Information on the following diseases can be found in the Related Disorders section of this report:

• Primary Biliary Cirrhosis

Primary sclerosing cholangitis is characterized by episodes of interrupted or obstructed bile flow from the liver (cholestasis), resulting from inflammation, thickening, and/or abnormal formation of fibrous tissue (fibrosis) within the passages that carry bile from the liver (bile ducts).

The most common presentation of symptoms of primary sclerosing cholangitis is fatigue and itching (pruritis), followed by jaundice. When the flow of bile from the liver is blocked, the bile may be absorbed into the bloodstream, resulting in yellowing of the skin, mucous membranes, and whites of the eyes (obstructive jaundice). Additional symptoms associated with primary sclerosing cholangitis include a general feeling of ill health (malaise); abdominal pain, especially the upper right portion of the abdomen; nausea; dark urine; light-colored stools; and/or abnormal enlargement of the liver (hepatomegaly) and/or spleen (splenomegaly).

In some cases, affected individuals may experience episodes of fever, chills, and night sweats resulting from infection of the bile ducts (bacterial cholangitis). In addition, primary sclerosing cholangitis may progress to cause scarring and damage to the liver (cirrhosis) and increased blood pressure in the veins carrying blood from the gastrointestinal (GI) tract back to the heart through the liver (portal hypertension).

As individuals with primary sclerosing cholangitis age, they may eventually develop life-threatening complications such as liver (hepatic) failure. Individuals with primary sclerosing cholangitis are at a greater risk than the general population of developing a form of cancer that affects the bile ducts (cholangiocarcinoma).

In approximately 50 to 70 percent of cases, individuals with primary sclerosing cholangitis may also have ulcerative colitis, an inflammatory bowel disease (IBD) of unknown cause that is characterized by chronic inflammation and ulceration of the lining of the major portion of the large intestine (colon). In addition, primary sclerosing cholangitis may also be associated with Crohn’s disease, retroperitoneal fibrosis, Peryronie’s disease, and/or several immunodeficiency syndromes. (For more information on these disorders, choose exact disorder name as your search term in the Rare Disease Database.)
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The exact cause of primary sclerosing cholangitis is not known. Several factors have been proposed as possibly being involved with the development of this disorder. These factors include improper copper metabolism, viral infections, genetic and environmental factors, and/or immune system abnormalities.
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Primary sclerosing cholangitis is a rare disorder predominately affecting middle-aged males, although it may affect males of any age.

Symptoms of the following disorders can be similar to primary sclerosing cholangitis. Comparisons may be useful for a differential diagnosis:

Primary biliary cirrhosis, also known as Hanot's cirrhosis, is a rare liver condition occurring mainly in females. It is characterized by yellow discoloration of the skin (jaundice) associated with obstruction and inflammation of the large bile ducts that normally transport bile. Additionally, abnormal cells accumulate in the liver associated with degenerative liver disease (cirrhosis). Blockage may not occur in small bile ducts. Some long-term severe cases of primary sclerosing cholangitis may develop into primary biliary cirrhosis. (For more information on this disorder, choose "Primary Biliary Cirrhosis" as your search term in the Rare Disease Database.)
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Diagnosis
A diagnosis of primary sclerosing cholangitis is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings, and a variety of specialized tests including cholangiography. A cholangiography is a type of X-ray test that is used to examine the bile ducts.

Treatment
There is no specific treatment for individuals with primary sclerosing cholangitis. Treatment is directed toward the specific symptoms that are apparent in each individual and at slowing the progression of the disorder.

Surgery to remove blockages and enlarge narrowed bile ducts may be of benefit to help prevent liver deterioration. Lost vitamins should be replaced when required to prevent complications related to these deficiencies. Antibiotics may be useful in controlling inflammation or infection. The drug cholestyramine may be effective in controlling itching. Additional treatment is symptomatic and supportive.
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Liver transplantation has proven effective in the treatment of individuals with advanced symptoms of primary sclerosing cholangitis (i.e., advanced end-stage liver disease). More research is necessary to determine the long-term safety and effectiveness of liver transplantation as a treatment for severe cases of primary sclerosing cholangitis. In some cases, the disorder has recurred after liver transplantation.

Additional treatments being tested include drainage of blocked bile through tubes inserted in ducts and enlarging abnormally narrowed bile ducts (at least temporarily) by inserting a tiny balloon inside the duct and inflating it (endoscopic balloon dilation). Effectiveness and side effects of these procedures and devices have not been fully documented and more extensive research is being pursued before their therapeutic value for primary sclerosing cholangitis can be evaluated.

The drug ursodiol (ursodeoxycholic acid) has been studied as a treatment for individuals with primary sclerosing cholangitis. In some cases, individuals have demonstrated a temporary improvement in symptoms after the administration of ursodiol. However, the drug did not slow the overall progression of the disorder. More research is necessary to determine the long-term safety and effectiveness of this treatment for primary sclerosing cholangitis.

Drugs that suppress the function of the immune system (immunosuppressive drugs) such as corticosteroids (e.g., methotrexate and cyclosporine) are being studied as potential treatment options for individuals with primary sclerosing cholangitis. More research is necessary to determine the long-term safety and effectiveness of these drugs for primary sclerosing cholangitis.

TEXTBOOKS
Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:812.

Fauci AS, et al., eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:1736.

Leevy CM, et al., eds. Diseases of the Liver and Biliary Tract: Standardization of Nomenclature, Diagnostic Criteria and Prognosis. New York, NY: Raven Press; 1994:79-80.

Yamada T, et al., eds. Textbook of Gastroenterology. 2nd ed. Philadelphia, PA: J.B. Lippincott Company; 1995:2231-40.

JOURNAL ARTICLES
Kaya M, et al. Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience. Am J Gastroenterol. 2001;96:1164-69.

Fleming KA, et al. Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing cholangitis. J Hepatol. 2001;34:360-65.

Benhamou JP. Primary sclerosing cholangitis. Rev Pract. 2000;50:2146-49.

Prall RT, et al. Current therapies and clinical controversies in the management of primary sclerosing cholangitis. Curr Gastroenterol Rep. 2000;2:99-103.

Stiehl A, et al. Therapy of primary sclerosing cholangits. Schweiz Rundsch Med Prax. 2000;89:975-77.

Gow PJ, et al. Liver transplantation for primary sclerosing cholangitis. Liver. 2000;20:97-103.

Stiehl A, et al. Primary sclerosing cholangitis. Can J Gastroenterol. 2000;14:311-15.

Lee YM, et al. Medical treatment of primary sclerosing cholangitis. J Hepatobiliary Pancreat Surg. 1999;6:361-65.

Harrison PM. Diagnosis of primary sclerosing cholangitis. J Hepatobiliary Pancreat Surg. 1999;6:356-60.

Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med. 1997;336:691-95.

Mitchell SA, et al. Review article: the management of primary sclerosing cholangitis. Aliment Pharmacol Ther. 1997;11:33-43.

Harnois DM, et al. Primary sclerosing cholangitis: evolving concepts in diagnosis and treatment. Dig Dis. 1997;15:23-41.

Kaplan MM. Toward better treatment of primary sclerosing cholangitis. N Engl J Med. 1997;336:719-21.