Paradigm Shift in Allergy...

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Answers for life. Restricted © Siemens AG 2014 All rights reserved. Paradigm Shift in Allergy Medicine Monet N. Sayegh, M.D. Physician Consultant

Transcript of Paradigm Shift in Allergy...

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Answers for life.Restricted © Siemens AG 2014 All rights reserved.

Paradigm Shift in Allergy MedicineMonet N. Sayegh, M.D.

Physician Consultant

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Annual US Prevalence Statistics for Chronic Disease:

Putting Allergy in Perspective

Parkinson's Alzheimer's Stroke Cancer CHD Diabetes Allergies &

Asthma

60

Million

Asthma and allergies strike 1 in 5 Americans

Asthma and Allergy Foundation of American, www.aafa.org

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Growth in Allergy Testing by Specialty: 2008-2011

49%46%

23%

0%

10%

20%

30%

40%

50%

60%

Primary CarePhysicians

Pediatricians Allergists

Per

cen

t G

row

th

ACAAI Health Trends: Allergy Report 2011

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Principle Practice Ownership Status A/I Physicians, 2004

Health Trends: Allergy Report 2011

ACAAI Health Trends: Allergy Report 2011

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Reported GPs active diagnostic intervention in drug allergies

Allergy, Asthma & Clinical Immunology (AACI),

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Allergen Testing

Goals

• Confirm the suspicion of allergy

• Identify the offending allergens

• Determine the degree of sensitivity

Limitations

• A positive test does not mean allergic disease is present.

• History must correlate 50% of the population when skin/blood test is positive.

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Th2-Cell B-lymphocyte Plasma Cell

Unbound IgE

MacrophageAllergen

IL-5, IL13

The Mechanism Of Allergic Reaction

Eosinophils

IL-3,5,GM-CSF

Basic Protiens

Leukotrienes

PAF,Cytokines

BasophilsHistamine,IL-4

Chronic Rhinitis

Acute Rhinitis

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SYMPTOMS

Cumulative Allergic Threshold

Dog

Dander

Dust

Mites

Dog

Dander

Pollen

Dust

Mites

Dog

Dander

Pollen

Dust

Mites

Situation A

Sub-clinical

Situation B

Symptomatic

NO AVOIDANCE

Situation C

Sub-clinical

AVOIDANCE

▪ Situation C: The person found out what he is allergic to and reduced exposure to the dog dander by having the dog stay out of the bedroom. Putting dust mite covers on bedding, and removing curtains and carpeting from the bedroom also reduced dust mites. When pollen is added, he does not go over this threshold and remains asymptomatic.

▪ Situation A: A pet owner is exposed to dog dander and dust mites but does not have any allergy symptoms

▪ Situation B: It is hay fever season and he is exposed to pollen. He is now over his threshold and is symptomatic.

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Atopic

Dermatitis

GI disorders Otitis media Allergic

rhinitis

Asthma Adult

asthma

Sasai K, et al. J Periatr. 1996;128:834-40

ETAC™ Study Group Pediatr Allergy Immunol. 1998;9:116-24

The Allergy March

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Overlapping symptoms cause difficulties to differentiate and accurately diagnose

URD:

Nasal Congestion Nasal Congestion Nasal Congestion

Rhinorrhea Rhinorrhea Rhinorrhea

Excess Secretions Excess Secretions Excess Secretions

Sneezing Postnasal Drip Postnasal Drip

Watery, Itchy Eyes HeadacheHeadache

Differential Diagnosis: Upper Respiratory Disease

Allergic

RhinitisSinusitis

Non-Allergic

Rhinitis

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The Face of Allergy

Chelitis (Chapped Lips)Allergic Shiners

Nasal Salute Nasal Crease

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Decreased immune system stimulation

The hygiene hypothesis

Improved diagnostic tests

Increased awareness

Increased allergen exposure

Genetic susceptibility

Underlying disease

Increased exposure to food additives

Increased levels of pollutants

Allergies increasing

No one really knows why?

Why Are Allergies Increasing?

Curr Opin Immunol. 2001;13:701-708.

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The Hygiene Hypothesis

The hygiene hypothesis states that a lack of early

childhood exposure to bacterial and viral

infections may increase the susceptibility to

allergic diseases by modulating immune system

development.

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Common Seasonal/All Year- Around Allergens

Molds

GrassesTrees Weeds

Dust-Mites Animals Drugs

Venoms

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Common Occupational Allergens

Substance People at Risk

Ethylene Oxide Textile, Cosmetic, Solvent, Hospital (sterilization)

Isocyanates Painters, Insulation(Installers), Plastics, Foam

Anhydrides Users of Plastics, Epoxy resins

Latex Health Care Professionals, Food Handlers

FormaldehydeHospital Staff, Handlers of preserved Specimen, Building materials,

Cosmetics, textiles

Seafoods Seafood processing Workers

Chloramine-T Janitors, Cleaning Staff

Castor Beans Coffee Handlers, Chemist, Oil Industry worker

Flour Dust Farmers, Bakers, Plant Workers

Occupational Asthma: 11 Million exposed workers

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Incidence of Food Allergies

19%

16% 16%15%

14%

6% 6%

8%

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

Milk Shellfish Tree

Nuts

Peanuts Wheat Eggs Soy Fish

Food

Alle

rgie

s (%

)

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Children Can Outgrow Some Food Allergies

Food Outgrown

Milk 80%

Egg 60-70%

Peanut 20%

Tree Nut 20%

Fish 20%

Shellfish 20%

Sampson, J Allergy Clin Immunol 2004; 113:805-819

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Allergen Cross-reactivity

Allergen Potential Cross-reactive Foods

RagweedBananas, melons (watermelon, cantaloupe, honeydew), zucchini, cucumber,

dandelions, chamomile tea

BirchApples, pears, peaches, apricots, cherries, plums, nectarines, prunes, kiwi, carrots, celery, potatoes, peppers, fennel, parsley, coriander, parsnips, hazelnuts, almonds,

walnuts

Grass Peaches, celery, melons, tomatoes, oranges

MugwortCelery, apple, kiwi, peanut, fennel, carrots, parsley, coriander, sunflower, peppers

Alder Celery, pears, apples, almonds, cherries, hazelnuts, peaches, parsley

Latex Bananas, avocado, kiwi, chestnuts, papaya

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Oral Allergy Syndrome

Ragweed PollenRagweed

About 70% of people who suffer from pollen allergies,

especially ragweed allergy, experience oral allergy

syndrome.

The proteins in the fruits and vegetables causing OAS

are easily broken down with cooking or processing.

Therefore, OAS typically does not occur with cooked or

baked fruits and vegetables, or processed fruits such as

applesauce.

Oral allergy syndrome (OAS) is caused by cross-

reactivity between proteins in fresh fruits vegetables and

pollens.

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Food Allergy or Intolerance?

Allergy symptomsAllergic rhinitis/Conjunctivitis

▪Nausea/Vomiting

▪Stomach pain

▪Diarrhea

▪Atopic dermatitis

▪Asthma/Wheezing/SOB

▪Chest pain

▪Swelling of the airways

▪Urticaria/Hives

▪Anaphylaxis

Intolerance symptoms▪Nausea /Vomiting

▪Stomach pain

▪Gas, cramps, or bloating

▪Heartburn

▪Diarrhea /Constipation-IBS

▪Headaches /Migraines

▪Irritability or nervousness

▪Depression/Fatigue

▪Joint pain/Non-specific aches

▪Ear infection

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▪ Food Poisoning:

▪ Bacterial Contamination

▪ Heavy Metal Contamination

▪ Histamine Toxicity:

▪ Fish that is not properly refrigerated (Mackerel, Tuna)

▪ Cheese (Histamine can reach high levels in cheese)

▪ Wines (Histamine in various types of wine may reach high levels)

▪ Lactose Intolerance:

▪ Milk (Lack of Lactase enzyme in gut to digest Lactose)

▪ Food Additives:

▪ Monosodium Glutamate, MSG (Preservative, taste enhancer)

▪ Sulfites (May produce Sulfur dioxide gas by-product Ex. wines, light-colored dried fruits except prunes and raisins, dehydrated vegetables, and certain types of lemon, lime juice and butter flavouring materials).

Types of Adverse Reactions to Food:Non- IgE reaction (Delayed)

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Sampson H, J Allergy Clin Immunol. 2004;113:805-19

The double-blind, placebo-controlled oral food challenge (DBPCFC)

is the gold standard for diagnosing food allergy

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Types of Adverse Reaction to Food

IgE Antibody- Mediated Non-IgE T Cell Mediated type IV

▪Urticaria/angioedema Dietary protein, entercoltis

▪Immediate GI reaction Dietary protein, proctitis

▪Oral allergy syndrome Dietary protein enteropathy (Pollen-related)Celiac disease

▪Allergic rhinitis Dermatitis herpetiformis

▪Anaphylaxis Pulmonary hemosidrosis

▪Atopic Dermatitis

▪Asthma Food poisoning

Eosinophilic Gastroenteropathy

Eosinophilic Esophagitis

Histamine toxicity Lactose IntoleranceFood additives(MSG)

Drug intolerance

▪Immunologic Reaction

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Radiological Features of Eosinophilic Esophigitis

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Endoscopic features of Eosinophilic Esophagitis

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Microscopic Allergic Eosinophilic Esophagitis

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American College of Allergy, Asthma and Immunology (ACAAI)

▪Two key steps in the process of allergy diagnosis are the medical history and allergy test selection. Allergists use their

skills in these areas to help more patients feel well, stay active during the day, and rest at night.

American Academy of Allergy, Asthma and Immunology (AAAAI)

▪To determine if you have an allergy, your allergist will take a thorough medical history and do a physical exam. He or she

may perform allergy skin testing, or sometimes blood testing, to determine which substance is causing your allergy.

European Academy of Allergy and Clinical Immunology (EAACI)

▪The diagnosis of food allergy usually starts with a combination of an investigation into the patient's clinical history, a clinical

examination and a test for the detection of food-specific IgE antibodies.

National Institute of Allergy and Infectious Diseases (NIAID)

▪IgE antibody measurements generated by any serologic assay method alone are not diagnostic of allergy. They must be

ultimately interpreted within the context of the patient’s clinical history.

What Is the “Gold Standard” in Allergy Diagnosis?

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The Path For Allergists From Diagnosis To Treatment

Allergy specific

history & physical

In vivo/vitro allergy

testingSymptoms

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Allergy-specific History and Physical

Family

History

Medical

History

Hobbies

Occupation

Environmental

Factors

Likely Causes

Duration

Symptoms

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Who Can Benefit From Allergy Immunotherapy?

The patient and physician should base the decision regarding

allergy shots on:

• Length of allergy season and severity of symptoms

• How well medications and/or environmental controls are

helping allergy symptoms

• The desire to avoid long-term medication use

• Time available for treatment (allergy shots requires a

significant commitment)

• Cost, which may vary depending on region and insurance

coveragehttp://www.pennmedicine.org/health_info/allergy/000047.html

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US FDA Approved Sublingual Allergy Immunotherapy(SLIT)

Oralair tablets are to be taken daily starting four months before grass

pollen season to reduce allergic reactions to the grasses.

Oralair contains freeze-dried extracts

from pollens of grasses

▪ Kentucky Bluegrass

▪ Orchard Grass

▪ Perennial Rye Grass

▪ Sweet Vernal Grass

▪ Timothy Grass

Oralair dissolves rapidly under the tongue. The first dose must be taken

in the physician's office, so the patient can be monitored for any adverse

reactions, but after that, doses can be taken at home

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Who Should be Tested?

Patients complaining of allergy-like symptoms

Pediatric patients, especially those with a stubborn rash, chronic ear infections, or GI symptoms

Patients who chronically use antihistamines

Patients who may have obvious signs of an allergic reaction

Family Practice

Pediatricians

ENT Physicians

Pulmonologists

Dermatologists

Healthcare professionals

Allergists

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When Should I Refer My Patients to an Allergist?

▪ Those with severe or uncontrolled asthma.

▪ Patients with serious comorbidities such as cardiovascular disease, neoplastic

disorders, COPD, etc.

▪ Those with significant MAST cell and Eosinophilic disorders.

▪ Patients with immunodeficiency disorders or on immunomodulation medications.

▪ Patients who experience moderately severe collagen-vascular or systemic disorders or

uncontrolled seizure disorders.

▪ Patients using beta blockers or other contraindicated medications.

▪ Women who are pregnant.

▪ Patients with previous anaphylaxis to aeroallergens.

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Skin Prick Test(Subcutaneous)

Purified allergen extracts are pricked or scratched into your

Skin’s surface- ID-pollen.,mold, dander, mites

Purified allergen injected into the skin of your arm

Suspected insect venom or Rx penicillin

Patch Test (Epicutaneous)-T-Cell mediated

Purified allergen applied to a patch which is

then placed on your skin of your arm

Suspected contact dermatitis-Latex, hair

,preservative,metals,resins

, medications and fragrances

Egg white, cows milk, peanuts, soy, wheat, tree nuts,fish

and shell fish

In Vivo AllergyTesting

IntradermalTesting

Food AllergyTesting

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The lack of uniform criteria for grading skin test results

as positive or negative

The difference among natural, purified, and recombinant test allergen

The differential sensitivity of individuals sensitized to the same

allergen.

Results are variable—a positive reaction can be interpreted as a wheal

from 3–5 mm.

Risk of systemic reaction.

Limitations of Skin Prick Testing

The lack of uniform procedures for performing skin tests

Patients taking tricyclic antidepressives, Antihistamines,Corticosteroid

may give false negative results , while Beta blockers may give

false positive

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Situations in which Blood Testing May be

Indicated over Skin Prick Testing

Negative SPT test with a high clinical suspicion

Patients with dermatopathology ( Atopic Dermatitis,dermatographia,

chronic urticaria ,psoriasis)

Patients taking tricyclic antidepressives, Antihistamines,

Corticosteroid , Beta Blocker

Very young or older patients that may have a reduced histamine

response

Patients with an increased risk of anaphylaxis

Pregnant women

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0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0.1 1 10 100

IgE Antibody Concentration (kU/L)

Prob

abili

ty

Relationship between sIgE Levels and the Probability of Clinical Allergy

Class Concentration Comment

0<0.1 kU/L

0.1–0.34

Absent or undetectable

Very low

I 0.35–0.69 kU/L Low positive

II 0.70–3.49 kU/L Moderate positive

III 3.50–17.49 kU/L High positive

IV 17.5–52.49 kU/L Very high positive

V 52.5–99.99 kU/L Very high positive

VI 100 kU/L Very high positive

Never 0%

Never 100%

Sampson H, J Allergy Clin Immunol. 2004;113:805-19

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Published evidence has documented a value for

IgE cut-off’s in the diagnosis of food allergy

• Numeric values vary by the platform used

• Values are often population dependant

Cut-off’s and Clinical Interpretation

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Potential Reasons for Difference in Cutoff Values

Many factors can contribute to alternate numeric cut-off values:

• Patient’s age

• Patient population

• Allergen preparation

• Assay methodology

• Liquid vs. dried allergens

• Detection method

▪ Cross-reactivity with other allergens/components

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1st Gen. 2nd Gen. 3rd Gen.

1970s 1980s – 1990s 2000s

History of In Vitro sIgE Test

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Features

1st Generation

(RAST)

2nd Generation

(ImmunoCAP)

3rd Generation

(3g Allergy)

AllergensSolid Phase on

Paper disk

Solid Phase on

Cellulose Sponge

Liquid Phase

Allergens

Detection antibody Polyclonal Monoclonal Monoclonal

Signal detection IsotopicFluorescent or

Spectrophotometric

Enzyme-enhanced

Chemiluminescence

Lowest calibrator 25 kU/L 0.35 kU/L 0.0 kU/L

Zero calibrator No No Yes

Detection limit N/A 0.35 kU/L by default 0.1 kU/L by experiment

Functional sensitivity Not determined Not determined 0.2 kU/L

Results reported in“Arbitrary units”

& classes

WHO standardized

& classes

WHO standardized

& classes

Time-to-first-result 2 overnights 3.5+ hours 65 minutes

Automation level Manual BatchWalk-away operation

Cont. Random Access

Allergy Testing Methods

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Liquid Allergen Technology

YY

Y

Y

YY

Streptavidin Coated Bead

Biotin Labeled Allergen

Specific IgE from

Patient Serum

Alkaline Phosphatase

Labeled Antibody to IgE

Y

Y

YY

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Advantages of:Liquid Allergen Technology

• Liquid allergen maintains the native protein characteristics of allergen molecules

• The broad range of epitopes increases the sensitivity of liquid allergen system

• Native proteins conformations in liquid phase results in a greater binding capability

• Liquid allergen preserves the three dimensional structure of allergen molecules

• Results in rapid binding kinetics and allows for complete automation

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Types of Chemiluminescence

Direct label

ChemiluminescenceEnzyme-Enhanced

Chemiluminescence

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Centrifugal Wash Technique

▪ Consistent separation for consistent assay performance

▪ Efficient separation results in low nonspecific binding and increased sensitivity

The Separation Step:The Critical Component in a Heterogeneous Assay

Sump Chamber

Sample &coated

bead are

automatically

pipetted into test

unit&incubated for

30 minutes@37c with

intermittent agitation

and washed then

AP-labeled anti-

IgE is added and

Incubated for 30

min@37c

Following incubation.

The test unit is

Spun at high speed

about its vertical axis

Rxn fluid is forced

Up &completely

Captured in the

sump chamber

A series of washes

efficiently removes

Unbound material

From the bead and

Inner tube

Chemiluminescent

substrate is added

To the test unit.

Light emission

Is read with

a high- sensitivity

photon counter

Streptavirdin-coated bead are incubated

with biotinylated specific allergens

Patient sample

&coated bead

Unbound material

from the bead

and inner tube

as waist

Streptavirdin- coated bead with

specific allergens+ Pt.Aby+AP

labeled Anti-IgE

Chemiluminescent

substrate is added

to generate a light

Output that is measured

by detector

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Interassay comparison of ImmunoCAP

vs. IMMULITE® 2000 3gAllergy

Agreement of both methods with the

skin prick test

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Summary

Clin Chem 2005;51:1241-1249

In conclusion, laboratory testing for sIgE in atopic or

immediate-type allergies can be accomplished on a fully

automated, random-access immunoanalyzer, such as the

IML, at a diagnostic accuracy relative to clinical skin

testing comparable to that of the widely used CAP

technology for in vitro sIgE measurement.

Olert et al. Clin Chem 2005;51:1241-49

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Utilizing IgE Results from Alternate Methods for Food Allergy Cut-

Off’s

“These data indicate that specific IgE levels to

egg white, milk and peanut are highly correlated

and that differences between the systems are

circumscribed and modest”

“…IMMULITE has a mean of 2-5-fold higher than

ImmunoCAP”

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Correlation Plots for Egg Whites, Milk & Peanut

“These data support the conclusions of the 2010 proficiency-based intermethod

performance assessment that both assay methods detect IgE antibody to a

comparable degree in serum of symptomatic allergic patients. “

Hamilton et al. Ann Allergy Asthma Immunol. 2011;107:139 –144.

Egg White Milk Peanut

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Immulite to ImmunoCAP Ratios

Hamilton et al. Ann Allergy Asthma Immunol. 2011;107:139 –144.

Peanut specific IgE 1.86

Cow’s Milk specific IgE 2.33

Egg White specific IgE 4.85

Egg White Milk Peanut

“The clinician may choose to translate published ImmunoCAP-based

predictive data into comparable IMMULITE levels…. “

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Allergen Component Specific IgE Measurement With the Immulite 2000 vs ImmunoCAPSystems: Diagnostic Accuracy and Intermethod Comparison

Conclusions: A high diagnostic accuracy of the sIgE to allergen components measurement

with Immulite 2000 and a high agreement with ImmunoCAP platforms were shown in this

study.

J. Clin.Lab. Anal. 00:1–7, 2014. C 2014

Molecular (Recombinant) allergens, led to the development of a new concept in allergy

diagnosis called component resolved diagnosis.

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Clinical Case#1:

Is it Cross-reactivity or Primary Allergy?

▪ Since she was 6 y/o ,Emma, has had Rhinitis and conjunctivitis during pollen season. An allergy test

confirmed that she has sensitization to birch.

▪ At 16, she suddenly experienced a local reaction from eating peanuts.

▪ Extract based test were positive for peanut and the Dr. told her to strictly avoid peanut

▪ At a later visit to the clinic, a component based analysis was also performed and the results showed

that Emma was sensitized to all three peanut specific component Ara h 1,2,3.This shows that Emma

has a primary peanut allergy and recommendation of strict peanut avoidance and Auto Injector is

necessary (such as EpiPen, Twinject, Auvi-Q)

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Clinical Case#2:

Is it Cross-reactivity or Primary Allergy?

▪ Since she was 6 y/o Caroline,has had Rhinitis and conjunctivitis during pollen season. An allergy test

confirmed that she has sensitization to birch. At 16, she similarly,suddenly experienced a local reaction

from eating peanuts.

▪ Extract based test were positive for peanut by SPT and blood testing and the Dr. told her to strictly avoid

peanuts

▪ At a later visit to the clinic, a component based analysis was also performed and the results showed

that Caoline had no detectable levels to all three peanut specific component Ara h 1,2,3.

▪ Instead she had high levels of IgE antibody to Ara h 8 which is a cross reactive component and peanut

which is very similar to the main allergen in birtch

▪ Thus Ara h 8 sensitization indicated that Caroline had a cross reactive pollen related food allergy

which was confirmed by her food allergy

▪ Her Diagnosis was Pollen-associated peanut allergy and she is suitable for peanut reintroduction and

Auto injector is unnecessary

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Allergy Publications

▪Several important publications on 3rd Gen Allergy Blood Testing

• Dr. Ollert , Dr. Cobbaert, Dr. Li, Dr. Prates, Dr. Biagini

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A. Expanding the menu in allergy testing for recombinant allergens that is

biotechnologically produced allergen molecule originally identified form an allergen

extract

The trend from extract-based to molecule-based allergy or component-resolved allergy

diagnosis is gaining importance and being increasingly applied in routine care

B. Another area in which researchers have started working in the use of Multiplexing, or

the quantitative measurement of specific IgEs to numerous allergens simultaneously

using array technology, potentially may provide improved turn around time over

monoplexing.

What the future holds for Allergy Testing?

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C. A third area of research is to improve the cellular allergy tests, which use mast cell

activity as a measure of histamine release in allergic responsiveness. These tests have

the potential to improve the accuracy of food allergy diagnosis and may reduce the need

for challenge testing.

The new technologies ,combined with the use of pure allergens, will enable clinicians to

obtain a complete picture and to better advise patients about the best way to manage

their food allergy. This will be particularly useful for younger children from whom only

small amount of blood may be taken for testing

What the future holds for Allergy Testing?

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References &Further Reading

Sampson HA, Ho DG: Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and

adolescents. J Allergy Clin Immunol 1997, 100:444-51.

Sampson HA: Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001, 107:891-

6.

Jarvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA: Specificity of IgE antibodies to sequential epitopes of hen's egg

ovomucoid as a marker for persistence of egg allergy. Allergy 2007, 62:758-65

Celik-Bilgili S, Mehl A, Verstege A, Staden U, Nocon M, Beyer K, et al.: The predictive value of specific immunoglobulin E levels in

serum for the outcome of oral food challenges. Clin Exp Allergy 2005, 35:268-73.

Boyano Martinez T, Garcia-Ara C, Diaz-Pena JM, Munoz FM, Garcia Sanchez G, Esteban MM: Validity of specific IgE antibodies in

children with egg allergy. Clin Exp Allergy 2001, 31:1464-9.

Osterballe M, Bindslev-Jensen C: Threshold levels in food challenge and specific IgE in patients with egg allergy: is there a

relationship? J Allergy Clin Immunol 2003, 112:196-201.

Maloney JM, Rudengren M, Ahlstedt S, Bock SA, Sampson HA: The use of serum-specific IgE measurements for the diagnosis of

peanut, tree nut, and seed allergy. J Allergy Clin Immunol 2008, 122:145-51

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References &Further Reading

Allergic diseases: in Medical Immunology .eds ( Tristram G.Parslow, Daniel P. A Stites, Abba I.Terr.and John B. Imboden), 814 pages tenth edition. McGraw-

Hill/Appleton & Lange; 10 edition 2001)

Anaphylaxis and Urticaria: in Medical Immunology .eds ( Tristram G.Parslow, Daniel P. A Stites, Abba I.Terr.and John B. Imboden), 814 pages

tenth edition. McGraw-Hill/Appleton & Lange; 10 edition 2001)

Adkinson NF Jr. Middleton’s Allergy: Principles and Practice. 6th ed. Philadelphia, Pa: Mosby; 2003.

Rakel RE. Textbook of Family Medicine. 7th ed. Philadelphia, Pa: WB Saunders; 2007.

Miriam K Anand, Michael A Kaliner, et al., Advances in Immunology. N Engl. J.Med,. vol. 344, No.1. January4, 2001. Available from.

http://emedicine.medscape.com/article/136217-overview#a0104

Sell S, Rich RR, Fleisher TA, et al, eds. Clinical Immunology: Principles and Practice. ed. St. Louis, Mo: Mosby-Year Book; 1996:449-77

Center for Health Workforce Studies University at Albany, School of Public Health

1 University Place / B334 Rensselaer, NY 12144

Email: [email protected] Web: http://chws.albany.edu

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Lee NP, Arriola ER. How to treat allergic rhinitis. West J Med July 1999;171:31-4.

ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY ,March 2008; Volume 100, Number 3, Supplement 3

American Academy of Allergy, Asthma and Immunology (AAAAI). The Allergy Report: Science Based Findings on the Diagnosis &

Treatment of Allergic Disorders, 1996-2001. AAAAI. Task Force on Allergic Disorders. Executive Summary Report, 1998.

Forte GJ, E Salsberg, P Wing, M Beaulieu, and V Myers. The Allergy and Immunology Physician Workforce 2000. Rensselaer, NY:

Center for Health Workforce Studies, School of Public Health, SUNY Albany. 2000.

Beaulieu M, G Forte, and ES Salsberg. Volunteerism and the Allergist/Immunologist Physician Marketplace: A Summary of Responses to

an IBIS Panel Survey. Rensselaer, NY: Center for Health Workforce Studies, School of

Public Health, SUNY Albany. 2003.

Council on Graduate Medical Education. 16th Report: Physician Workforce Policy Guidelines for the United States, 2000-2020.

Rockville, MD: Health Resource and Services Administration, US Department of Health and Human Services. 2005; Cooper RA, TE

Getzen, and P Laud. “Economic Expansion is a Major Determinant of

Physician Supply and Utilization.” Health Services Research 38, 2 (2003): 675-696.

References &Further Reading

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Q&A