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Standardizing oral food challenge protocols in food protein-induced enterocolitis syndrome (FPIES): A call for consensus

Baker MG, Bird JA, Brown-Whitehorn T, Cosper A, Groetch M, Horak S, Leonard S, Scurlock AM et al.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2026

Abstract

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by delayed gastrointestinal symptoms. Oral food challenges (OFCs) are essential tools for confirming the diagnosis in uncertain cases and assessing resolution, yet the optimal procedure for conducting FPIES OFCs remains unknown. Current practice lacks standardization, with OFC protocols varying significantly across institutions and regions with regard to timing, IgE testing, intravenous access, dosing strategies, observation periods, and post-challenge guidance. Recent studies are paving a path toward FPIES OFC standardization. Emerging literature supports the safety and effectiveness of low-dose OFC protocols, with evidence indicating that administering 25% to 33% of an age-appropriate serving size can provoke symptoms in most individuals with persistent FPIES while reducing reaction severity. Furthermore, evidence suggests that the antiemetic ondansetron can ameliorate FPIES symptoms in some patients, potentially reducing the need for intravenous fluid resuscitation. Current gaps in FPIES literature include how to define positive OFCs after treatment with ondansetron, reaction severity classification, the role of corticosteroids in reaction management, and considerations related to atypical FPIES in diagnosis and OFC planning. Given the evolving literature, there is need for international consensus on updated FPIES OFC protocols. Ongoing initiatives, including multicenter…

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