Investigators may have uncovered factors associated with extraintestinal manifestations in patients with inflammatory bowel disease (IBD), according to a recent study published by Khrom et al in Gastroenterology. The investigators used data from the Cedars-Sinai Medical Center, NIDDK IBD Genetics Consortium, SHARE Consortium, and RISK cohort to examine the demographic, clinical, serological, and genetic factors of about 12,000 patients with IBD and European ancestry. Patients in the analysis included those who had extraintestinal manifestations such as ankylosing spondylitis, primary sclerosing cholangitis, peripheral arthritis, and skin and ocular manifestations. Patients who identified as female (odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.1–1.4), had Crohn’s disease (OR = 1.7, 95% CI = 1.4–2.0), and required surgery for either Crohn’s disease or ulcerative colitis (OR = 1.7, 95% CI = 1.5–1.9) were most likely to present with extraintestinal manifestations. A history of smoking was associated with a greater risk of extraintestinal manifestations but not of primary sclerosing cholangitis. Further, anti–nuclear cytoplasmic antibodies (ANCA), anti–Saccharomyces cerevisiae antibodies (ASCA), and anti–bacterial flagellin antibodies were correlated with a higher risk of primary sclerosing cholangitis; and ANCA, ASCA, and anti–Pseudomonas fluorescens–associated sequence antibodies were correlated with a higher risk of any extraintestinal manifestation. The researchers also discovered that the major histocompatibility complex was linked to overall extraintestinal manifestations (OR = 2.2, 95% CI = 1.7–2.9), ankylosing spondylitis (OR = 2.5, 95% CI = 2.0–3.1), primary sclerosing cholangitis (OR = 2.8, 95% CI = 2.0–3.8), and ocular manifestations (OR = 3.6, 95% CI = 2.3–5.6) and that the CPEB4 gene was linked to skin manifestations (OR = 1.5, 95% CI = 1.3–1.8). Tumor necrosis factor, Janus kinase–signal transducers and activators of transcription signaling pathway, and interleukin-6 were identified as potential therapeutic targets for extraintestinal manifestations in this patient population. In a companion press release on the research from Cedars-Sinai, the study authors concluded: “Our clinical [and genetic] findings … shed light on the risk factors for morbidity associated with IBD [and] highlight pathways that are targets for existing drugs or therapeutics in development. These discoveries are critical for developing more personalized approaches to the management of IBD and its various manifestations.”