eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Primary Sclerosing Cholangitis: Differential Diagnoses & Workup

Author: Lynette Gillis, MD, Assistant Professor, Director of Pediatric Hepatology and Liver Transplant, Division of Pediatric Gastroenterology, Hepatology and Nutrition and Division of Medical Genetics, Vanderbilt University
Contributor Information and Disclosures

Updated: Jun 19, 2009

Differential Diagnoses

Autoimmune Chronic Active Hepatitis
Cholestasis
Histiocytosis
Human Immunodeficiency Virus Infection

Other Problems to Be Considered

Workup

Laboratory Studies

The following studies may be indicated in primary sclerosing cholangitis (PSC):

  • Liver function tests
    • The most common abnormality is an elevated alkaline phosphatase or γ-glutamyltransferase (GGT) level.
    • 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.
    • Results from hepatic 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 are elevated in 48% and 80% of cases of primary sclerosing cholangitis, respectively. The serum globulin fraction may also be elevated in some patients with primary sclerosing cholangitis.
  • Perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) have been found to be present in 60-82% of patients with primary sclerosing cholangitis but lack diagnostic specificity for primary sclerosing cholangitis; frequency in ulcerative colitis (UC) is similar. 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 primary sclerosing cholangitis, independent of inflammatory bowel disease (IBD) 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.

Imaging Studies

  • Magnetic resonance (MR) cholangiography
    • Peripheral wedge-shaped areas of high T2 signal intensity and dilatation of bile ducts are characteristic MR findings in primary sclerosing cholangitis.
    • Pathologic correlation of MR cholangiography (MRC) findings suggests that these features may be related to underlying perfusion changes and bile duct inflammation.
    • The overall diagnostic accuracy of MRC in patients with primary sclerosing cholangitis is 90%, compared to 97% for endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC).2
    • The advantages of MRC include less risk for complications as compared with ERCP. In addition, MRC has the advantage of visualizing bile ducts proximal to obstructed areas.
  • Ultrasonography
    • Ultrasonography may reveal intrahepatic and extrahepatic ductal dilatation, increased echogenicity and heterogeneity observed with cirrhosis, and splenomegaly and ascites observed with portal hypertension.3
    • Ultrasonographic findings may be normal in as many as 50% of patients.

Procedures

  • ERCP
    • Cholangiography remains the criterion standard for establishing the diagnosis of primary sclerosing cholangitis.
    • Cholangiography demonstrates irregularly distributed areas of segmental bile duct fibrosis interposed by areas of saccular dilation that result in the characteristic appearance of beading. As many as 40% of children with primary sclerosing cholangitis 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 primary sclerosing cholangitis, with a decrease in cholestatic complaints and improvement of the cholestatic biochemical profile (alkaline phosphatase, γ-glutamyltransferase, conjugated bilirubin) for several years.
  • 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. 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 are periductal fibrosis with inflammation, bile duct proliferation, and ductopenia. This pathognomonic fibro-obliterative cholangiopathy has been occasionally observed in children with primary sclerosing cholangitis.

    Fibro-obliterative cholangiopathy. Image courtesy...

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

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    Fibro-obliterative cholangiopathy. Image courtesy...

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

Staging

  • The hepatic progression of primary sclerosing cholangitis is divided into 4 histologic stages. 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. 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.

More on Primary Sclerosing Cholangitis

Overview: Primary Sclerosing Cholangitis
Differential Diagnoses & Workup: Primary Sclerosing Cholangitis
Treatment & Medication: Primary Sclerosing Cholangitis
Follow-up: Primary Sclerosing Cholangitis
Multimedia: Primary Sclerosing Cholangitis
References
Further Reading
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References

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Keywords

primary sclerosing cholangitis, PSC, liver disease, cirrhosis, portal hypertension, liver failure, end-stage liver disease, hepatomegaly, liver transplantation, inflammatory bowel disease, IBD, ulcerative colitis, UC, hepatomegaly, cholestasis, pruritus, cholangitis, fat malabsorption, treatment, diagnosis

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Contributor Information and Disclosures

Author

Lynette Gillis, MD, Assistant Professor, Director of Pediatric Hepatology and Liver Transplant, Division of Pediatric Gastroenterology, Hepatology and Nutrition and Division of Medical Genetics, Vanderbilt University
Lynette Gillis, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Liver Foundation, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Disclosure: Nothing to disclose.

Medical Editor

Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology and Nutrition, Associate Professor, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania
Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David A Piccoli, MD, Chief, Division of Gastroenterology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine
David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

 
 
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