Skip to main content

Advertisement

SpringerLink
Log in

Management of Food Protein-Induced Enterocolitis Syndrome (FPIES): Current Approach and Future Needs

  • Food Allergy (M Fernández-Rivas, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Opinion Statement

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE, cell-mediated food allergic gastrointestinal disorder triggered by ingestion of food proteins (cow milk, soy, rice, oat, egg, and others). The acute FPIES begins approximately 1–4 h after food ingestion with profuse, repetitive emesis that is accompanied by lethargy and pallor and may be followed later by diarrhea; 15% will require hospitalization because of hypotension and hemodynamic instability due to severe dehydration. A chronic FPIES is less frequent and develops from few days to 4 weeks after the offending food has been introduced and fed daily. Chronic FPIES presents with intermittent emesis, bloody diarrhea, dehydration, weight loss, and failure to thrive and has been only reported in young infants fed with cow’s milk and soy-based formulas. Acute FPIES to seafood has been reported in older children and in adults. The majority of patients react to a single food; however, FPIES can be triggered by more than one food, especially between cow milk/soy and rice/oats.

Diagnosis of FPIES is based on the recognition of clinical manifestations, exclusion of alternative etiologies, and a physician-supervised oral food challenge (OFC). OFC is the gold standard; however, most patients do not need to undergo confirmatory OFC, especially if they have a history of severe reactions and become asymptomatic following elimination of the suspected food from diet until tolerance through OCF is proven. Management of FPIES is based on elimination of the trigger food in the diet, medical treatment of acute reactions due accidental exposure (intravenous hydration, methylprednisolone, ondansetron), nutritional counseling regarding avoidance of trigger foods, and introduction of the complementary foods and periodic oral food challenges to evaluate for resolution. The first international consensus guidelines on diagnosis and management of FPIES published in 2017 provide practical support for the providers caring for patients with FPIES.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

FPIES:

Food protein-induced enterocolitis syndrome

IgE:

Immunoglobulin E

OFC:

Oral food challenge

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

  1. •• Nowak-Wegrzyn A, Chehade M, Groetch M, Spergel JM, Wood RA, Allen K, et al. 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. 2017;139:1111–1126e4. These are the first FPIES guidelines providing practical recomenbations for the care providesr of patients with FPIES.

    Article  PubMed  Google Scholar 

  2. Gryboski J, Burkle F, Hillman R. Milk induced colitis in an infant. Pediatrics. 1966;38:299–302.

    CAS  PubMed  Google Scholar 

  3. Powell GK. Enterocolitis in low-birth-weight infants associated with milk and soy protein intolerance. J Pediatr. 1976;88:840–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Caubet JM, Ford FL, Sickles L, Järvinen KM, Sicherer SH, Sampson HA, et al. Clinical features and resolution of food protein-induced enterocolitis syndrome: 10-year experience. J Allergy Clin Immunol. 2014;134:382–9.

    Article  PubMed  Google Scholar 

  6. Pecora V, Prencipe G, Valluzzi R, Dahdah L, Insalaco A, Cianferoni A, et al. Inflammatory events during food protein-induced enterocolitis syndrome reactions. Pediatr Allergy Immunol. 2017; doi:10.1111/pai.12723.

  7. Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014;134:1016–1025 e1043.

    Article  PubMed  Google Scholar 

  8. Ruffner MA, Ruymann K, Barni S, Cianferoni A, Brown-Whitehorn T, Spergel JM. Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract. 2013;1:343–9.

    Article  PubMed  Google Scholar 

  9. • Katz Y, Goldberg MR, Rajuan N, Cohen A, Leshno M. 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. 2011;127:647–53. This is the first study of FPIES cumulative incidence on a birth cohort from a single hospital in Israel

    Article  CAS  PubMed  Google Scholar 

  10. Ludman S, Harmon M, Whiting D, du Toit G. Clinical presentation and referral characteristics of food protein-induced enterocolitis syndrome in the United Kingdom. Ann Allergy Asthma Immunol. 2014;113:290–4.

    Article  PubMed  Google Scholar 

  11. • Mehr S, Frith K, Barnes EH, Campbell DE. Food protein induced enterocolitis syndrome in Australia: a population based study 2012–2014. J Allergy Clin Immunol. 2017; doi:10.1016/j.jaci.2017.03.027. This is the first population-based study of FPIES incidence in Australia

  12. Fernandes BN, Boyle RJ, Gore C, Simpson A, Custovic A. Food protein-induced enterocolitis syndrome can occur in adults. J Allergy Clin Immunol. 2012;130:1199–200.

    Article  PubMed  Google Scholar 

  13. Gleich GJ, Sebastian K, Firszt R, Wagner LA. Shrimp allergy: gastrointestinal symptoms commonly occur in the absence of IgE sensitization. J Allergy Clin Immunol Pract. 2015;4:316–8.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  15. Miceli Sopo S, Monaco S, Badina L, Barni S, Longo G, Novembre E, et al. Food protein-induced enterocolitis syndrome caused by fish and/or shellfish in Italy. Pediatr Allergy Immunol. 2015;26:731–6.

    Article  PubMed  Google Scholar 

  16. Gonzalez-Delgado P, Caparros E, Moreno MV, Clemente F, Flores E, Velasquez L, et al. Clinical and immunological characteristics of a pediatric population with food protein-induced enterocolitis syndrome (FPIES) to fish. Pediatr Allergy Immunol. 2016;27:269–75.

    Article  PubMed  Google Scholar 

  17. • Weinberger T, Feuille E, Thompson C, Nowak-Wegrzyn A. Chronic food protein-induced enterocolitis syndrome: characterization of clinical phenotype and literature review. Ann Allergy Asthma Immunol. 2016;117:227–33. This is a review of chronic FPIES presentation

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Nomura I, Morita H, Ohya Y, Saito H, Matsumoto K. Non-IgE-mediated gastrointestinal food allergies: distinct differences in clinical phenotype between western countries and Japan. Curr Allergy Asthma Rep. 2012;12:297–303.

    Article  CAS  PubMed  Google Scholar 

  20. Morita H, Nomura I, Matsuda A, Saito H, Matsumoto K. Gastrointestinal food allergy in infants. Allergol Int. 2013;62:297–307.

    Article  CAS  PubMed  Google Scholar 

  21. Mehr S, Kakakios A, Frith K, Kemp AS. Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics. 2009;123:e459–64.

    Article  PubMed  Google Scholar 

  22. Mehr SS, Kakakios AM, Kemp AS. Rice: a common and severe cause of food protein-induced enterocolitis syndrome. Arch Dis Child. 2009;94:220–3.

    Article  CAS  PubMed  Google Scholar 

  23. Sopo SM, Giorgio V, Dello Iacono I, Novembre E, Mori F, Onesimo R. A multicentre retrospective study of 66 Italian children with food protein-induced enterocolitis syndrome: different management for different phenotypes. Clin Exp Allergy. 2012;42:1257–65.

    Article  PubMed  Google Scholar 

  24. Katz Y, Goldberg MR. Natural history of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol. 2014;14:229–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hwang JB, Lee SH, Kang YN, Kim SP, Suh SI, Kam S. Indexes of suspicion of typical cow’s milk protein-induced enterocolitis. J Korean MedSci. 2007;22:993–7.

    Article  CAS  Google Scholar 

  26. Nomura, I., Morita, H., Hosokawa, S., Hoshina, H., Fukuie, T., Watanabe, M., Ohtsuka, Y., Shoda, T., Terada, A., Takamasu, T., et al. 2011. Four distinct subtypes of non-IgE-mediated gastrointestinal food allergies in neonates and infants, distinguished by their initial symptoms. J Allergy Clin Immunol 127:685–688 e681–688.

  27. Kimura M, Shimomura M, Morishita H, Meguro T. Prognosis of infantile food protein-induced enterocolitis syndrome in Japan. Pediatr Int. 2017; doi:10.1111/ped.13305.

  28. Sicherer SH, Eigenmann PA, Sampson HA. Clinical features of food-protein-induced entercolitis syndrome. J Pediatr. 1998;133:214–9.

    Article  CAS  PubMed  Google Scholar 

  29. Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH. Food protein-induced enterocolitis syndrome caused by solid food proteins. Pediatrics. 2003;111:829–35.

    Article  PubMed  Google Scholar 

  30. Lee, E., Campbell, D.E., Barnes, E.H., and Mehr, S.S. 2017. Resolution of acute food protein-induced enterocolitis syndrome in children. J Allergy Clin Immunol Pract 5:486–488 e481.

  31. Miceli Sopo S, Buonsenso D, Monaco S, Crocco S, Longo G, Calvani M. Food protein-induced enterocolitis syndrome (FPIES) and well cooked foods: a working hypothesis. Allergol Immunopathol (Madr). 2013;41:346–8.

    Article  CAS  Google Scholar 

  32. Sopo SM, Iacono ID, Greco M, Monti G. Clinical management of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol. 2014;14:240–5.

    Article  Google Scholar 

  33. Tan, J., Campbell, D., and 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 873-874.

  34. Hwang JB, Sohn SM, Kim AS. Prospective follow-up oral food challenge in food protein-induced enterocolitis syndrome. Arch Dis Child. 2009;94:425–8.

    Article  PubMed  Google Scholar 

  35. Mane, S.K., Hollister, M.E., and Bahna, S.L. 2013. Food protein-induced enterocolitis syndrome to trivial oral mucosal contact. Eur J Pediatr.

  36. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol. 2010;126:1105–18.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Delaney AL, Arvedson JC. Development of swallowing and feeding: prenatal through first year of life. Dev Disabil Res Rev. 2008;14:105–17.

    Article  PubMed  Google Scholar 

  38. Mennella JA, Castor SM. Sensitive period in flavor learning: effects of duration of exposure to formula flavors on food likes during infancy. Clin Nutr. 2012;31:1022–5.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mennella JA, Lukasewycz LD, Castor SM, Beauchamp GK. The timing and duration of a sensitive period in human flavor learning: a randomized trial. Am J Clin Nutr. 2011;93:1019–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Beauchamp GK, Mennella JA. Early flavor learning and its impact on later feeding behavior. J Pediatr Gastroenterol Nutr. 2009;48(Suppl 1):S25–30.

    Article  PubMed  Google Scholar 

  41. Mennella JA, Nicklaus S, Jagolino AL, Yourshaw LM. Variety is the spice of life: strategies for promoting fruit and vegetable acceptance during infancy. Physiol Behav. 2008;94:29–38.

    Article  CAS  PubMed  Google Scholar 

  42. Forestell CA, Mennella JA. Early determinants of fruit and vegetable acceptance. Pediatrics. 2007;120:1247–54.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Northstone K, Emmett P, Nethersole F, Team AS. The effect of age of introduction to lumpy solids on foods eaten and reported feeding difficulties at 6 and 15 months. J Hum Nutr Diet. 2001;14:43–54.

    Article  CAS  PubMed  Google Scholar 

  44. Greenhawt M, Schultz F, DunnGalvin A. A validated index to measure health-related quality of life in patients with food protein-induced enterocolitis syndrome. J Allergy Clin Immunol. 2016;137(1251–1253):e1251–5.

    Article  Google Scholar 

  45. Schultz F, Westcott-Chavez A. Food protein-induced enterocolitis syndrome from the parent perspective. Curr Opin Allergy Clin Immunol. 2014;14:263–7.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sicherer SH. Food protein-induced entercolitis syndrome: clinical perspectives. J Pediatr Gastroenterol Nutr. 2000;30:45–9.

    Article  Google Scholar 

  47. Holbrook T, Keet CA, Frischmeyer-Guerrerio PA, Wood RA. Use of ondansetron for food protein-induced enterocolitis syndrome. J Allergy Clin Immunol. 2013;132:1219–20.

    Article  PubMed  Google Scholar 

  48. Sopo SM, Battista A, Greco M, Monaco S. Ondansetron for food protein-induced enterocolitis syndrome. Int Arch Allergy Immunol. 2014;164:137–9.

    Article  Google Scholar 

  49. Kimura M, Ito Y, Tokunaga F, Meguro T, Shimomura M, Morishita H, et al. Increased C-reactive protein and fever in Japanese infants with food protein-induced enterocolitis syndrome. Pediatr Int. 2016;58:826–30.

    Article  CAS  PubMed  Google Scholar 

  50. Kimura M, Shimomura M, Morishita H, Meguro T, Seto S. Serum C-reactive protein in food protein-induced enterocolitis syndrome versus food protein-induced proctocolitis in Japan. Pediatr Int. 2016;58:836–41.

    Article  CAS  PubMed  Google Scholar 

  51. Eigenmann, P.A., Sicherer, S.H., Borkowski, T.A., Cohen, B.A., and Sampson, H.A. 1998. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics 101:E8.

  52. Nowak-Wegrzyn A, Assa'ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS. Work group report: oral food challenge testing. J Allergy Clin Immunol. 2009;123:S365–83.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Gastroenterology and Nutrition, Children’s Hospital, University of Warmia and Masuria, Olsztyn, Poland

    Elżbieta Jarocka-Cyrta

  2. Allergy Department, University Hospital Fundación Jimenez Diaz, Madrid, Spain

    Marcela Valverde-Monge

  3. Department of Pediatrics, Division of Allergy and Immunology, Kravis Children’s Hospital, Icahn School of Medicine at Mount Sinai, Jaffe Food Allergy Institute, New York, NY, USA

    Anna Nowak-Węgrzyn

Authors
  1. Elżbieta Jarocka-Cyrta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcela Valverde-Monge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Nowak-Węgrzyn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Nowak-Węgrzyn.

Ethics declarations

Conflict of Interest

Dr. Elżbieta Jarocka-Cyrta declares that she has no conflict of interest. Dr. Marcela Valverde-Monge declares that she has no conflict of interest. Dr. Anna Nowak-Węgrzyn declares speaking for and receiving a research grant for wheat OIT molecular diagnosis from Thermo Fisher Scientific.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Food Allergy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jarocka-Cyrta, E., Valverde-Monge, M. & Nowak-Węgrzyn, A. Management of Food Protein-Induced Enterocolitis Syndrome (FPIES): Current Approach and Future Needs. Curr Treat Options Allergy 4, 383–394 (2017). https://doi.org/10.1007/s40521-017-0141-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40521-017-0141-5

Keywords

Search

Navigation