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primary sclerosing cholangitis (PSC)

Recurrent or persistent obstructive jaundice. Etiology: 1) autoimmune mechanism has been postulated - IgG4 disease associated with autoimmune pancreatitis 2) frequently occurs in association with ulcerative colitis* * 80-85% of patients with with primary sclerosing cholangitis have inflammatory bowel disease (generally ulcerative colitis), but only 4% of patients with ulcerative colitis have primary sclerosing cholangitis [3] Epidemiology: - most commonly seen in young men Pathology: 1) inflammation & obliterative fibrosis of the bile ducts, intrahepatic & extrahepatic 2) generally progresses to cholestasis, secondary biliary cirrhosis, portal hypertension, hepatic failure 3) concentric fibrosis of bile ductules Clinical manifestations: 1) frequently asymptomatic 2) progressive fatigue 3) pruritus 4) jaundice 5) intermittent or fluctuating symptoms - unlikely to manifest acutely [9] 6) bacterial cholangitis is uncommon without history of prior biliary tract surgery or instrumentation 7) 85% of patients have inflammatory bowel disease (generally ulcerative colitis) [3] - hematochezia Laboratory: 1) increased serum alkaline phosphatase 2) abnormal liver function tests a) increased serum bilirubin & serum conjugated bilirubin b) increased serum AST c) increased serum ALT d) increased serum GGT 3) IgG4 in serum may be increased (IgG4 disease) - does not preclude 1st line ERCP 4) CA 19-9 in serum for cholangiocarcinoma surveillance [3] 5) liver biopsy (diagnostic for intrahepatic bile duct disease) 6) complete blood count (CBC) - hematochezia due to association with ulcerative colitis Special laboratory: 1) MRCP shows gall bladder & bile duct - 1st line procedure [9] - establishes diagnosis ('string of beads') [3] - annually for cholangiocarcinoma surveillance [3] 2) ERCP combined with cholangiography, expensive [4] a) diagnostic if extrahepatic bile duct disease b) shows short strictures of bile ducts with intervening segments of normal or slightly dilated ducts (beaded appearance, "beads on a string ") c) facilitates diagnosis of cholangiocarcinoma 3) if ERCP is unsuccessful, percutaneous cholangiography should be attempted 4) colonoscopy at the time of diagnosis & every 1-2 years for survelliance [3] 5) patients with inflammatory bowel disease should have surveillance colonoscopy every year [3] Radiology: 1) ultrasound (screening) - screening patients with cirrhosis for hepatocellular carcinoma with ultrasound every 6 months 2) magnetic resonance imaging (MRI) as good as ERCP in patients with cholestatic biochemical profiles Complications: 1) bile duct stricture 2) cholangiocarcinoma 15% lifetime risk [3] a) higher risk for bile duct cancer b) generally develops within the 1st few years of PSC diagnosis 3) higher risk for gall bladder cancer 4) inflammatory bowel disease (85%) - rectal sparing, mild pancolitis, backwash ileitis - elevated risk of pouchitis after colectomy [3] 5) increased risk for colorectal cancer [3] 6) highest mortality among autoimmune liver diseases [3] Differential diagnosis: 1) AIDS cholangiopathy a) CD4 count < 100/uL b) due to CMV or Cryptosporidium [3] 2) ischemic cholangiopathy Management: 1) treatment is generally supportive a) cholestyramine to relieve pruritus b) vitamin supplements - vitamins A, D, & K malaborption may occur c) ursodiol to prevent gallstone formation d) consider obeticholic acid (start 5 mg/day) +/- fibrate if response to ursodiol at 12 months is inadequate [9] (use with caution in patients with decompensated liver disease) e) glucocorticoids for associated autoimmune pancreatitis with elevated IgG4 (IgG4 disease) [3] 2) proctocolectomy in patients with ulcerative colitis has no effect on development of primary sclerosing cholangitis 3) percutaneous or endoscopic balloon dilatation of bile duct strictures may offer palliation (pain, fever) 4) surgery for strictures not amenable to endoscopic or percutaneous intervention in non-cirrhotic patients [5] 5) antibiotics a) antibiotic treatment of superimposed infection b) prophylactic long-term antibiotics might be beneficial for patients with recurrent bacterial cholangitis [5] 6) many patients require liver transplantation [3] - only effective treatment [3]

Interactions

disease interactions

Related

primary biliary cirrhosis; primary biliary cholangitis ulcerative colitis (UC)

General

cholangitis

References

  1. Stedman's Medical Dictionary 26th ed, Williams & Wilkins, Baltimore, 1995
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 321
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Tischendorf JJ et al, Cholangioscopic characterization of dominant bile duct stenosis in patients with primary sclerosing cholangitis. Endoscopy 2006, 38:665 PMID: 16673310 - Arvanitakis M and Deviere J Primary sclerosing cholangitis and recognition of bile duct cancer. Problem solved? Endoscopy 2006, 38:743 PMID: 16810598
  5. Chapman R et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010 Feb; 51:660. PMID: 20101749 (corresponding NGC guideline withdrawn Nov 2015)
  6. Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology. 2013 Sep;145(3):521-36. PMID: 23827861
  7. Lazaridis KN, LaRusso NF Primary Sclerosing Cholangitis N Engl J Med 2016; 375:1161-1170. September 22, 2016 PMID: 27653566 http://www.nejm.org/doi/full/10.1056/NEJMra1506330
  8. Lindor KD, Kowdley KV, Harrison ME; Am Coll Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol. 2015 May;110(5):646-59; Epub 2015 Apr 14. PMID: 25869391
  9. NEJM Knowledge+ Gastroenterology
  10. NIDDK: Primary Sclerosing Cholangitis https://www.niddk.nih.gov/health-information/liver-disease/primary-sclerosing-cholangitis