Abstract Background Although extraintestinal manifestations (EIMs) are common in patients with inflammatory bowel disease (IBD), data on the natural history of EIMs in IBD remains limited. Most existing evidence derives from small-sample, single-center studies lacking regional representativeness, particularly data from Asia, and longitudinal follow-up. Methods This study (Fig 1) used five geographically diverse cohorts: East China Multicenter Survey (EC cohort, n = 624), ONE-IBD Cohort (Central-Southern China, n = 660), Hunan Medical Insurance Database (China, n = 18,690), UK Biobank (n = 6091) and U.S. CDC Wonder Database (n = 24,304). Analyses included two steps: (1) EIM prevalence was evaluated via electronic health records or questionnaires and latent EIM clusters were identified using latent class analysis; (2) Short- and long-term prognostic outcomes of IBD patients with EIMs were assessed via logistic regression (cross-sectional) and Cox proportional hazards models (longitudinal). Results EIM prevalence in IBD patients ranged from 20.5% to 32.7%. It was slightly higher in Crohn’s disease than ulcerative colitis across 4 of 5 cohorts, with no statistical significance (Fig 2A). EIM prevalence was comparable between Eastern and Western patients but notable differences existed in the EIM spectrum (Fig 2B). Both populations had high skin and joint (especially peripheral arthritis) manifestation rates; Eastern patients had higher skin (14.4% vs 6.9%) and hepatobiliary (7.6% vs 1.1%) EIM rates, while Western patients (UK Biobank) had higher joint EIM prevalence (6.7% vs 13.2%). Latent class analysis (Fig 2C) across four cohorts consistently identified two EIM clusters: one dominated by isolated joint manifestations, the other by multi-organ EIMs involving mucosal sites (skin/eye). Overall, EIM-positive patients had comparable prognosis to those without EIMs (Fig 2D), but prognosis notably varied by EIM subtype: patients with multi-organ EIMs involving mucosal manifestations (skin/eye; EC cohort Cluster 1; ONE-IBD Cluster 3; UK Biobank Cluster 5) had advanced Montreal phenotypes, higher disease activity and elevated risks of surgery, cancer (overall and colorectal) and mortality across three cohorts. Conclusion This multicohort study delineates the EIM landscape in Eastern and Western IBD patients, providing region-specific EIM spectra and novel data for diverse populations, particularly China. Latent class analysis highlights the need for tailored management of distinct EIM phenotypes, with multi-organ EIM screening recommended for patients with mucosal manifestations. Conflict of interest: Mr. Dan, Lintao: I have no COI related to submitted program Lu, Juntao: No conflicts of interests related to this program Zhang, Jialin: I have no COI related to this program Chen, Jie: None to Declare Wang, Xiaoyan: I have no conflict of interest to disclosure. Li, Lan: There is no conflicts of interests related to this program Sun, Jing: I have not COI related to submitted project.
Dan et al. (Thu,) studied this question.