Oral Food Challenge Protocols in Food Protein-Induced Enterocolitis Syndrome: A Systematic Review

BACKGROUND: Oral food challenges (OFCs) are essential for the diagnosis and follow-up of acute food protein-induced enterocolitis syndrome (FPIES) because no diagnostic or prognostic biomarkers are available. However, the optimal OFC procedure remains unclear. OBJECTIVE: This systematic review aimed to assess OFC procedures' design and clinical outcomes in patients with FPIES. METHODS: We searched 10 databases for studies published in English between 1978 and February 2024 involving children or adults undergoing OFC for FPIES. Critical appraisal followed Effective Public Health Practice Project parameters. RESULTS: In total, 52 studies met inclusion criteria, all observational studies. Of these, 35 were judged to have strong methodological quality. There was great heterogeneity in OFC procedures, particularly in cumulative dose, number, size, and timing between doses. Oral food challenge outcome reporting was often inadequate, especially regarding reaction symptoms and severity grading. In single-dose OFC protocols, most children reacted after at least 2 hours. Four small studies showed that a single dose of 25% of an age-appropriate portion was sufficient to trigger reactions in 80% to 100% of cases, and this was associated with less severe reactions. Owing to methodological heterogeneity and insufficient outcome reporting, further assessment of the OFC protocol characteristics associated with safer outcomes was not possible. CONCLUSIONS: There is significant heterogeneity in FPIES OFC practices. Current recommendations for OFC procedures and outcome assessments have limitations and should be revisited, because this may affect patient safety and diagnostic accuracy. Future studies should focus on standardizing clinical outcomes and generating evidence to support safer, more accurate OFC protocols in FPIES. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/ by/4.0/). (J Allergy Clin Immunol Pract 2025;13:814-32)