Primary sclerosing cholangitis and systemic lupus erythematosus

We report the case of a patient with primary sclerosing cholangitis associated with systemic lupus erythematosus. Only one similar case has been previously reported. The relationship between the two diseases is discussed.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown etiology frequently associated with inflammatory bowel disease and characterized by diffuse inflammation and fibrosis of the intra and/or extrahepatic bile ducts. Recent studies seem to favor autoimmunity in the context of a genetic predisposition as the most likely underlying mechanism for the development of the disease, however our knowledge on the pathogenesis of PSC is still incomplete and further work is needed. The most common manifestations are fatigue, pruritus, jaundice and abdominal pain; however, the increasing use of invasive cholangiography has led to diagnosing this condition in a high proportion of asymptomatic patients. PSC usually follows a progressive course leading to biliary cirrhosis with complications of portal hypertension and hepatic failure. Patients with PSC also may develop a number of other complications, including bacterial cholangitis, dominant biliary strictures, conditions of chronic cholestasis, colorectal cancer and cholangiocarcinoma. Currently, no medical therapy aimed at disrupting disease progression is available, although high-dose ursodeoxycholic acid and other medicines are being evaluated in clinical trials. A better understanding of the pathogenesis of the disease will serve as a guide for evaluating new medical approaches. Liver transplantation is the only therapeutic alternative that improves survival in patients with end-stage PSC. Prognostic models are useful in determining the timing of liver transplantation.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver disease of uncertain etiopathogenesis commonly associated with inflammatory bowel disease (IBD) and is characterized by patchy inflammation of the biliary tree progressing to fibrosis and strictures. The natural history of PSC is highly variable but characteristically follows a progressive clinical course leading to biliary tree strictures, cholestasis, and choledocholithiasis. The course of the disease may be complicated by cholangitis, secondary biliary cirrhosis, liver failure, and cholangiocarcinoma. The diagnosis of PSC is based on typical cholangiographic findings, supported by nonspecific clinical signs and symptoms, cholestatic liver biochemical tests, and liver biopsy. Uncommon and usually clinically obvious secondary causes of sclerosing cholangitis are excluded before establishing the diagnosis of PSC. Therapeutic approaches that show promise include endoscopic therapy and ursodeoxycholic acid. The only accepted therapy for end-stage PSC that can improve long-term outcome is liver transplantation. The diagnosis of cholangiocarcinoma--often difficult and elusive--usually precludes liver transplantation because its prognosis is very poor.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts. An estimated 80% of patients in North America and Europe have coexistent inflammatory bowel disease (IBD). The underlying pathophysiology of PSC remains poorly understood. As a result, there is currently no effective medical therapy to halt disease progression. Important complications from PSC include metabolic bone disease, colorectal neoplasia, and cholangiocarcinoma. Liver transplantation remains the only successful treatment option for patients with advanced liver disease from PSC. A diagnosis of PSC should be considered among individuals with IBD and elevated serum liver biochemical tests.     

Primary sclerosing cholangitis

Opinion statement There is no proven medical therapy for primary sclerosing cholangitis. The goal of management should be treatment of symptoms and complications of cholestasis, as well as attempts at treating the underlying disease process. In addition, efforts should be made to recognize and treat or prevent the known complications of primary sclerosing cholangitis, such as fat-soluble vitamin deficiency, osteopenia, dominant biliary strictures, and cholangiocarcinoma. Although some medical therapy has been shown to improve serum liver test or histology results, there has been no effect on survival or time to liver transplantation. However, preliminary data on high-dosage ursodeoxycholic acid have been encouraging. Liver transplantation remains the only effective treatment and is recommended for patients with end-stage liver disease and symptomatic portal hypertension, liver failure, and recurrent or intractable bacterial cholangitis.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a 'beaded' appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis is a cholestatic liver disease strongly associated with IBD. Considerable advances in the understanding of its pathogenesis have been made. The idea of autoimmunity affecting genetically susceptible individuals is largely accepted; however, much remains to be explained about the origin of this disease. Despite active investigation of different therapeutic modalities with the goal of modifying disease progression, liver transplantation continues to be the only option to provide survival benefit in these patients.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease leading to fibrotic biliary strictures and liver cirrhosis. The patient population is heterogeneous with regard to disease progression and the presence of co-morbidities, complicating the practical handling of patients as well as studies of pathogenetic mechanisms. The aetiology of PSC is unknown, but the recent findings of several robust susceptibility genes emphasise the importance of genetic risk factors. There is no effective medical treatment available to delay the disease progression, but endoscopic therapy of biliary stenoses may be indicated. Follow-up of patients includes management of the inflammatory bowel disease that is found in the majority of cases along with investigations aimed at the early detection of cholangiocarcinoma and colorectal cancer, which also occur at increased frequencies. In the present review, we aim to summarise the present knowledge of PSC with a particular emphasis on the possible basis of disease variability.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis is a chronic cholestatic disease characterized by periductal inflammation of intrahepatic and extrahepatic bile ducts with obliterative fibrosis and duct loss. Significant loss of bile ducts leads to interference with bile flow and ultimately results in cirrhosis of the biliary type. Aside from viral hepatitis and alcoholic liver disease, primary sclerosing cholangitis is one of the most common indications for liver transplantation. Although there is no known beneficial therapy for these patients, research aimed toward better understanding the pathogenetic mechanisms and clinical trials with promising new agents are ongoing.