Review Article

Autoimmune Pancreatitis: A Diagnostic Challenge for the Clinician

Authors: Jayakrishna Chintanaboina, MD, MPH, Zhaohai Yang, MD, PhD, Abraham Mathew, MD, MS


Autoimmune pancreatitis (AIP) is a rare cause of chronic pancreatitis that poses a diagnostic challenge to the clinician in that it mimics pancreatic cancer and presents with painless obstructive jaundice. In this review, we discuss the two types of AIP: type 1, known as lymphoplasmacytic sclerosing pancreatitis and type 2, known asidiopathic duct centric pancreatitis. Type 1 AIP is considered as a pancreatic manifestation of immunoglobulin G4-related disease. The etiopathogenesis of AIP, particularly type 2 AIP, is largely unknown. Both types of AIP have unique pancreatic histological features; however, the radiological and clinical features may mimic those of pancreatic cancer. The most commonly used diagnostic criteria, including the Japan Pancreas Society criteria, theMayo Clinic HISORt (histology, imaging serology, other organ involvement, and response to therapy) criteria, and the International Association of Pancreatology’s international consensus diagnostic criteria, that help to differentiate AIP from pancreatic cancer are reviewed in this article. Thetreatment of choice forinduction of remission for AIPis steroid therapy. Relapses are more common in type 1 AIP. In selected patients, immunomodulators such as azathioprine and rituximab are used to maintain remission.

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. Sarles H, Sarles JC, Muratore R, et al. Chronic inflammatory sclerosis of the pancreas--an autonomous pancreatic disease? Am J Dig Dis 1961;6:688-698.
2. Psarras K, Baltatzis ME, Pavlidis ET, et al. Autoimmune pancreatitis versus pancreatic cancer: a comprehensive review with emphasis on differential diagnosis. Hepatobiliary Pancreat Dis Int 2011;10:465-473.
3. Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal for the concept of autoimmune pancreatitis. Dig Dis Sci 1995;40:1561-1568.
4. Chari ST, Kloeppel G, Zhang L. Histopathologic and clinical subtypes of autoimmune pancreatitis: the Honolulu consensus document. Pancreas 2010;39:549-554.
5. Maire F, Le Baleur Y, Rebours V, et al. Outcome of patients with type 1 or 2 autoimmune pancreatitis. Am J Gastroenterol 2011;106:151-156.
6. Kanno A, Nishimori I, Masamune A, et al. Nationwide epidemiological survey of autoimmune pancreatitis in Japan. Pancreas 2012;41:835-839.
7. Hart PA, Kamisawa T, BruggeWR, et al. Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. Gut 2013;62:1771-1776.
8. Sah RP, Chari ST. Autoimmune pancreatitis: an update on classification, diagnosis, natural history and management. Curr Gastroenterol Rep 2012;14:95-105.
9. Okazaki K, Uchida K, Koyabu M, et al. Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease. J Gastroenterol 2011;46:277-288.
10. Okazaki K, Uchida K, Ohana M, et al. Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology 2000;118:573-58.
11. Uchida K, Okazaki K, Konishi Y, et al. Clinical analysis of autoimmune-related pancreatitis. Am J Gastroenterol 2000;95:2788-2794.
12. Aparisi L, Farre A, Gomez-Cambronero L, et al. Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis. Gut 2005;54:703-709.
13. Nishi H, Tojo A, Onozato ML, et al. Anti-carbonic anhydrase II antibody in autoimmune pancreatitis and tubulointerstitial nephritis. Nephrol Dial Transplant 2007;22:1273-1275.
14. Nishimori I, Miyaji E, Morimoto K, et al. Serum antibodies to carbonic anhydrase IV in patients with autoimmune pancreatitis. Gut 2005;54:274-281.
15. Asada M, Nishio A, Uchida K, et al. Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis. Pancreas 2006;33:20-26.
16. Frulloni L, Lunardi C, Simone R, et al. Identification of a novel antibody associated with autoimmune pancreatitis. N Engl J Med 2009;361:2135-2142.
17. Kawa S, Ota M, Yoshizawa K, et al. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology 2002;122:1264-1269.
18. Umemura T, Ota M, Hamano H, et al. Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients. Gut 2006;55:1367-1368.
19. Chang MC, Chang YT, Tien YW, et al. T-cell regulatory gene CTLA-4 polymorphism/haplotype association with autoimmune pancreatitis. Clin Chem 2007;53:1700-1705.
20. Guarneri F, Guarneri C, Benvenga S. Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry? J Cell Mol Med 2005;9:741-744.
21. Zen Y, Fujii T, Harada K, et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology 2007;45:1538-1546.
22. Muraki T, Hamano H, Ochi Y, et al. Autoimmune pancreatitis and complement activation system. Pancreas 2006;32:16-21.
23. Notohara K, Burgart LJ, Yadav D, et al. Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Am J Surg Pathol 2003;27:1119-1127.
24. Chintanaboina J, Patel BK, Lalos AT, et al. Autoimmune pancreatitis presenting as a focal pancreatic mass mimicking pancreatic cancer: a case report and review of the literature. J Med Cases 2013;4:29-33.
25. Ghadir MR, Sheikhesmaili F, Attari F, et al. Autoimmune pancreatitis mimicking carcinoma of the head of the pancreas: a case report. J Med Case Rep 2012;6:11.
26. Efeovbokhan N, Makol A, Cuison RV, et al. An unusual case of autoimmune pancreatitis presenting as pancreatic mass and obstructive jaundice: a case report and review of the literature. J Med Case Rep 2011;5:253.
27. Chandrasegaram MD, Chiam SC, Nguyen NQ, et al. A case of pancreatic cancer in the setting of autoimmune pancreatitis with nondiagnostic serum markers. Case Rep Surg 2013;2013:809023.
28. Kamisawa T, Chari ST, Giday SA, et al. Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey. Pancreas 2011;40:809-814.
29. Kim KP, Kim M, Lee YJ, et al. Clinical characteristics of 17 cases of autoimmune chronic pancreatitis. Korean J Gastroenterol 2004;43:112-119. [in Korean] .
30. Nishimori I, Tamakoshi A, Kawa S, et al. Influence of steroid therapy on the course of diabetes mellitus in patients with autoimmune pancreatitis: findings from a nationwide survey in Japan. Pancreas 2006;32:244-248.
31. Kamisawa T, Egawa N, Inokuma S, et al. Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy. Pancreas 2003;27:235-238.
32. Taniguchi T, Seko S, Okamoto M, et al. Association of autoimmune pancreatitis and type 1 diabetes: autoimmune exocrinopathy and endocrinopathy of the pancreas. Diabetes Care 2000;23:1592-1594.
33. Tanaka S, Kobayashi T, Nakanishi K, et al. Corticosteroid-responsive diabetes mellitus associated with autoimmune pancreatitis. Lancet 2000; 356:910-911.
34. Zen Y, Kasahara Y, Horita K, et al. Inflammatory pseudotumor of the breast in a patient with a high serum IgG4 level: histologic similarity to sclerosing pancreatitis. Am J Surg Pathol 2005;29:275-278.
35. Kamisawa T, Chari ST, Lerch MM, et al. Recent advances in autoimmune pancreatitis: type 1 and type 2. Gut 2013;62:1373-1380.
36. Hamano H, Kawa S, Ochi Y, et al. Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet 2002;359:1403-1404.
37. Yamamoto M, Takahashi H, Ohara M, et al. A new conceptualization for Mikulicz’s disease as an IgG4-related plasmacytic disease. Mod Rheumatol 2006;16:335-340.
38. Yoshimura Y, Takeda S, Ieki Y, et al. IgG4-associated prostatitis complicating autoimmune pancreatitis. Intern Med 2006;45:897-901.
39. Kawa S, Okazaki K, Kamisawa T, et al. Japanese consensus guidelines for management of autoimmune pancreatitis: II. Extrapancreatic lesions, differential diagnosis. J Gastroenterol 2010;45:355-369.
40. Okazaki K, Uchida K, Koyabu M, et al. IgG4 cholangiopathy--current concept, diagnosis, and pathogenesis. J Hepatol 2014;61:690-695.
41. Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines ofthe International Association of Pancreatology. Pancreas 2011;40:352-358. .
42. Ketwaroo GA, Sheth S. Autoimmune pancreatitis. Gastroenterol Rep 2013;1:27-32.
43. Iwashita T, Yasuda I, Doi S, et al. Use of samples from endoscopic ultrasound-guided 19-gauge fine-needle aspiration in diagnosis of autoimmune pancreatitis. Clin Gastroenterol Hepatol 2012;10:316-322.
44. Park DH, Kim MH, Chari ST. Recent advances in autoimmune pancreatitis. Gut 2009;58:1680-1689.
45. Kloppel G, Detlefsen S, Chari ST, et al. Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions. J Gastroenterol 2010;45:787-793.
46. Wakabayashi T, Kawaura Y, Satomura Y, et al. Clinical study of chronic pancreatitis with focal irregular narrowing of the main pancreatic duct and mass formation: comparison with chronic pancreatitis showindiffuse irregular narrowing of the main pancreatic duct. Pancreas 2002;25:283-289.
47. Horiuchi A, Kaneko T, Yamamura N, et al. Autoimmune chronic pancreatitis simulating pancreatic lymphoma. Am J Gastroenterol 1996;91:2607-2609.
48. Lara LP, Chari ST. Autoimmune pancreatitis. Curr Gastroenterol Rep 2005;7:101-106.
49. Sah RP, Chari ST. Serologic issues in IgG4-related systemic disease and autoimmune pancreatitis. Curr Opin Rheumatol 2011;23:108-113.
50. Morselli-Labate AM, Pezzilli R. Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: a systematic literature review and meta-analysis. J Gastroenterol Hepatol 2009;24:15-36.
51. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001;344:732-738.
52. Kawa S, Hamano H. Clinical features of autoimmune pancreatitis. J Gastroenterol 2007;42(Suppl 18):9-14.
53. Irie H, Honda H, Baba S, et al. Autoimmune pancreatitis: CT and MR characteristics. AJR Am J Roentgenol 1998;170:1323-1327.
54. Sahani DV, Kalva SP, Farrell J, et al. Autoimmune pancreatitis: imaging features. Radiology 2004;233:345-352.
55. Fujinaga Y, Kadoya M, Kawa S, et al. Characteristic findings in images of extra-pancreatic lesions associated with autoimmune pancreatitis. Eur J Radiol 2009;76:228-238.
56. Horiuchi A, Kawa S, Hamano H, et al. ERCP features in 27 patients with autoimmune pancreatitis. Gastrointest Endosc 2002;55:494-499.
57. Sugumar A, Levy MJ, Kamisawa T, et al. Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis: an international multicentre study. Gut 2011;60:666-670.
58. Zen Y, Bogdanos DP, Kawa S. Type 1 autoimmune pancreatitis. Orphanet J Rare Dis 2011;6:82.
59. Sun GF, Zuo CJ, Shao CW, et al. Focal autoimmune pancreatitis: radiological characteristics help to distinguish from pancreatic cancer. World J Gastroenterol 2013;19:3634-3641.
60. Kamisawa T, Takuma K, Anjiki H, et al. Differentiation of autoimmune pancreatitis from pancreatic cancer by diffusion-weighted MRI. Am J Gastroenterol 2010;105:1870-1875.
61. Ito T, Nakano I, Koyanagi S, et al. Autoimmune pancreatitis as a new clinical entity. Three cases of autoimmune pancreatitis with effective steroid therapy. Dig Dis Sci 1997;42:1458-1468.
62. Members of the Criteria Committee for Autoimmune Pancreatitis of the Japan Pancreas Society. Diagnostic criteria for autoimmune pancreatitis by the Japan Pancreas Society. J Jpn Pancreas Soc 2002;17:585-587.
63. Pearson RK, Longnecker DS, Chari ST, et al. Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist? Pancreas 2003;27:1-13.
64. Members of the Criteria Committee for Autoimmune Pancreatitis JPS. Diagnostic criteria for autoimmune pancreatitis (2011). Suizo 2012; 27:17-25.
65. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 2006;4:1010-1016.
66. Chari ST. Diagnosis of autoimmune pancreatitis using its five cardinal features: introducing the Mayo Clinic’s HISORt criteria. J Gastroenterol 2007;42(Suppl 18):39-41.
67. Chari ST, Takahashi N, Levy MJ, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol 2009;7:1097-1103.
68. Sumimoto K, Uchida K, Mitsuyama T, et al. A proposal of a diagnostic algorithm with validation of International Consensus Diagnostic Criteria for autoimmune pancreatitis in a Japanese cohort. Pancreatology 2013;13:230-237.
69. Hirano K, Tada M, Isayama H, et al. Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment. Gut 2007;56: 1719-1724.
70. Moon SH, Kim MH, Park DH, et al. 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 2008;57:1704-1712.
71. Kamisawa T, Shimosegawa T, Okazaki K, et al. Standard steroid treatment for autoimmune pancreatitis. Gut 2009;58:1504-1507.
72. Pannala R, Chari ST. Corticosteroid treatment for autoimmune pancreatitis. Gut 2009;58:1438-1439.
73. Hart PA, Topazian MD, Witzig TE, et al. Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience. Gut 2013;62:1607-1615.
74. Gupta R, Khosroshahi A, Shinagare S, et al. Does autoimmune pancreatitis increase the risk of pancreatic carcinoma? A retrospective analysis of pancreatic resections. Pancreas 2013;42:506-510.
75. Shiokawa M, Kodama Y, Yoshimura K, et al. Risk of cancer in patients with autoimmune pancreatitis. Am J Gastroenterol 2013;108:610-617.
76. Ikeura T, Miyoshi H, Uchida K, et al. Relationship between autoimmune pancreatitis and pancreatic cancer: a single-center experience. Pancreatology 2014;14:373-379.