The purpose of this review is to update what is currently known about the major non-IgE-mediated food allergies: food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). These conditions are similar in that symptoms are regulated to the gastrointestinal tract; therefore understanding their specific features is important for diagnosis and management.

The most progress has been made in understanding FPIES with several recent large cohorts being described. The first international consensus guidelines for FPIES were published in 2017 and propose specific diagnostic criteria for acute FPIES as well as guidance for diagnosing chronic FPIES. Recent studies in FPIAP have challenged our thinking about the recommended duration of food avoidance and that cow’s milk avoidance is the primary management with reports of self-resolution without dietary management. FPE continues to appear to be on the decline.

FPIES, FPIAP, and FPE are distinguished from one another by their main clinical features: delayed repetitive vomiting in FPIES, benign blood in stool in FPIAP, and chronic diarrhea in FPE. Due to the risk of nutritional deficiencies with food avoidance in both infant and maternal diets if breastfeeding, confirmation of diagnosis with challenges is encouraged. Additional studies are needed for these conditions to elucidate pathophysiology, search for diagnostic markers, and understand natural history.