Phenotypes and follow-up of chronic cow's milk food protein-induced enterocolitis syndrome: A 16-year prospective observational study.

Background: Chronic food protein-induced enterocolitis syndrome (cFPIES) is less well characterized than the acute form; the clinical features for defining the different clinical phenotypes have not been identified, and data on follow-up are lacking.

Objective: To describe a population of infants with cow's milk cFPIES (CM-cFPIES), providing a definition of clinical phenotypes and their evolution between the onset and our observation and the natural history over time.

Methods: A prospective observational study was conducted on all the patients with oral food challenge-diagnosed CM-cFPIES between January 2008 and January 2024. Descriptive analysis is reported.

Results: A total of 39 patients were included. Neonatal onset was observed in 48.7%. We characterized and identified the following 3 clinical phenotypes: Severe from the very beginning (16/39, 41%), including 11 newborns; 86% of exclusively breastfed patients were part of this group. Mild (17/39, 43.6%) or moderate (6/39, 15.4%) at the onset, remaining stable over time (n = 8) or with progressive worsening (n = 15) until a severe form. The most prevalent symptom was intermittent vomiting, followed by diarrhea. Bloody stools were almost exclusively reported in newborns. Leukocytosis, neutrophilia, and metabolic acidosis were the most frequently observed laboratory features; eosinophil levels were significantly higher in newborns. Imaging was not specific and was misleading in some cases. Atypical CM-cFPIES was observed in 30.7% of patients; multiple FPIES was developed by 28.2%. Overall, 92% outgrew CM-cFPIES.

Conclusion: Clinical suspicion of CM-cFPIES is difficult due to different phenotypes. Neonatal CM-cFPIES presents clinical and laboratory features that are partly different from those of the infant form. Exclusive breastfeeding might not be a protective factor. CM-cFPIES resolves in most children.