Summary and Look to the Future

Chapter

Abstract

Autoimmune pancreatitis (AIP) is a rare immunological disorder that requires a high degree of expertise from gastroenterologists, pathologists, and radiologists – as provided in this book. The diagnosis has traditionally been based on pancreatic imaging, principally ERCP and CT scans, but recent advances in endoscopic ultrasound (EUS) and MRI have provided improved accuracy. Biopsies of the pancreas, guided by EUS, have made it possible to provide a tissue diagnosis. In addition, ampullary and duodenal biopsies can provide tissue evidence of IgG4 plasma cell infiltration of the upper gastrointestinal tract. While international consensus definitions allow to distinguish between type 1 AIP (lymphoplasmacytic sclerosing pancreatitis) and type 2 AIP (idiopathic duct-centric pancreatitis), their underlying pathophysiology remains largely obscure. Future research will aim at a refinement of diagnostic tests, specifically for type 2 AIP where IgG4 is not elevated and for monitoring therapy. It will also have to identify parameters for recurrence, define the appropriate treatment intervals for long-term immunosuppression, and establish alternatives to corticosteroid treatment. We hope that enthusiasm to invest in clinical research on AIP shall not fade and patients with other varieties of pancreatitis may benefit from its progress as well.

Keywords

Europe Corticosteroid Pancreatitis Trypsin Cyclosporine 

Notes

Acknowledgment

Some of the points discussed here have recently been reviewed in a commentary in the journal Gut (2011 May;60(5):565–6). The authors thank Julia Mayerle for helpful discussions.

References

  1. 1.
    Sarles H, Sarles JC, Muratore R, Guien C. Chronic inflammatory sclerosis of the pancreas – an autonomous pancreatic disease? Am J Dig Dis. 1961;1:688–98.CrossRefGoogle Scholar
  2. 2.
    Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995;40:1561–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Varadarajulu S, Cotton PB. Autoimmune pancreatitis: is it relevant in the west? Gastroenterology. 2003;125:1557.PubMedCrossRefGoogle Scholar
  4. 4.
    Pickartz T, Mayerle J, Lerch MM. Autoimmune pancreatitis. Nat Clin Pract Gastroenterol Hepatol. 2007;4:314–23.PubMedCrossRefGoogle Scholar
  5. 5.
    Keim V, Bauer N, Teich N, Simon P, Lerch MM, Mössner J. Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene. Am J Med. 2001;111:622–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Gress TM, Müller-Pillasch F, Lerch MM, Friess H, Büchler M, Beger HG, Adler G. Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis. Z Gastroenterol. 1994;32:221–5.PubMedGoogle Scholar
  7. 7.
    Ellis I, Lerch MM, Whitcomb DC. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology. 2001;1:405–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Moon SH, Kim MH, Park DH, Hwang CY, Park SJ, Lee SS, Seo DW, Lee SK. 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;57:1704–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Topazian M, Witzig TE, Smyrk TC, Pulido JS, Levy MJ, Kamath PS, Chari ST. Rituximab therapy for refractory biliary strictures in immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol. 2008;6:364–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, Fukushima M, Nikaido T, Nakayama K, Usuda N, Kiyosawa K. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Aparisi L, Farre A, Gomez-Cambronero L, Martinez J, De Las HG, Corts J, Navarro S, Mora J, Lopez-Hoyos M, Sabater L, Ferrandez A, Bautista D, Perez-Mateo M, Mery S, Sastre J. Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis. Gut. 2005;54:703–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Chari ST, Kloeppel G, Zhang L, Notohara K, Lerch MM, Shimosegawa T; Autoimmune Pancreatitis International Cooperative Study Group (APICS). Histopathologic and clinical subtypes of autoimmune pancreatitis: the Honolulu consensus document. Pancreas. 2010;39:549–54.Google Scholar
  13. 13.
    Klöppel G, Detlefsen S, Chari ST, Longnecker DS, Zamboni G. Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions. J Gastroenterol. 2010;45:787–93.PubMedCrossRefGoogle Scholar
  14. 14.
    Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, Topazian MD, Clain JE, Pearson RK, Petersen BT, Vege SS, Lindor K, Farnell MB. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–15.PubMedCrossRefGoogle Scholar
  15. 15.
    Menges M, Lerch MM, Zeitz M. The double duct sign in patients with malignant and benign pancreatic lesions. Gastrointest Endosc. 2000;52:74–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Sugumar A, Levy MJ, Kamisawa T, Webster GJM, Kim MH, Enders F, Amin Z, Baron TH, Chapman MH, Church NI, Clain JE, Egawa N, Johnson GJ, Okazaki K, Pearson RK, Pereira SP, Petersen BT, Read S, Sah RP, Sandanayake NS, Takahashi N, Topazian MD, Uchida K, Vege SS, Chari ST. Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis: an international multicenter study. Gut. 2011;60:666–70.PubMedCrossRefGoogle Scholar
  17. 17.
    Frulloni L, Lunardi C, Simone R, Dolcino M, Scattolini C, Falconi M, Benini L, Vantini I, Corrocher R, Puccetti A. Identification of a novel antibody associated with autoimmune pancreatitis. N Engl J Med. 2009;361:2135–42.PubMedCrossRefGoogle Scholar
  18. 18.
    Halangk W, Krüger B, Ruthenbürger M, Stürzebecher J, Albrecht E, Lippert H, Lerch MM. Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation. Am J Physiol Gastrointest Liver Physiol. 2002;282:G367–74.PubMedGoogle Scholar
  19. 19.
    Löhr JM, Faissner R, Koczan D, Bewerunge P, Bassi C, Brors B, Eils R, Frulloni L, Funk A, Halangk W, Jesnowski R, Kaderali L, Kleeff J, Krüger B, Lerch MM, Lösel R, Magnani M, Neumaier M, Nittka S, Sahin-Tóth M, Sänger J, Serafini S, Schnölzer M, Thierse HJ, Wandschneider S, Zamboni G, Klöppel G. Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process. Am J Gastroenterol. 2010;105:2060–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Kamisawa T, Okazaki K, Kawa S, Shimosegawa T, Tanaka M. Research Committee for Intractable Pancreatic Disease and Japan Pancreas Society. Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP. J Gastroenterol. 2010;45:471–7.Google Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    Kamisawa T, Imai M, Yui Chen P, Tu Y, Egawa N, Tsuruta K, Okamoto A, Suzuki M, Kamata N. Strategy for differentiating autoimmune pancreatitis from pancreatic cancer. Pancreas. 2008;37:e62–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Chari ST, Takahashi N, Levy MJ, Smyrk TC, Clain JE, Pearson RK, Petersen BT, Topazian MA, Vege SS. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol. 2009;7:1097–103.PubMedCrossRefGoogle Scholar
  24. 24.
    Farrell JJ, Garber J, Sahani D, Brugge WR. EUS findings in patients with autoimmune pancreatitis. Gastrointest Endosc. 2004;60:927–36.PubMedCrossRefGoogle Scholar
  25. 25.
    Finkelberg DL, Sahani D, Deshpande V, Brugge WR. Autoimmune pancreatitis. N Engl J Med. 2006;355:2670–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Sepehr A, Mino-Kenudson M, Ogawa F, Brugge WR, Deshpande V, Lauwers GY. IgG4+ to IgG+ plasma cells ratio of ampulla can help differentiate autoimmune pancreatitis from other “mass forming” pancreatic lesions. Am J Surg Pathol. 2008;32:1770–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Harvard Medical SchoolMassachusetts General HospitalBostonUSA
  2. 2.Department of MedicineUniversity Hospital GreifswaldGreifswaldGermany

Personalised recommendations