Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated allergy without known biomarkers. We aimed to compare fecal biomarkers related to gut inflammation and immunity in children with FPIES, with resolved FPIES (tolerant), and in matched controls. Methods: Stools were collected from FPIES children on elimination diet, before and after an oral food challenge (OFC) performed to assess their natural tolerance, at the end of a follow-up in tolerant FPIES children, and in matched controls (1:1 ratio). Concentrations of calprotectin, EDN (eosinophilic derived neurotoxin), and secretory IgA (sIgA) underwent comparative paired analysis. Results: Thirty-eight patients were included (age: 1.3 years old, interquartile range: IQR [0.9 - 2.0]), of which 22 became tolerant during follow-up. Upon inclusion, allergic patients and controls had similar concentrations of calprotectin (38µg/g [8-85] vs 27µg/g [11-46], p=0.15) and EDN (504ng/g [275-1252] vs 516ng/g [215-844], p=0.86). However, concentrations of these inflammatory biomarkers increased transiently after a failed OFC (p<0.001 and p=0.01 respectively), without correlating with the severity of an allergic reaction. sIgA were higher in allergic than in tolerant patients: 2224µg/g [878-3529] vs 794µg/g [699-1767] (p<0.01). Calprotectin, EDN, and sIgA were comparable in tolerant patients and controls. sIgA less than 2637µg/g had a negative predictive value of 75.6% for the differentiation allergic patients from tolerant patients and controls (area under curve: 0.63, 95% CI: 0.52–0.74). Conclusion: A few days after an acute allergic reaction, there was no detectable chronic gut inflammation in FPIES. sIgA may be a useful tool for clinicians in timing OFC.

Background Food protein-induced enterocolitis syndrome (FPIES) is a non IgE-mediated food allergy, with potential dehydration secondary to vomiting. Differences exist regarding culprit foods, onset symptoms, and age of tolerance depending on the country of origin. We aimed to describe the characteristics of a French population of children with FPIES. Methods Data from 179 children who were referred for acute or chronic FPIES in two pediatric tertiary centers between 2014 and 2020 were retrospectively collected. The diagnosis of FPIES was based on international consensus guidelines. Clinical characteristics, culprit food and age at resolution were assessed. Results In the 192 described FPIES, the age at first symptoms was 5.8 months old. The main offending foods were cow’s milk (60.3%), hen’s egg (16.2%), and fish (11.7%). Single FPIES was observed in 94.4% and multiple FPIES in 5.6% of cases. The age at resolution of FPIES was 2.2 years old, and resolution occurred later for fish than for milk (2.9 years versus 2.0, p=0.01). Severe acute FPIES was a risk factor for delayed resolution (relative risk: 3.3 [1.2-9.2]), but not IgE sensitization. Performing an oral food challenge within 12 months after the first reaction increased the risk of failure (RR: 2.0 [1.2-3.5]). Conclusion In this French cohort of children with FPIES, the main culprit foods were ubiquitous. Rice, oat and soy were rarely or not involved. Multiple FPIES was infrequent. Our data confirmed the overall good prognosis of FPIES, the later resolution of FPIES to fish and in the case of severe acute FPIES.