Non-immunoglobulin E-mediated food allergy

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.