Eosinophilic esophagitis following oral immunotherapy- A systematic review and meta-analysis

BACKGROUND: Oral immunotherapy (OIT) has become a cornerstone in the management of IgE-mediated food allergies, offering the potential for desensitization and protection against accidental allergen exposure. However, the therapy carries the risk of adverse effects, notably eosinophilic esophagitis (EoE), a chronic, Th2-mediated inflammatory disorder of the esophagus characterized by eosinophilic infiltration, dysphagia, and esophageal remodeling. This systematic review aimed to identify and summarize all published cases of EoE arising in the context of OIT, characterizing patient demographics, comorbidities, allergens, diagnostic approaches, and treatment strategies. METHODS: A systematic search of MEDLINE and Embase from inception to July 1, 2025, was conducted in accordance with PRISMA and Cochrane guidelines. Eligible studies included case reports, case series, cohort studies, and clinical trials describing EoE during OIT. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. Data extracted included patient characteristics, atopic comorbidities, allergen type, OIT regimen, latency to EoE onset, diagnostic modality, and post-diagnosis management. Given the heterogeneity in study design and outcome definitions, a descriptive synthesis was performed. RESULTS: Thirteen studies (3 trials, 6 cohorts, 2 case series, 2 case reports) comprising 3,655 OIT patients were included. A total of 89 cases of EoE were identified, yielding an overall pooled prevalence of 1.8% (95% CI 0.87-2.79%). Prevalence varied by allergen, with peanut OIT associated with lower risk (0.82%, 95% CI 0.51-1.12%) compared with milk (6.9%, 95% CI 3.74-10.08%) and egg OIT (9.5%, 95% CI 2.78-16.13%). Males accounted for 74% of EoE cases. Diagnosis was confirmed endoscopically in nearly all patients. Most cases improved following proton pump inhibitor therapy and/or discontinuation of OIT, while fewer reports described dietary elimination or topical corticosteroids. CONCLUSIONS: EoE is an uncommon but clinically significant complication of OIT, occurring in approximately 1-2% of treated patients. Male sex, milk and egg OIT, and coexisting atopic disease may increase susceptibility. Recognition of early symptoms, routine monitoring in high-risk patients, and standardized diagnostic criteria are essential to ensure safe and effective OIT implementation. Future prospective studies are needed to clarify risk predictors and establish evidence-based management strategies for EoE in this context.