Understanding the safest approach to conducting food challenges in acute FPIES: A systematic review
Published online December 31, 2024
Acute Food Protein-Induced Enterocolitis Syndrome (FPIES) is an increasingly reported form of delayed food allergy, mainly affecting young children. It presents with profuse vomiting, usually 1-4 hours after eating the culprit food, often associated with marked lethargy, floppiness, pallor and diarrhea. In up to 1 in 6 cases, it can lead to hypotension and shock. Most children with FPIES develop tolerance over time. However, there is no diagnostic or prognostic biomarker. Thus, assessment for tolerance development involves trying the culprit food under clinician supervision, an Oral Food Challenge’ (OFC) procedure. OFC is resource-intense and potentially risky, as it can lead to a severe reaction. This possibility raises concern amongst patients, families, and clinicians. It is unclear what OFC protocol (i.e. which food doses and time intervals between doses) best balances patient safety and accuracy in identifying an FPIES reaction. Expert guidance is available and generally advocates administering 0.3g protein/kg (maximum 3g) in 3 equal portions over 30 minutes. However, its evidence base is limited.
In a recent study published in The Journal of Allergy and Clinical Immunology: In Practice, Ibrahim et al. conducted a systematic review of scientific literature to assess the OFC procedures and clinical outcomes used in patients with FPIES. The ultimate aim was to identify OFC features that might be associated with better safety and diagnostic accuracy.
The review included 52 studies and identified great heterogeneity in OFC procedures, particularly in cumulative doses, number, size, and timing between doses. OFC outcome reporting was often inadequate, especially regarding reaction symptoms and severity grading. No prospective randomized studies were identified.
Importantly, the review noted that in OFC protocols where a single dose was given, most children needed at least two hours to manifest symptoms. Also, four small studies showed that a single dose of 25% of an age-appropriate portion was sufficient to trigger reactions in 80-100% of cases. Two of these studies compared this approach with protocols using multiple (generally larger) doses within a single day and found that a single dose of 25% of an age-appropriate portion followed by at least 4 hours of observation was associated with less severe reactions. These observations raise concerns about OFC protocols that include multiple doses with relatively short intervals, as patients may receive doses beyond their individual threshold before symptoms present, which could contribute to more severe reactions. Due to the heterogeneity in methods and poor reporting of outcomes in studies, further assessment of the OFC protocol characteristics associated with safer outcomes was not possible.
The authors highlighted that the optimal OFC procedure for patients with FPIES remains unclear and further research (including head-to-head comparisons of standardized OFC protocols) was warranted to confirm these findings.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.
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