Non-immunoglobulin E-mediated food allergy

Abstract

Non-immunoglobulin E (IgE)-mediated food allergies are characterized by delayed gastrointestinal (GI) manifestations that occur after exposure to an inciting food protein; they include food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and food protein-induced enterocolitis syndrome (FPIES). Although the exact mechanisms underlying these disorders are not well understood, non-IgE-mediated food allergies likely represent a spectrum of disease with shared pathophysiological processes. Typically, these non-IgE-mediated food allergies begin in infancy or early childhood, although FPIES can present across the lifespan, with increasing reports in adults in recent years. Diagnosing non-IgE-mediated food allergies can be challenging due to the lack of noninvasive confirmatory tests or biomarkers for most of these disorders and the non-specific nature of GI symptoms. Thus, the diagnosis is usually made clinically, and relies on a constellation of typical symptoms that improve upon removal of the culprit food. The primary approach to management of FPIAP, FPE and FPIES is avoidance of the triggering food, and a multidisciplinary management approach that includes allergy/immunology may be required to avoid unnecessary food restriction and guide food reintroduction. This review outlines the clinical manifestations, epidemiology, pathophysiology, diagnosis, management, and prognosis of these non-IgE-mediated food allergies.

Fig. 1

Algorithm for the diagnosis and management of FPIAP. Images in figure are taken from the FPIAP handout (see supplementary appendix). The complete handout is also available at https://www.allergyvic.com/qi-project. The FPIAP handout was generated by: Francesca Reinbolt, Delane Peters & Dr. Scott Cameron, and updated by Matt Griffin, Dr. Victoria Cook & Dr. Scott Cameron in October 2024. FOB fecal occult blood, FPE food protein-induced enteropathy, FPIES food protein-induced enterocolitis syndrome, FPIAP food-protein-induced allergic proctocolitis, IgE immunoglobulin E, WBC white blood cell count

Fig. 2

Algorithm for the diagnosis and management of FPE. Images in figure are taken from the FPIAP handout (see supplementary appendix). The complete handout is also available at https://www.allergyvic.com/qi-project. The FPIAP handout was generated by: Francesca Reinbolt, Delane Peters & Dr. Scott Cameron, and updated by Matt Griffin, Dr. Victoria Cook & Dr. Scott Cameron in October 2024. FPE food protein-induced enteropathy, FPIES food protein-induced enterocolitis syndrome, IgE immunoglobulin E, TPN total parenteral nutrition

Fig. 3

Algorithm for the diagnosis and management of FPIES. FPIES food protein-induced enterocolitis syndrome, IgE immunoglobulin E, ED emergency department,  IM, intramuscular, IV intravenous, PO oral, SL sublingual, PRN as needed

Fig. 4

Example of pediatric ED letter. Letter adapted by Dr. Victoria Cook based on ED letter (for children) available on the International FPIES Association website at https://fpies.org/ (see “Resources” section)