eMedicine Specialties > Gastroenterology > Biliary

Primary Sclerosing Cholangitis: Differential Diagnoses & Workup

Author: Vikas Khurana, MD, FACP, FACG, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Graduate Hospital, Gastroenterology Associates, PC
Coauthor(s): Tejinder Singh, MD, Lead Physician, Section of Emergency Services, Overton Brooks Veterans Affairs Medical Center; Praveen K Roy, MD, Comments and Criticisms Editor, Cochrane Colorectal Cancer Group
Contributor Information and Disclosures

Updated: Aug 28, 2009

Differential Diagnoses

Abdominal Vascular Injuries
Biliary Trauma
Acalculous Cholecystitis
Cholangiocarcinoma
Autoimmune Hepatitis
Cholangitis
Bile Duct Strictures
Choledocholithiasis
Bile Duct Tumors
Papillary Tumors
Biliary Obstruction
Primary Biliary Cirrhosis

Other Problems to Be Considered

Other entities in the differential diagnoses include congenital diseases (eg, Caroli disease, choledochal cysts) and secondary cholangiopathy as observed in patients with collagen vascular diseases (eg, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis) and in those with infiltrative diseases (eg, mediastinal fibrosis, Riedel thyroiditis, eosinophilic cholangitis, histiocytosis X). Infectious causes from parasitic, fungal, viral, or bacterial infections, or from recurrent cholangitis itself, especially in patients who are immunocompromised, can cause multifocal liver abscesses that lead to a PSC-like appearance of the bile duct.

Workup

Laboratory Studies

  • Liver function tests: These tests are the most valuable in the laboratory workup.
    • Serum alkaline phosphatase dominates the profile, which is cholestatic in nature. Alkaline phosphatase levels are usually 3-5 times reference range values. Alkaline phosphatase can be divided into its various fractions to ascertain its origin from liver disease as opposed to bone disease. Serum gamma-glutamyl transpeptidase levels mirror this rise and can help differentiate cholestasis from bone disease. Some patients with hypothyroidism, hypophosphatemia, or zinc or magnesium deficiency may have normal alkaline phosphatase levels.
    • Serum aminotransferase levels are increased but not markedly so. Serum bilirubin levels, with the conjugated component, are usually increased, but fluctuations in the level can occur. Serum albumin levels decrease later in the course of the disease, and the presence of hypoalbuminemia earlier in the disease may indicate active IBD.
    • Hypergammaglobulinemia is present in 30% of patients, and 50% have increased immunoglobulin (IgM) levels. p-ANCA, aCL antibodies, and ANA are present in up to 84%, 66%, and 53% of patients, respectively.

Imaging Studies

  • ERCP is considered the criterion standard for confirming a diagnosis of PSC. Radiological features in ERCP include multiple strictures and dilations of the intrahepatic and extrahepatic biliary ducts.
  • Transhepatic cholangiography is performed when ERCP is unsuccessful.
  • Because it is noninvasive, magnetic resonance cholangiopancreatography (MRCP) is rapidly developing as the preferred study to evaluate the bile ducts. As image quality continues to improve, MRCP may become the criterion standard.

Procedures

  • Liver biopsy is rarely diagnostic of PSC, although it does help determine both the stage and the prognosis of the disease.

Histologic Findings

A variety of histopathologic liver changes are noted in patients with PSC. The most common characteristic feature is onionskin fibrosis, which describes the appearance of periductal concentric fibrosis around the interlobular and septal bile ducts. This is present in only half of all biopsy specimens from patients with otherwise typical PSC, whereas concentric fibrosis with obliteration of the small ducts (obliterative fibrous cholangitis)—a virtually diagnostic histopathologic lesion—is found in fewer than 10% of biopsy specimens.

Periductal fibrosis may be accompanied by infiltrates of inflammatory cells. Piecemeal necrosis, as occurs in patients with chronic hepatitis, may be observed as well.

Staging

In 1981, Ludwig and associates described 4 stages of PSC, as follows:

  • Stage 1 - Portal hepatitis, degeneration of bile ducts with inflammatory cell infiltrate
  • Stage 2 - Extension of disease to periportal area with prominent bile ductopenia
  • Stage 3 - Septal fibrosis and necrosis
  • Stage 4 - Frank cirrhosis

The most characteristic histological feature of onionskin fibrosis, which consists of concentric fibrosis around the septal bile ducts, is noted in only approximately 10% of biopsy specimens.

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
References
Further Reading
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References

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Further Reading

Related eMedicine Topics

Clinical Trials
 National Guideline Clearinghouse

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Keywords

primary sclerosing cholangitis, PSC, sclerosis of the liver, chronic liver disease, biliary cirrhosis, chronic hepatic disease, cholestasis, intrahepatic bile ducts, extrahepatic bile ducts, liver cirrhosis, portal hypertension, liver transplantation, liver transplant, inflammatory bowel disease, IBD,

ulcerative colitis, Crohn colitis, Crohn disease, bacterial cholangitis, cholangiocarcinoma, hepatomegaly, splenomegaly, endoscopic retrograde cholangiopancreatography, ERCP, magnetic resonance cholangiopancreatography, MRCP

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Contributor Information and Disclosures

Author

Vikas Khurana, MD, FACP, FACG, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Graduate Hospital, Gastroenterology Associates, PC
Disclosure: Nothing to disclose.

Coauthor(s)

Tejinder Singh, MD, Lead Physician, Section of Emergency Services, Overton Brooks Veterans Affairs Medical Center
Disclosure: Nothing to disclose.

Praveen K Roy, MD, Comments and Criticisms Editor, Cochrane Colorectal Cancer Group
Praveen K Roy, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and Canadian Association of Gastroenterology
Disclosure: Nothing to disclose.

Medical Editor

David Greenwald, MD, Fellowship Program Director, Associate Professor, Department of Medicine, Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine
David Greenwald, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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