Incidence and prevalence of immune-mediated extraintestinal manifestations in paediatric inflammatory bowel disease: a systematic review and meta-analysis

Abstract Background Immune-mediated extraintestinal manifestations (IM-EIMs) are common in paediatric inflammatory bowel disease (pIBD). This systematic review and meta-analysis aimed to summarise the incidence and prevalence of IM-EIMs in pIBD. Methods MEDLINE, EMBASE, CENTRAL and clinicaltrials.gov were searched up to May 6, 2024, for studies that included pIBD (2-17 years) patients diagnosed with IM-EIMs. Primary outcomes included the incidence and prevalence of IM-EIMs among pIBD. Meta-analysis included pooled proportions of prevalence with DerSimonian-Laird random-effects analysis. Results The pooled proportion of IM-EIMs among pIBD overall was 10% (95% CI, 8-12%; I2=97.2%) among 65 studies (35,343 patients). The pooled proportion of IM-EIMs was 10% (95% CI, 7-13%; I2=94.8%) among 37 Crohn’s disease (CD) studies (7657 patients), compared to 11% (95% CI, 7-15%; I2=93.3%) among 39 ulcerative colitis (UC) studies (4698 patients). Enthesitis was the highest reported individual IM-EIM (23%, 95% CI, 4-50%; I2=94.7%) in pIBD. Arthritis was the second highest reported individual IM-EIM (8%, 95% CI, 6-10%; I2=96%) in pIBD, followed by primary sclerosing cholangitis (PSC) in UC (5%, 95% CI, 4-7%; I2=81%). Uveitis, pyoderma gangrenosum, autoimmune hepatitis and PSC in CD were the lowest reported IM-EIMs at 1% or less. The largest difference in proportions between IBD phenotypes was PSC, which was 4% higher in UC than CD. Conclusions While musculoskeletal manifestations are common, fewer than 5% of pIBD patients experience ophthalmological, dermatological, and liver IM-EIMs. The small number of studies resulted in significant methodological and statistical heterogeneity. Multicentre collaborative efforts are needed to systematically describe the epidemiology of IM-EIMs in pIBD.