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Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 2-3/2015

01-06-2015

IgG4-Associated Cholangitis: A Comprehensive Review

Authors: Lowiek M. Hubers, Lucas J. Maillette de Buy Wenniger, Marieke E. Doorenspleet, Paul L. Klarenbeek, Joanne Verheij, Erik A. Rauws, Thomas M. van Gulik, Ronald P. J. Oude Elferink, Stan F. J. van de Graaf, Niek de Vries, Ulrich Beuers

Published in: Clinical Reviews in Allergy & Immunology | Issue 2-3/2015

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Abstract

IgG4-associated cholangitis (IAC) is a major manifestation of immunoglobulin G4-related disease (IgG4-RD), an inflammatory multiorgan disorder of unknown cause. IAC and autoimmune pancreatitis (AIP) may mimic sclerosing cholangitis, cholangiocarcinoma, or pancreatic carcinoma. Typically, elderly male patients present with abdominal discomfort, weight loss, jaundice, and itch. At present, no accurate diagnostic test for IAC and IgG4-RD is at hand, often causing significant diagnostic delay. Serum IgG4 is only diagnostic when markedly raised (>4× ULN). Imaging in IAC discloses mass-forming lesions and/or strictures in the biliary tract. Histology may show tissue infiltration of IgG4-expressing plasma cells. Diagnostic criteria for histologic and imaging findings, serum tests, organ manifestation pattern, and response to immunosuppressive therapy (HISORt) criteria are used for the diagnosis of IgG4-RD. Still, considering the difficulty in diagnosing IAC and AIP, unnecessary hepatic or pancreatic resections for presumed malignancies occur. The good response to corticosteroid therapy in IAC and other manifestations of IgG4-RD suggests an immune-mediated inflammatory disease. Maintenance immunosuppression after induction of remission is needed in the majority of patients to avoid relapse. The pathogenesis of IAC and IgG4-RD remains poorly understood. Unresolved questions include: (i) Does IgG4 have a pro- or anti-inflammatory role in IAC? (ii) Is IAC a B cell- and/or T cell-mediated disease? (iii) Which are the molecular targets attacked by the immune system in IgG4-RD? Here, we review the diagnostic and therapeutic management of the disease and discuss recent pathophysiological findings, which might help to better understand the molecular mechanisms contributing to IAC and other manifestations of IgG4-RD.
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Metadata
Title
IgG4-Associated Cholangitis: A Comprehensive Review
Authors
Lowiek M. Hubers
Lucas J. Maillette de Buy Wenniger
Marieke E. Doorenspleet
Paul L. Klarenbeek
Joanne Verheij
Erik A. Rauws
Thomas M. van Gulik
Ronald P. J. Oude Elferink
Stan F. J. van de Graaf
Niek de Vries
Ulrich Beuers
Publication date
01-06-2015
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 2-3/2015
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-014-8430-2

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