Differential Diagnosis from Primary Sclerosing Cholangitis

  • Sung-Hoon Moon
  • Myung-Hwan KimEmail author


Primary sclerosing cholangitis (PSC), a chronic progressive disease of unknown etiology, is characterized by fibrosis and strictures involving the intra- and extrahepatic bile ducts [1, 2]. PSC is a distinct entity from IgG4-related sclerosing cholangitis (IgG4-SC), but some IgG4-SC masquerades as PSC by way of similar manifestations, such as frequent stenosis of both intra- and extrahepatic bile ducts, bile ductal wall thickening, male predominance, cholestatic liver dysfunction, and initial mild symptoms [3–7]. The differential diagnosis between PSC and IgG4-SC is clinically important because their treatment modalities and prognosis are very different [2, 7, 8]. Timely diagnosis of IgG4-SC can lead clinicians to prescribe adequate corticosteroid therapy that can reverse bile duct strictures/wall thickening and cholestatic liver dysfunction and could potentially prevent future advanced liver disease [2]. A proper diagnosis of PSC, in turn, is crucial for optimizing the surveillance of the disease progression to hepatic decompensation and the need for liver transplantation.


  1. 1.
    Lindor KD, Kowdley KV, Harrison ME. ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol. 2015;110:646–59.CrossRefPubMedGoogle Scholar
  2. 2.
    Moon SH, Kim MH, Lee JK, Baek S, Woo YS, Cho DH, et al. Development of a scoring system for differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis. J Gastroenterol. 2017;52:483–93.CrossRefPubMedGoogle Scholar
  3. 3.
    Bjornsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology. 2007;45:1547–54.CrossRefPubMedGoogle Scholar
  4. 4.
    Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51:660–78.CrossRefPubMedGoogle Scholar
  5. 5.
    Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–15.CrossRefPubMedGoogle Scholar
  6. 6.
    Karlsen TH, Boberg KM. Update on primary sclerosing cholangitis. J Hepatol. 2013;59:571–82.CrossRefPubMedGoogle Scholar
  7. 7.
    Tanaka A, Tazuma S, Okazaki K, Tsubouchi H, Inui K, Takikawa H. Nationwide survey for primary sclerosing cholangitis and IgG4-related sclerosing cholangitis in Japan. J Hepatobiliary Pancreat Sci. 2014;21:43–50.CrossRefPubMedGoogle Scholar
  8. 8.
    Culver EL, Chapman RW. IgG4-related hepatobiliary disease: an overview. Nat Rev Gastroenterol Hepatol. 2016;13:601–12.CrossRefPubMedGoogle Scholar
  9. 9.
    Bonato G, Cristoferi L, Strazzabosco M, Fabris L. Malignancies in primary sclerosing cholangitis - a continuing threat. Dig Dis. 2015;33(Suppl 2):140–8.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Boonstra K, Weersma RK, van Erpecum KJ, Rauws EA, Spanier BW, Poen AC, et al. Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology. 2013;58:2045–55.CrossRefPubMedGoogle Scholar
  11. 11.
    Takakura WR, Tabibian JH, Bowlus CL. The evolution of natural history of primary sclerosing cholangitis. Curr Opin Gastroenterol. 2017;33:71–7.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Benito de Valle M, Muller T, Bjornsson E, Otten M, Volkmann M, Guckelberger O, et al. The impact of elevated serum IgG4 levels in patients with primary sclerosing cholangitis. Dig Liver Dis. 2014;46:903–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Molodecky NA, Kareemi H, Parab R, Barkema HW, Quan H, Myers RP, et al. Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology. 2011;53:1590–9.CrossRefPubMedGoogle Scholar
  14. 14.
    van Buuren HR, Vleggaar FP, Willemien Erkelens G, Zondervan PE, Lesterhuis W, Van Eijck CH, et al. Autoimmune pancreatocholangitis: a series of ten patients. Scand J Gastroenterol Suppl. 2006;243:70–8.CrossRefGoogle Scholar
  15. 15.
    Huggett MT, Culver EL, Kumar M, Hurst JM, Rodriguez-Justo M, Chapman MH, et al. Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort. Am J Gastroenterol. 2014;109:1675–83.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. Lancet. 2013;382:1587–99.CrossRefPubMedGoogle Scholar
  17. 17.
    Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology. 2013;145:521–36.CrossRefPubMedGoogle Scholar
  18. 18.
    Karlsen TH, Schrumpf E, Boberg KM. Update on primary sclerosing cholangitis. Dig Liver Dis. 2010;42:390–400.CrossRefPubMedGoogle Scholar
  19. 19.
    Ohara H, Nakazawa T, Kawa S, Kamisawa T, Shimosegawa T, Uchida K, et al. Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related sclerosing cholangitis: a Japanese cohort. J Gastroenterol Hepatol. 2013;28:1247–51.CrossRefPubMedGoogle Scholar
  20. 20.
    Gardner CS, Bashir MR, Marin D, Nelson RC, Choudhury KR, Ho LM. Diagnostic performance of imaging criteria for distinguishing autoimmune cholangiopathy from primary sclerosing cholangitis and bile duct malignancy. Abdom Imaging. 2015;40:3052–61.CrossRefPubMedGoogle Scholar
  21. 21.
    Boonstra K, Culver EL, de Buy Wenniger LM, van Heerde MJ, van Erpecum KJ, Poen AC, et al. Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology. 2014;59:1954–63.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Bjornsson E, Chari S, Silveira M, Gossard A, Takahashi N, Smyrk T, et al. Primary sclerosing cholangitis associated with elevated immunoglobulin G4: clinical characteristics and response to therapy. Am J Ther. 2011;18:198–205.CrossRefPubMedGoogle Scholar
  23. 23.
    Mendes FD, Jorgensen R, Keach J, Katzmann JA, Smyrk T, Donlinger J, et al. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006;101:2070–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Zhang L, Lewis JT, Abraham SC, Smyrk TC, Leung S, Chari ST, et al. IgG4+ plasma cell infiltrates in liver explants with primary sclerosing cholangitis. Am J Surg Pathol. 2010;34:88–94.CrossRefPubMedGoogle Scholar
  25. 25.
    Nakazawa T, Naitoh I, Hayashi K, Okumura F, Miyabe K, Yoshida M, et al. Diagnostic criteria for IgG4-related sclerosing cholangitis based on cholangiographic classification. J Gastroenterol. 2012;47:79–87.CrossRefPubMedGoogle Scholar
  26. 26.
    Nakazawa T, Ohara H, Sano H, Aoki S, Kobayashi S, Okamoto T, et al. Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc. 2004;60:937–44.CrossRefPubMedGoogle Scholar
  27. 27.
    Moon SH, Kim MH. The role of endoscopy in the diagnosis of autoimmune pancreatitis. Gastrointest Endosc. 2012;76:645–56.CrossRefPubMedGoogle Scholar
  28. 28.
    Kalaitzakis E, Levy M, Kamisawa T, Johnson GJ, Baron TH, Topazian MD, et al. Endoscopic retrograde cholangiography does not reliably distinguish IgG4-associated cholangitis from primary sclerosing cholangitis or cholangiocarcinoma. Clin Gastroenterol Hepatol. 2011;9:800–803 e802.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Itoi T, Kamisawa T, Igarashi Y, Kawakami H, Yasuda I, Itokawa F, et al. The role of peroral video cholangioscopy in patients with IgG4-related sclerosing cholangitis. J Gastroenterol. 2013;48:504–14.CrossRefPubMedGoogle Scholar
  30. 30.
    Naitoh I, Nakazawa T, Hayashi K, Miyabe K, Shimizu S, Kondo H, et al. Comparison of intraductal ultrasonography findings between primary sclerosing cholangitis and IgG4-related sclerosing cholangitis. J Gastroenterol Hepatol. 2015;30:1104–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92.CrossRefPubMedGoogle Scholar
  32. 32.
    Oh HC, Kim MH, Lee KT, Lee JK, Moon SH, Song TJ, et al. Clinical clues to suspicion of IgG4-associated sclerosing cholangitis disguised as primary sclerosing cholangitis or hilar cholangiocarcinoma. J Gastroenterol Hepatol. 2010;25:1831–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Kawakami H, Zen Y, Kuwatani M, Eto K, Haba S, Yamato H, et al. IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater’s ampulla and the bile duct. J Gastroenterol Hepatol. 2010;25:1648–55.CrossRefPubMedGoogle Scholar
  34. 34.
    Naitoh I, Nakazawa T, Ohara H, Ando T, Hayashi K, Tanaka H, et al. Endoscopic transpapillary intraductal ultrasonography and biopsy in the diagnosis of IgG4-related sclerosing cholangitis. J Gastroenterol. 2009;44:1147–55.CrossRefPubMedGoogle Scholar
  35. 35.
    Deheragoda MG, Church NI, Rodriguez-Justo M, Munson P, Sandanayake N, Seward EW, et al. The use of immunoglobulin g4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis. Clin Gastroenterol Hepatol. 2007;5:1229–34.CrossRefPubMedGoogle Scholar
  36. 36.
    Boberg KM, Chapman RW, Hirschfield GM, Lohse AW, Manns MP, Schrumpf E. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol. 2011;54:374–85.CrossRefPubMedGoogle Scholar
  37. 37.
    Parkes M, Booth JC, Pillai G, Mee AS. Do steroids help jaundice caused by primary sclerosing cholangitis? J Clin Gastroenterol. 2001;33:319–22.CrossRefPubMedGoogle Scholar
  38. 38.
    Zenouzi R, Lohse AW. Long-term outcome in PSC/AIH “overlap syndrome”: does immunosuppression also treat the PSC component? J Hepatol. 2014;61:1189–91.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2019

Authors and Affiliations

  1. 1.Department of Internal MedicineHallym University College of Medicine, Hallym University Sacred Heart HospitalAnyangSouth Korea
  2. 2.Department of Internal MedicineUniversity of Ulsan College of Medicine, Asan Medical CenterSeoulSouth Korea

Personalised recommendations