Non-IgE-Mediated Gastrointestinal Food Allergies in Children

Non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs) encompass a spectrum of disorders, including food protein-induced allergic proctocolitis (FPIAP), acute and chronic food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy (FPE), and food protein-induced motility disorders (FPIMDs). Cow’s milk, soy, and wheat are the three most common trigger foods. The pathogenesis of these disorders remains poorly understood, and diagnostic markers are still lacking. The results of the skin prick test or measurement of the food-specific serum IgE level is generally negative although positive results may occur in some form, e.g., “atypical” FPIES. Therefore, the diagnosis relies on the demonstration of clear clinical improvement after food allergen elimination and the reemergence of symptoms upon challenge. Non-IgE-GI-FAs may overlap in terms of clinical and histologic features among themselves and with eosinophilic gastroenteropathies, which makes diagnosis challenging in clinical practice. The treatment requires the elimination of offending food allergens until tolerance has developed. In breastfed infants, a maternal avoidance diet is sufficient to control symptoms in most cases. In formula-fed infants, treatment usually involves the use of an extensively hydrolyzed or amino acid-based formula in more severe cases. Generally, non-IgE-GI-FAs have a favorable prognosis; the majority resolve by 1 year in patients with FPIAP, 1–3 years in patients with FPE, and 1–5 years in patients with FPIES, with significant differences regarding specific foods. There is an urgent need to better define the prevalence and natural history of FPIES and the pathogenesis of non-IgE-GI-FAs in order to identify useful diagnostic markers.