Association of celiac disease with eosinophilic esophagitis: Nationwide register-based cohort study with sibling analyses

Background Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE). Objectives We aimed to examine the risk of EoE in patients with biopsy-verified CeD compared to matched controls and siblings. Methods Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in 2002-2017 in Sweden. CeD patients were age- and sex-matched with up to 5 reference individuals (n=134,987) from the general population. Cox regression estimated hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used CeD siblings as comparators to adjust for intrafamilial confounding. Results The median age at CeD diagnosis was 27.0 years, and 63.3% of the patients were females. During a median follow-up of 8.1 years, 17 CeD patients and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 vs. 0.01 per 1000 person-years respectively, and an adjusted HR for EoE of 6.65; 95% confidence interval (CI)=3.26-13.81. Compared with their non-CeD siblings, patients with CeD were however at a no increased risk of EoE (HR=1.39; 95%CI=0.55-3.51). Conclusion In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health seeking behavior or through shared genetic or early environmental factors since the excess risk disappeared in sibling analyses.