?Allergology should honestly admit that at present, genetic engineering, for

example, is a hypothetical possibility not feasible in the near future. Logically,

the next step should be to deal with these diseases on the level of their major

products—cytokines and mediators. The aim of the therapies should be the

restoration of balanced chemical production through the restoration of those

immune tools that are deficient. This would lead to the development of thera-

peutic agents capable of activating these tools, namely immuno- and neuro-

modulators. The repaired tools will acquire the ability to fight effectively on

their own, and their restored functioning may even correct the functioning of

the relevant genes. Since in many chronic diseases, the inefficient tools are

certain polysystemic cellular receptors and enzymes, their activation



should become the prime goal. Such interdisciplinary approach would lead to

the introduction of psychoneuroendocrineimmunology in clinical medicine,

whereas now, it exists mostly as a theoretical discipline.

Simply put, clinical allergy ought to recognize the vast basic knowledge

available to its field, and then properly consider and incorporate it. There are

many weighty reasons why asthma, allergy and other histamine-induced

diseases should and can be tackled right away:

■ They affect a large percentage of the population.

■ They are the fastest growing afflictions, now reaching epidemic proportions.

■ They are functional, at least at the beginning, and are therefore much more

reversible than other chronic diseases with organic changes.

■ Effective medications in the form of synthetic histamine and its congeners

exist.

■ Targeting one allergic condition may and, in most cases does, cover related

neurological symptoms.

Indeed, every aspect of the origin of allergic and related diseases and their

interdependence and therapy has solid support from basic science.

Only one thing is lacking—the desire of those in power to implement all

of this. Doctor, cure thyself first. Clinical allergy is in urgent need of curing

itself by reconsidering all “missing links” and focusing on how to help its

patients.

“Revolutions have never succeeded unless the establishment does three-

quarters of the work” (Peter Ustinov). Does the allergy establishment feel the

need of a revolution? Does it want to revolutionize its field? Or is it satisfied

with its own impotence and the suffering of its patients?99

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2. K. Melmon, R. Rocklin, R. Rosenkranz. American Journal of Medicine1981; 71:100-6

3. D. Beer, R. Rocklin, JACI 1984;73:439-52.

4. R. Rocklin. Clinical and immunologic aspects… JACI, 1983;72:323-334

5. S. Hill. Pharmacological Reviews 1990;42

6. I. Elenkov et al. Histamne potently suppresses human Il-12 and stimulates Il-10 production via

H2 receptors. The Journal of Immunology, 1998;161:2586-2593

7. H.R.Bourne, L.M. Lichtenstein, K.L. Melmon, et al. Modulation Of Inflammation & Immunity

by Cyclic AMP, Science 1974;184:19-28

8. M.Bourne, K. Melmon, L. Lichtenstein, Science 1971;173:743


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9. M. Khan and K. Melmon, Are Autacoids More Than Theoretic Modulators of Immunity?

Clinical Immunology Reviews 1985;4(1):1-30

10. K. Austen, ed. Therapeutic Immunology 1996:192,198

11. A. Kaplan ed. Allergy, Churchill Livingstone Inc. 1985

12. For a detailed analysis of this system see The Olivieri Report published by the Canadian

Association of University Teachers in 2001

13. S. Hill. Pharmacol Rev. 1990;42:69

14. S. Hill et al. Classification of Histamine Receptors. Pharmac Rev 1997;49:253-278

15. F. Ravikovich. H2/3 Effect in allergy. Allergie & Immunologogie 1992;24:72

16. The transcripts of my trial are in the public domain and can be checked by interested persons.

17. M.Bourne, K. Melmon, L. Lichtenstein, Science 1971; 173:743

18. L. Lichtenstein, E. Gillespie Nature 1973;24:287-8

19. L. Lichtenstein et. al. Selective Display of Histamine Receptors on Lymphocytes,

Science1977;195: 683-5

20. R. Bourne, L.M. Lichtenstein, K.L. Melmon, et al. Modulation Of Inflammation & Immunity by

Cyclic AMP, Science 1974;184:19-28

21. M. Ichinose, P. Barnes. Histamine H3 receptors modulate antigen-induced bronchoconstriction

in guinea pigs. JACI 1990;86:491-5

22. S. Hill. Pharmacological Reviews,1990;42:69

23. R. Leurs et al. Molecular pharmacological aspects of histamine receptors. Pharmac. Ther.

1995;66:413-463

24. R.G. Andersson et al. Studies of the mechanism of desensitization of anti-IgE-mediated

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25. M. Jutel, et al. Nature 2001,413:420-25.

26. W. Roszkowski, M. Plaut, L. Lichtenstein. Science 1977, 195:683-5

27. Allergy And The Immune System, Scientific American, Sept.1993:117-124.

28. Presidential address. JACI 1995;95:783-796

29. B. Zweiman, M. Rothenberg. Articles of Note. JACI 2002;109:375

30. Allergy and the immune system. Scientific American September 1993:117-124

31. Science 1974;184:19-28

32. Science 1977;195:683-5

33. AAAI Training Program Directors’ Committee: W. T. Shearer et al. Committee report. Core

content outline for clinical and laboratory immunology. JACI 1994;94:933-41

34. L. Lichtenstein et al. Inhibition of histamine release by histamine controlled by H2 receptor.

Nature 1973;244:287-8

35. Science 1974;184:19-28

36. S. Hill. New Perspective in histamine research. AAS 1991;33:145-159

37. G. Chrousos. Stress, chronic inflammation, and emotional and physical wellbeing: concurrent

effects and chronic sequelae. JACI 2000;106S275-91

38. JACI 2003; Volume 111 No 2

39. JACI 2000;106 No5 Suppl. and 2002;110 No 6 Suppl.

40. For worldwide efforts being made to change this situation see www.doctorsforresearchintegrity.com;

address: 81 Wychwood Park, Toronto, Ontario, M6G 2V5.

41. J. Imunol 1977;118:1734

42. J.A.Grant et al. Histamine-releasing factors and inhibitors: historical perspectives and possible

implications in human illness, JACI 1991;88:683-693

43. L. Lichtenstein et al. Selective Display of Histamine Receptors on Lymphocytes. Science

1977;195:683-5

44. Agents and Actions 1991;33Supl.:376

45. M. Clerici et al. An immunoendocrinological hypothesis of HIV.Lancet 1994:343:1552-3



46. JACI 1991;87:207

47. P. Kuna et al. Chemokines… JACI 1995;95:574-86

48. D. Beer, R. Rocklin, Histamine-induced suppressor-cell activity. JACI. 1984;73:439-452

49. JACI 1995; 95:574-86

50. For an overview of all these abusive prosecutions see www.collegeofphysicianswatchdog.com

51. MC Lilu et al. Immediate and late inflammatory responses… Am Rev Respr Dis 1991;144:51-8

52. Hebert et al. The regulatory effect of histamine on the immune response: characterization of

the cells involved. Cellular Immunology 1980;54:49-57

53. M. Kaliner. A Hierarchy of mediators of the allergic reactions. JACI 1992;90:727-8

54. Lancet 1983;1:520

55. L. Lichtenstein. Presidential Address JACI 1995;95:783

56. M. C. Gonzalez et al. Allergen-induced recruitment of bronchoalveolar helper (OKT4) and

suppressor (OKT8) T-cells in asthma. Am Rev Respir Dis 1987;136:600-604

57. Ed. by J.I. Gallin et al. 1988

58. B. Kay. Allergic diseases and their treatment. New England J Med 2001;344:109-113

59. JACI 2003;111:S261

60. I. Hasaelden et al. Late asthmatic reactions provoked by intradermal injections …JACI

2001;108:394-401

61. M. Church. H1-antihistamines and inflammation. Clinical and Experimental Allergy.

2001;31:1341-43)

62. I. Liu et al. Cloning and pharmacological characterization of a fourth histamine receptor (H4)

expressed in bone marrow. Molecular Pharmacology 2001;59:420-6


suppressor (OKT8) T-cells in asthma Am.Rev.Respr. Dis. 1987;136:600-604

64. New.England J Med. 1980;302:1212

65. K. Shirley et al. T-cells peptide epitopes in man may be associated with the induction/

expression of a population of regulatory/suppressor T cells. JACI 2001;1007(2):S67

66. I. Bachert. a major role in allergy? Clin Exper Allergy Histamine 1998;28,S6:15-19

67. A. B. Kay. Allergy and Allergic Diseases. The New Eng J of Med 2001; 344:30-7) (A. B. Kay

Allergic diseases and their treatment. New Engl J Med 2001;344:109-113


suppressor (OKT8) T-cells in asthma Am Rev Respri Dis 1987;136:600-604

69. ARIA: Global guidelines and new forms of allergen immunotherapy. JACI 2001:108:497-9

70. J. Elenkov et al. Histamine potently suppresses…J. of Immunol 1998;161:25-86-93

71. A. Mazzoni et al. Histamine regulates cytokine production in maturing dendritic cells, resulting

in altered T-cell polarization. J. Clin. Invest. 2001;108:1865-73

72. H. Tiemessen et al. CD4+ CD25+ regulatory T cells are not functionally impaired in adult

patients with IgE-mediated cows milk allergy. JACI 2002;110:934-6

73. G.Hoyne et al. Immunological tolerance to inhaled allergen. Am J Resp. Crit Care Med

2000;162:S169-S174

74. M. Jutel et al Differential Histamine H1 and H2-Receptor Expression Determines Up-regulation

of Th1 and Down-regulation of Th2 Responses Following Histamine Stimulation. JACI

2000;105(II):157

75. S. Holgate. The epidemic of allergy and asthma, Nature 1999;402:SB2-B4

76. C. Brightling et al. Mast-cell infiltration of airway smooth muscle in asthma. N. England J Med.

2002;346:1699-1705

77. J. Black. The role of mast cells in the pathophysiology of asthma. N Engl J Med. 2002;346:1742-3

78. S. Holgate. The cellular and mediator basis of asthma in relation to natural history. The Lancet

1997;350 SII:5-9

79. S. Holgate. Role of systemic leukotrienes…JACI 2003;111:S18-36.



80. S. Holgate, M. Peters-Golden. Introduction. JACI 2003;111:S1-4

81. Lancet 1997;350:SII:5-9

82. A. Mazzoni. Histamine regulates cytokine production in maturing dendritic cells, resulting in

altered T cell polarization. Journal of Clinical Investigation 2001;108:1865-1873

83. P.L. Harbinson et al. The effect of a novel orally active selective PDE4 isoenzyme inhibitor on

allergen-induced responses in asthmatic subjects. Eur Resir J 1997;10:1008-14

84. M. Ichinose, P. Barnes. Histamine H3 receptors modulate antigen-induced bronchoconstriction

in guinea pigs. JACI 1990;86:491-5

85. K. Knigge and J. Warder. Neuroendocrine functions of histamine. Agents and Actions

Supplement 1991;33:29

86. P. Barnes. New Directions in Allergic Diseases. JACI 2000;106:5-16

87. P. Barnes. Endogenous inhibitory mechansims in asthma. Am J Respir Crit Care Med

2000;161:S176-181

88. JACI 1990;86:589

89. S. Wasserman, Mast cell biology. JACI 1990;86:590-3

90. M. White The role of histamine in allergic diseases. JACI 1990;86: 599-605

91. S. Peters. Mast cells and histamine in asthma,. JACI 1990;86:645

92. J. Hanifin. The role of antihistamines in atopic dermatitis. JACI 1990;86:666-8

93. L. Mansfield. The role of antihistamine therapy in vascular headaches, JACI 1990;86:673-6

94. J. Mican and D. Metcalfe, Arthritis and mast cell activation, JACI 1990;86:677-83

95. P. Kuna et al. JACI 1995;97:574-86

96. R. Zeiger, M. Schats. Effect of allergists intervention on patient-centered and societal outcomes.

JACI 2000;106:995-1018

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2003;111:S766-73

98. The Lancet 2002;359:520-22

99. I did not lose my license, but was reprimanded for the use of histamine and forbidden its

future therapeutic use as well as any substance containing histamine. This ban on histamine

is indefinite and naturally sends a clear message to any other physician wishing to learn and

employ this method of therapy.

100. S. Holgate. The role of histamine in asthma. In Management of Allergy in 1990s; ed. M. Kaliner

1989:14-20 Hans Huber Publishers

101. ARIA Editorial. JACI 2001; 108:497-9

102. P. Sirios et al., Eds. Immunopharmacology. Elseveir Biomedical Press 1982.

103. A. Kaplan ed. Allergy Harcourt Publishers Ltd. 1997



PART FIVE

MEDICATIONS

SIDE EFFECTS OF MEDICATIONSWhat you have read in this book on the immune mechanisms of allergy is, in

fact, simplified cellular biology. Now, it is time to study immunopharma-

cology in the same simplified form. This the name of the science that studies

what medications do to the immune cells. Those who take medications for

such chronic conditions as allergy and/or asthma need more than just to

perceive them as good or bad. They should understand how these drugs inter-

fere with the work of the participating cells and affect the course of allergic

and related reactions. Immunopharmacology explains what immune mecha-

nism is targeted by each usually highly publicized “breakthrough” and

informs whether it is a new drug or a variant of an existing one. It is also

important to know what price we really pay for temporary relief: a mere spike

in the level of discomfort, lasting severe complications, or perhaps another

chronic disease? This is very relevant in today’s medicine, as, according to the

World Health Organization there are only 326 essential drugs, while, Health

Canada, for instance, has licensed over 5,200. Does this mean that almost 95%

of these are needless medications?

Dr. J. Lexchin in his book The Real Drug Pushers quotes an unpublished letter

to a Canadian newspaper, written by W. M. Garton, the 1980 President of

Pharmaceutical Manufacturers Association of Canada. The letter says, “The

pharmaceutical industry has never claimed to be motivated by altruism but

rather by profit for survival.” It is evident that the attitude of the industry

towards drug consumers is not motivated by even a basic notion of ethics,


and this attitude forms their policy and influence on doctors who do the

prescribing.

Drugs are usually more toxic than is indicated on the labels, and the

reasons for that are clearly outlined in the 1990 medical publication Drug

Protocol by J. Rovers:

1. Groups of patients who undergo testing are rather small.

2 Those who may potentially mar the drug efficacy coefficient are excluded

from the trials, such as old patients and patients with concurrent medical

conditions requiring medications—in short, most prescription-needy

clients.

3. The period of testing is too short to enable anybody to notice a delayed

adverse reaction, which may manifest years later.

4. The reports given by the doctors involved in trials have poor validity (the

author assesses it as “mediocre”).

Always keep in mind that the scientists and doctors who provide the infor-

mation on the clinical drug use are often sponsored by drug manufacturers

and thus have a conflict of interest.

Given the fact that the principal approach in allergy treatment, elimina-

tion of allergy triggers, does not solve the problem, an allergy sufferer is

forced into accepting occasional or daily allergy symptoms. Lucky are those

whose symptoms are mild, and they can manage without taking drugs. For

those whose symptoms become an obstacle to normal life, daily medications

are the only answer. I am going to discuss allergy medications. Medications

for asthma will be covered separately in the part entitled “Bronchial Asthma.”

ANTIHISTAMINES The largest group of allergy medications is antihistamines, which act on H1

receptors. The fact that they are the world’s most commonly used medica-

tions is not surprising in view of the increasing number of allergy patients.

The name, antihistamines, indicates that medicine knows that histamine is at

the heart of the problem, and to control its activity is to control the symp-

toms. As we know, the H1-receptor messages become exaggerated if H2/3

receptors are inefficient. Antihistamines block H1 receptors to prevent the

negative effects of histamine. The blocking effect lasts only while the level of

the drug in the body is high enough. Following the drug’s natural excretion,

its concentration falls, so does the potency, and another pill is needed.



The first antihistamine was developed in France in the early thirties,

which makes this drug group 70 years old. Since their first appearance, H1

antihistamines have changed in two ways. One change affects the prolonga-

tion of their action, and as the packaging of some newer antihistamines

promises, they work for up to 24 hours. The other change is the elimination

of the sedative effect although, according to patients and even scientists, this

adverse effect is never completely removed. The absence of sedation has,

however, its negative aspect. If before, drowsiness would serve as an alarm

against the overdose, now, the deceptive “harmlessness” of the drug invites

patients to take more than is recommended on the label. Regrettably, this

happens often in view of the low efficacy of antihistamines. I have seen people

who actually tripled the dose and then experienced ringing in their ears, were

drowsy, but still, the drug did not control their allergy symptoms. If at the

same time, for another condition, a patient takes tranquillizers or other

“downers,” or has an alcoholic drink, even as mild as a beer, the sedative effect,

absent at the recommended dose, may intensify.

This logically leads us to the question of whether the concept of a “proper

dose” exists. The answer is no, since everything depends on the individual

sensitivity and concurrently taken medications. Even with the recommended

“safe” dose of a non-sedative antihistamine, some patients complain of

drowsiness or a slowing reactivity to their surroundings. Children and older

people, as well as patients on other concurrent medications may experience

more adverse effects. The recently banned Seldane is confirmation. In 1997,

Seldane was taken off the market because, prescribed concurrently with

certain antibiotics and some other medications, or taken with grapefruit juice

(!) it could produce serious complications such as cardiac arrhythmia, or even

death. Presently, Seldane exists in a perfected form under the musical name

Allegra, and is free, according to the manufacturer, of the previous side effects,

but according to patients, it is also less effective than its predecessor. Similar

adverse effects led to the ban of Hismanal, the second oldest non-sedating

antihistamine. Are other antihistamines safer? Only time will tell, as they

came onto the market later than Seldane and Hismanal.

Non-sedating antihistamines are much more expensive than their pred-

ecessors. The price for one non-sedating pills may be up to 20 times higher

than the price for a pill of the old sedating group. Quite an impressive

difference!

Medications 175


SIDE EFFECTS OF ANTIHISTAMINESThere is no such thing in medicine as a totally effective drug; therefore the

question, which antihistamine is most potent, is pointless. Medication can be

chosen only by trial and error. Moreover, the body develops tolerance to any

chemical, and as a result, potent at the beginning, an antihistamine may lose

its effect days later. Besides, antihistamines only relieve symptoms and do not

mend the cause. Thus, with the progression of the disease, appearance of new

symptoms and intensification of the existing ones become the natural course,

and the formerly effective antihistamine starts to fail. All this forces one to

search for a replacement. Doctors recognize that the latest non-sedating anti-

histamines are often less effective than the first-generation drugs, which are

still popular on the market, Benadryl, Atarax, etc. In their attempts to find

relief, allergy sufferers may jump from one drug to another and eventually

resort to the older group. This group creates an occupational hazard through

drowsiness, impaired coordination and poor concentration. If you take these

drugs, don’t drive, or perform work requiring concentration or dexterous

functions. Lucky are those having work where they can relax, but they are rare.

From the generally available information on the adverse effects of antihist-

amines, we are led to believe that they are much safer than other medications.

Most common adverse reactions of antihistamines made known to us are dry

mouth, upset stomach, drowsiness, fatigue, nervousness, palpitations, dizziness,

insomnia, rash (including hives). Pharmaceutical compendia also mention

occasional weight gain as a possible side effect. All this is fairly innocent. The

worst “side effect” of occasionally taken antihistamines, their relatively poor effi-

cacy, leads to their overuse. The abuse is easy because they are mostly over-the-

counter drugs and are thus easily accessible. Regular consumption changes the

view on the complications. Nowhere will you be able to read about the most

severe side effects of antihistamines. Below are some of them.

GENETIC INTERFERENCEFrom basic science, it is known that a certain gene plays the dominant role in

the metabolism of histamine. This gene activates the enzyme called HNMT,

which facilitates histamine break-up and hence, prevents its accumulation in

the body—an anti-allergy effect, so to say. Thus, the functional activity of this

gene and its individual variation may determine the occurrence of allergies,

their course and response to therapies. Antihistamines potently inhibit the

HNMT enzyme and, therefore “it might not be an ideal therapeutic strategy



to block the histamine (H1) receptor while also inhibiting at the same time

the major pathway for the metabolic inactivation of histamine in bronchial

epithelium.”1 Paradoxically, this means that antihistamines interfere with the

work of the gene that protects us from allergies and asthma. As a result, there

may be worsening of the allergies, occurrence of asthma in those allergy

patients who did not yet have it, or aggravation in those who had it along with

allergies. This makes the authors dream of developing new kinds of antihist-

amines “which do not inhibit HNMT.”

IMMUNOSUPPRESSION BY ANTIHISTAMINES The findings of the suppressive effect of antihistamines on the adrenals were

registered in trials on rats, and the description goes back to 1982. In 1992, an

article covering this drug effect said: “The antihistaminic activity… is well

documented in vitro (in a tube) but has not been investigated as thoroughly

in vivo (in a live body).”2 Quite naturally, over time, the low level of the

adrenals. Vital hormones diminishes the fighting ability of the immune

system. If we logically extend the idea, the long-term use of antihistamines

will, in turn, necessitate later on the consumption of corticosteroid drugs,

which, being immunosuppressive by definition, weaken the immune system

even further. Now, twenty years after the first alarm sounded, it still remains

unknown to clinicians if there have been similar investigations in people.

Those rat trials were done by several major medical schools and clinics in the

U.S. and supported by National Institutes of Health grants, but something

must have prevented studies on humans from being done.

ANTIHISTAMINES AND CANCER?As all chronic diseases, allergies tend to intensify over time, and so a patient

may become a regular antihistamine user. In a series of articles, oncologists

from the Manitoba Institute of Cell Biology, expressed their concern over

tumor promotion, melanoma in particular, in those who took Seldane and

Hismanal. The researchers compared the tumor-contributing effect of

Tamoxifen (breast cancer drug) for which “a 300% increase in uterine cancer

has been documented,”3 with the effects of antihistamines: “given the simi-

larities in the pharmacological profiles of the antidepressants4 and antihista-

mines (with Tamoxifen), we have real concerns.”5

Most of the evidence comes from studies on mice, but some, from inves-

tigations on humans. The first data on these serious possible connections

Medications 177


were published in the early eighties, but allergists, the most passionate advo-

cates of antihistamines, remained silent. In 1994, the information started to

leak into lay magazines. To comfort the public, televised interviews with the

producers of Seldane and Hismanal followed. They reassured the public by

stating that mice could not serve as a model for making decisions regarding

humans, and only epidemiological studies could prove or disprove similar

side effects in humans. Besides, the defenders said, antihistamines did not

cause new tumor formation but just accelerated the development of already

existing cancers, and even then, not in all kinds of cancer.5,6

One can only ponder such declarations in silent amazement. First, due to

the great similarity of the immune systems of mice and man, mice are used as

the model to study the basic immune mechanisms. In the past, the tobacco

industry created exactly the same defence, and it took half a century to arrive

at the evident conclusion that the effect of tobacco on mice was the same as

on people. Second, in many cases, it takes years for a cancer tumor to develop

out of a few existing cancer cells. Any of us may have cancer cells, but they are

regularly destroyed by our immune systems with the assistance of our H1

receptors. What if H1 antihistamines really speed up tumor growth? Seldane

and Hismanal are the oldest medications of the non-sedating group, and, by

the way, were taken off the shelves for side effects unrelated to cancer. Can the

manufacturers of antihistamines guarantee that their newer products will not

show similar carcinogenic effects over time? Is this possibility being tested

elsewhere? After all, there are definite similarities in the effect of all H1 anti-

histamines despite some of the differences in their ingredients.

Since you know how cells and their receptors work, it is easy to under-

stand why H1 antihistamines may contribute to cancer. T-cells cannot effi-

ciently function as cancer fighters, when they are deprived of histamine, as

cytotoxic or T-killer cells become efficient when activated with histamine.

Therefore blocking H1 receptors leads to a histamine deficit and thus under-

mines the efficiency of cancer-fighting T-cells. If an occasional disruption of

immune functions in this area cannot harm severely, a regular blocking can.

The individual potency of each antihistamine may only influence the speed of the

cancer-contributing effect, and we should not be surprised if with time, other

drugs of this group join Seldane and Hismanal in their probable carcinogenic

effect. Do we have the luxury of postponing a decision for two or three

decades, pending epidemiological studies, if chances of tumor growth in anti-

histamine consumers exist today? Will a belated “sorry” be enough if this



turns out to be true? So far, the US Food and Drug Administration doubts the

need of epidemiological studies, since it considers the drugs safe.7 Have there

been additional studies to prove or disprove the findings of the Manitoba

researchers? I personally failed to find any such data.

The initial shock and interest in the cancer connection with antihistamines

soon subsided. Considering the few choices for allergy sufferers, antihista-

mines will continue to enjoy a wide market. New kinds will be synthesized,

and only future generations may realize the full extent of the problem.

One more thought to consider: epidemiological studies last decades, not

years, since they have to cover different health-related events and their causes

in order to determine the significance in the development of the given

disease. Since the creed of medicine is to weigh the pros against the cons, the

dilemma of whether to take or not to take antihistamines does not exist. This

is because concerns for the few of those who may get tumors are superseded

by the multitude of consumers wishing to get at least some relief from their

allergy symptoms. An indirect confirmation of the possible tumor-

promoting effect of antihistamines comes from two articles on tumor regres-

sion due to the histamine therapy.8 Quite logical: if histamine deprivation

contributes to tumor growth, histamine stimulation shrinks tumors.

H2-ANTIHISTAMINES?Although, from the scientific standpoint, activation of the inefficient regula-

tory tools is the only logical solution, allergy has predominantly pursued the

path of suppressing those body’s immune tools, which become overactive as

a result of the inefficiency of their counterparts. Such is the case with H1 anti-

histamines, such has become the case with H2 antihistamines that target the

already inefficient H2 receptors. H2-receptor blockers already exist as medica-

tions for stomach problems, such as Zantac and Pepcid.

The main idea behind the suggested use of H2 antihistamines in allergy is

that they prolong the clearance time of the conventional H1-antihistamines by

acting through liver enzymes. Basically, it means that H2 antihistamines

should be taken together with the conventional H1 antihistamines, and with

that, the latter will be more effective. The drug industry will definitely find the

idea most attractive: two drugs instead of one! For patients, H2 antihistamines

will be a disaster as they will further paralyze the already deficient receptors

and thus inhibit the self-remedial action of histamine. This will deprive the

body of the major means of defense against allergy.

Medications 179


The knowledge of the danger of H2 blockers in allergy has been around for

over 2 decades. Look what the highest ranking allergist, R. Rocklin, says in a

textbook: “Their administration to patients in vivo might. …potentiate hista-

mine release and worsen allergic symptoms. In fact, this seems to be the case.”9

An article by world-renowned immunopharmacologists informs us that

“…H2-receptor antagonists might increase the bronchoconstrictor response

by facilitating the release of histamine...”10 Simply speaking, it means asthma

gets worse.

With the knowledge of the protective effect of H2-receptors in allergy,

their blockers should be contraindicated, and allergists should know that. Do

they? It seems unbelievable, but is true that an article was published by

leading Canadian allergists at the same time as the two above-quoted sources,

in which they actually recommended (!) H2 blockers for those who develop

anaphylactic reactions.11 Anaphylactic reactions are the extreme stage of

allergy, at times fatal due to an explosion of histamine and histamine-induced

pro-disease chemistry. It may happen upon eating a highly allergenic food,

taking a drug or being stung by an insect. By excluding H2 receptors from the

game, the body is left helpless at the mercy of the disease.

DECONGESTANTS Decongestants form another very popular group of short-term relief allergy

medications, although their primary indication is for a stuffy nose in colds.

Among them are Sudafed, Dristan, Otrivin. They constrict nasal vessels, and

the resultant shrinkage of the swollen mucous membrane allows air to pass.

These drugs should be taken in moderation in view of their well-known

rebound action, that is, paradoxical aggravation, that may set in shortly after

one starts using them. It is all right to take a decongestant for a cold that

usually lasts a few days only. Allergies, however, have a lasting course, and

after some period of using a decongestant, an allergy sufferer can never be

sure whether the symptoms persist due to allergy, or they are the ricochet

action of the drug. At times, just by discontinuing the drug, the patient may

have a symptomatic improvement.

The best known decongestant is ephedrine, a synthetic version of a plant

ephedra used since ancient times. It also stimulates cardiovascular tone and

the central nervous system, and for that reason, is sometimes used by athletes

as an “upper.” By the way, Maradona, a world famous soccer star, and Laumann,

a Canadian gold medalist in rowing, were both disqualified for using ephedrine.



Medicine does not put decongestants into the category of harmful drugs

although, as adverse reactions to the stimulatory effect of ephedrine, its users

may experience hyperactivity, anxiety, palpitation, tightness in the chest,

general weakness, vomiting and fainting.

As with Seldane and Hismanal revelations that came years after the drugs

had virtually flooded the market, certain side effects of decongestants, undis-

closed for decades, drew attention. The 1997 annual meeting of the American

Academy of Neurology heard a report by Dr. L. Vives-Castro from the

University of Pennsylvania on the risk of medications that contribute to

vascular constriction. Among the high risk group are migraine sufferers and

postmenopausal women on replacement estrogens. Instability of the vascular

tone in migraineurs and the medications they take, as well as the predisposi-

tion to various vascular problems in estrogens users, put these patients at risk

even if they do not abuse decongestants. The researchers suggested retroac-

tive studies of patients with brain hemorrhage to see if there was a

contributing factor from decongestants. They also considered the possibility

of tightening the regulations covering this drug group, since, like antihista-

mines, decongestants are among the most common over-the-counter

medications and can, thus, be easily abused.

Within the five years that followed, those who suffered from migraine

headaches or took synthetic estrogens had a choice: nasal congestion or a

possibility of brain damage by a stroke. In May 2001, the FDA and Health

Canada banned 63 “cold remedies” that contained a certain decongestant.

Among them, there were the familiar Dimetap Cold and Sinus, Contac Cold

and Alka-Seltzer Plus. American authorities documented about 200 to 500

strokes a year in young people who took these medications, the population

group normally not known for such accidents. Numerous bleeding strokes

were registered in adults under 50, women in particular. My suspicion is

that the number of cases is higher. Many deaths could have been attributed

to a different medical condition, since hardly any doctor would blame

“innocent” decongestants for fatalities.

As is to be expected, manufacturers will reformulate their cough and sinus

medications and will replace the decongestant. Only time will show how safe

the new ones are. Do not forget that the banned drugs had a long history of

use and had originally been recognized as safe.

Naturopaths and herbalists often suggest taking ephedra instead of

synthesized decongestants. In essence, the net results are similar. Ephedra has

Medications 181


recently been banned in this country. So has pure ephedrine. Strangely, the

legions of ephedrine-containing drugs continue to be widely used.

COMBINATION DRUGSIt has become fashionable to design drugs that combine several into one, thus

creating an allegedly new breakthrough product for diverse purposes. For

instance, ephedrine and ephedrine-like drugs are often added to painkillers

and antihistamines. You may recognize these compound drugs through the

letter D for decongestant or word Extra on the label, for example, Claritin

Extra, Tylenol D(econgestant). The only benefit of such medications is in taking

one compound drug instead of taking two pills separately. Do not forget that

although the combination drug offers all the benefits of the ingredients, their

side effects are also preserved.

Antitussives are drugs that suppress a cough, and codeine, a narcotic, is the

most common cough-suppressive ingredient. Decongestants and antitussives are

a popular combination. Cough-suppressing syrups, so often offered to your kids,

are nothing more than a sweetened dose of codeine added to something else.

One of the combo-drugs for allergy is Actifed. I chose it not because it is

more dangerous than others, but due to the heated discussions it produced a

decade ago. The experimental mice who were fed it showed a higher incidence

of liver tumors. It may be that liver tumors do not develop in humans,

although, even a low probability of having such a side effect makes a stuffy

nose preferable. My purpose here is different: Actifed is a combination of an

antihistamine, decongestant, antitussive and sometimes a painkiller. It is a

typical pharmacological amalgam with the benefits and side effects similar to

other combinations.

The entry in the Canadian Compendium of Pharmaceuticals on Actifed,

spells out under Precautions who should not take the drug: children under six

years of age, people with persistent or chronic cough such as occurs with

smoking, asthma or emphysema, patients with high blood pressure, heart or

thyroid disease, diabetes or difficulty in urination, pregnant women and

nursing mothers, patients on antidepressants. Also cautioned are those who

may drive a motor vehicle or operate machinery requiring mental alertness.

From this list one very important point is missing—the instruction as to who

can take the medication that has so many contraindications. A healthy, non-

pregnant adult who uses public transportation and can afford to be mentally

relaxed at work? Are there many such people among allergy patients?



The compendium also expresses concern over an overdose of Actifed,

which may result in nervousness, insomnia and dizziness. Sensitivity to a

medication, as we know, is a highly individual feature; thus, the dose recom-

mended to an “average” person may become an overdose for a hypersensitive

person. I repeat, I use Actifed as an example only. Similar effects are common

for other drug combinations of this group.

Antihistamines, decongestants and antitussives are limited in their action

and provide relief for only a short time. Coupled, tripled or quadrupled, the

ingredients do not prolong the effect, while their side effects are additive. Yet,

these products are in common use by allergy patients.

CORTICOSTEROIDSCorticosteroids, or simply steroids, are the most potent drugs generally prescribed

for asthma and becoming more and more common as the treatment of choice

in other allergies. The name corticosteroids is used to denote, first, natural

hormones produced by our body and, second, the drugs, which are synthetic

versions of these hormones. The general public often knows about a different

kind of steroids (anabolics) that also exist in the form of drugs and are illegally

taken by some athletes to build up muscles and increase performance. However,

our topic is corticosteroids, and the short form steroids will be substituted.

Synthetic steroids have been on the market for half a century. They are the

first-line medications in such life-threatening conditions as shock, coma,

poisoning, severe asthmatic attacks or allergic reactions. They are an integral

part of the medical regimen of organ transplant recipients: by suppressing the

immune system that tries to rid itself of a foreign organ, doctors suppress the

rejection and prolong the patient’s life. Modern medicine extensively

prescribes them in a lot of chronic diseases such as rheumatoid arthritis, ulcer-

ative colitis, Crohn’s disease, cancer, etc.

Steroid drugs are produced in various forms depending on their intended

use: in pills; in injections that can be administered intramuscularly, directly

into an inflamed joint or lesion, or are infused intravenously; in creams,

lotions and ointments for skin application; in eye and ear drops; in sprays for

nasal and chest allergies; as a rectal suppository. Should today’s dentists fall

under the charms of the steroid manufacturers, we will find steroid tooth paste

on the shelves tomorrow.

What is there about steroids that allows their wide-spectrum use and calls for

manufacturing them in so many forms? Steroids are one of the greatest discov-

Medications 183


eries of medicine. This group of drugs is a miracle, for it saves lives in emer-

gency situations and in severe debilitating illnesses. The picture changes when

steroids are taken regularly. Any drug taken on a long-term basis may be

harmful, still, few drugs can compete with steroids in the seriousness of their

complications. All textbooks, articles and lectures on steroids urge dose reduc-

tions as soon as the patient’s condition allows. However, in view of their

growing market share, transparency regarding steroid-related side effects is very

limited. Moreover, the legend of their safety has been recently created in allergy,

and this has skyrocketed their use. But I want to tell you what you will rarely

hear from your doctors, but what you, as an allergy patient, should know.

I intend to unravel the facts about one of the main causes of the growing

severity of all allergic diseases and rising mortality from the most serious of

them, bronchial asthma. The truth is thoroughly concealed from the public

although, I admit, an inquisitive steroid consumer can find it in the drug insert

or a pharmaceutical compendium. But who reads a terminologically compli-

cated scientific text, especially if written in tiny letters? It is similar to the former

microscopic warning against cigarette smoking on an attractive package with

the brand name in capital letters. Generally, patients rely on the information

they get from their doctors. Doctors, in turn, are expected to obey the practice

guidelines which dictate the wide use of steroids. These are formulated by their

own associations, usually with strong input from the pharmaceutical compa-

nies whose representatives sit on the medical councils; the doctors on these

councils and professional associations are often themselves in conflict of

interest due to the fact that their research grants are funded by pharmaceutical

companies.12 Besides, very few doctors will tell you that, in the long run,

steroids aggravate the very condition they are prescribed for. Some conceal this,

others simply do not know.

ADRENALSSince corticosteroid drugs are a synthesized equivalent of the body’s

hormones, we should know about the organ that produces the natural version

of the chemical. We should also know what role steroids play in the func-

tioning of the body, and what happens to their natural producer when

synthetic hormones flow in the blood.

The steroid producer is the adrenals, pea-size, paired endocrine glands

situated above the kidneys. In Latin, ad means near, and ren stands for kidney.



The adrenals are vital for the body. This tiny gland has a wide spectrum of

action: through its hormones, it regulates and maintains the metabolism of

proteins, carbohydrates, fats and minerals, controls water balance and is also

a source of sex hormones. Knowing this, it is easy to understand that

malfunctioning of the gland may impact all of these processes. Steroids

produced by the outer layer of the adrenals, its cortex (bark, shell, rind in

Latin), correspondingly got their full name, namely corticosteroids. They are

our power source—hormones give us strength and resistance and life itself.

Along with steroids, our body draws these powers from another hormone

produced by the inner layer of adrenals—epinephrine. Its synthetic version,

adrenalin, is also given to patients in emergency situations. The well-known

Epipen carried by those prone to anaphylactic reactions is, actually, a syringe

filled with adrenalin.

We know that in critical situations, a man can lift a weight he is normally

not able to lift, run away from danger at a speed inconceivable under normal

circumstances and withstand the most extreme conditions for a certain

period of time. This is possible because of the adrenals that start to work

instantaneously at a high capacity in demanding situations and supply us

with their wonder hormones.

The adrenals’ hormones also protect us from stress. If in lay language,

stress is usually associated with a psychological strain, as a medical term,

stress has a much wider notion. It is defined as a body’s reaction to any

adverse stimulus that may disturb its homeostasis. This includes hard phys-

ical effort and severe emotional pressure, intense pain and an infection—all

extreme situations which put an extra load on the body and require adapta-

tion to the situation. The adrenals are directly involved in the required adap-

tation process by increasing the production of corticosteroids and

epinephrine, which mobilize the body’s resources.

Immune diseases put great demands on the adrenals, and without corti-

costeroids and epinephrine, the body may perish. Severe allergy, and especially

asthma, create a situation of stress, and for these patients, activity of the adrenals

is of prime importance. In short, the hormones of the adrenals are the fuel,

which this endocrine gland supplies for the proper functioning of all organs.

The body cannot work without this organ, just as an engine cannot work

without fuel. Therefore this gland should always be in good shape, not only to

meet the every day demands of its hormones but also to be ready for any unex-

pected emergency.

Medications 185


HYPOTHALAMIC-PITUITARY-ADRENAL AXISTo understand the vital importance of the adrenals to the functioning of the

whole body, we must know the gland’s connection with the two other supe-

rior organs situated in the brain—the pituitary and the hypothalamus. Their

functioning is inseparable. Different endocrine glands join the pituitary and

the hypothalamus to form an axis, and each axis regulates the production of

the hormones specific for the given gland. The adrenals team up with the

pituitary and hypothalamus to form the hypothalamic-pituitary-adrenal

axis, for short, HPA. The axis controls the production of steroids generated

by the adrenals. It is a three-story structure: the adrenals are subordinate to

the pituitary gland which, in turn, is subordinate to the hypothalamus.

THE PITUITARYFrom the lower story, the adrenals, we can move up to the pituitary. Medicine

calls it the master gland because it regulates the work of almost all endocrine

glands. Hormones affect everything—growth, maturation, reproduction,

behavior. The pituitary plays the role of a meter that determines the appropriate

levels of hormones released by other glands into the blood and adjusts them

to the required level. It communicates with other glands such as to intensify

or slow down the production of their hormones. The body’s need of different

hormones at any given moment depends on the time of the day, period of life,

emotions, etc. For example, the need of adrenalin and steroids during sleep is

lower than during daily activity. This, by the way, explains why asthmatics

often feel worse at night or early in the morning: less defensive hormones are

produced, and so allergic processes run against less resistance.

The pituitary is “multilingual”: it uses its own special stimulatory hormones

as a language of communication, different for each subordinate gland. Thus,

“the language” it uses to communicate with the adrenals is the hormone called

corticotropin. The pituitary assesses the amount of steroids in the blood that

reaches it, decides if their production should be reduced or increased and corre-

spondingly adjusts the amount of corticotropin that stimulates the adrenals.

The master gland is not interested in whether the hormones are generated by

the body itself or taken as medications. Its decisions are made purely on the

quantitative measurements of their levels in the blood.

THE HYPOTHALAMUSThe hypothalamus is on the upper level of the HPA axis. This miniature regu-

latory center is a complex, supremely important structure of the brain, which,



similar to the pituitary, is the bridge between the nervous and endocrine

systems. Although a tiny organ, the hypothalamus activates, controls and inte-

grates the work of the major endocrine glands, some parts of the nervous

system and the cardiovascular system. It supervises our behavior, sleep,

appetite, body temperature, emotions, libido, etc. Hardly anything is left

beyond its supervision. The pituitary is attached to the hypothalamus and

receives all important directions from its superior, also in the form of special

hormones. These hormones help the pituitary to properly regulate the

endocrine glands at the periphery. Both the pituitary and the hypothalamus

are a part of the brain, therefore in addition to hormones, they use another

language of communication used by nerve cells—neurotransmitters.

SUPPRESSION OF ADRENALSThe human body is a clever structure. For survival, it is programmed by

nature to sacrifice less important substances or parts to preserve its most vital

organs. Thus, in severe frost, the circulation to the extremities is shut off to

keep enough blood supply for the internal organs. From the biological point

of view, extremities are a small loss compared to life itself. Reasoning by

analogy, the ultimate level of blood hormones is more important for the

functioning of various organs than the normal performance of just one

gland—adrenals. An excess or a deficit of hormones equally impair the

steady, homeostatic level needed by the body to function normally.

A doctor’s prescription of steroids in immune-related inflammation has a

logical basis: the body needs these power hormones to cope with a stressful

situation. When steroid medication reaches the pituitary with the blood flow,

it is perceived by the “meter” in the same way as would the natural hormones.

The addition of the synthetic hormone to the natural hormones produced by

the adrenals creates a surplus. The pituitary, indifferent to the source of the

hormones, tries to correct the impaired imbalance by ordering the adrenals to

diminish their steroid output and does this by reducing the amount of its

corticotropin. Less stimulation by corticotropin means less active adrenals.

Deactivation of the adrenals lasts as long as the steroid medications are

taken. During periods of prolonged drug use, the adrenals, similar to muscles

weakened by inactivity, also weaken. Their ability to generate steroids steadily

reduces. The longer the drug is taken, the longer it takes the gland to restore

its functioning when the medication is stopped. Therefore, when the patient’s

condition improves, and the drug is discontinued, the long-suppressed adrenals

are often unable to meet the body’s demand. During their regeneration

Medications 187


period, the patient is forced to rely on the synthetic steroids that make up for

the deficit of the natural hormones. This physiological dependence is the

reason why, unlike other medications, steroids cannot be stopped abruptly

but should be weaned slowly, even if the disease for which they were

prescribed, is controlled. In such situations, steroids are taken because of

dependency and not because of the original symptoms.

“What happens if steroid tapering is done too suddenly?” This was a ques-

tion from an interview given by Dr. Teik Chye Ooi, and Associate Professor of

Medicine at the University of Ottawa.13 His answer was that “a number of

problems may arise,” and “in the most extreme situation, sudden death can

occur.” This happens due to the adrenals’ shut-down and hence, sudden

systemic shortage of their vital hormones. With sustained steroid consumption,

the adrenals may atrophy, and such patients are doomed to take synthetic

steroids for the rest of their life.

The body possesses an amazing ability to keep the balanced production of

its chemicals. Therefore, when synthetic hormones become a daily interfer-

ence, the adrenals become redundant, and the body sacrifices them. Their

atrophy is the price for the relative balance of the level of steroids in the

blood. The result is the body’s dependence on the steroid drugs.

STEROIDS AS REGULAR MEDICATIONSThe immediate effect of steroid drugs is striking in many of the cases. Since

every cell has receptors responding to steroids, the whole body reacts to the

synthetic version. Steroid drugs act like the adrenals functioning at full

power. The dramatic relief they provide, creates the illusion of their safety.

However, it is important to distinguish between an emergency need of steroid

drugs and their chronic use. Asthma and allergies are chronic diseases. As

their resistance to other medications grows, more and more often, steroids

become the treatment of choice, and their consumers become victims of the

medication.

Synthetic steroids mimic the internal hormones, therefore the HPA axis is

deceived. The best drug protocol cannot compete with the flexibility, with

which the body conducts self-regulation of its chemicals. Just compare how

skillfully the body monitors its blood sugar level in non-diabetics, even if they

are chocoholics and cake abusers, and how jumpy sugar levels can be in those

on insulin, despite regular careful adjustments of the dose. Similarly, with

daily steroids, the most expert titration of the dose is still basically artificial



and clumsy by comparison to nature’s way. In a healthy body, the pituitary

knows exactly how much corticotropin it needs in order to stimulate suffi-

cient steroid production by the adrenals, whereas a steroid user is constantly

deceived by the drug. The drug interferes with the regulatory processes. As,

the production of all chemicals in the body is interrelated, the fluctuating

levels of steroids affect the balanced production of others, and this leads to

additional malfunctioning of different tissues, organs and systems.

Synthetic steroids primarily affect the adrenals. As was said, the pituitary,

satisfied with the steroid medications, reduces its production of the stimula-

tory corticotropin until it does not involve the adrenals at all. Without stimu-

lation from the pituitary, the adrenals slowly die away and with time, become

atrophied. The situation looks even grimmer as the advanced suppression of

the adrenals may extend to the production of its other hormones.

In a stress situation, adrenals protect us by increasing the synthesis of their

hormones, and their failure shatters the whole body. It is a well-known fact

that in a patient with failing adrenals, pneumonia and other infectious

diseases become abnormally frequent and life-threatening. Equally life-

threatening is the ensuing adrenal failure itself. Now, all this starts a vicious

circle: the compensatory dose of daily steroid medications goes up, and with

it, complications grow. As we know, immunosuppressive steroids suppress the

activity and the very life of all immunocompetent cells, T-cells specifically.

Therefore, the patient’s health is further undermined by the direct suppres-

sive effect on the T-cells’ protective activity, and he now faces a more severe

course of chronic immune-related diseases, allergy and asthma among them.

PROS AND CONS OF DAILY STEROIDSIf daily steroids are so dangerous, why are they still prescribed so often? Apart

from acute life-threatening situations, there are circumstances when regular

steroids are irreplaceable. As was said, they are an inherent part of the manage-

ment of organ recipients. Rejection of a transplanted organ is a normal reac-

tion of our immune system that tries to eliminate everything alien, be it a sliver

or a transplanted organ. However, this protective immune response turns out

to be fatal for a recipient who cannot survive without the transplant, and

immunosuppressive drugs are prescribed to reduce the body’s innate ability to

reject. Steroids are among them. Their prescription in the event of organ

transplantation is justifiable because between the two evils—life with a vulner-

able immunity or death without an organ—the first choice is preferable.

Medications 189


Treatment options are different for allergy patients. Their diseases,

excluding resistant asthma and severe anaphylactic reactions, are not fatal and

cause discomfort or distress. For these patients, steroids are not vital, and

potential consumers should be given this information so that they could weigh

the pros and the cons before they opt for the serious side effects of or the phys-

iological dependency on steroids. The patients are rarely, if ever, get to know

the necessary information, and a lot of them take daily steroids even for mild

asthma, without a clue that they may end up with a more severe form.

COMPLICATIONS OF STEROIDSGiven the critical need of adrenal steroids for the normal functioning of all

organs, we should not be surprised that many organs and systems suffer in

cases of inadequate supply with a synthetic version. Complications arising

from steroid use can be divided into:

a) temporary adverse reactions which usually go away when the drug is

discontinued;

b) lasting complications which may subside with drug discontinuation,

but may turn into a chronic condition due to the sustained drug use;

c) development of new chronic diseases.

Most drugs are known to have unwanted side effects, but few are as notorious as

steroids. Among the temporary adverse reactions listed by pharmaceutical

compendia are nausea and vomiting, indigestion, headaches, dizziness, fainting,

irregular heartbeat, elevated blood pressure, nose bleeds, frequent urination,

moon-like face, weight gain, unusual tiredness, weakness, mood swings, insomnia,

muscular cramps, joint pains, unusual bruising, etc.

Allergology is full of paradoxes, and steroids prescribed in allergy is one of

them: they may result in allergic reactions of various degrees—from skin

rashes and hives to systemic reactions. As was reported at a semi-annual

meeting of the American Contact Dermatitis Society by the chairman of the

department of dermatology in a New Orleans hospital, Dr. R. Rietschel,

“corticosteroid allergy is real and more common than expected.” This doctor

referred to systemic reactions and reported the findings in five comprehen-

sive studies conducted in Europe and North America.14

Steroids produce numerous serious side effects that may not go away when

the drug is discontinued after protracted use. They include hypertension, water

retention, growth retardation in children, fragile skeletons in older people and

menopausal women due to calcium loss (i.e osteoporosis), obesity and suscepti-



bility to diabetes due to the impairment of fat and carbohydrate metabolism,

peptic ulcer, poor wound healing (an obstacle for any surgery), glaucoma,

cataracts, various infections, excessive facial hair growth, etc. (The latter alone

could stop women from taking steroids, since most would put up with any

side effect but not loss of their femininity.)

Read the list attentively. These are not just temporary adverse reactions,

but rather diseases. These complications may diminish when the patient

discontinues steroid use, but considering the chronic nature of allergies and

asthma and the resultant equally chronic drug dependency, chances are high

that the adverse effects will become diseases. Thus tendency to hyperglycemia

(high blood sugar) may become diabetes, loss of bone mass leads to osteo-

porosis and fractures as well as stunned growth in children, elevated blood

pressure turns into permanent hypertension, etc. Indeed, irreversible damage

of organs and systems of organs is not so uncommon among steroid users.

Steroids also affect our nervous system. A neuron conducts electrical-like

impulses from one part of the body to another. It is a wire connecting the

centre—the brain, with the periphery—the rest of the body. Neurons are the

basis of our nervous system, and without them, we would not be able to see,

hear, move, or think and exist as a live being. Neurons suffer immensely from

the toxicity of steroids even when the hormone is excessively produced by one’s

adrenals. Thus, a person who experiences a lasting stressful situation becomes

depressed, his memory span diminishes, and his learning ability falls.

The psychological effect from the stress is augmented by the higher than

normal amounts of internal steroids released to help us in overcoming this

stress. They produce additional biochemical brain changes. For decades,

medicine has known that lasting exposure to steroid drugs reduces the ability

of nerve cells to survive in demanding situations and leads to their premature

ageing and even death.15 Their premature ageing is our ageing.

Since adrenal hormones regulate the metabolism of carbohydrates and

fat, steroid drugs affect these too. They also affect the synthesis of insulin, the

hormone that reduces higher levels of blood sugar. It is textbook knowledge

that corticosteroids are a contra-insulin factor, and naturally, their surplus

compromises the levels of insulin, and this, in turn, may lead to diabetes.

Another grave side effect is suppression of growth hormone. For young

steroid consumers, it means that the normal development of their bones is

impaired, and they may not reach the height charted for them by nature. In

medicine, however, growth is also understood in a broader sense than just

Medications 191


linear development. It is a qualitative process that involves cellular life and

regeneration. Therefore, for older people, suppression of growth hormone

means acceleration of the ageing processes.

Growth hormone is also important for the maturation of the immune

system. Our immunity is regulated by T-cells. Differentiation and maturation of

T-cells takes place in and is propagated by the thymus, a tiny gland situated near

the thyroid, and the letter T in T-cells comes from thymus. Stimulation of the

thymus by growth hormone is one of the components of the maturation process

of all T-lymphocytes. Synthetic steroids have a doubly serious adverse effect:

first, they directly suppress all lymphoid tissues and cells and thus, the thymus;

second, they suppress the growth hormone that stimulates thymus functioning.

The thymus ceases its functioning with the completion of the body’s develop-

ment. Therefore, if the steroid consumer is a child, the retardation of his T-cell

maturation by the drug, will leave the immune system underdeveloped.

Every chemical in the body has a special affinity with certain cells. For

instance, T-cells, T-suppressors in particular, are especially responsive to hista-

mine. The effect is stimulatory in nature, beneficial for us. Thus, upon hista-

mine stimulation, T-suppressors grow in number, and their activity grows

along with the strengthening of H2 receptors. T-cells are also very responsive

to steroids but in a different way. Like no other cell, T-cells respond to the

suppressive action of steroid medications. The suppression is both quantitative

and qualitative, covering all T-cells and preventing their specialization.

Steroids produce the effect of a tank moving against an army of tiny

soldiers: the tank squashes all central immunity fighters. Among them, there

are natural killer cells that fight cancer, B-lymphocytes that produce protec-

tive antibodies, T-cells that fight infections, T-suppressors that oppose aller-

gies, etc. The latter is especially important for an allergy/asthma patient, since

it results in a more severe course of the disease, now caused by the drug itself.

All this contributes to the development of all sorts of immune diseases. A

steroid user may start with just one problem, namely allergies, but end up

with many more.

The most far-reaching complication of steroid drugs is that they are capable

of mutating genes. Steroid medications bind to the intracellular steroid receptor,

which translocates to the nucleus and binds to DNA. This changes gene func-

tioning, or as science calls it, gene expression. Distorted genetic instructions to

the cells inhibit the production of regulatory cytokines, the balance of which

determines the state of health or disease. The most aggravating factor is that



there is only one receptor that mediates the action of the steroid drugs. This

makes it impossible to achieve only the desired positive effects and avoid the

undesired negative effects of steroids, and the easy access of the corticosteroid

receptor to the genetic material makes synthetic steroids especially

dangerous.16 Compare this with the flexibility of histamine: different recep-

tors implement stimulatory and inhibitory effects, which enables physicians

to achieve the desired effect by targeting the ones needed. There is a huge

difference between playing a one-key musical instrument and an instrument

with several keys.

Genes are interdependent in their work. Mutation of one gene may affect

numerous characteristics and lead to complex abnormalities in the immune

functioning. Therefore, any organ and even system of organs may suffer as a

result of gene mutation. Genetic mistakes have a tendency to repeat in future

generations, and the offspring of steroid consumers may inherit undermined

health.

Bernard Shaw once remarked, “Science is always wrong: it never solves a

problem without creating ten more.” His remark is fully applicable to the use

of steroids in allergies.

THE QUESTION OF THE DOSEAsk the doctor who prescribes you steroids about their side effects, and almost

as a reflex, the answer will come that these are dose-related, that only oral

steroids may be harmful, and that the drug taken in sprays or ointments is

practically harmless. However, numerous medical investigations indicate the

opposite. The statements that a sustained use of steroid creams or sprays are

safe and only of local effect mean that those who prescribe them either do not

know how the drug works or are hiding the truth. There are drugs introduced

through patches or given in sprays, and even their manufacturers emphasize

their systemic effect. For example, Nicoderm (nicotine patch) is applied to the

skin surface only, but the drug administration is effective enough to mimic the

nicotine effect in cigarettes. So do patches that replace oral hormones. Another

example is smoking, which is a process of inhaling but may still result in cancer

anywhere in the body.

The complications associated with drugs are not eliminated when the

delivery routes change. Of course, the dose matters a lot, and that is why pills

are more harmful than sprays or creams. Still, even small doses can be detri-

mental if they are used daily. The results may not be evident for a while, but

Medications 193


as a constant flow of water wears away a stone, chronic use of steroids wears

away the immunity.

Here is one of the most recent confirmations coming from an annual

meeting of the AAAAI.17 The authors write about steroid-containing nasal

spray: “…data using more sensitive parameters suggest that low doses of

inhaled fluticasone propionate (flonase) are associated with a significant

degree of detectable systemic bio-activity, including HPA axis suppression.”

The article gives many references and concludes that doctors should use

“caution in terms of assessing the effects of therapeutic low doses of flonase on

HPA axis.”

To say that there is no side effect at a lower dose also suggests that patients

respond equally to that same dose, while certain groups, such as children,

pregnant women, older people, patients on concurrent drugs, or those who

have an innate exaggerated sensitivity to medications, can hardly be cate-

gorised as an “average” group. It is peculiar that with steroids having been

around for half a century,“well-controlled studies relating the safety of inhaled

corticosteroids in pregnant women are not available,” there are “limited clin-

ical data” on the use of inhalers in children, and “it is not clearly established

whether inhaled corticosteroids are excreted in breast milk,” etc. The quota-

tions are from the Canadian Compendium of Pharmaceuticals 2000.

But one does not even need trials on these groups. A thorough retrospective

analysis of those kids, pregnant and lactating women who were forced, due

to their asthma, arthritis or ulcerative colitis, to take steroids would be

enough to draw appropriate conclusions. Most probably, this has been done,

and not just once. Most probably, the results turned out to be unpleasant for

the producers, and, most probably, a gag clause in the contract prevents the

researchers from disclosing the results.

All this indicates that the dose shown to be safe during the drug testing on

“healthy young males” cannot be automatically applied as such to other cate-

gories. The history of Seldane is a classic example of how an extensively tested

and supposedly safe medication turned out to be fatal in certain patients

years later. The same is true for decongestants that have been on the market

for well over a century, and only today, we learn that a recommended dose,

meant to unplug a stuffy nose, may lead to a stroke in a migraine sufferer.

This means that these medications were known to have side effects before, but

only when these reached numbers too high to conceal, the truth came out.

There is no such thing as a safe dose, especially if this dose is repeated daily.



STEROIDS AND ALLERGIC DISEASES“Nearly all men die of their remedies and not of their illnesses,” Moliere once

said. One may wonder if his genius was predicting corticosteroids propagated

more and more indiscriminately by Western medicine.

Pharmaceutical compendia in each country list all the drugs produced

there. All of them describe the numerous side effects of steroids, but the

compendia rarely reach a lay person, and this knowledge remains the prop-

erty of pharmacists and physicians. The entries on all steroid drugs—oral,

injectable, inhaled or used on the skin—are strikingly unanimous in their

recommendations to reduce the dose immediately in case of adverse reactions

and to discontinue the drug in case of severe side effects. Regrettably, the

descriptions do not indicate what to take instead. Is it because in the majority

of cases, there is no other option? Still, while different complications are thor-

oughly described by the manufacturers, who otherwise could face legal prob-

lems, one side effect cannot be found in any source—textbooks or pharmaceutical

compendia, the fact that steroids have a direct negative effect on allergies and

asthma. Taken daily as ANTI-inflammatory medications, they are, in the long

run, inflammation pro-inflammatory.

Not only do steroids suppress the activity and reduce the number of all

kinds of T-lymphocytes, but they also inhibit other immune cells. As it follows

from the lecture given a decade ago (!) at a postgraduate course by an allergist

from the Harvard Medical School, steroids directly facilitate the release of the

greatest evil in allergy: inflammation promoting cytokine (Il-4). Furthermore,

steroids increase the production of the pathological antibodies IgE, both of

which are recognized by conventional allergy as indicators of allergic condi-

tion.18 Now, we face a paradox. The nature of allergic diseases is the

inability of the immunocompetent cells, T-cells in particular, to produce

enough disease inhibiting chemistry. Steroids, the most potent and common

drugs in allergies and asthma, actually support and advance this defect by:

a) suppressing the cellular lab on the whole;

b) reducing the number of the main allergy-fighting cells, the T-suppressors;

c) augmenting the output of the disease-promoting chemistry (Il4 and IgE).

Prescribed to relieve allergies and asthma, steroids eventually make the

body absolutely defenceless against these diseases. On top of that, the weak-

ening of the immunity on the whole paves the way for other chronic and

acute medical conditions to set in. Doctors actually paralyse the immune

Medications 195


system by recommending the daily use of the drugs which, as they claim, are

supposed to bring allergies under control.

The alleged “safety” of steroids is evident from the earlier-cited interview

with Dr. Teik Chye Ooi published in The Parkhurst Exchange, April 1994:

“Patients should wear a Medic Alert bracelet to show that they are on steroid

therapy, and they should carry a prepackaged syringe with 4 mg of dexam-

ethasone phosphate (also a steroid) for emergency use.”

Look around: more and more people suffer from severe allergies and

asthma. Ask them what medications they have been taking and for how long.

The majority are on steroids. At times, this becomes evident from the names

of their medications that contain cort, which stands for corticosteroids—pulmi-

cort, nasocort, rhinocort, etc. Still, many steroid preparations are unrecogniz-

able because they have been given decorous names. Consumers seldom read

the inserts in the drug packaging, they are often convinced that their medica-

tions have nothing to do with the dangerous hormonal preparations they may

have heard about. Should we be surprised by the growing severity of allergies

and the rising curve of asthma mortality if we, doctors, help create this situa-

tion day by day?

An alert should sound in every medical office and at every doctors’

conference. Allergy patients should also be informed of this drug’s danger, no

matter in what form it is taken, and behind what name it is hidden. Do not

expect that to happen soon, though. The reason is simple: there is no drug in

conventional allergy can use to replace steroids. We started with Moliere and

will finish with D. Jerrold, the English humorist who said: “In this world,

truth can wait, she’s used to it.”

THE TREE OF ALLERGYTo treat patients properly, a doctor should understand what underlies the

symptoms. For example, a doctor cannot treat a chronic pain in the back

without knowing what caused it: a twisted muscle, a nerve pinched by degen-

erated discs, or a tumor growth. A painkiller will be helpful only as a tempo-

rary measure, and the treatments will range from physiotherapy to complex

surgery. In a similar way, if a doctor sees a wheezing patient and treats only

his wheeze, or prescribes a decongestant to a patient who complains of a

stuffy nose, he treats the secondary events. Steroids contained in many allergy

prescriptions permit the doctor to assure you that, unlike symptomatic drugs,

these are directed at the primary cause—allergic inflammation. If this is the



case, and inflammation is indeed at the core of the problem, why do steroids

never cure? Why are they needed again and again? Moreover, why does the

course of allergies/asthma often get worse, and the dose of steroids rises

accordingly? Because inflammation itself is not the origin of the problem.

To sort out what is primary, and what is secondary in allergy, let us

imagine an allergic disease as a tree. Its branches are the symptoms, its trunk

is an allergic inflammation that gives rise to “the branches.” The roots that

feed the trunk are the malfunctioning cells that produce predominantly

inflammation-promoting chemistry. If the roots are rotten, no matter how

thoroughly the gardener trims the branches or props up the trunk, the tree

sickens and dies. Therefore, to keep the tree growing, he must be sure that the

roots are healthy.

Basic sciences provided us with the knowledge how to access the faulty

genes, the seed from which this tree started: through the receptors of the cells

that deliver messages to the genetic material. The main carrier of the protec-

tive immune messages, H2 receptor, if active, delivers the histamine/cAMP

messages to the genes and corrects (yes, corrects!) their functioning. This

process of accessing is called immunotherapy or immunomodulation. It can

also be called geneomodulation. A term I have not come across, but suitable in

this situation. This approach would be the best therapeutic modality for

allergy sufferers. But the “gardeners” neglect the roots and start with the

branches. They try to rid allergy patients of their cough, itch and sneeze by

identifying and eliminating the allergens which, in their opinion, provoke the

symptoms. As a rule, elimination fails, and doctors turn to antihistamines,

decongestants and bronchodilators that relieve those symptoms for a period

of time dependent on the drug’ clearance time and with a different degree of

efficacy. In too many cases, such tending does not work at all or works

insufficiently, and the failure shifts the attention from the “branches”

to the “trunk”—allergic inflammation.

The notorious side effects of steroid drugs prompt some authors to

caution in prescribing them for allergic disease. But some suggest even more

potent immunosuppressive medications, which, although they ruin the

immune system, can, at least, be discontinued at once since they do not

produce physiological dependence. Indirectly, allergists admit that the

essence of the problem is malfunctioning immunocompetent cells: “allergic

rhinitis and asthma need to be understood as inflammatory diseases arising

from mediator release cytokine secretion.” This statement comes from L.

Medications 197


Lichtenstein’s university department.19 Despite this knowledge, the causative

immunogenetic defects are disregarded, and the most powerful treatment

weapons are aimed at the secondary event, inflammation, with such force that

they reach the roots and burn them out. Steroids destroy the immune cells

and by that, stop the synthesis of all natural protective chemistry.

I respect the honesty of Dr. S. Wasserman, past president of AAAAI, as the

only frank participant at the round-table discussion of January 28, 1995.20 He

disagreed with his powerful colleagues and sadly admitted that “immunology

is… considered clinically irrelevant,” and “we probably have far more aller-

gists and immunologists than we need to take care of the severe end of the

spectrum.” It means that we hardly need so many specialists to treat the end

organ damage, instead of heeling the immunological roots of allergies.

IMMUNOTHERAPY VERSUS IMMUNOSUPPRESSIONThe word therapy comes from the Greek therapeia—service done to the sick.

In allergy, the sick immune system needs service. The purpose of immuno-

therapy is to do this service. If properly conducted, immunotherapy can be

highly successful. The interrelation of the immune, nervous and endocrine

systems makes it inevitable that the whole body gains from this healing of the

immunity. The other approach, blocking and suppressing, is doomed for two

main reasons:

a) In the same way, a tear or rip grows in size if not mended, the disregarded

immune defect has a tendency to advance and to affect more and more

mechanisms.

b) All suppressive methods result in the adjustment of the body to the

consumed medications, their foreign chemistry, their doses and their

adversities. This adjustment, coupled with the ongoing disease, necessi-

tates still more drastic measures and causes more and more damage to

the cells. The stronger the suppression, the deeper the damage to the

participating cells and, unfortunately, to the non-targeted cells.

How do allergists view immunotherapy? On paper, they may say that it “lies

at the heart of our specialty.”21 In real life, the general opinion of specialists is

that immunotherapy should be tried only when other medications fail. Many

suggest it be used only as an adjunct to anti-inflammatory treatments. It is

hard to believe that allergists suggest first to immobilize the immune cells by

the antiinflammatory drugs, which in their vague vocabulary means



immunosuppressive steroids, and only then to start reactivating these very

cells with immunotherapy. It is still harder to accept the idea of the simulta-

neous use of these two diametrically opposed treatment approaches. Here we

have yet another immunologic oxymoron.

A PIECE OF THE ACTIONAllergies, asthma and related diseases are the largest group of chronic

diseases. Just this factor alone provides a permanent patient supply. I do not

think that the past president of AAAI, Dr. M. Kaliner had reasons to worry

when he said: “We are a small subspecialty, overlapped by large and

powerful groups of physicians who would gladly absorb our patients”22

Inefficient therapies will surely keep the patient within the field of allergy.

An allergy patient is perceived by many as a real dainty pie shared by other

doctors as well. Different specialists get a tiny piece of an allergy patient

here and there. Asthma patients, unable to receive help from allergists, visit

respirologists; those with itchy skin wander off to dermatologists; congested

noses often end up in the offices of ear-nose-and throat surgeons. The

failure of allergists to relate the accompanying nonspecific symptoms with

their field, forces their patients to roam from office to office of every imag-

inable doctor—neurologists, psychiatrists, gastroenterologists, etc.

Allergists are twice “blessed” in that their patients are generated by the

general practitioners who dispatch their patients with signs of asthma and

allergies to them. After a tour for allergy skin testing, the patients come back

to their family doctor if not for physical help, at least, to share their frustra-

tion. This frustration is justified, since the diagnosed conditions often fail to

respond to the prescribed medications, and in addition, there are undiag-

nosed symptoms, which, are, in fact, allergy-related. The lack of diagnosis

comes from the poor understanding of the underlying mechanisms of allergy

and their inseparability from the neurological mechanisms.

Allergists do not limit themselves: the awesome and expensive procedure

of skin testing has become almost a must even though it does not influence

the pre-determined steroid-oriented therapy. Immunotherapy should have

become a logical continuation of skin testing. Instead, it is conducted prima-

rily in cases of allergic rhinitis, and even textbooks recognize its inefficiency:

“immunotherapy fell in disrepute with the scientific community at large.”23

The dismal statistics on allergies and asthma necessitate a continuous search

for more potent drugs (mostly versions of the already existing ones), and

Medications 199


allergists are undoubtedly the first to get paid by the pharmaceutical industry

for their research, development and testing.

In support of the allegedly wide spectrum of allergology, Dr. M. Kaliner,

Chief Allergist in the National Health Institute, said at a round-table discus-

sion24 that “allergists provide certain aspects of care that may not be given by

other physicians, including an emphasis on the environmental control of aller-

gens and other triggers.” Indeed, during patients’ visits to their offices, aller-

gists may conduct individual educational classes on the makes of appliances,

breeds of non-allergenic pets, delivery devices of medications and techniques

of inhalers’ use. Of course, their time has a high price tag, although these

aspects are hardly in the department of immunology. But if leading specialists

say so…

Medicine and the areas servicing it should be grateful to allergists for job

creation. Due to the success of allergists in breaking up the medical problem

into a myriad of irrelevant issues, they keep themselves in the business, and

also let many other medical professionals do so as well.

A NARROW FIELDSomebody once said that if you have one instrument only, and this instrument

is a hammer, everything around will look like a nail. Allergy has one instru-

ment, steroids, and they are as powerful as a hammer hitting all body cells at

once. It may look as though histamine, I suggest using for all allergies and

related diseases, is also a hammer in my hands, but this is wrong. I suggest

medicine should accept the stimulatory approach. This would facilitate

creation of various agents able to activate its immunomodulatory receptors.

The advantage of histamine is that it and its congeners are already available

and have undergone clinical and double-blind studies. All of them could be used

right away for the sake of those who cannot find relief with conventional

medications. Immunomodulation with histamine would be the natural way of

restoring the functioning of the immune system. But allergology ignores and

prohibits this approach.

A quoted high profile allergist declared at the above-referred roundtable

discussion that allergists “are a small specialty with a narrow focus”25 Is this

so? Is immunology a narrow field isolated from other medical areas? I person-

ally disagree. The narrower the specialization of a doctor, the broader his general

knowledge of the body’s processes should be. For example, before performing

complex operations, top heart surgeons do not just wield their scalpels, but



consider the multiple influences of other co-existing medical problems, as

well as the ones that may develop afterwards. Immunotherapy, as the only

logical and promising management, requires an understanding of the immune

processes in disease and health.

Instead, the vital information on the causative immune mechanisms of

allergies and asthma is silenced, distorted and substituted with insignificant

and irrelevant minutia, and the knowledge provided by contemporary text-

books is narrowed to fit an artificially designed framework. It is strange that

having created this situation the leading allergists complain at their discus-

sions that “…immunology is so poorly understood, practitioners simply do

not see how it impacts on practice patterns.” At the same time, they defend

this illiteracy by saying that “people are not referred for mechanisms; they are

referred because they have wheezing bronchial tubes, or stuffy noses.”

Therefore doctors “do not see their problems as T-cell problems—they see

wheezing patients who need to be kept out of the hospital.”26 Such views

justify and support the use of medications that, at best, relieve symptoms

temporarily. Healthy immunity does not seem to have a place in clinical

allergy, therefore immunotherapy is not applicable. No wonder that allergy

patient always remains on drugs and nothing but drugs.

Medications 201


ENDNOTES 1. Lan Yan et al. Histamine N-methyltransferase pharmacogenetic. Pharmacogenetics 2000;10:261-62. M. Reilly, E. Sigg Suppression of histamine-induced adrenocorticotropic hormone release by

antihistamines and antidepressants”, J Pharmacol Exp Ther 1992;222(3):583-5883. This is not a typographical error: Tamoxifen increases the risk of cancer especially in the liver,

while slightly reducing cancer risk in the breast. See oncologist S. Epstein, M D, The BreastCancer Prevention Program, 1999

4. For the adverse effects, including the 7-fold increase in cancer risk associated with antidepres-sants see Harvard University’s J. Glenmullen, Prozac Backlash, 2001, and D. Healey, Let The EatProzac, Lorimer, 2003

5. Brandes L.J. et al: Results of a clinical trial in humans with refractory cancer of the intracellularhistamine antagonist in combination with various single antineoplastic agents, J.Clin Oncol1994; 12:1281-90

6. Note: according to the regulations governing safety standards in Canada and the USA (notalways followed, of course), the reason studies are conducted on mice, is because they largelyshare the same enzyme system with humans; extrapolating from mice to people regarding toxi-city and carcinogicity has proven to be totally reliable.

7. FDA reviews antihistamine mouse study. FDA Talk Paper 1994; May 17:28. C.Brutin et al To the editor, The New England Journal of Medicine, 1983;308:591-2, S. Borgstrom

et al To the Editor, The New England Journal of Medicine, 1983; 308:5929. Immunopharmacology 1982:52

10. M.Ichinase, P. Barnes. Histamine H3 receptors modulate antigen-induced bronchioconstrictionin guinea pigs. JACI 1990; 86:491-5

11. G. Sussman., J. Dolovich. Seminars in Dermatology 1989;8:15812. According to the Journal of the American Medical Association, 87% of doctors who get clinical

practice financially tied to the pharmaceutical industry. JAMA 2002;287;612-713. Parkhurst Exchange, April, 1994:76-914. Dermatology Times of Canada, Sept. 1996, p. 115. R. Sapolksy, et al Pulsender Wa Science, 1985;229(4720):1397-1400 16. P. Halloran. Four decades of glucocorticosteroid immunusuppression. Can Med Assoc J

1992;147(5):613-417. B.Lipworth, C. Jacson Effects of oral and inhaled corticosteroids on the hypothalamic-pituitary-

adrenal axis, JACI 1999;104:1318. R. Geha. Regulation of IgE synthesis in humans. JACI 1992;90:143-519. P. Creticos. Immunology and Allergy Clinics of North America, 1992; 12:2620. JACI 1995; 97:87021. Frew et al. Sublingual immunotherapy. JACI 2001;107:44122. M. Kaliner. Presidential address. JACI 1997:99:729-3423. Kaplan ed. Allergy 1985, p.67924. JACI, 1995;9725. Visions in Allergy: Impact on Health Care Reform. JACI 1995;97:86426. Justifying a mechanism-based specialty. N. F. Adkinson et al. JACI 1995;97:868-71



PART SIX

ALLERGY SKIN TESTING AND IMMUNOTHERAPY

THE GOAL OF THIS CHAPTERThis chapter is written as continuation of Medications, since immunotherapy is

logically and scientifically the best means of management of such reversible

diseases as allergies and asthma are. Application of therapy to the ailing

immune system and restoration of its ability to fight the disease rids the

patients of the above-discussed medications or, at least, drastically diminishes

the need for them. Analysis is required as to why conventional immunotherapy

tends to fail and is mostly avoided. Since criticism is helpful only when it is

accompanied by recommendations on how to improve the situation, we will do

both—provide an overview of today’s immunotherapy and show what should

be done to turn it into the most effective therapy for all kinds of allergic

diseases.

With steroids being mainstream therapy, doctors believe that they can

only “reduce the intensity of the inflammatory response” and never cure the

disease. Therefore in 2001 “more than 5,000 people die of asthma (in the

U.S.) every year, and death rates….have increased or remained stable over the

past decade.”1 Asthma now is “one of the commonest, if not the commonest,

chronic disabling diseases of children and young adults in the western world,”

stated the textbook Allergy already back in 1985 (p. 367).3


The situation with asthma, the most serious allergic disease, is a reflection

of the situation in allergy medicine as a medical field. The only treatment that

could repair the ailing immune system is immunotherapy, but, as the same

textbook wrote back then, “with little evidence of efficacy for the technique as

commonly practised, immunotherapy fell into disrepute in the scientific

community at large” (p. 679).3 Allergists blame the quality of the allergen

extracts for this failure and produce guidelines to improve their standardisa-

tion and storage conditions. They also modify the production of the extracts

to prevent aggravations and even deaths from them. Still, within the past two

decades, nothing has changed the low efficacy and potential danger of “allergy

shots,” as laymen call immunotherapy. It is required to last from 2 to 5 years

and the first results (if any) manifest not earlier than 6 months after the start.

It is not uncommon that immunotherapy is discontinued because of the

various adverse reactions, both local and generalized, while the disease is still

not controlled.

For safety reasons, this treatment, meant to repair the ailing immunity,

may be prescribed along with immunosuppressive steroids. It is mostly

limited to allergic rhinitis and hay fever and is never recommended for skin

allergies. All guidelines caution against using it in asthma even though it is

asthmatics that need it most in view of the gravity of their disease.

Immunotherapy is not even considered as a possibility for the related neuro-

logical and non-specific symptoms because their common roots with aller-

gies are unknown to clinicians. All this has assigned a Cinderella role to

immunotherapy among allergy/asthma therapies.

So hopeless for patients and compromising for doctors is immunotherapy

that an ex-president of AAAI, M. Kaliner acknowledged at a prestigious gath-

ering of American allergists: “…immunotherapy is easy and lucrative. If we

didn’t have it, we would have a better specialty. Having said that, I think we

are going to go where immunotherapy is going to be restricted.”2 Something

must be terribly wrong with this most logical and scientifically founded

procedure if a top allergist thinks of restricting this already unpopular

therapy. Actually, for patients, this means being condemned to medicalization

for life. Dr. Kaliner is right in one respect though: any therapy based on its

profitability for doctors instead of its benefit for patients ought to be

restricted or even banned.

Before suggesting changes, we should thoroughly scrutinise immuno-

therapy in its present performance. The scrutiny should start with allergy skin



testing, AST, the diagnostic procedure that always precedes immunotherapy

and provides the basis for the doctors’ judgement regarding the subsequent

management. If we can prove that the procedure that forms the foundation

of today’s immunotherapy is deficient, we will prove that the subsequent

treatment failure is inevitable, just as would be the collapse of a structure

erected on shaky grounds. The opposite is also true: the properly done proce-

dure becomes the prelude to successful immunotherapy.

THE MISGUIDED PURPOSE OF SKIN TESTING“What am I allergic to?” is the question insistently asked by all allergy patients

who seek skin testing as the answer to their symptoms. They believe that by

identifying the trigger and eliminating or avoiding it, they will find relief.

Doctors support them in this belief. They conduct skin testing to pinpoint the

offenders and offer advice on their avoidance or removal from the environ-

ment in which the patients live, work, rest. Every allergy patient knows how

successful (or rather, unsuccessful) implementation of these measures is in

every day life, and this is the best proof that today’s allergy skin testing has

a misguided purpose.

Ideally, any diagnostic procedure should be performed not only to diag-

nose the condition but to find the best possible treatment. Unlike other

medical tests, AST seldom satisfies these mandated criteria in medicine.

Doctors are taught that skin testing should be nothing other than a trigger

indicator. Therefore, AST is considered to have fulfilled its task with the

avoidance advice. The treatment for the majority of allergy sufferers

continues to rely on the same pills, puffers and sprays they used before. Even

in the smaller portion of patients who are prescribed immunotherapy, it

never aims at ridding them of their hypersensitivity, but at lessening the

response to one or several allergens allegedly revealed by the testing.

Skin testing, as a diagnostic means, fails in finding a therapy that will

make the ailing immune system unresponsive or less responsive in general.

THE TECHNICAL PART OF SKIN TESTING Let us see what AST consists of. The most common skin testing is epidermal.

The word comes from the Greek derma—skin and epi—over. Thus, epidermis

is the upper skin layer. The dry scales we see when our skin peels are, actually,

epidermis. Epidermal skin testing in allergy starts with a mandatory hista-

mine test called positive control—a drop of histamine and a prick through

Allergy Skin Testing and Immunotherapy 205


the epidermis at that spot. Usually, an itchy wheal forms at the prick site often

surrounded by redness or a flare, as it is called. A few minutes later, drops of

allergen extracts (pollen, mould, house dust mite, animal dander, etc.) are put

on the skin followed by a series of pricks at each spot. The size of the wheal

and flare formed by each allergen is compared to that formed by the hista-

mine prick, which is thus used as sort of the yard stick in the evaluation of the

local reaction. As a rule, allergists also use a negative control, which is a drop

of saline, to see if the patient’s sensitivity is so exaggerated that his skin reacts

even to a neutral substance. The use of saline is not mandatory according to

the FDA recommendations. Each allergen extract, to which no skin reaction

occurs, becomes a negative control due to its “neutrality” in the host’s body.

A localized reaction developing upon a prick is a typical appearance of what

allergy calls allergic inflammation. Doctors explain it this way: “Do you see the

hives where I put mould (mites, pollens, etc.) extracts? It means you are allergic

to them.” In the majority of cases, at this stage, the patient is given a prescrip-

tion for a conventional drug and told to avoid the “offenders.” In rare cases,

when immunotherapy becomes the treatment of choice, the mixture prescribed

for injections almost invariably contains those allergens that showed the most

marked skin reactions. The doctor says: “I will prescribe you the mixture of

these allergens. By getting them in gradually increasing doses, you will be

desensitized to the triggers and hopefully will get rid of your allergies.” The

explanation sounds logical. The patients are impressed by the solemn proce-

dure and by the knowledge of the specialist who can do it and become opti-

mistic of a successful outcome. Through this lengthy course of immunotherapy,

the patients usually continue to use their previous medications.

On the surface, the explanation given by specialists is faultless, but then,

why do top specialists state that they “would have a better specialty” without

immunotherapy?

THE CONCEPT OF ALLERGEN-TRIGGERED ALLERGIESSkin testing is based on the IgE concept proclaimed as central in allergies. It

teaches that patients’ exposure to triggers results in the formation of the

corresponding IgE antibodies that reside on mast cells. At the testing, if an

allergen is introduced through a prick, the already existing antibodies bind to

it to form complexes, and the new chemistry leads to a local histamine spill

from the mast cells. The wheal and flare on the site of the prick are said to be

the signs of this spill, and the indicators of the “culprit(s).” But, how solid is

the IgE-based hypothesis? Skin testing exposes the flaws in this concept.




■ First, the name of the outer skin layer where testing is performed is

epidermis, and the epidermis does not contain mast cells! No mast cells—no complexes—no reaction!

■ Second, there is almost always a skin reaction to the initial prick with

histamine which is not an allergen. So, what is this reaction in the absence

of antibodies?

■ Third, textbooks teach that in response to various stimuli, IgE-mediated

“histamine release with human mast cells requires 15–40 minutes.” In other

words, skin reaction upon a prick with an allergen can not be observed

right away. Then, why do doctors often see it within minutes?

Conventional allergy does not provide answers to these questions. The defi-

ciencies of AST do not end here. According to statistics, only 20% of urticaria

(hives) and less than 50% of asthma are allergen-related, and therefore skin

testing is not applicable for the remaining majority. Such non-IgE-mediated

factors as, for instance, temperature or weather changes, touch to skin, stress,

sun light or exercise cannot be verified in skin testing. Neither can be the vast

group of pollutants, for example perfumes, as they do not exist in the form of

standard allergen extracts.

An additional complicating factor is that allergy patients overwhelmingly

have symptoms in response to mixed triggers, i.e. specific and non-specific. In

such patients, even if the offensive allergen is detected and eliminated, non-

specific factors remain still unidentifiable by pricks, and pinpointing specific

triggers will not significantly change these patients’ management. Only those

few “lucky” patients whose symptoms are solely allergen-produced may hope

that skin testing will reveal their triggers. Ironically, it is in these cases that

skin testing may often prove to be redundant. For example, if your symptoms

always come in the same season when the radio stations remind us every hour

of the rising ragweed count, and ingratiating TV ads incessantly promote

medications for the pollen-triggered allergies, do you still doubt you have hay

fever due to exposure to ragweed? Nevertheless, patients with obvious triggers

are skin-tested.

All these flaws make the procedure of AST useless even in reaching its

narrow goal—detect the offensive allergens. Paradoxically, allergy patients

leave specialists’ offices with the assurance that they can depend on the conclu-

sions regarding the causative allergens. They are promised either to be desen-

sitized against those or to get instructions on how to control the offenders.

Doctors are also satisfied with the impression they produce by this procedure.


Besides, the subsequent allergy shots are lucrative, as we are informed by an

ex-president of AAAI, Dr. M. Kaliner. An all round win-win situation!

Although only a smaller part of allergy cases is allergen-related, search

for a trigger, and hence, AST, is proclaimed to be the main avenue in the

management of allergy patients.

FALSE POSITIVE AND FALSE NEGATIVE SKIN REACTIONSA diagnostic procedure must be reliable. In AST, skin reactions, its main indi-

cator, is deceptive. A textbook states, “A positive skin test reaction can be

produced in any person allergic or non-allergic, if the test materials are suffi-

ciently concentrated.”3 A more recent publication states: “IgE and positive

AST indicate allergen sensitization, but are not necessarily indicators of

allergic diseases.”4

Even medical sources for lay people admit the unreliability of skin testing.

For instance, The Canadian Allergy & Asthma Handbook 1996 admits on page

29 that “if given skin tests, up to half the population would have a localized

reaction to at least one common allergen, but the number of people with

allergy problems is much less.” This means that an extract of, say cat dander,

which is a strong chemical, may form a large wheal and a flare, while testing

does not find the corresponding IgE antibodies in the patient’s blood and

tissues. The patient may have had a cat for years, without developing any

symptoms. However, solely on the basis of the skin signs, doctors invariably

recommend that the owner should part with his pet. How many a heart has

been broken due to this needless separation? One can only wonder what

prevents physicians from informing their patients about the imprecision of

local reactions. The wheal and flare to an allergen extract not supported by

corresponding symptoms are called false positive. They may confuse, rather

than identify the trigger, if the doctor relies on them more than on the

medical history. Too often allergists do exactly this.

False negative reactions, although less common, may also occur. This

means that an antigen that triggers allergy symptoms produces no skin reac-

tion. The existence of false positive and false negative reactions creates addi-

tional doubts for the need to do testing with the sole purpose of detecting

offensive allergens. All this renders the judgment regarding the contents of the

therapeutic mixture for the following allergy shots even more questionable.



SKIN REACTION IN THE ABSENCE OF MAST CELLS?One of the questions that allergy leaves unanswered is: if the epidermis does

not contain mast cells, what are the skin signs produced as a result of AST?

During the course of an allergic disease, all the participating cells of the

host’s immune system become “competent,” that is, acquire the ability to

release various cytokines and mediators. Although there are no mast cells in

the epidermis, it contains T-cells able to respond to any trigger directly, “inde-

pendent of IgE.”5

The skin also has Langerhans cells, LCs. So fascinating is their multifunc-

tional and especially in immunomodulatory activity that they have become

the subject of books, international conferences and workshops. LCs carry the

explanation of the processes that underlie skin reactions at the testing. Similar

to mast cells and basophils, LCs have been shown to possess the receptor that

binds to IgE antibodies, which means that, similar to mast cells, they may

become the platform for an antigen/IgE antibody reaction. LCs are also the

central antigen-presenting cells in the skin. They inform T-cells about an

antigen on the skin. For that, they produce a protein in response to the

antigen, and this protein binds to the stranger before presenting the latter to

T-cells. Unlike stationary mast cells, LCs possess a unique migratory ability

and chemical attraction to T-cells, and they transport the captured antigens

to the regional lymph nodes for presentation. The new chemistry activates the

T-cells, and they, in turn, engage other cells.

LCs are a the depository of numerous pro- and anti-inflammatory

cytokines and mediators, histamine among them; “…the homeostasis of LCs

seems to be tightly controlled by a delicate balance of mediators… Minor

perturbations of this homeostasis by chemical, physical, or biological

factors… may signal danger to shift this balance.”6 This means several things.

First, LCs respond with their mediator spill even if the trigger is not an

allergen, and a local reaction to the prick with histamine at skin testing is

proof of this fact. Second, LCs’ activity is more than local, and they directly

affect other cells’ functioning. When they respond to a stimulus, they chemi-

cally engage other cells. LCs’ relationship with nerve cells is yet another

impressive fact. As a part of the dendritic or branched cells, LCs stretch their

extensions to the dendrites of the nerve cells and thus spread their messages.

This explains the exchange of chemical information between nervous and

immune systems and coexistence of allergic and neurological symptoms. To

summarise the functions of Langerhans cells:



■ Like mast cells, LCs possess IgE antibodies.

■ LCs may respond to an antigen directly or by binding it with their own

chemistry and delivering to T-cells.

■ LCs may respond to an antigen immediately by changing their own chem-

istry and affecting the chemistry of other immune cells.

■ LCs may change their chemistry not only in response to antigens but to any

stimulus and thus bypass IgE antibody mechanism.

■ LCs have direct connections with nerve cells, and a change in their

chemistry may produce systemic effects in the nervous systems as well.

HOW IMPORTANT IS THE KNOWLEDGE OF LCs?You may be puzzled by now: does it really matter on what cells the

antigen/IgE complex “dances”? What is the reason to hide the data that some

other cells do what mast cells do? Why don’t allergists know this? The answers

are complex.

The well researched knowledge of the navigating and recruiting abilities

of Langerhans cells is so overwhelmingly important that the pharmaceutical

industry has long been using it to develop therapies for allergic dermatitis.

The effect of topical (placed on the skin) medications is due to the response

of the Langerhans cells’ and their messages of the medications’ presence on

the skin. This allows the use of nicotine or hormonal patches, for instance.

Regrettably, what is essential in drug development loses its attraction in other

areas and may even become a stumbling block, and the most explosive find-

ings may be blocked from access. This is exactly what has happened with the

information that immunocompetent cells, Langerhans cells in particular, are

able to respond to any trigger on the skin, not just to allergens, and spread the

news by secreting mediators. The knowledge that skin manifestations at

testing may not be the antigen/IgE antibody reactions raises the question of

what they are. As it turns out, “Many authors believe that the allergic skin

reaction occurs chiefly because of the liberation of histamine.”7 Thus,

wheal and flare are just a local spill of allergy mediators, first of all histamine,

in response to a foreign protein (not necessarily allergenic) or any stimulus.

Skin reactions do not specifically identify the triggers but indicate one

thing: readiness of the hypersensitive immune cells in the skin to react chem-

ically, i.e. this is spontaneous hyperreleasability. The situation can be

compared to a scream in a dark house: “A robber!” The shout wakes up the

whole family and makes them rush around without knowing exactly who the



robber is. The vagueness of the “scream” (the wheal and flare) in identifying

the “culprit” (allergen), is confirmation of the diagnostic imprecision of the

today’s AST.

The true knowledge that the local reactions are mostly non-indicative is

at best presented in a piecemeal way in professional papers. It is doubtful that

practical physicians ever read them because the demands of daily practice

leave little time for keeping up with the literature, while the work of finding

the needed material, and especially interpreting it, is time-consuming. It is

also highly undesirable to reveal the fact that LCs’ activity is not limited to the

skin but echoes all over the body. Langerhans cells’ relatives, other dendritic

cells, exist not just in the skin but in the lungs, nasal mucosa and conjunctiva.

The chemical signals sent by LCs from the skin surface involve the whole

network of immune and nerve cells. The involvement requires, histamine

spill from mast cells and basophils followed by other chemical events. Thus,

a local process started and spread by LCs turns into a cause for the whole

body reaction. In other words, by touching the skin we “touch” other organs.

This leads to a most important revelation: by treating the skin, we treat the

whole body! However, what the drug industry can do, clinical medicine is

prohibited from doing. And the best minds are used to help skilfully hide the

fact that histamine can engage the whole body into recovery, and that LCs can

help do the main job.

You may think that I am splitting hairs, that this is a purely theoretical

exposition, which is irrelevant to practical allergy medicine and not needed

by allergy patients whose central concern is improvement. Wrong. This seem-

ingly theoretical issue has a very practical outcome for patients. At present,

the judgment regarding what you are allergic to, what components of the

surrounding environment you should avoid or eliminate, and what allergen

extracts must be used in your shots depends totally on what allergens form

skin hives. You may be forced to spend money on irrelevant and impractical

elimination measures, make an emotionally difficult decision to part with

your pet, or turn your otherwise happy life upside down by deciding to move

to a place where the offender does not exist.

My prediction is: in either case, you will remain a consumer of allergy

medications because mostly, the measures will not work. An incorrect judg-

ment also dooms any subsequent immunotherapy because the therapeutic

cocktail contains invariably irrelevant or therapeutically useless allergen

extract(s).



DO WE NEED SKIN TESTING?If AST is so confusing practically and unsubstantiated theoretically, do we

need it? Yes, but for a different purpose, performance and interpretation of

the events that take place in its course. Today, this test is an isolated event that

ends up with advice on the elimination of a trigger, which, as we found,

cannot even be detected reliably. AST must be a dependable diagnostic proce-

dure, the bridge that leads to a successful immunotherapy. Accordingly,

immunotherapy must also change its targets: instead of trying to desensitise

a patient to one or two triggers allegedly revealed by local skin reactions, it

should strive for reduction of general spontaneous hyperreactivity and

hyperreleasability of the ailing cells. No therapy can be successful if based on

the premises that it is “easy and lucrative.” “There are no immunology

patients in practice, so the rank and file make their living on allergy, and

asthma, and sinusitis.”8 Conventional immunotherapy has this dubious basis

and is, therefore, a failure. It needs to become science- and patient-oriented.

Changes must start with an understanding of the processes that underlie skin

testing, because a diagnostic procedure as unreliable in all aspects as the

conventional AST is cannot be the correct guide for action.

We are going to show what elements of allergy skin testing should become

the basis for the doctor’s judgment regarding the subsequent therapy, and

why the suggested approach logically leads to effective immunotherapy.

THE SKIN AND SYSTEMIC REACTIONS As we are speaking about skin testing, we should know the basics of what the

skin is. Not only it is an external case or cover for other organs, but it is also

a large, live, highly sensitive organ full of immunocompetent and nerve cells.

Therefore, the skin often becomes the victim of allergies and other immune

and neurological diseases. This negative aspect has positive side in that the

skin may become “a prime target for therapeutic interventions to suppress,

stimulate, or deviate cutaneous and systemic immune responses,” and it has

“wide clinical use in the specific treatment of … allergy.”6

It is well known that even superficial contact of the skin with an allergen,

for instance, with a cat’s fur, may provoke a reaction going beyond the skin—

cause nasal congestion or an asthmatic attack. In other words, skin reaction

may grow into a systemic response because the same cells that populate the skin

populate various organs. Their coordinated response to a trigger makes it clear

that at AST, allergens and histamine get into the epidermis or dermis with



pricks and engage the network of related cells into a reaction. The immune and

nerve cells work in unison and respond to a histamine spill in different parts of

the body because they possess histamine receptors, and it does not really matter

what cells start the reaction. The histamine-induced shift of the cellular chem-

istry is bound to bring about symptomatic bifocal changes—improvement or

worsening—basically depending on the prevalence of anti- or pro-inflammatory

cytokines. The more mediator-releasing cells a diseased organ contains, the

more potential it has to be involved in the reaction, and the more pronounced

the changes are in the corresponding symptoms.

All this explains why it is only natural to expect that allergy skin testing

may lead to systemic reactions. If the doctor who conducts skin testing does

not detect systemic changes, it is because he does not anticipate and therefore

does not observe them. In medical school, he was taught only how to assess

the wheal and flare occurring on the skin surface and to view them only as an

IgE antibody-mediated event pointing to a trigger. Doctors are never told that

they should expect a histamine spill regardless of IgE existence. They also

remain unaware of the involvement of other organs and systems through

chemical changes started by skin pricks. Strangely, they do know about

systemic reactions, up to anaphylactic shock, that may result from skin

testing. They also know about whole-body reactions to topical medications,

steroids in particular. Still, at AST, they limit their observations to the local

skin signs and never ask patients about their baseline symptoms right before

the testing and the symptomatic change afterwards. And this is the biggest

diagnostic flaw of the procedure.

Like a mirror, our skin reflects the chemical processes occurring in the

tissues and organs stricken by immune and related diseases.9 A localized skin

reaction at a prick site is the manifestation, first of all, of a local histamine spill.

However, it is followed by a systemic reaction—general effects elsewhere due

to the histamine-initiated changes all over the body.

Doctors cannot see the organs inside the body, but monitoring of the

symptoms before and after the pricks would help determine how the allergy-

involved organs respond to the body’s chemical changes. Just a few questions

asked directly before the pricks could elicit all the needed information: Is your

nose stuffy (runny)? Are your eyes watery (itchy)? Do you feel the urge to

cough? Are you short of breath? etc. As histamine is a major neurotransmitter,

the doctor should also ask about neurological or related symptoms such as a

headache, fatigue, bloating, muscular pains, etc. The same questions asked



10–15 minutes after the procedure may reveal changes and thus the relevance

of these symptoms to allergies. Among the relevant symptoms, there may be

those of migraine, depression, chronic fatigue syndrome, irritable bowel

syndrome, etc. Some of these diseases are poorly interpreted, therefore undi-

agnosed and mostly unattended.

Conventional interpretation of skin tests sees the tip of the iceberg only,

but presents it as the whole iceberg. Allergists measure the size of the wheal

without “measuring” the more essential part—the hidden immune mecha-

nisms which are inevitably engaged in the process when histamine or aller-

gens encounter the immune cells through skin pricks. The changing body

chemistry reflected in such systemic reactions is not in the picture.

If you have had allergy skin testing, try to remember whether the doctor who

did it asked you questions about possible symptomatic changes. I bet he did not,

although this is a must for a physician performing any diagnostic procedure.

Apart from lack of proper theoretical knowledge, there are two banal

reasons why no attention is given at AST to the accompanying systemic reac-

tions. First, clinical observation is not a subject taught well enough at medical

schools, hence, the inability of doctors to observe. Second, the “Time is

money” slogan has become the creed of our life, and doctors simply do not

want to invest time and effort to observe, analyze or make decisions. They

prefer to follow standard guidelines.

Lack of understanding what underlies local skin manifestations during

allergy skin testing prevents clinicians from noticing systemic immune reac-

tions and making the right judgment regarding the response of the numerous

body organs.

REACTIONS WITH AGGRIVATIONAs was said, allergists are aware of a possibility of severe systemic reactions.

The very title of the paper written by an ex-president of AAAI in the central

periodical on immunology reveals this knowledge; it was entitled “Fatalities

From Immunotherapy And Skin Testing.”10

The official medical and government sources also caution doctors about

such reactions.11 Further proof of awareness comes from clinical medicine:

allergists avoid skin testing in symptomatic patients with moderate to severe

asthma as well as in small children for fear of provoking an attack. This is

recognition of the test as an invasive procedure with the risk of severe adverse

reactions, including fatality. Severe systemic reactions may become the basis



for a liability suit. Still, if the reactions do occur, obeying the technical rules

of the procedure removes all liability from the doctor even in event of a

patient’s death.

It is of interest that theoretical sources have noticed that anaphylactic

reactions after skin pricks may occur “with minimal to no skin reactivity.”12

In other words, a severe systemic reaction may occur to a prick that reveals

few or no IgE antibodies. This, more than anything else, should tell allergists

that systemic reactions are more important than the notoriously imprecise

wheals and flares, since the chemical changes produced in the whole body are

more important than the superficial, often non-indicative skin signs.

An important point not taken into account by doctors, but suggested by

common sense, is that reactions with aggravations do not necessarily lead to

the death of a patient. The scope of worsening can be wide, ranging from a

minor worsening to anaphylaxis, depending on the individual sensitivity.

While the most sensitive patients respond with a severe reaction, in the rest,

it is easy to detect minor changes only by comparing the symptoms before

and after the pricks. Only a doctor who understands that the whole body

becomes involved in the reactions following skin pricks expects a change and

asks about the symptoms.

It is natural that if at the testing, the patient’s attention is not drawn to the

symptoms, he will not inform the doctor about symptomatic changes unless

there is a dramatic worsening. Since ups and downs are normal in any allergic

disease, the patient will accept a mild or moderate aggravation as such. As was

said, selection of the therapeutic mixture for allergy shots is made solely on the

basis of wheals and flares, and the cocktail of allergens may contain the aggra-

vating ones. Unlike homeopathy that employs the method of administering

tiny doses of offensive substances, conventional allergy starts with much

higher doses and drastically raises them. Thus, if a mild dizziness or a more

congested nose escapes the doctor’s attention, the situation may worsen during

the subsequent immunotherapy.

The lack of attention to the symptoms at allergy skin testing continues

during immunotherapy and accounts for the fact that the worsening may be

noticed only when it reaches a serious level. This is not so uncommon: a lot

of patients experience acute systemic reactions. Besides, there is a general

(unfounded) belief that it gets worse before it gets better, and the patients

may still go on with their injections assuming that side effects are an

inevitable part of the treatment. The expectations set during allergy skin



testing were so high! The situation is complicated by the fact that often,

weekly injections are given by nurses according to a standard schedule of dose

increment, and the doctors are unaware of the transitory aggravations until

they strike severely.

Unrecognized systemic reactions with aggravation during skin testing are

the reason why conventional immunotherapy may be dangerous.

REACTIONS WITH IMPROVEMENTIt is strange that pricks are not viewed as initial shots, which they actually are.

No matter what skin layer the extract penetrates, the histamine spill, which it

provokes, engages all the immunocompetent and related cells in the reaction.

Therefore skin testing should be considered as the initial session of potential

immunotherapy. Paradoxical is the fact that while the therapeutic cocktail

selected on the basis of the testing pricks is given in injections to improve the

symptoms, doctors do not expect an improvement during the testing with the

highly concentrated ingredients of this cocktail. This is just further confirma-

tion that allergy medicine views localized skin reactions as an event unrelated

to the rest of the body. The scope of improvement may vary from slight relief

to complete disappearance of the symptoms, and the degree depends on the

individual’s “chemical” sensitivity.

Medical sources do at least caution doctors about the possibility of an

aggravation at skin testing, but there has never been a single (!) description of

improvement within the 130 years since the introduction of the procedure by

Dr. Blackley. Relief obviously has more chances to go unnoticed by doctors

because, unlike a severe aggravation, it is not fraught with liability and there-

fore draws less attention. As a result, if at AST, an allergen produces a sympto-

matic improvement and by that creates the perfect ground for its subsequent

use in allergy shots, the chance of eliciting this particular allergen is missed.

Patients do not observe a minor improvement for the same reasons they do not

observe a mild worsening: volaility of their symptoms. Moreover, they may not

inform their doctor even about pronounced relief: we tend to pay attention to

our body only when something is wrong. Thus, we never think or say: “None

of my ten fingers hurts” but will definitely recognize when one of them does.

There is another factor contributing to positive reactions being missed:

after AST, the majority of patients continue taking their medications regard-

less. Regular use of a pill or a puffer prevents knowing whether the improve-

ment results from the testing or from the drug.



As was cited before, even fatalities may occur in the absence of local skin

reactions. Similarly, symptomatic relief does not always correlate with the

degree of the localized reaction. This is an important fact, since the cocktail

prescribed for immunotherapy is based on those allergens that produce the

most impressive wheals at the testing. If among the allergen extracts, one is a

good match for a particular patient, even the prick with this extract may

result in improvement. Thus, the potentially effective allergen may be excluded

from the cocktail only because it does not produce a wheal, whereas systemic

reactions with improvement, which could help finding the specific allergen

suitable for immunotherapy, go unnoticed. This makes the judgment

regarding allergy shots even more flawed.

There is another factor that is not helpful in detecting positive systemic

reactions. For fear of causing an aggravation, allergy and especially asthma

patients are tested mostly in remission or under the “protection” of strong

medications. However, to reveal an improvement, testing should be conducted

in symptomatic patients, with the exception of those with life-threatening

asthma or who are in a severe allergic episode, and the patients should

certainly not take allergy medications at that time.

Unrecognized systemic reactions with improvement make immuno-

therapy ineffective because the potentially effective allergen(s) may not be

selected for the treatment.

SYSTEMIC REACTION TO HISTAMINESystemic reactions to allergens at skin testing, positive or negative (apart from

severe ones), are not observed because doctors ignore the basic facts that the

skin is an immune organ, and that, by touching it, we may incite a reaction

elsewhere in the body. Moreover, the sources that warn doctors about adverse

reactions do not provide an explanation for what causes these reactions, and

whether the reactions are preventable. The articles just caution about skin

testing in asthmatics as a particularly unsafe group and instruct doctors to

keep an emergency kit in the office.

Completely ignored is the fact that allergy skin testing starts with a hista-

mine prick, and that histamine is one of nature’s most potent biological

substances contained, by the way, in almost all allergen extracts. In manufac-

turing allergen extracts, the biological activity of allergens is routinely meas-

ured against the biological activity of histamine. This makes histamine the

measuring unit for the potency of allergen extracts. Since histamine possesses



both pro- and anti-inflammatory effects, theoretically speaking, an aggrava-

tion is as possible as an improvement. The scope of either reaction can be

wide, and again, the degree depends on the individual’s sensitivity. Knowing

all this, can we be sure that the fatalities described in scientific journals are

due to an allergen and not to the prick with histamine? Of course we cannot.

Today, the role of histamine at skin testing is reduced to comparison with

localized reactions: the wheal and flare formed by each allergen extract are

measured against the wheal and flare produced by the histamine prick. Since

systemic reactions are disregarded, allergists do not measure the systemic

response to allergen extracts against the systemic response to histamine in the

same manner they measure localized manifestations. Grave consequences can

arise from this method of testing in highly sensitive patients. A histamine

prick may overstimulate the H1 receptors and call to life allergy pro-

inflammatory mediators and cytokines. This will drastically aggravate the

patient’s condition. If it is asthma, an attack may occur. Those who are prone

to anaphylaxis may now have that reaction.

Histamine is not in the picture in any article warning of possible compli-

cation and even fatalities at AST. If doctors knew about the phenomenon of

systemic reactions in general and to histamine in particular, diluted histamine

would be used for the first prick. A mild adverse reaction to a histamine prick

such as a headache or increasing tightness in the chest, would warn the doctor

not to proceed with another prick at an increased dose and thus prevent a more

serious aggravation. Doctors are not taught this, moreover, the use of histamine

as a placebo in double-blind trials of allergen extracts illustrates how little aller-

gists know about this substance. As a result, a standard testing kit contains only

concentrated histamine for a control prick. Unaware of the potential danger of

this full-strength histamine, allergists use it in their every day practice.

Don’t be surprised that a small prick can result in a tragedy: a sting by a

bee may kill, and histamine is the main active ingredient in bees’ venoms, up

to 36%. Treating patients with histamine in my practice I observed that, in

highly sensitive patients, the slightest dose elevation could lead to transient

side effects—flushing, dizziness, a headache or tightness in the chest.

Therefore one cannot exclude the possibility that the fatal reactions described

in medical sources were the result of a prick with undiluted histamine.

If even the well documented pro-inflammatory properties of histamine

are not taken into account at skin testing, it is only natural that systemic

improvement upon a prick with histamine escapes doctors’ attention. Doctors



are totally uninformed about the anti-inflammatory properties of histamine,

even though these are observable even at a rather low concentrations. If a

patient’s medical history indicates high sensitivity, allergy testing should start

with diluted histamine. Some of my patients responded positively to histamine

diluted 1,000 times, which correlates with the findings provided by Rocklin on

the highly individual responses to histamine in allergy patients.

In those patients who respond to a prick with mild improvement, a higher

dose may provide further relief. Thus, for a patient with high sensitivity, one

diluted prick may be enough to improve his pre-testing condition, while less

sensitive patients may need several pricks to feel better. It is of interest that,

like in the cases of allergen extracts, the size of the local reaction to histamine

does not necessarily correlate with the degree of the systemic reaction: a

minor skin hive may be accompanied by a dramatic symptomatic relief or the

other way around.

To monitor patients’ reaction, it is imperative to separate the histamine

prick from the pricks with other extracts. They should be given at two

different visits, not at the same visit as is done today. This will allow accurate

observation of the reactions, to make the correct judgment as to what

produced positive or negative effect, and what concentration of histamine is

sufficient to produce it. All this could be applied later in decisions regarding

immunotherapy: in choosing between histamine and an allergen extract and

in finding the suitable starting dose of histamine if it becomes the treatment

choice. The very fact that the histamine prick is given together with other

allergens is proof that its biological potency and its dual action are completely

disregarded, and it is erroneously perceived as a substance that forms a skin

hive only. Since by pricking the skin, we activate immune and chemically-

related cells, allergy skin testing is an immunologic test, described in Allergy

1985 as “the most sensitive technique for demonstrating the presence of

immediate hypersensitivity” (p. 217).3 Immediate sensitivity means, first of all,

histamine liberation and thus, a potential systemic effect. Strangely, allergists

do not consider that theoretical immunology is relevant in the clinical setting.

Allergy skin testing will always be potentially dangerous if the powerful

biological activity of histamine is disregarded. Immunotherapy will never

be successful if the substance with the best potential immunemodulatory

effect is not considered for therapy. Allergy will never be a science if in prac-

tice, it disregards and/or conceals the basic scientific data.



DELAYED SYSTEMIC REACTIONSLet us speak about yet another very important flaw of conventional AST.

Different people react to the environment and to the body’s internal events

differently. For instance, some of us can tolerate cold or heat better than

others. Another example: there are lucky ones who have a metabolism that

burns the calories consumed in cakes and chocolate so fast that not a gram of

fat is deposited under the skin, while for many, it seems that each consumed

calorie results in weight gain. Our immune systems also function differently in

different people. The inner chemical lab contained in each cell may work fast

or slowly, gently or furiously, easy-to-be-ignited or hard-to-be-turned on.

Thus, when allergy skin testing is performed, the speed with which a person’s

immune system will respond is unknown. The systemic response may take

place immediately or be delayed in time. This is not taken into consideration

in conventional skin testing. If immunotherapy becomes the treatment choice,

the decision on the composition of the allergen cocktail is made on the basis

of the localized wheals right upon the testing. However, judgment needs to be

delayed and based on systemic responses, because those are actually reliable.

In this connection, an immediate systemic reaction with aggravation does

not mean that a certain allergen cannot be used in the allergy shots. The

patient should be instructed to monitor his symptoms for the next day. If later

on, he feels better, does not need his regular medications, or is able to reduce

their dosage, the overall effect should be considered as favorable. The initial,

exaggerated response can be attributed to the patient’s innate hypersensitivity,

and small doses at the start of immunotherapy may do the work.

Allergen extracts may lead to both aggravation and relief even at the

testing stage. Aggravation is rooted in the fact that some extracts may be the

triggers of the symptoms. The improvement is the result of the initiation of

desensitization: the offender given in a small dose challenges the cells to do

their protective job. The same is true of a histamine prick given prior to aller-

gens. It may also produce a delayed systemic reaction with improvement or

aggravation. Both, in the case with allergen extracts and in the case of hista-

mine, only lasting symptomatic improvement becomes a reliable ground for

successful immunotherapy.

Any allergic reaction signals the spill of histamine and the activation of

histamine-induced chemistry. Thus, by measuring what produces a stronger

reaction on the skin and systemic worsening—histamine or allergen

extracts—physicians can actually measure what provokes more histamine



release locally and all over the body. Documented are anaphylactic reactions

occurring within seconds or minutes after pricks in the absence of any skin reac-

tivity. They are the best examples that even the most severe allergic symptoms

may not have anything to do with IgE antibodies. The most powerful example

instantaneous death due to a bee sting in a person never exposed to bees

before and thus not having IgE antibodies to the venom. Histamine gushing

from the mast cells of the bee sting victim is the cause. This proves that it is

senseless to conduct skin testing solely for the purpose of finding IgE anti-

bodies that allegedly point to the trigger(s). It is similarly improper to start

immunotherapy based on such an unreliable diagnostic procedure and hope

it will be successful.

WHO GETS PUBLISHED IN MEDICINE?I can imagine your disbelief that the trivial observations I just described, such

as systemic reactions with improvement, have not been described by others.

This has an explanation. Certainly, there are doctors who notice such events.

However, with the theoretical knowledge being unavailable, they may not

know what is behind the relief or may consider it coincidental and, therefore,

do not make their observations public. My knowledge of these theoretical data

can, of course, be explained by my general interest to basic science, but to a

great extent, it was expanded due to the extensive detective search of medical

sources, which I undertook under the pressure of my being prosecuted. The

medical licensing authorities were not satisfied with the demonstration that

my patients recovered and the numerous scientific references I provided. They

demanded I find confirmation from the leaders in allergy research. The inves-

tigation was an eye-opener for me regarding the undercurrent life of the

medical society, and rules governing it, including privileges for publication.

The primary reason why such information does not turn up in journals is

the difficulty involved in having an article published. For an author who does

not have a name in the scientific world and is not supported by the authorities,

the chances for publication are almost nil, especially so, if the expressed view

goes against the existing trends. The primary sponsors of almost all medical

publications are the pharmaceutical giants, and periodicals sponsored by them

are full of ads promoting their products. The profile of the journals is in direct

correlation with the manufacturing profile of the sponsors and the advertised

products. Before being published all articles are censored, or, as it is called in

science, peer-reviewed. The reviewers are usually the elite of the given medical



field whose names are on the lists of the Editorial Boards and Boards of

Directors of all central journals. The majority, openly or in a hidden way, are

connected with the drug manufacturers.

Information about a symptomatic improvement in response to a prick

with histamine would prove its systemic response, hence its curative proper-

ties. This could become hard evidence in favor of its beneficial employment in

therapy. Histamine would become a strong competitor of the medications

advertised in these very journals, and therefore information related to its

neuro- and immunomodulatory properties will never pass censorship. The

best proof that histamine must be considered a dangerous competitor for over

two decades is found in the following fact: its successful use in double-blind

trials conducted on asthma and allergy patients in the medically advanced

Japan have not been published in English, the main language of science. I

started to thoroughly study bibliographic sources after I had found that occa-

sionally such information slips through inadvertently. Here are several of such

papers published in the December 1997 issue of JACI:17

1. K. Ito. “Clinical evaluation of histaglobin for bronchial asthma—

a double-blind study using human gammaglobulin as control.”

(in Japanese). Rinshoutokenkyuu 1979;56:3085-69.

2. A. Ito et al. “Clinical effect of histaglobin on nasal allergy double-blind

study” (in Japanese). Jibiinkokatenbo 1979:22:38-49.

3. J. Kukita. “A double-blind study of histaglobin on allergic dermatitis.”

(in Japanese) Nishinipponhifuka 1980;42:470-7.

It is peculiar that the references warn you not to try to find the material in

English by writing in brackets “In Japanese.” By pure luck, I was able to read

the English translation of these articles done by a patient of mine. My

personal experience also shows how undesirable for clinical immunology

effective methods are. In the early 1990s, in Toronto, an international confer-

ence on chest diseases took place, and asthma was one of the topics. I

submitted an abstract on my successful use of histamine on about 2,000

patients. The conference organizers rejected the abstract due to “logistics”

problems: “a noncompetitive problem,” the answer stated. A new practical,

and successful approach was of no interest to those who were organizing a

conference on that disease. All this at the time when the mouthpiece of aller-

gists, their central journal admits: “Despite advances in the understanding and

management of asthma, it remains the only treatable (!?) condition in the

western world with increasing morbidity.”13



ALLERGY SKIN TESTING AND IMMUNOTHERAPY—SUMMARYHere is what makes allergy skin testing and, hence, immunotherapy based on

it, failed enterprises. The interpretation of skin testing is based on the scientif-

ically unfounded hypothesis that allergies are strictly IgE-based diseases, and

that all triggers can be revealed at the testing. In fact, it is mainly mast cells’

histamine hyperreleasability that underlies the pricks. Since the majority of

patients have non-specific or mixed forms of allergies, skin testing aimed solely

at searching for IgE antibodies is frequently pointless, they are just bystanders.

■ Many have allergies to substances that do not exist in the standard form of

allergen extracts and cannot thus be used in testing; numerous pollutants

are an example.

■ There may be false-positive skin reactions to those allergens, which do not

produce symptoms in real life.

■ There may be false-negative skin reactions to allergens that provoke

symptoms. This event completely undermines the IgE dogma.

■ The selection of allergens to be employed in immunotherapy is made solely

on the basis of the skin manifestations without taking into account the

accompanying systemic reactions.

■ Mild and moderate systemic reactions with aggravations are missed at the

testing, therefore the subsequent allergy shots may contain aggravating and

life-threatening allergen(s).

■ Systemic reactions with improvement are missed because they are not

expected to be observed, therefore the allergens potentially effective for

therapy may be excluded from the therapeutic allergen cocktail.

■ The judgment on the therapy does not include the delayed systemic

response, whereas it is the net result that matters, and not the transitory

initial reaction.

■ Histamine’s high dual systemic activity is disregarded, and it is reduced to

a measuring unit of the local reactions produced by other allergens.

■ Histamine pricks and allergen pricks are given together, which prevents

differentiation between the two systemic effects.

■ Conventional diagnostic kits contain only concentrated histamine, and its

high potency may lead to a severe reaction and even fatality in patients

with high sensitivity.

■ Histamine’s immunemodulatory effect is not known to clinicians. Therefore

a possible improvement after a prick is left unheeded, and the chance to use

histamine in therapy is lost.



■ The fact that histamine is a neuromodulator is unknown. Therefore

potential changes in neurological or nonspecific symptoms that accompany

allergies are missed and remain untreated.

A chain is as strong as its weakest link, and in today’s allergy practice, hista-

mine is the one. This is because basic science teaches us that allergic reactions

occur due to the inability of the protective histamine-related immune tools to

control the negative histamine-related forces. In the chain of events during

allergic reactions and their reversal, histamine is the central link. Since the

theoretical knowledge about histamine, especially about its protective prop-

erties, is ignored in clinical allergy, the strongest turns into the weakest. The

elimination of this vital information from medical textbooks has necessitated

a substitution with nonessential data. The resultant misinformation has led to

invalid concepts, redundant procedures, mistaken judgments, failed thera-

pies, grave accidents and escalating morbidity in all allergic and related

diseases and, most tragically, an ever-increasing rate of mortality in asthma.

Allergy skin testing could be the test conducive to successful immunotherapy.

Today, it is a procedure, which doctors cannot support theoretically or imple-

ment properly in practice.

Conventional AST is a helpful decoy—a sort of placebo involving both the

patient and the doctor in illusion. It inspires patients with hope and brings them

to the offices of allergists who eagerly perform numerous pricks. The more

pricks, the higher the pay. I saw a patient tested for camel (in Canada!). Many are

tested for various foods even though such tests are considered inconclusive by

allergists themselves. Almost all are tested for hay fever, even if no symptoms

occur during the pollen season. When the purpose that guides the doctor is of a

monetary nature, the pricks to camel in northern countries and to polar bears

in California can be considered the norm. Today’s skin testing is a performance

impressively staged, lucrative for the performer and protected from any liability

and/or responsibility if performed according to the existing guidelines.

THE BRIDGE TO SUCCESSFUL IMMUNOTHERAPYOnly successful and risk-free immunotherapy can rid allergy patients both

of their symptoms and daily medications. For immunotherapy to be effec-

tive, skin testing must become its reliable first step, and the following rules

must be observed at the testing:

■ Systemic reaction should become the focus in the interpretation of the tests,

while the skin signs should be secondary in importance.



■ Patients should be skin-tested when they have symptoms, otherwise doctors

will be unable to elicit the changes after having made pricks—exactly what

we have now. Hay fever patients are the exception, as their seasonal symp-

toms are always indicative of the diagnosis. However, testing in season with

the provoking allergen may severely aggravate their condition.

■ A histamine prick and pricks with allergen extracts should be given sepa-

rately, one-two days apart, to observe and compare the systemic reactions

after both sessions.

■ The initial prick should be made with diluted histamine, and histamine

concentration in further pricks should gradually increase either reaching

the standard concentration or until a systemic reaction is observed, not just

a skin hive. This will take into consideration the individual hypersensitivity

and will, thus, help avoid accidents that may occur with the currently

employed concentrated histamine.

■ The decision regarding what to use for immunotherapy—histamine or an

allergen extract—should be made upon the assessment of the delayed

systemic response, and not only the immediate one.

■ Symptoms other than allergic ones should also be elicited by proper ques-

tioning before and after the procedure, and the patients told to monitor the

changes within the 24–48 hours after the testing.

■ Systemic reaction with improvement and not the size of the wheals should

be the criterion for what should be used in allergy shots.

Today, skin testing does not preclude the use of steroids, even though the

drug’s suppression of the immune responses stifles systemic reactions. Patients

who do not have physiological dependence on steroids should stop taking

them. In the case of dependence, the weaning process requires special meas-

ures and even then, it may not be possible due to the aggravation of asthma or

drug dependence. Today, AST does not take into account delayed reactions.

Therefore the patients are only instructed not take antihistamines shortly

before the procedure, but they should refrain from taking any of their regular

medications a day afterwards. Asthmatics should observe if their need for

bronchodilators changes and not to use any if there is no breathing difficulty.

All this will make the judgment regarding the systemic response unmarred.

ANTI-CHALLENGE TESTThere is a notion in medicine called a challenge test. To confirm the diagnosis,

doctors create a situation in which the patient is exposed to a major trigger, and



the symptoms are bound to occur. In other words, the purpose of a challenge test

is to provoke an aggravation. For instance, to confirm the diagnosis of asthma, a

patient inhales a substance that causes an asthma attack. If there is a recorded

aggravation, doctors conclude that this asthma challenge test is diagnostically

valuable. However, if a diagnostic test leads to an improvement, it stops being a

challenge test and requires a different name. The fact that doctors are warned

regarding possible adverse reactions and even fatalities means that allergology

sees (at least subconsciously) AST as a variant of a challenge test to the skin.

After having monitored hundreds of cases, the idea came to me that skin

testing should also be viewed as a potential anti-challenge test, a non-existing

notion in medicine. An anti-challenge test should be done with the purpose

opposite to the challenge test—to provoke symptomatic relief and use it as a

guide in choosing the therapy. One prerequisite is needed for that: the doctor

must know that skin testing is a procedure not only with a potential systemic

reaction with aggravation, but one with possible improvement as well. Any

physician who conducts the test must know the duality of the immune system’s

functioning. Only then, will he expect symptomatic relief as a possibility both

upon a histamine prick and at the next session with allergen extracts. Having

done both, he should compare the degree of the relief that occurs with each test.

Before skin testing, the examiner obviously does not have a clue as to the

possible reaction: will there be an aggravation? an improvement? no sympto-

matic change? The doctor will be able to find what to use in the subsequent

immunotherapy only if the purpose of testing is to find what will improve

the symptoms, and not what produces the biggest wheal. Already at the

testing stage, the patients should be taught to observe their symptoms. Before

testing, a thorough questioning about the symptoms experienced at the given

moment and their changes afterwards clarifies the common origin of allergic

symptoms and the ones that initially do not seem to be allergy-related.

Among them, there may be an abdominal discomfort, muscular pains,

headaches, irritability, fatigue, etc. Because AST can improve a number of

symptoms and conditions, often nonspecific, it should be considered an anti-

challenge test worthy of conducting.

During the course of immunotherapy, the observation continues. In fact,

every allergy shot should be looked at as an anti-challenge test, since its purpose

should be improvement. Do patients continue to improve? What symptoms go

away and for how long? If the symptoms reappear, are they as strong as they

were before the last injection or milder? Does the patient’s requirement for



drugs continue at the same level, or does he needs less drugs? Patients learn to

inform the doctor about all the changes as well as the mildest side effects, so

that further adverse effects are prevented by dose adjustment. Their feedback

will also allow the doctor to speed up the recovery by accelerated dose increases,

if the recovery is slow. The treatment based on the patient’s observations makes

the patient responsible for providing the needed details. He becomes an active

participant in the treatment process, and my experience shows patients love it.

Reactions to allergen extracts or histamine are a pendulum that may sway

in both directions—pro-disease or anti-disease. Following the above-

suggested separation of histamine and allergens, use of diluted histamine and

monitoring systemic reactions will inevitably lead to a safe test and later, to an

effective immunotherapy. The use of a test which will reverse the symptoms is

a dream come true in any field of medicine, and this dream is easier to realize

in allergy than in other less reversible chronic conditions. Allergy can use skin

testing and subsequent allergy shots as a tool to substantially improve the

patients’ condition, or often even cure them.

Recently, I found the information that gives legitimacy to my idea of anti-

challenge testing. The biological mechanism that underlies this test is explained

by hormesis, the phenomenon especially common for the immune system

functioning. Hormesis is the stimulatory effect produced by small concentra-

tions of any offensive substance or any harmful effect on the organism, the

immune system in particular. Mild stimulus cannot cause a significant aggra-

vation; on the contrary, it challenges the protective forces. Even radiation in

small doses can be beneficial for the health, as Japanese sources inform us. In a

similar way, psychological stress, when short-lived and/or not too overwhelming,

is helpful in making us stronger in withstanding stress in general. Introduction

of “sub-toxic” amounts of offensive substances or influences “teaches” the cells

to defend us.

Defensive performance of the immune system is its production of protec-

tive chemistry. The symptomatic relief at AST is the result of the chemistry

implemented, first of all, by the local units made up of T-suppressors, LCs,

mast cells and then further involvement of other related cells. This proves the

logic of conducting this diagnostic procedure with the expectation of relief,

that is, as an anti-challenge test. Actually, homeopathy is based on the prem-

ises of hormesis; ironically, so is immunotherapy employed by allergists

themselves. “Mechanisms underlying immunotherapy remain obscure. Thus,

it is difficult to develop a logical strategy for improving the treatment,” states



an editorial of JACI and concludes: “The onus is now on immunologists to

develop coherent strategies from which improvements in treatment can be

developed.”14 All allergy medicine should do, is to accept the unarguable

proof that histamine-related mechanisms underlie immunotherapy as they

underlie all allergic processes, good and bad. This will allow them to use skin

testing and subsequent allergy shots not blindly, as it is done today, but with

the knowledge of the fundamental laws of nature.

ALLERGENICITY AND IMMUNOGENICITY Conventional immunotherapy is based on the postulate that the elevating

doses of the offensive allergen extracts should desensitize the patient, i.e.,

make them less sensitive to these allergens. Such an improvement should be

due to the protective immunogenic effect of the extract its immunogenicity.

However, the expectation of the positive results is often shattered by adverse

reactions. This is not surprising because the very penetration of a trigger into

the body challenges the “pendulum” of the immune system and harbors the

danger of a negative reaction, namely allergenicity. It is only individual sensi-

tivity that delays an adverse reaction, but each dose increment potentially

increases this risk. Patients with a higher sensitivity may have side effects even

at an early stage, and the doctor’s disregard for these may lead to most severe

accidents. Medical journals provide descriptions of deaths of asthmatics

caused by ragweed or dust mite extracts provided during immunotherapy.

At the same time, surprised authors write that patients desensitized to one

allergen stop reacting to other triggers. Those who read Rocklin’ explanation

of this phenomenon in Allergy 1985 (p. 192),3 would not be surprised: any

successful immunotherapy results in the development of H2 receptors and in

generation and maturation of T-suppressors. The suppressors gain the control

over all allergic reactions, irrespective of what activates their receptors,

allergen-specific triggers (allergen extract) or nonspecific triggers (histamine).

PEPTIDESAny allergen extract that includes a trigger is potentially dangerous. Medicine

dreams of a substance devoid of allergenicity and possessing only immuno-

genicity, a substance that could rid patients of their allergies, no matter what

their trigger is. Do they exist? They do. Non-stimulatory peptides. Remember

that word. Peptides are coming into fashion in allergy. Regrettably, not in clin-

ical settings despite (or due to?) their potential efficiency.



An allergen protein consists of peptides (a group of amino acids). Non-

stimulatory peptides are only fragments of the protein. If the whole protein can

provoke symptoms when used in shots, a peptide, with its allergenic part

removed, cannot. This almost completely eradicates the side effects of allergen

extracts. Conventional allergy recognizes only specific immunotherapy, the one

that eliminates hypersensitivity to the injected allergen. Injections of peptides

are this, a nonspecific immunotherapy, since their specific, allergenic part is not

there. Nonspecific peptides may invoke an immunomodulatory effect

depending on what receptors they activate.

For example, it is possible to develop peptides that will be able to stimu-

late only our protective H2/3 receptors and thus contribute to allergy-protective

cytokine production. A peptide vaccine “was shown to inhibit histamine

release…(it) reduced IgE antibody formation and serum histamine concen-

tration, and abolished systemic anaphylactic reactions in response to allergen

challenge. This peptide may form the basis of a vaccine in a new approach to

the immunotherapy of atopic (allergic) disease.” This comes from the most

prestigious British medical journal The Lancet.15 Note the year of the publi-

cation—1990.

A Canadian source written five years later agrees that a peptide based on

house dust mite extract “has the potential for controlling and eliminating the

patient’s specific allergy while providing a glimpse of the future.”16 In fact,

house dust mite extract, even if not reduced to its safe part, may play the role

of a non-stimulatory peptide when it is administered to a patient who is NOT

specifically allergic to it. When skin-testing with dust mite, I always watched

for improvement. If there was one, I employed the dust mite extract for

therapy, no matter what size of wheal it formed.

The use of a nonspecific, so to say, ‘irrelevant’, substance for treatment is

not new in medicine. It is done to stimulate defensive forces. Thus,

substance P is the number one pro-inflammatory neuropeptide among

sensory nerve mediators (like histamine among allergy mediators). However,

substance P also possesses modulatory features (also like histamine), and its

positive effect manifests in the pharmacological agent Capsaicin. This plant-

derived product provides relief when used in an ointment for arthritis

(zostrix) and intranasally in chronic rhinitis (another proof of common roots

of immune and some neurological symptoms). Although neither pharma-

ceutical compendia, nor researchers clearly explain the mode of action, the

stimulatory effect of this seemingly irrelevant chemical is, actually, rather



simple. It is based on the principles of dual function of the immune and

nervous systems. Capsaicin evidently activates those receptors that conduct

anti-disease chemistry.

Another example of therapy is successful treatment of bladder cancer

with bacillus of tuberculosis vaccine, even though there is no immediately

understood relationship between cancer and tuberculosis. However, in

applying the weakened bacteria from the diagnostic TB vaccine, the bacilli

appear collaterally to activate a lot of protective immune-related chemistry

that usually accompanies the body’s fight against TB. Because the body works

as a system, immune-related chemistry is rather like an army of mercenaries:

properly invoked, they will fight anything and everything. Among the

invoked newly-formed chemicals, there may be protective cytokines that

nonspecifically reverse allergic reaction reactions.

Allergy medicine knows that to reverse an allergic reaction, one must, first

of all, inhibit histamine release. An immune stimulant can achieve this only

via H2/3-receptor activation. Therefore we can confidently state that these

“extraneous” substances possess the ability to activate the H2/3 receptors, and

through this, contribute to the activity of T-suppressors and the release of

anti-allergy mediators and cytokines. Active T-suppressors do not care what

activates them and reverse any allergic reaction.

My personal view is that, if peptides are effective in trials and show they

can reduce not only the hypersensitivity to specific allergens, but also affect the

general, nonspecific factors, they will most probably be kept in laboratories for

decades similar to histamine and histamine congeners. The proof may be

found in the fact that they were developed at least a decade and a half ago, but

have not been used even on those for whom all other means have failed. The

reasons are familiar: the range of a drug’s effect must not exceed the desirable

(by the manufacturer) effect and must comply with the basic marketing prin-

ciples of repeated sales. No single drug is allowed to become the replacement

of the rest of the existing drugs/allergen extracts. Only an extremely naïve

person can hope that the drug industry will willingly give up its numerous

medications for the sake of allergy patients.

HISTAMINE VS. ALLERGEN VACCINES AND PEPTIDESWhich of the three— histamine, allergen extracts or peptides— makes the best

choice for immunotherapy?



Comparison of histamine with conventional allergen extracts is in favor

of histamine. Histamine is a synthesized body product with well-studied

immunomodulatory properties. Its virtue is that it obeys the laws of nature.

Allergen extracts are substances which may unpredictably provoke a strong,

even severe allergenic responses. Their foreign nature and allergenicity

preclude predictability during immunotherapy; it is impossible to know which

of the ingredients, and at what dose, they will induce an adverse reaction. This

introduces a great risk and explains why specific immunotherapy is often

accompanied by complications and is, therefore, often conducted “under the

protection” of steroids and/or with resuscitation facilities at hand.

Comparison of non-stimulatory peptides with allergen extracts favors

peptides. The reason is that potentially hazardous elements of the substance

are eliminated. At worst, peptides are ineffective but not harmful, since they

are devoid of allergenicity, which is so common in allergen extracts.

Comparison of histamine with peptides favors histamine. Since any

successful immunotherapy inevitably results in the growth of the H2 receptors,

we can hardly create a chemical better than the one nature specifically

designed for developing them, namely histamine. Should we go against nature

because drug companies say so? Besides, peptide-use in every day practice is in

the remote future; they will definitely have a much higher price than hista-

mine, and this burden will be borne by the consumers. No matter which

consideration one explores, from the simple standpoint of cost effectiveness,

therapy with the inexpensive histamine is more logical. Peptides can be devel-

oped as one more immunomodulatory tool. For now, we should not forget

that we already have an inexpensive remedy available and at our fingertips.

The wide scope of histamine’s activity in the body, its ability to involve the

nervous system in the process of recovery, and through it, the rest of the body,

adds further weight in its favor. The picture may look different depending on

what motivates one: if one is trying to help patients who suffer, one’s priori-

ties are radically different from the point of view of the pharmaceutical

alliance whose sole interest is their revenues. What is good for a patient is not

necessarily good for the industry.

DEVELOPING THE NEW METHOLDDiscoveries often come in the following manner: we all know how things are,

but then someone comes along and wonders why they cannot be different.



Something of this sort happened to me. My understanding of reactions char-

acterized by systemic improvement go back to my work in the Soviet Union.

When I was in residency in internal medicine, allergic diseases were not

taught. Allergy as a branch of science was only emerging in the world. IgE

antibodies were discovered in 1966, and they were soon proclaimed to be

the foundation for this new field which gained its general recognition as

allergy medicine because of this discovery. I was among the first doctors in

the former Soviet Union to specialize in allergy at the Moscow Allergy

Institute that had opened in the early seventies. The knowledge I gained

during my specialization adhered to the traditional scheme: allergic diseases

and asthma are always allergen-triggered and therefore IgE-mediated; skin

testing should focus on the signs produced on the skin which reveal the

specific “offenders”; these offenders should be eliminated and/or used in

extracts for desensitization.

After specialization, I continued my work in the central teaching hospital

in Petrozavodsk, the capital of Russia’s Northwest republic of Karelia. This

hospital was the basis for teaching medical students and also the consulting

centre for local hospitals. Complicated cases were referred here from all over

the republic for diagnosis and initiation of the treatment, which was then to

be continued by the referring doctors where the patients lived. Allergies and

asthma were common but often remained undiagnosed and were treated as

recurrent pneumonia and/or infectious bronchitis with antibiotics (as they

are still now, by the way). An important difference between medicine in the

Soviet Union and the West was the fact that drug pushing did not exist where

I worked because of the absence of a market economy, the lack of influence

by drug companies, and the resulting unavailability of many drugs. This

explains why medicine in the Soviet Union, although technologically inferior

to the West, placed a much higher value on the needs of the patient and

doctors were trained to be far more attentive in their clinical approach.

Doctors there were reluctant to prescribe steroids as frequently as their

Western colleagues did, even when they became available. Experience had

taught us that the immune system, not suppressed by steroids, is more

resilient, and properly selected immunotherapy is more efficient in this

setting than in cases of a steroid-scorched immune systems. This simple fact

accounted for my success with immunotherapy which, from the very start, I

perceived as the most logical treatment.



Medical service was free for everybody in the Soviet Union. The hospital

where I worked provided free accommodation to the referred patients for a

week or two. Within that short period, I had to be ready with the diagnosis

and was expected to start the treatment. I did not have the luxury of

rejecting severe asthmatics as candidates for immunotherapy, since the very

fact of their being referred to his hospital meant that they had exhausted all

other means at their local hospitals. Nor could I wait until they were in

remission to skin-test them, even though, according to the accepted stan-

dards, symptomatic asthma patients were not suitable for testing. I was the

last hope for those asthmatics. Under those conditions, necessity became

the mother of invention.

A thorough medical history was the first step in the decision whether to do

skin testing. I was taught that in severe asthmatics, pricks with allergens could

aggravate the condition. To prevent any adverse reaction to histamine, uniformly

described in allergy medical literature as Evil Number One, I separated histamine

pricks from the pricks with allergens and started to use diluted histamine. This

enabled me to determine, in the case of aggravation, which of the two was the

real cause of the reaction. In order to monitor the patients’ condition, I asked

them about their symptoms right before giving the first pricks. My actions were

dictated by professional prudence. Knowing the dangerous side of histamine, I

repeated my questions regarding the symptoms after the pricks. To my surprise,

time after time, I heard about systemic improvement, a fact I had not been taught

and hence, had not expected. Testing with allergens the next day showed that

they too could render an improvement. I learned that both histamine and aller-

gens could sway the pendulum for the better, and this was not accidental. I

started to compare when relief was more pronounced: with histamine or with

allergens. The logic guiding me was that if a prick improved the symptoms, injec-

tions with the same substance could improve the condition still further.

Naturally, this would apply the other way around—the substance that produced

side effects during the tests should not be used for therapy, as it might worsen the

symptoms. I worked intuitively, and my intuition was base on my initial obser-

vations and eleven-year clinical experience.

In Russia, like in many European countries, along with allergen extracts,

histaglobin (histaglobulin) was available as a conventional means of treating

allergies, while histamine was used in testing only. The combination drug—

histamine plus gammaglobulin—owed its effectiveness to histamine, since the



very small amount of gammaglobulin in it was below any biological effect. I

started to use histaglobin effectively in various allergies and in asthma.

I saw my patients daily for about two weeks and made detailed recordings

of their symptoms. These records helped me understand many things, and

among them, the importance of the delayed systemic reaction. I saw patients

whose symptoms could change for better or worse within minutes after the

pricks, and those in whom response would become evident hours later. I

learned to instruct the patients to monitor their symptomatic changes, not

only immediately upon the testing, but also within the 24 hours after they left

the office. If a person listens to his body, he notices even a mild difference in

his condition, as did my patients who readily shared their observations. I took

the delayed response to the pricks into consideration before making decision

on what to start immunotherapy with—histaglobulin or allergen(s). The

analysis of the recorded symptoms revealed that even if there was an adverse

reaction, it did not necessarily mean that histamine or the chosen allergen

could not be used for treatment. A prick with histamine could be an overdose

for a sensitive immune system, and thus could cause an immediate aggrava-

tion. However, the reaction was usually mild and brief, and after that, the

patient often had a partial or complete symptomatic relief. I figured out that

in such cases, the treatment should start with a lower dose and be effective.

On the other hand, if the immediate relief was short-lived, it meant that

the patient’s sensitivity was low, and to prolong the relief, the treatment

would have to start with a higher dose. This practice of observation proved

the accuracy of my interpretation of the responses. Developing this method

further, I came to the conclusion that even if there was no reaction at the

testing, positive or negative, this did not mean that the patient was not a good

candidate for immunotherapy. For some non-responding patients, the testing

dose could have been too low to invoke an immune response at once, but a

higher dose could still make a breakthrough. I usually started treatment

cautiously by gradually increasing the doses of histaglobulin. If several injec-

tions did not change the patient’s condition, I did the same with the selected

allergen, and noticed that house dust mites produced the best effect among

the extracts. The majority of patients at AST reported greater symptomatic

relief after a histamine prick than after pricks with allergens, and for them,

histaglobin became the treatment choice.

What I was doing was not an experiment with severe asthmatics, since

histaglobulin had been used all over the world. The novelty lay only in my



specific approach. First, I precluded the occurrence of aggravation by sepa-

rating the pricks with allegedly dangerous histamine from the allergen

extracts and also by using diluted histamine. Secondly, trying to avoid aggra-

vation, I introduced detailed questioning and observation before and after

the pricks. I did not conduct uniform skin pricking, but tailored it to each

individual. Similarly, my immunotherapy was customized and not a one-size-

fits-all approach. To my mind, this is a more scientifically rigorous approach.

My thorough questioning and observations had one more benefit.

Although I was treating allergies and asthma, I noticed that certain symptoms

disappeared along with the targeted ones. Sometimes, it happened right after

the skin testing. A question, “What other symptoms are you having now?”

asked before the testing and, “Are you still having (headache, stomach discom-

fort, fatigue, etc.) now?” asked after the testing would often reveal that many

non-allergic symptoms were, in fact, allergy-associated. Twice a year, when

the patients would come for a follow-up consultation, they told me about the

disappearance or improvement of unrelated medical problems in the course

of their immunotherapy. Well matched therapy, be it histamine or an allergen

extract, worked broadly and systemically.

I published my observations regarding systemic reactions and how to

handle the transition to immunotherapy in the most prestigious Russian

medical journals, Therapeutic Archive and Clinical Medicine. My observations

and conclusions about systemic reactions with improvement at allergy skin

testing were the first, and as far as I know, the last of this kind in the world’s

medical literature. In 1978, I spoke about my asthma treatment based on the

evaluation of systemic reactions at the fourth International Symposium on

Circumpolar Medicine in Novosibirsk, the scientific centre in Siberia. There, I

reported that certain neurological symptoms, hypothalamic (or, as it was

called in Russia, diencephalic) syndrome disappeared in a patient who was

successfully treated for asthma.

For several years, apart from a pediatrician who specialized in allergy, I

was the only allergist in the republic and thus did not have any one else to

consult with. Great personal responsibility for each case dictated that I should

be on the lookout for even the slightest symptomatic changes. By nature, I

attend painstakingly to details, and I am always inclined to analyze, assimilate

and co-ordinate the numerous details I observe. All the while, I tried to relate

my observations to what textbooks taught and found there were gaps in

theory, which affected clinical application.



With much better access in Canada to the numerous theoretical sources,

using the data that had accumulated within the 15 years of allergy research as

a specialty, I searched for the scientific basis to my approach. I felt allergy

alone was unable to explain the chemical processes of the immune system as

well as its synchronized work with other major systems. It took me years of

reading hundreds of theoretical sources in various fields to understand the

basic mechanisms of the immune system and its interrelated functioning

with other body systems. I discovered for myself psychoneuroimmunology,

PNI, a new science that emerged in 1981, and understood it was the only one

to have the explanation of the regulatory processes underlying immune and

related diseases. I saw that basic scientific data related to allergic diseases were

not recognized by conventional medicine and hence, not taught to medical

students. I suddenly realized an appalling fact: anything that might lead to the

application of these data in clinical medicine tended to be immediately

concealed, and this concealment appeared to be very well organized. This

secrecy in clinical medicine continues.



ENDNOTES 1. S. Szefler. Challenges in assessing outcomes for pediatric asthma.JACI 2001;107:456-642. General discussion. JACI 1996;97:8853. Kaplan, ed. Allergy 1985, pp. 367,679,219,217,1924. S. Repka-Ramirez et al. IgE levels in chronic fatigue and control subjects. JACI 2000; 105:S3595. A. Kay. NEJM 2001;334:306. T. Jakob et al. Multistep navigation of Langerhans/dendritic cells in and out of the skin. JACI

2001;108:688-967. D. Engle et al. Comparison of the sensitivity and precision of four skin test devices. JACI

1992;90:985-918. M. Kaliner. Vision in Allergy: Impact on Health Care Reform. General discussion. JACI

1996;97:8859. A. Frew, A. Kay. JACI 1988;81:1117-21

10. F. Lockey et al. JACI 1987;79:660-7711. US Federal Register 1985;50,15:309712. K. Kelly et al. Skin and sereologic testing in the diagnosis of latex allergy.JACI 1993:91:1140-513. I. Amirav et al. What do pediatricians in training know about the correct use of inhalers and

spacer devices? JACI 1994;94:66914. M. Chapman. Editorial. JACI 1991;88:300-215. D. Stanworth et al. Allergy treatment with a peptide vaccine. Lancet 1990; 336:1279-8116. I. Ferguson. House dust mites and asthma, The Can. Journal of Diagnosis, 1995;12:1-217. H. Yoshii et al. A couple of histamines… JACI 1997;100:816



PART SEVEN

BRONCHIAL ASTHMA

THE GROWING PROBLEM OF ASTHMAAmong diseases of hypersensitivity, bronchial asthma deserves special atten-

tion because, as the leading immunology journal states “Asthma is the most

common chronic disease among children and the most frequent cause of

hospitalization,” and “it is a major cause of disability.”1 Like all allergic diseases,

asthma is growing both in incidence and mortality, however, unlike the rest of

them, the seriousness of asthma is due to its risk of death. Interestingly, the

disease has been known for at least five thousand years but until recently, was

not generally considered as fatal. The statistics on asthma fatality given in 1987

in the leading textbook on internal medicine, Harrison’s Principles of Internal

Medicine, cite 3 people per million dying as a result of asthma. According to

The Medical Post,2 mortality in Western countries was at 1–5% when the

asthma epidemic began in the ’60s. Within the 3 decades, the rate went up to

15% and then 25–30% in certain areas, with New Zealand and Australia gener-

ally recognized as having the highest mortality rate. Today’s numbers differ

from source to source and from country to country, but if we are to believe the

most recent statistics, Canada now is the leader in death from asthma with a

shocking annual 10 deaths per 10,000 patients aged 5 to 45.3

The increase in mortality is tremendous all over the world and among

different groups of the population, but the speed with which the asthma statis-

tics are rising among children is beyond belief. Indeed, in 2002 the World

Health Organization was forced to declare asthma a global epidemic.


“In Canada and other western countries, morbidity has increased most

among pre-school children, with a 300% increase in hospital admissions.”4 In

2000, the leading immunological journal wrote in the chapter “Crisis in

Asthma Care” that there has been a 75% increase in prevalence since 1980,

and a 160% (!) increase in children under 5 years of age.5

The increasing severity and mortality of asthma observed lately in all coun-

tries but especially in the developed world necessitate a thorough analysis.

There is no doubt that our technological and chemically-focused civiliza-

tion with its characteristic abuse of nature is a contributing factor. This

phenomenon is described by so many authors that there is no need to repeat

the already well known facts. However, an exclusive focus on the environ-

mental issues would mean turning environmental factors into the only causes

of the disease, which would be unscientific. The priority of relatively non-

polluted New Zealand and Australia in asthma rates is proof, so is existence of

people who live exactly in the same or much more polluted conditions without

asthma. This results in another conclusion: “Avoidance of allergens that

provoke asthma is a keystone of treatment but is often easier said than done.”6

Furthermore, it is not just the difficulty of the elimination of triggers that

makes the treatment a failure, but rather the subsequent approach that turns

the allergens into the cause.

There is a major problem here and it is recognized by a leading expert in

his article entitled “The Epidemic of Allergy and Asthma.”7 He observed:

“The past 30 years have witnessed a spectacular increase in our knowledge of

the cellular and molecular mechanisms of allergic disease, which has been

paralleled by the rising trends in the incidence and health impacts of these

diseases worldwide.” (Emphasis added by me.) This can mean one thing only:

something must be terribly wrong with this knowledge so spectacular only

because of its failure to help people; the treatments based on it must be recon-

sidered and a new approach must be found. Medicine ceases to be a useful

science if it cannot help people, as that is its only goal.

The purpose of the following sections is to discuss purely medical factors

which underlie the origin of asthma and contribute to its severity. They are

related to the misinterpretation of the disease of asthma, the manner in which

it is misdiagnosed, and the way in which is management, which by any stan-

dard, cannot be considered effective. We will disclose some the information

known to only few leaders in the field. This information is not generally

known to doctors or the public. Only by changing our conceptual under-

Bronchial Asthma 239


standing of asthma, can we help the patients. The price asthma patients pay

is too high, and society must do its utmost to save them.

PROBLEMS WITH CURENT DEFINITIONS OF ASTHMAJudging by the results of conventional management, what asthma really is

remains unknown not only to the general public but to doctors as well. Once,

I came across an article, in which two European respirologists wrote: “In light

of this enormous research effort, little real progress has been made since 1980s

to clearly define asthma. To some degree, defining asthma is like defining love:

we all know what it is, but no one can actually define it.” This inspires lyrical

images of the disease but gives little clarity.

Medical textbooks define bronchial asthma as a disease of the airways.

Then, they list the symptoms and potential triggers. This is correct only in the

sense that the lungs and bronchi are the organs that manifest the symp-

toms. Emphasizing the role of allergens in a definition does not elucidate the

nature of the disease, nor does it explain why symptoms may arise without any

trigger, or why only some people respond to the triggers with symptoms, while

others remain asymptomatic. Such definitions do not specify the origin or

nature of the disease. It is like saying that a headache is a disease of the head

characterized by pain in the head.

An international panel of experts working under the auspices of the World

Health Organization defined asthma as “a chronic inflammatory disorder of

the airways in which many cells play a role.” With all due respect to the experts

of the WHO, I find this wording rather vague because, after all, in all diseases,

“many cells play a role.” For example, rheumatoid arthritis also fits this defini-

tion, so does chronic bronchitis, which even has the same locality as asthma.

Another inaccuracy is that by calling asthma an inflammatory disease, one

accentuates the general, non-specific, secondary aspect, whereas the primary

defects that lead to the inflammation are not mentioned. Thus, the flu is not

an inflammatory disease of the nose and throat but a viral disease. Moreover,

the term inflammatory, mostly known as an infectious event, blurs the differ-

ence between two different medical notions, which are worlds apart: a

microorganism as a causative agent in infections as opposed to a genetically

predetermined malfunctioning of immunocompetent cells in asthma. The

only precise thing in the WHO’s definition is the location of the symptoms,

but even that is not specific to asthma.



Dr. M. Sears, a leading Canadian asthma specialist, states that “an all-

encompassing definition remains difficult to construct.” He assumes that

“genetic studies may help” but looks for the causes outside the body, and

again, we hear about house-dust mites, indoor pollutants, passive smoking,

childhood infections and their treatments. It is not surprising that the super-

ficial, triggering events replace the inner predisposing factors, and his specu-

lations over the definition of asthma relate it to the time of the first wheeze,

sensitisation with cigarette smoke, risk of mother’s smoking, etc.9 The

leaders in allergy have recently started to present asthma as a disease charac-

terized by degenerative structural changes in the bronchial tree and the lungs.

The term invented for this is “remodelling.” In this interpretation, asthma is

no longer the most reversible disease driven by the abnormal regulatory

processes in the immune system, but an affliction characterized by tissue

degeneration and scarring. Organic changes in the bronchi and lungs cannot

occur without underlying pathological processes, but allergists do not

provide clarification as to what these processes are. This new concept of

“remodelling” is dangerous in several aspects.

First, it dissociates the structural changes from the cause, without which

they cannot occur, and which by definition cannot be reversed/ corrected.

Second, it changes the perception of asthma as an immune disease and

turns it into a disease of tissue degeneration.

Third, it changes the general perception of asthma as being a reversible

condition, into an irreversible one whereas organic tissue changes are

observed in very advanced stages of the illness.

If this concept is accepted, we will see the statistics in asthma getting

grimmer day by day, because the treatment, should be applied to the core of

the disease, not just the organ in which it develops. Otherwise, doctors will just

manage the illness and wait and see if structural damage will occur.

FUNCTIONAL DEFINITION OF ASTHMAThe definition of any disease must specify, apart from location, the etiology—

the cause, the pathogenesis—the inner defects—leading to the disease. It is

hard to expect such a definition for asthma, since the received wisdom is that

“although many factors are known to trigger asthma attacks, relatively little is

known about the underlying causes.”10 The most reputable textbook also

admits that “No detailed definition of asthma has won universal acceptance.



The reasons are… the histopathology… is poorly understood, and most

importantly, the underlying etiology is unknown.”11 In asthma, as in all aller-

gies and related diseases, triggers are presented as the causes and inflamma-

tion as the primary event. Medicine does not explain what factors predispose

a person to this inflammation, as well as what is behind spontaneous asthma

attacks that do not have an identified trigger.

A scientific definition of asthma should incorporate

■ the location—airways;

■ the causes—the defects in the genes regulating immune responses and the

resultant defects on three levels: biochemical, molecular, cellular;

■ the primary molecular defect consequent to the genetic flaws—H2/3-receptor

inefficiency;

■ the primary cellular defect consequent to the same receptor insufficiency—qualitative and/or quantitative T-suppressor deficiency and exaggerated

histamine releasability by mast cells/basophils;

■ the primary biochemical defect accompanying the same receptor

insufficiency or resulting from it—low levels of the intracellular enzyme

cAMP, central for the normal functioning of the immune system;

■ the cumulative effect when mostly pro-disease chemistry results in immune-

related, inflammation-like process;

Such a definition would meet all the criteria needed to understand not only

where in the body the disease develops but also where it originates, and what

the stages of its development are. It would suggest the key target for treat-

ment, i.e. the need for activation of the inefficient receptors, and through it,

to activate the whole protective allergy-responsible aspect of immunity. A

definition of this kind would also be in harmony with existing theoretical

data. Moreover, the combination “inflammation-like” would indicate that

allergic inflammation is different from the infectious form, hence the treat-

ments should be different too. An accurate asthma definition should be

similar to the definition of all allergic diseases, with the main difference being

the organ in which they develop. Here is one possible version:

Bronchial asthma is a reversible immune disease affecting the bronchial

tree and the lungs. It is caused by the genetically predetermined ineffi-

ciency of histamine-inhibiting H2/3 receptors resulting in T-suppressor

cells’ deficiency, mast cells’ and basophils’ hyperreleasability of histamine

and histamine-induced pro-disease chemistry, and also low levels of



cAMP—all leading to an inflammation-like process characterized by

recurrent and variable airways obstruction (e.g. cough, shortness of

breath, wheezing).

Unfortunately, this kind of definition is unacceptable in contemporary

allergy medicine because it would require accepting the following facts:

■ the allergy-mediating aspects of immunity have their own protectors and

regulators, namely T-suppressors;

■ T-suppressors are able to control the disease only when their H2-receptors

are well developed;

■ H2 receptors, like all receptors, develop when activated;

■ H3 receptors are synergetic with H2 receptors both in the way they become

activated and in their effects;

■ nature’s best activator of H2/3 receptors is histamine, and, hence, it is the

best generator of T-suppressors;

■ both immunocompetent and nerve cells possess H2/3 receptors, and hence,

with receptor activation, the chemistry of both kinds of cells may change to

a disease-inhibiting mode of action;

■ stimulation of H2-receptors and T-suppressors is immunotherapy or

immunomodulation;

■ histamine messages via the H2 receptor increase the levels of cAMP and

rectify the faulty genetic messages to the cells, which is a natural gene

modulation;

■ successful H2/3-receptor stimulation with histamine would in many

instances replace the existing drugs for asthma and related diseases.

These revelations are apparently too revolutionary for conventional allergy and

its sponsors and they seem to find it necessary, therefore, to bury them. This is

the reason why we still do not have a clear scientific definition of asthma.

ASTHMA SYMPTOMSAsthma is not an age-related disease, although most cases develop in early

childhood. It hits men and women alike. It is marked by recurrent bouts of

shortness of breath, wheezing, and cough. In the majority of cases, the disease

is characterized by spontaneous attacks, and the length of symptom-free

periods differs from patient to patient. The severity of the disease may fluc-

tuate over the course of time. Some patients remain symptom-free for years.



This makes them believe they are disease-free, which is not the case for most

asthmatics. Very few children outgrow asthma, but even in the lucky ones who

experience a lasting remission, asthma may reoccur when it is least expected.

An asthmatic attack is characterized by a spastic narrowing of air passages

and/or swelling of the mucous membranes that may start to secrete phlegm.

The constriction of the bronchi and/or their obstruction with phlegm result

in shortness of breath. The spasm and/or phlegm moving with respiration in

the narrow canal produces an effect of a whistle—a wheezing sound. Cough

occurs due to the need to overcome the spasm and/or evacuate the excessive

accumulation of phlegm. Classic cases present all of these symptoms, while

others are limited to one or another only. This leads to diagnostic mistakes:

too often a resistant dry cough is diagnosed as a cold, while a cough with

expectoration (coughed up phlegm) is taken for infectious bronchitis. A

wrong diagnosis leads to the wrong therapy.

The lung’s function is to enrich the incoming blood with oxygen. Oxygen

enters the lungs during inspiration. There, it gets into the blood vessels, and

the oxygenated blood delivers it to other organs. When the bronchi are

constricted in attacks, the lungs become hyper-inflated because the obstruc-

tion prevents the air from being exhaled. The trapped air cannot get out, and

at the same time, the patient gasps for more and more air—all this worsens

ventilation and blood oxygenation. The functioning of the organs becomes

impaired if not enough oxygen reaches them. The lack of oxygen supply to the

tissues is called hypoxia. Hypoxia alone may lead to death in the worst cases.

This clearly indicates that although asthma is a disease developing in the

airways, it is a systemic disease and may affect the whole body when it strikes.

In severe cases, attacks may follow one another with practically no break.

This condition is called status asthmaticus. It requires urgent measures, at

times, resuscitation. Over the years, protracted asthmatic attacks, with

constant lung over-inflation, may result in degeneration of the lung tissue

leading to an incurable disease called emphysema. In emphysema, lung tissue

loses its elasticity, and live tissues are replaced by non-functional ones, and

eventually, the lungs’ functional ability gets irreversibly reduced.

WHAT UNDERLIES THE SYMPTOMSAllergists recognize their lack of understanding of asthma/allergy etiology and

pathogenesis and even “speculate about future avenues to reduce our ignorance

about the relevant causal factors for the inception of allergic diseases.”12 And



again: “the precise biologic mechanism underlying cellular responses is

unknown,” and “despite the insights, a clear understanding of the pathogenesis

of atopic asthma is lacking.”13 In the year 2000, a Harvard group wrote that

“Little is known about the cellular mechanisms promoting the development of

the allergic phenotype.”14 In other words, the leading immunological periodical

admits that the immune defects from which asthma, as well as the pathological

mechanisms leading to it, originates are unknown. This is not true. Science

knows very well that in asthma, like in other allergic diseases, no matter what

the trigger is—an allergen, a physical phenomenon such as exercise or a

weather change, or a physiological factor such as an invisible change in the

body’s chemistry—the host’s hypersensitive mast cells respond with an initial

excessive liberation of histamine followed by other pro-inflammatory media-

tors. The end organ where allergic disease develops is the host’s “Achilles’ heel,”

and for asthma patients, it is the bronchial tree and the lung. Besides, mast cells

and basophils are deposited in the lungs more than any other part of the body,

and therefore histamine-induced pro-inflammatory chemistry concentrates

there. It produces the bronchial muscle spasm and causes mucosa to swell and

form phlegm—all leading to physical obstruction.

The seething cytokine/mediator soup and the responding surrounding

tissues produce what medicine calls allergic inflammation. But, this inflamma-

tion is secondary to the histamine spill. The symptoms—bronchial constriction,

obstruction and phlegm—are the end effects of the pro-disease chemistry.

Structural changes occur only in very advanced and complicated forms of

asthma.

Thus, the latest classification of asthma as a “remodeling” disease is as

scientifically lame as it distorts the chain of events. To identify asthma as an

inflammatory disease is incorrect because the inflammation is the resultant and

not the initiating event. With the true operating forces ignored and not

discussed, but kept hidden, it becomes easy to (mis)present the secondary

and third-rate events as primary. And this is what allergist do.

ANTIBIOTICS FOR ASTHMA?The difference between allergic and infectious inflammations was thoroughly

discussed before. However, inflammation as the cause is emphasized in asthma

more than in any other allergy, and anti-inflammatory medications are heavily

prescribed. Therefore certain important points need to be clarified. We already

know what the differences between allergic and other inflammations are:



1. In infection, there is always an external causative agent, while in allergy,

the cause is an internal, inborn or acquired cellular malfunctioning.

2. Infection is an acute episode in the majority of cases, while allergy is a

chronic immunologic condition, readily apparent or smoldering, with

possible recurrent acute attacks or spontaneous remissions.

3. The clinical picture of asthma vs. infectious bronchitis or pneumonia is

different in that, like any infection, bronchitis and pneumonia are usually

accompanied by pus formation and, as a rule, by fever, whereas asthma is not.

4. A graph of an acute infectious bronchitis, pneumonia or a severe cold is a

time-limited curve which first climbs and then descends, while a graph of

asthma, a recurrent disease by definition, looks more like unpredictable

rises, falls and plateaus stretched indefinitely over time.

Asthma is an inflammatory disease only in the sense of an erratically occur-

ring chemical imbalance in the airways. Regrettably, doctors often handle the

situation as if there is little or no difference between asthma and bacterial or

viral inflammation. Asthma patients are too often diagnosed as having bron-

chitis or pneumonia and prescribed antibiotics, especially if their cough is

productive (with phlegm). Certain antibiotics may provide temporary relief

(although relief can also be spontaneous), which is not surprising because

medications may have a collateral effect in addition to the direct one. For

instance, the well-known aspirin, apart from its direct pain-reducing and

anti-inflammatory properties, also works as an anticoagulant. Similarly,

antibiotics may have a collateral effect in addition to their direct ability to

destroy microorganisms, but it does not make them suitable as asthma drugs.

They do not eradicate the original problem, and in the long run may even

harm. Although antibiotics are not exactly a topic which a book on allergies

should cover, in view of their frequent use in asthma, it is worth stressing the

relevant points. Those who take antibiotics several times a year, and especially

mothers whose children are frequent consumers of this drug category, should

know certain facts.

WHAT YOU SHOULD KNOW ABOUT ANTIBIOTICSIn its fight against an infectious agent, the body acquires the ability to defeat

this particular agent on its own by imprinting the knowledge about that agent

on the T- and B-cell memory. When antibiotics are taken, the body relies on

the medication and does not participate in the fight. If there is another



encounter with the same agent, the memory of the T- and B-cells, previously

excluded from the fighting process, is blank, and we need another prescrip-

tion for antibiotics. Therefore, their use must be limited to cases of confirmed

bacterial infection.

If the causative agent is a virus, antibiotics are irrelevant since they are

unable to fight viruses. A virus, like any live organism, has a limited life span.

Therefore a viral infection is a self-limited condition that, as a rule, resolves

spontaneously with as little effort as bed rest and drinking a lot of fluids.

Asthma patients are often convinced by the appearance of the phlegm that

they have infectious bronchitis. This is an unreliable sign because the colour

and thickness of the phlegm depend on the ease of its removal from the

airways. An airway obstruction may delay mucus evacuation, and its colour

may change to green or dark yellow and resemble pus; it may even acquire a

stale smell. To confirm pneumonia, a chest x-ray should be taken. Helpful for

diagnosing pneumonia are the accompanying fever and distress, which usually

increase in severity very rapidly.

Antibiotic users should abide by the rule of completing the therapy course

as prescribed. However, these drugs are toxicity, and various symptoms such as

weakness, dizziness, various abdominal distress, etc. may develop during a

treatment course. This forces patients to discontinue the medication as soon

as the symptoms disappear. If not all bacteria are killed, they become resistant

to the drug, and the next time, a new, stronger antibiotic may be needed to

combat the same infection. Frequent and unnecessary courses of antibiotics

may lead to unpleasant and even dangerous toxic and immune reactions.

Some of these drugs are allergenic and may, thus, intensify allergy and asthma

symptoms. Most important is that when they are prescribed to an asthmatic,

antibiotics do not deal with the cause, and the patient’s asthma may continue

to progress while the patient consumes irrelevant medications.

WHY ARE ANTIBIOTICS PRESCRIBED FOR ASTHMA?There are several reasons for prescribing antibiotics to asthmatics. Poor

differentiation between an infectious and an allergic inflammation leads to

misdiagnosis. The explanation lies in the doctors’ lack of knowledge of the

immune processes underlying allergic inflammation in asthma. The confu-

sion is deepened by the fact that the two different types of medications,

antibiotics and steroids, are both called anti-inflammatory despite the



absolutely different nature of their action and hence, different pharmacolog-

ical meaning and classification. Still, with the overwhelming number of asth-

matics who visit doctors’ offices, it is inexcusable for a physician to

misdiagnose the disease even if it is not the classical form as described by text-

books. No less a reason for the ease with which antibiotics are prescribed is

that the social status of doctors is such that he or she gets away with it. A

doctor is a figure put on a pedestal by our society and maintained there due

to the efforts of the medical profession itself. In this position of grandeur it is

easy to forgo additional learning about one’s field of expertise, and this leads

to ignorance. Only in purely medical publications, can one read such admis-

sions as: “It is paradoxical that the past decades have provided … the intro-

duction of new and more potent anti-asthma medications, especially inhaled

corticosteroids, but the success of controlling morbidity from asthma has

been rather limited.”15 The patients are never informed about the weaknesses

of the profession, and are often prescribed antibiotics for an alleged ‘infec-

tion’, often along with a bronchodilator ‘to breathe easier’, and not infre-

quently, along with a steroid puffer as well. Asthmatics are assured that they

are prone to bacterial bronchitis and remain unaware that a prescription for

an inhaled bronchodilator is an unspoken confirmation of asthma.

Dr. S. Wolfe, the author of Worst Pills Best Pills writes in the chapter on

antibiotics: “After congressional hearings and numerous academic studies..., it

has become the general consensus that 40 to 60% of all antibiotics in this

country are misprescribed.”We know very well the tendency to downplay unre-

solved medical problems, therefore, the actual figures are assuredly higher.

Canadians should be especially wary, for according to statistics in this

country, we have one of the world’s highest figures of asthma incidence. This

may explain the fact that physicians here prescribe antibiotics twice as often

as in US and five times the rate of European countries. It is due to the indis-

criminate prescription of antibiotics that we face problems with antibiotic-

resistant tuberculosis, flesh-eating infection resistant to all antibiotics, as well

as the more common condition of resistant strep throat which can lead to

permanent heart damage. The problem of antibiotic abuse has become so

overwhelming that it has become known through the mainstream media.

Regrettably, journalists write about the over-prescription of antibiotics in

case of plain colds and totally miss the fact that these drugs are grossly abused

in asthma.



IF YOU ARE PRESCRIBED ANTIBIOTICS...… you need to do the following:

■ ask your doctor to take a swab, when possible, to confirm the infectious

origin of the symptoms before you or your child start taking them;

■ be very cautious in the case of a recurrent cough or “cold” in the absence of

fever. It may be allergy or asthma;

■ question the diagnosis of respiratory infections if you have a history of

frequent “colds” in the absence of fever, and are otherwise healthy;

■ know that even if several members of your family have afebrile (without

fever) “colds” at the same time, these may still be allergies arising due to the

same trigger(s) and a shared genetic defect;

■ if an inhaler is prescribed along with antibiotics, make sure you understand

that you (or your child) have asthma, and the antibiotic is for a superim-

posed (though very rare) infectious bronchitis or pneumonia as proven by

x-ray;

■ in the case of true infection, make sure you do not stop taking the drug for

the indicated period, otherwise, you may become a carrier of a resistant

microorganism(s), and the infection may flare up again any time.

If you have asthma, exacerbations slowly undermine airway functioning and

potentially pave the road for superimposed infections. This worsen your

asthma and prevents a differential diagnosis, increases prescriptions for

antibiotics, and eventually undermines immunity still further. This vicious

circle can be broken only through repair of the inefficient self-regulatory

immune mechanisms. Unfortunately, a patient is not able to do that alone,

and the majority of doctors do not know how to proceed.

THE PROBLEMS OF ASTHMA DIAGNOSIS“In the past 40 years asthma has become the most prevalent chronic disease

of childhood in developed countries. Recent studies suggest that most asth-

matic patients are diagnosed by the age of 6 years, with symptoms first occur-

ring during infancy and early childhood,” observed writers in JACI.16 This

means that for 6 years, young children go undiagnosed, and hence, improp-

erly treated. Not the best recommendation for contemporary medicine! I

have my personal opinion why asthma often remains undiagnosed until the

age of 6 and not 5 or 10 years. Inhaled steroids, as the central asthma medica-

tions, have according to standard practice guidelines not been recommended



under the age of 6, and only recently, the trend has changed towards

prescribing them to children of 3–4 years old and even younger. Thus, chil-

dren may cough for months, take courses of antibiotics without any effect or

with only temporary relief and still be diagnosed as having colds or bronchitis

instead of asthma. Finally, they reach the “steroid-permissive” age, asthma is

diagnosed, and a prescription for a steroid inhaler is made. Not being able to

relieve asthma symptoms effectively without steroids, doctors, actually, delay

the diagnosis until they can prescribe them.

The percentages of undiagnosed asthmatics vary in different sources, and

some report up to 25–40% undiagnosed cases. This significantly raises the

official asthma figures. How the situation is downplayed can also be seen

through a strange but fashionable trend to split asthma into several different

conditions. Here are examples. Co-existence of a postnasal drip (back drip)

and asthmatic cough is common, since their origin lies with the same

immunologic imbalance. Recently, several sources presented postnasal drip as

one of most common causes of chronic cough. No textbook has diseases called

postnasal drip or chronic cough because they do not exist. This misinterpreta-

tion elevates postnasal drip to the level of a new and separate medical condi-

tion that allegedly provokes a chronic cough. Moreover, the very term “chronic

cough” is diagnostically incorrect, since it is a symptom and not a disease.

Although of no help to the patient, this helps the asthma figures look better.

Another semantic innovation may also serve as an example of the contin-

uous trend of belittling the asthma drama. Thus, a Canadian doctor, recog-

nized in 1999 as Number One allergist, proudly announced her invention of

a new term and therefore new medical disease—rhinobronchitis. Her expla-

nation, however, did not differ from the postnasal drip/chronic cough

phenomenon. In both cases, the first part, chronic rhinitis, is presented as the

cause of the second, chronic bronchitis. Time will show whether the new term

and the underlying meaning will be accepted, but I doubt it will be easier to

cope with allergic rhinobronchitis than with asthma.

Among other euphemisms for asthma I found in the works of specialists

are “wheeze” and “rattle” given not as symptoms but as medical conditions,

and these, allegedly, go away with time. There is also a disease called “hyper-

responsive airways” strangely treated as asthma. Not uncommon is the diag-

nosis of alveolitis, although it is a totally different immunological

degenerative disease of the lungs, mostly found in an occupational setting

and caused by repeated inspiration of organic particles (such as pigeon



breeder’s lung). One thing is definite though: the innovative terminology that

creates new diseases improves the asthma statistics.

Some allergists and respirologists try to explain the statistical rise in

asthma as being ‘over-diagnosed.’ “There is now a trend towards over-diag-

nosis,” say two authors, one of whom is director of the Toronto Asthma

Centre and president of Canadian Network for Asthma Care, Dr. K.

Chapman.17 In these authors’ opinion, another disease “must always be

considered when treatment fails.” “If it is not asthma, what could it be?” asks

the article rhetorically and answers: emphysema, left ventricular failure,

angina, cystic fibrosis, localized obstruction, vocal cord dysfunction, etc.

How plausible is it? First, the common frequency of asthma compared to

the rarity of the other named diseases increases the probability of asthma

being the correct diagnosis. Secondly, emphysema is a disease that results

from lasting and severe asthma or long-time smoking. This excludes emphy-

sema as the diagnosis in young children, the fastest growing group of asth-

matics. Similarly, angina should also be very low on the list of possibilities in

those who are under 40. Ironically, the authors do give an involuntary expla-

nation as to what lies in the origin of these symptoms at the beginning of

their article: “Despite an improved understanding of asthma and the many

new treatments available for its control, a surprising number of patients

appear refractory or unresponsive to the best management.” Evidently, impo-

tence in the management of the most prevalent chronic disease of our time

prompts the medical profession to conveniently break it down into several

allegedly different conditions, and by that remove the responsibility of recog-

nizing the ineffectiveness of treatments.

The internationally known authors of the book Asthma Epidemiology

write on page 9: “Virtually all reviewers have concluded that the increases (in

asthma mortality) are real and are not solely due to changes in the diagnosis

or classification of asthma.”18

The non-wheezing form of asthma, or the one without shortness of breath,

may present some diagnostic difficulty. Still, with the officially recognized 10%

among adults and 15–20% among children, every general practitioner has a

fair number of patients with similar symptoms and must therefore detect the

disease even in its non-classical form. A patient of mine treated for asthma

immediately understood that her six month old son was also asthmatic when

doctors in ER diagnosed “croup” and gave him a ventolin mask. Croup is an

acute obstruction of the larynx due to infection (the child did not run a high



fever), new growth or a foreign body. The boy’s mother understood that it was

asthma simply because he was prescribed a bronchodilator—as usual, “to

breathe better.” One may only ponder why a medically illiterate woman could

use her previous personal experience and diagnose the illness better than those

who had studied the subject for years, and whose practice included a high

percentage of asthmatics. Most probably the explanation is simple: if you diag-

nose a disease, you have to treat it effectively. As physicians fail with asthma,

they, consciously or subconsciously, avoid the diagnosis. In other words, when

they hear trotting, they think of zebras instead of horses.

THE DIAGNOSTIC TESTS FOR ASTHMAIn general, conventional medicine relies too heavily on measurements and

mathematics in diagnostics, and it does so with asthma as well. This is

contrary to what the main medical textbook, Harrison’s Principles of Internal

Medicine, teaches: “It is difficult to establish the diagnosis of asthma in the

laboratory, for no single test is conclusive.”19 Let us discuss why all diagnostic

tests in asthma are unreliable.

Pulmonary function testing measures the lung capacity and pattern of

ventilation. It consists of a deep inspiration followed by an expiration into a

device called a spirometer. The findings can be inconsistent because lung

function is not impaired in mild asthma and is often also preserved in

moderate asthma. Therefore, poor air flow may show only in a period of exac-

erbation. Even severe asthmatics may have normal air flow measurements in

remission. When used for diagnosing, normal testing parameters (not an

uncommon thing in asthmatics) only confuse. The patient is told that he does

not have asthma, which can make him feel psychologically happy, but be

puzzled as to what causes his recurrent cough and chest discomfort. Allergists

and respirologists recognize the diagnostic deficiency of these tests but still

conduct them even in cases of definite asthma, which only adds to the cost of

asthma management but does nothing for asthma patients. Logically,

pulmonary function testing should be used with discrimination, only in cases

of a difficult differential clinical diagnosis.

The daily measurements of peak expiratory flow through a portable device

are a version of pulmonary function testing and are recommended to every

asthmatic. Regrettably, this test is too often used as diagnostic means, despite

it being helpful mainly in adjusting the dose and type of medications. As the

majority of asthma drugs are notorious for their side effects, the flow meter

may allow the patient to self-reduce the dose if the air flow improves.



Inhalation bronchial challenge test is another diagnostic procedure, and

quite an aggressive method of determining hyperreactivity of the airways

with the help of a spirometer. The patient is asked to inhale histamine (or

metacholine) or a suspected allergen/trigger to provoke an asthmatic attack,

after which the airway obstruction is measured. This test is used by allergists

and respirologists only in specialized asthma centers, since the patient may

require resuscitation.

You may wonder why the inhaled histamine provokes an attack, whereas

being injected, it relieves the symptoms. Surprisingly, even certified allergists

are unable to answer this question. For example, the only expert witness asked

by the CPSO to assess my work during my trial, Dr. A. Knight, a professor at the

University of Toronto, was unable to answer as well. This means that allergists

cannot explain the similar phenomenon with allergenic: extracts the use in

immunotherapy: inhaled dust mites trigger symptoms, whereas dust mites

extract is used in allergy shots to improve the symptoms. The reasons for the

two opposite effects, be it histamine or an allergen extract, are as follows. A

small dose of injected histamine (or a well matched allergen extract) comes into

direct contact with the immune cells and corrects their work by gently stimu-

lating the H2/3 receptors. It is different with inhaled histamine or a potentially

offensive allergen given in a large dose. They go directly into the disease-stricken

organ, lungs which is already enveloped in allergic inflammation. There, they

trigger predominantly the H1 receptor effect and thus intensify the symptoms.

This explains why the bronchial challenge test with histamine may result in a

serious attack, even death, whereas histamine injections are curative. The lack

of understanding of the dual nature of histamine and knowledge that it can

only provoke asthmatic attacks upon its inhalation resulted in declaring hista-

mine as nothing but dangerous.

Skin testing is not exactly a test for asthma diagnosis in today’s clinical

medicine, whereas it could become one of the most sensitive tools for this very

purpose. Conventional allergy skin testing is used to establish specific IgE anti-

bodies to the trigger(s) given in pricks in order to find “what you are allergic

to” although, even in this, as was said in the chapter on skin testing and

immunotherapy, AST is not reliable. In fact, monitoring systemic reactions can

provide reliable evidence for asthma if patients are tested during a sympto-

matic stage. Change in the breathing patterns before and after the pricks would

indicate asthma because symptoms of bronchitis or pneumonia do not

respond to the skin challenge with histamine or allergens. With systemic reac-

tions left unobserved, and histamine pricks given simultaneously with



numerous allergens, the diagnostic value of standard allergy skin testing in

asthma is almost zero. Not only is skin testing more accurate than other tests,

but in many cases, it also provides a gentle challenge followed by improve-

ment, unlike the dangerous provocation of an asthmatic attack in bronchial

challenge testing.

WHAT IS RELIABLE IN ASTHMA DIAGNOSTICS?In the absence of reliable laboratory findings, a thorough medical history

becomes the basis for asthma diagnosis, while tests can only support it,

when needed.

Family history is an inherent part of the medical history. The hereditary

factor in asthma origin is confirmed by its clustering in families. Therefore,

the family history should cover not only the parents, children and siblings but

also more distant relatives—grandparents, uncles, aunts and cousins.

Allergies and asthma may skip a generation or a group of immediate relatives,

though still be carried in the faulty genes. Often, adult relatives (who are

symptom-free) of a young asthmatic do not know about their hidden defect

and thus consider themselves to be allergy-free. This is why an inability to

trace asthma in the family history does not rule out its genetic roots. As with

any allergic disease, the family members may not necessarily have asthma but

another allergic or related condition due to a similar immunologic error. To

elicit the essential facts, it is imperative that doctors know the common roots

of allergies and borderline diseases and ask relevant questions.

Asthma is striking younger patients more often than ever before, and chil-

dren are diagnosed with asthma at a much earlier age than their parents were.

This can be explained primarily by the naturally growing number of people

who inherit flawed genes from their parents. It is only natural to expect the

defects to be increased in the kids who have both parents with such genes.

Another factor that explains the rise of asthma among children is the well

documented innate progressive mutation of the genes defined by basic science

as spontaneous or natural. Accumulating adverse environmental effects

contribute to earlier manifestation of the disease.

The clinical picture is most indicative for the diagnosis. It may include one

or all of the following: cough (especially nocturnal), shortness of breath

and/or wheezing upon exercise or exposure to a pet, house dust, smoke, cold

air, etc. Co-existing allergy symptoms such as eczema, chronic or recurrent

nasal congestion, migraine headaches, constant or intermittent unexplained



tiredness or hyperactivity—all point to asthma rather than a cold. The

volatility, long duration, and recurrence of the symptoms prompt the diag-

nosis of asthma and exclude an infection—especially so, if they are not accom-

panied by a high temperature. Low-grade fever may also be a manifestation of

an accompanying neurological symptom, temperature dysregulation, and not

a sign of an infection.

The leading medical textbook, Harrison’s Principles of Internal Medicine, in

defining what is required for accurate diagnosis states in Chapter 1, “The

Practice of Medicine”: “Each item of data must be interpreted in the light of

what is known about the structure and function of the involved organs(s).

Knowledge of anatomy, physiology and biochemistry must be combined into

a plausible pathophysiologic mechanism.”20 The sad truth is that the conceal-

ment of the true mechanisms, which underlie asthma, has made physicians

ignorant in this area, and this prevents them from asking patients questions

relevant to the main disease and from properly interpreting the accompa-

nying symptoms. This is the reason why asthma remains too frequently undi-

agnosed, and the accompanying, allergy-related, often nonspecific symptoms

are diagnosed as a separate disease.

ELIMINATION AS TREATMENT OF ASTHMA Let us assume that asthma is diagnosed. What should the management of this

immune disease start with? Correction of the faulty immune mechanisms,

would say a knowledgeable doctor. Trigger elimination, says conventional

medicine. What to eliminate? Everything. House dust mite has always been

the main culprit. Then come pets, and parting with them tends to result in

broken hearts. Yet, it is true that many people, especially children, are

prepared to suffer but not to give away their beloved dog or cat. Next come

foods that need to be eliminated, and usually it is the most delicious.

Am I against trigger elimination? Not at all. If there is an evident sole

trigger, avoid it. However, it is next to impossible to eliminate triggers such

as house dust mite or pollen. Even if you are lucky enough to succeed, the

next day, you may realize there is yet another trigger for your symptoms,

which is even more difficult to avoid. An asthmatic attack may also occur

spontaneously, and you may not be able to figure out what triggered it, or

your symptoms may intensify without any change in the environment, food

or habits. The reason may well lie in the fact that, while you are chasing the

offenders, the disregarded primary ‘crack’ in you immunity deepens.



“The western societies’ questions about the role of atopy (allergens) in

asthma sound almost absurd,” states the editorial with the self-explanatory

title—“Is asthma really linked to atopy?” The author of this observation, E.

von Mutius, an expert in asthma epidemiology, discusses the contradictory

figures of IgE-mediated asthma in various countries and concludes with:

“Such reflections are not of purely philosophical interest, but may well help

us to understand why current paradigms of, for example, allergen avoidance

strategies aiming at reducing atopic sensitization, have failed to prevent the

development of asthma.”21

Paradoxically, elimination as the core of allergy treatment (confirmed by

numerous studies) peacefully coexists with the ideas (also confirmed by

multiple studies) that asthma rates are higher in regions with good outdoor air

as well as among families with high cleanliness standards. Some researchers

even dare to suggest that, it is a lack of exposure to allergens that plays the deci-

sive negative role in the development of asthma, and the presence of a cat in

the house is actually associated with a decreased risk of asthma, especially in

young children.

THE SEARCH FOR ASTHMA CAUSESTo know the origin of asthma is to be able to treat it. Allergy medicine obvi-

ously failed to find the cause(s) of asthma in the environment, otherwise why

would Dr. L. Lichtenstein write that “the incidence of asthma and the number

of deaths it causes surged by more than 60 percent in the 1980s. The reasons

for the rise are mysterious. Hypotheses to explain the overall mortality figures

range from overuse or ineffectual use of bronchodilators to an increase in

environmental pollutants and allergens.”22 Asthma figures are so frightening

in children, and especially among teenagers, that the World Health

Organization formed a program called ISAAC, The International Study of

Asthma and Allergies in Childhood, which conducts epidemiological studies.

While this effort is commendable, the problem remains: allergists look for

causes outside the body, and the wider the scope of their search, the further

they are from the true inner causes of asthma.

The strangest thing is that the findings of a general science called connec-

tionism is closer to understanding asthma origin than the specific medical field

devoted to the disease. Connectionism studies various things and phenomena

not in isolation but in their complexity, as systems with multiple tasks: the

inner causal connections, self-regulation through excitatory or inhibitory



processes, and the “learning” patterns, that is, how the system adapts and

changes in order to restore its ability to self-regulate. The orientation of

connectionism is that “causality forms the basis for scientific understanding.”

Although this general science does not provide the answer to what causes

asthma, it correctly points that: “asthma is a fault in the activation pattern of

the body’s self-regulatory network, and this fault is causally prior to the known

inflammatory mediators.” Asthma is “a breakdown in the efficiency of that

part of the network controlling inflammatory self-regulation in the lung” that

“gives rise to the inflammatory mediators,” while triggers are exacerbating or

risk factors only. Correct understanding of the causative mechanisms, enables

connectionist theory of asthma to name the “regulation of the internal envi-

ronment” as the treatment target, and it predicts that “if asthma is, in essence,

a form of faulty learning within a network, then asthma can, in principle, be

cured.”23 If a general science looks at asthma as the disease with internal

causes, why do those who specialize in asthma look for external causes?

The title of the article written by the world’s leading experts in asthma

epidemiology cited earlier—“How much asthma is really attributable to

atopy?”—is proof that allergy concentrates on the wrong aspects of the disease.24

This article, as well as a number of others are written primarily by the same

group of researchers from New Zealand, who also wrote Asthma Epidemiology.25

The book summarizes hypotheses of asthma origin. The search concentrates on

triggers and risk factors that remain speculative. Both the book, and the article

that refers to the statistical investigation among 13–14 year old asthmatic chil-

dren from 42 countries,26 reveal that the most striking figures are especially

characteristic for English-speaking countries. Reading that, one inevitably starts

to wonder what evil role the English language plays in the course of asthma.

Does it mean that French-speaking Canada should have lower rates than the rest

of the country? Are asthma statistics lower in New Mexico and California where

a large part of the population speaks Spanish? Why does India, with English as

an official language, have one of the lowest asthma mortality figures of all coun-

tries included in the study? What is the mysterious link between the English

language and asthma in such geographically, climatically, culturally and other-

wise different countries such as New Zealand and United States? Indeed, one of

the world’s cleanest countries, New Zealand, with its mild climate differs greatly

from the United States, with its wide range of climatic zones and various degrees

of pollution in different areas. How to explain the fact that China, Algeria and

India, countries where there is hardly any law enforcement with respect to envi-



ronmental pollution, show mortality figures from asthma 20 or even 60 times

lower than Australia and New Zealand? Beasley’s research does not provide the

answers.

Asthma Epidemiology states that even such a hazardous factor as smoking

does not directly affect asthma occurrence and severity. Thus, China with its

overwhelming number of smokers is at the lower end of the official scale. All

this challenges the generally accepted views on the direct effect of environ-

mental pollution upon asthma figures and forces the authors of the book to

admit that “air pollution is not a major risk factor for the development of

asthma.” These confusing data question the practice of trigger elimination as

the main trend in asthma management.

The book also dismisses race as a possible explanation for asthma rates.

Indeed, tracing of the genetic roots in a major part of the population in such

multi-racial countries as United States or Australia would inevitably lead

investigations to Easter Europe, China or India in which asthma prevalence,

severity and mortality are incomparably lower according to official figures.

Asthma Epidemiology only presents various hypotheses as to what coun-

tries with high asthma rates might have in common. I will suggest my own

opinion based on the facts about what English-speaking countries share with

respect to these tragic figures.

WHAT AFFECTS ASTHMA STATISTICS ?First of all, we should distinguish two things—incidence and morbidity/

mortality. Higher than average incidence of asthma in the countries such as

New Zealand, Australia, Ireland and some smaller islands can be explained by

their isolation in the past and hence, smaller groups participating in the

genetic exchange. In such circumstances, the offspring had higher chances to

get defective genes from their parents and have genetically related diseases,

including asthma, just as inbreeding produces defects in pedigree animals.

Severity and death rates in asthma, however, belong in a different category.

“Civilization” has undoubtedly brought things that undermine the

immune system. Paradoxically, many of them are means to improve the

quality of our lives, save time and effort: air humidifying and dehumidifying,

food preservation, acceleration of cattle and poultry growth, tooth whitening,

breath freshening, pesticides, etc. In our haste, only the immediate effect

matters. Therefore, the fact that the improvements might, in the long run, lead

to severe consequences has always been of minor, if any, consideration for



consumers and even the medical profession. These improvements are desired

by the governments and industries as revenue-generating factors, and they are

highly advertised and supported by government policies.

Among the powerful consumer goods proclaimed to improve our lives,

medications are of immense importance. They inundate the market in all indus-

trialized countries. The high living standard there allows every person to resort

to these drugs even if the discomfort is mild. A painkiller? Here it is. An antibi-

otic? No problem. You are going through a family problem and having trouble

sleeping? The best remedy is a sleeping pill and/or a tranquillizer. Vaccination is

now available even for the non-life-threatening chickenpox. Our immunity no

longer has to develop naturally. The drugs will do the work instead. Side effects

may show up in the future, moreover, the cause and the effect may be stretched

over time for years or decades and will be hard to trace and prove. The pharma-

ceutical industry’s main role is to please the consumer and temporarily relieve

the symptoms, not to heal, as it falsely claims. To capture a customer, it uses

seductive advertisement. Just listen to the TV ad offering a medication that

allows one to get rid of toe-nail fungus. The sweet voice encouraging you to buy

the medication inspires such a strong desire to have beautiful nails that liver or

kidney damage listed at the end as possible complications sound almost like a

reward. In other words, drugs have become a commodity and, paradoxically, one

of the most potent health-aggravating factors.

The birth country of the drug industry is Germany. However, being defeated

during the war, it lost its priority in this area, and England and the US took over.

It is only natural that the companies opened their branches in developed

English-speaking countries. The largest of them made the US neighbor, Canada,

their stronghold, and also stretched their tentacles to other industrial colonies,

dominions and territories of the Commonwealth. And here comes the feature

common to all countries with the highest asthma figures—England, US, New

Zealand, Australia, Canada, Ireland: they are connected to the pharmaceuticals

industry like a child to its mother by the umbilical cord. All these countries are

industrially advanced and their well-off citizens are able either to pay for the

drugs out of their own pocket or through the generous insurance plans. The

populations in those countries abuse drugs from an early age. Medications are

prescribed at the slightest sign of any discomfort, and an asthmatic can resort to

the “best” remedies the moment he produces his first cough. In contrast, in

India, although English-speaking, the percentage of the poor population is too

large, and the social system of the country is unable to distribute these remedies



for free. Ironically, India’s poverty saves its people from the overwhelming

morbidity and mortality caused by asthma in developed countries.

Drug production in European countries lagged behind that in the rich

North America, and the opposition to the ‘foreign intrusion’—drug

imports—delayed the consumption there. The highly unsafe medications for

asthma were therefore introduced in Europe later and at a slower pace, and

this positively affected the asthma morbidity and mortality rates. The asthma

figures in the former East Germany and West Germany may serve as a

comparative example: in the heavily industry-polluted East Germany, asthma

rates were paradoxically much lower than in its cleaner neighbor but have

inexplicably started to rise lately.

In my opinion, the aggressive medicalization of the population is the

central factor uniting the countries with the highest figures of asthma

morbidity and mortality. My assumptions are supported by a leading profes-

sional, Dr. W. Busse, the 2001 president of AAAAI. He blames conventional

medications for the morbidity: “It is estimated that about 5% to 10% of

patients with asthma have severe disease that is recalcitrant to typical treat-

ment modalities, including administration of systemic corticosteroids.” This

“may occur as a result of …chronic exposure to beta-agonists or corticos-

teroids.”27 “A recent report from the Centers for Disease Control and

Prevention stated that the prevalence of and mortality due to asthma continue

the upward trajectory that was begun more than 15 years ago,” says another

article from the same issue of the leading immunological periodical.28

We are witnessing a dramatically growing morbidity of asthma accompa-

nied by the development of chronic conditions. The process is in parallel with

the use of bronchodilators in the past, and now continues in parallel with the

growing abuse of immunosuppressive corticosteroids that started to be aggres-

sively advertised in the mid eighties. This is confirmed by the first-class source,

an article written by researches from the National Institutes of Health,

Bethesda.29 The authors investigated what factors make immune-related

inflammatory diseases resistant, and say that corticosteroids modify the clin-

ical phenotype and worsen the course of these diseases. Under phenotype,

science understands the entire physical, biochemical and physiological

makeup of an individual as determined both genetically and environmentally.

In other words, a person formerly responsive to medications becomes resistant

due to the consumption of the most common asthma medications. Is this not

a direct recognition of the danger of these medications?



Admissions of this kind are done rarely and mainly in purely theoretical

articles, with no proper conclusions (such as: let’s give up on such medica-

tions), with no solution (which the authors mostly do not know). The public,

including the medical profession, must not be disturbed. No high profile

specialist has ever raised (or will raise) the question why, despite the fact that

these drugs “have been available for the treatment of asthma for almost 50

years and are still the most effective medication for this condition,” “informa-

tion about their effects in vivo is limited.”30

The lack of data on the complications of these highly prescribed medica-

tions for the most prevalent chronic disease cannot be accidental. Moreover,

since no other drug is as effective in asthma as steroids, even such occasional

admissions of their harm disappear in the ocean of steroid-supporting liter-

ature. Thus, the editor-in-chief of the Canadian Respiratory Journal started

his editorial by saying that “the most common topic in papers so far

submitted to the Journal concerns the high rate of mortality from asthma in

young people.” After having consulted with specialists, one of whom was the

world-famous Dr. M. Sears, the editor concludes that poverty and inadequate

use of steroids are the central reasons.31 Strangely, neither the editor nor

his consultant notices the obvious contradiction with the statistical data: the

polluted India and China where steroid medications are unknown to and/or

inaccessible for the majority of asthma patients lag behind the steroid-

advanced New Zealand and Australia in asthma mortality.

The 1993 president of AAAI, L. Lichtenstein, was once “confident that the…

pharmaceutical and biotechnology industries and academia will help resolve

these issues (effective and safe drugs for asthma) to a significant extent within

the next few years.”32 We do not see it happening now, a decade later. Judging

by the almost universal switch to steroids and the massive inappropriate use of

antibiotics for asthma during the last two decades, the drug industry only serves

itself, and academia faithfully serves the industry. The industrially advanced

English-speaking countries lead the trend and the rising statistics.

PERSONAL IMPRESSION ON THE OFFICIAL STATISTICS IN ASTHMAMy recent visit to India made me question some of the data in the book

Asthma Epidemiology. Seeing asthma patients every day, I have a good idea of

how asthma sounds, and in India, I heard almost everybody around coughing

a phlegmy cough. With the temperature in the soaring 30°C+, it was hard to



suspect an epidemic of a flu or pneumonia. My interest prompted me to talk

to a dozen of people, mostly young non-smokers, and I learned that many had

shortness of breath, wheeze and typical accompanying symptoms such as

allergic rhinitis, itchy skin, headaches, etc. They also had family members with

similar symptoms. None of those I talked to had seen a doctor and hence, the

had not been diagnosed as an asthmatic and included into the official data.

This confirmed my suspicion that the official statistical figures were unreliable.

I am sure that that the asthma incidence in India is underrated. My expe-

rience tells me the same is true in other third-world countries. However, we

should distinguish incidence, which may be higher in polluted countries, and

mortality that may really be much lower there than in the first-world coun-

tries—exactly what we see today. There are reasons for the discrepancy

between the reality and statistics. Densely populated India does not have a

government-funded medical insurance system that could create a flourishing

drug market, and the drug industry is not going to supply its products for

free. “The total cost of asthma in United States was estimated to be $4.5

billion in the mid-80s, whereas in the first half of the 1990s, the estimate

increased to a range from $6.2 to $10.7 billion.”33 If the US suffers from the

economic impact of asthma, a country like India would simply be crushed

under such a financial burden. I am not aware of the source of the distorted

figures that appear in the books and articles, but it is apparent that the greatly

belittled asthma prevalence in the third world countries conceals both the

scope of asthma and the urgency to treat the sufferers. This satisfies the

governments and allows international medical bodies and the pharmaceutical

enterprises to save face instead of saving patients. The positive side of this

perverted situation in allergy is that without conventional drugs, which even-

tually do more harm than good, asthmatics in poor countries live longer.

In 2002, I found a confirmation of my ideas in an article written by a

professor of pharmacology at London University in the UK. “Prior studies in

near-fatal asthma have suggested that a contributing factor may be inadequate

access to health care; however, the study by Mitchel et al. would suggest this is

not true. In fact, the index cases had more contact with health-care systems

than the control subjects, especially asthma specialists.”34 This is a straightfor-

ward admission that those who regularly see specialists have near-fatal asthma

more frequently. And it is not a secret that specialists are more aggressive in

prescribing “effective” asthma medications than general practitioners.



THE IMMUNE SYSTEM UNDER ATTACKNo matter how hard we try, we cannot avoid accumulation of toxins in view

of their wide-spread use and our inability to eliminate them in the food, air

and water. One lifetime will not be enough to fight all the industrial giants

that pollute the environment, while our deeply corrupted governments delay

the introduction of laws that could make the environment cleaner. Is there a

way out? In this grim situation created by our civilized world, there is only

one immediate and inexpensive way out: a helping hand extended to our sick

immune system so that it can regain its fighting ability. The human body tries

to adjust to this growing pollution. Of course, environmental hazards may

eventually destroy it, and for now they seem to promote various chronic

diseases, including diseases of hypersensitivity. However, the combined

impact of the pollution from outside and the abuse by medications acceler-

ates the damage. The much lower asthma mortality in countries with the

highest environmental pollution and the lowest drug consumption is

irrefutable evidence.

THE CONFUSION GROWS No other chronic disease can beat asthma in its growth rates. It has also become

a champion among all existing chronic diseases in morbidity and mortality,

while among children, the figures quadrupled since the late seventies. This is

because modern medicine never targets the prime events. “Strategies aimed at

secondary prevention would reduce morbidity and mortality,” states Foreword

in the prestigious journal, the Lancet.35 The article admits that patients would

like asthma to be prevented or cured, but “neither is likely to occur unless we

understand why people develop asthma.” One would think the author would

suggest studying the cellular mechanisms that underlie the disease. Not at all.

She suggests “focusing on epidemiological factors rather than genetic factors

…(as) they may be more amenable to manipulation.” Thus, the search for the

true asthma causes is bypassed again. This approach has led to the proliferation

of numerous irrelevant theories seriously discussed by allergists and delivered

to the public by the media. So mind-boggling and contradictory are they, that

at least some of them should be presented to the readers, so they can arrive at

their own judgment about them.

A popular hypothesis on asthma/parasite relationship was suggested in

1979 by A. B. Kay, a co-editor of the journal Clinical Allergy and Immunology.



L. Lichtenstein, also referred to the absence of parasite infestation or parasite

“infections” as the cause of asthma in his article in Scientific American36 in

which he states that allegedly, “in the response to both allergens and parasites,

the body produces high quantities of molecules known as immunoglubulin E

(IgE) antibodies.” Conventional allergy research presents IgE antibodies as

the main indicator of allergy, but also as a defence mechanism against para-

sites. This is what is going on in the body, according to allergy moguls Kay and

Lichtenstein. We inherit the immune system geared to fighting parasites but,

unfortunately, now, when the civilized world successfully cleans the body, we

are clear of them. So, we must suppose that the immune cells, not used to

idling, busy themselves with creating IgE to innocent substances. (Should we

assume that this is the reason of the statistically low asthma incidence in para-

site—infested third-world countries?) To the credit of Dr. Lichtenstein, he

admitted that animal studies in this respect were inconclusive and thus left

the relevance of the hypothesis up for speculation.

In the nineties, it has become a part of the highly elaborated hygiene theory

by the Italian researcher S. Romagnani. “Eppur si muove!” is the title of his

article which uses the famous phrase ascribed to Copernicus in relation to the

Sun/Earth relationship; he supposed to have said to his prosecutors about the

Earth, “And yet it does move!”37 In other words, in the chaos of ideas on the

origin of allergies, Romagnani’s concept, which included the worm aspect, has

proclaimed that idea of cleanness (including “wormlessness”) is central in the

origin of allergies. Numerous allergists picked up this idea that has conquered

the minds of many. Thus, Dr. Weiss, a Harvard University professor, published

an article under the title: “Parasites and asthma/allergy: What is the relation-

ship?”38 He wrote that “individuals who are genetically the most resistant to

helminthic infection may be the ones who have the most severe allergy and

asthma in its absence.” This makes worms look more attractive, and asth-

matics, or at least those with a severe form, may start seriously thinking about

acquiring parasites instead of gasping for air. (Just imagine how damaging the

concept of parasites could become for the fast developing industry that offers

various remedies to cleanse our bodies, which are allegedly full of worms!)

Still, the absurdity of the idea is such that after his extensive deliberations, the

Harvard professor is forced to conclude that “decrease in helminthic infection

cannot be seen as causally related to the asthma epidemic,” although it may

“help to explain how other environmental exposures are contributing to the

increased asthma burden in Western industrialized countries.”



Nostalgia for the good old times when parasites and real infections, as

counterbalance to IgE antibodies, were accessible to everybody still enjoys

overwhelming recognition among scientists. The Cambridge University

pathology professor, Anne Cooke, suggests developing an extract that would

play a trick on the body: it will chemically imitate a worm and thus cause

positive immune responses. In the Canadian newspaper The Globe & Mail on

May 17, 2001, I read about another believer in such ideas, professor Koichiro

Fujita of Tokyo Medical and Dental University who had implemented this

idea in real life. He had suffered from hay fever and, encouraged by the

worm/no-allergy hypothesis, had consumed three kinds of worm eggs to find

relief. The inference one can draw from all this is that, being unable to

perform immunomodulation, allergists should hand their jobs over to para-

sites. Surprisingly, the conclusion that exposure to infections, dirt and worms

is allergy-protective, co-exists with the generally accepted and heavily dissem-

inated ideas of the need to eliminate/avoid all potential environmental trig-

gers. The contradictions are overwhelming.

Numerous articles discuss hypotheses forwarded by different researchers

but leave them as speculations. One idea is that “large head circumference at

birth is a risk factor for subsequent development of asthma.”39 The conclu-

sion here is that this “intriguing finding” may be associated with mothers’

higher nutritional habits that affect “programming of the developing

immune or respiratory system, predisposing to the subsequent development

of asthma.” So, better and more abundant maternal nutrition is supposedly

the cause of asthma.

Another article assumes that “a small family size (is) associated with an

increased risk of development of asthma.” According to the researchers, large

families have a chance to avoid asthma because natural infections, some of

which may protect against asthma, are transmitted among the siblings,

whereas an only child is protected from contamination through low contact

with other children. Asthma Epidemiology refers to researches that name

several infections allegedly incompatible with asthma. For instance, “positive

tuberculin responses have been found to protect against atopy (allergy) in

Japan, and hepatitis A infections were found to protect against atopy in Italy.”

It simply means that those who have tuberculosis and hepatitis A do not

develop asthma. The author refers to another team of scientists who

concluded that “measles infections have been found to protect against atopy

in Guinea-Bisseau,” and therefore “it is also possible that immunization may



contribute (!?) to the development of asthma and atopy.”40 This assumption

actually questions government-enforced plans of massive immunization of

the global population, since it would be better to suffer once through measles

or hepatitis A, than to suffer life-long from asthma.

I cannot resist the amusing notion that the one good thing about all these

hypotheses is that they are democratic. In Soviet Russia, where I came from, if

a person had asthma, he had to live with it all his life. In a democratic society

we have the choice of hepatitis A, tuberculosis or parasites instead.

The role of respiratory infections in asthma is another highly debatable

question. The views are so conflicting that in one and the same paragraph of

an editorial in the most prestigious journal, we read that infections “may

cause asthma,” but “as a whole (they are) probably protective against the

development of asthma.”41 In an interview, Dr. Andrew Saxon, the chief aller-

gist at the UCLA Medical School, dwelled on the idea that during infections,

the immune system learns to identify the attacker and eliminate it when it re-

enters the body. Nowadays, with fewer infections, the body looks for another

target and attacks the more benevolent environment. This again raises the

idea of the need of vaccination: if it predisposes children to allergies, then, by

vaccinating our children, we consciously expose them to the potential of

developing various allergies, including the potentially fatal asthma. I have not

read any practical suggestions in this respect made by allergists.

Asthma Epidemiology refers to the work of scientists who consider higher

family income and “overly hygienic condition in early life” among high risk

factors. The authors of the article published at the same time go even deeper

in their conclusions: “contamination from maternal microflora along the

birth canal could be an advantage.”(?)42 That article makes a further specula-

tion: “increasing maternal age decreases the risk of asthma and particularly

allergic rhinitis.” This concept obviously contradicts the reality: nowadays,

women in the first-world countries where asthma figures are especially high

tend to get married later and therefore have children later. If this should lead

to the reduction of asthma rates, why do we observe the opposite?

In general, the tendency to diminish the key role of genetically-driven

immune-related defects and factors in allergies and asthma and to turn the

attention instead to questionable contributing events becomes more and

more pronounced in the works of numerous authors. Even the scientist with

encyclopaedic knowledge in allergies, such as Stephen Holgate, states that

“Release of histamine… account(s) for most of the early- and late-phase



responses,” and that mast cells’ histamine releasability supposedly lies in the

origin of allergic reactions. Although the author knows very well what

compromised immune mechanisms make these cells leaky, he does not say so.

Instead, in the very same article he points to environmental allergens as the

central factor and names supposedly “new (?) allergens such as nuts, soya and

latex.”43 If latex can rightly be considered as a recent industrial product, nuts

and soya seem to have existed from time immemorial. We can only speculate

why they have suddenly turned into potent allergens, and what made the

immune system react viciously to them.

Here is another example of looking for the causes of asthma outside the

body. With bewilderment, one reads in a leading periodical in the section The

New Millennium: Conquest of Allergy, that “lifestyle factors relating to the

socio-economic status of a population or a family, its size, and the number of

siblings of a given individual,… early childhood infections with viruses and

bacteria, and a subject’s dietary habits” account for the high incidence of

allergies, while “genetic factors are unlikely to explain” the prevalence of aller-

gies.”44 Medicine has come to the point when genetic predisposition to

chronic diseases, well established a century ago, is almost completely

discarded. Strangely, it is genetics and not the environment that is highly

recognized in the breeds of our pets. Allergy tries to create picture that will

more easily fit into the frame it has created. This position is dangerous and

has its precedents. In Stalin’s Russia, genetics was also officially disregarded,

which led to the degradation of science and perishing of its supporters in the

Gulag. Shouldn’t we learn from the past?

The article, to which we referred earlier, contains more surprises. One of

them is that “out-door pollution of sulphur dioxide…, diesel exhaust” are not

causally related with allergies. In other words, there is no need to fight for

clean air. The other surprise is that “passive smoking has convincingly been

shown to increase the risk for asthma and bronchial hyperresponsiveness

among exposed children.” This does not correlate with the findings presented

in Epidemiology of Asthma, written by the same author, that “the lowest preva-

lence of asthma was observed in the community living in mainland China,

despite the highest level of cigarette consumption.” Now that tobacco compa-

nies are forced by the courts to pay for the casualties they have caused with

their products, they have the unexpected support from allergists and may

suggest that eliminating second hand smoking is unnecessary, so everyone

should be an active smoker. Will this reduce asthma incidence in the first-



world countries to the officially recognized low level in China? The paradoxes

of allergy in the new millennium!

Along with the growing number of articles on the advantage of early-life

exposure to common inhaled allergens, the popular dogma still reigns that dust

mites, pet dander and cockroaches remain the key factors in asthma. Thus, the

already cited article states that “early-life cockroach allergen exposure at 3

months of age predicts” activation of pro-inflammatory T-cells (helpers) and

hence, asthma. The word cockroach is even given as a key word to the article.45

In general, the allergen/IgE-based theory “became a citation classic,” as is

still believed by a world renowned North American allergist and respirologist Dr.

D. Cockroft. In a recent article, the author claims that asthma is caused (not trig-

gered) by allergens: “IgE-mediated airway inflammation is, perhaps, the most

important cause of airway hyperresponsiveness in asthma.”46 Dr. Cockroft calcu-

lated that a “classic” paper written 23 years before by himself and three other

Canadian specialists had been cited almost 800 times proving by that that this

hypothesis on the origin of allergies and asthma is immortal. All of this despite

the epidemiological evidence that ”the population-based proportion of asthma

cases that are attributable to atopy (allergy) is usually less than one half,” that

“there is a component to the ‘asthma syndrome’ which is not related to atopy.”47

I would suggest, however, that if more than half of asthma cases are allergen/IgE-

unrelated, it is high time to reconsider the classical but unfounded concepts.

An American critic Eric Bentley once said: “Ours is the age of substitutes:

instead of language we have jargon; instead of principles, slogans; and instead

of genuine ideas, bright ideas.” Allergy is full of bright ideas on the origin of

asthma. Contradictory and confusing, they peacefully co-exist, and nobody has

made a critical review that would select the ones, which are scientifically sound.

This creates real chaos, and in such a situation, the conquest of allergies is

unlikely. The truth—the genetically mediated malfunctioning of immune

cells—drowns in the ocean of inconsistent hypotheses, controversial data and

collateral events. Instead of studying the faulted immune mechanisms and

attempting their correction, immunologists look for numerous triggers of

symptoms. Millions of dollars are wasted on investigations, at times laughable

in their essence, on the role of unsubstantiated factors upon the occurrence of

allergies and asthma. Research that distracts from the core of the problem

receives unrestricted grants from the drug industry, and the results are

published in most prestigious journals. Drug developers nurture pseudoscien-

tific hypotheses because without a concrete therapeutic target, the asthma



problem will never be solved, and meanwhile, they can continue with their so-

called pharmacologic “advances” aimed always and invariably at the secondary

events.

The bleakness of the asthma reality is confirmed in the very first article

that covers the 2000 annual meeting of American allergists: “In many ways,

the epidemiology of asthma is in a situation similar to that of cancer

epidemiology or cardiovascular disease epidemiology before major advances

in understanding of the causes of these diseases in the 1960s.”48 This is recog-

nition that the knowledge of asthma lags behind even cancer.

Time has come to differentiate science from pseudoscience. It is normal

that in the course of scientific development, 80–90% of all hypotheses turn out

to be erroneous, but errors are not pseudoscience. Pseudoscience in clinical

immunology is born out of purposeful lack of access to the true information

and the resultant overwhelming illiteracy in the field. If the reasons for this

illiteracy are not exposed, we will chase cockroaches and pets in futile attempts

to curb asthma and see its ever-rising trajectory.

ASTHMA MENAGEMENT AND MEDICATIONS

BRONCHODILATORS

Asthma medications provide the best proof that allergy is operating in the

dark. Allergists make it look as if there are numerous asthma medications,

while in fact, there are actually only two groups. One, categorized as relievers

or rescue drugs, cannot be avoided by any asthmatic. The real name of these

drugs are bronchodilators—they dilate the constricted windpipe. They are

the oldest anti-asthma medications. One such agent, ephedrine, was

employed as a herbal preparation for asthma as far back as 5000 years ago in

China and is still recommended for use by herbalists, though restricted by

conventional medicine. Strangely, it is incorporated into various unrestricted

decongestants and combo medications such as Claritin Extra. In the past,

different tinctures, plant extracts, and even inhalation of morphine and mari-

juana were used for that same bronchodilating purpose.

At the end of the nineteenth century, another fast-acting agent, adrenalin,

came into practice. It is a synthetic analogue of a hormone produced by adrenals.

Adrenalin is similar in action to ephedrine but has a much stronger effect. Both

substances are still in use, although with the advent of the drug industry, other

remedies have appeared on the market. At present, different types of bron-

chodilators—inhaled, injectable and oral—exist. Some provide immediate relief,



some delayed, the effect of others starts only with sustained consumption. There

are bronchodilators taken in the event of an attack, others are taken on a daily

basis. All of are similar in their purpose—to open up the air passages.

Take notice: The mode of action of all bronchodilators is their activation of

the enzyme cAMP and subsequent inhibition of the release of histamine and

histamine induced inflammation promoting chemistry.49 This is proof that

the best activator of cAMP, histamine, is intentionally substituted by less

effective stimulants.

INHALED BRONCHODILATORS

Inhaled bronchodilators, although younger than their oral relatives, are the most

commonly used “relievers.” They belong in the group of Beta-adrenergic

agonists, that is, activators of Beta-adrenergic receptors that open the bronchi.

“Beta-agonists are the most widely prescribed bronchodilator drugs for the

symptomatic treatment of reversible airways disease. They alone generated

revenues estimated at US $194 million in 1988, and represent a class of drug

where the number of prescriptions is growing annually.”50 The effect of short-

acting bronchodilators starts within few minutes and may last up to 6 hours.

The spontaneity and unpredictability of asthma dictate that these rescue drugs

be carried in a pocket or purse even by patients with a mild form of the disease.

An attack—an inhalation of the magic stuff, and the patient can go on in the

majority of cases. In the past, the fast symptomatic relief created the impression

of the drugs’ safety. For decades, inhalers were recommended for use not only

during attacks but also as a preventive measure—to keep the bronchi free at all

times. Certain adversities of bronchodilators were accepted as inevitable:

dryness in the mouth and throat, trouble sleeping, restlessness, “hyperness”

(especially in children), rapid heart beats, “shakiness,” dizziness, headaches and

elevated blood pressure. However, weighing the “cons” against the “pros” was in

favor of the inhalers. They gave the ability to breathe and literally saved lives.

Not a common but possible consequence of their use is a paradoxical

bronchoconstriction—when instead of opening the bronchial tube, the

bronchi constrict. This was described in occasional cases but did not get any

publicity, although pharmaceutical compendia do warn about this possible

side effect. Like many other drugs, bronchodilators have a rebound effect:

with long-term use, they start to worsen the condition instead of improving

it. This rebound effect as a consequence of their frequent use became known



soon after their introduction. The five-fold increase in mortality rates

among their users compared to non-users was reported in the forties. Only

during the first major epidemics of asthma deaths in 1960s, did the matter

receive extensive coverage. Regrettably, only the inhalers containing high

concentrations were blamed for the casualties and not the group as a whole.

The full scope of the damage of all types of bronchodilators was not realized

until the early eighties. Only then, studies turned to all medications of this

class.

The dramatic rise of asthma morbidity and mortality hit English-

speaking industrialized countries the hardest and necessitated epidemiolog-

ical studies. Epidemiology investigates the relationship of different factors

that determine and influence the frequency and distribution of phenomena

in a defined human population. In this case, the object of the investigations

was the effect of the lasting consumption of the life-saving bronchodilators

upon the course of asthma. England, Australia and New Zealand initiated

local trials as they were the countries that had a sevenfold (!) increase in the

death rate among children between 1 and 14 years of age since the drug’s

introduction. The U.S.A. and Canada followed.

The findings shocked the medical community. “Morbidity and mortality

from asthma appear to be increasing, and it has been suggested that medica-

tions used to treat asthma are contributing to this trend,” informed an article

in The New England Journal of Medicine in 1992. These findings were based

on the unusually long (10 years) investigation period conducted in the

province of Saskatchewan, Canada. “We found that the use of. ..bronchodila-

tors... was associated with an increased risk of the combined outcome of fatal and

near-fatal asthma, as well as of death from asthma alone.”51 The facts revealed

that those asthmatics who used a placebo were much safer than the ones

treated with bronchodilators. Placebo is a dummy medical treatment that has

no specific pharmacological activity against the patient’s illness. It is a ‘sugar

pill’, in the language of lay persons, that is administered to the control group

in a scientific trial. In other words, the clinical control study concluded that

putting up with some difficulty in breathing was, in the long run, better than

to always have open airways. Therefore the countries most able to afford

bronchodilators became the victims of the drug’s accessibility.

Many of the side effects of overuse are still unknown. One of them is, the

rebound effect of bronchodilators, which turned out to be stronger and more

lasting than had been assumed. Worn out by frequent stimulation, Beta-



receptors may completely atrophy, that is, lose their natural ability to dilate

the bronchi. One day, they may not respond to the inhaler, or respond para-

doxically by constricting. This is fatal for the patient. It is worth mentioning

that all this knowledge had occasionally appeared in periodical literature

within the two decades before the catastrophe became official, but the special-

ists had been too busy with prescribing bronchodilators to read and seriously

consider the material. Those who set guidelines usually have close ties with

the drug industry and have personal reasons to keep silent.52

A further well known side effect of the sustained use of bronchodilators is that

they affect the cardiovascular system, and this may account for cardiac arrest.

Another potential grave complication is that the patient’s body may start

to produce antibodies to the receptors, and the immune system rejects them.

Finally, one complication is the finding that bronchodilators shift the

underlying chemistry in favor of allergy promoting inflammation. This

explains “the paradoxical increase in asthma morbidity and mortality associ-

ated with the chronic use of … Beta-adrenergic agonists.”53 Thus, not only do

inhalers make the body defenseless locally by paralyzing the work of the vital

receptors, but they also promote the underlying immune inflammatory

process and by that, accelerate the progress of asthma on the whole. This,

however, increases their consumption, and thereby their profitability.

Up until now, most professionals, not to mention the public, remained

unaware of all of this information. However, the declared facts were a blow to

the inhaler manufacturers. They needed to save face (and revenues) and started

to defend their products. Thus, in 1992, Glaxo Canada (i.e.GlaxoSmithKline),

the world’s largest producer of the most frequently prescribed bronchodilator,

ventolin (salbutamol sulphate), distributed a flyer thanking doctors for

prescribing it. The flyer claimed that the drug had “over 18 years of safety and

efficacy behind it.” It stated that by prescribing ventolin, doctors helped the

company to sponsor special programs, in particular, respiratory fellowships, a

career counseling program for medical students, support for symposia and the

distribution of reference materials. The flyer said, “So the next time you write a

Ventolin-no-substitution prescription, do it with confidence and pride! Both

your patients and your profession will benefit.” To tell the truth, I don’t think

that Glaxo needed to worry. Considering the current state of asthma manage-

ment, no patient can escape.

At the time of the numerous epidemiological studies in the eighties,

asthma rates in the North America, though on the rise, did not reach the



same high level as in other English-speaking countries for two main reasons.

First, Australia and New Zealand, for better efficiency, used stronger

concentrations of the aerosols than North America. Second, North America

was ahead in the aggressive introduction of steroids, the use of which

temporarily reduced the need for bronchodilators. The shocking statistics

on the link between bronchodilators and mortality necessitated changes,

i.e. cut the drug use. The conclusion was that doctors “over-treated”

patients with these symptomatic medications and disregarded the under-

lying inflammation. This gave the green light to anti-inflammatory steroids

whose casualties we have already started to count.

Ironically, despite the universal caution concerning frequent use of

inhaled bronchodilators, they have remained the most commonly (ab)used

medications. In fact, we witness the rising resistance of asthma to all conven-

tional medications, including steroids, and the need for air necessitates that

asthmatics use bronchodilators more and more regardless of their risk.

LONG-ACTING BRONCHODILATORS

Bronchodilators that possess a prolonged mode of action—12 hours—are a

fairly recent product on the drug market. Basically, they are a variation of the

short-acting bronchodilators because they merely target the same receptors.

The lasting action of the newer subgroup is due to their delayed clearance,

which means that their effect is similar to a frequent or sustained use of short-

acting type inhalers. Long-acting inhalers became front-line medications but

at the same time remained an ‘add-on’ type. Thus, the entry of serevent

(salmeterol) in the Canadian Compendium of Pharmaceuticals 2002 states that

the drug “is not a substitute for inhaled or oral corticosteroids,” and that

“corticosteroids should not be stopped or reduced.” The effect of long-acting

inhalers starts 10 to 20 minutes after inhalation, this is why the use of long-

acting relievers still necessitates the concurrent use of fast relievers for emer-

gency purposes. This recommendation simply means patients end up with two

bronchodilators instead of one, and as a result, get much higher doses.

The pharmaceutical giant, Novartis is the producer of a long-acting bron-

chodilator—foradil. Novartis is frank in describing the limitations of the

product. Its brochure states that there is no data indicating that foradil

“provides greater efficacy than or additional efficacy to short-acting” inhalers.

Among the side effects, the manufacturer lists “serious acute respiratory

events, including fatalities” and claims to be unable to determine whether



there is a causal relationship between long-acting inhalers and such acute

events. However, the dismal experience with all types of bronchodilators

seems to have motivated Novartis into discouraging the use of foradil in

patients with worsening asthma. Most probably, this drug is neither worse,

nor better than similar products from other manufacturers.

Some authors in North America have started to associate long-acting

inhalers with grave statistics of adverse reactions, as was the case with their

short-acting relatives because, in principle, these drugs have the same mode

of action: used twice daily, long-lasting bronchodilators differ from their

short-lasting relatives only by the longer duration of their effect. Their

delayed clearance may be handy in sparing the patient from getting up at

night and searching for short-acting inhalers, but both preserve the same or

similar adverse potential. Moreover, the prolonged mode of action contra-

dicts, even violates the spirit of the generally accepted guidelines worked out

in the early nineties, that warn about the danger of regularly using bron-

chodilators of any kind. “…long-acting Beta-agonists, such as salmeterol,

…have little place in the treatment of asthma if one follows the guidelines for

therapy,” concludes the article written in the early ’90s.54

In medicine today, however, everything serves the drug industry, not the

patients, and epidemiological studies on the lasting use of long-acting

inhalers may only be done if the mortality figures become outrageous. I

doubt doctors know about a study conducted back in 1992 that “found a

threefold, though not statistically significant (?!) excess of asthma deaths

among approximately 15,000 patients dispensed the long-acting agent salme-

terol (serevent), compared with subjects taking the short-acting salbutamol

(ventolin) four times a day.” 55

I did not expect my predictions about the drugs’ danger would come at the

peak of its aggressive imposition on each and every person with asthama. On

August 15, 2003, when my book was already with the publisher, a letter from

Glaxo, signed by the Vice President and the Chief Medical Officer Anne

Phillips, was sent to each doctor in Canada stating that multi-centre research

studies had been stopped in the United States “due to a small but significant

increase in asthma-related deaths in patients receiving Serevent.” Now, it has

become a restricted medication, and doctors are advised “to protect the well-

being of their patients” and cautioned about prescribing the drug.



THEOPHYLLINE

Theophylline, oral and injectable, is another older kind of bronchodilator. It

does not produce the immediate effect of inhalers and is therefore prescribed

for regular use along with them. With theophylline, there is a fine marginal

line between a safe dose and an overdose, and the manufacturer writes in the

pharmaceutical compendium that “the margin of safety above therapeutic

doses is small.” This means that a dose considered therapeutically normal may

easily induce side effects, or any minor increase may pose a threat.

Theophylline has a cumulative effect, and its clearance from the body depends

on many medications that may be concurrently taken both for asthma and for

other medical problems. It is always an adjunct in the management of asthma, and

an overdose may occur because of the other consumed drugs and their interac-

tion. Smokers are in a higher risk group: they require larger doses due to chemical

incompatibility of the drug with certain tobacco ingredients. To avoid an over-

dose in the case of poor clearance, all patients who continually take theophylline

should undergo periodic blood tests to determine its level. Regrettably, less

serious symptoms do not always show up as a warning before grave ones occur—

convulsions, cardiac arrhythmia, circulatory collapse, coma and even death.

The world-famous 10 year Canadian survey conducted by Dr. Spitzer reveals

that not only does the use of short-acting inhalers increase mortality, but “the

use of theophyllines, … was also associated with an excess risk of a major

adverse event.” A major adverse event is the euphemism for death. Naturally,

when theophylline is used together with short-acting bronchodilators, which

is not so infrequent, the risk drastically rises. Their combined use is not so

infrequent due to the growing asthma resistance and doctors’ desire to

prescribe anything that will help their patients breathe.

However, the main thing about theophylline is that, in addition to all its

adverse potential, its potency is negligible. It used to be “the first-choice bron-

chodilator.”56 “It was highly prescribed in the past because its role in asthma

management was overestimated,” but “at present, there was complete accord

among the consensus members about the declining role of theophyllines.”57

This was said when bronchodilators as a group fell into disfavor. Resistant

asthma prompted the leading allergists to develop drugs with an effect similar

to theophylline, despite all the criticism of it in the recent past. The develop-

ment of these drugs is currently led by L. Lichtenstein and S. Holgate, the

world’s two most knowledgeable immunologists.



CONCLUSION ON BRONCHODILATORSTextbooks do not disclose the scientifically recognized mechanism of

bronchial obstruction in asthma, which is the enzyme cAMP-dependent

histamine-induced pro-inflammatory chemistry. This fact, however, has been

known since 1968, when it was first described by L. Lichtenstein.74 Neither do

pharmaceutical compendia disclose the cAMP-related mode of action of

bronchodilators. Silent about this is the entry for ventolin, the most common

short-acting bronchodilator. Still, the year 2000 entry on its cousin serevent,

a long-acting inhaler, spills the beans: the medication “offers more effective

protection against histamine-induced bronchoconstriction.” The side effects

of this are well known: “While such pharmacological effects are welcomed by

patients, the practice of continually inhibiting mast-cell degranulation may

not be as beneficial as originally believed.” The text of this already-quoted

article explains what makes the use of bronchodilators undesirable: “Beta-

agonists can upregulate IgE production” and “induce a reduction in suppressor/

cytotoxic T-cells.”58

You will recall that IgE antibodies are a pro-disease element, and that a low

number of T-suppressors allows allergies to progress. As for cytotoxic cells,

they help destroy viruses, bacteria and cancer cells. Now make your own judg-

ment as to what is good for you. The effect of these drugs is known as being

wide spectrum. By suppressing mast cells, they not only suppress their produc-

tion of pro-inflammatory mediators and cytokines, but also of the ones that

“may be broadly considered anti-allergic or anti-inflammatory.” The suppres-

sion “could result in chronic tissue damage” and “increased scar tissue forma-

tion.” “Such changes are certainly consistent with the observed deleterious

effects of regular treatment of asthmatics with beta-agonists,” the article

informs us. And so “…the wisdom of allowing this to occur on a chronic basis

is questionable”; the author thinks it is time “to begin to clearly identify the

underlying mechanisms.” These mechanisms are known, but now, 10 years

later, they still out of reach.

If beta-agonists are “deleterious,” what about other drugs of this group?

Since information on histamine is usually hidden, only an educated reader

will understand that theophylline also aims at its inhibition. The 2002

Canadian Compendium of Pharmaceuticals writes on page 1683 that “The

actions of theophylline may be mediated through… a resultant increase in



intracellular cAMP.” Although the compendium states that “the exact mecha-

nisms(s) has not been determined,” this is not true. As we know, the mecha-

nism of increasing cAMP by different agents (theophylline included) was

studied by L. Lichtenstein who said that histamine, like no other agent is

effective in increasing cAMP, which, in turn, results in the inhibition of the

cellular histamine release. Oh, this omnipresent histamine!

For now, bronchodilators are a compulsory medication for all asthmatics.

Their high use under the circumstances of growing asthma morbidity

remains a cause of concern. Two authors, a medical doctor from the

Washington Institute for Asthma and Allergy and a mother of an asthmatic

child, who made the fight for better asthma treatment her life’s mission,

grieve that “the published literature is lacking in data on the frequency and

severity of medication side effects in the general asthma population.”59 They

say that up to 79% of the surveyed 1834 asthmatics had “unwanted side-

effects from their bronchodilators.” When those patients complained to their

doctors, the advice was either to change the brand (which helped little if at

all) or put up with the complications. The authors conclude that “there is a

need for new, rapid-acting bronchodilators with fewer side effects.”

Given the current situation of complete secrecy surrounding histamine,

asthmatics do not stand a chance of getting such medications. The knowledge

that could lead to the reduction in the use of bronchodilators will not get

through the barriers established by the drug producers who are readily

supported by the medical Establishment.

Solid proof of this claim is that Dr. M. White, one of the two authors of the

article, had previously written the chapter Histamine in the extensive book

Inflammation in co-authorship with M. Kaliner, Head of Allergic Diseases

Section in the National Institutes of Health in Bethesda. Dr. M. White is also

the author of the article The Role of Histamine in Allergic Diseases.60 Her works

as well as her (earlier quoted) presentation at the symposium Histamine and

Disease in 1989 on the cardinal role of the H2/3-receptor reveal that she is

knowledgeable in the underlying mechanisms of allergy. There must be reason

that prevents Dr. White from informing her co-author, Mrs. N. Sander, of that

substance that has self-inhibiting and self-remedial properties—histamine.

This substance, if used in therapy, would probably help Mrs. Sander’s daughter

to avoid the dangerous bronchodilators.



NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

INTAL AND TILADE

Modern medicine dictates that relievers be taken only with the protective back-

ground created by another group of medications, taken daily and allegedly

targeting the underlying allergic inflammation. These drugs are called

controllers and represent the second largest group of common asthma medica-

tions. The group is subdivided into corticosteroids and non-steroidal remedies.

Among the non-steroidal anti-inflammatory, there are Intal and Tilade

used as inhalers. Intal has been in regular use for decades, and mostly in chil-

dren. Tilade is much younger. Both are “intended for regular daily usage” and

should not be used as an alternative to bronchodilators,” state pharmaceutical

compendia. This simply means that they are adjunct drugs, and bronchodila-

tors are their imperative companions. Consequently, not only bronchodila-

tors are needed but, too often, steroid therapy is used as well.

The pharmacological action of Tilade is inhibition of the release of medi-

ators from mast cells, both pre-formed and generated, during an allergic reac-

tion, as pharmaceutical compendia inform us. Since there is only one pre-formed

mediator in mast cells, histamine, and the rest are induced by its initial spill,

we can arrive at the only one logical conclusion: the anti-inflammatory

action ascribed to Intal and Tilade is accomplished essentially through their

inhibition of histamine release.

ZADITEN

Zaditen is a product of the early nineties. Its primary consumers are children,

therefore the medication is sold mainly as a syrup. “Our success is child’s

play,” assures a picture advertising Zaditen. Let us see if it is so.

The prescribing information classifies the medication as a “paediatric

asthma prophylactic and anti-allergic agent,” as an “add-on-medication in the

chronic treatment of mild asthmatic children.” Furthermore, “several weeks

of Zaditen therapy may be necessary before the therapeutic effect becomes

clinically evident.” Zaditen is recommended for children over three years of

age, twice daily for six to twelve weeks, the objective being to achieve the

greatest effect and to reduce the use of other concurrent medications, steroids

in particular. The adverse effects are mentioned as being of “a relatively low

incidence.” Among them are sedation, weight gain, rash, respiratory infec-

tions, headache, sleep disturbance, abdominal pain, rashes, ear infections,

nose bleeds, puffy eyes. The text warns about amplification of the sedative



effect in kids taking antihistamines concomitantly, which is not so

uncommon.

The ad advises that “Zaditen can significantly decrease the frequency and

severity of acute asthma attacks,” and there is a possibility of lessening the dose

of other medications: “It is not fully established, but some patients may be able

to reduce corticosteroids.” Wait a minute, there is a contradiction here: Zaditen

is indicated for mild asthma, which in itself excludes the chances of severe

attacks. However, if a child is on steroids but still has severe attacks, then his

asthma is not that mild, and Zaditen should hardly be prescribed. The ad

described in detail the danger of steroids and the weaning process, and this gave

me a feeling that steroids were not among the product line of the Zaditen’s

developer. The Compendium of Pharmaceuticals confirmed that.

There is no need to argue that danger from Zaditen is minimal, especially

compared to other asthma drugs. However, do not forget that Zaditen, Intal,

and Tilade are supplementary medications, and the chances of adverse reac-

tions from any drug increase in proportion to the length of its use. From

childhood, an asthma patient is turned into a slot machine for ineffective

drugs which have to be taken for a long time in combination with other

allegedly more effective medications. All this in the expectation of a tempo-

rary improvement. This makes sense when seen in economic terms: “Profits

can only be harvested from chronic disease,” investigative reporter Jeffrey

Robinson was told by the CEO of a giant pharmaceutical company.61

It is of interest that among the pharmacological properties of Zaditen, the

compendium lists its ability to inhibit histamine release through blocking the

H1 receptors, which turns the drug into just another antihistamine. Indeed,

Zaditen is often called a “mast cell stabilizer.” So far, due to the oversight by

allergists, human mast cells are still described by all dictionaries and text-

books primarily as carriers of histamine granules, and “to stabilize” these cells

can only mean to control their histamine spill.

ANTILEUKOTRIENES—NEW DRUGS FOR ASTHMA

“Antileukotrienes are the first novel class of therapy introduced for asthma in

the last 30 years,” writes P. Barnes, one of the world’s leading immunopharma-

cologists and the chief consultant to asthma drug producers.62 This admission

is striking in that every year, we hear about new breakthrough medications, and

it turns out there were none for 3 decades. What are these novel drugs? They are

inhibitors of a group of pro-inflammatory allergy mediators called leukotrienes



and work in a manner similar to the antihistamines’ blocking histaminic effect.

Antileukotrienes, actually, guarantee the future prosperity for the drug manu-

facturers, and be assured, we will see many on the market.

This is what P. Barnes says: “Many inflammatory mediators are involved in

atopic diseases, and in asthma, over 50 different mediators have been identi-

fied. This implies that inhibitors of single mediators would be unlikely to be of

major clinical benefit.” The author adds that some mediators “may play a more

dominant role,” which means they will have priority for suppression. It is of

interest that antileukotrienes are described by Dr. Barnes under the subtitle

Mediator Antagonists. He starts the list with antihistamines, however, as is

common today, and manages to write about them without once mentioning

histamine to which they are “anti”!

Accolate and Singulair are the first antileukotrienes ever developed.

Singulair, the product of the pharmaceutical giant Merck-Frosst, received the

Prix Galien Canada 2000 as the best drug of the year. When it appeared on the

market it was called in the media “bronchial Viagra.” One can only hope that

the real Viagra works better. Judge for yourself how effective antileukotrienes

are. Before coming on the market, they had been tested on several hundred

children with mild to moderate asthma for a few-week period—a time too

short to make reliable conclusions. The drug’s safety for pregnant women is

not known, neither is safety for a fetus or nursing mothers. They are add-on

medications, and the producer of Singulair insists it be taken along with the

“management drugs”—another nice euphemism for steroids. As was

admitted by antileukotriene researchers, the drugs are relatively efficacious

only in asthma triggered by exposure to cold and exertion and also in aspirin-

sensitive patients, but even these groups should not part with their rescue

bronchodilator. In a recently conducted study, adding an antileukotriene to

inhaled steroids in a mild asthma did not show the results better than with the

inhaler alone.63 Although anything that can relieve the fate of asthma patients

would be great, the above-listed limitations do not permit one to seriously

consider antileukotrienes as solution of asthma problem.

ANTI-IgE AGENTS—ANOTHER NEW PROJECT

Another group of novelty drugs is the anti-IgE agents tested mostly on

animals and expected to be FDA-approved several years from now. The posi-

tive aspect of these drugs is that, unlike the most commonly used medica-

tions, they do not compromise the immune system. However, the best way to



expose an untenable position is to do it through the person’s own admissions.

The true efficacy of anti-IgE medications becomes evident from the state-

ment made by the group of scientists who conducted the study on them:

“after 20 weeks, serum free IgE concentrations decreased by a mean of more

than 95 percent, but the patients still continued to suffer from asthma” (!?).64

Not only does this show the limited effectiveness of these new agents, but also

indicates the insignificance of specific IgE antibodies in the production of

asthma: cleared from antibodies, patients continued to suffer from asthma.

Of special interest are accidental revelations made by the developers of

anti-IgE medications: these drugs possess a stimulatory effect on T-cells and

anti-inflammatory cytokines. Although the producer does not specify how it

occurs, the mentioning of T-cells in this context can have one meaning only.

The only established biochemical pathway for a positive effect is T-suppressor

activation, which then activates anti-inflammatory cytokines, while T-helper

activation plays mainly a negative role in allergy since they help to produce

pro-inflammatory chemistry, including IgE antibody formation. In any case,

the solution lies not in suppression of T-helpers and pro-disease chemistry by

daily medications, but in T-suppressor activation that may free the patients of

all drugs.

THE OXYMORON OF IMMUNOSUPPRESSIVE IMMUNOMODULATORSDr. Barnes’ extensive review of asthma medications65 includes “cytokine modu-

lators,” and corticosteroids are among them. Remember, the scope of their

suppressive action goes beyond the quelling of the targeted disease-promoting

cytokines and mediator and covers total cellular production. By definition,

“modulator is a specific inductor that brings out characteristics peculiar to a

definite region.”66 As the peculiar characteristic of the immune system is to

defend, a modulator should facilitate this protective function. Steroids do the

opposite: they suppress the immune system. The dictionary also defines

immunomodulation as “adjustment of the immune response to a desired level.”

Immune system suppression can hardly be desirable in asthma. Add to the

suppression of immune cells another well-known pharmacological effect of

steroids, namely gene suppression at large, and you have the basis for under-

mined health of the children of steroid users. Thus, by twisting the meaning of

the term, allergists present a dangerous drug group as healing agents.

Another “immunomodulator” suggested by Dr. Barnes is cyclosporine.

Although new in asthma, this drug is old and has been used in cancer



chemotherapy to suppress tumor growth and in organ transplants to prevent

graft rejection. Cyclosporine belongs to the group of drugs called cytostatic,

the term defined by medical dictionaries as “an agent that suppresses cell

growth and multiplication.”67 In other words, aiming at the reduction of

allergic responses, the drug scorches the immunity. A bright prospect for its

consumers! Still, cyclosporine has certain advantages over steroids: it does not

cause such an array of complications, nor does it develop physiological

dependence and can, therefore, be discontinued at any moment. This is the

reason why allergists have turned to it.

OTHER OPTIONS IN ASTHMA MANAGEMENTIn his review, P. Barnes sincerely admits that gene therapy is not feasible

“because atopic diseases are polygenic.” In saying so, he undermines the rosy

future professed for “DNA immunization” by two authors in the same

journal.68 Barnes also mentions the positive results in allergy prevention from

BCG (tuberculin) vaccination in Japan. Since later tests in Sweden failed to

confirm this, the scientist does not propose, at least for now, the idea of using

tuberculosis vaccine for asthma prevention,

Despite the obvious deficiencies of the existing asthma medications,

allergy medicine will not admit its impotence, and Dr. Barnes declares that

“Inhaled corticosteroids have dramatically improved the treatment of asthma

and are now first-line treatment for persistent asthma in all patients.” He

forgets that just two paragraphs earlier, he made the contradictory statement

that in order to “avoid their (steroids’) side effects,” there is a need for the

development of new treatments that deal with more severe asthma (which) is

currently not well controlled by high doses of inhaled corticosteroids.”

THE CHOICES ALLERGISTS GIVE TO ASTHMA PATIENTSConsidering that the latest guidelines insist that steroids be prescribed even for

mild recurrent asthma, patients have two drug choices—steroids and bron-

chodilators—and both are considered compulsory. Bronchodilators are taken

for an immediate relief, steroids are taken daily as a means to prevent attacks.

Neither of them cures asthma, and even combined and accompanied by

adjunct medications, they are still, too often, inefficient. Therefore, an asth-

matic is forced to “choose” not between two evils but both evils. The latest

invention, combo drugs consisting of long-acting bronchodilators and inhaled

steroids, cannot be proclaimed as particularly effective either. “What to do at



step 3 of the asthma guidelines—increase the dose of inhaled steroids or change

the dose of a long-acting Beta-agonist drug?” asks the title of the most recent

editorial, one of the authors of which is R. Beasley, a renowned asthma

epidemiologist.69 Step 3 is the state when the combo drug fails to relive asthma,

while a higher dose of steroids gives serious side effects. The (doomed, in my

opinion) decision is to continue to perscribe both drugs, and merely adjusting

the dose. An embarras du choix, an embarrassment of choices, as the French say.

In the eighties, the more alarming statistics on asthma in the United

Kingdom compared to those in North America allowed two prominent

Canadian allergists, Dr. M. Newhouse and Dr. J. Dolovich, to blame their less

lucky colleagues for the high fatality rate caused by their “failure to treat

promptly,” that is, use daily steroids. The comments caused an angry response

from the British allergists who said that such “theory unfairly stigmatizes the

entire medical profession of certain countries such as England and Australia.”70

They felt that the cause of the skyrocketing mortality was attributable to the

extraordinarily high-dose bronchodilators used in their countries and not to

their professional deficiency or bronchodilators in general.

Who was right? At present, 15 years later, one can come to the conclusions

that neither side saw the roots of the problem. Of course, high-dose bron-

chodilators could be blamed for the soaring death rates in the ’80s. Yet, now

that patients in all first-world countries are in steroids up to their neckties,

why are asthma morbidity and mortality still on the rise? Why haven’t the

overwhelmingly prescribed steroids diminished the need of bronchodilators?

A much higher consumption of bronchodilators today is warranted by the

combo medications that are becoming more and more popular even though,

as we quoted earlier, “long-acting beta-agonists…have little place in the treat-

ment of asthma if one follows the guidelines for therapy.”71

The rising popularity of such combo drugs makes one wonder about their

mode of action, and this makes one suspect a well-organized plot. The idea

behind this must be the ability of steroids to facilitate the stimulatory biochem-

ical effect of Beta-agonists on cAMP with the resultant temporary inhibition of

release of histamine and histamine-induced inflammation producing chemistry.

This is stated as being the work designated for postgraduate courses; one of the

authors is an ex-president of AAAAI, Dr. W. Busse.72 Dr. Busse has always

worked on the histamine-related immune mechanisms, and this was the reason

why during our meeting at the international symposium in 1989, S. Holgate

recommended I talk to him. He cannot be unaware of the fact that histamine acts



through the same mechanism via H2-receptor stimulation and that it acts in a

sustained and profound manner. It is obvious that attempts to achieve the desired

effect by using less efficient tools cannot be accidental.

A popular ad in medical periodicals shows a pretty young asthmatic woman

who is able to extinguish candles on her birthday cake with such force that the

cake itself flies away. This colourful ad assures that Advair, the first of such

combo drugs, is more beneficial than bronchodilators and inhaled steroids

taken separately. Besides, as the text on the ad indicates, the patients taking this

combo drug must use short-acting bronchodilators for acute symptoms. The

asthma candle is being burnt from both ends by the hazardous agents.

Would you trust a technician who came to your house to repair your TV

with a hammer and saw? Do you think our body is any less complex than a

TV set? An immunosuppressive drug has become the main instrument in

repairing the sophisticated ailing machinery—our immune system!

The book has been with the publisher, in October 2003, when the news came

that the Canadian provice of Quebec was removing the combo medications,

Advair by Glaxo and Symbicort by Astra-Zeneca from the drug plan formulary

to prevent physicans from using them as first-line therapy. Other provinces will

follow. This is the beginning of the end: the best asthma medication turned out

to be so hazardous that caution is advised when they are prescribed. Now, the

internationally accepted guidelines that had supported their priority among

other drugs have to be reconsidered. Had the situation with asthma not been so

grim, the conclusions of the medical elite could have been considered laughable:

as a replacement of the combination of steroids and bronchodilators, these

drugs ae suggested separately, steroids as the first and bronchodilators as the

second line of therapy! Another embarrassment of choices!

OLD GUIDELINES Two periods can easily be traced in the management of asthma. They become

obvious through the history of steroids. When steroids were first introduced

in pills and injections, their powerful effect and the feeling of being able to

move mountains, was so great that doctors started to prescribe them not only

for rheumatoid arthritis and more rarely, in asthma, but also as a life style

drug. The fact that steroids were a synthetically produced body chemical

created the illusion of their safety. The realization of danger came soon when

withdrawal symptoms and numerous side effects were noted, and this forced

the medical profession to became cautious prescribing in the drug.



The prescribing pattern started to change with the appearance of the

inhaled form in the seventies. Inhaled steroids (allegedly) worked in the lungs

and bronchi, and this (allegedly) greatly reduced, almost eliminated, their

side effects. With inhaled steroids, the era of a non-aggressive use of steroids

came to an end. The late ’80s and mid-90s became the transition period from

the cautious use of steroids to their becoming the remedy of practically

unlimited use. The change was necessitated by the situation in the mid

eighties: asthma was becoming more and more resistant to all therapies, and

mortality from bronchodilator abuse became too obvious to conceal.

The need to prescribe more steroids was explained in the May 1993 guide-

lines on asthma management published in The British Medical Journal. On

page 776, we read, “Mortality and morbidity from asthma are unacceptably

high. Many deaths and much unnecessary morbidity have been associated

with over-reliance on bronchodilators, underuse of inhaled and oral corticos-

teroids...”73 These guidelines were based on controlled trials and endorsed by

the British Thoracic Society, Pediatric Association, the Research Unit of the

Royal College of Physicians of London, and other authoritative medical soci-

eties of Great Britain. Although the recommendations promoted the greater

use of inhaled steroids even in patients with apparently mild asthma, they still

allowed the more timid, five-step approach to the disease. Steroids were to be

introduced only if nonsteroidal anti-inflammatory drugs failed. The guide-

line creators said that their recommendations “should be seen as a general

framework within which most patients with asthma can be managed.” This

meant that the guidelines were not of a compulsory but of an advisory kind,

as they should be.

At that time, immunology moguls occasionally expressed their reservations

about adverse effects of steroids. Thus, the same year, when the said British

guidelines were published, Dr. S. Holgate wrote in the Lancet that the risks of

early use of inhaled steroids in treating mild to moderate asthma could

outweigh the benefits when treatments with long records of safety and proven

efficacy are available as a prior alternative. It is a pity Dr. Holgate did not name

the drugs with “proven efficacy” as an alternative to steroids. Do they exist?

It is not a secret that medicine has become a subsidiary of the pharma-

ceutical industry and for this reason often disregards scientific data and the

ethical norms of the profession.

The lack of independence of medical scientists in expressing views becomes

especially obvious when one looks at the sponsors of conferences. Their names



forecast what medications will be praised by the speakers. The Second

Canadian Asthma symposium held in Ottawa in 1994 chaired by S. Holgate

with speakers from Canada, U.S. and U.K. serves as an example. Fisons

Pharmaceuticals, producer of Tilade and Intal, was the sponsor of the event.

As should be expected, the participants somewhat exaggerated the effect of

these drugs by equating it to the effect of steroids. The general opinion was

similar to the one expressed by Dr. P. Konig from Columbia School of

Medicine who said that “the efficacy of nonsteroidal and steroidal drugs is

comparable, but safety is better with nonsteroidal treatment,” and “the

risk/benefit ratio, therefore, favors nonsteroidal agents.”

After 1994, symposia are sponsored, as a rule, by steroid producers, and, as

should be expected, their products are now considered the only efficient and

also safe asthma remedies. All practising doctors have to obey the steroid-

dominated guidelines, irrespective of their professional and legal rights not to

accept any guidelines. They know that the disobedient will be skinned,

scalped or at least weeded out. As the great Polish writer Ezhi Lentz once said,

the word likemindedness is put together by cut-off heads. Only the growing

awareness by the public of the side effects of steroids slightly tempers the zeal

of prescribing these drugs.

WILL YOU COME INTO MY PARLOR?The drug industry is at its best when presenting its products that lure both

doctors and patients. The steroids’ packaging is attractive, the devices are easy

to use. While steroids can be injected or taken in tablets, the most common

way is to inhale them. Because a high percentage of the drug consumers are

children, the most wily ways are used to attract them and make the delivering

device appealing. The plastic is of bright colours, and the medications look

more like toys. Indeed, I have seen a puffer made in the shape of an animal.

There are regular metered-dose inhalers, a spacer device with or without a

mask for younger children, devices with compressors for babies and toddlers.

The impression one gets from looking at the pictures of smiling mothers who

hold their baby with a mask covering the kid’s face is that the parents are

happy to see nicely fitting masks on their children. Young users may imagine

they are playing war games as they wear their masks. Complete satisfaction!

In other words, steroids to satisfy any taste! Shouldn’t asthma patients be

grateful to drug developers for their far-reaching care?



We must remember, however, a simple axiom: the worse our health, the

higher the industry’s profits. The natural chain of events fits this axiom: a

chronic medical condition—chronic use of a medication—the body’s adjust-

ment to the drug and the need for a higher dose—more and more pro-

nounced side effects—drugs to relieve the side effects, etc. In asthma, even if

a patient starts with inhaled steroids, the finale is dependence on them due to

the failing or atrophied adrenals and decreasing ability of the stifled

T-suppressors to defend the host. Even if the side effects of steroids do not

appear at once and are minor for some time, the patient inevitably ends up

with a cascade of them hitting different organs and eventually undermining

the whole body. You say you take steroids in innocent small doses? For how

many months? Years? Decades? Doesn’t it remind you of smoking “safe” ciga-

rettes with filters?

DOUBLETHINKINGThe universal acceptance of steroids was unable to exclude a hesitation: to

give or not to give these drugs? What to use as a substitute if they produced

significant side effects? Are there treatments with “proven efficacy,” as Dr. S.

Holgate called them? At their meetings in the early nineties, allergists argued

with each other, and at times, even with their own views. The inconsistency

in the opinions of professionals on asthma is well demonstrated in the 1996

report Canadian Asthma Consensus.75 Here are some examples:

■ “Theophylline remains an effective anti-asthma drug.” (p. 95)

■ “Theophyllines should not be used as first-line therapy in asthma” (p. 96)

(Why not, if the drug is effective?)

■ (add-on medications are) “warranted in asthma... when toxicity or fear of

toxicity from corticosteroids is a major concern” (p. 96)

■ If symptoms persist (when taking add-on medications), inhaled corti-

costeroids should be prescribed instead.” (p. 96) (Despite their toxicity?)

■ “Immunotherapy is generally not recommended in the management of

asthma.” (p. 96)

■ “At present, immunotherapy... may be considered if disease activity

is inadequately controlled by allergen avoidance and pharmacological

therapy.” (p. 96) (To consider the least effective treatment after all

“effective” have failed?)



■ “Air pollution is the principal outdoor irritant... linked to exacerbations

of asthma” (p. 92)

■ “Indoor irritants... appear to represent an even greater hazard to the

health of the asthmatic.” (p. 92) (Where should an asthmatic live—

indoors or outdoors?)

■ “Various types of indoor air cleaners are available... shown to reduce

levels of irritants significantly” (p. 92)

■ “… health benefits (of air cleaners) have yet to be consistently demon-

strated.” (p. 92) (So, to buy air cleaners or not to buy?)

Only deep dissatisfaction with one’s own results can produce such contradic-

tory remarks within a single document ironically called Consensus, the word

which dictionaries define as unanimity in opinions.

CONSENSUS ON THE LACK OF CONSENSUSDue to the dramatically rising incidence of childhood asthma and its growing

severity, meetings in the late eighties and early nineties, followed one another

in the hope of working out acceptable guidelines. An impressive one

including delegates from 22 countries was held in 1991.76 The participants

agreed that “there have been many new questions but no dramatic advances

in either the understanding of the condition or its management.” They spoke

about the “vast literature of confusing information about virtually every

aspect of the condition,” “the lack of hard data in many areas of manage-

ment,” and “increasing concerns about many of the pharmacotherapies

(drugs) at our disposal.”

From the legal point of view, in any medical field, guidelines are under-

stood to be of purely educational and advisory nature, not as a compulsory

directive. Therefore, inexplicable became the fact, that despite complete

confusion and absence of any definitive knowledge in all areas of asthma, the

participants called for strict guidelines in the management of asthma.

Obligatory guidelines in an area full of questions can pursue only one aim—

to be authoritative, mandatory. And these guidelines were just that. Thus,

after having recognized their lack of knowledge of asthma and the ineffec-

tiveness of the treatment methods, the participants concluded that their

guidelines must be “a challenge to experts who have suggested alternative

protocols.” That’s it: we don’t really understand the disease or its treatment,

but don’t dare try new ways without our regal permission! These reputable

specialists warned that “management which deviated from the consensus



recommendations might be viewed unfavorably in legal proceedings.” Indeed,

the threat of litigation is the best deterrent against potential deviations and

the best way to enforce the undisputed orthodoxy. Such guidelines serve to

ensure obedience, not the search for of better management of asthma.

Why do specialists drive everybody into narrow regulations instead of

searching for something more effective? Because a choir sounds impressive

only when all vocalists sing in unison. Because the ‘vocalists’ feel more confi-

dent if they hide their professional impotence behind their togetherness.

Because abiding by the guidelines, no matter how confusing, can save them

from potential liability. Because an alternative can destroy the thoroughly

built structure of the ranks and therefore has to be subdued by the threat of

potential litigation. Because the painted facade—the consensus—conceals the

decrepit scientific and medical structure, i.e. ignorance in all areas of asthma.

This can be admitted in a closed circle and in whispers only. It is necessary for

a choir to sing in unison although the universal agreement on any single

opinion is in science dangerous both for science and for patients. The proof:

a decade after these enforced guidelines we have such admissions as the

following ones in the leading immunological publication: “No treatment can

consistently induce a lasting remission of asthma in adults,” and “Inadequate

asthma control is a serious, widespread problem among children.”77

Winston Churchill is supposed to have said that in the Soviet Union

“where everything was prohibited, what is not prohibited is compulsory.”

Today’s treatment of asthma reminds me of the Soviet regime. An asthma

patient has two choices: bronchodilators and steroids. Both choices are

compulsory. All the rest is prohibited.

INHALED STEROIDS: ARE THEY LOCALLY ACTING DRUGS?Even the most fervent fans of inhaled steroids agree that these should be taken

in as small doses as possible. The question is why if, as allergists assure us,

inhaled steroids are supposedly safe. Since these drugs have become an

inherent part of asthma management, we must thoroughly study their effects

and dangers.

Inhaled steroids were first introduced in 1972 with the purpose of reducing

the notorious side effects of oral steroids, tablets. Allegedly inhalers work

primarily locally in the lungs, and this spares the patient the systemic side

effects. This is not true: “There is minimal evidence for active biotransforma-

tion in the lung, and therefore most of the drugs reaches the systemic circulation.



Eighty percent of the systemic effect of these agents is via this route.”78 Potential

liability for not disclosing a drug’s adverse effects forces drug companies to

reveal them. At the same time, their desire to downplay side effects results in

the kind of paradoxical entries as the one on Vanceril (Beclomethasone), a

product of Schering. One sentence states that the drug has a strong local effect

and “minimal systemic effect.” The next sentence reveals that only “10–25% of

a dose reaches the respiratory tract; the remainder is swallowed and absorbed

from the gastrointestinal tract,” and “orally absorbed drug is metabolized by

the liver.” The drug producer does not explain how the drug, 75–90% of which

goes from the lungs into the liver, has a “minimal systemic effect.” If most of

the inhaled steroids are absorbed by the gut, (which is systemic), they are akin

to oral steroids, and this should stop all talk about the negligible adverse effects

of inhalers. Moreover, steroids are “by no means a cure, as symptoms recur

soon after discontinuation in most patients.”79 A recurrence means a return to

the drug, and repeated drug courses lead to permanent complications.

INTERVIEWING THE COMPENDIUM OF PHARMACEUTICALSCompendium of Pharmaceuticals and Specialities, CPS, lists all drugs on the

market and their effects and side effects. However, it seldom reaches a lay person,

therefore I suggest an imaginary conference with the manufacturers of most

popular steroid inhalers—Flovent (fluticasone) and Pulmicort (budesonide).

The answers to the questions commonly asked by asthma sufferers are the quota-

tions taken from the 1998 and 2001 editions of Canadian CPS. I put in brackets

my own remarks on the discrepancies in the texts. The answers are not snatched-

out phrases but the text selected to match the questions. Besides, having atten-

tively read the texts on several inhaled steroids in several compendia, I could find

only insignificant differences in them.

Q. What sort of drugs are inhaled steroids?

A. They are potent anti-inflammatory medications with strong topical

(local) and weak systemic activity. (As was said, only Schering, the manu-

facturer of beclomethasone, acknowledges that 75–90% of the inhaler is

absorbed systemically, whereas other producers of inhaled steroids avoid

this vital subject or distort it.)

Q. What are they prescribed for?

A. For treatment of steroid-responsive asthma. (This is an admission that

not all asthma is responsive to steroids)



Q. To whom are steroid inhalers prescribed?

A. To asthmatic patients who do not respond adequately to conventional

therapy; and corticosteroid-dependent asthmatics when a reduction of

systemic (oral) steroids is desirable. (This contradicts recent guidelines

recommending inhaled steroids as first line medications even in a mild

recurrent form of the disease.)

Q. Why is it desirable to use inhaled steroids instead of systemic ones?

A. Since with therapeutic doses, the minute amounts absorbed do not exert

any significant systemic effect, inhalers can replace oral steroids with the

elimination of the untoward effects of systemic therapy.

Q. Does it mean that the inhaled drug is contained in the lungs?

A. After administration by inhalation, approximately 10 to 25% of a dose

reach the respiratory tract, the remainder is swallowed and absorbed

from the gastrointestinal tract. (This statement implies that 75–90% are

systemically absorbed and thus contradicts the previous assertion that only

“minute amounts” are systemically absorbed.)

Q. How often and how long should the drug be taken?

A. Regularly, even when the patient is asymptomatic. (All his life? Then, why

do all guidelines recommend the dosage reduction upon improvement and

weaning whenever feasible?)

Q. Is it safe to take inhalers daily for a long time?

A. The long-term effects in human subjects are still unknown. (After 3

decades of the drugs’ use the adverse effects are unknown! Are retrospective

studies undesirable, or are the results silenced?)

Q. How effective are inhaled steroids?

A. Pre-treatment for 1 to 4 weeks may inhibit the immediate bronchial

reaction. (Does it mean it may not?)

Q. What if it does not?

A. Exacerbations of bronchial asthma should be treated with a short course

of systemic steroid which is gradually tapered as these symptoms subside.

Q. Why is it necessary to taper off the drug instead of simply discontinuing it?

A. Deaths due to adrenal insufficiency have occurred in asthmatic patients

during and after transfer from systemic corticosteroids to inhaled corti-

costeroids.



Q. Is adrenal insufficiency reversible?

A. A number of months is required for recovery of HPA function. The

inhaler and the systemic steroid must be given concomitantly while

the dosage of the latter is gradually decreased. If withdrawal symptoms

appear, the previous dosage of the systemic drug should be resumed

for a week before further decrease is attempted.

Q. Are all patients able to discontinue steroids?

A. There are some patients who cannot completely discontinue the oral

corticosteroids. In these cases, a minimum maintenance dosage should

be given in addition to inhaled steroids.

Q. Can patients stop taking inhaled steroids when they wish?

A. Treatment should not be stopped abruptly but tapered off gradually.

(Why, if there is no or only a negligible systemic dependence/effect?

Withdrawal is a systemic response.)

Q. Can children use the inhaler?

A. The inhaler is not presently recommended for children younger than 4

(6). (What should the younger kids be prescribed?)

Q. Can pregnant women take the inhalers?

A. There is inadequate evidence of safety during human pregnancy.

(Why, if they have a low or no systemic effect?)

Q. Is there a possibility of harm to the baby?

A. Well-controlled trials relating to foetal risk in humans are not available.

Like other glucocorticoids, the drug is teratogenic (producing birth

defects) in rodent species. (Teratogenic effect can only result from the

systemic effect. Can a drug known to be hazardous to an animal foetus be

safe for a human foetus?)

Q. Is there any danger to the baby of getting steroids with the mother’s milk?

A. The drug excretion into human breast milk has not been investigated,

but it is suspected to be likely. (Aren’t the producers interested in the effect

after the 30 years of inhaled steroids on the market? How can a drug that

works not mostly in the lungs get into mother’s milk?)

Pharmaceutical compendia also advise that inhaled steroids’ “long-term

effects in human subjects are still unknown,” and “there is also no informa-

tion about the possible long-term systemic effects, and therefore “HPA axis



function and hematological status (blood) should be assessed periodically.”

GlaxoSmithKline, the manufacturer of Advair, that combines an inhaled

bronchodilator with a corticosteroid, suggests in its fine print warning, under

the drug’s advertisement, published in medical journals: “height should also

be regularly monitored in children and adolescents receiving prolonged

treatment with inhaled corticosteroids,” which means that the locally acting

medication affects growth! A real paradox.

The principal defenders of the pharmaceutical products are doctors. If the

drug manufacturers are legally obliged to express caution about their product,

doctors do not do their best trying to “expose the myths of allergies and

asthma,” one of which is that inhaled steroids are dangerous. Considering that

the current guidelines both in Canada and US point out that steroids are

rather underused than overused and are the first-line therapy in asthma, there

is little wonder that doctors assure us: “Inhaled medications, including corti-

costeroids, are currently the safest (?!) and most effective means to treat

asthma.” The quotation is taken from the July 1999 issue of the Canadian

medical periodical Family Practice and expresses the consensus opinion.

SYSTEMIC STEROIDSOral and injectable steroids are called systemic for their ability to affect the

whole body. The published entries on oral steroids are carbon copies of the

ones on inhaled steroids only in darker colours. They say that systemic steroids

are prescribed for “incapacitating allergic conditions” and “to steroid-respon-

sive patients.” The latter is admission that not every asthmatic responds to

steroids in any form. These entries cautiously warn that drugs are able to affect

any organ or system of organs. When taken for long periods of time, they are

difficult or impossible to wean, even when the asthma, for which they are

prescribed, comes under control.

The compendium lists both the immediate and the long-term effects of

oral steroids:

a. cardiovascular system—progressive development of atherosclerosis, cardiac

arrhythmia, increased mortality after a recent myocardial infarction; eleva-

tion of blood pressure, excessive bleeding, stroke;

b. metabolic complications—salt and water retention (that is, weight gain

and/or oedema); increased protein and bone loss as well as calcium excre-

tion (osteoporosis) leading to spontaneous fractures and suppression of

growth in children; increased appetite (weight gain); development of



diabetes mellitus and poor metabolism of the injected insulin in the existing

diabetes; increased fat deposition.

c. eye complications—cataracts, glaucoma, possible damage of the optic nerves;

d. immunologic complications—high susceptibility to infections, development

of severe resistant infections; poor healing or recovery process;

e. psychoneurologic complications—from insomnia and mood swings to

personality changes, severe depression, seizures, psychic derangement;

f. skin manifestations—thinning of the skin to atrophy, allergic dermatitis,

fungal infections;

g. hormonal changes—menstrual irregularities, miscarriages, infertility;

reduced libido, impotence, hirsutism (facial hair growth), adrenal suppres-

sion to fatality; growth hormone suppression and hence, poor wound

healing and stunt linear growth in children;

h. muscular system complications—muscle weakness, loss of muscle mass;

i. gastrointestinal complications—peptic ulcer with possible perforation and

haemorrhage, perforation of the small and large bowel, particularly in

patients with inflammatory bowel disease.

Some complications cannot be distinctly referred to a certain category but are

rather related to several interdependent systems that are affected by oral

steroids. It is impossible to predict at what dose and after what period of use

the side effects occur. “Dosage ranges are extremely wide, and patient

responses are quite variable,” states the compendium and suggests the use of

the lowest possible dose that provides adequate relief. The relief, nevertheless,

can be partial, no matter what the dosage is, and the disease may re-appear

and in a more severe form if the drug is discontinued. This, actually, turns

chronically ill patients into life-long users of steroids doomed to developing

all sorts of additional health problems.

We should not be surprised that the statistical data about all these complica-

tions are practically unavailable. Epidemiological studies need funding, and steroid

producers will not be among the sponsors of the investigations that may undermine

their profits. At times, the truth comes out indirectly, through articles

promoting medications other than steroids. The purpose is clear—to make their

own products more appealing, the manufacturers reveal the danger of steroids.

UNANSWERED QUESTIONSA lot of legitimate questions are left unanswered by pharmaceutical

compendia and the allergy elite:



■ If steroids are prescribed for steroid-responsive asthma, what should be

prescribed to the fairly large group of non-responders—about 30%, but

probably more?

■ What is the alternative therapy for the patients who show severe side effects

to steroids, but the dose cannot be reduced in view of the asthma severity?

■ Since steroids contribute to diabetes, hypertension, peptic ulcers, obesity,

osteoporosis, etc., what should those asthmatics be prescribed who already

have these medical conditions?

■ Manufacturers advise to weigh pros and cons when prescribing steroids.

If the cons outweigh the pros, what else is there for resistant asthma apart

from steroids?

■ What should pregnant women or nursing mothers be prescribed if their

asthma does not respond to other medications?

■ Since inhaled steroids are not recommended for children under 4 (often

under 6), what should the younger asthma sufferers be prescribed in case

other medications fail?

■ Why is it that neither the medical profession, nor the drug producers is

interested in the delayed effects of inhaled steroids? Why is that within the

more than 3 decades of their use, no retrospective epidemiological studies

exist on any of the effects of inhaled steroids on young children? Nor on

adults who have used them non-stop for many years? Nor on babies whose

mothers were using the drug during breast-feeding? Nor on the babies born

to mothers who used inhaled steroids during pregnancy?

■ Steroids are lymphocyte-toxic and genotoxic, which means they paralyze

both the functioning of the central immune cells and genes. Why is there

only a rare mention of this in medical sources, including pharmaceutical

compendia, and when it is mentioned, it appears as if only pro-inflammatory

forces are suppressed? The fact that only one receptor conducts steroid

messages makes it impossible to discriminate its effects and means that the

suppression covers all immune forces.

The inhalers have been on the market long enough to enable access to such

data. Were asthma a short-term disease, we would not have to worry about

the side effects. However, in Greek, Chronos means time, and thus, chronic

denotes a disease persisting over a long period. Chronic use of steroids, even

in the inhaled form, must be re-evaluated by the medical profession rather

than imposed more and more aggressively. As the number of asthmatics

grows, with it grows the chance of having a huge percentage of the population



with undermined immune systems and numerous serious conditions (wors-

ening asthma among them). The most “effective” and “safe” medications

create the setting for this immense potential epidemic.

WHAT DOSE IS SAFE?The early ’90s was the period when the wide-scale campaign of imposition of

steroids began upon every asthmatic. This put pressure on those doctors who

had a cautious prescribing pattern of the drugs always perceived as

dangerous. The knowledge of the potential adverse effects resulted in the

galvanizing effect of the word “steroids.” Here is one example. The Canadian

Journal of CME covered the first Annual Pediatric Refresher Course at the

University of British Columbia, and in its June 1993 issue on page 44, we read:

“Most children can be managed on low-dose steroids... Higher doses of

inhaled steroids are required for some children and should be used to reduce

oral steroid requirements. Alternate-day oral steroids are preferred to daily

steroids on a chronic basis.” Almost the same wording is preserved six years

later, in The Canadian Asthma Consensus Report of 1999. Such stuttering has

become a scientific habit when the topic of steroids is touched upon.

The September 2000 issue of the central journal of allergists covered a

meeting specifically devoted to asthma. One article writes: “We have very little

information on the long-term effects of asthma medications, especially

inhaled glucocorticoids … when administered to young children for

prolonged periods of time. It has not been shown definitely whether gluco-

corticoids as a treatment strategy are the drugs of choice.”80 The author also

refers to a 1998 FDA documentation: “The recent FDA meeting … (showed)

that there are no minimally effective and maximally safe doses (?!) of

inhaled glucocorticoids defined for children. The effect of specific variables

such as age, gender, race and genetics on the risk for adverse events, or lack of

effects of medication also remains to be determined.” On page 168 of the

same issue, one may read another reference to this meeting of the FDA:

“Information was presented that suggested all ICSs (inhaled corticosteroids)

have the ability to suppress short- and intermediate-term growth velocity.”

Even “Low doses of most popular inhaled corticosteroids Flonase and

Pulmicort are associated with a significant degree of detectable systemic

bioactivity, including HPA axis suppression,” states the earlier quoted source.81

In this connection, the order by the FDA ,which was obeyed by the manu-

facturers, to label inhaled steroids as drugs that may temporarily slow chil-

dren’s growth, should be questioned regarding its accuracy.



This all means that among the numerous unknowns that surround

inhaled steroids, one thing is unquestionable—their serious side effects at any

dose. They are just a matter of time. The fact that in children, the side effects

manifest earlier is not surprising, since they are the most sensitive group of

the steroid consumers. Similarly, the deaths of canaries in coal mines warn of

the dangers that are yet unknown.

A “safe” dose does not exist. What is proclaimed safe by some authors may

be found by others to be dangerous. A dose,“safely” inhaled for few weeks may

necessitate a drastic increase over a longer period of time, since asthma has a

relentless tendency to relapse with time and/or dose reduction. In fact, any

suggestion of a dose cut-back, be it in a textbook, periodical or pharmaceutical

compendium, is accompanied by a warning of a possible worsening of the

symptoms that can often be only by a high dosage. Steroid defenders assure us

that side effects are usually reversible upon dose reduction or discontinuation

of the drug. Can they guarantee the reversibility after repeated relapses and

hence, repeated courses of steroids? Is a few months’ period, in which trials are

conducted, long enough to come to conclusions about a safe dose if asthma, a

life-time disease, may necessitate indefinite doses? With the phrase “the clinical

significance of these changes in the long-term treatment is not known,” authors

and drug developers free themselves from liability as well as the responsibility

of answering these questions with “yes” or “no.”

As a rule, conclusions are made on the basis of small groups studied for a

short time, several months at most, although within the 30 years of inhaled

steroids being on the market, it is logical to expect that data on their long-term

complications be made available. More than a decade after the wide use of inhaled

steroids, the chapter in the textbook Allergy 1985 (page 658) says: “The effects, if

any, of IS (inhaled steroid) drugs… have not been adequately studied to date.”

Another decade later, in 1996, a world-renowned scientist warns that “the long-

term risks of their use… are still a concern to many, patients and physicians

alike.”82 A textbook published in the new millennium again states: “As with oral

GC (glucocorticoid) therapy, high-dose inhaled GC therapy has been associated

with adverse systemic effects, and it is still unclear whether long-term administra-

tion of inhaled GC will result in growth suppression and osteoporosis.”83 The

laments of the medical profession about inadequate information have not initi-

ated an investigation into the thirty year use of inhaled steroids. Will steroid

consumers sue the manufacturer and/or doctors years later when they realize that

sustained drug use did produce irreversible side effects? We have examples of

physicians admitting their wrongful support of smoking. We know the tobacco



industry has apologized to its victims by paying millions of dollars in liability

payments.

Despite all the recommendations to limit steroid use to the inhaled form,

it is often impossible to avoid the oral form, and this dramatically increases

the consumption and hence, complications. It may happen when the course

of asthma worsens, and the patient has to switch from inhaled to oral steroids

or takes both. It may also happen when, as a result of a protracted disease or

severe injury, oral steroids are added to enable the patient to go through an

ordeal. The very fact of adding oral steroids to the inhaled ones confirms that

doctors do know that the patients using the “safe” inhaled steroids may, in

fact, have a certain degree of adrenal deficiency and therefore need replenish-

ment.“Lucky” are those asthmatics who face elective surgery and can be given

high doses of injected or oral steroids beforehand. Those in emergency face a

danger of perishing in case of an accident, for their adrenals may not be able

to supply enough of the vital hormones, and there may not be enough time

to provide an additional dose.

OPINIONS ON STEROIDS AND BONE DENSITYBasically, asthmatics cannot avoid steroids today and must, therefore, know the

most common side effects. One of them is loss of bone density. It is an over-

whelmingly important health factor leading to osteoporosis and growth

retardation in children. The link of steroids to low bone density and hence,

fragility, initiated numerous discussions even though it is common knowledge.

Thus, the pharmaceutical compendium in its entry for Fosamax, the drug

described as a bone metabolism regulator, lists under the heading Indications two

main reasons to prescribe it—for prevention of osteoporosis in postmenopausal

women and for treatment and prevention of steroid-induced osteoporosis.

Despite the evidence, the tendency to downplay bone amelioration due to

steroids can be found in numerous high profile sources.

As is stated in the 2001 textbook Allergic Diseases. Diagnosis and Treatment

on page 401, “unfortunately almost all of the studies that have attempted to

determine the effect of inhaled GC (glucocorticoids) on growth have been

limited, making definitive conclusions regarding growth suppression diffi-

cult.” Page 402 informs us that “some studies have shown that short-term

suppression (of growth) can occur in some children,” and “significant reduc-

tions in bone density of the femoral neck of asthmatics treated with inhaled

GC compared to age-matched controls.”84



Once Dr. L. Fraher from the Lawson Research Institute said, in his speech

at an annual meeting of the American Society of Bone and Mineral Research

in Minneapolis, that steroid users may “end up with translucent skeletons full

of holes that you can see through.” We can add to this that for older patients,

disabled by fractures occurring due to steroid consumption, these drugs may,

actually, be fatal.

WHEN DOES THE HPA AXIS START TO CRACK?Another common consequence of steroid use is suppression of hypothalamo-

pituitary-adrenal (HPA) axis, the regulatory system for the production corti-

costeroids. Although less obvious than bone amelioration, suppression of the

axis is even more damaging to health and can be fatal. Therefore every article

on steroids and every insert into the steroid packaging mentions the possi-

bility of the HPA axis suppression. In the fourth decade of the inhaled

steroids existence, there is no (and can be no) consensus on the dose at which

the axis starts to decline, and a tendency exists to tie this complication solely

to the oral form.

A work published in JACI states that “data using more sensitive parame-

ters suggest that low doses of most popular inhaled corticosteroids are asso-

ciated with a significant degree of detectable systemic bioactivity, including

HPA axis suppression.”85 Further, the article writes that within four (!) days of

using 220 micrograms (the lowest dose in guidelines) twice daily produced

on average 40% suppression of the axis. These data were collected among

adults, and one can only speculate about the drug’s effect on children.

Indeed, “Adrenal suppression, decreased bone metabolism, and decreased

growth are of particular concern in children, in whom asthma is increasing in

frequency,” states an article that describes a herbal remedy.86 We can only

expect more of such side effects since inhaled steroids “are now introduced

earlier in the course of asthma treatment in both Canada and the United

States, and they are also used at higher doses than ever before.”87

STEROIDS AND THE GENESAs was said earlier, steroids obliterate gene expression, the functioning of the

genes. As usual, we are told not a lie, but half truth: “A key molecular mecha-

nism by which glucocorticoids reduce airway inflammation in asthma is their

suppression of the proinflammatory genes activated in allergic inflamma-

tion.”88 The reference is made at that point to the article with the title “Efficacy



and safety of inhaled corticosteroids. New developments.” Since the authors

of that reference are P. Barnes, the main strategist on asthma therapies, and

W. Busse, the year 2001 president of AAAI, one is expected to believe them.

Can steroids, universally known as indiscriminate immunosuppressors, be

discriminate in their suppression of the genes? Can they selectively hit

inflammation-promoting genes and avoid anti-inflammatory ones? They

cannot. Steroids do a sweeping pharmacological job: quench equally the good

and the bad. Thus, not only their consumers, but also their children may pay

a high price for taking these “safe and efficient” medications.

THE HISTORIC OPINIONS ON ASTHMA The understanding of the chemical processes characteristic for each given

disease is central to finding drugs for its treatment. The 2000 issue of JACI,

whose cover depicts Hercules cutting off the heads of the monster called

allergy/asthma, explains the meaning of the picture on page 5A: “The aller-

gist/immunologist seeks to stem the increasing prevalence of allergic diseases

through a better understanding of their mechanisms.” Thus, what is asthma?

Until the eighties, asthma was proclaimed to be a disease of spasm-prone

airways. Although information existed on what caused spasms, and why the

airways in some people were so hyperreactive, this information was frag-

mented and never resulted in a clear concept of how to reach these causal

mechanisms. The theory of hypersensitive bronchi led to the belief that

asthma was treatable. Accordingly, bronchodilators started to be heavily used

to keep the bronchi open at all times.

In the late ’80s to early ’90s, the tragic aftermath of this management

system forced medicine to look for another way to look at asthma which

would allow the patients to breathe freely and physicians to explain away their

previous failure. The old notion of the immune inflammation lying in the

origin of asthma was pulled out of oblivion, and inflammation became the

central target for medications. The lack of interest in causes allergic inflam-

mation was obvious. Medicine was again fighting secondary events instead of

paying attention to the primary causes. The frightening statistics on the effects

of bronchodilators permitted an end to all discretion in prescribing steroids.

In the same manner, a dress style enters the market and gradually

conquers it until one does not see anything but the advertised pattern. The

occasional voices about the underlying inflammation as the cause of asthma

have now merged into a well rehearsed choir. Finally, at the 1997 Annual



Meeting of the AAAI in San Francisco, the choir sang in unison that allergic

inflammation was the only proper dress to wear. All other “styles” were

proclaimed as illegitimate. Asthma has become solely an inflammatory

disease. Steroids, formerly prescribed with caution, flooded the drug market.

Paradoxically, despite their proclaimed effectiveness, “asthma morbidity and

mortality have increased dramatically in the United States during the last 20

years” necessitating still wider use of bronchodilators.89

The adverse effects of steroids are so obvious that even Peter Barnes, a

consultant to the producers of asthma medications, admits that “there is a

need for the development of new treatments” that would “avoid the side

effects that may be associated with … anti-inflammatory drugs such as corti-

costeroids.”90 He is pessimistic though: “the possibility of developing a cure

for atopy is remote.” One may only wonder as to what destroyed his optimism

expressed a year before in another article of his that was assuring us of the

opposite: “in the future there are real possibilities for the development of

preventative and even curative treatments.”91

Asthma patients cannot be overly optimistic either: according to the

February 14, 2002 issue of the New England Journal of Medicine, drug makers

spent $2.5 billion U.S. dollars in 2000 for advertising (for “educational

purposes”) mostly anti-inflammatories and antihistamines. The revenues

received from this investment by the manufacturers are impressive: “In 1998,

the annual cost of asthma was estimated at $12.7 billion, with medications

the single largest cost component.”92 Drug markets have no interest in a cure.

Despite the numerous side effects of steroids and despite the dramatically

rising mortality among their users, many authors see the problem of asthma

in doctors’ prescribing too little steroids and too late in the disease course.

They accuse parents of asthmatic children of noncompliance with the

management based on steroids. They even invented a new term for this—

parental prednisone phobia. As usual, the ends do not meet: as was reported by

a group of scientists from Iceland at the 58th annual meeting of AAAAI,

“inhaled glucocorticoids are widely and successfully used” in “over 90% of

patients with moderate to severe asthma.”93 This is almost universal successful

coverage of asthmatics, and it is doubtful that American doctors are lagging

behind their Iceland colleagues in their prescription patterns.

However, even a figure as high as 90% does not satisfy the Chicago team

whose report in the same issue (page S183) declares: “There are a large

number of persistent asthmatics who are not prescribed these medicines by



their primary physicians.” This time, not parents, but physicians are suppos-

edly reluctant to prescribe. What are the reasons for not prescribing steroids

to every single asthma patient? Who dares not follow the steroid-enforcing

guidelines? The article reveals that “A significant percentage of pediatricians

surveyed have discontinued inhaled corticosteroids due to perceived (!?) side

effects.” It is of interest that “urban pediatricians and pediatricians who grad-

uated from medical school after 1989 were more likely to use inhaled corti-

costeroids for all classes of persistent asthma.” It means that in small towns

and villages, where doctors know each person, they seem to discontinue

medications when their young patients experience adverse effects. However,

when the older doctors retire and urbanization reaches these small commu-

nities, steroids will reign in that obedient and impersonal world.

So, now, we have an asthma epidemic. Soon, with the rising number of

prescriptions for steroids, we may have an epidemic of deaths among asthma

patients, but wait: the scientists will find new explanation for this too.

IS ASTHMA AN INFLAMMATION?It is important to understand why steroids should never have become first-line

asthma remedies. We have already spoken about the phenomenon of allergic

inflammation, immunogenic in nature. Unlike in other inflammations, the

tissues may long remain physically intact even with the changing chemistry.

For years, the integrity of the bronchi and lungs in asthma may be preserved,

and their dysfunction may remain reversible. Tissue scarring appears only in

advanced stages of the disease. Calling asthma an inflammatory disease

without specification as to what causes this inflammation is wrong, in the

sense that the inflammation in the respiratory tract is the process resultant

from the histamine-induced cascade of mediators and cytokines.

There is a parallel with migraine that occurs due to histamine- and

serotonin-induced chemical changes in the neurovascular tissues, but is only

occasionally labeled as a neurogenic inflammation. It is also unscientific to

omit the specific causative chemicals when speaking about inflammation in

asthma, because anti-inflammatory medications should have specific targets,

concrete inflammatory mediators or cytokines. The generally accepted term

inflammatory regarding asthma is dangerous because it justifies an early

introduction of steroids as potent anti-inflammatory drugs allegedly

targeting the cause of the symptoms, while in reality, targeting the

secondary events. Contemporary allergy supports this term and, correspond-

ingly, the aggressive use of steroids.



The dangerous signs of the suppressive approach are seen everywhere but

are silenced, downplayed or distorted. Maybe one day, a daring journalist or

a scientist will share with us the figures of steroid-dependent asthmatics who

are crippled by frequent fractures (osteoporosis), suffer from diabetes, die of

strokes (hypertension), undergo cardiac surgery or surgery for peptic ulcers,

suffer vision loss because of cataracts, become infertile or have miscarriages… .

Will there be a journal that will publish this medical information and these

statistics? Will there be a daring lawyer who files a class action suit similar to

those against tobacco and asbestos industries? Will there be a court that will

grant a judgment in favor of the victims, as were the judgments in those cases?

Peer pressure forces even apparently independent leading experts to

change their position (probably, not really their views) in favor of steroids. We

have already quoted Dr. O’Byrne, a leading Canadian respirologist, who said in

1996 that “the long-term risks of (steroid) use are still a concern to many,

patients and physicians alike.”82 In April 2000, the same scientist told the 200

professionals at the annual Allergy Update symposium in Toronto that inhaled

steroids were free of unwanted effects in proper doses, and that they provided

optimal control in most cases. Unfortunately, Dr. O’Byrne did not share with

the audience what those encouraging data might be, and when and from

where he had received them within the 4 year period between his declarations.

The 1997 president of the Canadian Society of Allergy and Clinical

Immunology, Dr. Z. Chad, proudly said in his interview with Family Practice

that Canada was a world leader in treating asthma with higher doses of

inhaled steroids, and even the U.S. was lagging a little behind in their early

introduction. The Canadian updated guidelines recommend steroids at a very

early stage, and this dubious practice makes the country the frontrunner. The

guidelines start and end with steroids. This, certainly, has not helped to

improve the asthma situation, and “Asthma remains the only preventable

disease where the morbidity and mortality are still increasing in most parts of

the world.”94

Of certain interest is that usually, guidelines recommend what to use and

do not indicate what NOT to use, especially in resistant asthma, when

anything that relieves the plight of the patients should be encouraged. So, the

Canadian allergists became the frontrunners in advising against the use of

histamine in their guidelines! I guess I should be flattered that my case has

created a precedent in the century-old history of histamine. Regrettably, this

is a dirty history, and the document produced by the Guideline Advisory

Committee in February 2002 is the best illustration of this miserable situation.95



It indicates the “areas of high need and the identification of future topics,” in

other words, what medical areas require most of the attention. Asthma is not

even among them; in comparison, nonfatal, rather infrequent bronchitis has

found its place there. This can be explained either by the reluctance of special-

ists once again to reveal their impotence with asthma, or because the effect of

the efforts to conceal helpful knowledge has been so effective that even the

guideline creators mix up asthma with trivial bronchitis.

COMPARISON OF MEDICINE AND LAWDuring my discipline hearings at the CPSO and in the subsequent courts, I

became acquainted with the underlying mechanisms of litigation that, prob-

ably, have not changed since Shakespeare when the proverbial desire to kill all

lawyers was annunciated. Lawyers on both sides make long speeches, and,

judging by the bills, their preparation takes even more hours. They bring in

irrelevant facts, dwell on redundant aspects and dress their ideas into a

flowery garment of verbiage. They are not responsible for the results, since

there is always a judge above them. His decision may not depend on the logic,

documentation or evidence, but on the hidden interests of some powerful

entities. The higher the profile of the case, the more dependent is the judge’s

decision on these powers, and the more it is predetermined. However, this

book is not about the legal system, it is about medicine. Regrettably, medical

research is similar to litigation.

Any research must have a grant, since its conductors need to have food on

their plates. The grants come mostly from pharmaceuticals. If the results of the

research are published and/or presented at a symposium (also sponsored by the

drug companies) in addition to “food,” the scientists receive high “tips”—free

flights to and accommodation at the exotic or grand places where most of the

gatherings take place. Therefore, the subject of study becomes of lesser importance

than the generation of the number of topics to be researched. This produces

numerous, irrelevant and redundant studies, even such laughable ones as

asthma prevalence among those who are born with a large head circumference

or in families following an anthroposophic philosophy.

In the “medical courts,” the “judges” are the drug companies. They are

guided by one desire only—to increase the revenues from drug sales. Cure of

a chronic disease means a loss of profit and must be prevented. Research in

the areas distracting from the curative paths serves the purpose. The costs of

the grants given to scientists are nothing compared to the returns from the



drug sales, and this explains why subsidies for research that prevents revealing

dangerous true facts are especially lavish.

If lawyers impress the audience by their court attire, doctors use their

titles to impress. The opposing and even contradictory data look like profes-

sional dialogues, while the judge called Big Pharma (Big Brother?) allows this

verbiage to continue and knows the decision in advance. The audience in the

“medical courts” is the patients. They are misguided about the validity of new

hypotheses through the medically uneducated and, therefore, easily misin-

formed media who are also usually misguided by the spokespersons for the

drug companies. The public trusts journalists more than drug companies and

does not suspect the behind-the-scene brainwashing of those who write the

stories on the new “discoveries.” These stories cause enthusiasm through their

terminology and the titles of the researchers. Patients try to fit their symp-

toms into the framework of every newly theory to find the explanation for

their symptoms. The choice is so wide that there is always a suitable theory.

While the deception of lawyers has become proverbial, patients still cannot

believe that doctors may be corrupt as a profession.

Three different provincial governments of Ontario knew about my

“Histaminegate.” None interfered despite the letters they received from the

patients deprived of histamine that had allowed them to live drug-free, despite

major media coverage most sympathetic to my patients, and despite emergency

rooms full of asthmatics. Governments lament the lack of money in the public

health system, and with the quadrupling of asthma figures within the last two

decades in Canada that necessitate over 600 million dollars annually, there

was no intervention. All the courts, including the Supreme Court of Canada,

disregarded the exhibits proving the great public interest in the asthma solu-

tion. They overlooked the forged and misrepresented the key evidence

submitted by the CPSO in their court documents. They even turned a blind

eye to the College’s violation of its own bylaw as well as its violation of the

federal law. The courts protected Verbatim, the court reporters, in their

production of two versions of transcripts, one with a forged signature of a

court reporter, and disallowed the cross-examination of the manager and/or

the court reporter.

The interests of the medical and legislative bodies merged somewhere. This

was probably easy to do, since, like all legislative bodies, the College, is headed by

lawyers. No appeal was ever granted. No explanation was ever given. This despite

the fact that the tape produced by the Canadian Broadcast Corporation showed



a gathering of about 200 of my patients requesting the treatment, which,

according to Canadian Law means that the appeal is in the interest of not only

the appellant, but a group of people and has therefore to be considered.

Up until now, on the Internet, the College presents false data of allegedly 5

existing complaints from my patients, whereas there never were (and are)

none. The details of the improprieties would require a book, not a paragraph.

For now, all I want to say is that although there are good and bad judges, hista-

mine therapy created a problem that was beyond the ability of any judge or

panel to decide upon.

All laws are trampled when the Medical Mafia is in charge. When billions

of dollars are at stake, the only judge is His Majesty Corporate Money. The

idea is not new. John Polanyi, a Nobel Laureate said in March 1999 at the

conference Secrecy in Science, which took place in the US, that “scientists’

freedom to speak is being restricted today by industry and governments’

attempts to protect commercial interests.” Secrecy in medicine is much

deeper than in any field, since the profits from its product sales, drugs, are

incomparably higher than in any other field. Secrecy in allergy is probably

higher than in other medical areas first, due to the high prevalence of aller-

gies and asthma, and second, due to their reversibility and hence, the poten-

tial resultant loss of patients as customers.

Asthma patients, you are in the medical court. The medical elite enjoy

their “litigation process”: they discuss what kind of steroids to prescribe and

in what dose. They write papers on which is better—asthma, hepatitis A or

tuberculosis. They try to solve the puzzle why asthma figures are much lower

in the polluted India than in the sterile-clean New Zealand. Only in the US a

“judge” enjoys the $10 billion plus from the annual sales of asthma therapeu-

tics and provides unlimited grants for research that covers these topics.

Meanwhile, the asthma figures get more frightening from day to day, and

medical professionals have started to blame patients for the increase. “Patient

ignorance about asthma and its management has been identified as a major

cause of morbidity and mortality,” writes The Canadian Journal of CME in the

March of 1996. In this context, ignorance means lack of interest in the knowl-

edge of how and what inhaled or oral medications to use.

Centers that proudly call themselves “educational” have opened in North

America, and physicians teach asthmatics how to use inhalation devices prop-

erly and when to escalate the steroid dosage depending on the measurements

of the peak flow meter. Another novel strategy has been dreamed up in



Canada with the purpose “to change patient behavior such that they would be

able to control their asthma rather than be controlled by their asthma.”

Sponsored by Health Canada and GlaxoSmithKlein, “a new milieu for asthma

care—the community pharmacy” has been created, “with pharmacists taking

responsibility for outcomes, assessment of a patient’s readiness to change and

tailoring education to that readiness… and physician consultation to achieve

asthma prescribing guidelines.” Some 27 pharmacies and 33 pharmacists took

part in the study, which showed the approach was cost-effective, as it reduced

the number of visits to doctor’s offices as well as ER admission. There is no

mention of the medications used that allegedly improved the situation;

instead, the article emphasizes educational value of the enterprise.

However, with no other means than steroids, we can be sure that the educa-

tion included the proper use of puffers and the intensified use of steroids, most

probably, the combination drugs, as is the fashion now. If this approach96

becomes accepted, the specialty of allergy as a medical discipline will be wiped

out: the proper use of immunosuppressive medications will replace the need to

study the immune mechanisms and repair them. Even by a wide stretch of the

imagination, one cannot call these measures educational, since what they teach

is skill, while education would mean the knowledge on what underlies asthma.

But then, the doctors involved are not knowledgeable themselves.

Doctors have actually removed themselves from the grim asthma statistics,

and it is now the patients that shoulder the burden of the problem. Asthmatics

should take care of themselves in every day life and inhale, swallow and sip

steroids, while specialists operate in their “medical courts,” and “save” their

patients in emergency rooms.

IMMUNOTHERAPY IN ASTHMA—STATE OF THE ART Immunotherapy is the only way to cure asthma because it repairs the failing

immune tools. Asthmatics are rarely prescribed it because.” …immuno-

therapy is an effective treatment under optimal conditions, but of course its

safety is currently being questioned.”97 This article published in JACI says: “It

has been observed that patients with asthma are particularly prone to develop

systemic reactions during immunotherapy.” Complications of conventional

immunotherapy are rooted in the improper way of conducting and inter-

preting allergy skin testing, as we spoke about that at length earlier.

Although in its potential, immunotherapy has remained “the heart of our

specialty”98 allergists turn to it only when all other means fail. Absurdly, there is



consensus among the leading immunologists that immunosuppression by

steroids should precede attempts to repair the immune system. The absurdity of

this sequence is disregarded. Thus, the medical director of the Johns Hopkins

Asthma and Allergy Centre in Baltimore told the delegates of the Tenth Annual

Allergy Update symposium in Toronto in 1993 that immunotherapy is

warranted only in the cases where medications are unsatisfactory or produce

intolerable side effects. Evidently, the prescribers do not expect much from

immunotherapy in a clinical setting. Otherwise, why did they suggest the already

failed steroids to be taken concurrently with immunotherapy? Just think:

specialists recommend steroids not only after they are discontinued due to their

adversities, but along with immunotherapy. There can be one explanation only:

the protection afforded against possible severe systemic reactions to allergy

shots. Immunotherapy conducted along with steroids is deprived not only of a

scientific basis but simple logic: two diametrically opposite treatments target the

same T-cells! Steroids suppress them, while allergy shots try to restore!

In view of unpredictability and growing morbidity of asthma and in view

of the serious side effects of the primary medications, asthmatics are the most

vulnerable group of allergy sufferers. Therefore, more than others, they need

the immune repair. Unfortunately, their chances to get proper immuno-

therapy are almost zero. The conventional way of allergy testing can never

lead to successful immunotherapy.

IN FAVOUR OF HISTAMINE THERAPYMy criticism of the conventional asthma treatments, steroids in particular,

inevitably sounds like advocacy for histamine. A critical reader may be suspi-

cious that, like any drug, histamine is not devoid of side effects. There is only

one—the possibility of triggering an aggravation if the dose is higher than

needed. But then, everything is good in moderation. Given in a dose higher

than the body needs, even some of the worshiped vitamins and minerals are

harmful. In other words, histamine therapy may have a dark side, but is it

equal to steroids in producing side effects? Not in the least. We are talking

about two opposite treatments.

Steroids are immunosuppressants, even though allergists call them

immunomodulators, and the side effects of different doses differ only by the

degree of the suppression of the cellular functioning. Histamine is recognized

by science as immuno- and neuromodulator, and it is the extent to which it

is able to regulate or modulate the cellular production that varies with the dose



and the individual. We thus compare the degree of the weakening of the

immune system by steroids vs. the degree of its restoration by histamine. This

is a huge difference.

With daily suppressive steroids, the defensive part of the whole immune

system slowly dies, and due to the shriveling adrenals and the growing resistance

of asthma, the body starts to rely on the drugs more and more. Never forget that

side effects of daily steroids are a reality at any dose. Many of the adverse effects

are diseases, and some are more debilitating than asthma itself. At the same time,

side effects of histamine are limited to temporarily intensified allergic and

related symptoms: dizziness, a headache, a more congested or runny nose, more

pronounced skin itch or heavier breathing. Even these manifestations are tran-

sitory, lasting only minutes and rarely a few hours. An observant doctor can

reduce the adverse effects to minimum and provide a smooth recovery from the

very start by asking the relevant questions before and after the skin testing and

during treatment, before and after each therapeutic injection.

The key difference between steroids and histamine lies in the fact that the

degree of the (temporary) improvement due to steroids is proportional to the

general suppression of the immunocompetent cells on the whole, including

their production of the protective chemistry, whereas the strengthening of the

targeted H2/3 receptors leads to the restoration of the normal cellular func-

tioning of all receptor-bearing cells and hence, normalized production of

histamine and numerous anti-disease mediators. Another fact in favor of the

histamine immunotherapy is that one can stop it at any time, whereas

steroids often require tapering because of the physiological dependence on

them.

Unlike steroids that are not recommended for kids under 4 or 6, histamine

is especially effective in children and babies. As I said in my presentation at the

international symposium in 1989 in West Berlin, the younger the child, the

better the results. It can be due to a more resilient immune system of a young

body. A lot of people, especially children, whom I treated with histamine

remained symptomless and drug-free for years.

Is there interaction of histamine with other medications? Yes. Histamine is

incompatible with steroids since it tries to restore the functioning of the same

cells the steroids extinguish. If steroids were taken before therapy with hista-

mine, such immunotherapy may be less successful and require a longer treat-

ment period, because to revive the suppressed cells is more difficult than to

activate the ones that are untouched. Cells suppressed by steroids, T-cells first



of all, may never be able to regain their functioning. This explains why the

immunotherapy conducted concurrently with steroids cannot thus be effective.

Histamine therapy is also less effective in those patients who take H2-

receptor suppressors such as Zantac and Pepcid, prescribed for gastroin-

testinal problems. This is because histamine injections activate H2 receptors,

and their simultaneous activation and suppression are impossible.

Histamine injections are the therapy that repairs the flawed receptors and

increases the efficiency of T-suppressor cells. In the majority of cases, the effect

may even last months or years. Only in those with the most inflexible immune

system, the treatment may continue throughout the patient’s life. Chances are

high that the patients become independent from daily medications. Histamine

may also eliminate the accompanying symptoms, seemingly allergy-unrelated,

often nonspecific and therefore undiagnosed. Suffice to say that the normal-

ized function of T-cells in general not only rids patients of allergies, but also

strengthens the whole immune system and by that, rids them of superimposed

infections. T-cell strengthening may also be beneficial in another respect.

Recent studies in San Diego and Goteborg, Sweden, showed that the combi-

nation of histamine and inflammation-promoting mediators in melanoma

increased the number of killer cells by 62 times, whereas the mediators alone

provided only 5-fold increase. Since any defense against cancer is based on

killer cells’ ability to destroy tumor cells, it is logical to assume that histamine

can be beneficial in cancer. This subject was thoroughly studied in the ’80s and

early ’90s and discussed in the publications of the Histamine Research Society

Agents and Actions.

The revived cellular talk of the immunocompetent cells with the nerve cells

and the cells of endocrine glands positively affects the functioning of the nervous

and endocrine systems. Most remarkable is the bolstering effect of histamine on

the adrenals (via corticotropin) that synthesize corticosteroids. Their activation

diminishes the need of the outside help with the synthetic version.

Almost always, the improvement starts at the very beginning of the hista-

mine treatment, actually, at the skin testing. By restoring the efficiency of

T-suppressors and allowing them to fight allergic inflammation, histamine

injections reduce the body’s need for ‘crutches’—other medications, including

histamine itself. It is different with all other drugs when, due to the body’s

adjustment to their regular use, the need of increasing dosages continues.

Last but not the least I need to emphasize the cost of histamine therapy. It

is very low compared to daily drugs and thus, saves personal and public



money. It is this advantage, however, that is viewed as a huge threat by the drug

industry, and this outweighs all the beneficial properties of histamine therapy.

The purpose of any treatment should be to rid patients of the disease,

whenever possible, or at least control the rate of decline and symptoms for the

longest period possible and by the safest means possible. Histamine injections

reach the goal other medications are meant to reach, but does it with an

immeasurably higher effect and lesser degree of complications. I saw that in

asthma, histamine worked better than in any other allergic disease. This can

probably be explained by several factors.

Compared to other tissues, the lungs possess the highest concentrations of

mast cells and basophils. The number of these cells exceeds those in other

organs also due to the large lung surface and to the permeation with blood

vessels for oxygenation. Thus, when histamine injections inhibit the leakage of

histamine from these cells, the magnitude of the effect is most apparent in the

lungs. The positive aspect of this is that the very same facts make asthma a very

dynamic and reversible disease, in the absence of organic tissue changes

common for advanced or neglected cases.

AN UNFAILING DRUGYou may wonder if histamine works in all cases. Nothing is absolute in nature.

There are, after all, asthmatics who do not respond to steroids. Basic sciences

explain this phenomenon as the result of an irreversible defect of steroid

receptors. One learns whether one is a responder or not only after trying a

treatment. If steroids do not work, they should be stopped because they may

only harm. The high doses prescribed in the hope of improvement may lead

to serious consequences, particularly unreasonable because their consumers

get no relief from their asthma. Unfortunately, in view of the lack of any

substitute, steroids are still prescribed in escalating doses with the accompani-

ment of add-on drugs. These patients, in addition to having resistant asthma,

acquire dependence on steroids plus numerous side effects.

Histamine may not produce any effect when there is a genetically prede-

termined irreversible defect and/or irresponsiveness of the H2/3 receptors.

However, a trial with histamine can do no harm. A potential temporary

aggravation can be reduced to a minimum through a slow dose increment,

and the attempts can be stopped at any moment. Practice proves overwhelm-

ingly that the majority of patients who are not steroid-dependent, respond to

histamine injections.



Would you want to try histamine therapy? Even if you would, you can’t.

Even if steroids fail in your case. Even if your condition forces you to abuse the

condemned bronchodilators. Histamine therapy is not in the guidelines. In

Canada, it was even banned when the medical Establishment realized that

patients with allergies and asthma, whom I treated, recovered in large numbers.

Regrettably, doctors all over the world who conduct histamine therapy are

forced to do this empirically, since the theoretical knowledge that could support

their therapy is hidden. They grope in the dark trying to select the dose. Having

been taught that histamine is allergy-conducive only, they are afraid of aggra-

vations, unable to explain them and may give up on the therapy that could save

their patients. They cannot speed up the improvement because a higher dose

does not necessarily mean a faster recovery. They often combine histamine

therapy with different irrelevant substances and do not understand that the

effect is due to histamine. The flaws in conducting histamine therapy belittle

its wonderful properties and accentuate its negative role in allergy. The vital

information disappeared even from those few textbooks that had once

contained it. Medicine dictates you swallow or inhale daily steroids and bron-

chodilators and be happy if you are a responder.

TO USE A DRUGThe US Food and Drug Act is based on the general premise that “…once a

drug is approved to be marketed for any one indication, physicians are legally

free to use it for any other indication without any additional evidence.”99 This

quotation is from an article published in one of the most prestigious medical

periodicals, the Journal of American Medical Association. It is written by Dr. D.

Eddy, Professor of Medicine and Mathematics, consultant to the U.S.

Government on drug use and author of the monthly column Clinical Decision

Making. Histamine therapy, described in the remote past in detail even in

textbooks100 and later substantiated theoretically101 should be available and

free to be employed by a trained doctor. As Eddy describes, “hundreds of

diagnostic tests, devices, procedures and services are currently used and paid

for without any evidence of effectiveness for any indication.”

By contrast, the efficacy and safety of histamine are confirmed by

numerous open clinical and double-blind studies. The recognition of its

safety comes from the fact that histamine is a non-prescription drug. The

most astounding fact exposing the deplorable lack of knowledge by immu-



nologists of the dual action and potency of histamine is its common use as a

placebo (?!) in controlled trials for allergen extracts.

Basic sciences know more about histamine than about most medications.

It belongs to the group of autacoids due to its natural remedial effect. The

regulations of the central legislative body of the drug industry do not prohibit

the use of histamine since it fits into the framework of hundreds of other

drugs referred to by D. Eddy as those “once approved to be marketed.” The

1988 Helsinki Accord on Human Rights, signed by the governments of all the

participating countries, including US and Canada, states that a practitioner

can use any remedy at his discretion if it is not more dangerous than the

conventional means. So far, there has never been a report on the danger of

histamine in clinical practice. On the contrary, clinical trials proved its

success. But the august medical authorities will not allow it. Any pretext is

good. Some say it is dangerous—then, why is it used as a placebo in trials?

Others say it gives a psychological effect only—then, why is it the standard of

the biological activity of allergen extracts? Logic and scientific facts become

redundant when the decision makers violate the very laws they created.

Ultimately, you are just an asthma sufferer without medical knowledge,

power or the right to make a decision for yourself or your child. You are

doomed to succumb to the management imposed on you by the medico-

pharmaceutical conglomerate conveniently supported by governments and

legal bodies, but not by law.

FREEDOM OF CHOICE IN SCIENCEWhat is the future for asthma sufferers? In my opinion, it is grim. “Asthma

must be viewed as a chronic and possibly irreversible (!) disorder,” and

“therefore, prevention of this disorder will be the most effective treatment,”

declared Dr. W. Busse, the 2001 president of AAAAI, in his article published

in the special issue of JACI covering the conference sponsored the National

Institute of Allergy and Infectious Diseases.102 As the title of this meeting

indicates—21st Century Management of Upper Respiratory Allergic Diseases: A

Focus on Allergy and Asthma—its purpose was to establish the guidelines for

the next millennium. Since prevention in the language of allergists means

steroids that allegedly prevent allergic inflammation, the verdict—“irre-

versible”—sentences asthma patients to life-long consumption of steroids.

This is confirmed by the Canadian Compendium of Pharmaceuticals 2001 that



lists inhaled steroids under the heading Asthma Prophylactics (p. 1642).

Manufacturers of inhaled steroids are multinational companies, therefore the

entries in the compendia in other parts of the world are the same or similar.

The hands of those who offer an effective resolution to chronic medical

problems are tied, and the recent strict guidelines are the manacles. “Legally”

is a robust adverb—it justifies many ill-gotten gains,” said Honore de Balzac.

Guidelines that should never be legislative, have become legal restrictions in

allergy practice. The reasons for the restrictions are simple. Grants and funds

for research are the central elements that drive the developments in medicine.

The high costs of funding can more readily be turned into continuous profit

streams by drugs that only offer temporary relief instead of an actual cure.

Therapies that may provide full or lasting independence from daily drugs are

unacceptable as loan repayments. Asthma patients from all over the world are

paying the pharmaceutical industry for research into the drugs that may

cripple or even kill them.

As an extreme mockery, our democratic society gives asthma sufferers

freedom of choice: 1) a bronchodilator of any kind with any imaginable

delivery system; 2) a steroid drug in any form: oral, injectable, inhaled; 3) the

recently developed (and already restricted) combo drugs consisting of a bron-

chodilator and a steroid; 4) a number of ineffective adjunct medications to be

taken along with the main two. All the choices are compulsory. Asthmatics

can also choose to wait until medicine sorts out all the genes, studies their

interrelationship, develops methods of genetic engineering in asthma and

starts using them on a wide scale. How soon will it happen? “Gene therapies

currently show little promise for treating this prevalent and generally non-

morbid disease,” states another speaker of the conference.103 Paradoxically, we

can be grateful for the fact that it is not going to happen soon, since, as

legends say, the ancient Atlantis perished because its medical professionals got

the false idea of their grand abilities and created genetic monsters such as

mermaids and centaurs.

It is evident that the status quo satisfies all parties involved in asthma but

the patients. Drug developers get back what they invest into the new research,

plus a little more (a little?), researchers get their grants and bonuses, doctors

have an unceasing stream of asthmatics in their offices, engineers develop

devices for asthmatics, hospitals enlarge the areas to accommodate all those

who gasp for air, nurses get special training in teaching asthma patients how



to avoid environmental triggers and how to use their inhalers properly and

become experts in reduction of steroid doses. And finally, pharmacists have

joined the party and now not just dispense the medications, but consult

patients and their doctors (!) on how to intensify the use of steroids.

You may ask where the governments are that spend millions on health

services? Governments’ corruption is an open secret, and their protection of

the most lucrative industry is not a secret either. In the case of asthma, the

annual direct casualties provided by the official statistics (definitely below the

real figures) are only (!) 60,000 deaths annually among the 130 million

sufferers in western countries.104 “Death from asthma is rare,” informs us a

flyer sponsored by The Lung Association of Ontario. Is it? Are the figures of

5,000 plus and growing for the US and over 500 for Canada still too low for

the governments to be bothered about? What figure will be good enough to

start an inquiry?

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10. N. Pearce et al. Asthma Epidemiology: Principles and Methods, New York, Oxford UniversityPress, 1998, preface

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29. T. Kino, G. Chrousos. Tissue-specific glucocorticoid resistance-hypersensitivity syndromes.JACI 2002; 109:609-13

30. M. Liu et al. Effects of prednisone on cellular response… JACI 2001; 108:29-3831. N. L. Jones. Can Respir J 1995;2:8832. L. Lichtenstein, Allergy and the Immune System, Scientific American 1993;269:117-2433. P. Gergen. Understanding the economic burden of asthma. JACI 2001;107:S445-834. C.P.Page. Beta-agonists and the asthma paradox. Practical Allergy & Immunology. 1992;7:87-9435. A. Tattersfield. Foreword. Lancet 1997;350:SII36. 1993;269:117-2437. S. Romagnani. The Th2 hypothesis in allergy– Eppur si muove! Allergy Clin Immunol Intern

1998;10:158-6538. JACI 2000;105:205-1039. R. Beasley et al. Prevalence and etiology of asthma JACI 2000;105:S466-7240. N. Pearce et al. Asthma Epidemiology. University Press 199841. P. Avila Interactions between allergic inflammation and respiratory viral infections. JACI

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revisited. Can Respir J 2000;7:182-18747. E. von Mutius. Editorial. Clinical and Experimental Allergy 2001;31:1651-248. E. Grant et al Observations on emerging patterns of asthma in our society JACI 1999;104:S1-949. H. Bourne, L. Lichtenstein, K. Melmon et al. Modulation of inflammation and immunity by

cyclic AMP. Science 1974;184:19-2850. A. Page. Beta-Agonists and the asthma paradox. Practical Allergy & Immunology 1992;7:87-9451. F.E. Spitzer et al. Beta agonists and the risk of asthma death and near fatal asthma. Br. Med. J.

1992;326:501-652. According to the Journal of the American Medical Association, Feb. 2002, 87% of the experts

who formulate practice guidelines for the whole profession have financial ties to the drugindustry. Their subsequent published guidelines favor, in more than 90% of the cases, thosevery drugs that those drug companies make.

53. S. Agarwal, G. Marchall Jr. Beta-adrenergic modulation of human type-1/type 2 cytokinebalance, JACI 1999;104:91-8

54. A. Page. Beta-agonists and the asthma paradox. Practical Allergy & Immunology 1992;7:87-9455. M. Fitzgerald , p. Macklem. Proceedings of a workshop on near fatal asthma. Can Respr J

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PART EIGHT

ALLERGIC DISEASES

CHRONIC RHINITIS, SKIN ALLERGIES, HAY FEVER

All allergic diseases have, in principle, the same immune roots, but as they

affect different organs, the manifestations are different.

INTRODUCTION

A. CHRONIC RHINITISWe know its root rhino from the familiar rhinoceros, and both words come

from the Latin—nose. This chapter covers chronic rhinitis, which is a pro-

tracted, often life-long non-infectious, allergic inflammation of the nasal

mucous membrane.

The nose is a protective filter against physical, chemical and infectious

agents. Its sieve-like structure with its narrow passages prevents particles from

getting inside. The secretions of its mucous membrane are designed to

neutralize those chemicals and disease-causing bacteria that do get in. Both

Plot/Allergies•318-395 11/21/03 2:00 PM Page 318

infectious and allergic inflammation contribute to the impairment of the

mucous membrane. As the lining loses its protective ability, the door to

secondary infections is opened.

The statistics on chronic rhinitis vary from source to source, but it is

agreed that more than 25 per cent of the population suffers from it. However,

it is important to note that chronic rhinitis is much more common than

asthma. Then, the data reflect the diagnosed cases, while a lot of people have a

mild form and these people do not become part of the numbers; for them it is

mostly an inconvenience, too mild to visit a doctor. Many have episodic attacks

which are usually misdiagnosed as a recurrent cold. All this distorts the statis-

tics, and the true figures for rhinitis may be closer to 40% in the population.

CLASSIFICATIONChronic rhinitis exists in several forms. One is allergic rhinitis, which can be

divided further into two kinds. A seasonal form provoked by pollen is a part

of hay fever. The other group includes patients with perennial symptoms trig-

gered by other allergens, for instance, dust mites.

There is yet another form of chronic rhinitis, in which the symptoms are

triggered not by allergens but by nonspecific factors such as changes of envi-

ronmental temperature, air impurities, emotions, change of posture, awak-

ening, biological cycles, etc. Nonspecific triggers are innumerable, and therefore

these people may suffer all year round or have spontaneous relapses. Their

rhinitis is called vasomotor and its Latin roots indicate that the condition is

related to the fluctuations of blood flow in the vessels: vasus—vessel and

motor—movement. In fact, the term is not very precise, as similar vascular

changes are present in all forms of rhinitis. Allergen-related seasonal and/or

perennial forms of rhinitis often coexist with nonallergic or vasomotor rhinitis

in one and the same patient.

Although conventional medicine labels these forms as allergic and non-

allergic, the underlying mechanisms of all forms of chronic rhinitis are basi-

cally the same: they are all caused by malfunctioning immunocompetent

cells, which are responsible for the allergy-controlling part of the immune

system. Change in the body chemistry provoked by a histamine spill leads to

two events which then lead to the symptoms of rhinitis:

1. an engorgement of the vessels and thus, an increase of the blood flow in the

nasal mucosa;

2. excessive secretions, i.e. nasal discharge and/or obstruction.

Allergic Diseases 319


THE SYMPTOMSIt is fairly easy to differentiate chronic rhinitis from an infection, as it is often

accompanied by other allergic or related symptoms. These may vary from

patient to patient and include a chronic cough as a sign of the accompanying

asthma, or various ear discomfort, or allergic dermatitis. The fluctuating nature

of the symptoms is another clear indication of the allergic origin of chronic

rhinitis. Family history often elicits allergies, asthma or related diseases in close

relatives, and thus provides another proof of the allergic nature of the illness.

Chronic rhinitis is a trivial disease when compared to the numerous

debilitating conditions also found in this area of medicine. However, its

persistent course and the accompanying allergic inflammation spreading to

the surrounding areas create a dismal picture. Inflammation of the nasal

membranes may produce local swelling and irritation leading to a prolonged

itchy, drippy, plugged or runny nose and sneezing attacks. The obstruction,

due to the swelling, can make simple breathing a difficult or even painful act.

Nasal drippings become a nuisance and force the sufferers to carry boxes of

tissue with them. Non-stop sneezing attacks are exhausting also. The symp-

toms, benign at first sight, can make a person’s life miserable. At times, they

are similar to a severe cold or flu without a high temperature. Indeed, in hay

fever season, it looks as if there is a flu epidemic going around. The inability

to breathe through the nose wakes the patients up at night. They often snore

and thus may affect the sleep of others as well. The broken sleep pattern may

lead to irritability, depression and insomnia. Thus, a simple condition—a

stuffy nose—often turns into a devastating medical problem.

Allergic inflammation of the nasal mucous membrane is seldom a space-

limited disease. It often spreads beyond the nasal area into the sinuses—air

cavities on the sides and above the nose. This creates a feeling of heaviness in

the area, and patients with rhinitis often have “sinus headaches.” The term for

this combined condition is allergic rhinosinusitis. As with other diseases of

hypersensitivity, the term allergic is not accurate in relation to chronic

rhinitis, since allergens may have nothing to do with the symptoms. Just how

common this condition is becomes evident from the repeated TV advertising

of drugs for the relief not only nasal symptoms but also of “sinus headaches”

as well. These combo drugs contain antihistamines, decongestants and

painkillers in different proportions.

Postnasal drip is another unpleasant accompanying symptom. The

phlegm formed by the secretions from the nasal lining gets into the throat



and causes discomfort, soreness and a throaty cough (not to be mixed up with

the chesty cough in asthma). Unfortunately, doctors do not routinely differ-

entiate between a viral and bacterial throat infection and an allergic pharyn-

gitis. Even worse, some allergy patients are diagnosed as having chronic

tonsillitis and enlarged adenoids. As a result, many, especially children, end up

having unwarranted tonsillectomy and/or adenoidectomy, and adults go

through nasal surgery. It always reminds me of the saying that the best

remedy for dandruff is a guillotine. Just how unnecessary and harmful such

surgery tends to be is well described by a well-known American pediatrician

R. Mendelssohn in his book Confessions Of A Medical Heretic.

Lately, there is a strong tendency to single out postnasal drip as a separate

condition leading to asthmatic-like cough instead of recognizing it as a

symptom that may accompany chronic rhinitis and/or asthma.

RECURRENT OTITIS?Ear, nose and throat form one apparatus, hence the name of physicians who

treat the diseases in this area—ENT specialists. The spread of allergic inflam-

mation to the eustachian tube that connects nasal passages with the eardrum

area is accompanied by poor drainage and thus, accumulation of non-infec-

tious fluid in the middle ear. The condition is called otitis. This term implies

any inflammation in the ear, infectious or non-infectious, which naturally

leads to confusion. As a result, recurrent allergic otitis, which usually appears

in parallel with allergic rhinitis, is almost always misdiagnosed. When allergic

inflammation spreads to ear passages, it may produce signs similar to infec-

tious otitis, such as fluid accumulation behind the eardrum, plugged ears and

poor hearing, itch, discomfort or even pain.

The absence of a fever and/or pus points to an allergic nature of the

condition and, therefore, does not call for antibiotic treatment. Besides, like

any disease of hypersensitivity, allergic otitis has a characteristic course of

frequent recurrence and fluctuations and is accompanied by other allergy

symptoms; pre-existing chronic rhinitis is most common among them.

Regrettably, a proper differential diagnosis seems to be a challenge for a lot of

doctors. Furthermore, even though allergic otitis is so common, its discussion

is virtually absent from medical textbooks as a disease in its own right or as a

companion to chronic rhinitis.

Allergic otitis often becomes the reason for numerous troubles in school-

children. Due to plugged ears, these young patients may not hear well and are



ashamed to admit that to their teachers. They may not even be aware of the

problem. Poor hearing affects their concentration and comprehension of the

material. Add to that the constant symptomatic discomfort from the other

accompanying allergy symptoms, and you will understand why such a child

is in trouble. The symptoms may be mild, and therefore the child disregards

them. However, they distract from studies, and such a child is often labeled by

the teachers as a poor learner. The child may carry the label through his entire

school years. It may become a lasting psychological wound especially for

sensitive children who, in reality, may be quite bright. The situation may trau-

matize the whole family. The number of kids having allergic rhinitis grows in

proportion to the rising incidence of all allergies that are hitting the younger

generation more and more frequently. This basically harmless illness (it

doesn’t kill one) does, however, continue to create various chronic medical

and social problems.

Mothers, not familiar with the medical subtleties, sometimes overreact to

their child’s symptoms, and with the very first complaint, take their kid to a

doctor. Unfortunately, very few doctors take a swab, to confirm or disprove an

ear infection, if they see redness in the external canal, which they interpret as

inflammation. Hence, antibiotics are routinely over-prescribed. It is almost as

if a prescription seems to be ready and waiting for the patients. In fact, even

if the ear passages do look red and inflamed, these signs are nonspecific and

common for allergic condition as well. Antibiotics may temporarily improve

the condition due to their collateral non-specific action, although it is

possible that a remission is spontaneous and reflects the fluctuating course of

any allergy. The frequency of these prescribed courses of antibiotic drugs

contributes to the evolution of antibiotic-resistant strains of bacteria, now

one of the worst problems in world medicine.

However, the real reason for prescribing antibiotics so liberally and unnec-

essary is the growing incidence of respiratory allergies and the inefficiency of

allergy drugs. Antibiotics are, in fact, prescribed to camouflage the impotence

of allergy therapy. Their danger to society prompted a series of articles in

professional sources and in the media. Special medical committees started to

warn doctors against over-prescription of antibiotics, and pamphlets addressed

to patients began to explain the harm of the drugs. But the harm has already

been done and is continuing: fatal, antibiotic-resistant infections threaten our

civilization. As it often happens in medicine, it counts its losses decades later. It

is of more than passing interest that Alexander Fleming, the discoverer in 1928



of the first antibiotic, penicillin, warned in his 1945 Nobel Prize acceptance

speech against bacterial antibiotic resistance as a very real danger that could

make this great drug discovery helpless against infectious disease.

Another way of treating chronic otitis is insertion of tubes into ears “for

better drainage” even though it is a fact that many of the “otitis” cases are an

allergic condition. Indirect confirmation of this comes from the skyrocketing

incidence of allergies, chronic rhinitis in particular, and the correspondingly

rising frequency of “infectious” otitis.

TREATMENT OF ALLERGIC RHINITISIf you are diagnosed with allergic rhinitis, the first advice given will be the

same as in asthma: eliminate from your life anything suspected of triggering

your symptoms. This will hardly relieve your nasal congestion, and there

will be no escape for you from various drugs. However, the question arises,

are those drugs really “various”? What the patients may chose from is as

usual: antihistamines—one, decongestants—two, steroids—three... It turns

out that those numerous names are ultimately many versions of these same

three categories. And just how effective are they for chronic rhinitis? Only a

small portion of allergy sufferers receives real relief from the existing treat-

ments. The poor effects of the “nondrowsy” type of antihistamines, forces

doctors to suggest the sedating ones instead because they, at least, allow the

patient to get a good night’s sleep. In other words, if antihistamines fail to

perform their direct role of histamine inhibition, they play the role of

sleeping pills.

Decongestants in pills, syrups and nasal drops are used alone or in most

fanciful combinations with antihistamines and painkillers. Their presence is

marked with letter D or the words extra and sinus. The drug industry has the

best word-smiths, and their latest contribution is the word liberator! The

effects and side effects of decongestants were described earlier in the chapter

Medications, but as they also possess a rebound effect, it is important to

remember this: consumers should be careful not to worsen their symptoms by

using the medication daily. The vasoconstrictive effect of these medications is

especially dangerous for those allergy patients who have concurrent hyperten-

sion or other vascular conditions of the brain (one of them is simple

migraine). For them, decongestants even in the generally recommended doses

may be outright fatal. The seriousness of the problem (up to 500 strokes a year

in US in young people!) forced the FDA to ban such popular decongestants as



Dimetapp, Contac-C, etc. However, it is easier to give advice to avoid frequent

use of decongestants than to follow it, as patients take them for the simple

need to be able to breathe. Over the time, patients develop tolerance to them,

the efficiency of the medication fails, and this leads to the drug abuse.

First-line therapy in chronic rhinitis is steroids, as they are in asthma. The

best known steroid sprays are Flonase, Rhinocort, Nasocort and Nasonex.

Specialists assure us that nasal sprays are not absorbed to the extent that they

become harmful. However, what really happens we learn eventually from an

allergy-unrelated area. Thus, an endocrinologist who assesses the effects of

intranasal steroids states that these drugs “can be absorbed into systemic circu-

lation through airway and gastrointestinal routes,” and that “the absorbed

drug would retain its native high potency in the systemic circulation.”1 In case

you are wondering why an endocrinologist makes this assessment, remember

that one of the dangers of steroids is their harmful effect on the adrenal func-

tioning and metabolism in general—the areas studied by endocrinologists.

Since manufacturers could be found liable for hiding the facts, they need

to be more frank than allergists. The entries in the pharmaceutical directories

clearly state that pregnant and lactating women, children under 6 years of age,

people with elevated blood pressure and patients with certain chronic

diseases should avoid steroids even in the form of nasal sprays. The drugs’

formal descriptions provided to professionals tell us that these sprays can

decrease resistance to infections, suppress the adrenals and inhibit wound

healing in those who have surgery or trauma. Such complications are proof

that steroidal nasal sprays have an obvious systemic effect.

There is more to steroids: even if they are effective, the groups that should

avoid their use are astonishingly large: they include women during periods of

pregnancy and breastfeeding, which may take place several times during their

life time; young children; trauma/surgery patients, and patients with concur-

rent diseases that can be aggravated by steroids such as hypertension,

diabetes, osteoporosis, peptic ulcer, etc. Add to that the steroid-resistant

population (approximately one/third of the drug consumers), as well as those

who experience severe side effects.

The compendia advise to institute “proper” treatment in case where a

patient falls into one of these categories. Since steroids are usually prescribed

if antihistamines are ineffective, and decongestants fail or are contraindi-

cated, the question arises: what should these patients take? All medical

sources are silent on what proper means in these situations.



Oral steroids in chronic rhinitis are suggested only as short emergency

courses at the height of the pollen season or during severe exacerbation of

perennial rhinitis. Even then, they are to be used only for patients who do not

have certain concurrent illnesses. The textbook Allergy 1985 recommends

(p. 348) a “burst” of steroids to help patients discontinue the abuse of decon-

gestants. However, with all their proclaimed potency, oral steroids not infre-

quently fail in severe allergic rhinitis. Otherwise, why would the authors

recommend using them together with decongestants, which are the very

drugs they want to discontinue? Are two ineffective drugs better than one?

And on what known biochemical basis?

Among other remedies, the textbook lists cool saline irrigations and

humidified hot air. My impression is that the authors do not really believe

that these simple methods will do anything for chronic resistant rhinitis, as

they only casually mention these therapies at the end of the chapter on

chronic rhinitis.

NASAL SURGERY AS A MEANS OF TREATMENTWhen all else fails, surgery is the treatment for the poor noses. Polypectomy

(removal of nasal polyps) is not rare in patients with chronic rhinitis. Due to

the constantly present allergic inflammation, the mucous lining loses its

integrity, and secondary growth of excessive tissue is common. This paves the

way to the formation of polyps (a Greek word for abnormal growth). Polyps

together with the generally swollen mucous membrane create a physical

obstacle, and surgery becomes the only way of giving the sufferer a chance to

breathe. A swollen nasal lining may look on examination as if there is a polyp

and thus become, in the interpretation of doctors, an indication for surgery.

There are enough unscrupulous surgeons around who skillfully wield their

scalpels and are ready to remove any extra part. Some of them do not even need

evidence for polyps, and may settle for a swollen nasal lining. The patients, frus-

trated by their constant nasal congestion, which has resisted all of the “effective”

therapies, out of sheer desperation agree to have an operation. Of course, given

the fact that chronic rhinitis is actually a disease of the immune system and not

a local problem in the nasal cavity, the operation cannot stop its progression. In

most cases, the surgical procedure helps temporarily at best. Then a new lining

grows, swells, and the congestion comes back. An allegedly deviated nasal

septum is also commonly blamed for the problem of narrow nasal passages,

and this adds another kind of surgery to the treatment of resistant rhinitis.



An interesting article was published in The Medical Post of November 9,

1993. On page 46 we read: “At least one otolaryngologist has questioned the

efficacy of functional sinus surgery, even though the procedure has been used

to treat thousands of young children with chronic sinusitis over the past few

years.” The article covers the views of an ENT specialist from Florida.

Speaking at a meeting of the American Academy of Otolaryngology and Head

and Neck Surgery, he rejected surgery in chronic rhinitis and instead,

suggested long courses of antibiotics. But are infections the cause of the

chronic sinusitis? No. There may be cases of superimposed infections in

people with compromised immunity, however, in the overwhelming majority

of cases, constantly inflamed nasal lining is an allergy-related syndrome,

which is misrepresented as the primary event of an infectious nature. In this

situation, antibiotics can do more harm than good because, while targeting

not very probable events, they allow the core defect to advance. Besides, in

some patients, antibiotics may, and often do, aggravate allergies. The

specialist’s speech did not include repair of the immunity. Instead, he blamed

mothers for frequent surgeries. “I don’t do it until I’m pushed,” he said and

suggested education of the mothers to make them more compliant with the

long-term medicalization of their kids.

One should feel sorry for the mothers who are ready to subject their chil-

dren to the knife. Tired of perpetual courses of ineffective antibiotics, they

evidently cannot bear to see their offspring suffer all the time. Besides, their

own sleepless nights must be taking their toll, and, out of despair, they may

push doctors for surgery. From any point of view—science or logic—it is

absurd to treat an immune disease surgically. I would say that surgery is quite

an exaggerated method in this situation, almost comparable to using a guil-

lotine for dandruff. The blame for such operations should be placed on the

doctors, not on mothers.

Why does a stuffy nose need a scalpel? The answer is: even if doctors do

confirm the allergic origin of rhinitis, they do not have an effective remedy

to treat it, and surgery delays admission of their impotence in this field.

Sadly but not unexpectedly, the scalpel does not cure the patient from the

underlying problem, which is hyperreleasability of the immunocompetent

cells. I know patients with chronic rhinitis who underwent several “sinus

surgeries” in the past and continued to carry around boxes of paper tissues

as ever before.



IMMUNOTHERAPY IN CHRONIC RHINITISDespite the fervent devotion of allergists to steroids, ENT specialists to the

knife, and general practitioners and pediatricians to antibiotics, one may hear

their occasional confessions that the existing means are less than satisfactory.

Through the chorus advising these extreme means of treating the afflicted

noses, admissions by allergists break through at times, and they agree that

immunotherapy is “the only immunomodulator that is available to reduce

symptoms.”2 Its value, as assessed by a Toronto allergist, is noteworthy: “Used

properly in appropriately selected cases, about 70% of patients got some relief

with immunotherapy.”3 Why is it only “occasionally, relief can be dramatic,

but more often it is incomplete, and therapy with medications is still

required”? What prevents doctors from using immunotherapy ‘properly’ and

‘appropriately selecting’ it? There are a number of reasons.

First, conventional allergy shots, as we learned before, can lead to severe

reactions and even be fatal. Although complications of immunotherapy are

less dangerous for a runny/stuffy nose than for constricted bronchi in asthma,

it is too early for the rhinitis group to rejoice: immunotherapy can be poten-

tially dangerous even with them. They may be hidden or undiagnosed asth-

matics, and unproperly selected allergy shots may reveal this by provoking an

attack. Since all allergies are diseases of hypersensitivity, patients with chronic

allergic rhinitis may also be prone to developing anaphylactic reactions with

life-threatening respiratory distress and vascular shock. “It is essential to

balance the risk of anaphylaxis with the need to relieve symptoms,” says Dr.

Greenberger cited above. It means that before subjecting a patient to

immunotherapy, doctors have to weigh the impact of the nasal congestion vs.

the danger of anaphylaxis. I personally would reject any immunotherapy for

a stuffy nose that carries even the slightest risk of death.

Conventional immunotherapy has another limitation: it is indicated for

allergic rhinitis, mostly in hay fever, and when skin testing reveals wheals to

dust mite. Even then, it is indicated only “when there is unavoidable and

inescapable exposure to allergens.” The larger groups of the vasomotor rhinitis

and the patients with mixed type are to be excluded.

Dr. Greenberger says that immunotherapy promises great savings for the

Public Health system because it provides for “the reduction of symptoms,

greater productive hours in school and at work, and the avoidance of costly

medications and electric bills for air conditioning.” Thus, even conventional



immunotherapy, with all its side effects and limitations, still looks like a

worthy treatment, and this contradicts the humble role it plays in today’s

practical allergy therapies.

FINAL REMARKS ON STUFFY NOSES Thousands of people miss days of work because of sinus headaches or sleep-

less nights due to inability to breathe normally. Thousands of children give

the “allergic salute” by rubbing their itchy noses while tilting their heads

upwards. Millions of dollars are spent on the development of yet another

antihistamine, decongestant, their fancy combinations, or a steroid spray.

Daily medications, dangerous, inefficient or irrelevant are the norm in the

management of chronic nasal congestion. Effective immunotherapy is just a

dream expressed on the pages of periodicals. Therefore, patients with chronic

rhinitis would like to know the answers to the questions that bother them:

Why does a nasal problem require daily medications? Why should a

patient with a congested nose be medicalized to the extent that he may end up

with a stroke? Why can a stuffy nose ruin the future of a person who, because

of his medical problem, was labeled a poor learner in his childhood and

became one as a result of this condition? Why should a stuffy nose ruins the

life of a family that has a member who is unable to enjoy spring, summer, or

fall due to pollens? Why should loving mothers be reduced to such despair that

they urge doctors to perform surgery on their children who are unable to sleep

or eat because of a clogged nose? Why does trivial nasal congestion lead to

huge expenses for special electric appliances, covers, even trips abroad to flee

the hay fever season?

Histamine therapy is very successful in treating chronic rhinitis regardless of

its type: be it in its seasonal allergic, perennial allergic, or vasomotor form. As with

all allergies, the improvement often starts right at the point of the skin testing.

B. SKIN ALLERGIESGENERAL DESCRIPTION

The general idea of skin allergies covers several types of diseases. As with other

allergies, the term allergic is fundamentally wrong in the usual sense, since in

the majority of cases, the symptoms are allergen-unrelated or only partially

related. Like asthma and chronic rhinitis, skin allergies are diseases of hyper-

sensitivity. To simplify the overview, I will still abide by the accepted termi-

nology and use the term allergic.



Although the skin is a cover for our internal organs, it is not just a passive

enclosure of the organs, but a large, living and very sensitive organ. The skin is

the first physical barrier that protects the body as walls protect the inside of a

house. It is also a chemical barrier due to the presence of blood vessels, nerve

endings, and various cells with their several million kinds of receptors. These

receptors respond to chemicals, environmental and body temperature changes,

pain, pressure, light, vibration, etc., and the cellular chemistry induced by their

signals protects us by neutralizing the enemies that contact the skin or try to

penetrate it.

The presence of immunocompetent cells makes the skin an immune

organ, while the extensive spread of nerve cells indicates its close relation with

the nervous system. The skin’s involvement in allergic reaction does not differ

from the involvement of the bronchi or the nose. It may occur upon contact

with an allergen, an assault of a nonspecific factor such as exposure to an

environmental or physical factor, as a result of the host’s own changing chem-

istry, or it may arise spontaneously, without any apparent trigger. Usually,

immune cells adjust both to outer attacks and to inner changes, and only if

the impact is too strong, there may be a temporary symptomatic reaction. If

the cells are generally healthy and, most importantly, able to restore their

normal functioning, a spontaneous relief sets in after a while. In a patient

with malfunctioning immune cells, various triggers may lead to the initial

histamine overspill from the sensitive mast cells followed by an exaggerated

response to that by other cells in the surrounding tissues. The inability of the

cells to adjust to the insult protracts the reaction. The nerve cells in the

vicinity become engaged too. The receptors disseminate the signal all over the

body, and the reaction may spread to other tissues and organs in the same way

as a fire that starts in a small area may engulf the whole house.

ATOPIC DERMATITIS—THE RIGHT TERM?Atopic dermatitis is one of most common allergies. As was said before, the

Greek derma means skin. Atopy is interpreted in the medical dictionaries as

allergic, that is, an IgE-mediated condition, which, in relation to dermatitis, is

scientifically unfounded. All medical sources agree that no consistent link between

allergens/IgE antibodies and atopic dermatitis has ever been demonstrated. The

statistics on atopic dermatitis vary in the percentage of allergen-related cases,

but even with the lowest figures (20% of the population), we are dealing with

an IgE antibody-unrelated condition. From the point of view of science, a



finding of one fifth of all cases being unrelated to IgE mediation, is a high figure

because that means that this is an allergic disease in which allergens may play no

role! However, unfortunately allergists do not explain this phenomenon.

Chapter 10 written by R. Rocklin in the 1985 textbook Allergy thoroughly

spells out all the mechanisms of allergy. This description is applicable to any

allergic condition, and atopic dermatitis is no exception. (Strange as it is,

another author writes on page 417 that “the etiology and pathogenesis of atopic

dermatitis remain enigmatic,” whereas, all the author had to do was to read

Chapter 10 in the same book.) In fact, the most essential component in atopic

dermatitis is a skin reaction to a local histamine overspill followed by a cascade

of the allergy mediators joining in. Like in any allergy, the genetic defect mani-

fests in weak T-suppressors unable to counterbalance the pro-allergy chemistry

produced by mast cells, basophils, Langerhans cells and T-helpers.

THE SYMPTOMSAn allergic skin inflammation in dermatitis manifests in an intensely itchy

rash. The skin also becomes scaly, crusty and cracks. Patches of affected areas

usually cover the arms and legs, especially behind the knees and the inside of

the elbows, the neck and face but may easily spread all over the body. At times,

the itch is merciless. The constantly scratched surface becomes damaged, and

this may cause a superimposed infectious inflammation.

Children are more common sufferers of allergic dermatitis than adults, and

another name for the disease is infantile eczema. Their eczematous skin may

become infected because children are often unable to observe hygienic meas-

ures as well as refrain from scratching. With age, their dermatitis may disappear,

but the skin may remain damaged with numerous scars. Disappearance of the

dermatitis does not mean that the pathological immune process is over. It is

known that often, it transforms and manifests years later in another allergic

condition. Many asthmatics had atopic dermatitis in childhood, and it is gone

by the time the first asthma symptoms appeared. This should prompt doctors

to view allergic skin problems in a child as an early sign of potential allergic

rhinitis and/or asthma in the future. All three diseases are known to medicine

as the atopic triad.

Allergic dermatitis may be a traumatizing disease not only because of its

itchy cracking skin but also psychologically. The sight of the skin lesions may

put off and scare those who are unfamiliar with the non-contagious nature of

the disease. Parents may forbid their youngsters to play with a child who



suffers from allergic dermatitis. The situation may turn dramatic when peers

mock or tease the child. Even adults suffer psychologically when lesions are

on the face, but the emotional impact of this on a child is especially severe.

One can only hope that the child outgrows the disease, and his emotions will

stabilize as well. Both can be wishful thinking, though.

THE MANAGEMENT OF ATOPIC DERMATITISThe lack of understanding of what mechanisms underlies atopic dermatitis

dooms its treatment. It addresses what is on the surface—the symptoms. The

same textbook Allergy sees the goal of treatment as “the reduction of itching.”

As in other allergic diseases, once again the end organ becomes the target for

treatment, not the malfunctioning immune cells.

Calling the disease atopic (allergic) implies that the first step should be

elimination of the trigger. Although in the majority of cases, the offender is

unidentifiable, elimination of the standard culprits—foods, house dust mites,

pets, etc. has become the norm in the management of dermatitis. However,

environmental control and dietary restrictions are rarely successful. Helpful

or not, these measures are especially difficult to implement with children

whose active nature hates restrictions of any kind. Besides, the disease is rarely

a result of a single trigger, and elimination of one or a few factors or a food is

usually not enough to stabilize the condition and may help partially at best.

Topical means pertaining to the surface, and in relation to drugs, the term

means creams, ointments, and lotions—all remedies that are put on the skin.

Standard, non-medicated topical remedies include lubricating oils to reduce

skin dryness, and special bath preparations or non-irritating soap-like lotions

instead of regular soaps. Those who have allergic dermatitis know how these

means work, or better, do not work.

One can rarely achieve pronounced relief of the itch with antihistamines.

Doctors admit this but still prescribe them, probably, out of helplessness.

Often patients are given the first generation antihistamines, which are seda-

tive: to let the patient at least get a good night’s sleep. Delayed sedation is

common, and the next day, a drowsy child can hardly be a good learner at

school, nor can a sleepy adult perform work that requires concentration.

Like other allergy sufferers, patients with atopic dermatitis cannot escape

steroids. In fact, steroids are the main and, actually, the only relatively effec-

tive remedy, which often provides temporary relief of symptoms. Numerous

steroid-containing creams, ointments and lotions differ primarily in the



dosage of steroids, which determines the degree of their effect, both positive

and adverse. The 1999 CPS writes on page 590 in the entry on Elocom that

comes in a cream, ointment and lotion: “(it) has been shown to have topical

and systemic pharmacologic and metabolic effects characteristic of this class

of drugs.” And further: “Any of the side effects that have been reported

following systemic use of corticosteroids, including adrenal suppression, may

also occur with topical corticosteroids, especially in infants and children.” All

this is not surprising, since the skin is an excellent absorbent of the drug.

Children, as the most frequent victims of allergic dermatitis, become the

main consumers of the steroid-based topical remedies. The producers warn

of the increased danger of applying topical steroids over a large surface and

for a long time. The disease is, however, chronic, and in many, the lesions

cover large areas. All this means no escape from the drug’s side effects.

Paradoxically, one of the listed complications is skin thinning or even

atrophy. Just think: the skin may get irreparably damaged due to the medica-

tions meant for its treatment!

Steroids are frequently combined with antibiotics. Such topical centaurs

are supposed to act like the stone that kills two birds: steroids aim directly at

allergic dermatitis, while antibiotics treat secondary infections, which may

develop due to the damaged skin. Infections may also be the result of the

adverse affect of the steroids that make the skin more susceptible to infec-

tions. In such a case, one medication in the combo drug relieves the adverse

effect of another—a common phenomenon in medicine.

The paradoxes of allergy treatments continue: there is a possibility of an

allergic reaction to antibiotics, the penicillin group in particular. The reaction

may be skin-limited, which means appearance of rashes or lesions in response

to the drug; it may also be systemic—emergence of new allergic symptoms

and/or worsening of the existing ones. And we know all too well what the

most effective drug for all allergic reactions is—steroids! This time, patients

take them in inhaled, oral or injectable form.

Oral steroids are prescribed in allergic dermatitis when topical ones fail,

and the itchy rash becomes intolerable. Even in those patients who improve,

the itchy rash may and often does come back as soon as the drug is discon-

tinued. It is the same vicious circle that we saw in asthma treated with steroids.

To avoid serious side effects of and dependence on steroids, medicine occa-

sionally offers another group of “miracle” drugs—Cyclosporin, Tacrolimus and

the most recent Pimecralimus. The CPS classifies them as highly potent



immunosuppressants. Allergists call them immunomodulators even though

these drugs disable the immune system. Those authors, who suggest oral

Cyclosporin and topical Tacrolimus recognize that these medications do not

resolve the problem, have a lot of side effects, and a rapid exacerbation is

common once the treatment is stopped. Only desperation would prompt the

use of such drastic means for allergic dermatitis—a disease, which according to

all standards, is not life-threatening.

It is of interest that Allergy 1985 mentions, in passing, a theoretical possi-

bility of resorting to immunotherapy in atopic dermatitis if it is accompanied by

other allergy symptoms. Of course, only if all other methods fail. The fact that,

except for few timid failed attempts, clinical allergy never uses immunotherapy

for allergic dermatitis is understandable. First, how can one treat an impaired

immune system if the problem still remains “enigmatic and elusive”? Second,

allergists refer to allergen/IgE antibody-unrelated dermatitis as “nonimmuno-

genic,” that is, immune-unrelated.

Dissatisfied with conventional methods, despondent patients try various

sorts of herbs. They put oatmeal, camphor oil or baking soda into their bath

to soothe the itch. Some travel to Israel and spend months on the Dead Sea,

others go to geographically remote sites to swim in pools filled with exotic

skin-eating fish. Publications and TV programs for lay people are full of such

stories. A classic example of a sufferer is Marat, a leader of the French

Revolution at the end of the 18th century. He was a doctor by profession. He

regularly took soothing baths for his constant agonizing itch, and was

murdered while taking one. The management has not become more

successful since, and baths have remained the safest and least expensive

means in the treatment of allergic dermatitis.

DO MASSAGE AND ACUPUNCTURE HELP?A study on children with atopic dermatitis conducted by the Touch Research

Institute sponsored by the U.S. National Institute of Mental Health was

conducted some time ago. Half of the young patients received only standard

treatment, while the other half also received a 20-minute all-body daily massage

done by their parents. The second group felt better and became calmer. A

participating doctor explained it as a psychological effect of touching. However,

skin itch is a symptom that has a material basis—cellular malfunctioning, and

the explanation must go to the root and be consistent with the concepts existing

in psychoneuroimmunology. Thus, during the massage, sensory nerve endings



in the skin are engaged directly and invite the neighboring immunocompetent

cells into the process by sharing their chemistry. It may also be the other way

around: Langerhans cells and T-cells get activated by touch and involve others

by their chemicals. In any case, both groups become participants in the reac-

tion. A gentle massage does not over-activate H1 receptors. At the same time,

the signals from the tender touching activate the inefficient H2/3 receptors, the

cells start to produce more anti-disease mediators and cytokines, and this

arrests the allergic reaction. Massage, acupressure and acupuncture work simi-

larly in this respect. Highly qualified specialists in massage therapy and acupres-

sure empirically know that pressure to the skin should not be too light but

should not exceed a certain level. Only through experience, they acquire the feel

of how much is too much or too little.

It is also possible that the involved nerve cells send the message of the

physical pleasure of the touch to the brain. The involvement of the brain is

important for any immune process. In this case, the brain cells start to

produce the inner “morphine” (endorphins) and anti-inflammatory

cytokines. The favorably changing chemistry reverses the aftermath of the

local histamine overspill, which initiated the disease.

Is acupuncture helpful in atopic dermatitis? My answer: it is justifiable on

theoretical grounds, although these are unknown or vaguely known to the

practitioners who conduct the procedure, and, of course, it is safer than

steroids or Tacrolimus. The efficacy of acupuncture is probably limited. I have

seen very few cases when it had, at best, produced a slight, temporary relief,

and never a case of substantial relief or a cure. Besides, those parents whose

children have allergic dermatitis should welcome a chance to avoid or reduce

the amount of steroid creams by resorting to daily skin massaging.

Concluding thoughts on atopic dermatitis: I have treated many patients

with atopic dermatitis. The majority improved to different degrees—from

diminished itch to complete recovery. In young children, the success was

especially notable.

URTICARIA

GENERAL DESCRIPTION

Another kind of skin allergy is itchy hives, the scientific name for which is

urticaria. The Latin word urtica means stinging nettle—an herb armed with

pricking, stinging hairs. This gives you an idea of the symptoms.



Unlike atopic dermatitis that has a chronic course, urticaria is a disease of

a more spontaneous kind. Red, itchy wheals may develop all of a sudden

either as a short episode, or may last, mostly intermittently, for months or

even years. This makes the notion chronic urticaria rather conditional. Some

textbooks define as chronic a disease that lasts over three weeks, while others

indicate six weeks. In my view, this arbitrary mathematical approach (i.e. two

weeks are acute urticaria, and six are chronic) makes no sense especially when

it comes to the management of such patients. This condition should be

considered chronic if patients are prone to frequent, recurrent hive develop-

ment, no matter how long each episode lasts.

As in other diseases of hypersensitivity, occurrence of chronic urticaria is

unpredictable in the majority of cases. Only a few patients know exactly what

provokes their symptoms and try to avoid those triggers. I saw many patients

with a history of almost non-stop hives who were unable to pinpoint the

stimuli. Statistics differ in the percentage of allergen-triggered urticaria. Older

medical textbooks state that the atopic (allergen/IgE-related) form is as

common as non-atopic. Other, more recent publications reduce the atopic

kind to 20%, which means that up to 80% of all urticaria cases are due to non-

specified triggers. This means that only 20% of cases of this allergic disease are

allergies in the conventional sense. What about the rest? To get a feeling for this

situation imagine viral diseases, 80% of which are not caused by viruses!

URTICARIA AS A PURELY HISTAMINE-INDUCED CONDITIONAs specialists say, “Chronic urticaria is a common condition, frustrating for

both patients who suffer from it and for the many physicians involved in its

management.”4 In fact, urticaria is the simplest of all allergies. Why the

simplest? Dictionaries define urticaria as a formation of wheals or hives,

which are mostly itchy. An encounter with an allergen, a prick or pressure to

the skin of a person with the innate predisposition to allergy may cause a

histamine leak from the local mast cells and lead to a hive at the site. Doesn’t

it remind you of allergy skin testing when a prick with an allergen or hista-

mine is actually a purposeful formation of hives?

Hives in skin testing and hives in disease possess similar characteristics:

redness, swelling, itch, rapid development and spontaneous resolution. They

are a model of an allergic reaction, in which histamine plays the predominant

role as a mediator. To watch the hive formation and regression both in

urticaria and at a skin testing is to watch the highs and lows of an allergic



process not only on the skin but also processes hidden inside the body. When

examining patients with urticaria, one can literally see their hives fade and

disappear. Some authors write on similarities in the pattern of response

observed in the lungs as being also observable on the skin. Allergy knows that:

“As a superficial part of the immune system, the skin makes a perfect object

for a visual observation of how allergic inflammation goes on elsewhere

during a disease and correlates with the processes in other immune organs.”5

Thus, the simplicity of urticaria, which is purely a phenomenon of hista-

mine-induced proinflammatory chemistry, allows one to observe with the

naked eye the course of this disease and at the same time understand that

similar ups and downs take place in other diseases of hypersensitivity.

Other allergies are more complex than urticaria. They cannot be seen and

are mostly judged on the basis of the information given by the patient and are

rarely amenable to conventional testing. This makes their understanding and

treatment more difficult. Even atopic dermatitis, which is also a skin disease,

cannot provide precise information in this regard due its multifactorial

nature. It is a blend of two medical fields—allergy and dermatology, and has

lower reversibility than most allergic conditions and asthma because of the

potential of severe lesions and possible scarring. All this allows one to

conclude that understanding of the true immune mechanisms involved in the

simplest allergic disease, urticaria, helps us understand allergies in general.

There is general lack of understanding of the similarity of the underlying

mechanisms in urticaria and the phenomena observed during skin testing.

Because for allergists, superficial signs are more important than the essence of

the immune reactions, doctors conducting allergy skin testing do not monitor

systemic reactions. Thus, they miss the reactions with improvement, which

could form the basis for immunotherapy, or allergy shots. This, in turn, makes

it clear why immunotherapy is never conducted in skin allergies. If allergists

fail with the management of urticaria, how can they be expected to properly

manage the more complex asthma, chronic rhinitis or atopic dermatitis?

TRIGGERS, CAUSES AND THE IMMUNE PROCESSES IN URTICARIADr. A. Kaplan, the editor of the textbook Allergy (1985) is also the author of the

chapter on urticaria in that same textbook. On page 464, he writes that “in most

cases, the cause and pathogenesis are unknown.” It is difficult to explain why he

says so, since, as an author of numerous articles, which we discussed in the



chapter “Histaminegate,” he indicates that allergies are, actually, the prevalence of

histamine-induced proinflammatory factors (cytokines) over histamine-

induced anti-inflammatory factors. These factors are the products of partici-

pating immunocompetent cells. Indeed, Kaplan’s chapter points on page

460–461 to a “ten-fold increase in the number of mast cells” and “increased

amount of histamine” at the site of hives. By pointing to this, Dr. Kaplan actually

reveals the pathogenesis of urticaria as it is directly related to the genetically

predetermined mast cells’ histamine hyperreleasability. Their histamine overspill

creates the foundation for an allergic reaction, with hives as its manifestation.

Another contradictory declaration made by A. Kaplan in the textbook is

that he is not sure if allergen-unrelated urticaria is a process which “is

immunologically mediated.” This uncertainty is more than strange because,

in addition to the accumulation of mast cells, he states that there is a four-

fold increase in T-cells in the areas affected by urticaria. If, according to

Dr. Kaplan, interactions of these cells and their products are NOT immuno-

logic mechanisms of allergies, what other department do they belong to?

Such paradoxical statements are the result of the incorrect perception of

what underlies allergies in general and hence, urticaria. Dr. Kaplan’s reveals

this in the above-quoted phrase: “in most cases the cause and pathogenesis

are unknown.” In fact, basic science informs us that in all cases, the cause

(genetic make up) and pathogenesis (histamine-induced imbalanced cellular

production) are the same. The misconception of the etiology and pathogen-

esis, the misinterpretation of the notion of a trigger, and the inability to

differentiate between triggers and causes are common for all diseases of

hypersensitivity, and urticaria is not an exception.

The best illustration of the confusion is the editorial written by a leading

Canadian allergist, an ex-president of both the Ontario and Canadian Society

of Allergy, Asthma and Clinical Immunology whose area of expertise is

urticaria. The author combines under the name trigger such incompatible

phenomena as true triggers (allergens), cellular by-products (proteins that

accompany various immune reactions in the body) and cytokines (regulatory

mediators of immune reactions). Not surprisingly, this confusion results in the

statement similar to the one made by Dr. Kaplan: “the exact cause of chronic

urticaria remains unknown.”6 If Dr. A. Kaplan, the 2003 President of the World

Allergy Organization, and a leading Canadian allergist, both specializing in

urticaria, do not understand this condition’s immunologic nature and mix up

a trigger with the cause, one cannot expect more from an ordinary doctor.



LOGICAL QUESTION IN RELATION TO URTICARIAAllergy medicine is a field of immunology. As 80% of urticaria are nonim-

munologic in origin, shouldn’t allergists pass these “non-immune” cases to

other departments of medicine?

■ What specialists should those patients see whose urticaria is

“nonimmunologic”?

■ Who should treat cases of mixed urticaria?

■ Should patients visit an allergist solely when they have allergen-triggered

symptoms such as, for instance, hives in response to pet exposure, but not

when their hives develop spontaneously, without any evident reason?

■ Why should we stress the significance of allergen elimination in the mostly

allergen-unrelated urticaria?

■ Why are immunosuppressive medications prescribed in “nonimmunologic”

urticaria?

Only a clear picture of the underlying mechanisms can lead to proper

management. I have not come across a work that would specify those.

ANGIOEDEMAIn a way, angioedema is urticaria at a different level. The skin has two layers,

and symptoms reflect the degree of their involvement. In urticaria, the surface

layer is primarily involved in the disease. Angioedema is a condition in which

the reaction goes to the deeper skin layer as well as the subcutaneous layer,

both of which have blood vessels. The Greek roots of the term mean vascular

swelling. Urticaria has a vascular component with the swelling of the tiny local

capillaries, while angioedema involves the bigger vessels as well. As a rule,

both diseases are presented together in textbooks as different degrees of the

same process, both local and systemic. Angioedema affects mostly the face,

extremities, genitalia and occasionally respiratory and gastrointestinal

mucosa. The condition is dangerous and may be fatal in cases where systemic

swelling spreads to the throat and closes the airway.

Those people are predisposed to angioedema who inherited or acquired

impaired immune mechanisms governing the work of the allergy department

of the immune system. Therefore, angioedema is not different from all other

diseases of hypersensitivity. Like urticaria, angioedema may develop when the

patient is allergic to certain foods and substances, insect bites, drugs, exposure

to cold temperatures or to other physical triggers. In a lot of cases, triggers in

angioedema, as in urticaria, are not identifiable.



Angioedema is usually classified into four major types. First, the heredi-

tary type which is mostly the familial form, resulting from the body’s failure

to synthesize certain enzymes and/or proteins, does not belong in diseases of

hypersensitivity. Among the three other forms, there is an allergen-specific

kind. Another type is nonspecific or “physical” allergy. The third is

angioedema of unknown origin or idiopathic, as it is called in medicine.

Idiopathic angioedema is, actually, a susceptibility to react in a hypersensitive

way, a chronic form of the disease. Only one kind, allergen-specific, is poten-

tially fatal. These patients develop reactions through exposure to certain trig-

gers, among which peanuts are considered to be especially dangerous. At

times, even the smell or touch of a peanut-containing product may cause a

severe response. Reactions to penicillin, especially in injections, are another

example. Such hypersensitivity is incurable, and the triggers, once identified,

should be absolutely avoided. This type should not be confused with food

allergies, which may be curable.

TREATMENT OF URTICARIA AND ANGIOEDEMAIn acute severe urticaria and angioedema, an injection of adrenalin is given, and

the emergency kit, which people prone to angioedema carry, contains it. In

chronic and recurrent cases, contemporary allergy recommends antihistamines

and, of course, oral steroids. Neither resolves the problem. Since urticaria and

angioedema are mostly allergen-unrelated, conventional allergy cannot even

resort to its habitual mantra of avoidance and elimination. It views these condi-

tions, as the rest of allergies, as incurable. Immunotherapy is never considered

as a choice, whereas, being histamine-based more than any other disease of

hypersensitivity, chronic urticaria and angioedema can be successfully treated

through a “tune up” of the ailing immune tools. Synthetic histamine, as a

nonspecific immunomodulator, is the best means of therapy that can restore

the imbalance induced by cellular histamine. With the confidence of a person

who treated urticaria patients with histamine injections, I say that the majority

of cases are treatable; many are helped and some even curable.

C. HAY FEVERThis section on hay fever will be short despite the high incidence of this

disorder. The reason is that hay fever is like a bouquet of the diseases already

described earlier, only in this case, they are seasonal and are triggered by pollen.

Allergic rhinitis is the central manifestation although occasionally, it may not



be present. In addition come itchy/watery eyes, plugged/itchy ears, sore/itchy

throat, throaty or chesty cough with wheezing, increased headaches, extreme

tiredness, poor concentration—rather like a severe flu lasting for months,

might be the best comparison. Strangely, despite the variety of symptoms, the

overwhelming presence of rhinitis in the majority of cases makes many authors

wrongly identify hay fever solely with seasonal rhinitis. Thus, Diagnostic Codes

in the Ontario Health Insurance Plan provide for these diseases just one code,

and the codes are suggested by specialists.

Indirectly, statistics of hay fever prove that the statistical figures for

chronic rhinitis are definitely higher than 20–25%. Thus, official sources state

that about 20% of the population suffer from hay fever. At the same time,

since hay fever is included into the group of chronic rhinitis, the large group

of those who have a vasomotor or mixed type is left unaccounted for. These

simple arithmetic calculations tell us that the prevalence of chronic rhinitis,

also about 25%, is seriously downplayed.

Dr. John Bostoch was the first to describe hay fever in 1819, and in 1873,

Charles Blackley showed that it is triggered by exposure to pollen. Every year,

the approaching pollen season is announced by the escalating number of TV

commercials on antihistamines which are lately called “allergy drugs” (to hide

the very existence of histamine?). Newspapers and magazines are full of articles

written by the journalists who often know about hay fever first-hand. We recog-

nize that the season is coming upon us by seeing people with swollen faces, red

eyes and noses, each carrying a box of tissue under the arm or in a half-open

purse. We know the season is in full swing because people around us sneeze,

cough, wheeze at the time most unsuitable for colds and flu, when the temper-

atures are 20–30 degrees Celsius above zero. In emergency rooms at this time of

the year, one hears coughing and wheezing in surround sound, and a line-up of

frightened kids expecting a mask or an IV with steroids is the norm.

This is the time when allergists provide their advice in newspapers, maga-

zines, on the radio and TV. The quintessence of their recommendations was

once expressed by a Canadian lay source as three “A’s”: awareness, avoidance

and action. In other words:

■ be aware that your season is coming. (As if sneezing attacks, itchy eyes and

incessant cough will let you forget your annual agony!)

■ Avoid make sure that the windows in your home, car, office are hermeti-

cally sealed. Put on a mask when outside. (We have already discussed the

chances of relief through these measures).



■ Act by listening to the announcements of the pollen count, start taking

antihistamines two weeks prior to the season, stock up in advance with

decongestants, puffers, eye drops and nasal sprays; stop all outdoor activ-

ities. (Does it mean to change one’s profession if one is a gardener, a

farmer, a landscape engineer, a constructor, a taxi or a bus driver?) In

short: limit the area of your activity in general (no field trips or summer

classes if you are a teacher, and no home visits if you are a doctor). Limit

your company to a computer, a telephone, and a fax machine.

Does it help? Judging by the number of people who dread the coming of

warm days, not a lot. Of course, the best choice would be to leave the

country (province, or state) for the season. Do not forget to take your chil-

dren with you because, most probably, they have inherited your allergies.

You think such trips are expensive? Never mind, to be in debt is better than

to suffer physically.

There are several additional tips patients with hay fever can use on top of

the Three A’s Program. Drive your car carefully in hay fever season. The roads

are full of drowsy people either due to the drugs they take or to the sleepless

nights they have had because of cough, congested nose and itchy skin. Driving

may also be dangerous in another sense: spontaneous sneezing attacks are

fraught with accidents. In 1989, while being in London, England, I read an

article about a car accident, in which the driver’s mother was killed. He was

acquitted because he suffered from hay fever, and a severe sneezing attack had

been the cause of a car crash. On August 16, 1997, a lucky Canadian driver got

away with just few minor injuries after his car had turned upside down

during a similar sneezing fit. As you see, hay fever is not an innocent condi-

tion to sneeze at.

No matter how severe your cough is, do not rush to take antibiotics

prescribed by your doctor for alleged bronchitis. First, the weather is getting

warmer and warmer, second, you do not have a high fever. Even if your

family “got infected from you” or the other way around, it may not be due to

a viral epidemic, but simply because your children, siblings, parents and

grandparents probably suffer from the same medical problem—hay fever. Be

positive: suffering together may unite your family still more. If antihista-

mines, decongestants and inhalers do not work, try to put up with the

temporary inconvenience, for even the longest season is over with the first

frost. You live in a place where pollens are in the air all year round? I am sorry



for you, but either you change your location or keep hoping that you will

outgrow hay fever. Of course, it may take quite a few years or decades, but

you still have a chance.

In case the agony is intolerable or becomes dangerous due to your wors-

ening asthma, you have one choice only—steroids in nasal sprays, eye drops,

inhalers, and pills. Their consumption during the pollen season goes up dras-

tically, and lucky are those consumers who have hay fever limited to only a

specific pollen and can restore their health from the steroid aftermath during

the rest of the year.

Pre-seasonal or year-round allergy shots are not very effective for the

majority, at least judging by the seasonal demand of daily medications. The

medical articles, though, often say the opposite. As soon as you start experi-

encing minor side effects from your shots, inform your doctor about that, and

consider discontinuing them if the side effects become more and more

pronounced. Remember: UK doctors prefer to have resuscitation facilities

around when they provide allergy shots, and medical papers warn doctors

about possible liability in administrating immunotherapy in their offices. Is

your doctor’s office close to a hospital?

My mockery is directed at the specialists proclaiming the high efficacy of

allergy medications and the efficiency of their Three A’s Program and similar

programs. Besides, laughter is the best cure, and smiling at this nonsense may

help an allergy sufferer feel better at least while reading.

Real help may come from histamine injections. Hundreds of my

patients started to live a normal life due to histamine injections. Many hay

fever patients came to me in a symptomatic stage. Within minutes of

allergy skin testing, the eyes would stop itching, congested noses would

open, headaches lift, shortness of breath or cough would disappear. The

main change, however, was disbelief that it was so simple to feel better. It

was still harder for them to believe that they would not be able to have this

therapy anywhere else. Some of them traveled a long distance to get the

treatment. Thanks to histamine, the majority of my patients became able

to enjoy summer camping, do the unthinkable such as mow grass, keep

their windows open, and drive without a fear that a sneezing attack could

turn fatal.



ENDNOTES1. D. Allen. Systemic effects of intranasal steroids: an endocrinologist’s perspective. JACI

2000;106:S179-902. P. Greenberger, Immunology and Allergy Clinics Of North America, Preface, vol. 12, No 1, Feb.

19923. K. Binkley. Seasonal Allergic Rhinoconjunctivitis. The Canadian Journal of Diagnosis, June

2001:93-84. J. Sharma et al. Chronic urticaria. Journal of Cutaneous Medicine and Surgery, 2000;4:89-935. S. Worfel, L. Lichtenstein et al. JACI 1995;96:57-656. G. Sussman. Editorial. Allergy, June 1985



PART NINE

FUNCTIONALENCEPHALOPATHIES

WHAT IS ENCEPHALOPATHY?This word consists of two Greek roots: Cephalic meaning pertaining to the

head, and pathos—related to disease. Medical textbooks refer to encephalo-

pathy only as a degenerative, organic disease of the brain often resulting from

a systemic disease elsewhere in the body. Such are, for instance, advanced

hepatic diseases, kidney failure resulting in dialysis, or lead poisoning. This

interpretation of encephalopathies is incomplete, since many people have

neurological symptoms in the absence of organic disorders. Their symptoms

are solely due to the imbalance of neurotransmitters in the brain, a condition

that should be classified as functional encephalopathy. Although very

common, these diseases have never been described before as one group, and

the classification functional encephalopathy does not exist in medicine. In this

sense, mental and neurological diseases such as headaches, attention deficit and

hyperactivity syndrome, depression and anxiety, chronic fatigue syndrome,

autism, many seizure disorders, schizophrenia, etc. are functional encephalo-

pathies. The general notion of functional encephalopathy does not have any

place in nosology, the science that classifies diseases according to their origin

and body mechanisms involved in disease causation. The explanation lies in

the lack of understanding what mechanisms underlie the disorders united

under this name.


Our nervous system consists of the center—the brain and spinal cord,

and peripheral neurons and neural elements. Their distribution all over the

body explains why chemical changes in the center may involve any tissue or

organ in the disease. The central mediator in allergies, histamine, is also a

major neurotransmitter in the central nervous system. It does both—medi-

ates neurological processes and regulates many. The pathways through which

neurons in the brain and elsewhere conduct histamine messages form a hist-

aminergic neuron system. This section deals with those common

encephalopathies that result from the chemical disturbances in neurotrans-

mission and assesses to what extent histamine imbalance contributes to func-

tional encephalopathies.

HISTAMINE AS A NEUROTRANSMITTERHistamine is an omnipresent cellular substance of a high physiological

potency and multifaceted effects. Its messages are distributed by the receptors

marked by the letter H. Each type of H receptor has its own function, that

may differ depending on the organ in which this receptor is situated.

Launched by a local trigger in any part of the body, histamine reaction can

invoke not only local but also systemic effects. Therefore, inefficient perform-

ance of any of the histamine receptors may alter the normal signals in the whole

histaminergic system and create a chemical imbalance both of histamine itself

and also of other numerous chemicals whose activity and release depend on its

regulatory messages.

Like histamine, many of these chemicals are both allergy mediators and

neurotransmitters. The role of histamine is magnified due to the fact that the

main histamine producers, mast cells and basophils, are highly disseminated

in various tissues including the brain. The degree of the involvement of the

nerve cells determines the severity of neurological symptoms. They may

accompany allergies but, if pronounced, can be isolated as a functional

neurological disease.

Long ago, observant clinicians noticed the co-existence of neurological

and allergic symptoms. Indeed, immune and neurological diseases seem to

cluster in families, although the predominance of certain symptoms over

others may differ among the members of the same family. The earlier-quoted

article by L. Mansfield1 gives historic references that go as far back as 1921,

when the relationship between the occurrence of asthma and rhinitis (the

immune system) and migraine (the brain) was noticed. Mansfield also refers

Functional Encephalopathies 345


to the works of the ’70s and ’80s that confirm an increased histamine output

in allergic dermatitis, food allergies as well as during migraine attacks. In

many aspects, pathological processes in these functional encephalopathies are

similar to the ones in allergies. This allows us to view these neurological

manifestations as allergic conditions of the nervous system or rather, hyper-

sensitivity of the nervous system.

HYPOTHALAMUS, HISTAMINE AND ENCEPHALOPATHIES The presence of histamine in the brain was first discovered in 1943. Since that

time, basic sciences have progressed to identifying it as a central neurotrans-

mitter and neuroregulator. The theoretical work by H. Wada et al.2 reviews

the wide distribution of histaminergic neurons, and their effect on brain

activity. Wada’s research identifies the hypothalamus as the regulatory center of

the histaminergic messages. This portion of the brain is like the hard drive of the

body’s computer. It controls many vital functions in the body, including the

hormone production by the endocrine glands, the vascular tone and the tone

of our muscles and joints. It also regulates such bodily functions as water

balance, appetite, thirst, temperature, sleep, sexual drive, etc. Hypothalamus

is the governing level of the HPA axis (hypothalamus-pituitary-adrenals),

which also regulates the functioning of our immune system.

Since the hypothalamus is a reservoir of histamine and contains more of

it than any other brain tissue, nature evidently planned a major role for hista-

mine in the work of this vital organ. Quite recently, the main histaminergic

pathway was identified and described. This pathway is called CRH-mast

cells-histamine axis.3 This axis conducts histamine messages between the

endocrine, nervous and the immune systems, and the connecting elements

are hypothalamic corticotropin-releasing hormone (CRH), that governs the

production of corticosteroids (through the pituitary’s corticotropin), and

mast cells, whose histamine spill initiates allergic reactions. The axis is the

best proof of histamine’s influence on the functioning, regulation and inter-

play of all three systems.

U. Knigge and J. Warberg described in their fundamental work the

importance of histamine for the functioning of the hypothalamus and

through it, for the rest of the body: “Electrophysiological experiments have

shown that microinfusion of histamine induces both excitatory (generally

H1-mediated) and inhibitory (generally H2-mediated responses) in different

hypothalamic areas.”4



The presence of histamine receptors everywhere and the diversity of their

effects emphasize the need for the knowledge of its involvement in the functioning

of the regulatory systems. Without it, there cannot be any understanding of the

origin of numerous immune and neurological symptoms (generally H1-medi-

ated) and no possibility of developing treatments that cause their reversal

(generally H2/3-mediated). This invariably leads to the idea, that the H2/3

effect vs. the H1 effect of synthetic histamine can successfully be employed

not only for allergies but also for functional encephalopathies, especially

those that originate in the hypothalamic disturbances.

With numerous tasks to regulate, the activity of the hypothalamus

becomes of immense importance to the work of all organs and systems.

Therefore its malfunctioning may affect each of them and cause numerous

symptoms that can be united under the syndrome called diencephalic.

European clinicians acknowledge the diencephalic syndrome, but do not

support its origin by theoretical data. In North American textbooks, the core

symptoms are not even acknowledged. Some other symptoms are listed as

diencephalic and ascribed to children only. The reasons for the confusion and

misinterpretation may lie in the fact that this syndrome, by nature, is highly

inconsistent in its clinical manifestations and does not have confirmatory lab

tests. Among the symptoms are shakiness, severe and unusual dizziness,

perspiration, palpitations, chest discomfort, sudden imperative urge to

urinate or defecate, etc. They are of neurological origin and may strike in

different combinations, unexpectedly and often unrelated to any evident

stimulus. All this makes the syndrome a poorly defined medical condition.

Women have diencephalic symptoms more frequently than men, which is

most probably attributable to their hormonal fluctuations. Pre-menopausal

women are the group that suffers most from this syndrome, at the same time,

their blood tests may show normal levels of all hormones. The explanation is:

their symptoms, including so-called “hot flushes,” are not only due to the age-

related fading ovaries but also, to a great extent, due to the reduction in the

ability of the hypothalamus to conduct its regulatory chemical messages to

the nervous and endocrine systems.

Although there are encephalopathies rooted in the chemical disturbances

of other parts of the central nervous system, those that originate in the hypo-

thalamic malfunctioning are the clearest and best researched indications of

this system’s imbalance. Considering that the hypothalamus is full of hista-

minergic neurons, we may assert that diencephalic symptoms may, at least in



part, depend on histamine messages and are relieved if the histamine path-

ways re-acquire their normal regulatory functioning.

PITUITARY, HISTAMINE AND ENCEPHALOPATHIESThe pituitary gland is another part of the brain and constitutes the second

level of both the HPA axis and the CRH/mast cell/histamine axis. As the

subordinate of the hypothalamus, the pituitary implements the directions

given by its superior. It is called a master gland for its direct and indirect

control over all hormonal production by other endocrine glands. It monitors

growth, sexual behaviour, lactation, labour, insulin production, functioning

of the thyroid, water retention and excretion. It also governs the body’s

response to any stress through the regulation of the synthesis of various

adrenal hormones including corticosteroids. The role of histamine in the

performance of the hypothalamus, the existence of the histaminergic path-

ways between the hypothalamus and pituitary in the brain and their dissem-

ination in the rest of the body make it inevitable that those diverse body

functions involving the pituitary depend directly on histamine activity.

The above-quoted theoretical source also states: “The neurotransmitter

histamine participates in the neuroendocrine regulation of pituitary hormone

secretion by an indirect action at a hypothalamic level where histaminergic

neurons are abundant.”5 The authors describe the stimulatory (!) effect of

histamine on the functioning of adrenals. The importance of the inner steroids

is evident from the fact that synthetic steroids are the number one medication

in such chronic diseases as asthma, rheumatoid arthritis, and ulcerative colitis.

In this connection, the idea that synthetic histamine can naturally stimulate the

functioning of adrenals and thus eliminate the need for immunosuppressive

synthetic steroids should sound appealing to the medical profession. Apparently, it

does not, for how else could one explain the existence of such data in the theoret-

ical sources and their complete absence in clinical medicine?

Among other hormones whose production histamine regulates, the

authors name prolactine (lactation), growth hormone (linear growth, cellular

repair, wound healing), oxytocin (labour, lactation), antidiuretic hormone

(water balance), thyroid hormones (general metabolism), etc. Some of the

effects of histamine are well researched, others less so; some are studied on

animals, many on humans as well. One thing is clear—the regulatory ability

of this neuro- and immunomodulator is hard to overestimate, and its impli-

cations in clinical medicine are of prime importance. “Nature heals, but hista-



mine cures,” said a world-famous neurologist, Bayard Horton, several decades

ago. The total silence around histamine in clinical medicine is not just surprising,

but shocking.

The effect of histamine imbalance is disabling for the body because it

affects the production of other major neurotransmitters. Among them, there

are serotonin and noradrenalin (central participators in vascular headaches,

depression and anxiety and irritable bowel syndrome), dopamine (a partici-

pator in parkinsonism and schizophrenia), endorphins (mediators of mood

and pain relief, including vascular headaches).6

The presence of histaminergic pathways between the center—hypothalamus

and the pituitary, and the periphery—the vascular wall, makes it inevitable that

the vascular tone also depends on the activity of histamine.

HISTAMINE IMBALANCE IN THE BRAIN AND DISEASESHistamine is a major participant of the interrelated functioning of our regu-

latory systems—central nervous, immune and endocrine—and through

them, of other systems and organs. When histamine release and activity is out

of balance, different organs and systems may become affected. Histamine

provides the solid proof that our body is an entity. Its imbalance affects the

whole body and can manifest in the most varied symptoms: dizziness, poor

appetite, increased thirst, raised or lowered blood pressure, low libido (the

brain is, in effect, the main sex organ), increased or decreased locomotor

activity (hyperactivity or muscular/joint weakness), slow linear growth in

children, poor wound healing after surgery or trauma, heightened sensitivity

to pain, depression, anxiety, insomnia, temperature dysregulation (for

example, a mild fever is not necessarily a sign of an infection, so eagerly diag-

nosed by doctors).

Since histamine activity is well researched, it can be viewed as a biological

marker of interrelated regulatory systems, and the symptomatic changes in

different organs may serve as indicators of its effects in the given area. The

stimulatory effect of histamine, through the CRH/mast-cells/histamine axis,

on the functioning of the adrenals is of special importance. Adrenal failure

alone may reveal itself in an array of symptoms, especially those related to

different areas of immunity. Too often, medicine views each symptom as an

event disconnected from other accompanying symptoms and interprets it as

a separate disease. The chronic nature of the symptoms leads to aggressive

consumption of artificial steroids especially in asthe, which eventually results



in a still deeper depletion of the body’s hormones. Despite the supporting

theoretical grounds, stimulation of the adrenals by histamine and the

resultant normalized production of natural steroids is not considered even as

a possibility.

The strongest support of the profound involvement of H in encephalo-

pathies comes from the fact that cAMP enzyme activates the nervous system

in the way it activates the IS. “Alterations of the cAMP second-messenger path

way… are essentially involved in the etlopathogenesis of mood disorders.” Direct

targeting of this pathway “may be a promising strategy for developing novel ther-

apeutic agents for the treatment of depression.”21 Treatment of depression would

be similar to the treatment of all encephalopathies. With H being the best acti-

vator of cAMP, we naturally come to the conclusion of its involvement not only

in the origin of encephalopathies but their reversal.

A. VASCULAR HEADACHES

HEADACHES ARE A HEADACHE FOR ALL MANKIND

We exclude here those headaches that occur due to malignancy, inflammation,

injury, etc. and limit our description to the ones originating from functional

disruptions in the brain. Generally, textbooks do not present headaches as

encephalopathies, although any medical condition brought about by a chem-

ical imbalance in the brain is an encephalopathy. The three most common

types of headaches arising from purely chemical processes—migraine, cluster

and tension headaches—will be the topic of discussion here. All three are

called vascular headaches. As the vascular tone depends primarily on the

release of neurotransmitters, these headaches obviously belong in the category

of encephalopathies. The medical term for a headache, irrespective of its kind,

is cephalgia.

According to Harrison’s Principles of Internal Medicine, 1987, up to 30% of

the population suffers from migraine alone.19 During the eighties, a drastic

increase in the cases of vascular headaches was registered. It was estimated in

the 1989 survey conducted by the National Institutes of Health in the U.S.

that the incidence was up by a shocking 60%. Some ascribe the figure to

better diagnosis, others, to a real jump. However, in the light of the dramati-

cally increasing rates of asthma and allergies and their common roots with

functional neurological diseases, the rising occurrence of headaches does not

look coincidental. It is difficult to give precise figures because of the discrep-



ancies of the official statistics. Besides, those having mild headaches may not

consult doctors, and neither do the patients who, after having unsuccessfully

tried numerous medications, realized the impotence of medicine in this area

and are resigned to putting up with the pain.

About 85% of male and 70% of female sufferers do not consult doctors

after initially unsuccessful visits. Even if we assume that these figures from a

lay magazine are exaggerated, they are still demonstrative, and with the

unrecorded cases, the cost of headaches to the health system and the economy

in all countries is enormous. The same U.S. survey in 1989 found that lost

productivity due to headaches was estimated to be $1.4 billion annually. In

1999, the costs of migraine headaches to the Canadian economy were esti-

mated at $592 million a year. The population of Canada is about one tenth

the size of the U.S. Make your own calculation as to what this costs our

neighbor.

Conventional medicine offers only symptomatic relief for headaches,

hence, there is no hope that in the near future, the medical, social and fiscal

aspects of the problem will improve.

THE ROLE OF HISTAMINE IN VASCULAR HEADACHES

A detailed description of the symptoms is not my purpose. A reader may find

an abundance of medical and lay sources that do that. My intention is to show

that apart from the headaches resulting from organic causes, all other

headaches (and they are the majority) have the same or similar chemical

origin, and their treatment should thus be similar. The focus is on the role of

histamine in the production of purely “chemical” headaches.

The fact that vascular headaches are related to histamine imbalance is

undisputed and found in standard medical dictionaries and textbooks. For

instance, The Dorland’s Illustrated Medical Dictionary writes that the “former

name for migrainous neuralgia” is histamine cephalgia. Harrison’s Principles

of Internal Medicine (1987) points at “the imbalance of neurotransmitters

found in nerve fibers that innervate cerebral blood vessels” as the cause of

cluster headaches and directly labels them as histamine cephalgia. Referring to

patients with migraine and tension headaches, the textbook again states that

histamine “can also cause (these) headaches.” Another official name for

cluster headaches is Horton’s syndrome19 given to them in honor of the

neurologist who first thoroughly described the condition. The latest 2001

edition of the textbook has inexplicably ascribed cluster headaches to another



researcher—Raeder.20 By taking away the priority from Horton whose career

was tied to histamine, the textbook has reliably concealed the histamine-

based origin of clusters. In every day life, stealing is punished. Probably in

science, it is normalcy.

Although the knowledge on the histamine role in clusters has existed in

the basic sciences for decades, it has not been utilized in practical medicine,

despite the fact that the scope of the problem is such that there is a special

journal called Headache. Clinical medicine does not even mention histamine

in the production of headaches. An obvious similarity with allergy medicine:

there we have antihistamines without knowing their core target, and here we

have histamine headaches attributed to the imbalance of other mediators, but

not histamine.

MIGRAINES

Migraine headaches take a special place due to their high prevalence, severity

and, as a result, their grave monetary impact on society and the health system.

They do not spare even small children. Although different studies give

different figures on the percentage of children under 12, the latest estimates

say that the headache frequency among them does not really differ from that

in adults. In the early years, girls and boys suffer in equal proportions, but this

changes by the age of puberty. Women are hit by migraine two-three times

more often than men. Thus, the more frequent migraine attacks during

menses are related to the fluctuations in the estrogen levels, while the change

in hormones during pregnancy usually reduces their occurrence. Once again,

the relationship of hormones and neurotransmitters leads us to the hypo-

thalamus with its regulatory histaminergic neurons.

Migraine is a temporal, mostly unilateral, throbbing headache, often

accompanied by nausea, vomiting, and extreme sensitivity to light and sound.

Complicated migraine may have wide-spectrum symptoms up to a transient

hemiplegia or blindness. The sufferers usually sense an approaching attack

through various bizarre signs, especially eye symptoms, but are powerless to

prevent it. This makes them irritable and anxious in advance of the attack.

To arrive at the diagnosis of migraine headache should not present great

difficulty in the majority of cases. Despite that, the fuss about inaccurate diag-

nostics goes on in periodicals and at conferences. A proverb teaches that when

you hear trotting, first think of horses, then of zebras. Medicine often looks

for the zebras first. As a result, patients with obvious symptoms and a family



history of migraine headaches undergo CT scans or other complex expensive

testing meant to rule out tumors or other organic changes irrelevant to the

case—needless waste of public money.

CLUSTERS

These headaches are non-throbbing, unlike in migraine. They are extremely

intense, last from 15 minutes to an hour and occur one after another—in

clusters. Similar to migraine headaches, the pain is mostly unilateral and

located over the eye area. It can be excruciating and accompanied by a

number of symptoms such is flushing, watering of the eyes, runny nose,

temperature elevation. Attacks can be severe to the point of loss of conscious-

ness. Clusters often develop during the dreaming stage of sleep called REM—

rapid eye movements. In contrast to migraine, clusters affect mostly men.

They may occur weeks or even months apart and be followed by long remis-

sions lasting for years.

A lot of research indicates the involvement of the hypothalamus in clus-

ters. The fact that the hypothalamus is actually packed with histamine-

synthesizing neurons serves is the best evidence of the major role histamine

plays in clusters. Still, scientific articles on clusters or headaches in general do

not provide any clue that histamine plays any role at all. In fact, one would

not be able to find the very word histamine in these publications even though

old textbooks and medical dictionaries call clusters histamine cephalgia or

histamine headaches or Horton’s cephalgia. Not only did Dr. Bayard Horton

discover their histaminic origin, but he also achieved wonderful results by

treating his patients with histamine injections. For that, he was criticized by

his peers blaming him for “obsession” with histamine—an obsession for

which his patients were, nonetheless, very grateful.

TENSION HEADACHES

These headaches are usually bilateral, often throbbing, lasting from hours to

months. They are usually explained by the tension of neck muscles.

Electromyographic investigations deny the neck muscle tone as their origin,

and the fact that muscle relaxants do not really work for tension headaches is

also proof. Tension headaches are secondary to the disorganized cerebral

vascular tone, and as in migraine and cluster headaches, the pain is due to

swollen dilated vessels that press on the brain structures. Since the vascular

wall is lined with nerve cells, which are closely connected with mast cells, and



both possess histamine receptors, it is only natural that histamine plays an

important, in fact, the leading role in the production of this kind of headache.

The histaminic nature of tension headaches is also supported by their

frequent co-existence with allergies. Often, patients have both tension and

migraine headaches.

TREATMENT TARGET IN HEADACHESAll three types of vascular headaches are chronic conditions. As in most

chronic diseases, conventional treatment is directed at the end organ and

almost never at the underlying mechanisms, namely the dysregulation of the

mediator/neurotransmitter production. In the same manner as allergists

confuse triggers with causes and look for allergens and irritants to imply that

these are causes, neurologists look for psychological and environmental

factors. Insomnia, stress due to problematic relationships, emotional and

physical abuse, some foods or pollutants in the environment—all are turned

into causes. These should be avoided, eliminated, rectified, normalized...

easier to say than to implement.

Moreover, even with identified offenders, in the majority of cases, taking

such measures does not solve the problem. Infections such as sinusitis and the

rather rare meningitis are also given exaggerated attention in the origin of

headaches. Of course, all such factors may play a part in the production of

headaches. However, recurrent sinusitis is mostly a misdiagnosed allergic

condition, while the relative rarity of meningitis can never explain the vast

occurrence of headaches. Therefore, in the end, after CT scanning, electroen-

cephalograms and sinus x-rays, the sufferers of vascular headaches remain in

solitude with their diagnosed but mostly untreatable headaches.

All articles on headaches strongly emphasize the need to distinguish them

and at the same time, provide a surprisingly small difference in their treatment.

I am not trying to diminish the importance of the diagnosis, but the similarity

of the origin should unite vascular headaches rather than differentiate them for

the purpose of treatment. The majority of existing medications are, at best, able

to relieve one single headache. This fact contradicts the existing theoretical

knowledge that, with the exception of the headaches caused by organic phen-

omena such as tumors, hemorrhages, infection or injury, all of them result from

the changing brain chemistry, and this abnormality is reversible.

In their reversibility, headaches are similar to allergies and early-stage

asthma. Science knows that increased levels of histamine correlate with



migraine attacks as well as with other vascular headaches, and this makes

them analogous to allergies. Mansfield, quoted earlier, made a statement that

migraine “is probably atopic (allergic) disease”7 He also established a bridge

between therapies of neurological and allergic symptoms by saying: “A

productive approach to migraine treatment and prophylactics will require the

same type of integrated analysis that is leading to better therapy of such

disorders as asthma.” His article points out that the histaminergic neuron

system regulates serotonergic and noradrenergic activity via activation of H3

receptors and suggests H3-agonists as “prophylactic agents for people who

suffer from vascular headaches.” This attributes to histamine far greater

importance than to serotonin, at least in the production of vascular head-

aches. Clinical medicine ignores this scientific fact.

The pioneering ventures of some doctors to correct histamine imbalance

with histamine injections are discouraged quickly. Horton, being so famous,

could at least publish his articles, whereas attempts by practitioners of a lower

rank are doomed.

DRUGS FOR HEADACHESExisting therapies leave untouched the heart of the problem, therefore their

ineffectiveness is only to be expected. Painkillers are the most common

prescription. Aspirin is one of them. The name is as familiar as that of a

friend. Its side effects range from simple allergic reactions to anaphylaxis.

Luckily, the latter is not so common. When used for a long period even in

small doses, aspirin contributes to heavy bleeding from cuts and wounds and

for this reason is contraindicated before elective surgery. It may upset the

stomach or even lead to bleeding ulcers and is therefore recommended after

meals, with food or in coated pills. Caution is advised against taking aspirin

in late pregnancy in order to avoid prolonged labor, profuse hemorrhaging

during labor and unwanted effects on the fetus—from low birth weight to

death. The most recent finding of American scientists inform us that aspirin

contributes to pancreatitis and even pancreatic cancer in women.

Another common medication is Tylenol. It would not be an exaggeration

to say that it is the most abused drug. Tylenol exists as a plain pill as well as

in combination with codeine. Plain Tylenol is one of the least harmful drugs

on the market if taken occasionally. However, its regular use, interaction with

other medications and consumption in more than the recommended doses

may result in rather serious complications such as serious damage to the liver



and kidneys. Forbes Magazine, in the December 1997 issue, states there were

hundreds of fatalities of Tylenol overdose that year. Patients with headaches

must be the prime drug consumers. The amount of dollars paid for liabilities

is easily absorbed by the profits from the general drug sales, and the number

of casualties remains unknown to the general public under the terms of the

agreements between the manufacturer and the beneficiaries.

Tylenol #2 contains 15 mg of codeine, while Tylenol #3 has 30 mg of the

narcotic. Naturally, the more narcotic content, the better the pain relief. With

time, headaches become refractory to medications, the transitory relief

shortens, and correspondingly, the need of medications escalates. Narcotics

taken for a long time and/or in large doses form a habit. Simply put, headache

sufferers may involuntarily become drug addicts. Sadly, even upon the real-

ization of the drug dependency, they may not be able to stop the medication

because of withdrawal symptoms. In fact, a lot of headache sufferers are

hidden drug addicts, and addiction is the price paid for the relief of every

attack. Considering the amount of the narcotic ingredient consumed by the

patients with headaches, one should not be surprised to find referrals to reha-

bilitation facilities among the treatments offered by Pain Management

Clinics. The word rehabilitation is a substitution for detoxification. Narcotic-

containing painkillers are especially dangerous for pregnant women, as their

babies may suffer withdrawal symptoms upon birth. Luckily, nature took care

of the potential disaster created by medicine, and the hormonal changes are

often favorable in that they rid pregnant women of headaches.

Whether another painkiller, Advil, is better or worse than aspirin or

Tylenol in relieving a headache, depends on the individual. Most patients

with headaches experiment with all of them at some stage.

Since headaches are common in allergy patients, Tylenol, Aspirin and

Advil are often combined with other medications—decongestants, antihista-

mines, antitussives (cough suppressants), and expectorants. These all claim to

relieve headaches, the accompanying cough, nasal congestion, and “cold.” The

latter is mostly misinterpreted allergic rhinitis. Each of the ingredients has its

side effects. I do not dare speculate about their interactions and cumulative

effect, which is highly probable because the chronic nature of headaches and

allergies forces a lot of patients to abuse the combo drugs.

For fear of liability, the producers list complications of their products, and

the responsibility lies entirely with the prescribers. Depending on the ingre-

dients, the combination drugs may be contraindicated for patients with a



liver, kidney disease, peptic or intestinal ulcers, asthma or allergies, a heart

problem, problems with urination, mental illness, thyroid disease, etc.

Pregnant women and small children would be better to stay away from them.

The advice given to these groups is to consult their doctor. Probably, the drugs

show good temporary results within the several months’ testing on people

who do not take concurrent medications and, apart from headaches, are

generally healthy. Unfortunately, the prescriptions are often given to people

who do not fit into this ideal.

In addition to the inherent potential for adverse reactions from the ingre-

dients contained in the headache medications and a possible addiction

resulting from their most effective component—narcotics, the existing thera-

pies give a boomerang effect: a medication-induced headache has become a

problem. This means that without painkillers, the headache sufferers might

have been better off. Again and again, we face the same predicament in the

treatment of chronic diseases: regular symptomatic drugs may aggravate and

complicate the very condition for which they are prescribed.

Only out of desperation would one resort to such procedures as cocainiza-

tion of nervous knots, or surgery. However, these chop-off-your-head proce-

dures created by Western medicine are among the headache therapies. Luckily,

they are not very effective, as is admitted by the editor of journal Headache Dr.

J. Edmeads, and therefore are not popular: “surgical ablation of the trigeminal

root or nervus intermedius is a last resort that helps only some.”8

Intramuscular, intravenous and oral steroids are among the treatments.

Fortunately, they are not very effective either. I say ‘fortunately’ because other-

wise, headache sufferers, would not only face the plight of becoming drug

addicts but, similar to asthmatics, could start counting the complications

resulting from steroid therapy.

The knowledge of the ineffectiveness of the available treatments and the

danger of the medications is thankfully growing among lay people. They try

elimination diets, exercise, physical activities, but in the majority of cases,

these measures are, at best, only partially helpful. The genetically predeter-

mined chemical imbalance in the brain may manifest without any evident

trigger or be precipitated by one which may be hard to eliminate. Among the

unavoidable triggers are stress, environmental phenomena and natural phys-

iological body changes. When all means fail, patients often end up having

lessons on how to cope with the pain psychologically and physically. Self-

support groups multiply.



Although prevention of headaches by medications is considered to be a

part of the treatment, it is hardly ever achieved by the available therapies. In

fact, it is wishful thinking. For prevention, antidepressants, calcium-channel

blockers or beta-blockers, are sometimes prescribed. Their rather infrequent

prescription is tacit admission of their inefficiency. Moreover, while the effect

is negligible, the side effects may add up. For instance, the co-existence of

asthma and headaches is common, and beta-blockers are antagonists to bron-

chodilators. This means the blockers may stir up a hidden asthma or aggra-

vate the existing one.

Dr. J. Edmeads suggests lithium and corticosteroids for prophylaxis. There

is no need to dwell again on steroids, whereas lithium deserves a few comments.

This is the drug used to treat manic states like manic depression. The side

effects are gastrointestinal distress, irreversible renal failure, and neuromuscular

symptoms. Lithium affects the central nervous system including epileptic

seizures, leads to significant cardiac arrhythmia, thyroid hypofunctioning and

goitre formation. Patients on lithium require regular blood tests to avoid toxi-

city. Still, even if toxicity is determined, there is no antidote to the drug, and the

condition may be fatal.

Ergot is a fungus that grows on such grains as wheat, has a high histamine

content, and was once used for the production of medicinal histamine. The

names of ergotamine and cafergot, conventional medications for migraine,

have ergot as a root. In trials, ergotamine, if taken for a long time, showed a

better and more lasting effect than Imitrex, considered by conventional medi-

cine to be the king of all drugs for migraine headaches. Dr. Edmeads also

recognizes the prophylactic value of ergotamine. Its connection with hista-

mine is not acknowledged.

Children are in a worse position compared to adults. They cannot be

prescribed narcotics, and controlled studies on children for prophylactic

remedies have not been conducted. Many drugs can be prescribed for teens

only. By nature, children are impatient and reluctantly accept measures such

as placement in a dark room and relaxation techniques. Counseling as to how

to cope with the pain and psychotherapy sessions are almost of no help to

young patients. School attendance and the child’s ability to learn naturally

suffer. Teachers’ impatience and inability to understand (believe in) the

child’s disease is another complication. A medical problem turns into a social

one that involves the family, the school, and even the community.



THE PARADOXES WITH IMITREXThe drug industry’s revenues due to headaches must be enormous. Spend

half an hour in front of the TV set, and you will see several commercials for

“the best” drugs for the purpose. Once again, I go to Imitrex, the recognized

champion for the relief of migraine headaches, the 1994 Winner of the Prix

Gallien, the highest prize given to the best medication of the year. The flyer by

its manufacturer, Glaxo Canada, is persuasive in showing the advantage of

Imitrex over other medications. The drug producer reveals that Canadians

annually consume 29 million analgesic tablets. The flyer refers to prescrip-

tions only.

Plain and extra strength Tylenol can be bought over the counter and are

thus not included in the statistics. The actual figures must be frightening. The

flyer admits that Canada has become a champion in per capita consumption

of codeine, and that most patients start out with just episodic migraines and

thus, an episodic pill but often end up as drug abusers. These statistics on the

addictive nature of painkillers serve well in promoting Imitrex, which is not

addictive. As was said before, it is an analogue of serotonin, a neurotrans-

mitter known to play an important role in migraine headaches. Unlike

painkillers, which relieve pain by blocking certain mediators of pain, Imitrex

is an agonist of particular serotonin receptors. Its administration results in

the inhibition of serotonin release. Now, let us conduct an investigation.

HISTAMINE VS. SEROTONIN“Histamine H3 receptors have been found to inhibit the release of serotonin,”

wrote L. Mansfield in the paper cited earlier and theorized that “use of this

regulatory pathway may prove to benefit migraine sufferers.”9 His statement

is based on the well established theoretical knowledge, which allows one to

make a logical conclusion: serotonin balance is achieved by regulation of its

governing substance, namely histamine.

Long before Mansfield, this theoretical postulation had been proven clini-

cally by B. Horton who had successfully used histamine for various neurolog-

ical conditions, headaches in particular. Horton’s follower, Professor S.

Diamond, the head of the Chicago Diamond Clinic, was once proud of his 40%

excellent results to intravenous histamine in patients who “were treatment fail-

ures to more conservative and conventional outpatient therapies.10 The article

says that the results of histamine therapy “did not appear to diminish over time,



and that prolonged remission of chronic cluster may be achieved by this type

of treatment, thus confirming the results of Horton.” In spite of this informa-

tion, the editor of Headache, Dr. Edmeads, states on page 62 in Conclusions that

“no biochemical or imaging markers have been observed” in headaches, and

“the nature of the central nervous system dysfunction is unknown.”11

Ironically, this very article exposes the “nature of the dysfunction.” It has

abstracts in English and in French. In the English version, the title is Cluster

headache, in French, it is La cephalee vaculaire de Horton, that is Horton’s

headache. Before a cluster headache was renamed as Horton’s vascular head-

ache, it had been called histamine cephalgia. Although Horton’s name has

been omitted in the main medical textbook, it still exists unchanged in

medical dictionaries and clearly points to the cause of headaches.

An interesting situation is created:

■ theoretically, the more significant role of histamine (compared to serotonin)

is well established;

■ one kind of vascular headache—cluster—is directly called histamine

headache, and the central role of histamine in the two others is recognized;

■ a prominent scientist (Mansfield) speculates about histamine agonists in

headaches in his work based on 32 references;

■ histamine congeners exist in the Stanford laboratory;

■ histamine agonists are reported to be effective (by J. Arrang);

■ oral histamine derivative (Serc) and injectable histaglobin underwent

double-blind and open clinical studies, which are reported to be successful;

■ a world-famous neurologist (Horton) leaves 1402 medical charts of the

patients with neurological conditions, mainly headaches, whom, in the

majority of instances, he successfully treated with histamine. The 1985 neuro-

logical symposium, where he was given awards posthumously, recognized him

as an outstanding scientist whose belief that “nature heals, but histamine

cures” was based on “his considerable knowledge of pathophysiology”;

■ a group of contemporary professors of medicine (Diamond et al.) used

histamine with a rather high degree of success in clusters that had not

responded to other medications.

We have the solid grounds to employ histamine or its congeners at least on

those headache sufferers who are failures to any other therapy. Inexplicably,

in the same article, Mansfield turns 180o from being a proponent of hista-

mine to becoming a promoter of its antagonists. The knowledge of histamine



congeners and agonists are no longer detailed anywhere. Horton’s medical

charts are forgotten. The Chicago Diamond Clinic has never published

another paper on their treatment of cluster headaches with intravenous hista-

mine, and the annual seminars organized by the Clinic do not have histamine

therapy on their agenda.

All this looks, at the very least, strange. Two mediators—histamine and

serotonin—are recognized to be important in the origin of migraine, with the

superior, regulatory role given (in theory) to histamine. Medicine elevates the

inferior serotonin to the position of the central player and gives it the green

light in the form of a drug, which relieves only one given headache at a time.

The superior, histamine, which could regulate its own balance plus the sero-

tonin production, becomes an unspoken taboo. It is not studied, used, or even

mentioned. It has become a medical secret.

Allergology that developed hundreds of antihistamines is silent about

histamine as the primary allergy mediator. In this connection, should we be

surprised that histamine is eliminated from neurology where it is not the

primary but one of the primary neurotransmitters? Why is the knowledge on

histamine so dangerous? Unexpectedly, the answer can be found in another

area, mathematics, which unemotionally explains a lot of things.

I came upon interesting figures in The Medical Post, on March 7, 1995: the

annual cost of migraine treatments in the “pre-Imitrex era” in Britain was $30

million (US). The estimated costs of Imitrex injections would exceed $2

billion. Of course, the price of the drug limits access to it, no matter how

successful it may be, and not everybody will be able to afford it. However,

because there is no better medication in relieving migraines, an agonizing

pain may force even many needy sufferers to resort to Imitrex. As each

headache necessitates another injection or pill, the revenues from the drug

sales will be high.

The picture would be different with histamine that could completely rid

the sufferers of any vascular headache, including classical migraines. Besides,

taken for headaches, histamine could relieve some neurological symptoms

that also developed because of histamine imbalance. Add allergy and asthma

symptoms which could also be drastically reduced with histamine therapy.

No drug developer of sound mind would go for such an all encompassing and

effective drug. Especially so, if it manufactures both allergy and migraine

medications.



B. CHRONIC FATIGUE AND IMMUNE DYSFUNCTIONSYNDROME

THE HISTORY OF THE SYNDROME

The word syndrome is of Greek origin and means a set of symptoms which

occur together. The abbreviated form for the disease is CFIDS or—CFS. Look

attentively at the name of the disease. It sends the message that immune-

related and neurological events coexist, which is compatible with the

morphology (structure) and physiology (functioning) of our body. Another

message is that dysregulation in one of these systems finds, as a rule, finds its

way to the other. In fact, CFS is the best illustration of the coordinated func-

tioning of various regulatory mechanisms, their unity and interdependence

in health and disease. The affliction of the two regulatory systems, nervous

and immune, may manifest in such an assortment of symptoms that there has

hardly ever been another disease causing so much discussion on its very exis-

tence. For doctors to master the concept of disease in principle and to under-

stand the pathogenesis of this complex syndrome in particular, the

knowledge of psychoneuroimmunology, PNI, becomes a must. PNI is the

only science that studies the total body. Failure of the medical profession with

CFS both diagnostically and treatment-wise is a perfect illustration of what

happens when medicine excludes this science from its agenda.

Since the end of the seventies, an unexplained epidemic has been

spreading all over the world, especially in the developed countries. The main

complaint was an unusual tiredness unrelated to the load of work performed

or stress endured. It often affected young, otherwise healthy people, espe-

cially so-called “yuppies.” The question of why CFS has been initially regis-

tered among the younger and more educated people is of great interest, and

does not have one answer. Definitely, ambition and psychological stress

among the “yuppies” are higher than in the average population, and this

contributes to the development of diseases. Another thing is that educated

people care more about their health and hence, notice their ailments earlier.

There is also a high professional demand to be fit, which explains their

interest in medical achievements and desire to turn those into their service.

Thus, “yuppies” consult doctors and start taking medications earlier than

other groups of people, and the disease in this case had more to do with the

awareness than with environment or genetics. The reasons are mainly of

social, not medical nature.



Among the symptoms accompanying fatigue, there are headaches, poor

concentration, confused thinking, memory loss, depression, poor sleep, poor

appetite and as a result, weight loss; migrating aches and pains in muscles and

joints; gastrointestinal symptoms with bloating, gas, constipation or diarrhea,

sore throat without fever or with a mild one and enlargement of lymph nodes.

The combination of the symptoms was so individual and fluctuating that it

produced the impression of several co-existing medical problems rather than

one common condition. The symptoms were ascribed to separate illnesses

according to the organs that showed symptoms. Up until now, the approach

has not changed much. Thus, constant tiredness is mostly conceived as a

purely psychological factor or depression. The cause for migrating pains in

muscles and joints is sought in blood tests, which are mostly non-indicative.

Sore throat is taken for recurrent pharyngitis. Nonspecific gastrointestinal

symptoms, after a series of demanding and uncomfortable tests are mainly

undiagnosed or related to eating habits. Allergy and asthma symptoms also

remain unconnected with the concurrent neurological symptoms of CFS.

The CFS patients have become the most unlucky group that simply

appears to be suffering from numerous concurrent diseases or “psychological

instability.”

The medical profession has been extremely resistant to recognizing a

disease with such an indefinite clinical picture and unpredictable course.12

Besides, nothing decisively shows in blood tests, x-rays or other parameters

needed by conventional standards to consider a medical condition real and

not imaginary. This attitude has been taken despite the fact that there are

numerous precedents with diseases not confirmed by such tests, and vascular

headaches are the most demonstrative example. The same is true for psychi-

atry, a whole field of medicine. For a long time, medical professionals were

unable, and probably therefore reluctant to deal with the syndrome. With

time, however, the epidemic became too widespread to be ignored. Doctors

and their families have not been spared, and this might have contributed to

the recognition of the disease, although only after heated professional battles.

THE TRIGGER, THE CAUSE—AN ETERNAL PROBLEMAll diseases are given a name. David Bell in his The Disease of a Thousand

Names13 says about CFS, “…the number of symptoms is probably exceeded

only by the number of theories proposed to explain them.” The name of the



disease was changing: Yuppie flu—due to an allegedly unknown causative

virus spread predominantly among yuppies; the Epstein-Barr syndrome—the

virus at first suspected and later rejected as causative; myalgic encepha-

lomyelitis or fibromyalgia—a poorly understood syndrome, which, in fact, is

nonspecific muscular or joint pain due to an inflammatory-like process in the

nervous and immune systems. These are just few of the many names. A patient

of mine once gave an amazingly descriptive name—whole-body migraine!

Trying to explain the origin of CFS, medicine followed the well-trodden

path: the triggers were described as causes. The question of the cause has not

yet been solved. Up until now, official medicine has not completely ruled out

a virus as the cause (not as a trigger). Thus, the FDA does not recommend

blood donation from the patients with CFS in “active form,” although the

question remains of what “active” means in regard to this chronic condition.

The viral theory contradicts the fact that the majority of patients with CFS

have the symptoms in the absence of any infection. It is especially interesting

that a previous exposure to Epstein-Barr virus can be found in healthy people

without CFS. Other not detected viruses are also suspected in the origin of

CFS, even in patients whose symptoms came spontaneously, without any

preceding infection. The explanation given by doctors is: these people must

have had an infection without noticing it. A convenient way of thinking!

Through the years, more and more researchers were coming to the conclusion

that the central nervous system played a major role in this syndrome. In 1988, the

disease acquired its latest name—chronic fatigue syndrome. The involvement of

the immune system became evident later, through the omnipresent statistics. The

figures showed that about 20% of the population suffered from CFS, and at least

half of them had asthma, while the overwhelming majority, up to 80%, had other

respiratory and/or skin allergies. All of these observations resulted in final accept-

ance of the name. It includes chronic fatigue as the main symptom developed due

to brain dysfunction and allergies as the sign of the malfunctioning immune

system, plus some vague symptoms, which can be the result of the malfunc-

tioning of either of these systems. Strangely, most doctors still ascribe the disease

to a virus or say the cause is unknown.

The growing statistics in CFS are consistent with the rising incidence and

morbidity of allergies and asthma. This should not come as a surprise to whose

who know how cells function. Abnormal brain chemistry involves immuno-

competent cells (or the other way around) due to their proximity, involvement

of the same receptors, synthesis of the same cytokines, mediators and neuro-



transmitters. Like many chronic diseases, CFS may not have any identifiable

trigger. Therefore, the understanding of the genetically predetermined regula-

tory defects in the functioning of the immune and nervous systems becomes of

utmost importance, while what triggers the process is of lesser significance.

Nevertheless, the attention of clinical medicine is focused solely on the

secondary events, and the fight is going on to eliminate those potential trig-

gers, which are the products of our abusive attitude towards nature. The fight

for cleaner air and water is justified. However, this fight for an improved envi-

ronment would in no way be less justified if doctors started to focus on

tuning up the immune and nervous systems of those who are now paying the

high price for the “progress” of our civilization. Trigger elimination and envi-

ronmental purification can hardly help them at their most immediate level.

CFS AS A SOCIAL PROBLEMSlowly, this disease, which mostly remains undiagnosed by lab tests, is

becoming a physical and not a fictitious condition in the eyes of the medical

profession. As with many things in medicine, the purely medical problem—

the recognition of the disease—depends on other parts of the social

organism. In the case of CFS, it lies with the rising insurance claims from

those temporarily or permanently incapacitated whose laboratory findings

are normal. So, real patients are often labeled as false claimants.

The bizarre combination of the symptoms, the inability to confirm them

through testing, and the very poor understanding of the underlying mecha-

nisms of the disease, in combination with the resistance of the financial insti-

tutions, have created a situation unprecedented in medicine: the existence of

a disease not fully recognized by the medical world. For a long time, patients

with CFS were unable to even find a doctor with a sympathetic ear. Although

those fairly rare doctors could not change the plight of the sufferers, they were

able, at least, to make their life easier in the sense that the patients were

believed not to be feigning the symptoms.

In addition to the physical suffering, the CFS patients often have to put up

with a stigma of being shams. Within the last decade, the disease is being

recognized only by a portion of the medical profession. Ontario, for instance,

still does not have a diagnostic code for CFS among the codes used by physi-

cians in their billing. The plight of the CFS sufferers is worse than, say, the

predicament of patients with severe hay fever. At least, the latter have an illu-

sory “three A’s program” advertised by allergists—awareness, avoidance and



action. CFS patients are not given even this illusion of hope. Their disease does

not have a specific season to make them aware of its approach. They do not

know what to avoid, as there are no certain identifiable stimuli. They cannot

act because not only are they physically unable, but they do not know what to

do. The doctors are helpless, and the most sincere of them admit the fact.

A lot of self-help groups have appeared. Probably, psychologically it is

easier to know that you are not alone, and that many others suffer from the

same mysterious general malaise that is often difficult to describe. A lot of

patients see their families falling apart because other members are unable to

cope with a permanently sick (pretending?) person or to comprehend that a

severe illness may exist and not show in tests. Financial difficulties add up due

to the inability of the sufferer to work. The combination of the untreatable

physical symptoms and the resulting social problems takes its toll, and the

number of suicides among CFS patients is rising.

THEAPIES FOR CFSCan we expect successful treatment for a disease not understood or fully

recognized by the medical profession? Can medicine treat a condition the

origin of which is a mystery, and which has the assortment of the symptoms

that cannot be explained by any existing theory? The answer is “No.” I have

read both scientific sources and literature written mostly by sufferers them-

selves. There is only one big difference between the two in their approach to

resolution. While lay persons are ready to use and share any approach in

search for improvement, doctors are a lot more reserved in their recommen-

dation of remedies, which are not “scientifically proven,” that is, have not

undergone double-blind trials. However, several patients having doctors in

the family who suffer from CFS told me that those people were trying every-

thing and anything without making it public knowledge. I do not blame these

doctors, as they are between a rock (their disease) and a hard place (the estab-

lishment represented by their critical peers).

Among the therapeutic modalities recommended by the sufferers them-

selves, there are relaxation techniques, exercise programs, meditation, herbal

remedies, acupuncture, and avoidance of certain allergenic foods. The latter

indicates the growing awareness of the patients of the co-existence of allergic

and neurological symptoms. Patients ingest tons of vitamins and minerals,

drink herbal tinctures, elixirs, and brews. No magic happens. I am not critical



of these therapeutic means. I am merely stating the sad fact of their failure to

produce any significant positive effect.

The list of medications prescribed by doctors includes antidepressants

such as Prozac and Elavil, symptomatic drugs for intestinal disturbances,

painkillers for aches, muscle relaxants for tense muscles, anti-inflammatory

drugs for aching joints, antihistamines for allergic symptoms, and antibiotics

for recurrent sore throat (despite the absence of any bacterial proof of such

“infections”). As is the case with all chronic diseases, the drugs target the

organs affected at a given moment. What if a patient has numerous symp-

toms at once? Imagine starting the morning with a pile of pills in front of you!

To know how ineffective the medications are, one only needs to open any

book on CFS or read patients’ pleas on the Internet.

The panacea for all chronic conditions—steroids—has already put its foot

in the door. Steroids are not yet the main drug in CFS, as they are in asthma,

but wait, it is only the beginning. The idea of using them was born when a lab

testing revealed that patients with CFS often have a decreased level of adrenal

corticosteroids. A prescription for their replenishment with oral or injectable

steroids was ready at once, with all the possible consequences. And again we

hear assurances about the harmlessness of the low doses in which steroids are

prescribed. Such is, for instance, the conclusion of one of the initiators of

steroids in CFS—the research team at the National Institute of Health in

Bethesda, Maryland, that has studied the illness since 1979. This idea has

supporters. We have steroids as the first-line therapy in asthma and know

their effect on the immune system. In case of CFS, steroids will inhibit the

host’s already weakened immune system and also adrenals and thus deprive

the sufferers of their central natural defense. For these patients, steroids may

prove even more harmful, as depression is a common symptom of CFS, and

it is also a typical side effect of steroids. The drugs may deepen the existing

depression and increase the need of antidepressants later. The logic of medi-

cine never fails to amaze me.

CFS FROM THE STANDPOINT OF PSYCHONEUROIMMUNOLOGY (PNI)Basic science possesses all the data that can explain what causes CFS.

According to PNI, the central systems of the body are interconnected in their

functioning, and imbalanced release of just one regulatory chemical can



involve the whole body in disease. Similarly, correction of the defect can

rectify numerous problems. The following is what should be widely known

about the functioning of the central regulatory systems and histamine’s

involvement in it:

■ the total body is not a mechanical construction made up of different

isolated parts but an artful indivisible design of nature;

■ the functioning of the nervous, immune and endocrine systems is reciprocal;

■ the crossroads of these systems is the hypothalamus and pituitary unit—the

brain structures controlling neuro-endocrine and immune mechanisms;

■ histaminergic neurons are abundant in the hypothalamus and only rela-

tively less in the peripheral nervous system;

■ histamine is an inherent chemical in all body tissues and a major product

of immunocompetent cells;

■ all cells possessing histamine receptors form the histaminergic system that

conducts and realizes its messages;

■ histamine messages are central in allergy, asthma and are very important

in other chronic immune inflammatory diseases; they also carry regulatory

instructions to neurotransmitters in neurological disorders;

■ histamine messages work through the CRH/mast-cell/histamine axis and

thus involve the HPA axis (CRH stands for corticotropin-releasing hormone)

■ histamine regulates CRH—the pituitary hormone-messenger, which acti-

vates the work of the adrenals, our main organ in adapting to all situations

stressful to the body.

■ histamine imbalance can affect the functioning of the whole body due to the

spread of histamine-generating cells and histamine receptors.

Since any functional encephalopathy arises as a result of a chemical imbalance

in the brain, histamine’s ability to modulate the release of other important

mediators and neurotransmitters may become crucial. Histamine governs

■ serotonin, which is central to the origin of vascular headaches, depression,

chronic fatigue syndrome, irritable bowel syndrome;

■ norepinephrine, whose imbalanced release leads to depression, anxiety,

chronic fatigue syndrome;

■ dopamine, whose release is central in schizophrenia and Parkinsonism, and

■ endorphins that affect mood and control any pain, including headaches.

The impaired regulatory activity of histamine becomes the cause for functional

encephalopathies, including CFS. You might say that dysregulation of any other

major mediator or neurotransmitter can be equally responsible for the symp-

toms, and thus, histamine is not unique. That is correct, but partially only.



Science recognizes that it is histamine that regulates these mediators and

neurotransmitters and not the other way around. Histamine reaches our genes

and positively changes their functioning—the task no other neurotransmitter

can fulfill. Histamine is the best activator of the intracellular enzyme cyclic

AMP system whose activity is crucial for the immune and nervous systems

and also for the production of various hormones, including the vital corti-

cotropin-releasing hormone responsible for the functioning of the adrenals.

Science may never fully understand the intricacies of mediator and neuro-

transmitter activity or their relationships, however, the already existing

knowledge allows us to trace the basic processes and to make the conclusions

needed to help the forsaken group of patients with CFS now.

STATE OF THE ART WITH CFSThe 1,600 page of the textbook Merck Manual, Home Edition 1999 allotted

only a tiny part of a page to CFS where it lists the symptoms and names the

formerly suspected and later rejected Epstein-Barr virus as the cause. This,

better than anything else, reflects the situation with this disease.

As is with allergies, modern medicine does not seek support in basic

sciences when it deals with CFS and takes the easy, superficial approach. Such

symptoms of CFS as dizziness or headaches are allegedly the result of abnor-

mally constricted/dilated brain vessels. Why the vascular tone is often

impaired in those who are young is not explained. Depression is often viewed

as the patient’s lack of motivation in life. There again the question remains

unanswered as to why so many young people, often well educated, successful

in their careers and living seemingly balanced lives all of a sudden become

depressed. Fibromyalgia, common for CFS, is perceived as vague muscular

and joint pains. Medicine explains these pains as resulting from the lack of

exercise, whereas for many, this is not the cause but the effect of their disease.

Frequent urge to urinate or “hyperactive bladder”, as the diaper-advertising

companies often call this condition, is often explained as urinary tract infec-

tion even though urine culture test comes negative.

Of course, each of these symptoms may be a manifestation of the malfunc-

tioning of the corresponding organ. However, all together, in one patient, in

combination with other signs and symptoms, allergies among them, they

create a picture of one disease—a major chemical dysregulation in the central

nervous systems and its inability to properly govern the functioning of end organs.

The treatment should target the cells releasing mediators and neurotransmitters



in disproportionate amounts and strengthen the inefficient receptors of these

cells. Instead, medicine treats the symptoms as isolated conditions with daily

painkillers, antidepressants, antihistamines, and supplementary hormones. Why?

“Daily” is the answer.

Doctors found a convenient escape: many of them assure patients that CFS

is mostly a self-limiting disease, and they can expect to recover or improve

within a few years. Those who suffer from CFS know better after many years.

I saw patients who had been suffering from it without being diagnosed for

decades, and in many cases, their condition was getting progressively worse,

not better. Pay attention to the second part of the syndrome’s name: immune

dysfunction. This is a better guide than prophesies of well-wishing doctors:

immune defects hardly ever spontaneously self-repair.

There is a pressing need to resolve the problem. Histamine injections

could be a way out for many. Unlike other important mediators and neuro-

transmitters, that may not have even been synthesized, histamine has had its

commercial version for almost a century, therefore employment is just a

matter of the willingness of the medical elite to do so.

I treated CFS directly and also as a condition concurrent with allergies and

asthma. Often, the results were amazing. I suggest to those who want to accuse

me of professing the same treatment for every disease under the sun: look at the

approach taken by conventional medicine that uses steroids for almost every

existing chronic condition. Look up the words histamine and steroids in the

Compendium of Pharmaceuticals at least from the standpoint of their poten-

tial side effects. Compare the entries. You will read a lot on the complications

from steroids but very little from histamine. Even the acute reactions listed for

histamine are the result only of the huge dose given in a specific diagnostic

procedure; such a dose is never given in allergy treatment. Unlike the

Compendium that warns against histamine in asthma, Dorland’s Illustrated

Medical Dictionary 1988 on p. 769 informs us that histamine “has been used

in treating various allergic manifestations... and in the treatment of periph-

eral vascular diseases, Meniere’s disease, and headache.”

As you see, medicine spills the beans at times and recognizes that immune,

vascular and neurological symptoms respond to the same therapy. All this is

strong confirmation of the common histamine-grounded roots of the

ailments that affect these systems’ functioning. Is it not worth looking for the

answer in basic sciences? Clinical medicine does not try to do that. On the

contrary, it suppresses any attempt in this direction.



C. DEPRESSION AND ANXIETYDepression and anxiety are two very common encephalopathies. Depression

means a low level of psycho-emotional activity. Anxiety is exaggerated fear,

uncertainty and apprehension. Although superficially, these are two diamet-

rically opposite ailments, their coexistence is not infrequent. One may observe

polar mood swings in one and the same patient, and manic-depressive illness

is the climax of the fluctuating chemical imbalance in the brain. We exclude

from our description depression and anxiety, which are secondary events

of other disorders such as thyroid disease, stroke, certain tumors, Alzheimer’s

disease, etc., and will cover only those disorders of dysregulation that arise from

the abnormal release and correlation of brain neurotransmitters. As basic

science states and clinical medicine accepts, anxiety and depression are

mostly norepinephrine and serotonin-related. As science states and clinical

medicine does not acknowledge, the balanced production of both is governed

by the histaminergic system.

The brain is the location not only of histaminergic neurons but also of

immunocompentent cells, including the main histamine depots, mast cells. In

depression and anxiety, similar to other encephalopathies, the correlated

functioning of the nervous and immune systems is obvious: psychological

and neurological symptoms are often accompanied by allergy symptoms and

vice versa. Even if a patient does not have allergy symptoms, his family history

often elicits these. Like all diseases of chemical imbalance, anxiety and depres-

sion may appear irrespective of the surrounding events, without any apparent

stimulus. In other words, the luckiest people who live and work in a congenial

environment and enjoy good health, may develop either of these conditions

if their nerve or immune systems are predisposed to malfunctioning.

Episodes of depression are specifically related to the chemical imbalance

of serotonin and norepinephrine in the brain. The symptoms range from

sadness, reduction in vitality to the degree of suicide attempts. Anxiety arises

mostly from norepinephrine imbalance and manifests in a feeling of tension,

apprehension, uncertainty, and trepidation. Panic attacks may come sponta-

neously and last from minutes to hours. The feeling of pervasive fear may be

accompanied by profuse sweating, palpitation, shakiness, etc. It is of interest

that both conditions are common in patients with chronic fatigue syndrome,

which adds to the idea that they have the same origin.

The inability of patients with these disorders to function properly is a great

psychological burden not only for them but also for the family. The patients



are either depressed or agitated, or their mood inexplicably swings. Often, this

is perceived as bad manners or an evil disposition. These people present a

huge economic burden to society due to the treatment expenses, the low

performance level at work, the high absenteeism and the disruptive effects on

co-workers, family and friends.

THE EXISTING THERAPIESConventional treatment depends on what symptoms prevail: antidepressants

for depression and tranquillizers for anxiety. Both kinds of drugs are prescribed

for daily use. Among the most common complications of antidepressants are

drowsiness, dizziness, headaches, and weight gain. The Winnipeg group that

studied the effects of antihistamines and antidepressants in mice, timidly

mentioned their cancer-contributing features.14 It is predictable that

epidemiological studies on humans may never be conducted. Who would pay

for them? Obviously not the manufacturers of antidepressants who have

neglected to do so for decades since the development of this drug group.15

However, evidence has now accumulated to show that drugs like Prozac carry

a 700% risk of cancer in women, while smoking carries only a 400% risk.

Tranquilizers prescribed for anxiety are notorious for their side effects. The

most known and prescribed drugs are Valium and Ativan. According to statis-

tics, in 1986, in the U.S., more than 86% of prescriptions filled were for minor

tranquillizers or anti-anxiety pills. The figures are definitely higher now,

almost two decades later. These drugs are too often prescribed for older

people, and one of the known drug-induced complications is dementia. A lot

of elderly patients with intellectual impairment surprisingly restore their

mental ability when they stop taking tranquilizers. The main risk of tranquil-

izers is daytime sedation, profound confusion, and poor coordination. This

makes the older consumers prone to falls, and the incidence of fractures is high

among them. Tranquilizers are of even more danger for those many older

people who take steroids for asthma or arthritis, as steroids decrease their

bone density and make them especially vulnerable to fractures.

Depression is one of the side effects of tranquilizers, which is the last thing

needed for those patients who have a co-existing depression. These drugs also

impair mental ability and concentration, and their users should not drive.

The chance of an accident rises when tranquilizers are combined with other

drugs or alcohol, even something as mild as a beer. The worst of all unwanted

effects is an addiction that may develop after only several weeks of continuous



consumption. An abrupt discontinuation may bring on withdrawal symp-

toms such as anxiety, sweating, and hallucinations. Therefore, tranquilizers

should be tapered down rather than abruptly discontinued.

It is not the intention of this book to suggest which of the existing tran-

quilizers and depressants are more effective, less hazardous, and what inter-

actions may occur in those who concurrently take other medications, etc. A

patient may receive this information from his doctor, read in the

Compendium of Pharmaceuticals and Specialties or the inserts put into the

drug packaging, or find it in books such as The Worst Pills, The Best Pills.

Instead, I want to point to the inexpensive, safe and effective therapy, which

is not accepted by the medical profession ironically, due to the fact that it is

inexpensive, safe and highly effective. You guessed it, I am referring to hista-

mine injections. I treated allergy patients who had accompanying anxiety and

depression, and the majority greatly improved or recovered with histamine

therapy. For them, histamine was both effective and devoid of the side effects

of the drugs used in the treatment of depression and anxiety.

D. ATTENTION DEFICIT AND HYPERACTIVITY DISORDER OR ADHD

ADHD is yet another encephalopathy also called minimal brain dysfunction or

damage. The figures of school-aged children suffering from the disorder vary

in different sources from 5 to 10 %. As usual, we cannot fully rely on the offi-

cial statistics. My personal experience tells me that almost half of the children

with allergies and asthma have ADHD of a different degree.

As the name indicates, the disease is characterized by two symptoms.

Patients may have just one part of the syndrome—attention deficit or hyper-

activity, or the disease may manifest both in deficient attention and in hyper-

activity. Because of the more ingenuous nature of children who do not hide

their problems, until recently, the disease was thought to happen solely

among the young who allegedly outgrow it.

Lately, medicine has started to recognize that this is not so, and that it is

almost as common in adults as it is in children. The reason for this delayed

recognition lies in the familiar phenomenon: reliance of the medical profes-

sion solely on laboratory tests for diagnostics. Similar to chronic fatigue

syndrome, ADHD does not show in tests either. The underlying chemical

imbalance, not caused by organic changes in the brain, is a fluctuating

phenomenon, which is difficult to measure accurately. The lack of concrete



measurements of the neuro-chemical composition of the brain at any given

moment doomed adults with ADHD to suffer without any diagnosis. Years

later, often because their children were diagnosed with the syndrome, some of

the adults became aware that it had not been short temper or an evil nature

that had dictated their strange and aggressive actions or prevented them from

comprehending academic material. It had been their disease. Despite the

recognition of ADHD in adults, most of the medical and lay sources still

continue to present it as a disorder affecting solely children.

One of the components of the syndrome, hyperactivity, is on the surface,

especially in children. They are fidgety, restless, aggressive, may attack others,

including their parents, kick and bite their peers or undertake unreasonably

risky actions. Although ADHD affects boys and girls in more or less the same

proportion, it is diagnosed better in boys due to more pronounced manifesta-

tions of hyperactivity.

The other component, attention deficit, may not be so obvious. You may

talk to these children without knowing that they are not listening to you.

Deficient concentration and memory make them poor learners. ADHD may

not be diagnosed in their early years because the tasks in the elementary grades

are not demanding, and the teachers are, as a rule, more patient. The student-

teacher adjustment is also easier because a young child has only one or two

teachers. With the higher grades, the responsibilities grow, the number of

teachers increases, and more and more attention is required to develop

memory and perform academic tasks. At that stage, the teachers start to notice

not only an impulsivity, unruly conduct and poor peer communication, which

are more on the surface, but also the less evident easy distractibility, low atten-

tion span and difficulty in remembering. Often, the label of a poor learner

sticks to the person for life.

Children labeled as aggressive and dumb may, in fact, only appear as such

due to ADHD. There may be numerous reasons, other than chemical imbal-

ance in the brain, that result in behavioral problems. Thus, disease-related

behavior must not be confused with the misconduct of a spoiled child. Poor

attention may also be rooted in innate low mental ability. The opposite may be

true as well: our mainstream education program does not provide enough

stimuli for bright children to learn. Some children may also have a poor envi-

ronment at home or have some psychological problems in the family, or with

friends, and their erratic behavior may be the reflection of that.



The diagnosis of ADHD requires participation of parents and teachers. In

cases where the disease goes unattended, the chances of ADHD children

becoming normal members of society are slim. The reasons are: first, the

aggressive behavior of these children alienates their peers and teachers; second,

because of their poor learning ability, they are undereducated. Both factors

may turn them into school dropouts and antisocial people in their later life.

Lucky are those who have loving understanding parents, sympathetic

teachers, and knowledgeable doctors. Growing into adults, many of them

cope with the symptoms, although with difficulty. They may carry through

life their anger against those who could not tolerate their disease-caused

misconduct. Many of these adults, often intelligent people, remember their

unhappy childhood when they felt miserable among their “normal” school

peers and were forced into therapy with child psychiatrists who were

unable to help them. The disease remained undiagnosed at that time. Now,

they see similar symptoms in their own children whose ADHD is, at least,

recognized.

In reality, the diagnosis of ADHD is not as complex as medicine often

suggests. Certain physical and environmental factors, which may interfere

with school, should be excluded as the main cause of low learning ability.

Among them are poor hearing or eyesight, stressful home environment,

innate low intellectual ability. The family medical history is indicative

because, as other encephalopathies, ADHD is genetically predetermined, and

at last, medicine has started to accept the genetic basis of the syndrome. It is

of utmost importance for the doctor to understand that family members may

not necessarily suffer from the same symptoms but allergies, asthma,

migraine, CFS or other encephalopathies. The relation of hyperactivity to

food allergies was noticed a long time ago by more observant doctors but

laughed off by a lot of highbrow specialists. It looks like some are now forced

to recognize the coexistence of allergies and ADHD.

RITALINEvery doctor agrees that the diagnosis of ADHD is of prime importance both

from the medical and social points of view. Let us assume the doctor arrived

at the diagnosis of ADHD. Can the disease be controlled? Yes, says mainstream

medicine and prescribes Ritalin on a daily basis. At present, Ritalin is the

principal medication for ADHD and, therefore, necessitates a special review.



Ritalin belongs in the group of brain-stimulating medications. The drug’s

“mode of action in man is not completely understood,” writes the pharma-

ceutical compendium. This means that it may not produce the desired effect,

or there may be unknown complications. Among the adverse reactions are

nervousness, hyperactivity and insomnia as the most common—just what a

hyperactive child needs! Transient neurological symptoms may include dizzi-

ness, drowsiness, and psychotic episodes including hallucinations. There may

be nausea and abdominal pain, skin rashes, hair loss, blood pressure change,

and cardiac arrhythmia. Among the warnings, Compendium lists possible

weight loss and growth suppression in prolonged use. There is no explanation

of what “prolonged” means—weeks, months or years. “Long-term effects...

have not been well established,” states the drug description, and ADHD may

be a lifetime disease requiring the drug. The manufacturer assures that side

effects usually disappear with dose reduction or drug discontinuation. The

question of how to reduce or discontinue Ritalin and still have control of

ADHD is left unanswered.

Unanswered also is the question of whether discontinuation is feasible due

to the psychophysical dependence that develops in its consumers. The manu-

facturer is aware of potential addiction and recommends “drug holidays”—no

Ritalin during weekends and vacations. Children who may start the drug at the

age of 6 and take it until puberty, 13–15, run the risk of becoming addicts by

the time when, according to the producer, they can discontinue Ritalin use.

The bitter truth is that many children with ADHD cannot escape daily

Ritalin for two reasons. First, parents and teachers often do not have enough

patience to deal with behavioral problems such as short temper, which may grow

to aggressiveness, easy distractibility and poor concentration and memory.

Second, ADHD is a chronic disease, and chronic patients have little chance of a

spontaneous recovery. All this turns Ritalin into a straight jacket for these chil-

dren, and unfortunately, too often, for simply misbehaved ones as well. It is

easier to manage a drugged, docile lamb than to challenge a bright mind.

Thus, even children without ADHD may become victims of the poorly

managed educational system and school-pressured parents who put them on

Ritalin. A lot of children who lag behind at school due to their inability to

concentrate are prescribed the drug. If we exclude the kids under 6 years of

age who should not be prescribed Ritalin, the majority of those remaining

receive it because the diagnosis almost inevitably leads to a prescription.



Teenagers, always the most troublesome group, quickly understood the

“attractive” brain-stimulating effect of Ritalin. For them, it has become an

inexpensive legalized “upper” used at parties and gatherings just for fun. This

increases the number of victims of this drug. Fatalities have been reported

when Ritalin was combined with alcohol.

OTHER MEANS FOR ADHDAlthough almost universally prescribed for ADHD in children and adults,

Ritalin, like all medications, does not work for everybody, and about one

third of patients with ADHD do not respond to it. A large percentage

remains untreated because there is no alternative drug. Non-medicated

approaches to ADHD are educational and psychosocial interventions. Can

these radically help a child whose brain is flooded with disease-promoting

chemistry?

The flaws in the management of ADHD are obvious to the medical

profession, and in search for more effective ways, medicine suggests at times

intriguing methods. One was studied by the department of psychiatry in

Durham, Northern Carolina, and was described in The Medical Post on

March 5, 1996. In this article entitled Nicotine Patches Useful for Hyperactive

Children, Adults? it showed how desperate doctors must be to seriously

suggest that kids use nicotine and how hopeless parents must feel to agree to

turn their kids onto nicotne. Of special interest is that the same Canadian

periodical on page 74 carries an article titled Doctors Must Do Everything They

Can To Fight Tobacco Lobby. The paradoxes of medicine!

Similar to chronic fatigue syndrome, ADHD is a chemical imbalance of

neurotransmitters, mostly norepinephrine and dopamine. As you know, both

are regulated by histamine. Mothers of the young patients whom I treated for

allergies and asthma told me about the dramatic changes in their children’s

behaviour. In some young patients, I observed similar changes minutes after

the scratch test. A thorough questioning of the parents showed that often, the

kids’ behaviour normalized even before their allergy and asthma symptoms

were controlled. The success was compatible with the scientific grounds I dug

out from basic science: along with immunomodulation, histamine provided

the needed neuromodulation. Besides, H3 receptors, found in abundance on

nerve cells, are more sensitive to histamine, which accelerates the response of

the nervous system to histamine injections.



I usually explained to the parents the concurrence of neurological symp-

toms with allergies and suggested they monitor the child’s behaviour during

the therapy. It worked. Not a single parent complained that his child suffered

from Ritalin deprivation.

E. IRRITABLE BOWEL SYNDROME—AN ENCEPHALOPATHY?Irritable bowel syndrome or, for short, IBS, is not exactly an encephalopathy,

nor is it a purely gastrointestinal disorder. It is both. Its origin lies in the

dysregulated neurotransmission in the brain as well as the gut. Among the

descriptive definitions of the syndrome we come across, hypersensitive bowel

is especially indicative. The most authoritative medical source, the textbook

Harrison’s Principals of Internal Medicine, calls it “neuromuscular hypersensi-

tivity of the gastrointestinal area secondary to mental distress.”

The dependence of the stomach and intestine in their functioning on the

central nervous system is a fact known not only to doctors but to laymen as

well. We know that our gut responds with symptoms to anxiety and panic

attacks. You may remember a knot in your stomach while taking an exam, or

an urgent bowel movement upon receiving bad news. Advice given in jest to

never wear one’s best pants when going to war seems to be devised by

someone who knew what IBS was. History gives us an example of how accu-

rate the diagnosis of some doctors was at the time when no theoretical data

were available to explain the origin of the disease. Thus, Rasputin’s lover, a

rich Russian aristocrat, was diagnosed with “neurasthenia of the bowel” by

her doctor. Both Stalin and Hitler suffered for years from gastrointestinal

symptoms with no organic pathology registered in either, therefore one can

assume they had IBS, especially probable in view of their severe psychopathic

make-up or personalities.

The information exists now that explains the origin of the syndrome. A

chemical change originates in the brain chemistry and then echoes in the

nerve functioning of the intestines. An occasional change in the brain chem-

istry produces a sporadic effect in the bowel, while chronic or recurrent

imbalance of neurotransmitters results in a chronic bowel condition known

as motility dysfunction. Similar to allergies and many other encepha-

lopathies, IBS affects women 2–3 times as often as men. And as with other

encephalopathies, the explanation is in their fluctuating hormonal levels, and

hence, neuro-endocrine instability, the regulation of which starts in the hypo-

thalamus. It was thought that the disease occurred mostly in adults, however,



more and more frequently, it is diagnosed in children. One can easily see the

similarity in the growing prevalence of IBS along with the increase of other

functional disorders such as allergies, asthma, chronic fatigue syndrome and

attention deficit disorder.

As all syndromes, IBS consists of a number of typical symptoms, which

occur in various combinations. Among them, there is abdominal pain of varying

intensity, at times so severe that the patients are rushed to ER. Abdominal

discomfort, loose bowel movements or diarrhoea with mucus in the stool,

constipation, bloating, gas, nausea, etc. are common. As a rule, patients with

IBS undergo numerous tests in the offices of gastroenterologists to exclude

peptic ulcer disease, inflammatory bowel disorders, lactase intolerance, etc.

They learn, finally, that the tests do not show any organic cause. Lucky are those

whose doctor at least diagnoses IBS and assures them that it is not a malignancy.

The majority remain without any definite diagnosis, or are misdiagnosed.

The textbook Harrison’s Principles of Internal Medicine (1987) starts the

description of the disease on page 179 with the following paragraph: “The irri-

table bowel syndrome is the most common gastrointestinal disease in clinical

practice, and although not a life-threatening illness, it causes great distress to

those afflicted and a feeling of helplessness and frustration for the physician

attempting to treat it.” The textbook also explains the reasons for the frustra-

tion: “Unfortunately, no specific drug or dietary regimen affords good relief in19

all patients, and thus a number of therapeutic manoeuvres need to be tried.”

The 2000 statistical data given by Dr. G. Kandel from the University of

Toronto state that “the symptoms of IBS are present in about 30% of the

general population.”16 This leads us to the inevitable conclusion that this is the

single most prevalent disease in medicine. Since the disease has no treatment,

it is especially interesting to see what medicine does for the people with IBS.

Quite naturally, a poorly understood and generally misdiagnosed disease

cannot be treated properly. Doctors do not treat the condition as a neuro-

regulatory disorder but as a gastrointestinal disease. It is not different from

the treatment of allergies and asthma that are also dealt with in the end organ.

Antacids and painkillers are common medications for abdominal cramps;

opiates are given for diarrhoea and soluble fibre for constipation.

Only a patient with IBS can understand how embarrassing it is to have a

severe bloating or to feel an urge to defecate in the middle of a serious

meeting. The few doctors who understand that its roots are in the brain

chemistry, may prescribe antidepressants. This, however, does not resolve the



problem either. The chronic nature of the disease can make antidepressants

regular medications and thus lead to a number of complications. The need to

deal with additional symptoms intensifies the patients’ dissatisfaction and

depression and by that, aggravates the course of IBS. Antidepressants may

also be prescribed to patients with IBS because many of them become deeply

frustrated with their never-ending bowel symptoms and do develop depres-

sion and/or anxiety.

Some doctors may suspect an infection and prescribe antibiotics, medica-

tions completely inappropriate for IBS. This often creates paradoxical situa-

tions. Thus, one of the adverse effects of antibiotics is constipation—the

symptoms the patient may already have. Other adverse reactions include

headaches and muscle aches or pains; and again, the patients may already have

those, as these symptoms commonly accompany encephalopathies.

Modern medicine recognizes the presence of numerous symptoms that

point to the central role of the brain in IBS. Dr. Kandel, for instance, discusses

a constellation of them: mood swings, panic attacks, anxiety and depression

as well as non-specific brain-related symptoms such as headaches, backache,

fibromyalgia and urinary tract symptoms. Saying that, one would think

science should seek the roots of all these manifestations in the chemistry of

the brain as uniting regulatory arm. However, as with allergies and other

encephalopathies, medicine points to the more evident superficial connec-

tions. This author, for instance, says that 40% of the patients with IBS have a

history of sexual or physical abuse and pronounces these factors as central in

the origin of the disorder. No argument, a severe stress, no matter of what

nature, may contribute to the development of any chronic disorder, but such

factors are not specific to IBS per se.

This Canadian gastroenterologist makes another assumption that may

even insult many syndrome sufferers: “IBS is a disease of physician-seeking

behaviour.” In other words, patients see a physician in order to attract his

attention or out of fear that their symptoms are the result of cancer or

another dreadful disease. No wonder the author suggests that reassurance

should become “the pivotal point of management.” Other specialists also

support psychological encouragement, which in some cases is better than

medications, at least from the standpoint of side effects thereby avoided.

The answer to IBS, its cause and treatment is similar to that in all

encephalopathies. The underlying cause lies in imbalanced neurotransmis-

sion in the brain-gut pathways. This inevitably indicates the involvement of



histamine, as a major neurotransmitter. The significance of histamine in the

functioning of the gastrointestinal tract, although never indicated in clinical

textbooks, becomes obvious from the fact that the intestines contain over

50% (!) of the body’s immunocompetent cells with their innate histamine

activity. The description of CRH/mast cell/histamine axis in 2000 allows one

to understand the interactions of the immune and nervous system via hista-

mine pathways.17 The axis unites the hypothalamus through its corticotropin-

releasing hormone and the immune system through mast cells with their

most distinctive mediator, histamine. Its impaired production affects the gut,

while correction rectifies neurotransmission in the gut.

As Dr. W.G. Thompson, a Montreal professor who serves on international

committees studying IBS states in his interview, “80% of serotonin activity is

in the gut; it’s likely that drugs acting on the serotonin receptors could also

modulate gut hypersensitivity.”18 There is, however, not a word on histamine

in his work, even though scientists working in this area recognize H2-anti-

histamines (Zantac, Pepsid) as the central medications for gastrointestinal disor-

ders, and by that recognize the presence of histamine there as the main chemical

event. They should also know that serotonin release is regulated by the hista-

minergic system. As everything related to histamine, the histaminergic

neuron system is taboo in clinical medicine, and science is adjusted to the

needs of the pharmaceutical industry. Therefore, the priority is given to sero-

tonin. Indeed, Dr. Thompson informs us about the development of drugs

influencing serotonin. The above-quoted gastroenterologist, Dr. Kandel, also

suggests a 5-HT3 antagonist, which is a sort of antiserotonin. How effective

will “antiserotonins” be? Dr. Kandel admits that the drug’s effectiveness is

limited and is close to placebo response.

An analogy comes to mind. In migraine headache, Imitrex and its

analogues stimulate certain serotonin receptors and by that, relieve a

headache, but only the current headache. At the same time, even in those

headaches that are known as histamine cephalgia, the very word histamine is

concealed by renaming them. We may assume that serotonin-targeting

medications for IBS will be as helpful as serotonin analogues in migraines—

at best, they will curb one attack at a time. Migraine sufferers say that another

headache may start hours later. We may expect similar events with the

serotonin-suppressing drugs for IBS.

Just think of this peculiar approach: medicine prefers symptomatic relief

to cause eradication. Serotonin-targeting drugs will create yet another lucra-



tive product, as they will also deal with the effects secondary to histamine

imbalance. Patients should be happy if these medications provide at least

short-lived improvements. The drug industry, with support of the medical

academia, successfully fights nature in all that involves histamine.

Almost half of the patients with allergies present with various degree of

IBS, and it is most typical of patients with chronic fatigue syndrome. This is a

direct indication that in their origin, these three most common chronic

diseases merge.

The majority of my patients came for the treatment of their allergies or

asthma. I invariably asked them about their gastrointestinal symptoms, which,

as a rule, they neglected to mention, not knowing the connection. It usually

took a long time to explain what IBS was, and how it related to their other

symptoms. To the patients’ surprise, my prediction that relief of their bowel

symptoms might be a bonus often came true. Similar to other encephalo-

pathies, the improvement was often obvious at the allergy skin testing: those

who were experiencing symptoms at the time of the testing felt relief.

Histamine therapy worked in almost all cases.

The sad conclusion is: IBS, a disease of the highest incidence, is poorly

understood, mostly misdiagnosed and does not have any treatment. Any

“manoeuvre,” as the main medical textbook says, is worth trying in order to

relieve the plight of these patients. Histamine could render that help. Still, it

may never be allowed despite the available theoretical substantiation from

basic sciences of its modulatory capacity, and despite its availability in several

forms. The “problem” with histamine is that in all relevant areas, it turns out

to be too effective and would thus shrink the drug market.

F. OTHER HISTAMINE-RELATED ENCELOPATHIES It would be arrogant on my part to present myself as a specialist in neurology

or psychiatry. However, I have read volumes on brain chemistry and treated

quite successfully hundreds of patients with various vascular headaches, depres-

sion and/or anxiety, CFS, fibromyalgia, ADHD, and IBS. As a rule, they came to

me with allergies, while the accompanying encephalopathies were revealed

through questioning at the first examination. Apart from the above-described

encephalopathies, there were autism, seizure disorder, menopausal symptoms as

well as diverse nonspecific neurological manifestations. Using histamine

therapy for their main symptoms, I indirectly reached the related neurological

symptoms. My observations led me to the conclusions that histamine therapy



was highly effective in a wide variety of diseases. Correcting imbalance of

neurotransmitters is nothing but neuromodulation. This is analogous to

immunotherapy in allergies. A different name does not change the essence:

histamine shows its self-regulatory ability in both body systems. Conventional

immunotherapy, although not very effective, exists as a treatment, and although its

goal is to reduce response to a specific allergen, in essence, successful immuno-

therapy is due to the inhibition of the excessive histamine release.

Medical sources do not describe the relief of the accompanying neurolog-

ical symptoms during successful immunotherapy, although, I am sure, this did

occur, as both the immune and the nervous systems are parts of one hista-

minergic system that conducts histamine messages. Neuromodulation is never

mentioned even as a possibility despite the fact that it is theoretically

supported by the description of the neuroimmunologic mechanisms in basic

science research. Irrespective of what sort of encephalopathy is diagnosed, in

the absence of an organic cause, histamine therapy should be tried. It can be

highly effective in many cases. Encephalopathies are sort of allergies of the

nervous system, therefore their treatment with H is only logical.

Among the neurological conditions responding to histamine therapy,

fibromyalgia takes a special place. Conventional medicine has only started to

cautiously recognize it as a disorder related to chemical imbalances in the

brain and singled it out as a separate disease. In fact, it is mostly part of

chronic fatigue syndrome. Since CFS is poorly diagnosed, and the mecha-

nisms of its occurrence are not understood, fibromyalgia that stems from the

same brain events also remains obscure. This has become the reason for its

isolation from the syndrome, whereas very rarely do joint and muscle pains

and/or stiffness present as the only symptoms. As a rule, they go along with

other symptoms characteristic for CFS and are therefore a part of it.

No matter, diagnosed as a separate disease or left undiagnosed, fibromyalgia

is treated only with painkillers and reassurance. Joint pains, even in young

people, are often diagnosed as arthritis and are treated correspondingly. As one

may expect, the results are nil. .

My experience with encephalopathies also includes patients with seizure

disorder without an organic cause. It surprised me when several patients

whom I treated for allergic conditions noticed disappearance of their seizures.

Later on, I purposefully monitored the seizure occurrence in patients with a

history of seizure disorder while treating them for allergies and asthma.

Success was inevitable.



I had four patients with autism. The degree of improvement ranged. The

best results were achieved in a boy with advanced autism, a savant, who stayed

on the treatment for over two years. He was brought initially for food allergies,

without the slightest expectation of improvement in his main problem. In the

end, his performance at school improved dramatically, he started to make eye

contact and logically answer questions. In fact, only a very close observation

could find some minor deviations from the norm in his behavior. Prior to the

histamine treatment, the boy had received a vast variety of unconventional

treatments from North American and European specialists that his well-off

parents could pursue. Another four-year old autistic child, for the first time in

his life started to pronounce words after just four or five injections.

Regrettably, the family could not travel the long distance and stopped the

treatment. The third patient was a small girl with an advanced form of autism.

She was treated for her allergies but showed better behavior, became calmer

and stopped gritting her teeth. Her treatment was stopped because of the ban

of histamine therapy imposed upon me by the CPSO, and this probably

deprived her of further improvement. The forth was a young adult who

became calm and compliant after a few injections. His elderly parents were

unable to bring him on a regular basis, and the treatment stopped.

Considering that no treatment exists for autism, histamine could at least be

used on a trial basis.

I also treated several children with uncontrolled urgency to urinate or with

bedwetting. As it is common in medicine, if an organic cause is not found, the

symptoms are considered to be of psychological origin. Therefore, parents of

these children planned a visit to a psychiatrist on the advice of their family

physician. I suspected the allergy-associated chemical imbalance in the area of

the brain that regulated the bladder functioning. On my advice, the parents

postponed the visit to a psychiatrist for the few weeks that I was treating their

children for allergies and asthma. In all these cases, the symptoms of inconti-

nence disappeared, often faster than the allergy symptoms.

Of interest is a case of a nonspecific condition. The patient, a 7 year-old boy,

suffered from nightmares. He would get up at night and walk around the house.

His mother called my office several days after the initial prick test with hista-

mine. The boy stopped his night wandering, and she decided to postpone the

next visit, to see whether this was coincidental. She brought her son back half a

year later when the symptoms resumed. A short treatment was successful.



There was another peculiar case—an elderly man with ALS, amyotrophic

lateral sclerosis, a fatal disease due to progressive degeneration of the neurons.

The patient could not swallow and suffered from severe pains in his jaw. The

neurologist who had seen him before and after my histamine treatment stated

in his report, “Interestingly, his pain was relieved by histamine injections.”

The menopausal hot flushes related to hypothalamic/pituitary dysfunc-

tion are treated by gynecologists and family physicians generally by synthetic

hormonal replacement therapy—HRT. The studies on HRT are contradictory

in their findings, but lately, in view of dangerous complications, this treat-

ment is recommended only in cases of severe symptoms. Histamine therapy

almost completely eliminated or greatly relieved these symptoms as well as

some others that often accompany menopause, such as insomnia, perspira-

tion, dizziness, depression and anxiety. In these cases, the patients needed

maintenance shots for a lasting period in view of the continuing hormonal

changes. None reported any side effect but only positive changes.

Blood vessels do not exactly belong in the area of neurology. However,

vascular tone is regulated by neuro-endocrine processes and is thus affected

by the hypothalamus. The abundant presence of histamine in the hypothal-

amus and histamine receptors in the vascular wall is the reason why hyper-

tension may respond to histamine. The normal activity of histamine

receptors improves the tone of the vessels, and blood pressure normalizes.

There is another important point in the treatment of hypertension. Beta-

blockers often prescribed for high blood pressure may become a trigger for asthma

patients who have inefficient beta-adrenergic receptors. These receptors need

stimulation, not suppression. Thus, not only does histamine therapy normal-

izes the vascular tone by activating H2/3 receptors in the vascular wall, but it

also eliminates the need of beta-blockers and the resulting worsening in

current asthma or the possibility of inciting a latent form.

You may say that no drug is a panacea, and histamine cannot be one either.

Right. However, human beings are whole entities. Our central regulatory

systems function in coordination, and successful immuno- or neuromodula-

tion resonates through the whole body by restoring numerous functions. The

word holistic is defined in dictionaries as relating to the conception of man as

a functioning whole. This is in perfect harmony with the most comprehensive

field of medicine—psychoneuroimmunology, which remains primarily in the

domain of theoretical sciences. Our market-focused medicine has lost the



holistic approach of ancient medicine. This is when other sciences are parting

with the old hard-nosed materialism of the XIX century and switching to inte-

grative holism of the XX century.

Medicine has reached that shocking state where it cannot exist without its

sponsor—the drug industry. If in the remote past, the industry was supposed

to serve medicine, it is the opposite today. This has made medicine an excep-

tion among sciences and, as a result, it has become hostile not only to every-

thing new but also to everything old that can be useful and healing. This is

especially obvious in the most reversible diseases—allergies, asthma and func-

tional encephalopathies.

ENDNOTES1. JACI 1990;86:673-762. Is the histaminergic neurone system a regulatory centre for whole-brain activity? Trends on

Neuroscience 1991;14:415-83. G. Chrousos. Stress, chronic inflammation…JACI 2000;106:S275-914. U. Knigge, J. Warberg, The Role of Histamine in the Neuroendocrine Regulation of Pituitary

Hormone Secretion, Acta Endocrinologica, Copenhagen 1991;124:609-195. U. Knigge, J. Warberg, The Role of Histamine in the Neuroendocrine Regulation of Pituitary

Hormone Secretion, Acta Endocrinologica, Copenhagen 1991;124:609-196. H. Wada et al. Trends on Neuroscience 1991;14:415-87. L. Mansfield. The role of antihistamine theraphy in vascular headaches. JACI 1990;86:673-76 8. J. Edmeads. Cluster headache and its cousins: A family of pain management problems. Pain Res

Manage 2000;5:58-639. JACI 1990:673-76

10. S. Diamond et al., Treatment of Intractable Cluster. Headache, Jan.1986:44-4511. Pain Res Manage 2000;5(1):58-6312. For a full discussion of the medical politics of this condition see the investigative report by

H. Johnson, Osler’s Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic,Penguin, 1996

13. Pollard Publishing 199014. Brandes L.J.et al. Stimuilation of malignant growth in rodents by antidepressant drugs at

clinically relevant doses. Cancer Res 1992;52:3796-380015. For full understanding of the known danger of antidepressants, I refer you to the study by

David Healey, Let Them Eat Prozac, 200316. G. Kandel. Irritable Bowel Syndrome. The Canadian J of Diagnosis, December 2000: 82-9117. G. Chrousos. Stress, chronic inflammation and emotional and physical wellbeing: concurrent

effects and chronic sequalae. JACI 200;106:S275-91)18. Parkhurst Exchange Nov. 1999, p. p. 76-919. Harrison’s Principles of Internal Medicine, 198720. Harrison’s Principles of Internal Medicine, 200121. Thome J. et al. Cyclic AMP response element-binding protein and depression. Expert Reviews in

Neurotherapeutics 2002; 2:347-54



EPILOGUE OR: “EPPUR SI MOUVE!”1

Exactly one week before the submission of this manuscript to the publisher,

the saga on histamine took an unexpected turn when I opened the latest issue

of The Journal of Allergy and Clinical Immunology. To say that I was stunned

is an understatement: there was a review article with the content-revealing

title of Histamine in the Immune Regulation of Allergic Inflammation.2 The

rubric under which the article was published was no less remarkable:

Rostrum—this in Roman times, was the platform a person stepped onto in

order to gain the public’s ear. I do not have an explanation of how such an

exotic fish could slip through the thick net that had solidly protected the

steroid-saturated journals for more than a decade. However, the very appear-

ance of this publication gives me a slight hope that the truth and medical

ethics will one day be victorious in allergy.

The authors are clinical immunologists from the Swiss Institute of Allergy

and Asthma Research, and their work was sponsored by grants form the Swiss

National Foundation (not a pharmaceutical company, but a tax-payer-funded

national body). The paper is the most comprehensive and accurate overview

of histamine and its functions since the times of R. Rocklin. It is based on 73

references and covers the histaminergic system and the four known histamine

receptors on which its functioning depends. The theoretical work revives

almost all the buried information on the histamine-related mechanisms of

allergy with the emphasis on those that participate in the reversal of allergic

inflammation. The authors

■ unearth the immune- and neuromodulatory role of histamine;

■ suggest a novel therapeutic approach in man: using H3-receptor agonists

and implementing through them the negative “feedback loop” enables one

to control “excessive inflammatory responses”;


■ point to the same mode of action (negative feedback) of H2 receptor in

allergies: “H2-receptor effector function seems to be an essential, potent

suppressor of inflammatory and effector functions” especially useful “in

immune regulation during specific immunotherapy.”

■ resurrect T-suppressors and their central anti-inflammatory product—histamine-induced suppressor factors (HSF): “histamine stimulation

induced Il-10 production in both dendritic cells and T-cells,” and the

activity of “regulatory-suppressor T cells represents a key event in the

control of specific immune response”;

■ specify the mechanism through which histamine realizes its anti-inflammatory

effects: “histamine dose-dependently enhances intracellular cAMP levels

and stimulates Il-10 secretion through H2 receptor”;

■ state that most of the existing therapies for asthma, including the leading

pharmaceutical developments (the combination of steroids with long-acting

Beta-agonists) are based “on the same signal transduction patterns” where

“B2-adrenergic receptors might function similar to H2 receptor in human

subjects.”

The concept that all living organisms possess autoregulatory systems is recog-

nized in science, and its proponent, Belgian chemist Ilya Prigogine, was

awarded the Nobel Prize in 1977.

Our immune and nervous systems, as the central parts of a living complex

organism, are self-regulated, and there is a controller for each operation and

production of immune and nervous cells. I share the ideas expressed in that

article: in allergy and asthma, the major controllers are, indeed, the H2/3

receptors, cAMP, T-suppressors and the anti-inflammatory chemistry, which

is the product of their interdependent work. They are the links of the chain

that provides the balanced release of histamine and, therefore, histamine-

induced chemistry. The genetically-predetermined weakness of these mecha-

nisms is the cause of allergies.

When earlier in the book, I said that the truth will fly in through the

window if not allowed to come in through the door, I did not expect this to

happen so soon. Now, that the truth has been given rostrum, even if acciden-

tally, clinical medicine should acknowledge its existence. It is a crime to hide not

just the substance, histamine, but the knowledge of the whole histaminergic

system that spreads all over the body and is vital for the functioning of the

immune and nervous systems. It is high time to acknowledge the existence of

the protective H2/3-receptor effect and then introduce it into every day clinical



Epilogue 389

practice in order to help those millions who suffer needlessly only because

somebody, obviously for personal reasons, decided to conceal the truth.3

Clinical allergy can break away from the drug industry and significantly

reduce its dependence on it if, instead of medicating its patients with immuno-

suppressive steroids, it will start to revive the body’s sick regulatory tools with

well-researched, safe, effective and inexpensive histamine. This would allow

the national health systems to save billions of dollars that could be channeled

into different problems. The statements coming from the rostrum should not

fall on deaf ear. In this sense, this book is a litmus paper for the Medical

Establishment: the way they treat the material presented here will be indicative

of whether the patients’ interests are truly above their own interests.

ENDNOTES1. This statement is attributed to Copernicus who is said to have muttered it as he left a trial

before the Inquisition where he was forced to recant his mathematical proof showing that the sun, not the earth, is at the centre of our solar system.

2. C. Akdis, K. Blaser. Histamine in the immune regulation of allergic inflammation. JACI2003;112:15-22

3. K. Melmon’s letter of August 28, 1991, to Dr. Ravikovich, that recognizes therapeutic “H2/3 activity”: See Appendix. p. 404.

Plot/Allergies•318-395 11/24/03 11:46 AM Page 389

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APPENDIX


Appendix 397


Appendix 399


Appendix 401


Appendix 403


Appendix 405


NOTICE TO THE READER

If you wish to join in political action on behalf of asthma and allergy patients and the

doctors who want to help them (but are not allowed to do so) consider the following:

writing to KOS Publishing Inc, 1997 Beechgrove Road, Alton, On, L0N 1A0; write to your

local MPP, the Premier of Ontario, the Minister of Health, and the opposition critics. For

their addresses call 416-325-7200 (LIB) 416-325-7272 (PC) 416-325-7116 (NDP). Below

is a sample of the facts upon which you can base your demand for lifting the ban on

histamine therapies.

SAMPLE

To The Premier of Ontario

Your area MPP

The media (TV, newspapers, radio)

(Adjust the text to include your own story as a patient or physician.)

Dear . . .

I have read The Plot Against Asthma and Allergy Patients by Dr. Felix Ravikovich

(KOS Publishing Inc. 2003) and learned that effective treatment for asthma and allergy

exists and that it has been actively suppressed by the College of Physicians and Surgeons

of Ontario (CPSO). I urge you to read this book and examine the documented facts

regarding the highly effective and scientifically supported histamine therapy.

The CPSO has indefinitely and arbitrarily forbidden its use in the absence of patient

complaint or harm, despite scientific support and public protest by hundreds of patients

helped by this treatment and denied access to it since 1992. One request that you:

1. order the CPSO to lift its ban on Dr. Ravikovich’s use of histamine therapy and

2. take steps to allow Dr. Ravikovich to teach doctors willing to learn his technique.

I base my demand on the Helsinki Accord on Human Rights, an international treaty to

which Canada signed in 1988. Among its clauses you will find one by the World Medical

Association, which in 2000 became part of Ontario’s Medicine Act in 2000, but has been

effectively ignored by the CPSO. It states the following:

“In the treatment of the sick person, the physician must be free to use a new diag-

nostic and therapeutic measure, if in his or her judgment, it offers hope of saving life,

reestablishing health, or alleviating suffering.”

I am looking forward to your reply.

Signed


Index

AADHD . . . . . . . . . . . . . . . . . . . 372, 376adrenals . . . . . . . . . . . . . . . . . . . . . . 185

suppression of. . . . . . . . . . . . . 187 ffallergens . . . . . . . . . . . . . . . . . . . . . . 82allergic inflammation . . . . . . . . . . . . 99allergy . . . . . . . . . . . . . . . . . . . . . 71, 93

borderline diseases, and. . . . . . . . 81causes vs. triggers in . . . . . . . . . 69 f

angioedema . . . . . . . . . . . . . . . . . 338 ffanimal dander . . . . . . . . . . . . . . . . . . 86antibiotics . . . . . . . . . . . . . . . . . . . . 101

and asthma. . . . . . . . . . . . . . . . . 245anti-challenge test . . . . . . . . . . . . . . 226antigen. . . . . . . . . . . . . . . . . . . . . 70, 72antihistamines

and cancer . . . . . . . . . . . . . . 36, 177and FDA. . . . . . . . . . . . . . . . . . . . 36and genetic interference of . . . . 176and immunosuppression. . . . . . 177and side effects . . . . . . . . . . . . 176 ff

anti-inflammatory drugs . . . . . . . . 102anti-IgE agents . . . . . . . . . . . . . . . . 280antileukotrines . . . . . . . . . . . . . . . . 279asthma

antibiotics. . . . . . . . . . . . . . . . . . 101as chronic inflammatory

disease . . . . . . . . . . . . . 156, 302as a growing problem . . . . . . . . 238causes of . . . . . . . . . . . . . . . . . . . 256conventional treatment for . . . . . 12current definition. . . . . . . . . . . . 240diagnosis of . . . . . . . . . . . . . . . . 249historic understanding of . . . . . 300

old guidelines for . . . . . . . . . . . . 284reversibility. . . . . . . . . . . . . 110, 143statistics . . . . . . . . . . . . . . . . . . . 258symptoms. . . . . . . . . . . . . . . . . . 243tests. . . . . . . . . . . . . . . . . . . . . . . 254theories . . . . . . . . . . . . . . . . 256, 263vaccines . . . . . . . . . . . . . . . . . . . . . 6

atopic dermatitis . . . . . . . . . . . . . 329 ffautacoid . . . . . . . . . . . . . . . . . . . . 2, 112

BB-cells . . . . . . . . . . . . . . . . . . . . . . . . 71Barnes . . . . . . . . . . . . . . . . . . . . . 156 ffbasic science . . . . . . . . . . . . . . . . . . . 63bronchiodilators

long-acting . . . . . . . . . . . . . 269, 275

CcAMP. . . . . . . . . . . . . . . . . . . . . . 37, 50cells . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

immunocompetent . . . . . . . . . . . . 5Chronic Fatigue Syndrome. . . . . . . 361

social problem . . . . . . . . . . . . . . 364therapies for . . . . . . . . . . . . . . . . 365psychoneuroimmunology and . 367f

cluster headaches . . . . . . . . . . . . . . 351combination drugs . . . . . . . . . . . . . 182conventional classification of allergy 80corticosteroids. . . . . . . . . . . . . . . . 183 fcytokines . . . . . . . . . . . . . . . . . . . . . 40 f

Ddecongestants . . . . . . . . . . . . . . . . 180 fdendritic cells . . . . . . . . . . . . . . . . . . 18depression . . . . . . . . . . . . . . . . . . . . 370


Index 409

Diamond Headache Clinic . . . . . . . . 33Dristan . . . . . . . . . . . . . . . . . . . . . . 180drugs for headaches . . . . . . . . . . . . 354duality in allergy . . . . . . . . . . . . . . . . 59in medicine . . . . . . . . . . . . . . . . . . . . 60in patients . . . . . . . . . . . . . . . . . . . . . 62

Eeconomics in medicine . . . . . . . . . . . 56encephalopathy . . . . . . . . . . . . . . . . 343

and histamine . . . . . . . . . . . . . . 347eosinophils . . . . . . . . . . . . . . . . . . . 141European Histamine Research

Society . . . . . . . . . . . . . . . . . . . . 125

FFDA bans. . . . . . . . . . . . . . . . . . . . . 181food allergy . . . . . . . . . . . . . . . . . . . . 89

Ggene mutations . . . . . . . . . . . . . . . . . . 3genetic functions (histamine). . . . . . 51genomodulation . . . . . . . . . . . . . . . . . 4

Hhay fever . . . . . . . . . . . . . . . . . . . . 339 fheadaches . . . . . . . . . . . . . . . . . . . 349 fhistaglobin . . . . . . . . . . . . . . . . . . . 32 fhistaglobulin . . . . . . . . . . . . . . . . . . 32 fhistamine. . . . . . . . . . . . . . . . . . . . . . 17

as a cure . . . . . . . . . . . . . . . . . . . . 33as neurotransmitter . . . . . . . . . . 344asthma, and . . . . . . . . . . . . . . . . . 29bias against. . . . . . . . . . . . . . . . . . 30cellular vs synthetic . . . . . . . . . . . 23congeners of . . . . . . . . . . . . . . . . 120corrects genetic defect . . . . . . . . . 51degranulation and . . . . . . . . . . . . 17derivatives of . . . . . . . . . . . . . . . 120disease and . . . . . . . . . . . . . . . . . 162drug industry and. . . . . . . . . . . . 65fdual activity of . . . . . . . . . . . . . . . 43encephalopathies and . . . . . . . 345 fhomeostasis and. . . . . . . . . . . . . . 22induced cytokines . . . . . . . . . . . 41 f

Japanese research into . . . . . . . 222 freceptors. . . . . . . . . . . . . . . . . . . . 23serotonin and . . . . . . . . . . . . . . . 358synthetic . . . . . . . . . . . . . . . . . . . . 54systemic reactions and . . . . . . . . 217therapy . . . . . . . . . . . . . . . . . . 308 ffvs. allergen vaccine. . . . . . . . . . . 231

histidine. . . . . . . . . . . . . . . . . . . . . . . 19Hismanal . . . . . . . . . . . . . . . . . . . . . 181Holgate. . . . . . . . . . . . . . . . . . . . . 151 ffhomeostasis. . . . . . . . . . . . . . . . . . . . . 9H receptors . . . . . . . . . . . . . 24, 46f, 117house dust mites . . . . . . . . . . . . . . . . 85Horton . . . . . . . . . . . . . . . . . . . . . . . 33hypothalamic-pituitary-adrenal axis

(HPAA). . . . . . . . . . . . . . . . . . 186 ffhypersensitivity . . . . . . . . . . . . . . . . . . 7

IImitrex . . . . . . . . . . . . . . . . . . 57, 357 ffimmunomodulation . . . . . . . . . . . . 136immunotherapy . . . . . . . . . . 225, 232 fimmunotherapy versus

immunosuppression . . . . . . . . . 198 immunosuppression . . . . . . . . . 13, 103inhalation bronchial challenge test . 253Intal . . . . . . . . . . . . . . . . . . . . . . . . . 277intracellular enzyme cAMP . . . . . . 48 fIrritable Bowel Syndrome. . . . . . . . 377

KKaplan. . . . . . . . . . . . . . . . . . 131, 133 ffKay . . . . . . . . . . . . . . . . . . . . . . . . 138 ff

LLangerhans cells . . . . . . . . . . . 18, 210 fLichtenstein . . . . . . . . . . . . . . . . . 122 ff

Mmast cells. . . . . . . . . . . . . . . . 16ff, 139 f

as protective . . . . . . . . . . . . . . . . 163medications. . . . . . . . . . . . . . . . . . . 173

side effects of . . . . . . . . . . . . . . 173 fskin reactions and . . . . . . . . . . . 209

Melmon . . . . . . . . . . . . . . . . . . . . 117 ff



migraines. . . . . . . . . . . . . . . . . . . . . 351

Nnegative feedback . . . . . . . . . . . . . . 158neurotransmitters . . . . . . . . . . . . . . . 20non-steroidal anti-inflammatory

drugs (NSAID) . . . . . . . . . . . . 277 ff

PPeptides . . . . . . . . . . . . . . . . . . . . . . 229

Rrhinitis . . . . . . . . . . . . . . . . . . . 318, 323

and immunotherapy . . . . . . . . . 326Ritalin . . . . . . . . . . . . . . . . . . . . . . . 375Rocklin. . . . . . . . . . . . . . . . . 421, 110 ff

Sscience and freedom . . . . . . . . . . . . 313Seladane . . . . . . . . . . . . . . . . . . . . . 181serotonin . . . . . . . . . . . . . . . . . . . 358 ffskin allergies . . . . . . . . . . . . . . . . . . . . . signal transduction . . . . . . . . . . . . . . 10signal transmission . . . . . . . . . . . . . . 10skin testing . . . . . . . . . . . . . . . 203, 253

and immunotherapy . . . . . . . . . 223delayed systemic reaction . . . . . 220false positive/negative . . . . . . . . 208potential dangers of . . . . . . . . . . 219reactions to as improvement . . . 216systemic reaction to . . . . . . 212, 214

steroids . . . . . . . . . . . . . . . . . . 188, 289allergic disease and . . . . . . . . . . 195bone loss and . . . . . . . . . . . . . 297 ffcomplications of . . . . . . . . . . . . 190genes and . . . . . . . . . . . . . . . . 299 ffmarketing of . . . . . . . . . . . . 286, 292problems with . . . . . . . . . . . . . . 294safety of . . . . . . . . . . . . . . . . . . . 295

suppressor factors,histamine-induced. . . . . . . . . . . . 42

TT-cells. . . . . . . . . . . . . . . . . . 14, 70, 144T-suppressors . . . . . . . . . . . . . . . . . 15 f

as defence against allergy . . . . . 44 fftension headaches . . . . . . . . . . . . . . 352Tilade. . . . . . . . . . . . . . . . . . . . . . . . 277Theophylline . . . . . . . . . . . . . . . . . . 274treatments

elimination as. . . . . . . . . . . . 84, 255antibiotic. . . . . . . . . . . . . . . . . . 99 ff

triggers vs causes . . . . . . . . . . . . . . . . 92nonspecific . . . . . . . . . . . . . . . . . . 74

Uurticaria . . . . . . . . . . . . . . . . . . . . 334 ff

Vvascular headaches . . . . . . . . . . . . . 350

histamine in . . . . . . . . . . . . . . 351 ff

ZZaditen . . . . . . . . . . . . . . . . . . . . . . 278


The Plot Against Asthma and Allergy Patients

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