Diagnosis
Primary sclerosing cholangitis
A chronic, progressive inflammatory stenosing disease of the bile ducts.
Etiology
Cause [1ib]
Unknown
Genetic predisposition (HLA-B8 and HLA-DR3)
Exposure to an environmental antigen
Aberrant immunologic response
Associated with ulcerative colitis (70%), Crohns disease (10%), pancreatitis, diabetes and cholangitis
Pathophysiology [1ib]
Chronic inflammation of the bile duct causes fibrosis, biliary strictures, cholestasis
Biliary obstruction might facilitate cholangitis
Parenchymal injuries --> cirrhosis:
Portal hypertension
Liver failure
Complications [qss][1ib]
Fat-soluble A, D, E, and K vitamin deficiencies
Osteoporosis
Biliary strictures
Cholangitis
Portal hypertension
Liver failure
Hepatocellular carcinoma in patients with cirrhosis
Cholangiocarcinoma (15%)
Gallbladder cancer
Colon cancer in patients with concomitant ulcerative colitis
Cholelithiasis
Epidemiology
Incidence per 100.000 [kdy][pwf][qss][91f][szc][cad][cvr][1ib]
Symptoms & findings
Symptoms
Confusion, Dark urine, Fatigue, Fever, Hepatomegaly, Hyperpigmentation, Icterus, Pruritus, Splenomegaly, Weight loss
Clinical findings
ANA, ANCA, Anti-cardiolipin antibody, Anti-SMA, Ascites, Bile duct stenosis, Bilirubinuria, Cholestasis, Decreased Albumin, Elevated ALAT, Elevated ALP, Elevated ASAT, Elevated Bilirubin, Elevated PT-INR, Hypergammaglobulinemia, Jaundice
Anamneses
None listed.
Localized findings
Approach
Blood test: Antineutrophilic cytoplasmic antibodies, Antinuclear antibodies, and anticardiolipin antibodies
MRCP
ERCP
PTC
Colonoscopy and biopsy every 6-12 months for surveillance of colorectal carcinoma
CA 19-9 levels every 6-12 months for surveillance of cholangiocarcinoma
Treatment
No curative pharmacotherapy exists for PSC [ibm]
Treatment of cholestasis: [1ib]
Ursodeoxycholic acid 15 to 20 mg/kg daily for the treatment of cholestasis
Bile acid sequestrants
Rifampin
Naltrexone
Immunosuppression: control the disease progression
Prednisolone, budesonide, colchicine, penicillamine, azathioprine, tacrolimus, methotrexate, mycophenolate mofetil, and antitumor necrosis factor antibodies
ERCP with balloon dilatation: if pruritus/cholangitis and
Defined stenosis (<1.5 mm common bile duct, <1 mm in the hepatic ducts)
Surgery:
Choledochoduodenostomy
Choledochojejunostomy
Liver transplantation is the definitive treatment
Differential diagnoses
Acalculous cholecystitis, Acute pancreatitis, Ampullary carcinoma, Autoimmune hepatitis, Benign bile duct tumor, Bile duct stricture, Biliary obstruction, Cholangiocarcinoma, Cholangitis, Choledocholithiasis, Cholelithiasis, Cirrhosis, Gallbladder cancer, HIV, Langerhans cell histiocytosis, Primary biliary cirrhosis, Viral hepatitis
References
[1] Rawla P, Samant H. Primary Sclerosing Cholangitis. Updated 2023 Feb 12: https://www.ncbi.nlm.nih.gov/books/NBK537181/
[2] Leung KK, Li W, Hansen B, Gulamhusein A, Lapointe-Shaw L, Shaheen AA, Ricciuto A, Benchimol EI, Flemming JA, Hirschfield GM. Primary sclerosing cholangitis–inflammatory bowel disease: Epidemiology, mortality, and impact of diagnostic sequence. JHEP Reports 2025. vol. 7 - 1-11.
[3] Liang H, Manne S, Shick J, Lissoos T, Dolin P. Incidence, prevalence, and natural history of primary sclerosing cholangitis in the United Kingdom. Medicine (Baltimore). 2017 Jun;96(24):e7116.
[4] Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol. 2012 May;56(5):1181-1188.
[5] Bambha K, Kim WR, Talwalkar J, Torgerson H, Benson JT, Therneau TM, Loftus EV Jr, Yawn BP, Dickson ER, Melton LJ 3rd. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003 Nov;125(5):1364-9.
[6] Boberg KM, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol. 1998 Jan;33(1):99-103.
[7] Toy, E., Balasubramanian, S., Selmi, C. et al. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol 11, 83 (2011).
[8] Trivedi PJ, Bowlus CL, Yimam KK, Razavi H, Estes C. Epidemiology, Natural History, and Outcomes of Primary Sclerosing Cholangitis: A Systematic Review of Population-based Studies. Clinical Gastroenterology and Hepatology 2022;20:1687–1700.
[9] http://emedicine.medscape.com/article/187724 (2014-01-02); [Medscape]