• Raghuwansh P. Sah
  • Suresh T. Chari


Autoimmune pancreatitis (AIP) is frequently associated with involvement of several extrapancreatic organs. This recognition has led to the concept of IgG4-related disease, of which the pancreatic manifestation is type 1 AIP. IgG4-positive lymphoplasmacytic infiltrate and characteristic pattern of fibrosis (storiform fibrosis) are seen in the involved organs. Bile duct and lymph nodes are commonly involved in AIP. Additionally, involvements of retroperitoneum, kidneys, lungs, liver, salivary and lacrimal glands, prostate, and thyroid have been well characterized. The spectrum of organs involved in IgG4-related disease continues to grow with increasing awareness of the disease, and recently a systematic nomenclature has been proposed. Diagnosis of involvement of other organs in AIP is based on symptoms, clinical exam, radiologic review, and often histology. While manifestations in the involved organs mimic other organ-specific diseases, a dramatic response to steroids is characteristic. Recognition of other organ involvement has significance for diagnosis of AIP and is incorporated in the diagnostic criteria for AIP.


Primary Sclerosing Cholangitis Sclerosing Cholangitis Lacrimal Gland Membranous Nephropathy Tubulointerstitial Nephritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Pearson RK, Longnecker DS, Chari ST, et al. Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist? Pancreas. 2003;27(1):1–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol. 2006;4(8):1010–16; quiz 934.PubMedCrossRefGoogle Scholar
  3. 3.
    Naitoh I, Nakazawa T, Ohara H, et al. Clinical significance of extrapancreatic lesions in autoimmune pancreatitis. Pancreas. 2010;39(1):e1–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Hamano H, Arakura N, Muraki T, et al. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41(12):1197–205.PubMedCrossRefGoogle Scholar
  5. 5.
    Kamisawa T, Nakajima H, Egawa N, et al. IgG4-related sclerosing disease incorporating sclerosing pancreatitis, cholangitis, sialadenitis and retroperitoneal fibrosis with lymphadenopathy. Pancreatology. 2006;6(1–2):132–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Kamisawa T, Okamoto A. IgG4-related sclerosing disease. World J Gastroenterol. 2008;14(25):3948–55.PubMedCrossRefGoogle Scholar
  7. 7.
    Kamisawa T. IgG4-positive plasma cells specifically infiltrate various organs in autoimmune pancreatitis. Pancreas. 2004;29(2):167–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Deshpande V, Chicano S, Finkelberg D, et al. Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol. 2006;30(12):1537–45.PubMedCrossRefGoogle Scholar
  9. 9.
    Vlachou PA, Khalili K, Jang HJ, et al. IgG4-related sclerosing disease: autoimmune pancreatitis and extrapancreatic manifestations. Radiographics. 2011;31(5):1379–402.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang L, Notohara K, Levy MJ, et al. IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis. Mod Pathol. 2007;20(1):23–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Zamboni G, Luttges J, Capelli P, et al. Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch. 2004;445(6):552–63.PubMedCrossRefGoogle Scholar
  12. 12.
    Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366(6):539–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Chari ST, Kloeppel G, Zhang L, et al. Histopathologic and clinical subtypes of autoimmune pancreatitis: the Honolulu consensus document. Pancreatology. 2010;10(6):664–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Carruthers MN, Stone JH, Khosroshahi A. The latest on IgG4-RD: a rapidly emerging disease. Curr Opin Rheumatol. 2012;24(1):60–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Stone JH, Khosroshahi A, Deshpande V, et al. IgG4-related disease: recommendations for the nomenclature of this condition and its individual organ system manifestations. Arthritis Rheum. 2012;64(10):3061–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Hirano K, Kawabe T, Komatsu Y, et al. High-rate pulmonary involvement in autoimmune pancreatitis. Intern Med J. 2006;36(1):58–61.PubMedCrossRefGoogle Scholar
  17. 17.
    Yamamoto M, Harada S, Ohara M, et al. Clinical and pathological differences between Mikulicz’s disease and Sjogren’s syndrome. Rheumatology (Oxford). 2005;44(2):227–34.CrossRefGoogle Scholar
  18. 18.
    Nakazawa T, Ohara H, Sano H, et al. Clinical differences between primary sclerosing cholangitis and sclerosing cholangitis with autoimmune pancreatitis. Pancreas. 2005;30(1):20–5.PubMedGoogle Scholar
  19. 19.
    Deshpande V, Sainani NI, Chung RT, et al. IgG4-associated cholangitis: a comparative histological and immunophenotypic study with primary sclerosing cholangitis on liver biopsy material. Mod Pathol. 2009;22(10):1287–95.PubMedCrossRefGoogle Scholar
  20. 20.
    Koyabu M, Uchida K, Fukata N, et al. Primary sclerosing cholangitis with elevated serum IgG4 levels and/or infiltration of abundant IgG4-positive plasma cells. J Gastroenterol. 2010;45(1):122–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Comings DE, Skubi KB, Van Eyes J, et al. Familial multifocal fibrosclerosis. Findings suggesting that retroperitoneal fibrosis, mediastinal fibrosis, sclerosing cholangitis, Riedel’s thyroiditis, and pseudotumor of the orbit may be different manifestations of a single disease. Ann Intern Med. 1967;66(5):884–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Bartholomew LG, Cain JC, Woolner LB, et al. Sclerosing cholangitis: its possible association with Riedel’s struma and fibrous retroperitonitis. Report of two cases. N Engl J Med. 1963;269:8–12.PubMedCrossRefGoogle Scholar
  23. 23.
    Dahlgren M, Khosroshahi A, Nielsen GP, et al. Riedel’s thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res (Hoboken). 2010;62(9):1312–18.CrossRefGoogle Scholar
  24. 24.
    Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40(3):352–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Chari ST, Takahashi N, Levy MJ, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol. 2009;7(10):1097–103.PubMedCrossRefGoogle Scholar
  26. 26.
    Ghazale A, Chari ST, Zhang L, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134(3):706–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Takahashi N, Ghazale AH, Smyrk TC, et al. Possible association between IgG4-associated systemic disease with or without autoimmune pancreatitis and non-Hodgkin lymphoma. Pancreas. 2009;38(5):523–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Masaki Y, Dong L, Kurose N, et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009;68(8):1310–15.PubMedCrossRefGoogle Scholar
  29. 29.
    Tabata R, Tabata C, Okamoto T, et al. Autoimmune pancreatitis associated with myelodysplastic syndrome. Int Arch Allergy Immunol. 2009;151(2):168–72.PubMedCrossRefGoogle Scholar
  30. 30.
    Miyagawa-Hayashino A, Matsumura Y, Kawakami F, et al. High ratio of IgG4-positive plasma cell infiltration in cutaneous plasmacytosis – is this a cutaneous manifestation of IgG4-related disease? Hum Pathol. 2009;40(9):1269–77.PubMedCrossRefGoogle Scholar
  31. 31.
    Kubota K, Wada T, Kato S, et al. Highly active state of autoimmune pancreatitis with mikulicz disease. Pancreas. 2010;39(1):e6–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Raissian Y, Nasr SH, Larsen CP, et al. Diagnosis of IgG4-related tubulointerstitial nephritis. J Am Soc Nephrol. 2011;22(7):1343–52.PubMedCrossRefGoogle Scholar
  33. 33.
    Takahashi N, Kawashima A, Fletcher JG, et al. Renal involvement in patients with autoimmune pancreatitis: CT and MR imaging findings. Radiology. 2007;242(3):791–801.PubMedCrossRefGoogle Scholar
  34. 34.
    Rudmik L, Trpkov K, Nash C, et al. Autoimmune pancreatitis associated with renal lesions mimicking metastatic tumours. CMAJ. 2006;175(4):367–9.PubMedGoogle Scholar
  35. 35.
    Cornell LD, Chicano SL, Deshpande V, et al. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease. Am J Surg Pathol. 2007;31(10):1586–97.PubMedCrossRefGoogle Scholar
  36. 36.
    Watson SJ, Jenkins DA, Bellamy CO. Nephropathy in IgG4-related systemic disease. Am J Surg Pathol. 2006;30(11):1472–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Takato H, Yasui M, Ichikawa Y, et al. Nonspecific interstitial pneumonia with abundant IgG4-positive cells infiltration, which was thought as pulmonary involvement of IgG4-related autoimmune disease. Intern Med. 2008;47(4):291–4.PubMedCrossRefGoogle Scholar
  38. 38.
    Kobayashi H, Shimokawaji T, Kanoh S, et al. IgG4-positive pulmonary disease. J Thorac Imaging. 2007;22(4):360–2.PubMedCrossRefGoogle Scholar
  39. 39.
    Taniguchi T, Ko M, Seko S, et al. Interstitial pneumonia associated with autoimmune pancreatitis. Gut. 2004;53(5):770; author reply -1.PubMedGoogle Scholar
  40. 40.
    Kamisawa T, Matsukawa M, Ohkawa M. Autoimmune pancreatitis associated with retroperitoneal fibrosis. JOP. 2005;6(3):260–3.PubMedGoogle Scholar
  41. 41.
    Kamiya K, Yoshizu A, Nakazato T, et al. High serum immunoglobulin G4-related retrosternal fibrosclerosis. J Thorac Imaging. 2012;27:W190–2.PubMedCrossRefGoogle Scholar
  42. 42.
    Hamano H, Kawa S, Ochi Y, et al. Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet. 2002;359(9315):1403–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Swartz RD. Idiopathic retroperitoneal fibrosis: a review of the pathogenesis and approaches to treatment. Am J Kidney Dis. 2009;54(3):546–53.PubMedCrossRefGoogle Scholar
  44. 44.
    Kasashima S, Zen Y, Kawashima A, et al. A clinicopathologic study of immunoglobulin G4-related sclerosing disease of the thoracic aorta. J Vasc Surg. 2010;52(6):1587–95.PubMedCrossRefGoogle Scholar
  45. 45.
    Sah RP, Chari ST. Clinical hypothyroidism in autoimmune pancreatitis. Pancreas. 2010;39(7):1114–16.PubMedCrossRefGoogle Scholar
  46. 46.
    Leporati P, Landek-Salgado MA, Lupi I, et al. IgG4-related hypophysitis: a new addition to the hypophysitis spectrum. J Clin Endocrinol Metab. 2011;96(7):1971–80.PubMedCrossRefGoogle Scholar
  47. 47.
    Umemura T, Zen Y, Hamano H, et al. Immunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology. 2007;46(2):463–71.PubMedCrossRefGoogle Scholar
  48. 48.
    Chung H, Watanabe T, Kudo M, et al. Identification and characterization of IgG4-associated autoimmune hepatitis. Liver Int. 2010;30(2):222–31.PubMedCrossRefGoogle Scholar
  49. 49.
    Uehara T, Hamano H, Kawakami M, et al. Autoimmune pancreatitis-associated prostatitis: distinct clinicopathological entity. Pathol Int. 2008;58(2):118–25.PubMedCrossRefGoogle Scholar
  50. 50.
    Nayar M, Charnley R, Scott J, et al. Autoimmune pancreatitis with multiorgan involvement. A case of pericardial involvement. JOP. 2009;10(5):539–42.PubMedGoogle Scholar
  51. 51.
    Shinji A, Sano K, Hamano H, et al. Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration. Gastrointest Endosc. 2004;59(4):506–11.PubMedCrossRefGoogle Scholar
  52. 52.
    Kaji R, Okabe Y, Ishida Y, et al. Autoimmune pancreatitis presenting with IgG4-positive multiple gastric polyps. Gastrointest Endosc. 2009;71(2):420–2.PubMedCrossRefGoogle Scholar
  53. 53.
    Matsui H, Watanabe T, Ueno K, et al. Colonic polyposis associated with autoimmune pancreatitis. Pancreas. 2009;38(7):840–2.PubMedCrossRefGoogle Scholar
  54. 54.
    Leise MD, Smyrk TC, Takahashi N, et al. IgG4-associated cholecystitis: another clue in the diagnosis of autoimmune pancreatitis. Dig Dis Sci. 2011;56(5):1290–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Internal MedicineMayo Clinic RochesterRochesterUSA
  2. 2.Division of Gastroenterology and Hepatology, Internal MedicineMayo Clinic College of MedicineRochesterUSA

Personalised recommendations