Smoking is Associated With Extra-intestinal Manifestations in Inflammatory Bowel Disease

BACKGROUND AND AIMS: Smoking affects the course of disease both in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in Inflammatory Bowel Disease (IBD). METHODS: We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: 1. the COIN-cohort, designed to estimate healthcare expenditures in IBD, 2. the Groningen-cohort, focused on cigarette smoke exposure and disease behaviour in IBD and 3. the JOINT-cohort, evaluating joint and back manifestations in IBD. RESULTS: In the COIN-, Groningen-, and JOINT-cohort, 3,030, 797 and 225 patients were enrolled of whom 16%, 24% and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN-cohort: 39.1% vs. 29.8%, p <0.01; Groningen-cohort: 41.7% vs. 30.0%, p <0.01), in both CD and UC. In the JOINT-cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3% vs. 13.0%, p <0.01). EIMs appeared to be more prevalent in high than in low-exposure smokers (56.0% vs. 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels of never smokers (lag time COIN-cohort: 1-2 years, Groningen-cohort: within one year). CONCLUSIONS: There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.