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

Currently, the recommended dose for oral food challenges (OFCs) for food protein–induced enterocolitis syndrome (FPIES) is not evidence based. This systematic review was done to determine the validity of the recommended dosing for OFCs for FPIES and whether alternative doses could be used with similar or improved clinical outcomes.This included 2429 children and 226 adults across 11 countries who either were suspected of having FPIES or were already diagnosed with FPIES.Ten databases were searched to produce 52 observational studies from 1978 to 2024 across 11 countries. A total of 3556 OFCs for FPIES were included in the study. These challenges were performed for both primary diagnoses and assessment for resolution of FPIES. Data were compiled and underwent quality assessment and statistical analysis. The primary outcome was OFC protocol designs. The secondary outcomes were the clinical outcomes including accuracy of diagnosis and adverse events.There was significant heterogeneity among protocols used for OFCs within the studies. Although older consensus guidance had suggested a challenge dose of 0.3 g of protein per kilogram (with a maximum of 3 g), the authors found that much smaller doses are likely to be adequate to determine FPIES reactivity while providing a greater margin of safety with less severe reactions.There was a wide variety of doses used for OFC in FPIES with heterogeneity noted throughout both the study designs as well as what outcomes were reported. This heterogeneity made it difficult to analyze outcomes between different designs and OFC doses. This review suggests that FPIES can be accurately diagnosed using only 25% of a typical dose for an OFC in many (but not all) patients.OFCs for FPIES have historically been performed in larger cumulative doses than may be necessary and under medical observation. Still, most children who undergo a challenge for FPIES do not experience a reaction severe enough to require intravenous rehydration. Recently, innovative paradigms of care have emerged that consider more gradual doses for FPIES challenges, with some protocols giving very small, gradually escalating challenge amounts over several weeks in a home setting for patients with nonsevere reaction histories. The current review highlights the ongoing need for innovation when considering FPIES challenge protocols and setting to minimize risk of severe reactions and maximize the role of shared decision-making with families.