Clinical characteristics of patients with overlapping eosinophilic esophagitis and inflammatory bowel disease in a national real-world cohort.

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated gastrointestinal disorders with a recognized epidemiologic association, yet the clinical phenotype of overlapping disease remains incompletely characterized. We performed a retrospective cohort study using the All of Us Research Program Controlled Tier dataset mapped to the Observational Medical Outcomes Partnership common data model. Adults with EoE were identified using International Classification of Diseases, Ninth Revision (ICD-9), International Classification of Diseases, Tenth Revision (ICD-10), and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) codes requiring ≥2 distinct diagnosis dates. IBD overlap was identified using Crohn's disease (CD) and ulcerative colitis (UC) diagnoses. Analyses evaluated disease sequence, atopic comorbidities, medication exposure, symptom burden, and fibrostenotic complications. Among 797 patients meeting EoE criteria, 28 (3.5%) had overlapping IBD (13 CD, 17 UC), representing a 3.2-fold enrichment over the general All of Us cohort (1.1%). Overlap patients had higher rates of asthma (57.1% vs 36.8%; OR 2.29, P = 0.045) and allergic rhinitis (71.4% vs 48.5%; OR 2.65, P = 0.020). Corticosteroid exposure was substantially greater, including systemic (96.4% vs 66.1%; OR 13.8, P < 0.001) and topical corticosteroids (75.0% vs 48.1%; OR 3.23, P = 0.006). Disease sequence was bidirectional, with IBD preceding EoE in 53.6% and EoE preceding IBD in 42.9%. Despite greater treatment exposure, overlap patients demonstrated similar rates of dysphagia, food impaction, stricture, and esophageal dilation. Patients with overlapping EoE and IBD demonstrate a distinct phenotype characterized by increased atopic comorbidity without increased fibrostenotic severity. The bidirectional temporal relationship supports shared immune susceptibility rather than unidirectional disease progression.