The spectrum of allergic diseases

Hugo Van Bever Department of Pediatrics National University Singapore APAPARI workshop – Hanoi, Vietnam – May 2008

HDB flat skyline 1. Clean - well organized - tropical 2. High prevalence of allergic diseases 3. A lot of HDMs (Blomia tropicalis) 4.

Strange food allergies (bird nest, etc…)

Pediatric Allergy in Asia (APAPARI)

Starting 1998 HR Lee SI Lee Morikawa Chen P Vichyanond J Debruyn BW Lee H Van Bever KH Hseih JL Huang A Tam G Wong S Siregar M Bautista

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-old 4 - 6 yrs-old 2002 -2003 6 – 7 yrs-old 12 – 15 yr-old 2001 2001

Increase in prevalence of allergic diseases changes in the environment Induction of the expression of allergy - asthma - rhinitis - eczema

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

= swelling - narrowing shock organs symptoms

Allergic diseases …

healthy eczema asthma enteritis rhinitis

ALLERGY

urticaria conjunctivitis migraine

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

ALLERGEN - HDM - Cat dander - Birch pollen - Grass pollen - ANY n 21 6 1 8 29 % 8 % 2 % 0 % 3 %

11 %

Allergy, one feature with many faces

AIRWAYS SKIN

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. microgr/g dust 10 1 0.1

0.01

ovomucoid b -lactoglobulin The amount of ovomucoid and b -lactoglobulin in 11 house dust samples 0.073 microg/g dust = detection limit ovomucoid 0.016 microg/g dust = detection limit b 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

Asthma Rhinitis Eczema

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

B. tropicalis D. pteronyssinus S .brasiliensis

T. granarius D. farinae A. malaysiensis C. malaccensis M. intermedius

% (n = 50)

94 80 84 44 26 20 24 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

1. both are negative 2. mother negative – father positive 3. mother positive – father negative 4. both positive 5. both strongly positive

Risk

18 % 40 % 50 % 70 % 90 %

Allergic diseases

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

Direction of immune responses in early life allergic profile (Th2 predominance) Allergic (Th2) Birth

Factors 1. constitution

2. bacterial load 3. allergen exposure Non-allergic (Th1)

Th1

ATOPY = inbalance

Th2 Th3

regulatory T cells IL-10, TGF-b

T helper lymphocytes Modified from S. Romagnani CEA, 36, 1357–1366

Roles of T cells

/ Allergic disease Orihara, Kanami et al., WAO 2008

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