Evidence of very delayed clinical reactions to cow's milk in cow's milk‐intolerant patients

Background: In patients with cow's milk protein intolerance (CMPI), delayed clinical reactions to cow's milk (CM) ingestion may be misdiagnosed if the clinical symptoms are not “classical” and there is a long time lapse between ingestion of CM and the clinical reaction. The aim was to evaluate the clinical outcome of CMPI in a cohort of CM‐intolerant children, with particular attention to the occurrence of clinical manifestations beyond 72 h after CM challenge. Methods: Eighty‐six consecutive patients (44 boys, 42 girls) with new CMPI diagnoses were enrolled; median age at diagnosis was 4 months. Patients were followed up for a mean period of 40 months. In all patients, CMPI diagnosis was made on the observation of symptoms, their disappearance after elimination diet, and their reappearance on double‐blind CM challenge. At CMPI diagnosis, immunologic tests to demonstrate IgE‐mediated hypersensitivity were performed. After 12 months of CM‐free diet, CM tolerance was re‐evaluated with a CM challenge continued at home for up to 30 days, according to a double‐blind, placebo‐controlled method. Patients who did not achieve CM tolerance continued a CM‐free diet and subsequently underwent yearly CM challenge. Results: The percentages of CMPI patients who became CM‐tolerant after 1, 2, and 3 years of CM‐free diet were 30%, 54.5%, and 70%, respectively. At the end of the follow‐up period, 26/86 subjects showed persistent CMPI; these patients had a higher percentage of positivity of total serum IgE (P