PSC

**Primary Sclerosing Cholangitis (PSC)**

**Epidemiology/Associations** - Classically a middle-aged man (30-50 y) with ulcerative colitis (~70% of PSC patients have IBD, mostly UC; only ~5% of UC patients have PSC). - Associated with HLA-B8/DRB1*03 and autoimmune features. Serum p-ANCA is positive in many patients (nonspecific). IgG4 may be mildly elevated; distinguish from IgG4-related sclerosing cholangitis (steroid-responsive).

**Pathophysiology** - Immune-mediated, progressive periductal (concentric "onion-skin") fibrosis and inflammation of medium and large bile ducts. This causes multifocal strictures alternating with dilated segments, leading to cholestasis, biliary cirrhosis, and portal hypertension.

**Clinical features** - Often asymptomatic, found incidentally with elevated ALP. Symptoms include fatigue, pruritus, jaundice, and RUQ pain. Recurrent ascending cholangitis can occur. - Labs: ↑ ALP, ↑ GGT, ± mildly ↑ AST/ALT, later ↑ bilirubin.

**Diagnosis** - MRCP (first-line, noninvasive) or ERCP shows multifocal strictures and dilations: "beads on a string." - Liver biopsy (if performed) shows periductal "onion-skinning" fibrosis, but it is not required for diagnosis. - Anti-mitochondrial antibodies are negative (vs. PBC).

**Complications** - Cholangiocarcinoma (a major cause of mortality), gallbladder cancer, and colorectal cancer (in those with UC). - Biliary cirrhosis, fat-soluble vitamin deficiency (A, D, E, K), osteoporosis, and dominant strictures.

**Management** - No medical therapy proven to alter the course. Ursodeoxycholic acid is not routinely recommended and high doses are harmful. - Endoscopic dilation/stenting for dominant strictures; cholestyramine for pruritus. - Liver transplant is definitive for end-stage disease (can recur in the graft). - Surveillance: colonoscopy, imaging for gallbladder and bile duct malignancy.

**PSC vs. PBC (high-yield comparison)** - PSC: male, UC, p-ANCA, large-duct disease, beading, onion-skin fibrosis, ↑ cholangiocarcinoma risk. - PBC: middle-aged female, anti-mitochondrial antibody, small-duct disease (granulomatous destruction of interlobular ducts), other autoimmune disease, ↑ IgM, treated with ursodiol.

**Other meanings of "PSC" (context dependent)** - Posterior subcapsular cataract (steroid use, radiation, diabetes). - Pluripotent stem cell. - Pulmonary (valve) stenosis is abbreviated PS, not PSC. - Pediatric surgery consult, Pancreatic serous cystadenoma (SCA), and Proximal Straight Convoluted tubule (proximal straight tubule segment, S3) are also occasionally seen.