1. PRACTICAL APPLICATION OF NUTRITION IN PATIENTS WITH FOOD ALLERGY John T. Stutts, MD, MPH Division of Pediatric Gastroenterology University of Louisville School of Medicine Louisville, Kentucky

2. LOUISVILLE.EDU Support for this program is provided by Abbott Nutrition The slides were developed by the Speaker with input by Abbott Nutrition This program is not intended for continuing education credits for any healthcare professional D ISCLOSURE

3. LOUISVILLE.EDU Any abnormal clinical response associated with ingestion of or exposure to a food or food additive Up to 25% of the US population report a symptom related to a food -Most cannot be confirmed Events where food relation can be confirmed can be further classified as: -Food intolerance -Food Allergy A DVERSE F OOD R EACTIONS

4. Adverse Food Reaction Food Intolerance Food Allergy Food Characteristics Host Characteristics Mixed Non-IgE mediated IgE mediated IgE mediated Graphic adapted from Reference 1

5. LOUISVILLE.EDU What is it? -The most common food allergy present in up to ~ 2.5-3% of otherwise normal infants within the first year of life 2. C OW ’ S M ILK P ROTEIN A LLERGY (CMPA)

6. LOUISVILLE.EDU IgE-mediated -Several systems involved: rarely an isolated gut syndrome -Most often in an infant with atopic dermatitis Non-IgE- mediated -More common in first part of first year -Symptoms usually affect gut only -Food protein-induced enterocolitis syndrome (FPIES) -Allergic proctocolitis (CMPA) I G E- MEDIATED AND N ON -I G E MEDIATED M ILK A LLERGY IN I NFANTS

7. LOUISVILLE.EDU How does it manifest? C OW ’ S M ILK P ROTEIN A LLERGY Gastrointestinal 50 – 60% Blood/mucus in stool Abdominal pain Iron deficiency anemia Hypoalbuminemia Failure to thrive (DIV) Skin 50 – 60% Atopic dermatitis Urticaria Respiratory Tract 20 – 30% Acute Laryngoedema Obstruction with difficulty breathing Anaphylaxis Reference 3.

8. LOUISVILLE.EDU Generally tests are not needed Wright stain: may be + neutrophils and possibly eosinophils Stool culture: Staphylococcus aureus, enteric pathogens, C. difficile Blood tests -Complete blood count (CBC) which may reveal anemia (if so, ? physiologic) -Mild peripheral eosinophilia -Coagulation profile Plain radiographs of the abdomen W HAT TESTS SHOULD I CONSIDER FOR CMPA?

9. LOUISVILLE.EDU Treatment? Dietary Change is the Key! COW’S MILK PROTEIN ALLERGY

10. LOUISVILLE.EDU Treatment in the breast fed infant -Mother must eliminate all dairy from her diet…. COW’S MILK PROTEIN ALLERGY

11. LOUISVILLE.EDU So what can the breast feeding mother eat? -Fresh meats -Fresh vegetables -Fresh fruits COW’S MILK PROTEIN ALLERGY

12. LOUISVILLE.EDU Treatment in the formula fed infant -Casein hydrolysate formulas -Elemental (Amino Acid) based formulas COW’S MILK PROTEIN ALLERGY

13. LOUISVILLE.EDU Casein hydrolysate formulas -Alimentum (Abbott) -Nutramigen (Mead Johnson) -Pregestimil (Mead Johnson) COW’S MILK PROTEIN ALLERGY

14. LOUISVILLE.EDU Elemental (Amino Acid) based formulas -EleCare (Abbott) -Neocate (SHS) -PurAmino (Mead Johnson) COW’S MILK PROTEIN ALLERGY

15. LOUISVILLE.EDU They can also develop Cow’s Milk Protein Allergy! W HAT ABOUT RECTAL BLEEDING IN THE P REMATURE INFANT ?

16. LOUISVILLE.EDU Swallowed maternal blood Dietary protein intolerance/allergy NEC Infectious colitis Hirschsprung’s disease with enterocolitis Duplication cyst Vascular malformations Hemophilia Maternal Idiopathic Thrombocytopenic Purpura Maternal NSAID use T HE D IFFERENTIAL D IAGNOSIS ?

17. LOUISVILLE.EDU What’s the natural history? -Most resolve by 9 mo of age, but 22% can still be intolerant at age 6 years When can regular formula be reintroduced? -9 months of age COW’S MILK PROTEIN ALLERGY

18. LOUISVILLE.EDU Is it lactose intolerance? -NO! Is it a life long allergy? -NO! COW’S MILK PROTEIN ALLERGY

19. LOUISVILLE.EDU Is it Eosinophilic Esophagitis (EoE)? -NO! COW’S MILK PROTEIN ALLERGY

20. LOUISVILLE.EDU Most commonly less than 3 months of age Like CMPA, due to allergic reaction to cow’s milk or soy protein Symptoms: diarrhea, nausea, projectile vomiting, dehydration Hospitalization is not uncommon Often confused with Viral Gastroenteritis Symptoms occur 1-3 hours after ingestion (non-IgE) Food protein elimination leads to resolution of symptoms in less than 72 hours W HAT ABOUT FPIES 4 ?

21. LOUISVILLE.EDU If the CMPA is IgE-mediated, soy protein is usually tolerated If the CMPA is non-IgE-mediated, soy protein is frequently not tolerated -In infant GI syndromes, >50% react to soy in most studies WHAT ABOUT SOY - BASED FORMULA?

22. LOUISVILLE.EDU Differences -Location within GI tract -Dysphagia (EoE) vs Bleeding (CMPA) -Age of presentation CMPA usually younger EoE usually older Similarities -Allergic reaction -Both are due to exposure to an allergen over time -Both show eosinophilic infiltration on biopsy Treatment for both…. -Removal of the Allergen! H OW IS IT DIFFERENT / SIMILAR TO E O E?

23. LOUISVILLE.EDU Eosinophilic Enteropathy 4 Eosinophils are present throughout the GI tract – but NOT the esophagus. Characterized by increased numbers of eosinophils within the GI tract mucosa. An example of Mixed Mediation Allergy. The most common form is Eosinophilic Esophagitis (EoE) E OSINOPHILIC -A SSOCIATED G ASTROINTESTINAL D ISORDERS

24. LOUISVILLE.EDU Seen in all ages. Similar presentation to GERD 2/3 have a personal or family history of asthma, eczema or allergic rhinitis. Diagnosis is by endoscopy with esophageal biopsy. E OSINOPHILIC E SOPHAGITIS

25. LOUISVILLE.EDU Infiltration of Eosinophils within the esophageal mucosa. GERD refractory to medical therapy. Greater than 65% of cases appear in childhood. 5 E OSINOPHILIC E SOPHAGITIS

26. LOUISVILLE.EDU Symptoms 6 Infants Feeding refusal Failure to thrive Regurgitation Vomiting Children Dysphagia Vomiting Abdominal pain Heartburn E OSINOPHILIC E SOPHAGITIS Adolescents/Adults Dysphagia Food impaction Heartburn Reflux

27. LOUISVILLE.EDU Diagnosis There must be biopsies! E OSINOPHILIC E SOPHAGITIS

28. LOUISVILLE.EDU Diagnosis The First International Gastrointestinal Eosinophilic Research Symposium (FIGERS) diagnostic guidelines. 7 -Eosinophil count of  15/HPF, along with normal gastric/duodenal biopsies. -Biopsies after 6 – 8 wk of twice daily acid suppression with PPI or have a negative pH probe result. -Biopsies obtained from  5 esophageal sites. E OSINOPHILIC E SOPHAGITIS

29. LOUISVILLE.EDU Pathogenesis 4 Driven by Th2 cytokine pathways. IL-5 and IL-13 are important mediators of the EoE inflammatory pathway. IgE can be detected on the surface of most cells and likely contributes to most cell activation. E OSINOPHILIC E SOPHAGITIS

30. LOUISVILLE.EDU Grossly E OSINOPHILIC E SOPHAGITIS

31. LOUISVILLE.EDU Management Two components Nutritional Management Pharmacologic Management E OSINOPHILIC E SOPHAGITIS

32. LOUISVILLE.EDU Management E OSINOPHILIC E SOPHAGITIS Nutritional Management 6 Food Elimination Milk Eggs Nut/Tree nuts Fish/Shellfish Wheat Corn Amino-Acid Based Diet Elemental Formulas as a “milk” source Allergy testing? Adapted from Reference 8

33. LOUISVILLE.EDU Management-Nutritional So, when should the eliminated food be re-introduced and how? If you ask 5 gastroenterologists, you might get 5 different answers. There is no consensus statement...YET. Once symptoms are resolved, I reintroduce one eliminated food no faster than every 2–3 months – Remember, delayed hypersensitivity! E OSINOPHILIC E SOPHAGITIS

34. LOUISVILLE.EDU Management-Pharmacologic E OSINOPHILIC E SOPHAGITIS Pharmacologic Steroids Topical vs. Systemic Proton Pump Inhibitors Adapted from Reference 10

35. LOUISVILLE.EDU Management-Pharmacologic PPIs -Eliminate GERD symptoms. 5 -Not effective alone for EoE. 5 -Duration of use? Topical Steroids -Effective in inducing remission. 8 -Duration of use? -Symptoms can recur after withdrawal. 9 Systemic steroids -Effective in inducing remission. 5 -Only for severe or refractory cases. 8 E OSINOPHILIC E SOPHAGITIS

36. LOUISVILLE.EDU Strictures What if a stricture is found? E OSINOPHILIC E SOPHAGITIS Pharmacologic and/or dietary therapy should be attempted prior to esophageal dilation. 6

37. LOUISVILLE.EDU When to refer? In any patient with dyspepsia, failure to thrive or feeding refusal who fails to respond to “typical” GERD therapy. In any patient with persistent dysphagia/food impactions. Consider referral to your allergy colleagues. E OSINOPHILIC E SOPHAGITIS

38. LOUISVILLE.EDU The Role of Allergy Testing? Cincinnati vs. Philadelphia Same research study….different conclusions! E OSINOPHILIC E SOPHAGITIS

39. LOUISVILLE.EDU H OW S HOULD W E A SCEND THE P RODUCTS P YRAMID ? Elemental Formulas Casein Hydrolysate Formulas Blood/mucus in stool Atopic dermatitis Eosinophilic Gastroenteropathies Short Bowel Syndrome Intact Protein Formulas

40. LOUISVILLE.EDU H OW S HOULD W E A SCEND THE P RODUCTS P YRAMID ? Elemental Formulas Casein Hydrolysate Formulas Blood/mucus in stool Atopic dermatitis Eosinophilic Gastroenteropathies Short Bowel Syndrome Intact Protein Formulas Continued blood/mucus in stool x 4 wks Improved but continued other signs/symptoms of milk protein allergy Eosinophilic Esophagitis* Short Bowel Syndrome*

41. LOUISVILLE.EDU Adverse Food Reactions -Food Intolerance -Food Allergy -Dietary Management is the key Cow’s Milk Protein Allergy -Dietary Management is the key Food Protein-Induced Enterocolitis -Dietary Management is the key Eosinophilic Esophagitis -Pharmacologic Management -Dietary Management is the key O VERVIEW

42. LOUISVILLE.EDU O VERVIEW

43. LOUISVILLE.EDU Thank You!

44. LOUISVILLE.EDU 1.Cianferoni A, Speigel JM. Food Allergy: Review, Classification and Diagnosis. Allergology International. 2009;58(4):1-10. 2.Sicherer SH, et al. Hypoallergenicity and efficacy of an amino acid-based formula in children with cow’s milk and multiple food hypersensitivities. J Pediatr. 2001;128(5):688-693. 3.Host A. Frequency of cow’s milk allergy in childhood. Ann Allergy Immunol. 2002;89(6 Suppl 1):33-37 4.Mansueto, et al. Food Allergy in gastroenterologic diseases: Review of Literature. World J Gastroetnerol, 2006;12(48):7744-7752. 5.DeBrosse CW, Rothenberg ME. Allergy and Eosinophil-associated Gastrointestinal Disorders (EGID). Curr Opin Immunol. 2008;20(6):703-708. 6.Lucendo, et al. Eosinophilic Esophagitis: Current aspects of a recently recognized disease. Gastroenterol Res. 2010;3(2):52-64. 7.Furutua GT, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-1363. 8.Guple AR, et al. Eosinophilic esophagitis. Word J Gastroenterol. 2009;15(1):17-24. 9.Liacuras CA, et al. Eosinophilic esophagitis: updated consensus recommendation for children and adults. J Allergy Clin Immunol. 2011;128(1):3-20. R EFERENCES