This is a disease of unknown etiology characterized by fibrosing inflammation of portions of the extrahepatic and intrahepatic biliary tree that impairs bile flow leading to signs and symptoms of cholestasis and eventually to biliary cirrhosis. Cholangitis infrequently occurs spontaneously. More often it occurs as the result of duct manipulation from endoscopic, radiographic, or surgical procedures involving the biliary system. This is a progressive disease that usually results in cirrhosis, portal hypertension, and liver failure. Disease occurs most often in young adult men (mean age at diagnosis is 39 years), and more than one-half of patients will have coexisting inflammatory bowel disease.

Symptoms consist mainly of fatigue and pruritis with jaundice occurring late in the disease course. Patients are usually asymptomatic early in the disease course. Laboratory abnormalities show that the alkaline phosphatase and bilirubin levels may fluctuate, but the alkaline phosphatase is nearly always twice the normal value. There may also be a mild concomitant transaminasitis. There are no serologic markers. The pathogenesis is most likely the result of an immunologic function. There is a clear association with HLA-B8 and HLA-DR3, suggesting autoimmune features. Hepatobiliary carcinoma develops in 10 to 15% of patients afflicted with PSC. Surgical therapy to include liver transplantation has not proved to be effective once carcinoma develops.

There are four histologic stages of disease:

Stage 1 is characterized by degeneration of bile duct epithelial cells along with bile duct infiltration by lymphocytes. Inflammation, scarring and enlargement of the portal triads with occasional portal edema are noted, but at this stage, pathology is not noted outside of the portal triads.

Stage 2 is characterized by fibrosis and inflammation which invade the periportal liver parenchyma. Periportal hepatocytes undergo piecemeal necrosis, and there is associated bile ductopenia.

Stage 3 disease manifests as portal to portal fibrous septa, and the disappearance or degeneration of bile ducts.

Stage 4 consists of hepatic cirrhosis.

The diagnosis is established by cholangiography (either ERCP or transhepatic), and liver biopsy is used for confirmation and staging. Other considerations in the differential diagnosis include bacterial cholangitis, ischemic bile-duct damage secondary to therapy with floxuridine, infectious cholangiopathy associated with HIV, previous biliary surgery, congenital abnormalities, and bile-duct neoplasms. Patients with inflammatory bowel disease, a cholestatic profile on biochemical liver testing, liver biopsy pathology consistent with PSC, and normal cholangiograms have a disease variant known as small duct PSC.

Therapy is focused to treating signs and symptoms of the disorder as well as broad spectrum antibiotics directed against gram-negative pathogens. Pruritis has been successfully treated with cholestyramine. Use of activated charcoal and phenobarbital has had limited success. Rifampin has been tried with some reports of success but requires further data to support its widespread use. Endoscopic balloon dilation with or without stent placement may relieve symptoms of jaundice, pruritis, and fever along with the biochemical abnormalities of an elevated alkaline phosphatase and aminotransferases. Vitamin deficiency particularly of the fat soluble vitamins A, D, and K may infrequently occur due to cholestasis-associated malabsorption. Clinically, consequences of a deficiency state are unusual; however, vitamin A, D, and calcium supplements seem empirically useful. Tight strictures in the distal locations can cause deterioration of liver function and biliary cirrhosis. These strictures can be treated via endoscope (ERCP) with balloon dilatation and/or stent placement. Other treatment regimens showing promise are the use of methotrexate and liver transplantation. The latter is used only in advanced disease states.