Identifying Predictors for the Acquisition of Tolerance to Cow’s Milk Protein in Infants with Food Protein-Induced Allergic Proctocolitis (FPIAP): Multifactorial Analysis of Two Italian Cohorts

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated gastrointestinal food allergy. Although tolerance to the culprit food is usually achieved within the first year of life, late acquisition occurs and remains poorly predictable. This study aimed to analyze clinical characteristics and explore factors that may potentially function as predictors of late tolerance acquisition to cow’s milk (CM). Methods: We conducted a cross-sectional study at two Italian pediatric clinics (2020–2024), including infants diagnosed with FPIAP. Clinical, dietary, and immunological variables; onset and duration of rectal bleeding (visible blood in the stools); and time to CM tolerance were analyzed. Late tolerance was defined as acquisition after 19 months according to the distribution of tolerance achievement in our population. Statistical analyses included χ2, Mann–Whitney U, Spearman’s correlation, and logistic regression. Results: Ninety-four infants were included (median age at onset 2.9 months [IQR 1.9–4.7]); 58 (62%) were exclusively breastfed and 18 (19%) were born preterm (<37 completed weeks of gestation). CM was the culprit food in all cases; tolerance was achieved in all infants at a median age of 12 months. Family history of atopy and atopic dermatitis were reported in 44% and 19% of infants, respectively. Late CM tolerance was associated with preterm birth, fortification of human milk, early antibiotic exposure, growth faltering, and recurrent infections. Logistic regression identified family history of atopy (OR 5.4 [95% CI 1.2–25.4]; p = 0.031), atopic dermatitis (OR 8.2 [1.7–40.7]; p = 0.010), rectal bleeding >18 days before elimination diet (OR 5.9 [1.3–27.7]; p = 0.023), and IgE sensitization (OR 6.4 [1.2–35.0]; p = 0.034) as factors that may potentially function as predictors of late tolerance acquisition to CM. Conclusions: Identification of factors that may potentially function as predictors of late tolerance acquisition to CM in infants with FPIAP may help providing a personalized clinical management for these patients.