The role of vitamin D in controlling esophageal inflammation in Eosinophilic Esophagitis

Introduction Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory disease of the esophagus, characterized by epithelial barrier dysfunction and a type 2 immune response predominantly mediated by IL-13. Vitamin D has been identified as a natural antagonist of IL-13, capable of regulating epithelial barrier integrity and modulating immune responses in murine models of EoE. However, no clinical studies to date have examined the effects of vitamin D supplementation in patients with EoE. Aims The primary objective of this study was to investigate the role of vitamin D in the pathogenesis of EoE through a multiphase approach, including a retrospective analysis followed by a prospective evaluation. Methods In the retrospective phase, all pediatric patients diagnosed with EoE and evaluated between January 2022 and December 2022 at the Eosinophilic Disorders Outpatient Clinic, Pediatric Gastroenterology Unit, Policlinico Umberto I - Sapienza University of Rome, were included. The prevalence of vitamin D deficiency was assessed and compared with a control group, and the association between serum vitamin D levels and the severity of histological alterations was evaluated using the EoE Histology Scoring System (EoEHSS). In the prospective phase, consecutively diagnosed pediatric patients evaluated between January 2023 and December 2024 at the same center were enrolled to assess the effects of vitamin D supplementation in patients with insufficient serum levels, focusing on both induction and maintenance of disease remission. Results In the retrospective phase, 48 patients with EoE (33 males, 68.7%; median age 13.5 years, IQR 8–17) and 50 controls (21 males, 42%; median age 12.5 years, IQR 8–16) were included. Among EoE patients, 37 (77.1%) exhibited insufficient vitamin D levels, compared with 27 (54%) in the control group (p = 0.01). Vitamin D levels inversely correlated with esophageal eosinophilia in both the distal and proximal esophagus (p < 0.001) and with total and partial EoEHSS scores (p < 0.001). In the prospective phase, 102 patients (76 males, 74.5%; 26 females, 25.5%; median age 16 years, IQR 12.3–17.2) were enrolled. At baseline, a higher proportion of vitamin D–deficient patients had active disease (56.6% active vs. 43.4% in remission) compared with patients with sufficient vitamin D levels (24.5% active vs. 75.5% in remission; p < 0.001). At follow-up, remission was maintained in a higher proportion of patients receiving vitamin D supplementation (82.6% in remission vs. 17.4% active) compared with those receiving EoE-specific therapy alone (51.4% in remission vs. 48.6% active; p = 0.01). Similarly, the proportion of patients achieving remission was higher in the supplemented group (83.3% in remission vs. 16.7% active) than in the non-supplemented group (41.7% in remission vs. 58.3% active; p = 0.006). Patients receiving vitamin D showed significant improvements in all histological parameters from baseline to follow-up (p < 0.0001). Multivariable analysis indicated that maintenance of remission was independently associated with vitamin D supplementation (p = 0.01). Conclusions These findings support a modulatory role of vitamin D in esophageal inflammation in pediatric EoE. Patients with EoE exhibit lower serum vitamin D levels compared with the general population, and deficiency may exacerbate histological disease severity by increasing esophageal eosinophilia, impairing epithelial barrier function, and promoting tissue remodeling. Vitamin D supplementation appears to contribute to long-term remission and, when combined with standard therapy, may increase the proportion of patients achieving sustained disease control.