Korean J Gastroenterol.  2022 Sep;80(3):107-114. 10.4166/kjg.2022.102.

Autoimmune Pancreatitis and Immunoglobulin G4-related Sclerosing Cholangitis: Past, Present, and Future

  • 1Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
  • 2Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 3Department of Internal Medicine, Hanyang University Changwon Hanmaeum Hospital, Changwon, Korea


new disease entity, has attracted considerable interest within the international gastroenterology community. The typical manifestations of AIP/IgG4-SC are obstructive jaundice and pancreatic enlargement in the elderly, which may mimic the presentations of pancreatobiliary malignancies. The timely diagnosis of AIP/IgG4-SC can lead to adequate glucocorticoid treatment, whereas a misdiagnosis can result in unnecessary major surgery. The diagnostic criteria used to diagnose AIP include several cardinal features of AIP that can be detected via pancreatic parenchymal imaging, ductal imaging, serum IgG4 levels, histopathology, other organ involvement, and response to glucocorticoid therapy. The differential diagnosis of AIP/IgG4-SC may include pancreatobiliary malignancies and primary sclerosing cholangitis. Although most patients with AIP/IgG4-SC respond well to glucocorticoid therapy, there is a frequent relapse of the disease in the long term. This review describes the evolution of the concept of AIP and IgG4-related disease, including the development of diagnostic criteria, discusses the current practice for diagnosis and treatment, and suggests prospects for research.


Autoimmune pancreatitis; Immunoglobulin G4-related disease; Diagnosis; Therapeutics


  • Fig. 1 Imaging and histopathologic features of autoimmune pancreatitis. (A) Diffuse enlargement of pancreatic parenchyma (sausage-shaped pancreas). (B) Periductal lymphoplasmacytic infiltration with slit-like obstruction of the pancreatic duct (hematoxylin and eosin stain [H&E], ×400). (C) Lymphoplasmacytic infiltration and luminal obliteration of interlobular vein (obliterative phlebitis) (H&E, ×200). (D) Dense infiltration of immunoglobulin G4 (IgG4)-positive cells around the duct and lobules (IgG4 immunostaining, ×400).


1. Löhr JM, Vujasinovic M, Rosendahl J, Stone JH, Beuers U. 2022; IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol. 19:185–197. DOI: 10.1038/s41575-021-00529-y. PMID: 34750548.
2. Okazaki K, Uchida K. 2018; Current concept of autoimmune pancreatitis and IgG4-related disease. Am J Gastroenterol. 113:1412–1416. DOI: 10.1038/s41395-018-0184-7. PMID: 30002467.
3. 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. PMCID: PMC4602507.
4. Sarles H, Sarles JC, Muratore R, Guien C. 1961; Chronic inflammatory sclerosis of the pancreas--an autonomous pancreatic disease? Am J Dig Dis. 6:688–698. DOI: 10.1007/BF02232341. PMID: 13746542.
5. Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N. 1995; Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 40:1561–1568. DOI: 10.1007/BF02285209. PMID: 7628283.
6. Hamano H, Kawa S, Horiuchi A, et al. 2001; High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 344:732–738. DOI: 10.1056/NEJM200103083441005. PMID: 11236777.
7. Kamisawa T, Funata N, Hayashi Y, et al. 2003; A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 38:982–984. DOI: 10.1007/s00535-003-1175-y. PMID: 14614606.
8. Pearson RK, Longnecker DS, Chari ST, et al. 2003; Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist? Pancreas. 27:1–13. DOI: 10.1097/00006676-200307000-00001. PMID: 12826899.
9. Sutton R. 2005; Autoimmune pancreatitis--also a Western disease. Gut. 54:581–583. DOI: 10.1136/gut.2004.058438. PMID: 15831898. PMCID: PMC1774489.
10. Kim KP, Kim MH, Lee SS, Seo DW, Lee SK. 2004; Autoimmune pancreatitis: it may be a worldwide entity. Gastroenterology. 126:1214. DOI: 10.1053/j.gastro.2004.02.044. PMID: 15057766.
11. Kim JY, Chang HS, Kim MH, et al. 2002; A case of autoimmune chronic pancreatitis improved with oral steroid therapy. Korean J Gastroenterol. 39:304–308.
12. Ryu JK, Chung JB, Park SW, et al. 2008; Review of 67 patients with autoimmune pancreatitis in Korea: a multicenter nationwide study. Pancreas. 37:377–385. DOI: 10.1097/MPA.0b013e31817a0914. PMID: 18953249.
13. Okazaki K, Kawa S, Kamisawa T, et al. 2006; Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol. 41:626–631. DOI: 10.1007/s00535-006-1868-0. PMID: 16932998. PMCID: PMC2780630.
14. 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.
15. Kim KP, Kim MH, Kim JC, Lee SS, Seo DW, Lee SK. 2006; Diagnostic criteria for autoimmune chronic pancreatitis revisited. World J Gastroenterol. 12:2487–2496. DOI: 10.3748/wjg.v12.i16.2487. PMID: 16688792. PMCID: PMC4087979.
16. 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.
17. Okazaki K, Kawa S, Kamisawa T, et al. 2022; Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020. J Gastroenterol. 57:225–245. DOI: 10.1007/s00535-022-01857-9. PMID: 35192048. PMCID: PMC8938398.
18. Wallace ZS, Naden RP, Chari S, et al. 2020; The 2019 American College of Rheumatology/European League against rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 72:7–19. DOI: 10.1002/art.41120. PMID: 31793250.
19. 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.
20. Stone JH, Zen Y, Deshpande V. 2012; IgG4-related disease. N Engl J Med. 366:539–551. DOI: 10.1056/NEJMra1104650. PMID: 22316447.
21. 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.
22. Xiao X, Lian M, Zhang W, Eric Gershwin M, Ma X. 2018; The immunologic paradoxes of IgG4-related disease. Clin Rev Allergy Immunol. 54:344–351. DOI: 10.1007/s12016-018-8679-y. PMID: 29460058.
23. Kim KP, Kim MH, Song MH, Lee SS, Seo DW, Lee SK. 2004; Autoimmune chronic pancreatitis. Am J Gastroenterol. 99:1605–1616. DOI: 10.1111/j.1572-0241.2004.30336.x. PMID: 15307882.
24. Kwon S, Kim MH, Choi EK. 2007; The diagnostic criteria for autoimmune chronic pancreatitis: it is time to make a consensus. Pancreas. 34:279–286. DOI: 10.1097/MPA.0b013e31802eff5f. PMID: 17414049.
25. Bang SJ, Kim MH, Kim DH, et al. 2008; Is pancreatic core biopsy sufficient to diagnose autoimmune chronic pancreatitis? Pancreas. 36:84–89. DOI: 10.1097/mpa.0b013e318135483d. PMID: 18192887.
26. 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.
27. Park DH, Kim MH, Oh HB, et al. 2008; Substitution of aspartic acid at position 57 of the DQbeta1 affects relapse of autoimmune pancreatitis. Gastroenterology. 134:440–446. DOI: 10.1053/j.gastro.2007.11.023. PMID: 18155707.
28. Lee TY, Kim MH, Park DH, et al. 2009; Utility of 18F-FDG PET/CT for differentiation of autoimmune pancreatitis with atypical pancreatic imaging findings from pancreatic cancer. AJR Am J Roentgenol. 193:343–348. DOI: 10.2214/AJR.08.2297. PMID: 19620430.
29. Moon SH, Kim MH, Park DH, et al. 2010; IgG4 immunostaining of duodenal papillary biopsy specimens may be useful for supporting a diagnosis of autoimmune pancreatitis. Gastrointest Endosc. 71:960–966. DOI: 10.1016/j.gie.2009.12.004. PMID: 20304394.
30. Park SH, Kim MH, Kim SY, et al. 2010; Magnetic resonance cholangiopancreatography for the diagnostic evaluation of autoimmune pancreatitis. Pancreas. 39:1191–1198. DOI: 10.1097/MPA.0b013e3181dbf469. PMID: 20467343.
31. Song TJ, Kim MH, Moon SH, et al. 2010; The combined measurement of total serum IgG and IgG4 may increase diagnostic sensitivity for autoimmune pancreatitis without sacrificing specificity, compared with IgG4 alone. Am J Gastroenterol. 105:1655–1660. DOI: 10.1038/ajg.2009.689. PMID: 20010924.
32. Moon SH, Kim MH. 2012; The role of endoscopy in the diagnosis of autoimmune pancreatitis. Gastrointest Endosc. 76:645–656. DOI: 10.1016/j.gie.2012.04.458. PMID: 22898422.
33. Song TJ, Kim MH, Kim MJ, Moon SH, Han JM. International Panel of Speakers and Moderators. 2014; Clinical validation of the international consensus diagnostic criteria and algorithms for autoimmune pancreatitis: combined IAP and KPBA meeting 2013 report. Pancreatology. 14:233–237. DOI: 10.1016/j.pan.2014.04.033. PMID: 25062869.
34. Moon SH, Kim J, Kim MY, et al. 2016; Sensitization to and challenge with gliadin induce pancreatitis and extrapancreatic inflammation in HLA-DQ8 mice: an animal model of type 1 autoimmune pancreatitis. Gut Liver. 10:842–850. DOI: 10.5009/gnl15484. PMID: 27114422. PMCID: PMC5003210.
35. 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.
36. Cho MK, Moon SH, Song TJ, et al. 2018; Contrast-enhanced endoscopic ultrasound for differentially diagnosing autoimmune pancreatitis and pancreatic cancer. Gut Liver. 12:591–596. DOI: 10.5009/gnl17391. PMID: 29699060. PMCID: PMC6143455.
37. 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.
38. Oh D, Song TJ, Moon SH, et al. 2019; Type 2 autoimmune pancreatitis (idiopathic duct-centric pancreatitis) highlighting patients presenting as clinical acute pancreatitis: a single-center experience. Gut Liver. 13:461–470. DOI: 10.5009/gnl18429. PMID: 30970429. PMCID: PMC6622566.
39. Yoon SB, Moon SH, Kim JH, Song TJ, Kim MH. 2020; The use of immunohistochemistry for IgG4 in the diagnosis of autoimmune pancreatitis: a systematic review and meta-analysis. Pancreatology. 20:1611–1619. DOI: 10.1016/j.pan.2020.10.028. PMID: 33060017.
40. Yoon SB, Moon SH, Kim JH, Park JW, Kim SE, Kim MH. 2021; Determination of the duration of glucocorticoid therapy in type 1 autoimmune pancreatitis: a systematic review and meta-analysis. Pancreatology. 21:1199–1207. DOI: 10.1016/j.pan.2021.05.303. PMID: 34090808.
41. Yoon SB, Moon SH, Song TJ, Kim JH, Kim MH. 2021; Endoscopic ultrasound-guided fine needle aspiration versus biopsy for diagnosis of autoimmune pancreatitis: systematic review and comparative meta-analysis. Dig Endosc. 33:1024–1033. DOI: 10.1111/den.13866. PMID: 33030283.
42. 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.
43. Song TJ, Kim JH, Kim MH, et al. 2012; Comparison of clinical findings between histologically confirmed type 1 and type 2 autoimmune pancreatitis. J Gastroenterol Hepatol. 27:700–708. DOI: 10.1111/j.1440-1746.2011.06934.x. PMID: 21929653.
44. Kamisawa T, Chari ST, Lerch MM, Kim MH, Gress TM, Shimosegawa T. 2013; Recent advances in autoimmune pancreatitis: type 1 and type 2. Gut. 62:1373–1380. DOI: 10.1136/gutjnl-2012-304224. PMID: 23749606.
45. Oh HC, Kim MH, Lee KT, et al. 2010; Clinical clues to suspicion of IgG4-associated sclerosing cholangitis disguised as primary sclerosing cholangitis or hilar cholangiocarcinoma. J Gastroenterol Hepatol. 25:1831–1837. DOI: 10.1111/j.1440-1746.2010.06411.x. PMID: 21091993.
46. Ha J, Choi SH, Byun JH, et al. 2021; Meta-analysis of CT and MRI for differentiation of autoimmune pancreatitis from pancreatic adenocarcinoma. Eur Radiol. 31:3427–3438. DOI: 10.1007/s00330-020-07416-1. PMID: 33146798.
47. Yoon SB, Jeon TY, Moon SH, Lee SM, Kim MH. Systematic review and meta-analysis of MRI features for differentiating autoimmune pancreatitis from pancreatic adenocarcinoma. Eur Radiol. 2022; Apr. 29. [Epub ahead of print]. DOI: 10.1007/s00330-022-08816-1. PMID: 35486167.
48. Moon SH, Kim MH. 2013; Autoimmune pancreatitis: role of endoscopy in diagnosis and treatment. Gastrointest Endosc Clin N Am. 23:893–915. DOI: 10.1016/j.giec.2013.06.005. PMID: 24079796.
49. Takahashi M, Fujinaga Y, Notohara K, et al. 2020; Diagnostic imaging guide for autoimmune pancreatitis. Jpn J Radiol. 38:591–612. DOI: 10.1007/s11604-020-00971-z. PMID: 32297064.
50. Kim JH, Kim MH, Byun JH, et al. 2012; Diagnostic strategy for differentiating autoimmune pancreatitis from pancreatic cancer: is an endoscopic retrograde pancreatography essential? Pancreas. 41:639–647. DOI: 10.1097/MPA.0b013e31823a509b. PMID: 22228050.
51. Jung YJ, Moon SH, Kim MH. 2021; Role of endoscopic procedures in the diagnosis of IgG4-related pancreatobiliary disease. Chonnam Med J. 57:44–50. DOI: 10.4068/cmj.2021.57.1.44. PMID: 33537218. PMCID: PMC7840337.
52. Notohara K. 2021; Biopsy diagnosis of type 1 autoimmune pancreatitis: does it bring a conclusion or confusion? DEN open. 2:e82. DOI: 10.1002/deo2.82. PMID: 35310716. PMCID: PMC8828250.
53. Moon SH, Kim MH, Park DH. 2008; Treatment and relapse of autoimmune pancreatitis. Gut Liver. 2:1–7. DOI: 10.5009/gnl.2008.2.1.1. PMID: 20485603. PMCID: PMC2871571.
54. 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.
55. Lee SC, Yang CH, Chang CT, Yu KH. Diagnostic utility of serum IgG4 in autoimmune pancreatitis: an updated comprehensive systematic review and meta-analysis. J Clin Gastroenterol. 2021; Sep. 9. [Epub ahead of print]. DOI: 10.1097/MCG.0000000000001612. PMID: 34516462.
56. Wallace ZS, Mattoo H, Carruthers M, et al. 2015; Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis. 74:190–195. DOI: 10.1136/annrheumdis-2014-205233. PMID: 24817416. PMCID: PMC4656194.
57. Carruthers MN, Stone JH, Deshpande V, Khosroshahi A. 2012; Development of an IgG4-RD responder index. Int J Rheumatol. 2012:259408. DOI: 10.1155/2012/259408. PMID: 22611406. PMCID: PMC3348627.
58. Wallace ZS, Khosroshahi A, Carruthers MD, et al. 2018; An international multispecialty validation study of the IgG4-related disease responder index. Arthritis Care Res (Hoboken). 70:1671–1678. DOI: 10.1002/acr.23543. PMID: 29457382. PMCID: PMC6098740.
Full Text Links
  • KJG
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2022 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr