Predicting Oral Food Challenge Outcomes in Children with Suspected Cow’s Milk Allergy: Clinical Utility of Casein-Specific IgE and Skin Test Ratios

Background: To investigate the diagnostic value of the SPT-to-histamine ratio, casein-specific immunoglobulin E (IgE), and cow’s milk-specific IgE in predicting oral food challenge (OFC) positivity in children with suspected cow’s milk allergy. Methods: In this single-center retrospective observational study, 126 children evaluated for suspected cow’s milk allergy who underwent OFC between January 2019 and July 2024 at a tertiary pediatric allergy and immunology center were included. Demographic and clinical characteristics, SPT parameters, and laboratory biomarkers were analyzed. Discriminatory performance was assessed using receiver operating characteristic (ROC) analysis, and independent predictors were identified using multivariable logistic regression. Results: OFC was positive in 66 patients (52.4%). Casein-specific IgE demonstrated strong discriminatory performance (AUC = 0.878), with 80.3% sensitivity and 85.0% specificity at a cutoff value of ≥2.55 kUA/L. The SPT-to-histamine ratio showed moderate discriminatory performance (AUC = 0.758). In multivariable analysis, only casein-specific IgE remained an independent predictor of OFC positivity (adjusted OR = 1.317, p < 0.001). Conclusions: Casein-specific IgE is a strong independent predictor of OFC positivity. Although SPT-derived ratios may provide complementary diagnostic information, their independent predictive contribution appears limited. These findings support the role of component-resolved diagnostics in pre-challenge risk stratification.