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

Food Allergy… Fact or Fiction? 1. Difficult problem group of diseases 2. Lot of 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”

Adverse reactions to food q Food intolerance (most common) q Food allergy (hypersensitivity) q Adverse reactions to food q Food intolerance (most common) q Food allergy (hypersensitivity) q Food aversion (phobia)

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

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

Prevalence of food allergy 1. General population: 2 % 2. Young children (< 3 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 %

Manifestations of food allergy 1. SKIN: urticaria – angioedema > eczema 2. RESPIRATORY: rhinitis 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… ?

Foods triggering anaphylaxis in Singaporean children (1992 – 1996) 124 children with acute anaphylaxis Foods triggering anaphylaxis in Singaporean children (1992 – 1996) 124 children with acute anaphylaxis at NUH mean age (yrs) 1. Egg and milk 11 % 0. 7 2. Bird’s nest 27 % 4. 5 3. Chinese herbs 7% 5. 0 4. Crustacean seafood 24 % 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.

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

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

FISH Sweden – 39% of foodallergic children are allergic to cod Uncommon in Singapore FISH Sweden – 39% of foodallergic children are allergic to cod Uncommon in Singapore - per capita consumption of 25. 05 kg

Every food has its own story… cow’s milk hen’s egg peanuts, fish, seafood, … Every food has its own story… cow’s milk hen’s egg peanuts, fish, seafood, … prevalence age 6 months 3 yrs 5 yrs

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

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

Allergy to cow’s milk proteins in mother’s milk or in hydrolyzed cow’s milk infant 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. mother’s milk ovalbumin peanut protein cow’s milk protein

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

Prenatal sensitization to allergens…does it exist? 1. clinical evidence (peanuts – ovalbumine – pollen 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

Exposure to peanuts in utero and in infancy and the development of sensitization to 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).

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

Direct evidence for transplacental allergen transfer. Szépfalusi et al. Pediatr Res 2000, 48, 404 Direct evidence for transplacental allergen transfer. Szépfalusi et al. Pediatr Res 2000, 48, 404 -7. maternal side BLG 8 Bet v 1 10 Human Ig. G fetal side 8 2 = increase = Ig receptor involvement

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

Utility of food-specific Ig. E concentrations in predicting symptomatic food allergy. Hugh A. Sampson. Utility of food-specific Ig. E concentrations in predicting symptomatic food allergy. Hugh A. Sampson. JACI 2001, 107, 891. Diagnostic decision points of 95% - cow’s milk - egg - peanut - fish 15 k. U/L 7 k. U/L 14 k. U/L 20 k. U/L n = 100, mean age = 3. 8 yrs

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

Alternative feedings in case of CMA 1. Breast milk 2. Soy formulas (? ) 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

Use of hypoallergenic formula in the prevention of atopic disease among Asian children. Chan Use of hypoallergenic formula in the prevention of atopic disease among Asian children. Chan et al. J Paediatr Child Health 2002; 38; 84 -8. ( ), Hypoallergenic milk group; (---) cow’s milk-based infant formula. p = 0. 093

Primary prevention of atopy: food allergen avoidance -- BREAST FEEDING Saarinen AM, Kajosaari M. 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.

The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic 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

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

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