Allergy March: from Atopic Dermatitis to Lifelong Allergy

Prof DR Dr Ariyanto Harsono SpA(K)

INTRODUCTION

Prof DR Dr Ariyanto Harsono SpA(K)

The term “allergic march” refers to the natural history of atopic manifestations, which is characterized by a typical se

quence of IgE antibody responses and clinical symptoms that appear early in life, persist over years or decades,

even lifelong.

1. Once IgE mediated allergy occurs, the process continues in a baby's life

2. Sensitization to another food proteins that would otherwise occur

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Usually the first sensitization to cow's milk

Food Allergens

• Fruits• Cow’s Milk• Egg• Fish• Nuts

Prof DR Dr Ariyanto Harsono SpA(K)

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4 Sorts of allergens

Prof DR Dr Ariyanto Harsono SpA(K)4

SensitizSensitizaattiionon in Uteroin Utero

T cells has been responding to the fetus at 22 weeks.

T cells have been responding navel at birth:

mite ~ 47% eggs, cow’s milk ~ 75% Low level of IFN- and high level of IL-4

& 10 IgE at birth to Cow's milk, wheat, eggs.

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Aktivasi sel-selImuno-kompeten•Sel T•Sel B•Sel Mast•Sel Langer- hans

Aktivasi sel-selstruk-tural

•Sel endotel•Sel epitel

Aktivasi dan Rekruitmen

•Sel Mast•Eosinofil•Neutrofil•Basofil

Pelepasan mediator

Kerusakan epitel

Stimulasi neural

Dilatasi & peningkatan permeabilitas vaskulerl

Bronkokonstriksi

Perbaikan epitel

•Proliferasi fibroblast•Deposisi kolagen•Hipertropi/hiperplasia otot polos•Ekspansi vaskuler

Penyempitan saluran nafas bawah

Symptom alergi

Bronkus hiper-reaktif

ALERGEN

A B C D E

Imunopathology of allergy

Airway remodelling

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Trigger

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Susu sapi

APC MHC-II Th0

IL-1

Th-2

Th.1

IL-12 IL-2, IFN-γ

B-Cell

IL-4

IL-5

SEL PLASMASEL MEMORI

IL-6

IL-10

A

Memory Cells

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ACTIVATION of IMMUNOCOMPETENCE CELLS By ANTIGEN

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(J Allergy Clin Immunol 1999;118:124-6)

Th1

Dendritic cell

Eosinophile

Neutrophile

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11Ariyanto Harsono MD PhD

Prof DR.dr. Ariyanto Harsono SpAK

VACCINATION

ACTIVATIONANTIGEN SPECIFIC

B CELL

GENERATION OF MEMORY

ACTIVATED CD4

+ Th-2 CELL IL-4

DIFFERENTIATION

& AFFINITYMATURATION

ANTIBODY SECRETING PLASMA CELLS

ANTIGEN PROCESSING &PRESENTATION

MHC Class II B CELL IMMUNOGLOBULINE

T CELL RECEPTOR ANTIGEN

B CELL

IL-5,IL-13

Cow’s Milk Protein

Cow’s Milk epitope

IgE mediated: Asthma, Rhinitis, Dermatitis Atopic, Urticaria, Abdominal colic11

Mast Cells and basophiles involve in allergic reaction in the context of antigen-IgE Prof DR Dr Ariyanto Harsono SpA(K)

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IgGIgG mediated: Protein loosing enteropathy, Gastro-intestinal haemorrhage, Abdominal Colic

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IgMProf DR Dr Ariyanto Harsono SpA(K)

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IgM mediated: Protein loosing enteropathy, Gastro-intestinal haemorrhage, Abdominal Colic

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BAKTIVASI SEL-SEL STRUKTURAL

Nature Rev Immunol 2003; 3: 867-78

Neutrophil

Eosinophil

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CMEDIATOR RELEASE

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Granule contents:Histamine,TNF-Proteases, Heparin, ECF, NCF Lipid mediators:

ProstaglandinsLeukotrienes

Cytokine production:Specifically IL-4, IL-13

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D EFFECTS of MEDIATOR RELEASE on TARGET ORGAN

Nature Rev Immunol 2004: 3:234-237Prof DR Dr Ariyanto Harsono

SpA(K)18

Target Organ

IgE-mediated disorder Non IgE-mediated disorder

Skin 

Gastro-intestinal    

Respiratory Tract Multi-system

Urticaria and angioedemaAtopic Dermatitis

Oral Allergy SyndromeGastrointestinal anaphylaxisAllergic eosinophilic gastroenteritis   Asthma; Allergic Rhinitis Food-induced anaphylaxisFood associated, exercise-induced anaphylaxis

Atopic DrmatitisDermatitis Herpetiformis

ProctocolitisEnterocolitisAllergic eosinophilic- gastroenteritisEnteropathy syndromeCeliac Disease

Heiner Syndrome

Clinical Manifestation E Symptoms

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Prof DR Dr Ariyanto Harsono SpA(K)

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Atopic Dermatitis

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Urtikaria

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Udema Quinke

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Oral Allergi sindrome

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Asma bronkial

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Rinitis Alergika

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Rinitis Alergika

Target organ Unusual Clinical manifestation

•Skin

•ENT

•Respiratory

•Gastrointestinal

•Multi system

Vasculitis; Fixed Skin Eruption

Chronic Serous Otitis Media

Chronic Pulmonary disease (Heiner Syndrome)

Hypersensitivity pneumonitis

Constipation; Gastroesophageal reflux

Irritability/Sleeplessness in infants; colic, Arthropathy;

Nephropathy; Thrombocytopenia

Unusual Clinical Manifestation

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Unusual Manifestation

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Unusual Manifestation

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Unusual Manifestation

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Fixed Skin Eruption

CE

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Unusual ManifestationAbdominal Colic

Prof DR Dr Ariyanto Harsono SpA(K)

Unusual Manifestation

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Abdominal Colic

Sensitization to environmental allergens from indoor and

outdoor sources requires more time and is generally observed

between the first and tenth years of life.

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THE FIRST STEP OF THE ATOPIC MARCH: ATOPIC DERMATITIS

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AD starts early in the first few years in life. Of the affected children, 45% of them had the condition during the first 6 months of life, 60% during the first year of life and up to 85% suffered AD before 5 years of age.Less than half of the patients with AD have complete resolution by 7 years of age and only 60% of them have resolution by adulthood, indicating the chronic nature of AD.

Several studies have demonstrated the allergic march from atopic eczema to the development

of asthma and allergic rhinitis.

• In general, atopic dermatitis is the first clinical manifestation of the IgE response, with the highest incidence during the first three months of life and the highest period prevalence during the first three years of life.

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Factrors Influencing Allergy March

Expsure to EndotoxinePollutants and Tobacco Smoke as

Adjuvant FactorsBowel flora, vaccinations, antibiotics

and allergyLifestyle and the Development of

Atopic Disease

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Exposure to endotoxin

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Endotoxin exposure is another possible protective factor against allergy in early life. Endotoxins consist of a family of molecules called lipopolysaccharides (LPS) and are an intrinsic part of the outer membrane of Gram-negative bacteria. It has been suggested that increased exposure to endotoxins on farms or in homes with animals could modify immune responses to reduce the prevalence of atopic diseases.

Pollutants and Tobacco Smoke as Adjuvant Factors

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Pollutants and Tobacco smoke, though not serving as allergens, are capable of upregulating existing IgE responses, leading either to disease manifestation or to an aggravation of symptoms.

Bowel flora, vaccinations, antibiotics and allergy

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The intestinal microflora might well be the major source of microbial stimulation of the immune system in early childhood. The intestinal microflora can enhance Th1-type responses.

Observations from Japan have suggested that positive tuberculin responses in children predict a lower incidence of asthma, lower serum IgE levels and a cytokine profile biased toward the Th1 type.

A few reports have described an association between the use of antibiotics during the first two years of life and an increased risk of asthma.

Lifestyle and the Development of Atopic Disease

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Observations from Germany suggest that within the population of an industrialized country with a Western lifestyle, high socioeconomic status is a risk factor for early sensitization and symptomatic manifestation of atopic dermatitis and allergic airway disease.

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THE END POINTS (PROGRESSION) OF THE ATOPIC MARCH: ALLERGIC RHINITIS AND

ASTHMA

It is important to identify infants at risk for developing lifelong chronic atopic diseases to provide a critical window of opportunity early in life for therapeutic intervention.

Early markers of increased risk for allergic disease

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A number of early markers for atopy indicating an increased risk for the development of subsequent allergy have been identified. elevated cord-blood IgE level (high specificity but low sensitivity), a positive skin-prick test to egg or to house-dust mite in the first year of life and the detection of specific IgE to common food and inhalant allergens during early infancy.

Natural History of Food Allergy

• Most children with allergies become tolerant to cow's milk, soy, and eggs in a few years.

•   Older children (15 years old) and adults generally do not experience immune tolerance.

• Peanut allergy, fish, and shellfish more persistent.

• Food hypersensitivity at an early age (ie cow's milk, eggs, peanuts) is a risk factor for additional food allergies, Atopic Dermatitis, and asthma.

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Conclusion Allergy is a hypersensitivity type I Cow's Milk is usually the first sensitization then

other foods. Allergy March begins with Atopic Dermatitis,

continues to Gasrointestinal Allergy, Allergic Rhinitis and Bronchial Asthma.

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Prof DR Dr Ariyanto Harsono SpA(K)

49Thank You