Pediatric Primary Sclerosing Cholangitis Clinical Presentation

Updated: Apr 26, 2017
  • Author: Henry C Lin, MD; Chief Editor: Carmen Cuffari, MD  more...
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Presentation

History and Physical Examination

The clinical presentation of primary sclerosing cholangitis (PSC) in children varies widely and frequently lacks the obvious features of cholestasis. Patients may be asymptomatic with elevated liver function test findings or hepatomegaly, prompting further workup for primary sclerosing cholangitis. Approximately 55% of patients have hepatomegaly and 30% have splenomegaly at presentation. Patients may also present with fatigue, pruritus, fever of unknown origin, intermittent jaundice, or weight loss. Some patients present with the stigmata of chronic liver disease and cirrhosis. The onset and progression tend to be insidious.

Modes of presentation include the following:

  • Asymptomatic patients present with incidental findings of hepatomegaly on examination or abnormal liver function test results

  • Symptomatic patients may present with nonspecific complaints, including fatigue, pruritus, abdominal pain, fever, weight loss, and intermittent jaundice

  • Patients with cholestasis present with complications of cholestasis, including pruritus, cholangitis, and fat malabsorption

  • Patients with cirrhosis present with complications of portal hypertension, including ascites, variceal bleeding, and splenomegaly

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Staging

The hepatic progression of primary sclerosing cholangitis is divided into 4 histologic stages, as follows: [20]

  1. Portal hepatitis, degeneration of bile ducts with inflammatory cells infiltrate

  2. Extension of disease to periportal areas, with prominent bile ductopenia

  3. Septal fibrosis and necrosis

  4. Frank cirrhosis

These stages are used to document histologic progression and may help evaluate treatment effect in clinical trials. At present, these stages have limited value in predicting the natural history of the disease, most likely because of the high degree of sampling variability in the hepatic pathology of primary sclerosing cholangitis.

Researchers at the Mayo Clinic have developed a multivariate statistical survival model from long-term survival data (Mayo risk score). The Mayo natural history model of primary sclerosing cholangitis computes the score on the basis of the patient's age, history of variceal bleeding, and serum levels of albumin, bilirubin, and aspartate aminotransferase. This has been a major step in identifying patients at low, moderate, and high risk of dying while early in the course of primary sclerosing cholangitis. [21, 22, 23]

In an age-adjusted multivariate analysis, each unit increase in the Mayo risk score was associated with a 2.5-fold increased risk of death, whereas the Child-Pugh classification for advanced cirrhosis had no significant impact on survival rate. The histologic stage of disease has consistently been useful in predicting survival rate, most likely because of a large sampling variability with liver biopsies. [21, 22, 23, 24]

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Complications

Cholangiocarcinoma (CCA) develops in 10-15% of adult patients with primary sclerosing cholangitis (PSC). CCA has been reported in children with primary sclerosing cholangitis. [25, 26, 27] Early detection of CCA is limited by a lack of reliable serologic, radiologic, and endoscopic findings. Serum CA 19-9 appears useful (75% sensitivity, 80% specificity) in discriminating which patients with primary sclerosing cholangitis have CCA.

The risk of colorectal cancer or dysplasia is increased in patients with ulcerative colitis (UC) and primary sclerosing cholangitis. Chronically active disease may be a risk factor, whereas folate may have a protective effect. Colorectal cancers associated with primary sclerosing cholangitis are more likely to be proximal, diagnosed at a more advanced stage, and fatal. Colectomy in patients with UC and primary sclerosing cholangitis does not alter the natural history of primary sclerosing cholangitis.

Patients who have undergone liver transplantation are susceptible to a wide array of complications secondary to chronic immunosuppression. The incidence of acute cellular and chronic ductopenic rejection is higher in patients with primary sclerosing cholangitis than in individuals of a non–primary sclerosing cholangitis control group. Chronic ductopenic rejection adversely affects patient and graft survival. Biliary strictures, both anastomotic and nonanastomotic, can occur.

Recurrent sclerosing cholangitis occurs in 10-33% of patients with primary sclerosing cholangitis who have undergone liver transplantation. [13, 18, 28, 29, 30, 31, 32] Data from the Mayo Clinic's review of 150 consecutive patients with primary sclerosing cholangitis who received 174 liver allografts suggests that postoperative biliary strictures or recurrence of primary sclerosing cholangitis does not impact patient survival.

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