FPIES Journal Articles


I believe that being familiar with the scientific literature about FPIES is the best tool we have in understanding and caring for our children with these allergies.  While the literature is fairly limited, there are some great papers available and the database is growing.  This page contains the citations and links to the studies/reviews that I have found along with some bullet points so that you know what you will find in the article.  I will try to organize it so that the most recent and helpful papers are toward the top of list (which is why I left some numbers blank, to be filled in later).  It is a work in progress so check back frequently and let me know if there are any papers that are missing.  I will also be citing these articles in some of my posts, so I will list the posts under the article.  I hope it is helpful to see how the scientific literature is reflected in our particular experiences (or to see where our experiences contradict the literature).  The links that are bolded are available online to the public, the others have be obtained through a library (feel free to contact me at cathybykowski at gmail dot com if you have trouble accessing a full text version).  Happy Reading!

Review Articles (Summaries of Original Studies)

4. Jarvinen, K.M., Nowak-Wegrzyn, A. (2013).  Food protein-induced enterocolitis sydrome (FPIES): Current management strategies and review of the literature.  Journal of Allergy and Clinical Immunology, 1, 317-322

  • Review of chronic, acute, milk/soy, and solid food FPIES
  • Provides description of common presentations via case examples
  • Reviews available tests including allergy tests, fecal tests, radiological studies, endoscopies, and oral food challenges
  • Offers some guidance for management of FPIES including introducing new foods, reintroducing trigger foods, and nutritional management
  • Cited in: Out of the Blue

5. Sopo, S. M., Iacono, I. D., Greco, M., & Monti, G.  (2014).  Clinical management of food protein-induced enterocolitis syndrome.  Current Opinion in Allergy and Clinical Immunology, 14, 240-245.

  • Review of current literature regarding management of FPIES, uses case studies to highlight key points
  • Outlines pharmacological treatment of acute reactions – IV fluids and steroids as needed.  Discuses research on epinephrine and Zofran.
  • Makes a case for complete avoidance of the allergen based on the high likelihood of outgrowing by age 5, the inability to define a threshold for reaction (and belief that it may be quite low), and the hypothesized mechanisms (involving T cells) suggests that heating the food (i.e., baking) would not break down the proteins enough to avoid recognition by the immune cells.
  • Provides guidance for introduction of new foods including the idea of challenging a mixture of at risk foods to determine if related foods are safe
  • Considers research on eliminating the allergens from the diet of the breastfeeding mother and concludes that it is only necessary if there is a clear relationship between the mother’s ingestion of the protein and the child’s reactions or if there is failure to thrive.
  • Suggests challenging cow’s milk between 18 and 24 months and other foods 12-18 months after the last reaction.  It is pointed out that skin prick test should be conducted prior to a challenge and an IgE protocol followed if there is any positive retain to the IgE test.
  • Cited in: Research Revelations

6.  Caubet, J. & Nowak-Wegrzyn, A. (2011). Current understanding of the immune mechanisms of food protein-induced enterocologis syndrome.  Expert Review of Clinical Immunology, 7, 317-327. 

  • Provides an overview of chronic and acute FPIES
  • Discusses pathology that may be seen on colonoscopy
  • Has a great, detailed section about immune/inflammatory cell involvement
  • Cited in: Hindsight is 20/20, Research Revelations, Food Trials and Tribulations

7. Feuille, E. & Nowak-Wegrzyn, A. (2014).  Definition, etiology, and diagnosis of food protein-induced enterocolitis syndrome.  Current Opinion in Allergy and Clinical Immunology, 14

  • Updated and very extensive review of pathophysiology
  • Discusses diagnosis, including the use of oral food challenges and patient’s history, and the lack of utility of atopy patch testing
  • Includes a detailed description of oral food challenge protocol and diagnostic criteria

8. Katz, Y. & Goldberg, M. R.  (2014).  Natural history of food protein-induced enterocolitis syndrome.  Current Opinion in Allergy and Clinical Immunology, 14, 229-239.

  • Review of studies on acute FPIES to determine the natural course of the syndrome
  • Contains very detailed tables of all FPIES studies (and case studies) by food – each table includes symptoms and outcomes
  • Most milk and soy cases were no longer reactive at age 3, though a recent large study reported most recover by age 5
  • Solid food FPIEs recover is usually much later, closer to age 5 (especially fish, shellfish, and egg)
  • The dose required for the first reaction tends to be much larger than doses required for subsequent reactions.
  • There are surprisingly high rates of FPIES “converting” to IgE allergies (especially for milk) but the mechanism is unclear

10. Nowak-Wegrzyn, A. & Muraro, A.  (2009).  Food protein-induced enterocolitis syndrome.  Current Opinion in Allergy and Clinical Immunology, 9, 371-377.

  • Includes great reference tables that aid in differential diagnosis (compared to other GI disorders),  describe the characteristics of acute and chronic FPIES to milk and soy as well as to solid foods, and oral food challenge protocol
  • Describes course of milk, soy, and solid food FPIES and some guidance for food introduction and avoidance in patients with FPIES
  • Summarizes findings of endoscopy in patients with FPIES as well as research on pathophysiology

13.  Sicherer, S.H.  (2005).  Food protein-induced enterocolitis syndrome: Case presentations and management lessons.  Journal of Allergy and Clinical Immunology, 115, 149-156.

  • Uses case presentations to highlight the symptoms, course, and treatment of milk and solid FPIES
  • Contains useful tables that are good references for acute/chronic FPIES symptoms, treatment options, and when to challenge.
  • Discusses the pathogenesis of FPIES as an immune disorder (allergy) rather than intolerance and describes research on the role of TNF-alpha in the pathogenesis of the disorder
  • Cited in: Research Revelations

15. Cianferoni, A. & Spergel, J.M.  (2009). Food allergy: Review, classification and diagnosis.  Allergology International, 58, 47-466.

  • A review of both IgE and non-IgE allergies (with more emphasis on IgE)
  • Discusses epidemiology, pathogenesis, and diagnosis
  • Includes information on therapies other than avoidance (sublingual immunotherapy, Chinese herbal therapy)

 16. van der Poel, L., Fox, A., duToit, G. (2009).  Food protein-induced enterocolitis syndrome (FPIES) : A review.  Current Allergy & Clinical Immunology, 22, 56-57  

  • Great article to take to your doctor!
  • Very short and to the point review of all of the information related to symptoms, differential diagnosis, and treatment of FPIES
  • Not a whole lot of details but you might find it a good starting point for learning about FPIES
  • Cited in: Research Revelations

17.  Leonard, S. A. & Nowak-Wegrzyn, A.  (2011).  Food protein-induced enterocolitis syndrome: An update on natural history and review of management.  Annals of Allergy, Asthma, & Immunology, 107, 95-101.

  • Review article of relevant literature through 2011
  • Discusses the differential diagnosis between FPIES and food protein-induced proctocolitis and food protein-induced enteropathy as well as GI virus and food poisoning
  • Provides a lot of detail regarding when and how to conduct an oral food challenge
  • Offers recommendations for management of FPIES (types of formulas and introducing solid foods)
  • Cited in: Research Revelations


Original Research Studies

105. Ruffner, M.A., Ruymann, K., Barni, S., Cianferoni, A., Brown-Whitehorn, T., & Spergel, J.M.  (2013).  Food protein-induced enterocolitis syndrome: Insights from review of a large referral population.  Journal of Allergy and Clinical Immunology: In Practice, 1, 343-349.

  • Reviews available prevalence data in the introduction
  • A retrospective study that describes the symptoms, allergy testing, demographics, and triggers of 462 patients at CHOP
  • Discusses the various criteria used by different centers to diagnose FPIES
  • This is the largest study published to date
  • Focuses more on acute FPIES reactions than chronic
  • Cited in: Hindsight is 20/20

106.  Caubert, J. C., Ford, L. S., Sickles, L., Jarvinen, K. M., Sicherer, S. H., Sampson, H. A., & Nowak-Wegrzyn, A.  (2014).  Clinical features and resolution of food protein-induced enterocolitis syndrome: 10-year experience.  Journal of Allergy and Clinical Immunology, in press.  

  • Combination prospective and retrospective study of 160 patients ages 6 months to 45 years(!) at Mount Sinai Allergy and Immunology Clinic
  • Food challenges were conducted a minimum of 12 months after reaction, some participants had multiple challenges to look for resolution, some patients underwent challenges to new foods that had been avoided as a precaution
  • Includes FPIES to milk, soy, and solids
  • Includes an interesting table that outlines the result of IgE tests for patients with milk FPIES who had positive IgE results and/or symptoms.
  • Median age for failed OFCs was significantly older (3.5) than for passed  (2.3)
  • The most serious reactions were to milk or soy, but there was also one serious reaction each to oat and wheat.
  • Concludes that FPIES typically resolves by age 5, but that the presence of positive IgE test usually results in a prolonged course.
  • Cited in: Research Revelations

108. Hwang, J.B., Sohn, S.M., & Kim, A.S. (2009). Prospective follow-up oral food challenge in food protein-induced enterocolitis syndrome.  Archives of Disease in Childhood, 94, 425-428.

  • Prospective research study to determine recommendations on oral food challenges in FPIES
  • Followed 23 patients with milk and/or soy FPIES (+2 patients who also had solid food FPIES) until over age 2
  • Soy was tolerated earlier (by 14 months) than milk (20 months); recommended that soy be initially challenged at 6-8 months and milk over 12 months.
  • Cited in: Hindsight is 20/20, Research Revelations

109. Katz, Y., Goldberg, M.R., 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.   Journal of Allergy and Clinical Immunology, 127, 647-653.

  • Prospective study of 44 patients with FPIES to cow’s milk only in Israel
  • Describes onset of FPIES symptoms (age as well as number of days exposed to milk before reacting)
  • One of the most cited studies of recovery from cow’s milk FPIES
  • Cited in: Research Revelations

110. Nowak-Wegrzyn, A., Sampson, H.A., Wood, R.A., & Sicherer, S.H. (2003). Food protein-induced enterocolitis syndrome caused by solid food proteins.  Pediatrics, 111, 829-835.

  • One of the first studies to describe solid food FPIES
  • Followed 14 patients with solid food FPIES
  • Describes the high rates of multiple food FPIES as well as FPIES to foods traditionally considered hypoallergenic
  • Cited in: Hindsight is 20/20

111.  Mehr, S., Kakakios, A., Frith, K., & Kemp, A.  (2009). Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics, 123, e459-e464.

  • Retrospective study over a 16 year period of 35 patients in Australia
  • Focuses more on acute, rather than chronic reactions
  • Discusses triggers, symptoms of reactions, and loss of sensitivity over time (most by age 3).
  • One of the first to report decreased body temperature and thrombocytosis as part of a reaction.
  • Rice was most common trigger in the study and produced more severe reactions than cow’s milk or soy
  • Cited in: Out of the Blue, Research Revelations

112. Sicherer, S.H., Eigenmann, P.A., & Sampson, H.A.  (1998).  Clinical features of food protein-induced enterocolitis syndrome.  The Journal of Pediatrics, 133, 14-19.  

  • Outlines more recent (and liberal) criteria for FPIES that is often cited (less than 9 months of age, diarrhea/vomiting within 24 hours of ingestion of food, only GI symptoms, and removal of food leads to improved symptoms)
  • Provides individual data for 16 patients with FPIES to cow’s milk, soy, rice, pea, turkey, and chicken
  • Describes diagnosis of FPIES (primarily via oral food challenge) and follow-up data for recovery from FPIES
  • Also considers patients with atypical FPIES (older age of diagnosis, IgE-sensitivities)
  • Suggests that positive IgE tests in patients at presentation or follow-up indicate a prolonged course of FPIES
  • Cited in: Research Revelations

113.  Mehr, S. S., Kakakios, A. M., & Kemp, A. S. (2009).  Rice: A common and severe cause of food protein-induced enterocolitis syndrome.  Archives of Disease in Childhood, 94, 220-223.

  • A retrospective study of patients in Australia that compares rice FPIES to cow’s milk/soy FPIES
  • Rice was a more common trigger than milk and soy in this sample
  • Those with rice FPIES were more likely to have multiple allergens and tended to have more reactions before and FPIES diagnosis was made
  • Reactions to rice were more likely to require IV fluids, suggesting the rice reactions were more severe

4 thoughts on “FPIES Journal Articles

  1. Pingback: Food Trials & Tribulations | F U FPIES

  2. Pingback: A Breath of Fresh Air and Summer Sunshine | F U FPIES

  3. Pingback: Out of the Blue – Acute FPIES Reactions! | F U FPIES

  4. Pingback: Hindsight is 20/20: What I’ve Learned About Chronic FPIES | F U FPIES

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