D3.36 - Chronic type non-IgE-mediated gastrointestinal food allergies, Clinical features and unclassified subgroup in the recent cohort

Chronic-type non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs), including chronic food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP), are increasingly recognized. However, there are few reports investigating the real-world clinical characteristics, and many patients cannot be classified into existing subtypes.

We conducted a retrospective cohort study of children diagnosed with non-IgE-GIFAs before 2 years of age at the National Center for Child Health and Development (April 2022–March 2025).Patients were classified based on modified Powell’s criteria:

1) symptom resolution after dietary elimination, 2) exclusion of differential diagnoses, 3) confirmed weight gain, 4) positive oral food challenge (OFC).Patients meeting criteria all of 1–3 were classified as “probable,” and those meeting all four as “definite.” A diagnostic OFC was defined as an OFC performed within 3 months of symptom onset, whereas a remission OFC was defined as an OFC performed ≥3 months after symptom onset.Children with acute FPIES, prematurity (<34 weeks’ gestation), surgical history, or negative OFCs were excluded. Definite cases were subclassified into chronic FPIES, FPIAP, or unclassified subgroups.

Of the 345 screened children, 222 were classified as acute FPIES. Among the remaining patients, 75 met the inclusion criteria. Of these, 25 were definite cases: 15 of 17 patients (88.2%) had a positive diagnostic OFC, and 10 of 52 patients (19.2%) had a positive remission OFC. The remaining 50 patients were classified as probable cases. No significant differences were observed in background or clinical characteristics between the definite and probable groups.

Among the definite cases, 7 were classified as chronic FPIES, 8 as FPIAP, none as FPE, and 10 as unclassified group. Half of the definite patients showed marked eosinophilia (>10%). Chronic FPIES patients exhibited severe features, including ICU admission (n=2), severe anemia (n=3), and hypoalbuminemia (n=5). FPIAP patients frequently showed marked eosinophilia (median peripheral eosinophil %: 16.9%) and positive fecal eosinophils (n=6). Among the 14 definite cases with bloody stool but not vomiting, 6 had symptoms such as diarrhea (>5 times a day), lethargy, poor weight gain, or >10% weight loss, indicating a phenotype distinct from FPIAP. Unclassified cases accounted for 40% of definite cases and exhibited diverse clinical presentations, spanning features of both chronic FPIES and FPIAP, as well as symptoms not covered by either definition.

A substantial proportion of children with chronic-type non-IgE-GIFAs could not be categorized under current definitions, highlighting the need for refined diagnostic frameworks. Marked eosinophilia observed in many cases raises the possibility that these conditions represent early-onset of eosinophilic gastrointestinal diseases.