Presented at The MSD Standing Alone: "From Atopic Dermatitis to Allergic Rhinitis: The Rational Management in Pediatrics". Surabaya June, 23, 2013.

1. Allergy March: from Atopic
Dermatitis to Lifelong Allergy
Prof DR Dr Ariyanto Harsono SpA(K)

2. 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
2
Usually the first sensitization to cow's milk

3. Food Allergens
• Fruits
• Cow’s Milk
• Egg
• Fish
• Nuts
Prof DR Dr Ariyanto Harsono SpA(K)
3

4. 4 Sorts of allergens
Prof DR Dr Ariyanto Harsono SpA(K)
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5. 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 IFN­γ and high level of IL­4
& 10
 IgE at birth to Cow's milk, wheat, eggs.
Prof DR Dr Ariyanto Harsono SpA(K)
5

6. Aktivasi
sel­sel
Imuno­
kompeten
•Sel T
•Sel B
•Sel Mast
•Sel
Langer­
hans
Aktivasi
sel­sel
struk­
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/hiper
plasia otot polos
•Ekspansi
vaskuler
Penyempitan
saluran nafas
bawah
Symptom
alergi
Bronkus
hiper-reaktif
A
L
E
R
G
E
N
A B C D E
Imunopathology of allergy
Airway
remodelling
6
Trigger

7. Prof DR Dr Ariyanto Harsono SpA(K)
7

8. 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
Prof DR Dr Ariyanto Harsono SpA(K)
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ACTIVATION of IMMUNOCOMPETENCE CELLS By
ANTIGEN

9. Prof DR Dr Ariyanto Harsono SpA(K)
9
(J Allergy Clin Immunol 1999;118:124-6)
Th1
Dendritic cell
Eosinophile
Neutrophile

10. Prof DR Dr Ariyanto Harsono
SpA(K)
10
11Ariyanto Harsono MD PhDProf DR.dr. Ariyanto Harsono SpAK

11. VACCINATION
ACTIVATION
ANTIGEN
SPECIFIC
B CELL
GENERATION OF
MEMORY
ACTIVATED
CD4
+
Th-2 CELL IL-4
DIFFERENTIATION
& AFFINITY
MATURATION
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 colic
11

12. Mast Cells and basophiles involve in allergic
reaction in the context of antigen-IgE Prof DR Dr Ariyanto Harsono SpA(K)
12

13. IgGIgG mediated:
Protein loosing enteropathy, Gastro-intestinal haemorrhage, Abdominal Colic
Prof DR Dr Ariyanto Harsono SpA(K)
1
13

14. IgM
Prof DR Dr Ariyanto Harsono SpA(K)
1
IgM mediated:
Protein loosing enteropathy, Gastro-intestinal haemorrhage, Abdominal Colic 14

15. B
AKTIVASI SEL-SEL STRUKTURAL
Nature Rev Immunol 2003; 3: 867-78
Neutrophil
Eosinophil
Prof DR Dr Ariyanto Harsono SpA(K)
15

16. C
MEDIATOR RELEASE
Prof DR Dr Ariyanto Harsono
SpA(K)
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17. Granule contents:
Histamine,TNF-α,Proteases,
Heparin, ECF, NCF
Lipid mediators:
Prostaglandins
Leukotrienes
Cytokine production:
Specifically IL-4, IL-13
Prof DR Dr Ariyanto Harsono SpA(K) 17

18. D EFFECTS of MEDIATOR RELEASE on TARGET ORGAN
Nature Rev Immunol 2004: 3:234-237
Prof DR Dr Ariyanto Harsono
SpA(K)
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19. Target
Organ
IgE-mediated disorder Non IgE-mediated
disorder
Skin
Gastro-
intestinal
Respiratory
Tract
Multi-
system
Urticaria and angioedema
Atopic Dermatitis
Oral Allergy Syndrome
Gastrointestinal anaphylaxis
Allergic eosinophilic gastroenteritis
Asthma; Allergic Rhinitis
Food-induced anaphylaxis
Food associated, exercise-induced
anaphylaxis
Atopic Drmatitis
Dermatitis Herpetiformis
Proctocolitis
Enterocolitis
Allergic eosinophilic-
gastroenteritis
Enteropathy syndrome
Celiac Disease
Heiner Syndrome
Clinical ManifestationE Symptoms
Prof DR Dr Ariyanto Harsono SpA(K)
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20. Prof DR Dr Ariyanto Harsono
SpA(K)
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Prof DR Dr Ariyanto Harsono SpA(K)
Atopic Dermatitis

21. Prof DR Dr Ariyanto Harsono
SpA(K)
21Prof DR Dr Ariyanto Harsono SpA(K)
Urtikaria

22. Prof DR Dr Ariyanto Harsono SpA(K)
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Udema Quinke

23. Prof DR Dr Ariyanto Harsono SpA(K)
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Oral Allergi sindrome

24. Prof DR Dr Ariyanto Harsono SpA(K) 24
Asma bronkial

25. Prof DR Dr Ariyanto Harsono SpA(K)
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Rinitis Alergika

26. Prof DR Dr Ariyanto Harsono SpA(K)
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Rinitis Alergika

27. 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
Prof DR Dr Ariyanto Harsono SpA(K)
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28. Unusual Manifestation
Prof DR Dr Ariyanto Harsono SpA(K)
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29. Unusual Manifestation
Prof DR Dr Ariyanto Harsono SpA(K)
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30. Unusual Manifestation
Prof DR Dr Ariyanto Harsono SpA(K)
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Fixed Skin Eruption

31. CE
Prof DR Dr Ariyanto Harsono
SpA(K)
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Unusual ManifestationAbdominal Colic

32. Prof DR Dr Ariyanto Harsono SpA(K)
Unusual Manifestation
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Abdominal Colic

33. Sensitization to environmental
allergens from indoor and
outdoor sources requires more
time and is generally observed
between the first and tenth
years of life.
Prof DR Dr Ariyanto Harsono SpA(K) 33

34. THE FIRST STEP OF THE ATOPIC
MARCH: ATOPIC DERMATITIS
Prof DR Dr Ariyanto Harsono SpA(K) 34
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.

35. 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.
Prof DR Dr Ariyanto Harsono
SpA(K)
35

36. Factrors Influencing Allergy
March
Expsure to Endotoxine
Pollutants and Tobacco Smoke as
Adjuvant Factors
Bowel flora, vaccinations, antibiotics
and allergy
Lifestyle and the Development of
Atopic Disease
Prof DR Dr Ariyanto Harsono
SpA(K)
36

37. Exposure to endotoxin
Prof DR Dr Ariyanto Harsono SpA(K) 37
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.

38. Pollutants and Tobacco
Smoke as Adjuvant Factors
Prof DR Dr Ariyanto Harsono SpA(K) 38
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.

39. Bowel flora, vaccinations,
antibiotics and allergy
Prof DR Dr Ariyanto Harsono SpA(K) 39
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.

40. Lifestyle and the Development of Atopic
Disease
Prof DR Dr Ariyanto Harsono SpA(K) 40
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.

41. Prof DR Dr Ariyanto Harsono
SpA(K)
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42. Prof DR Dr Ariyanto Harsono SpA(K) 42

43. Prof DR Dr Ariyanto Harsono
SpA(K)
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44. Prof DR Dr Ariyanto Harsono SpA(K) 44

45. Prof DR Dr Ariyanto Harsono SpA(K) 45
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.

46. Early markers of increased risk for allergic
disease
Prof DR Dr Ariyanto Harsono SpA(K) 46
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.

47. 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.
Prof DR Dr Ariyanto Harsono SpA(K)
47

48. 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.
Prof DR Dr Ariyanto Harsono SpA(K) 48

49. Prof DR Dr Ariyanto Harsono
SpA(K)
49
Thank You