To Örebro University

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is often complicated by extraintestinal manifestations (EIMs) that affect organs beyond the gastrointestinal tract. The EIMs can significantly impair quality of life and complicate disease management in patients with IBD. As the population ages, understanding the interplay between age, chronic inflammation, and EIMs becomes increasingly important for optimizing patient care and outcomes. Thus, the overall aim of the thesis was to assess the impact of age and inflammation on EIM of IBD.

We conducted all studies using Swedish national registers. To evaluate the accuracy of the National patient register (NPR), we compared International classification of diseases (ICD) coded IBD data with clinical records from 1403 IBD patients. For investigating spondyloarthritis (SpA) comorbidity, a cohort of 39,203 IBD patients diagnosed between 2006-2016 and 390,490 matched reference individuals were analyzed. The familial risk of SpA was assessed among 147,080 first-degree relatives (FDRs) and 25,945 spouses of IBD patients. The influence of colectomy on SpA and other EIMs was studied in 3246 ulcerative colitis patients, comparing EIM rates before and after surgery.

The NPR showed high positive predictive values (PPVs) for Crohn's disease (97%) and ulcerative colitis (98%) but a low PPV for IBD-unclassified (8%). Crohn's disease location and behaviour had variable PPVs, indicating frequent misclassification. A high PPV (95%) was observed for age at diagnosis of IBD. Patients with IBD had significantly higher relative risk estimates of SpA both before (odds ratio [OR]: 3.48) and after (hazard ratio [HR]: 7.15) IBD diagnosis compared to the general population. FDRs of IBD patients exhibited a higher risk of SpA (HR: 1.35). Spouses also had an elevated SpA risk, suggesting environmental influences. The highest risks were observed in Crohn's disease and pediatric-onset IBD. Post-colectomy, patients with ulcerative colitis experienced increased EIM rates (rate ratios [RR]: 1.83). In addition, de novo EIMs frequently occurred in patients with no history of EIMs before colectomy.

The NPR is a reliable source for subtype of IBD, although improvements are needed for phenotypic accuracy. IBD significantly increases the risk of SpA. The elevated SpA risk among FDRs and spouses points to shared genetic and environmental factors. Colectomyin patients with ulcerative colitis does not mitigate the risk of EIMs, indicating a need for continued monitoring and management post-surgery. This thesis underscores the importance of comprehensive care approaches that address both gastrointestinal and extraintestinal challenges in IBD.