Risk of Clostridium difficile Infection in Patients With Celiac Disease: A Population-Based Study

OBJECTIVES: Patients with celiac disease are at increased risk for infections such as tuberculosis, influenza, and pneumococcal pneumonia. However, little is known about the incidence of Clostridium difficile infection (CDI) in patients with celiac disease. METHODS: We identified patients with celiac disease based on intestinal biopsies submitted to all pathology departments in Sweden over a 39-year period (from July 1969 through February 2008). We compared risk of CDI (based on stratified Cox proportional hazards models) among patients with celiac disease vs. without celiac disease (controls) matched by age, sex, and calendar period. RESULTS: We identified 28,339 patients with celiac disease and 141,588 controls; neither group had a history of CDI. The incidence of CDI was 56/100,000 person-years among patients with celiac disease and 26/100,000 person-years among controls, yielding an overall hazard ratio (HR) of 2.01 (95% confidence interval (CI), 1.64–2.47; P<0.0001). The risk of CDI was highest in the first 12 months after diagnosis of celiac disease (HR, 5.20; 95% CI, 2.81–9.62; P<0.0001), but remained high, compared to that of controls, 1–5 years after diagnosis (HR, 1.85; 95% CI, 1.22–2.81; P=0.004). Among 493 patients with CDI, antibiotic data were available for 251; there were no significant differences in prior exposures to antibiotics between patients with celiac disease and controls. CONCLUSIONS: In a large population-based cohort study, patients with celiac disease had significantly higher incidence of CDI than controls. This finding is consistent with prior findings of higher rates of other infections in patients with celiac disease, and suggests the possibility of altered gut immunity and/or microbial composition in patients with celiac disease.