The spectrum of allergic diseases

Hugo Van BeverDepartment of Pediatrics

National University Singapore

APAPARI workshop – Hanoi, Vietnam – May 2008

1. Clean - well organized - tropical 2. High prevalence of allergic diseases3. A lot of HDMs (Blomia tropicalis)4. Strange food allergies (bird nest, etc…)

HDB flat

skyline

KH Hseih JL Huang

A Tam G Wong

HR LeeSI Lee

S Siregar

P Vichyanond

Chen

Pediatric Allergy in Asia (APAPARI)

J DebruynBW LeeH Van Bever

M Bautista

Starting 1998

Morikawa

APAPARI – JACIN MEETING, JAKARTA – APRIL 2006

APAPARI - Education 1. Joint meetings with Allergy Societies

- 2002: Japan (Tokyo)- 2003:Singapore (workshop)- 2004: Hong Kong (IPRAIC)- 2005: S-Korea (Seoul)- 2006: Indonesia (Jakarta)- 2007: Philippines (Manila) & WAO (Bangkok)- 2008: Singapore (SPS – Oct 2008)

2. Training courses on pediatric allergy- 2006: Jakarta (Indonesia) / Balikpapan (Borneo)- 2007: Phom Penh (Cambodia) / Jakarta / Ho Chi Minh (Vietnam)- 2008: Hanoi (Vietnam)

Vietnamese studies on paediatric allergy

- ISAAC-based asthma and atopic symptoms among Hanoi school children. Nga NN et al. Pediatr Allergy Immunol 2003, 14, 272-9.

- Obesity is associated with increased risk of allergy in Vietnamese adolescents. Irei V et al. Eur J Clin Nutr 2005, 59, 571-7.

- Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. Flohr C, et val. J Allergy Clin Immunol 2006, 118, 1305 – 11.

- Prevalence of asthma and asthma-like symptoms in Dalat Highlands, Vietnam. Sing Med J 2007, 48, 294 – 303.

ISAAC-based asthma and atopic symptoms among Hanoi school children. Nga NN et al. Pediatr Allergy

Immunol 2003, 14, 272-9.

- Hanoi

-cross-sectional study

-5 -11 year-old

-Response rate 66.4%

- 969 responders

Cumulative prevalence of asthma, rhinitis and eczema in Singaporean children.

1 - 2 yrs-old2002 -2003

4 - 6 yrs-old2000

6 – 7 yrs-old2001

12 – 15 yr-old2001

Increase in prevalence of allergic diseases

- asthma

- rhinitis

- eczemaInduction of the expression of allergy

changes in the environment

HYGIENE HYPOTHESIS

Allergy = a feature and NOT a disease !

= … the ability to produce specific antibodies (IgE) to different substances of the

environment (inhalant and food allergens)…

IgE inflammation

shock organs symptoms

= swelling - narrowing

Allergic diseases …

ALLERGYALLERGY

healthy asthma

rhinitisconjunctivitis

enteritis

migraine

urticaria

eczema

Positive skin tests in 273 HEALTHY children at the age 6-7 years (Belgium - 1996).

ALLERGEN n %

- HDM 21 8 %

- Cat dander 6 2 %

- Birch pollen 1 0 %

- Grass pollen 8 3 %

- ANY 29 11 %

Allergy, one feature with many faces

SKIN

AIRWAYS

Allergic diseases … mild to … severe

“ The Allergic March “

Environmental substances = allergens (proteins…)

1. Inhalant allergens house dust mites, pollen pets, moulds

2. Food allergens egg, cow’s milk, soy, wheat ( < 3 yrs) peanuts, fish, shrimp, etc… (> 3 yrs)

Contact with food allergens

eating – drinking

touching

smelling

breast milk - prenatal

Food allergens in house dust.

Witteman AM, van Leeuwen J, van der Zee J, Aalberse RC. Int Arch Allergy Immunol. 1995 Aug;107(4):566-8.

ovomucoid -lactoglobulin

microgr/g dust

10

1

0.1

0.01

The amount of ovomucoid and -lactoglobulin in 11 house dust samples

0.073 microg/g dust = detection limit ovomucoid0.016 microg/g dust = detection limit lactoglobulin

“ Kiss of death “

5% of adults with food allergy

Foods: peanuts, nuts, apple, pea, fish

Relationship: husband, boyfriend, etc.

Hallett et al, NEJM 2002, 346, 1833

House Dust Mites

Blomia tropicalis Dermatophagoides farinae

AsthmaRhinitisEczema

House Dust Mites in Singapore

• High temp and humidity provides perfect environment for HDMs

• High counts (> 100 mites/g dust) of HDM are isolated in Singapore

• A wide variety of mite species is isolated other than Dermatophagoides.

• Blomia tropicalis is predominant.

Mite Species Present in Singaporean Mattresses

Species % (n = 50)B. tropicalis 94D. pteronyssinus 80S .brasiliensis 84T. granarius 44D. farinae 26A. malaysiensis 20C. malaccensis 24M. intermedius 12

Chew FT 1999 Clin Exp Allergy 29:201-206

Allergic diseases

1. GENETIC CONSTITUTION

2. ENVIRONMENT - Prenatal (pregnancy) - Postnatal (first months of life)

Genetic constitution

Parents Risk

1. both are negative 18 % 2. mother negative – father positive 40 % 3. mother positive – father negative 50 % 4. both positive 70 % 5. both strongly positive 90 %

Allergic diseases

1. GENETIC CONSTITUTION

2. ENVIRONMENT - Prenatal (pregnancy) - Postnatal (first months of life)

Direction of immune responses in early life

Birth

Non-allergic (Th1)

Allergic (Th2)allergic profile (Th2 predominance)

Factors

1. constitution 2. bacterial load

3. allergen exposure

ATOPY = inbalance

Th3

Th1

Th2

regulatory T cellsIL-10, TGF-b

T helper lymphocytes

Modified from S. Romagnani CEA, 36, 1357–1366

Roles of T cells

Orihara, Kanami et al., WAO 2008

/ Allergic disease

Postnatal immune deviation from allergic (Th2) to non-allergic (Th1)

POSITIVE 1. Increased bacterial load

- family size, farming- day care attendance- probiotics (Lactobacillus sp.) prebiotics, etc.

2. Tolerance through high exposure to allergens (pets – other allergens)

NEGATIVE 1.House dust mite – pollen (low doses) 2. RSV 3. Pollution (DEPs – cigarette) 4. Antibiotics - paracetamol

Diagnosis of allergy 1. History 2. Clinical examination

3. SPT = golden standard !

4. Specific IgE 5. Other lab tests: ECP, cytokines, etc… 6. eNO

7. Allergen provocation test (nasal, bronchial, etc…)

Unproven diagnostic tests for allergy…

- IgG against everything you can dream

- Electrodermal tests (“ Bioreasonance tests “)

- Other “witchcraft” (“ Kinesiology ”)

APPLIED KINESIOLOGY

Skin prick testing

= golden standard for diagnosing allergy in children & adults