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Non–IgE-mediated Gl Food Allergy (FA)

Non–IgE-mediated Gl Food Allergy (FA). Dr. Raga Sirror , MBBS, FRCPC Thunder Bay Regional Health Sciences Centre Pediatrics, Allergy. Conflict of Interest Declaration:. Presenter: Dr. Raga Sirror Title of Presentation: Non IgE mediated Gastrointestinal Food Allergy

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Non–IgE-mediated Gl Food Allergy (FA)

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  1. Non–IgE-mediated Gl Food Allergy (FA) Dr. Raga Sirror, MBBS, FRCPC Thunder Bay Regional Health Sciences Centre Pediatrics, Allergy

  2. Conflict of Interest Declaration: Presenter: Dr. Raga Sirror Title of Presentation: Non IgE mediated Gastrointestinal Food Allergy I have no financial or personal relationship related to this presentation to disclose.

  3. Objectives: To identify different types of Non IgE mediated FA. To discuss the management of Non IgE mediated FA. To discuss the possible associations between common GI issues & FA.

  4. History of Food Allergy Hippocrates noted: cow’s milk (CM) caused GI symptoms, as well as urticaria, and that some infants fed CM had diarrhea, vomiting, and FTT that resolved only after removal of CM from their diets Wuthrich B. History of food allergy. ChemImmunol Allergy 2014

  5. Classification of gastrointestinal hypersensitivities to food

  6. Case No.1 2 m old, Frank A. Peter, breastfed with bloody stool. Aside from the diaper, the baby is well. What’s Frank A. Peter diagnosis? • FPIAP • FPIES • FPE

  7. Case No.1 2 m old, Frank A. Peter, breastfed with bloody stool. Aside from the diaper, the baby is well. What’s Frank A. Peter diagnosis? • FPIAP • FPIES • FPE

  8. Food Protein Induced Allergic Proctocolitis (FPIAP) Clinical presentation: • Mucousy, bloody stools in otherwise healthy infant • No vomiting • No FTT • No malabsorbtion • Occasional colic or diarrhea Elizur A. et al. Pediatr Allergy Immunol 2012

  9. What is one physical exam you don’t want to miss in an infant with suspected FPIAP?

  10. FPIAP Epidemiology: 60% of cases occur in breastfed infants Personal or FHx of atopy is not Mean age: 2 -8 wks,. Food most implicated: CM, soy 20% react to CM & soy or multiple foods Odze RD,et al . Hum Pathol 1993

  11. FPIAP Epidemiology (cont’d) A prospective population-based study from Israel, reported CM FPIAP prevalence of 0.16 % in 13,019 infants. Prevalence was much lower when infants were challenged at 3 m after initial presentation Elizur A, Cohen M, Goldberg MR, et al. Pediatr Allergy Immunol. 2012

  12. FPIAP in Children • Ravelli et al. reported 16 cases of rectal bleeding in children 2-14 yr; resolved with elimination of CM • The symptoms recurred in all cases with reintroduction of CM • Endoscopic and histologic findings were consistent with FPIAP Ravelli A et al. Am J Gastroenterol, 2008

  13. FPIAP Pathogenesis • Largely unknown • Dietary Ag complexed to breast milk IgA → eosinophil activation

  14. FPIAP Diagnosis: Typical presentation and resolution of symptoms with elimination Rechallenge in 4-8 wks is recommended Endoscopy – generally not needed • Patchy erythema, loss of vascularity in rectum, sometimes extending to colon • ↑ eosinophils (5-20/hpf) LozinskyAC,et al. J Pediatr (Rio J). 2014

  15. Is Is FPIAP over diagnosed?

  16. The etiology of small and fresh rectal bleeding(RB) in not-sick neonates: should we initially suspect FPIAP? Eur J Pediatr. 2012. Jang HJ1, et al. 16 , not sick neonates with fresh RB 10, satisfied endoscopic findings of FPIAP ECT in cases with over 4 d of persistent RB Only two confirmed as FPIAP by food ECT. In 14 , RB disappeared at 4 (1-8) d idiopathic neonatal transient colitis (INTC).

  17. FPIAP Management: Exclusively breastfed: • CM should be eliminated from maternal diet first, followed by soy, then egg • Clinical bleeding typically clears within 3d after complete elimination, but may take up to 2 wk

  18. Formula fed:  • Protein hydrolysate formula • Soy formula not generally recommended • 5-10% of infants need to be switched to amino acid based formula

  19. FPIAP Natural HX • Majority resolve by age 12 m • Reintroduction, over 3-5 d • Some experts- reintroduce at 4-6 m • Reintroduction can be done at home • If symptoms recur, try in 5-6 m Elizur A, et al. JACI, 2012

  20. Case No. 2 • 5 m old, Fred Pies, previously well, exclusively BF. At 4 m, introduced to CM formula • 2 wks after, fed CM formula for 2nd time. 2 h later, he developed repetitive vomiting, looked lethargic, hypotensive • Leucocytosis, Methemoglobimemia

  21. What is Fred Pies diagnosis? FPIAP FPIES FPE

  22. What’s Fred Pies diagnosis? FPIAP FPIES FPE

  23. Acute FPIES: • Intermittent exposure or re-exposure after a period of food avoidance • Severe, projectile emesis in 1 to 3 h, +/- diarrhea • Pallor, lethargy • Hypotension in 15% of reactions • Cyanosis • Hypothermia

  24. Hmm, This could be FPIES ER doc call Peds. re: an infant with possible septic shock: Allergist, on call for Peds

  25. Chronic FPIES • Infants with regular intake of the food, e.g. formula • Intermittent, progressive emesis, bloody diarrhea • FTT • Dehydration

  26. FPIES Supporting lab findings Leukocytosis,↑neutro Thrombocytosis Metabolic acidosis Methemoglobinemia Hypoalbuminemia Anemia Food skin prick test, +ve in 4 to 30%

  27. FPIES Implicated foods • CM & soy (present 3 to 6 m) • Rice, Oat • Chicken, green bean, sweet potato • Fish and shellfish FPIES observed in older children and adults Mehr S, et al. Pediatrics 2009

  28. FPIES Implicated foods (cont’d) Multiple food FPIES • Up to 50% of pts react to both CM & soy in US studies • 65% with CM or soy FPIES develop solid food FPIES • 50% infants reacted to >1 grain Nowak-Wegrzyn A, CurrOpin Allergy ClinImmunol 2008;9:371-7

  29. FPIES - Epidemiology Israeli population based cohort: • CM FPIES in 0.34% of 13,019 infants (0.5% IgE mediated CMA) in 1st yr of life • Slight male predominance • 40-80% have FHx of atopy • Personal Hx of atopy up to 30% Elizur A, et al. Pediatr Allergy Immunol. 2012

  30. FPIES - Pathophysiology • Mostly formula fed infants • Immunologic mechanism unclear • ? T cell mediated • Food allergens may cause local inflammation, subsequent increased intestinal permeability and fluid shift

  31. FPIES Diagnosis NIAID-sponsored panel in 2010 advise: • Diagnosis for FPIES based on typical presenting features, resolution with removal of the offending protein, and reoccurrence of symptoms with OFC • OFC is not necessary when Hx is convincing or the reaction was severe

  32. Management: Acute FPIES (symptoms resolve in hrs) Rehydration IV Methylprednisolone Ondansetron Methylene blue when necessary Food avoidance Epinephrine is not of help Holbrook et al.J Allergy Clin Immunol,2013

  33. Management( cont’d) Chronic FPIES Food elimination Sx resolved in 3-10 days 80% respond to hydrolysate formula Soy formula can be introduced under supervision Rechallenge in 1-2 yr in hospital setting

  34. Case No. 3: 9 m old, Fae P. Edward, presented with recurrent vomiting, diarrhea, FTT, malabsorption and anemia. Negative celiac screen Endoscopy findings: villous atrophy

  35. What’s Fae P. Edward diagnosis? FPIAP FPIES FPE

  36. What’s Fae P. Edward diagnosis? FPIAP FPIES FPE

  37. What dietary intervention is a risk factor for FPE?

  38. FPE (Food Protein Enteropathy) • Most likely to occur in infants fed intact CM prior to 9m • Described following gastroenteritis • The prevalence of FPE is obscure • Decline in the prevalence is noted Kleinman RE, J Pediatr,19991

  39. FPE Clinical Presentation: Usually induced by CM Diarrhea, emesis, abdominal distension, FTT Distinguishing features from FPIES: Malabsorption with steatorrhea in 80% Lack of acute symptoms

  40. FPE Diagnosis Overlap with other enteropathies, e.g. celiac Endoscopy with biopsy to confirm villus injury with a cellular infiltrate Generally resolves spontaneously after age 2

  41. FPE Management: Food elimination Symptoms clear in 1-3 wk Rechallenge in 1-2 yr

  42. Common GI Problems & Food Allergy

  43. GERD • A subset of infants with GERD can have CM allergy • More likely in pts with severe and persistent regurgitation, FTT, and eczema .

  44. GERD (cont’d) 204 infants diagnosed with GERD based on 24 h pH monitoring and histology CM free diet and two successive blind challenges confirmed CM allergy in 41.8% pts with GERD Giuseppe lacono, et al,Journal of Allergy ClinImmunol. 1996

  45. GERD (cont’d) Empiric trial of CM elimination for infants with problematic GERD can be considered Especially, those with gross or occult blood in stool, eczema, or a strong FHx of atopy

  46. Colic • A subgroup of infants with colic can have intolerance to CM • Specially, those with bloody stool, vomiting, and eczema • The transient nature of colic make the investigations of effect of diet restrictions difficult David J. Pediatrics 2005

  47. Constipation • 10 prospective clinical trials reported a CM protein free diet success rate 28-78% • More likely in pts with coexistent atopy • More likely to have anal fissures, perianal erythema and/or eczema Caubet et al. Pediatric Allergy and Immunology,2016

  48. Constipation and cow’s milk allergy: a review of the literature MiceliSopo S, et al. Int Arch Allergy Immunol. 2014 “We believe that a CM-free diet for 2-4 wk should be proposed for children with chronic functional constipation, even if it is not severe or resistant to laxatives”

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