Allergy march from atopic dermatitis to lifelong allergy
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Transcript of Allergy march from atopic dermatitis to lifelong allergy
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
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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.
Prof DR Dr Ariyanto Harsono SpA(K)5
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
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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