ESSENTIALS OF DIAGNOSIS
Most common in men aged 20–50 years.
Often associated with ulcerative colitis.
Progressive jaundice, itching, and other features of cholestasis.
Diagnosis based on characteristic cholangiographic findings.
At least 10% risk of cholangiocarcinoma.
Primary sclerosing cholangitis is an uncommon disease thought to result from an increased immune response to intestinal endotoxins and characterized by diffuse inflammation of the biliary tract leading to fibrosis and strictures of the biliary system (eFigure 18–53). From 60% to 70% of affected persons are male, usually 20–50 years of age (median age 41). The incidence is nearly 3.3 per 100,000 in Asian Americans, 2.8 per 100,000 in Latinx Americans, and 2.1 per 100,000 in Black persons, with an intermediate (and increasing) incidence in White persons and a prevalence of 16.2 per 100,000 population (21 per 100,000 men and 6 per 100,000 women) in the United States. In Europe, the incidence and prevalence are highest in Scandinavia and lowest in Mediterranean countries.
Liver biopsy specimens showing two views of the characteristic periductal fibrosis ("onion-skinning") of sclerosing cholangitis. (Reproduced, with permission, from Levy C, Bowlus CL. Primary and Secondary Sclerosing Cholangitis. In: Feldman M, Friedman LS, Brandt LJ [editors]. Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 2 vol set, 11th edition. Philadelphia, Elsevier; 2023.)
Primary sclerosing cholangitis is closely associated with IBD (more commonly ulcerative colitis than Crohn colitis), which is present in approximately two-thirds of patients with primary sclerosing cholangitis; however, clinically significant sclerosing cholangitis develops in only 1–4% of patients with ulcerative colitis. The association with IBD has suggested a role for intestinal microbial dysbiosis and altered bile acid metabolism in the pathogenesis of primary sclerosing cholangitis. Smoking is associated with a decreased risk of primary sclerosing cholangitis in patients who also have IBD. Coffee consumption is also associated with a decreased risk of primary sclerosing cholangitis, and statin use is associated with improved outcomes in patients with primary sclerosing cholangitis. Women with primary sclerosing cholangitis may be more likely to have recurrent UTIs and less likely to use hormone replacement therapy than healthy controls. Associations with CVD and diabetes mellitus have been reported. Primary sclerosing cholangitis is associated with the histocompatibility antigens HLA-B8 and -DR3 or -DR4, and first-degree relatives of patients with primary sclerosing cholangitis have a fourfold increased risk of primary sclerosing cholangitis and a threefold increased risk of ulcerative colitis. A subset of patients with primary sclerosing cholangitis have increased serum IgG4 levels and distinct HLA associations (with a poorer prognosis) but do not meet criteria for IgG4-related sclerosing cholangitis. The diagnosis of primary sclerosing cholangitis may be difficult to make after biliary surgery.