1. Food allergy in children Hugo Van Bever Department of Pediatrics National University Singapore APAPARI Workshop, Hanoi, May 2008

2. Food Allergy… Fact or Fiction? 1. Difficult problem group of diseases 2. Lot of non-scientific data … opinions… truths… tradition… stories. 3. Food other types of reaction (intolerance, intoxication, etc…) 4. Too many children are labeled as being “food-allergic”

3. Adverse reactions to food  Food intolerance (most common)  Food allergy (hypersensitivity)  Food aversion (phobia)

4. FOOD INTOLERANCE - toxins - infections - pharmacological properties of food - host factors (lactase deficiency)

5. Food allergy = an immunologically-mediated reaction against food 1. IgE-mediated Others… (less evidence) 2. Cell-mediated reactions (T lymphocytes - delayed onset) 3. Mixed types (atopic dermatitis) 4. Other mechanisms ( unknown - CIC – complement – etc…)

6. Prevalence of food allergy 1. General population: 2 % 2. Young children (< 3 yrs): 8 % 3. Singapore children: 4 – 5 % SPECIFIC GROUPS 4. Young children with severe eczema: 90 % 5. Children with asthma: < 10 %

7. Manifestations of food allergy 1. SKIN: urticaria – angioedema > eczema 2. RESPIRATORY: rhinitis – asthma 3. GI TRACT: diarrhea – vomiting – FTT - eosinophilic gastroenteritis - enterocolitis 4. GENERAL: anaphylactic shock 5. OTHER: migraine, hyperactivity, sleep disturbances etc… ?

8. Foods triggering anaphylaxis in Singaporean children (1992 – 1996) 124 children with acute anaphylaxis at NUH mean age (yrs) 1. Egg and milk11 %0.7 2. Bird’s nest27 %4.5 3. Chinese herbs 7 %5.0 4. Crustacean seafood24 % 11.0 5. Others *30 %7.0 * Chicken, duck, ham, fruits (banana, rambutan), cereals, gelatin and spices Goh et al. Allergy 54, 1999, 78-92.

9. Common culprits - Singapore children Infants: cow’s milk hen's egg

10. Common culprits - Singapore children Older children seafood (shellfish), bird’s nest, Chinese herbs, eggs

11. FISH Sweden – 39% of food- allergic children are allergic to cod Uncommon in Singapore - per capita consumption of 25.05kg

12. Every food has its own story… cow’s milk hen’s egg peanuts, fish, seafood, … prevalence age 3 yrs 5 yrs6 months

13. Sensitization to food… sensitization to allergens… 1. prenatal sensitization 2. postnatal sensitization

14. Sensitization to food… eating, touching and smelling… peanuts fish hen’s egg

15. Allergy to cow’s milk proteins in mother’s milk or in hydrolyzed cow’s milk infant formulas assessed by intestinal permeability measurements. Barau E et al. Allergy 1994; 49:295-8. ovalbumin peanut protein cow’s milk protein mother’s milk

16. Case 9 month old boy Totally breastfed 1st introduction of CM formula One minute after the first “bite”…

18. Prenatal sensitization to allergens…does it exist? 1. clinical evidence (peanuts – ovalbumine – pollen – house dust mite – cat - dog) 2. allergens in amniotic fluid & cord blood 3. active transport through placenta

19. Exposure to peanuts in utero and in infancy and the development of sensitization to peanut allergens in young children. Frank L, Marian A, Visser M, Weinberg E, Potter PC. Pediatr Allergy Immunol 1999, 10, 27-32. … mothers who consumed peanuts more than once a week during pregnancy were more likely to have a peanut-allergic child than mothers who consumed peanuts less than once a week (odds ratio=3.97, 98% confidence interval 0.73-24).

20. Allergic sensitization during pregnancy influences the offspring’s immune reactions. A study in a mouse model (H. Renz, 1999). study group control group Ovalbumin challenge (every second day) decreased INF-  ( x 8 – 9 ) PREGNANCY BIRTH

21. Direct evidence for transplacental allergen transfer. Szépfalusi et al. Pediatr Res 2000, 48, 404-7. maternal side fetal side BLG 8 8 Bet v1 10 2 Human IgG = increase = Ig receptor involvement

22. Diagnosis of food allergy 1. IgE-mediated food allergy - SPT – IgE 2. Non-IgE-mediated food allergy - patch test - in vitro: LTT (cytokine profile?) GOLDEN STANDARD = DBPCFC research …

23. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. Hugh A. Sampson. JACI 2001, 107, 891. Diagnostic decision points of 95% - cow’s milk 15 kU/L - egg 7 kU/L - peanut 14 kU/L - fish 20 kU/L n = 100, mean age = 3.8 yrs

24. Future immunomodulatory therapies for food allergy 1. Humanized monoclonal anti-IgE 2. Mutated allergen protein immunotherapy 3. Peptide immunotherapy 4. Immuno-stimulatory sequences 5. Probiotics (?) no effect on allergic reactions

25. Alternative feedings in case of CMA 1. Breast milk 2. Soy formulas (?) 3. Goat formulas (?) 4. Hypoallergenic formulas ( partial hydrolysate formulas) 5. Amino acid-based formulas (complete hydrolysate formulas

26. (  ), Hypoallergenic milk group; (---) cow’s milk-based infant formula. p = 0.093 Use of hypoallergenic formula in the prevention of atopic disease among Asian children. Chan et al. J Paediatr Child Health 2002; 38; 84-8.

27. Primary prevention of atopy: food allergen avoidance -- BREAST FEEDING Saarinen AM, Kajosaari M. Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old. Lancet 1995; 346: 1065 - 1069. -- HYPO-ALLERGENIC MILK Vandenplas Y et al. The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease. Eur J Pediatr 1995; 154: 488 - 494.

28. The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease. Vandenplas et al. Eur J Ped 1995, 154, 488. prevalence of CMP sensitivity

29. Conclusion: Food Allergy… Fact or Fiction? … a lot of non-scientific data … opinions… truths… tradition… stories … etc … scientific data … A fact… surrounded with lot’s of fiction

30. Conclusion… Still … breast is best …but… impossible to study … no contra-indications…