Download PDF
Endoscopy 2012; 44(01): 66-73
DOI: 10.1055/s-0031-1291540
Review
© Georg Thieme Verlag KG Stuttgart · New York

What an endoscopist should know about immunoglobulin-G4-associated disease of the pancreas and biliary tree

L. Maillette de Buy Wenniger
Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
E. A. Rauws
Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
U. Beuers
Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Publication Date:
23 December 2011 (online)

Also available at
    Permissions and Reprints

Autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC) are the recently recognized pancreatobiliary manifestations of IgG4-associated systemic disease (ISD). Clinically, ISD of the pancreas and/or biliary tree may mimic pancreatic cancer, sclerosing cholangitis, or cholangiocarcinoma. Patients often present with abdominal pain, weight loss, jaundice, itch, and biochemical signs of pancreatitis and cholestasis. Tomography may reveal enlargement of the pancreas or may mimic malignant pancreatic lesions, and cholangiopancreatography may disclose irregularities of the pancreatic duct and stenoses of the distal and/or proximal common bile duct and intrahepatic bile ductules. Serum immunoglobulin G4 (IgG4) is elevated in most patients but, unlike tissue IgG4-loaded plasma cell infiltrates, is not diagnostic of the disease. The application of consensus diagnostic criteria for laboratory investigations, imaging, and histologic findings can identify patients who qualify for corticosteroid treatment. The excellent response to immunosuppressive therapy suggests an immune-mediated etiology of the disease, but the exact pathophysiological mechanisms are still under investigation. Relapse may occur after tapering down of corticosteroids, which supports the rationale of maintenance immunosuppression after remission has been induced.

 

  • References

  • 1 Kamisawa T, Takuma K, Egawa N et al. Autoimmune pancreatitis and IgG4-related sclerosing disease. Nat Rev Gastroenterol Hepatol 2010; 7: 401-409
    CrossrefPubMedGoogle Scholar
  • 2 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
    Google Scholar
  • 3 Sah RP, Chari ST, Pannala R et al. Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology 2010; 139: 140-148 quiz e112-143
    CrossrefPubMedGoogle Scholar
  • 4 Kamisawa T, Funata N, Hayashi Y et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 2003; 38: 982-984
    CrossrefPubMedGoogle Scholar
  • 5 Raina A, Yadav D, Krasinskas AM et al. Evaluation and management of autoimmune pancreatitis: experience at a large US center. Am J Gastroenterol 2009; 104: 2295-2306
    CrossrefPubMedGoogle Scholar
  • 6 Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol 2010; 34: 1812-1819
    CrossrefPubMedGoogle Scholar
  • 7 Ghazale A, Chari ST, Zhang L et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology 2008; 134: 706-715
    CrossrefPubMedGoogle Scholar
  • 8 Hamano H, Kawa S, Ochi Y et al. Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet 2002; 359: 1403-1404
    CrossrefPubMedGoogle Scholar
  • 9 Van Moerkercke W, Verhamme M, Meeus G et al. A case of IgG4-related sclerosing disease with retroperitoneal fibrosis, autoimmune pancreatitis and bilateral focal nephritis. Pancreas 2009; 38: 825-832
    CrossrefPubMedGoogle Scholar
  • 10 Ohara H, Nakazawa T, Sano H et al. Systemic extrapancreatic lesions associated with autoimmune pancreatitis. Pancreas 2005; 31: 232-237
    CrossrefPubMedGoogle Scholar
  • 11 Ishida M, Hotta M, Kushima R et al. Multiple IgG4-related sclerosing lesions in the maxillary sinus, parotid gland and nasal septum. Pathol Int 2009; 59: 670-675
    CrossrefPubMedGoogle Scholar
  • 12 Saeki T, Nishi S, Imai N et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int 2010; 78: 1016-1023
    CrossrefPubMedGoogle Scholar
  • 13 Lee CS, Song JW, Chae EJ et al. Radiological findings and clinical features of thoracic immunoglobulin G4-positive plasma cell granuloma: two cases. Br J Radiol 2010; 83: e150-153
    CrossrefPubMedGoogle Scholar
  • 14 Shrestha B, Sekiguchi H, Colby TV et al. Distinctive pulmonary histopathology with increased IgG4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology. Am J Surg Pathol 2009; 33: 1450-1462
    CrossrefPubMedGoogle Scholar
  • 15 Yoshimura Y, Takeda S, Ieki Y et al. IgG4-associated prostatitis complicating autoimmune pancreatitis. Intern Med 2006; 45: 897-901
    CrossrefPubMedGoogle Scholar
  • 16 Uehara T, Hamano H, Kawakami M et al. Autoimmune pancreatitis-associated prostatitis: distinct clinicopathological entity. Pathol Int 2008; 58: 118-125
    CrossrefPubMedGoogle Scholar
  • 17 Uehara T, Hamano H, Kawa S et al. Chronic gastritis in the setting of autoimmune pancreatitis. Am J Surg Pathol 2010; 34: 1241-1249
    CrossrefPubMedGoogle Scholar
  • 18 Kamisawa T, Egawa N, Nakajima H et al. Gastrointestinal findings in patients with autoimmune pancreatitis. Endoscopy 2005; 37: 1127-1130
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Shen B, Bennett AE, Navaneethan U. IgG4-associated pouchitis. Inflamm Bowel Dis 2010; 17 (05) 1247-1248
    PubMedGoogle Scholar
  • 20 Chan SK, Cheuk W, Chan KT et al. IgG4-related sclerosing pachymeningitis: a previously unrecognized form of central nervous system involvement in IgG4-related sclerosing disease. Am J Surg Pathol 2009; 33: 1249-1252
    CrossrefPubMedGoogle Scholar
  • 21 Kakudo K, Li Y, Hirokawa M et al. Diagnosis of Hashimoto’s thyroiditis and IgG4-related sclerosing disease. Pathol Int 2011; 61: 175-183
    Google Scholar
  • 22 Leporati P, Landek-Salgado MA, Lupi I et al. IgG4-related hypophysitis: a new addition to the hypophysitis spectrum. J Clin Endocrinol Metab 2011;
    PubMedGoogle Scholar
  • 23 Sakata N, Tashiro T, Uesugi N et al. IgG4-positive plasma cells in inflammatory abdominal aortic aneurysm: the possibility of an aortic manifestation of IgG4-related sclerosing disease. Am J Surg Pathol 2008; 32: 553-559
    CrossrefPubMedGoogle Scholar
  • 24 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: 1587-1595
    CrossrefPubMedGoogle Scholar
  • 25 Okazaki K, Kawa S, Kamisawa T et al. Japanese consensus guidelines for management of autoimmune pancreatitis: I. Concept and diagnosis of autoimmune pancreatitis. J Gastroenterol 2010; 45: 249-265
    CrossrefPubMedGoogle Scholar
  • 26 Park DH, Kim MH, Chari ST. Recent advances in autoimmune pancreatitis. Gut 2009; 58: 1680-1689
    CrossrefPubMedGoogle Scholar
  • 27 Alderlieste YA, van den Elzen BD, Rauws EA et al. Immunoglobulin G4-associated cholangitis: one variant of immunoglobulin G4-related systemic disease. Digestion 2009; 79: 220-228
    CrossrefPubMedGoogle Scholar
  • 28 Aalberse RC, Stapel SO, Schuurman J et al. Immunoglobulin G4: an odd antibody. Clin Exp Allergy 2009; 39: 469-477
    CrossrefPubMedGoogle Scholar
  • 29 van der Neut Kolfschoten M, Schuurman J, Losen M et al. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 2007; 317: 1554-1557
    CrossrefPubMedGoogle Scholar
  • 30 Labrijn AF, Buijsse AO, van den Bremer ET et al. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nat Biotechnol 2009; 27: 767-771
    CrossrefPubMedGoogle Scholar
  • 31 Zen Y, Nakanuma Y. Pathogenesis of IgG4-related disease. Curr Opin Rheumatol 2011; 23: 114-118
    CrossrefPubMedGoogle Scholar
  • 32 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
    CrossrefPubMedGoogle Scholar
  • 33 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
    CrossrefPubMedGoogle Scholar
  • 34 Figueiredo CA, Barreto ML, Rodrigues LC et al. Chronic intestinal helminth infections are associated with immune hyporesponsiveness and induction of a regulatory network. Infect Immun 2010; 78: 3160-3167
    CrossrefPubMedGoogle Scholar
  • 35 Kitagaki K, Businga TR, Racila D et al. Intestinal helminths protect in a murine model of asthma. J Immunol 2006; 177: 1628-1635
    PubMedGoogle Scholar
  • 36 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
    CrossrefPubMedGoogle Scholar
  • 37 Aoki S, Nakazawa T, Ohara H et al. Immunohistochemical study of autoimmune pancreatitis using anti-IgG4 antibody and patients’ sera. Histopathology 2005; 47: 147-158
    CrossrefPubMedGoogle Scholar
  • 38 Song TJ, Kim MH, Moon SH et al. 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 2010; 105: 1655-1660
    CrossrefPubMedGoogle Scholar
  • 39 Ghazale A, Chari ST, Smyrk TC et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol 2007; 102: 1646-1653
    CrossrefPubMedGoogle Scholar
  • 40 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
    CrossrefPubMedGoogle Scholar
  • 41 Mizuno N, Bhatia V, Hosoda W et al. Histological diagnosis of autoimmune pancreatitis using EUS-guided trucut biopsy: a comparison study with EUS-FNA. J Gastroenterol 2009; 44: 742-750
    CrossrefPubMedGoogle Scholar
  • 42 Alexander S, Bourke MJ, Williams SJ et al. Diagnosis of autoimmune pancreatitis with intraductal biliary biopsy and treatment of stricture with serial placement of multiple biliary stents. Gastrointest Endosc 2008; 68: 396-399
    CrossrefPubMedGoogle Scholar
  • 43 Moon SH, Kim MH, Park do H et al. IgG4 immunostaining of duodenal papillary biopsy specimens may be useful for supporting a diagnosis of autoimmune pancreatitis. Gastrointest Endosc 2010; 71: 960-966
    CrossrefPubMedGoogle Scholar
  • 44 Kamisawa T, Tu Y, Nakajima H et al. Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis: a prospective study using IgG4-immunostaining. World J Gastroenterol 2006; 12: 2031-2033
    PubMedGoogle Scholar
  • 45 Kawakami H, Zen Y, Kuwatani M et al. IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater’s ampulla and the bile duct. J Gastroenterol Hepatol 2010; 25: 1648-1655
    CrossrefPubMedGoogle Scholar
  • 46 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: 1287-1295
    CrossrefPubMedGoogle Scholar
  • 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: 463-471
    CrossrefPubMedGoogle Scholar
  • 48 Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol 2011; 64: 237-243
    CrossrefPubMedGoogle Scholar
  • 49 Kamisawa T, Okamoto A. Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease. J Gastroenterol 2006; 41: 613-625
    CrossrefPubMedGoogle Scholar
  • 50 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
    CrossrefPubMedGoogle Scholar
  • 51 Webster GJ, Pereira SP, Chapman RW. Autoimmune pancreatitis/IgG4-associated cholangitis and primary sclerosing cholangitis – overlapping or separate diseases?. J Hepatol 2009; 51: 398-402
    CrossrefPubMedGoogle Scholar
  • 52 Mannion M, Cron RQ. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature. Pediatr Rheumatol Online J 2011; 9: 1
    CrossrefPubMedGoogle Scholar
  • 53 Chung H, Watanabe T, Kudo M et al. Identification and characterization of IgG4-associated autoimmune hepatitis. Liver Int 2010; 30: 222-231
    CrossrefPubMedGoogle Scholar
  • 54 Euscher E, Vaswani K, Frankel W. Eosinophilic pancreatitis: a rare entity that can mimic a pancreatic neoplasm. Ann Diagn Pathol 2000; 4: 379-385
    CrossrefPubMedGoogle Scholar
  • 55 Kamisawa T, Okazaki K, Kawa S et al. Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP. J Gastroenterol 2010; 45: 471-477
    CrossrefPubMedGoogle Scholar
  • 56 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: 523-526
    CrossrefPubMedGoogle Scholar
  • 57 Cheuk W, Yuen HK, Chan AC et al. Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol 2008; 32: 1159-1167
    CrossrefPubMedGoogle Scholar
  • 58 Kanda G, Ryu T, Shirai T et al. Peripheral T-cell lymphoma that developed during the follow-up of IgG4-related disease. Intern Med 2011; 50: 155-160
    CrossrefPubMedGoogle Scholar
  • 59 Khosroshahi A, Bloch DB, Deshpande V et al. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum 2010; 62: 1755-1762
    CrossrefPubMedGoogle Scholar
  • 60 Topazian M, Witzig TE, Smyrk TC et al. Rituximab therapy for refractory biliary strictures in immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol 2008; 6: 364-366
    CrossrefPubMedGoogle Scholar