- Non-immunoglobulin E (IgE)-mediated food hypersensitivity includes a spectrum of disorders that predominantly affect the gastrointestinal tract. This review will focus on the following more common non-IgE-mediated food hypersensitivity syndromes: food protein-induced enterocolitis syndrome (FPIES), allergic proctocolitis (AP), food protein-induced enteropathy (FPE) and celiac disease. FPIES, AP and FPE typically present in infancy and are most commonly triggered by cow’s milk protein or soy. The usual presenting features are profuse emesis and dehydration in FPIES; blood-streaked and mucousy stools in AP; and protracted diarrhea with malabsorption in FPE. Since there are no confirmatory noninvasive diagnostic tests for most of these disorders, the diagnosis is based on a convincing history and resolution of symptoms with food avoidance. The mainstay of management for FPIES, AP and FPE is avoidance of the suspected inciting food, with periodic oral food challenges to assess for resolution, which generally occurs in the first few years of life. Celiac disease is an immune-mediated injury caused by the ingestion of gluten that leads to villous atrophy in the small intestine in genetically susceptible individuals. Serologic tests and small intestinal biopsy are required to confirm the diagnosis of celiac disease, and management requires life-long adherence to a strict gluten-free diet.