Pediatric Primary Sclerosing Cholangitis Workup

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

Approach Considerations

In patients with primary sclerosing cholangitis (PSC), the most valuable lab studies are liver function tests, including serum alkaline phosphatase, serum aminotransferase, and hypergammaglobulinemia. Endoscopic retrograde cholangiopancreatography (ERCP) is the most important imaging study. Magnetic resonance cholangiography and ultrasonography are also utilized. The most characteristic histologic findings of primary sclerosing cholangitis are periductal fibrosis with inflammation, bile duct proliferation, and ductopenia.

Liver biopsy findings are nonspecific and are infrequently diagnostic. However, liver histology remains important to exclude other causes of chronic cholestasis and to stage the disease.

Current challenges in the diagnosis and treatment of primary sclerosing cholangitis in pediatrics are well recognized. [33]

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Laboratory Studies

No laboratory studies are specific for primary sclerosing cholangitis (PSC), but the most common abnormality is an elevated alkaline phosphatase or gamma-glutamyl transferase (GGT) level. Abnormal GGT levels have been noted in as many as 96% of children with PSC at the time of diagnosis. Serum transaminase levels may be normal or elevated to several times normal. The serum bilirubin level is elevated in advanced stages of primary sclerosing cholangitis. [13, 15, 17]

Liver synthetic function tests (eg, serum albumin, prothrombin time [PT]) become abnormal with advanced disease activity. Serum cholylglycine is often markedly elevated, out of proportion to the elevation of serum bilirubin.

Immunoglobulin G (IgG) and immunoglobulin M (IgM) levels (see Immunoglobulins) are elevated in 48% and 80% of cases of PSC, respectively. The serum globulin fraction may also be elevated in some patients with primary sclerosing cholangitis. Autoimmune markers noted at diagnosis include antinuclear antibody (ANA), found in 45%; anti–smooth muscle antibody (ASMA), found in 36%; and perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs), found in 60-82% of patients with primary sclerosing cholangitis. However, these all lack diagnostic specificity.

Assessment of the target antigens for ANCA (eg, catalase, alpha-enolase, lactoferrin) does not significantly contribute to their clinical importance. The presence of ANCA is associated with a more severe course of autoimmune liver disease. The anti– Saccharomyces cerevisiae antibody is also found in some patients with PSC, independent of inflammatory bowel disease status.

A serum carbohydrate antigen 19-9 (CA 19-9) level greater than 100 U/mL has 75% sensitivity and 80% specificity in identifying patients with primary sclerosing cholangitis who have cholangiocarcinoma.

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Magnetic Resonance Cholangiography

Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive tool that images abnormalities of the pancreaticobiliary tress. Peripheral wedge-shaped areas of high T2-signal intensity and dilatation of bile ducts are characteristic MRCP in primary sclerosing cholangitis (PSC). Pathologic correlation of MRCP findings suggests that these features may be related to underlying perfusion changes and bile duct inflammation.

The overall diagnostic accuracy of MRCP in patients with PSC is 90%, compared to 97% for endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). [34] The advantages of MRCP include less risk of complications, as compared with ERCP. In addition, MRCP has the advantage of visualizing bile ducts proximal to obstructed areas, especially in small children in whom ERCP is not a feasible option. The main limitation of MRCP is that it does not allow for therapeutic interventions. [35, 36, 37, 38]

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Ultrasonography

Ultrasonography may reveal intrahepatic and extrahepatic ductal dilatation; increased echogenicity and heterogeneity observed with cirrhosis; and splenomegaly and ascites observed with portal hypertension. [39] Ultrasonographic findings may be normal in as many as 50% of patients.

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Endoscopic Retrograde Cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) remains the criterion standard for establishing the diagnosis of primary sclerosing cholangitis (PSC). ERCP demonstrates irregularly distributed areas of segmental bile duct fibrosis interposed by areas of saccular dilation that result in the characteristic appearance of beading. [40, 41]

As many as 40% of children with PSC lack extrahepatic duct involvement at the time of diagnosis. Serial cholangiograms have shown that in most patients with disease limited to the intrahepatic ducts, the disease progresses to involvement of the extrahepatic ducts.

Therapeutic interventions, such as dilation of strictures or placement of an endoprosthesis, can be performed during ERCP, but they carry an increased complication rate. Short-term stenting for symptomatic dominant strictures may have a role in PSC [42] , with a decrease in cholestatic complaints and improvement of the cholestatic biochemical profile (alkaline phosphatase, gamma-glutamyl transferase, conjugated bilirubin) for several years.

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Liver Biopsy

Certain liver histologic findings are highly suggestive of primary sclerosing cholangitis. More often, liver biopsy findings are nonspecific and infrequently diagnostic. Nevertheless, liver histology remains important to exclude other causes of chronic cholestasis and to stage the disease.

Sampling variability is observed in needle or core liver biopsies secondary to the heterogeneous distribution of biliary lesions.

Histologic Findings

A wide range of histologic findings is observed in primary sclerosing cholangitis (PSC). Nonspecific features include a periductal concentration of mononuclear cells and ductular proliferation. Less specific liver histology can present with a picture resembling chronic active hepatitis. One series of childhood cases described consistent periportal copper-associated protein (orcein stain) positivity.

The most characteristic findings of primary sclerosing cholangitis is focal concentric edema and fibrosis around the interlobular bile ducts (“onion-skinning”). The pathognomonic fibro-obliterative cholangiopathy (see the image below) typically occurs in the early stage and over this lesion is replaced by loss of bile ducts. This ductopenia may be local, and in nonobliterated zones, bile duct proliferation may occur instead. With progression of portal fibrosis, biliary cirrhosis may develop. [43]

Fibro-obliterative cholangiopathy. Image courtesy Fibro-obliterative cholangiopathy. Image courtesy of Dr. Kay Washington.
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