Food allergy in children the gastroenterologist perspective

1. Food allergy in children the gastroenterologist perspective Ron Shaoul MD Pediatric Gastroenterology Bnai Zion Medical Center Maccabi Health Services

3. Major food allergens

4. Common food antigens • Cow’s milk protein • caseins, whey (beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin, bovine immunoglobulins). • Soy protein • 2S-globulin, soy tripsin inhibitor, soy lectin • Egg protein • Ovalbumin • Fish, shrimp, beef, pork

5. Common food antigens-2 • Peanuts, nuts, beans. • Cocoa, chocolate. • Citrus fruits, apples, strawberries. • Wheat, cereals. • Spices, yeast.

6. Predisposing factors • Positive family hx of atopic disease. • GI mucosal barrier defect. • Early antigen exposure during postnatal gut development

7. Epidemiology • Occurs in 0.3 to 7.5 percent of otherwise normal infants • 82 percent of whom have symptoms within four months of birth and 89 percent by one year of age.

8. Gastrointestinal manifestations • Gastrointestinal food allergies are often the first form of allergy to affect infants and young children and typically present as irritability, vomiting or "spitting-up," diarrhea, and poor weight gain. • Cell-mediated hypersensitivities predominate, making standard allergy tests such as prick skin tests and RAST tests of little diagnostic value

11. Food protein-induced enterocolitis syndrome FPIES)) • typically presents in the first several months of life with irritability, protracted vomiting, and diarrhea, not infrequently resulting in dehydration. • Vomiting generally occurs 1-3 hr after feeding, and continued exposure may result in bloody diarrhea, anemia, abdominal distention, and failure to thrive. • Symptoms are most commonly provoked by cow's milk or soy protein-based formulas but occasionally result from food proteins passed in maternal breast milk.

12. Food protein-induced enterocolitis syndrome • A similar enterocolitis syndrome has been reported in older infants and children from egg, wheat, rice, oat, peanut, nuts, chicken, turkey, and fish sensitivity. • Hypotension occurs in about 15% of cases after allergen ingestion.

13. Fourteen infants with FPIES caused by grains (rice, oat, and barley), vegetables (sweet potato, squash, string beans, peas), or poultry (chicken and turkey) were identified. • Symptoms were typical of classical FPIES with delayed (median: 2 hours) onset of vomiting, diarrhea, and lethargy/dehydration. • Eleven infants (78%) reacted to >1 food protein, including 7 (50%) that reacted to >1 grain.

14. Nine (64%) of all patients with solid food–FPIES also had cow’s milk and/or soy-FPIES. • Initial presentation was severe in 79% of the patients, prompting sepsis evaluations (57%) and hospitalization (64%) for dehydration or shock.

15. We presented a series of four babies, previously suspected as having cow milk protein allergy that presented with severe life-threatening episodes, all related to unsupervised self-challenge with either a cow milk based formula or a dairy product. • Parental decisions, physician recommendations, or inadvertent ingestion resulted in these serious clinical presentations.

16. Food protein-induced enteropathy • Often presents in the first several months of life with diarrhea, not infrequently steatorrhea, and poor weight gain. • Symptoms include protracted diarrhea, vomiting in up to two thirds of cases, failure to thrive, abdominal distention, early satiety, and malabsorption. • Anemia, edema, and hypoproteinemia occur occasionally.

17. Cow's milk sensitivity • is the most frequent cause of this syndrome in young infants, but it also has been associated with sensitivity to soy, egg, wheat, rice, chicken, and fish in older children.

18. Gastrointestinal anaphylaxis • generally presents as acute abdominal pain and vomiting that accompany other IgE-mediated allergic symptoms

19. Allergic eosinophilic gastroenteritis • occurs at any age and presents as symptoms similar to esophagitis as well as prominent weight loss or failure to thrive, which are the hallmarks of this disorder. • Up to 50% of patients are atopic, and food-induced IgE-mediated reactions have been implicated in a minority of patients. • Generalized edema secondary to hypoalbuminemia may occur in some infants with marked protein-losing enteropathy.

20. Allergic eosinophilic esophagitis • may present from infancy through adolescence. • In young children, it is primarily cell-mediated and presents as chronic gastroesophageal reflux (GER), intermittent emesis, food refusal, abdominal pain, dysphagia, irritability, sleep disturbance, and failure to respond to conventional reflux medications. • A study of children younger than 1 yr of age presenting with GER found that 40% had cow's milk-induced reflux.

21. Reflux and milk allergy • On the basis of studies using cow milk elimination and challenge, it is clear that a subset of infantile GER is attributable to cow milk allergy • The magnitude of the problem is not well-defined; it has been estimated that in 16% to 42% of infants, GER is attributable to CMA. • Risk factors for milk’s being causal seem to include esophagitis, malabsorption, diarrhea, and atopic dermatitis.

22. Reflux and milk allergy • Thus, for many infants with cow milk-associated GER, the reflux is not an isolated symptom. • One group identified that in infants with CMA-induced GER, the pH probe shows a “phasic” pattern with a gradual and prolonged fall in pH after milk ingestion. • However, the phasic pattern has not been demonstrated by other investigators. • Taking the studies together, it is evident that CMA accounts for GER in some infants. Sicherer SH Pediatrics 2003;111:1609 –1616

23. Oral allergy syndrome • Is an IgE-mediated hypersensitivity that occurs in many older children with birch pollen and ragweed-induced allergic rhinitis. • Symptoms are usually confined to the oropharynx and consist of the rapid onset of pruritus, tingling, and angioedema of the lips, tongue, palate, and throat, and occasionally a sensation of pruritus in the ears and/or tightness in the throat. • Symptoms are generally short-lived and are due to local mast cell activation by fresh fruit and vegetable proteins that cross react with birch pollen (apple, carrot, potato, celery, hazel nuts, and kiwi) and ragweed pollen (banana and melons-watermelon, etc.).

24. They hypothesized that intolerance of cow’s milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children.

25. They performed a double-blind, crossover study comparing cow’s milk with soy milk in 65 children with chronic constipation. • All had previously been treated with laxatives without success; 49 had anal fissures and perianal erythema or edema. • After 15 days of observation, the patients received cow’s milk or soy milk for 2 weeks. After a one-week washout period, the feedings were reversed. • A response was defined as eight or more bowel movements during a treatment period.

26. Forty-four of the 65 children (68 percent) had a response while receiving soy milk. Anal fissures and pain with defecation resolved. • None of the children who received cow’s milk had a response. • In all 44 children with a response, the response was confirmed with a double-blind challenge with cow’s milk. • Children with a response had a higher frequency of : • coexistent rhinitis, dermatitis, or bronchospasm • anal fissures and erythema or edema at base line • evidence of inflammation of the rectal mucosa on biopsy • signs of hypersensitivity, such as specific IgE antibodies to cow’s-milk antigens

27. Other GI manifestations ? • Recurrent oral aphtae • Bowel edema and obstruction • Occult GI bleeding • Infantile colic

28. Clinical applications

29. In infants with IgE-mediated CMA, most (86%) will tolerate a soy formula, but the rate of tolerance is lower (50%) for most of the cell-mediated disorders. • Infants with true CMA would be expected also to react to partially hydrolyzed formula, lactose-free cow milk-based formula, and most mammalian milks (eg, sheep, goat), so none of these is a good alternative.

30. In most cases (95%), infants with CMA will tolerate extensively hydrolyzed cow milk formula, but for the few who continue to react (presumably as a result of residual allergens), an amino acid-based formula is required for therapy.

31. Any need for amino acid formula ?

32. Intolerance to protein hydrolysate infant formulas: An underrecognized cause of gastrointestinal symptoms in infants • The purpose of this study was to determine the effectiveness of an amino acid–based infant formula in infants with continued symptoms suggestive of formula protein intolerance while they were receiving casein hydrolysate formula (CHF). • Twenty-eight infants, 22 to 173 days of age, were enrolled; each had received CHF for an average of 40 days (10 to 173 days) and continued to have bloody stools, vomiting, diarrhea, irritability, or failure to gain weight, or a combination of these symptoms.

33. Intolerance to protein hydrolysate infant formulas: An underrecognized cause of gastrointestinal symptoms in infants • Sigmoidoscopy with rectal biopsy was performed in all infants. • The infants then received an amino acid–based infant formula, Neocate, for 2 weeks. • After 2 weeks of treatment, 25 of the infants demonstrated resolution of their symptoms and underwent challenge with CHF. • Of the 25 who were challenged, eight tolerated the CHF and the remainder had recurrence of their symptoms. • The histologic features in these infants varied from eosinophilic infiltration to normal.

34. Intolerance to protein hydrolysate infant formulas: An underrecognized cause of gastrointestinal symptoms in infants • They concluded that not all infants with apparent formula protein–induced colitis respond to CHF (J Pediatr 1997;131:741-4)

35. Natural history of food allergy

36. Most food allergy is acquired in the first 1 to 2 years of life. • The prevalence of food allergy peaks at 6% to 8% at 1 year of age and then falls progressively until late childhood, after which the prevalence remains stable at 1% to 2%. • Most food allergy is indeed lost over time.

37. The process of outgrowing food allergies, varies a great deal for different foods and among individual patients. • It is also important to note that the process of outgrowing a food allergy may be helped by strict avoidance of the offending food, in that repeated exposures to even small quantities may delay the development of tolerance in some patients

41. Early intervention to prevent food allergyCan we do it ???

42. Aim: To assess the preventive effect of differently hydrolyzed formulas compared with cow’s milk formula (CMF) in high-risk infants. • Methods: 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and randomly assigned at birth to one of 4 blinded formulas: CMF, partially hydrolyzed whey formula, extensively hydrolyzed whey formula, and extensively hydrolyzed casein formula (eHF-C).

43. The primary end point at 1 year of age was the presence of allergic manifestation, which was defined as atopic dermatitis (AD), gastrointestinal manifestation of food allergy, allergic urticaria, or a combination of these factors.

44. Results: The incidence of allergic manifestation was significantly reduced by using eHF-C compared with CMF (9% vs 16%; adjusted OR, 0.51; 95% CI, 0.28-0.92), • The incidence of AD was significantly reduced by using eHF-C (OR, 0.42; 95% CI, 0.22-0.79) and partially hydrolyzed whey formula (OR, 0.56; 95% CI, 0.32-0.99). • Family history of AD was a significant risk factor and modified the preventive effect of the hydrolysates.

45. Conclusions: Prevention of allergic diseases in the first year of life is feasible by means of dietary intervention but influenced by family history of AD. • The preventive effect of each hydrolyzed formula needs to be clinically evaluated.

46. Seven studies compared prolonged feeding of hydrolysed formula to cow's milk formula for allergy prevention. • Meta-analysis of 4 studies (386 infants) found a significant reduction in allergy incidence in infancy (RR 0.63) • One study reported a significant reduction in allergy incidence in childhood (RR 0.54).

47. Significant reductions were found in • asthma prevalence in childhood • eczema incidence in infancy and prevalence in childhood • food allergy prevalence in childhood • CMA incidence in infancy.

48. Main results: Five eligible studies were found, all enrolling infants at high risk of allergy on the basis of a family history of allergy in a first degree relative. • Conclusions: Feeding with a soy formula should not be recommended for the prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance.

49. Conclusions: In breast-fed infants with atopy, gut barrier function is improved after cessation of breast-feeding and starting of hypoallergenic formula feeding.

50. Objective: a systematic review with meta-analysis of prospective studies that evaluated the association between exclusive breast-feeding during the first 3 months after birth and atopic dermatitis. • Methods: 18 prospective studies that met the predefined inclusion criteria. J Am Acad Dermatol 2001;45:520-7