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IgG4-related diseases of the digestive tract

Nature Reviews Gastroenterology & Hepatology volume 19, pages 185–197 (2022)Cite this article

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Abstract

IgG4-related conditions affecting the digestive tract are part of a multi-organ fibro-inflammatory disorder termed IgG4-related disease (IgG4-RD), with autoimmune pancreatitis and IgG4-related cholangitis being the most prominent manifestations. Gastrointestinal symptoms include jaundice, weight loss, abdominal pain, biliary strictures, and pancreatic and hepatic masses that mimic malignant diseases. IgG4-RD manifestations occur less frequently elsewhere in the digestive tract, namely in the oesophagus, retroperitoneum or intestine. Evidence-based European guidelines frame the current state-of-the-art in the diagnosis and management of IgG4-related digestive tract disease. Diagnosis is based on histology (if available), imaging, serology, other organ involvement and response to therapy (HISORt criteria). Few biomarkers beyond serum IgG4 concentrations are reliable. The first-line therapy (glucocorticoids) is swiftly effective but disease flares are common at low doses or after tapering. Second-line therapy might consist of other immunosuppressive drugs such as thiopurines or rituximab. Further trials, for example, of anti-CD19 drugs, are ongoing. Although an association between IgG4-RD and the development of malignancies has been postulated, the true nature of this relationship remains uncertain at this time.

Key points

  • IgG4-related disease (IgG4-RD) is a systemic condition that can affect nearly all organs but has a predilection for the pancreas (autoimmune pancreatitis) and bile ducts (IgG4-related cholangitis).

  • Diagnosis of IgG4-RD relies on elevated IgG4 levels in serum and typical imaging features.

  • Histological confirmation of the clinical findings should be sought, preferably with endoscopic ultrasonography-guided fine-needle biopsy.

  • First-line therapy consists of corticosteroid treatment; second-line therapy consists of conventional immunosuppressants, such as azathioprine, mycophenolate mofetil and ciclosporine, or CD20 depletion with rituximab.

  • Relapses are frequent, occurring in 10–20% of patients with autoimmune pancreatitis and 20–50% of patients with IgG4-related cholangitis.

  • New guidelines are helping to raise awareness and understanding of IgG4-RD of the digestive tract.

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Fig. 1: IgG4-related disease in the gastrointestinal tract.
Fig. 2: Potential mechanism of immune-mediated fibrosis in IgG4-RD.
Fig. 3: Pathology of IgG4-related disease in the pancreas and bile ducts.
Fig. 4: IgG4 in blood and tissue.
Fig. 5: Diagnostic algorithm for AIP and IRC.

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Acknowledgements

The work of J.M.L. is supported by a grant from United European Gastroenterology and the Swedish Rheuma League (Reumatikerförbundet R-856891).

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Authors and Affiliations

  1. Department for Upper Digestive Diseases, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden

    J.-Matthias Löhr & Miroslav Vujasinovic

  2. Department of Internal Medicine I, Martin Luther University, Halle, Germany

    Jonas Rosendahl

  3. Division of Rheumatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    John H. Stone

  4. Department of Gastroenterology & Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, Netherlands

    Ulrich Beuers

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All authors contributed to researching data for the article, made a substantial contribution to the discussion of content, and wrote, reviewed or edited the manuscript before submission.

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J.-M.L., M.V. and J.R. declare that they received honoraria for lecturing from Abbott, Dr Falk, Genentech and Mylan. In addition, J.H.S. declares that he received honoraria for lecturing from Abbott, and U.B. declares that he received honoraria for lecturing from Genentech.

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Nature Reviews Gastroenterology & Hepatology thanks K. Okazaki, G. Webster and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Löhr, JM., Vujasinovic, M., Rosendahl, J. et al. IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol 19, 185–197 (2022). https://doi.org/10.1038/s41575-021-00529-y

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