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Food Protein-Induced Enterocolitis Syndrome: a Comprehensive Review

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Abstract

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that has been well-characterized clinically, yet it is still poorly understood. Acute FPIES is characterized by vomiting 1–4 h and/or diarrhea within 24 h after ingestion of a culprit food. Chronic FPIES is the result of chronic exposure to an offending food that can result in chronic watery diarrhea, intermittent vomiting, and failure to thrive. FPIES typically presents in infancy and self-resolves by school age in most patients. Adult-onset FPIES is rare, but it has been reported. Cow’s milk and soy are the most common triggering foods in infants in the US, and as solids are introduced in the diet, FPIES reactions to grains (rice, oat) increase in prevalence. Variability in common trigger foods exists depending on the geographical origin—for example, fish is a frequent trigger in Spanish and Italian patients. Heavy reliance on a detailed history is required for the diagnosis as physical exam findings, laboratory tests, and/or imaging studies are suggestive and not specific for FPIES. Oral food challenges remain the gold standard for confirming diagnosis, and the challenge protocol may be for an individual depending on risk of reaction, prior reaction severity, and positive-specific IgE status. The recent development of diagnostic criteria in 2017 will serve to increase recognition of the disorder and allow for early implementation of management strategies. Acute management during reactions includes IV hydration, anti-emetics, and IV corticosteroids. Reaction prevention strategies include strict food avoidance until the physician deems a food reintroduction challenge clinically appropriate. Future efforts in FPIES research should be aimed at elucidating the underlying disease mechanisms and possible treatment targets.

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Abbreviations

CM:

cow’s milk

FPIES:

food protein-induced enterocolitis syndrome

sIgE:

specific IgE

OFC:

oral food challenge

References

  1. Nowak-Wegrzyn A, Chehade M, Groetch ME et al (2017) International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: executive summary-workgroup report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 139:1111–1126 e4

    PubMed  Google Scholar 

  2. Nowak-Wegrzyn A, Katz Y, Mehr SS, Koletzko S (2015) Non-IgE-mediated gastrointestinal food allergy. J Allergy Clin Immunol 135:1114–1124

    CAS  PubMed  Google Scholar 

  3. Powell GK (1976) Enterocolitis in low-birth-weight infants associated with milk and soy protein intolerance. J Pediatr 88:840–844

    CAS  PubMed  Google Scholar 

  4. Powell GK (1978) Milk- and soy-induced enterocolitis of infancy. J Pediatr 93:553–560

    CAS  PubMed  Google Scholar 

  5. Sicherer SH, Eigenmann PA, Sampson HA (1998) Clinical features of food-protein-induced enterocolitis syndrome. J Pediatr 133:214–219

    CAS  PubMed  Google Scholar 

  6. Ruffner MA, Ruymann K, Barni S, Cianferoni A, Brown-Whitehorn T, Spergel JM (2013) Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract 1:343–349

    PubMed  Google Scholar 

  7. Mehr S, Kakakios A, Frith K, Kemp AS (2009) Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics 123:e459–ee64

    PubMed  Google Scholar 

  8. Caubet JC, Ford LS, Sickles L, Järvinen KM, Sicherer SH, Sampson HA, Nowak-Węgrzyn A (2014) Clinical features and resolution of food protein-induced enterocolitis syndrome: 10-year experience. J Allergy Clin Immunol 134:382–389

    PubMed  Google Scholar 

  9. Weinberger T, Feuille E, Thompson C, Nowak-Wegrzyn A (2016) Chronic food protein-induced enterocolitis syndrome: characterization of clinical phenotype and literature review. Ann Allergy Asthma Immunol 117:227–233

    PubMed  Google Scholar 

  10. Hwang JB, Lee SH, Kang YN, Kim SP, Suh SI, Kam S (2007) Indexes of suspicion of typical cow's milk protein-induced enterocolitis. J Korean Med Sci 22:993–997

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Nowak-Wegrzyn A, Jarocka-Cyrta E, Moschione Castro A (2017) Food protein-induced enterocolitis syndrome. J Investig Allergol Clin Immunol 27:1–18

    CAS  PubMed  Google Scholar 

  12. Katz Y, Goldberg MR, Rajuan N, Cohen A, Leshno M (2011) The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: a large-scale, prospective population-based study. J Allergy Clin Immunol 127:647–653

    CAS  PubMed  Google Scholar 

  13. Mehr S, Frith K, Barnes EH, Campbell DE (2017) Food protein induced enterocolitis syndrome in Australia: a population based study 2012–2014. J Allergy Clin Immunol 140:1323–1330

    PubMed  Google Scholar 

  14. Nowak-Wegrzyn A, Spergel JM (2017) Food protein-induced enterocolitis syndrome: not so rare after all! J Allergy Clin Immunol 140:1275–1276

    PubMed  Google Scholar 

  15. Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH (2003) Food protein-induced enterocolitis syndrome caused by solid food proteins. Pediatrics 111:829–835

    PubMed  Google Scholar 

  16. Katz Y, Goldberg MR (2014) Natural history of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol 14:229–239

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Sopo SM, Giorgio V, Dello Iacono I, Novembre E, Mori F, Onesimo R (2012) A multicentre retrospective study of 66 Italian children with food protein-induced enterocolitis syndrome: different management for different phenotypes. Clin Exp Allergy 42:1257–1265

    PubMed  Google Scholar 

  18. Fernandes BN, Boyle RJ, Gore C, Simpson A, Custovic A (2012) Food protein-induced enterocolitis syndrome can occur in adults. J Allergy Clin Immunol 130:1199–1200

    PubMed  Google Scholar 

  19. Tan JA, Smith WB (2014) Non-IgE-mediated gastrointestinal food hypersensitivity syndrome in adults. J Allergy Clin Immunol Pract 2:355–7 el

    PubMed  Google Scholar 

  20. Gleich GJ, Sebastian K, Firszt R, Wagner LA (2015) Shrimp allergy: gastrointestinal symptoms commonly occur in the absence of IgE sensitization. J Allergy Clin Immunol Pract 4:316–318

    PubMed  Google Scholar 

  21. Tan J, Campbell D, Mehr S (2012) Food protein-induced enterocolitis syndrome in an exclusively breast-fed infant—an uncommon entity. J Allergy Clin Immunol 129:873 author reply—4

    PubMed  Google Scholar 

  22. Monti G, Castagno E, Liguori SA, Lupica MM, Tarasco V, Viola S, Tovo PA (2011) Food protein-induced enterocolitis syndrome by cow's milk proteins passed through breast milk. J Allergy Clin Immunol 127:679–680

    PubMed  Google Scholar 

  23. Nomura I, Morita H, Hosokawa S, Hoshina H, Fukuie T, Watanabe M, Ohtsuka Y, Shoda T, Terada A, Takamasu T, Arai K, Ito Y, Ohya Y, Saito H, Matsumoto K (2011) Four distinct subtypes of non-IgE-mediated gastrointestinal food allergies in neonates and infants, distinguished by their initial symptoms. J Allergy Clin Immunol 127:685–8 el-8

    CAS  PubMed  Google Scholar 

  24. Mehr SS, Kakakios AM, Kemp AS (2009) Rice: a common and severe cause of food protein-induced enterocolitis syndrome. Arch Dis Child 94:220–223

    CAS  PubMed  Google Scholar 

  25. Miceli Sopo S, Monaco S, Badina L et al (2015) Food protein-induced enterocolitis syndrome caused by fish and/or shellfish in Italy. Pediatr Allergy Immunol 26:731–736

    PubMed  Google Scholar 

  26. Vila L, Garcia V, Rial MJ, Novoa E, Cacharron T (2015) Fish is a major trigger of solid food protein-induced enterocolitis syndrome in Spanish children. J Allergy Clin Immunol Pract 3:621–623

    PubMed  Google Scholar 

  27. Richards DG, Somers S, Issenman RM, Stevenson GW (1988) Cow's milk protein/soy protein allergy: gastrointestinal imaging. Radiology 167:721–723

    CAS  PubMed  Google Scholar 

  28. Holbrook T, Keet CA, Frischmeyer-Guerrerio PA, Wood RA (2013) Use of ondansetron for food protein-induced enterocolitis syndrome. J Allergy Clin Immunol 132:1219–1220

    PubMed  Google Scholar 

  29. Miceli Sopo S, Battista A, Greco M, Monaco S (2014) Ondansetron for food protein-induced enterocolitis syndrome. Int Arch Allergy Immunol 164:137–139

    CAS  PubMed  Google Scholar 

  30. Caubet JC, Bencharitiwong R, Ross A, Sampson HA, Berin MC, Nowak-Wegrzyn A (2016) Humoral and cellular responses to casein in patients with food protein-induced enterocolitis to cow’s milk. J Allergy Clin Immunol 139:572–583

    PubMed  Google Scholar 

  31. Chung HL, Hwang JB, Park JJ, Kim SG (2002) Expression of transforming growth factor beta1, transforming growth factor type I and II receptors, and TNF-alpha in the mucosa of the small intestine in infants with food protein-induced enterocolitis syndrome. J Allergy Clin Immunol 109:150–154

    CAS  PubMed  Google Scholar 

  32. Morita H, Nomura I, Orihara K, Yoshida K, Akasawa A, Tachimoto H, Ohtsuka Y, Namai Y, Futamura M, Shoda T, Matsuda A, Kamemura N, Kido H, Takahashi T, Ohya Y, Saito H, Matsumoto K (2013) Antigen-specific T-cell responses in patients with non-IgE-mediated gastrointestinal food allergy are predominantly skewed to T(H)2. J Allergy Clin Immunol 131:590–2 el-6

    CAS  PubMed  Google Scholar 

  33. Goswami R, Blazquez AB, Kosoy R, Rahman A, Nowak-Wegrzyn A, Berin MC (2017) Systemic innate immune activation in Food Protein Induced Enterocolitis Syndrome (FPIES). J Allergy Clin Immunol 139:1885–1896.e9

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Miceli Sopo S, Monaco S, Cerchiara G, Bersani G (2017) A very unusual case of food allergy, between FPIES and IgE-mediated food allergy. Eur Ann Allergy Clin Immunol 49:42–44

    CAS  PubMed  Google Scholar 

  35. Ludman S, Harmon M, Whiting D, du Toit G (2014) Clinical presentation and referral characteristics of food protein-induced enterocolitis syndrome in the United Kingdom. Ann Allergy Asthma Immunol 113:290–294

    PubMed  Google Scholar 

  36. Sicherer SH (2005) Food protein-induced enterocolitis syndrome: case presentations and management lessons. J Allergy Clin Immunol 115:149–156

    PubMed  Google Scholar 

  37. Nowak-Wegrzyn A, Assa'ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS (2009) Work group report: oral food challenge testing. J Allergy Clin Immunol 123:S365–SS83

    PubMed  Google Scholar 

  38. Fogg MI, Brown-Whitehorn TA, Pawlowski NA, Spergel JM (2006) Atopy patch test for the diagnosis of food protein-induced enterocolitis syndrome. Pediatr Allergy Immunol 17:351–355

    PubMed  Google Scholar 

  39. Jarvinen KM, Caubet JC, Sickles L, Ford LS, Sampson HA, Nowak-Wegrzyn A (2012) Poor utility of atopy patch test in predicting tolerance development in food protein-induced enterocolitis syndrome. Ann Allergy Asthma Immunol 109:221–222

    PubMed  PubMed Central  Google Scholar 

  40. Gonzalez-Delgado P, Caparros E, Moreno MV et al (2016) Clinical and immunological characteristics of a pediatric population with food protein-induced enterocolitis syndrome (FPIES) to fish. Pediatr Allergy Immunol 27:269–275

    PubMed  Google Scholar 

  41. Hwang JB, Park MH, Kang YN, Kim SP, Suh SI, Kam S (2007) Advanced criteria for clinicopathological diagnosis of food protein-induced proctocolitis. J Korean Med Sci 22:213–217

    PubMed  PubMed Central  Google Scholar 

  42. Genere L, Pecciarini N, Peretti N, Villard F, Lachaux A (2017) Food protein-induced enterocolitis syndrome: a case report of diarrhea with hypovolemic shock and methemoglobinemia. Arch Pediatr 24:28–32

    CAS  PubMed  Google Scholar 

  43. Murray KCD (1993) Dietary protein intolerance in infants with transient methemoglobinemia and diarrhea. J Pediatr 122:90–92

    CAS  PubMed  Google Scholar 

  44. Hwang JB, Song JY, Kang YN, Kim SP, Suh SI, Kam S, Choi WJ (2008) The significance of gastric juice analysis for a positive challenge by a standard oral challenge test in typical cow's milk protein-induced enterocolitis. J Korean Med Sci 23:251–255

    PubMed  PubMed Central  Google Scholar 

  45. Gryboski J (1967) Gastrointestinal milk allergy in infancy. Pediatrics 40:354–362

    CAS  PubMed  Google Scholar 

  46. Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, Nadeau K, Nowak-Wegrzyn A, Oppenheimer J, Perry TT, Randolph C, Sicherer SH, Simon RA, Vickery BP, Wood R, Sampson HA, Randolph C, Bernstein D, Blessing-Moore J, Khan D, Lang D, Nicklas R, Oppenheimer J, Portnoy J, Randolph C, Schuller D, Spector S, Tilles SA, Wallace D, Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, Nadeau K, Nowak-Wegrzyn A, Oppenheimer J, Perry TT, Randolph C, Sicherer SH, Simon RA, Vickery BP, Wood R (2014) Food allergy: a practice parameter update—2014. J Allergy Clin Immunol 134:1016–25 e43

    PubMed  Google Scholar 

  47. Miceli Sopo S, Bersani G, Monaco S, Cerchiara G, Lee E, Campbell D, Mehr S (2017) Ondansetron in acute food protein-induced enterocolitis syndrome, a retrospective case-control study. Allergy 72:545–551

    CAS  PubMed  Google Scholar 

  48. Leonard SA, Nowak-Wegrzyn A (2015) Food protein-induced enterocolitis syndrome. Pediatr Clin N Am 62:1463–1477

    Google Scholar 

  49. Sopo SM, Iacono ID, Greco M, Monti G (2014) Clinical management of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol 14:240–245

    Google Scholar 

  50. Miceli Sopo S, Buonsenso D, Monaco S, Crocco S, Longo G, Calvani M (2013) Food protein-induced enterocolitis syndrome (FPIES) and well cooked foods: a working hypothesis. Allergol Immunopathol 41:346–348

    CAS  Google Scholar 

  51. Hwang JB, Sohn SM, Kim AS (2009) Prospective follow-up oral food challenge in food protein-induced enterocolitis syndrome. Arch Dis Child 94:425–428

    PubMed  Google Scholar 

  52. Groetch M, Nowak-Wegrzyn A (2013) Practical approach to nutrition and dietary intervention in pediatric food allergy. Pediatr Allergy Immunol 24:212–221

    PubMed  Google Scholar 

  53. Groetch M, Henry M, Feuling MB, Kim J (2013) Guidance for the nutrition management of gastrointestinal allergy in pediatrics. J Allergy Clin Immunol Pract 1:323–331

    PubMed  Google Scholar 

  54. Michelet M, Schluckebier D, Petit LM, Caubet JC (2017) Food protein-induced enterocolitis syndrome—a review of the literature with focus on clinical management. Journal of Asthma and Allergy 10:197–207

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Nowak-Wegrzyn A, Groetch M (2015) Nutritional aspects and diets in food allergy. Chem Immunol Allergy 101:209–220

    CAS  PubMed  Google Scholar 

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Agyemang, A., Nowak-Wegrzyn, A. Food Protein-Induced Enterocolitis Syndrome: a Comprehensive Review. Clinic Rev Allerg Immunol 57, 261–271 (2019). https://doi.org/10.1007/s12016-018-8722-z

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