Korean J Gastroenterol.  2020 May;75(5):257-263. 10.4166/kjg.2020.75.5.257.

Recent Updates of Immunoglobulin G4-related Pancreatobiliary Disease

• Lee GC
• Moon SH

• KMID: 2504246
• DOI: http://doi.org/10.4166/kjg.2020.75.5.257

Abstract

Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis (IgG4-SC) are the pancreatobiliary manifestations of IgG4-related disease. IgG4-related disease is a newly named fibroinflammatory condition that is characterized by tumefactive lesions that contain dense lymphoplasmacytic infiltrates rich in IgG4-positive cells and often by elevated serum IgG4 concentrations. IgG4-related pancreatobiliary disease is often disguised as pancreatobiliary malignancies owing to its tumefactive nature and clinical presentations, such as obstructive jaundice. The differentiation of IgG4-SC from primary sclerosing cholangitis is also essential because of the significant differences in treatment responses and prognosis. A timely diagnosis of IgG4-related pancreatobiliary disease can lead clinicians to prescribe adequate glucocorticoid treatment that can reverse the pancreatobiliary duct strictures and obstructive jaundice. On the other hand, the diagnosis of IgG4-related pancreatobiliary disease is sometimes challenging because there is no single diagnostic clinical test. The diagnosis of IgG4-related pancreatobiliary disease rests on fulfilling the diagnostic criteria, including imaging, serology, other organ involvement, histology, and response to steroids. Approximately 50% of patients with IgG4-related pancreatobiliary disease experience relapse, despite IgG4-related pancreatobiliary disease showings a favorable short-term prognosis after glucocorticoid therapy. To reduce the relapse, long maintenance treatment for 3 years may be necessary. The purposes of this review were to emphasize the clinical problem of diagnosing IgG4-related pancreatobiliary disease as well as to highlight the use of the published guidelines for the diagnosis and management of IgG4-related pancreatobiliary disease.

Keyword

Autoimmune pancreatitis; IgG4-related sclerosing cholangitis; Immunoglobulin G4-related disease

Figure

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  Fig. 1 Imaging features of autoimmune pancreatitis, immunoglobulin G4-related sclerosing cholangitis, and other organ involvement. (A) Diffuse enlargement of pancreatic parenchyma with a capsule-like rim. (B) Multiple round or wedge-shaped lesions (arrows) in the kidney. (C) Retroperitoneal fibrosis (arrows) encasing the aorta. (D) Diffuse irregular narrowing (arrows) of the main pancreatic duct. (E) Bile duct wall thickening (arrows) with a preserved bile duct lumen. (F) Hilar bile duct stricture with an intrahepatic bile duct stricture.

Reference

1. Kamisawa T, Zen Y, Nakazawa T, Okazaki K. 2018; Advances in IgG4-related pancreatobiliary diseases. Lancet Gastroenterol Hepatol. 3:575–585. DOI: 10.1016/S2468-1253(18)30121-3. PMID: 30047448.

2. Moon SH, Kim MH, Park DH, et al. 2008; Is a 2-week steroid trial after initial negative investigation for malignancy useful in differentiating autoimmune pancreatitis from pancreatic cancer? A prospective outcome study. Gut. 57:1704–1712. DOI: 10.1136/gut.2008.150979. PMID: 18583399.

3. Chari ST, Takahashi N, Levy MJ, et al. 2009; A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol. 7:1097–1103. DOI: 10.1016/j.cgh.2009.04.020. PMID: 19410017.

4. Inoue D, Yoshida K, Yoneda N, et al. 2015; IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 94:e680. DOI: 10.1097/MD.0000000000000680. PMID: 25881845.

5. Stone JH, Khosroshahi A, Deshpande V, et al. 2012; Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum. 64:3061–3067. DOI: 10.1002/art.34593. PMID: 22736240. PMCID: PMC5963880.

6. Hart PA, Zen Y, Chari ST. 2015; Recent advances in autoimmune pancreatitis. Gastroenterology. 149:39–51. DOI: 10.1053/j.gastro.2015.03.010. PMID: 25770706.

7. Doorenspleet ME, Hubers LM, Culver EL, et al. 2016; Immunoglobulin G4(+) B-cell receptor clones distinguish immunoglobulin G 4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies. Hepatology. 64:501–507. DOI: 10.1002/hep.28568. PMID: 27015613.

8. de Buy Wenniger LJ, Culver EL, Beuers U. 2014; Exposure to occupational antigens might predispose to IgG4-related disease. Hepatology. 60:1453–1454. DOI: 10.1002/hep.26999. PMID: 24407836. PMCID: PMC4258085.

9. Ishikawa Y, Terao C. 2020; Genetic analysis of IgG4-related disease. Mod Rheumatol. 30:17–23. DOI: 10.1080/14397595.2019.1621000. PMID: 31104539.

10. Miyabe K, Zen Y, Cornell LD, et al. 2018; Gastrointestinal and extra-intestinal manifestations of IgG4-related disease. Gastroenterology. 155:990–1003.e1. DOI: 10.1053/j.gastro.2018.06.082. PMID: 30012334.

11. Shiokawa M, Kodama Y, Kuriyama K, et al. 2016; Pathogenicity of IgG in patients with IgG4-related disease. Gut. 65:1322–1332. DOI: 10.1136/gutjnl-2015-310336. PMID: 26964842.

12. Shimosegawa T, Chari ST, Frulloni L, et al. 2011; International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 40:352–358. DOI: 10.1097/MPA.0b013e3182142fd2. PMID: 21412117.

13. Gardner TB, Levy MJ, Takahashi N, Smyrk TC, Chari ST. 2009; Misdiagnosis of autoimmune pancreatitis: a caution to clinicians. Am J Gastroenterol. 104:1620–1623. DOI: 10.1038/ajg.2008.89. PMID: 19574965.

14. Dai C, Cao Q, Jiang M, Sun MJ. 2018; Serum immunoglobulin G4 in discriminating autoimmune pancreatitis from pancreatic cancer: a diagnostic meta-analysis. Pancreas. 47:280–284. DOI: 10.1097/MPA.0000000000000994. PMID: 29351121.

15. Tanaka A, Tazuma S, Okazaki K, et al. 2017; Clinical features, response to treatment, and outcomes of IgG4-related sclerosing cholangitis. Clin Gastroenterol Hepatol. 15:920–926.e3. DOI: 10.1016/j.cgh.2016.12.038. PMID: 28111336.

16. Moon SH, Kim MH, Lee JK, et al. 2017; Development of a scoring system for differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis. J Gastroenterol. 52:483–493. DOI: 10.1007/s00535-016-1246-5. PMID: 27470434.

17. Huggett MT, Culver EL, Kumar M, et al. 2014; 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. 109:1675–1683. DOI: 10.1038/ajg.2014.223. PMID: 25155229.

18. Ghazale A, Chari ST, Zhang L, et al. 2008; Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 134:706–715. DOI: 10.1053/j.gastro.2007.12.009. PMID: 18222442.

19. Ohara H, Okazaki K, Tsubouchi H, et al. 2012; Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012. J Hepatobiliary Pancreat Sci. 19:536–542. DOI: 10.1007/s00534-012-0521-y. PMID: 22717980.

20. Culver EL, Chapman RW. 2016; IgG4-related hepatobiliary disease: an overview. Nat Rev Gastroenterol Hepatol. 13:601–612. DOI: 10.1038/nrgastro.2016.132. PMID: 27625195.

21. Kamisawa T, Nakazawa T, Tazuma S, et al. 2019; Clinical practice guidelines for IgG4-related sclerosing cholangitis. J Hepatobiliary Pancreat Sci. 26:9–42. DOI: 10.1002/jhbp.596. PMID: 30575336.

22. Okazaki K, Chari ST, Frulloni L, et al. 2017; International consensus for the treatment of autoimmune pancreatitis. Pancreatology. 17:1–6. DOI: 10.1016/j.pan.2016.12.003. PMID: 28027896.

23. Bi Y, Hart PA, Law R, et al. 2016; Obstructive jaundice in autoimmune pancreatitis can be safely treated with corticosteroids alone without biliary stenting. Pancreatology. 16:391–396. DOI: 10.1016/j.pan.2016.03.017. PMID: 27107633.

24. Lee HW, Moon SH, Kim MH, et al. 2018; Relapse rate and predictors of relapse in a large single center cohort of type 1 autoimmune pancreatitis:long-term follow-up results after steroid therapy with short-duration maintenance treatment. J Gastroenterol. 53:967–977. DOI: 10.1007/s00535-018-1434-6. PMID: 29362937.

25. Masamune A, Nishimori I, Kikuta K, et al. 2017; Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis. Gut. 66:487–494. DOI: 10.1136/gutjnl-2016-312049. PMID: 27543430.

26. Kubota K, Kamisawa T, Okazaki K, et al. 2017; Low-dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis: a long-term Japanese multicenter analysis of 510 patients. J Gastroenterol. 52:955–964. DOI: 10.1007/s00535-016-1302-1. PMID: 28062947.

27. Kamisawa T, Shimosegawa T, Okazaki K, et al. 2009; Standard steroid treatment for autoimmune pancreatitis. Gut. 58:1504–1507. DOI: 10.1136/gut.2008.172908. PMID: 19398440.

28. Tacelli M, Celsa C, Magro B, et al. 2019; Risk factors for rate of relapse and effects of steroid maintenance therapy in patients with autoimmune pancreatitis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 17:1061–1072.e8. DOI: 10.1016/j.cgh.2018.09.051. PMID: 30312787.

29. Hirth M, Vujasinovic M, Münch M, et al. 2018; Monitoring and predicting disease activity in autoimmune pancreatitis with the M-ANNHEIM-AiP-Activity-Score. Pancreatology. 18:29–38. DOI: 10.1016/j.pan.2017.10.005. PMID: 29158146.

30. Kamisawa T, Okazaki K, Kawa S, et al. 2014; Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis. J Gastroenterol. 49:961–970. DOI: 10.1007/s00535-014-0945-z. PMID: 24639058.

31. Hart PA, Topazian MD, Witzig TE, et al. 2013; Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab:the Mayo clinic experience. Gut. 62:1607–1615. DOI: 10.1136/gutjnl-2012-302886. PMID: 22936672.