Gastrointestinal manifestations during oral immunotherapy: A guide for pediatric allergists

Oral immunotherapy (OIT) is a promising therapeutic strategy for desensitizing patients with immunoglobulin E (IgE)-mediated food allergies. Although effective, OIT is frequently associated with adverse events (AEs), and gastrointestinal (GI) manifestations are among the most common and challenging AEs, which are the leading cause of OIT discontinuation. These reactions range from immediate IgE-mediated signs and symptoms to delayed, non-IgE-mediated, eosinophil-associated disorders, including eosinophilic esophagitis (EoE). While systemic reactions, such as anaphylaxis, are well-known concerns, GI manifestations are frequently encountered, although they are often less severe than systemic reactions. A thorough understanding of GI signs and symptoms is therefore essential for patients and clinicians to navigate OIT effectively. This narrative review provides a comprehensive overview of GI AEs observed during OIT, detailing their clinical presentation, underlying pathophysiology, and evidence-based management approaches. A clear understanding of these manifestations and their management is essential for optimizing patient safety and treatment adherence in the era of OIT.