Sclerosing Cholangitis, Primary

Key Features

Essentials of Diagnosis

• Progressive jaundice, itching, and other features of cholestasis

• Males, aged 20–50 years old

• Often associated with ulcerative colitis

• Diagnosis based on characteristic cholangiographic findings

• At least 10% risk of cholangiocarcinoma

General Considerations

• Characterized by diffuse inflammation of the biliary tract leading to fibrosis and strictures of the biliary system

• Associated with the histocompatibility antigens HLA-B8 and -DR3 or -DR4

• Occasional patients have clinical and histologic features of both sclerosing cholangitis and autoimmune hepatitis

• 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 is difficult to make after biliary surgery or intrahepatic artery chemotherapy, which may result in bile duct injury

• Primary sclerosing cholangitis must be distinguished from

  • Idiopathic adulthood ductopenia, a rare disorder affecting young to middle-aged adults who manifest cholestasis resulting from loss of interlobular and septal bile ducts yet who have a normal cholangiogram

  • Other cholangiopathies, including

    • Primary biliary cholangitis

    • Cystic fibrosis

    • Eosinophilic cholangitis

    • AIDS cholangiopathy

    • Histiocytosis X

    • Allograft rejection

    • Graft-versus-host disease

    • Ischemic cholangiopathy

    • Intra-arterial chemotherapy

    • Sarcoidosis

    • Post-COVID cholangiopathy

Demographics

• Between 60% and 70% of affected persons are male, usually 20–50 years old (median age 41)

• Incidence

  • Nearly 3.3 per 100,000 in Asian Americans

  • ~2.8 per 100,000 in Hispanic Americans

  • ~2.1 per 100,000 in Blacks

  • Intermediate incidence in Whites (and increasing)

• Prevalence: 16.2 per 100,000 population, 21 per 100,000 men and 6 per 100,000 women in the United States

• Closely associated with inflammatory bowel disease (more commonly ulcerative colitis than Crohn colitis), which is present in approximately two-thirds of patients

• However, clinically significant sclerosing cholangitis develops in only 1–4% of patients with ulcerative colitis

• As in ulcerative colitis, smoking is associated with a decreased risk of primary sclerosing cholangitis; so is coffee consumption

Clinical Findings

Symptoms and Signs

• Progressive obstructive jaundice, frequently associated with fatigue, pruritus, anorexia, and indigestion

• Esophageal varices on initial endoscopy are most likely found in patients with a higher Mayo risk score based on age, serum bilirubin, albumin, and AST and a higher AST/ALT ratio

• New varices are likely to develop in those with a lower platelet count and higher bilirubin at 2 years

• In patients with primary sclerosing cholangitis, ulcerative colitis is frequently characterized by rectal sparing and backwash ileitis

• Associations with cardiovascular disease and diabetes mellitus have been reported

• Women with primary sclerosing cholangitis may be more likely to have recurrent urinary tract infections

Differential Diagnosis

• Primary biliary cholangitis

• Choledocholithiasis

• Cancer of pancreas or biliary tract

• Biliary stricture

• Drug-induced cholestasis, eg, chlorpromazine

• Inflammatory bowel ...