Advertisement

Autoimmune Pancreatitis with Normal Serum IgG4 Concentrations: What Is the Correct Classification for Such Patients?

  • Seiichi Hara
  • Terumi Kamisawa
  • Taku Tabata
  • Sawako Kuruma
  • Kazuro Chiba
  • Satomi Koizumi
Chapter

Abstract

The autoimmune pancreatitis (AIP) seen in Japan occurs preferentially in older men, presents with jaundice in many cases, and is seldom associated with symptoms and signs of acute pancreatitis. Elevated serum IgG4 concentrations are noted in a high proportion of cases, and the pancreas characteristically shows a marked lymphoplasmacytic infiltrate with IgG4-positive plasma cells and fibrosis. This entity has been termed lymphoplasmacytic sclerosing pancreatitis (LPSP) and is now known also as type 1 (IgG4-related) AIP.

In contrast, data to date suggest that a different pattern (i.e., a different type) of AIP is more common in Western countries. In the West, AIP often presents at a younger age and has a balanced sex distribution. Moreover, AIP in the West is frequently complicated by inflammatory bowel disease. Most importantly, the pathological features of this other form of AIP, now termed type 2 AIP, consist of neutrophilic infiltration of the pancreatic duct epithelium: the granulocytic epithelial lesion (GEL). IgG4-positive plasma cells are generally absent from the tissue lesions of type 2 AIP, and serum IgG4 concentrations are usually normal.

In our experience in considering all cases of AIP, among patients with normal serum IgG4 concentrations, the percentage of women is high and symptoms of acute pancreatitis such as abdominal pain are common. Segmental as opposed to diffuse pancreatic swelling is common in this AIP subtype, but extrapancreatic lesions were few. In particular, salivary and lacrimal gland enlargement and dysfunction tend not to occur in this AIP subtype, and IgG4-positive plasma cells are not found on tissue specimens.

Patients with normal serum IgG4 concentrations should be classified as type 1 (IgG4-related AIP) if histopathologic examination and immunohistochemical studies of pancreatic specimens demonstrate the typical hematoxylin and eosin features of IgG4-related disease as well as increased numbers of IgG4-positive plasma cells. Type 2 AIP, which is usually associated with normal serum IgG4 concentrations and is linked to pathological findings that contrast sharply with those of type 1 (IgG4-related) AIP, is not a form of IgG4-related disease and should be regarded as a separate disease entity.

Keywords

Acute Pancreatitis Serum IgG4 Autoimmune Pancreatitis Serum IgG4 Concentration Elevated Serum IgG4 
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.

References

  1. 1.
    Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1997;40:1561–8.CrossRefGoogle Scholar
  2. 2.
    Okazaki K, Kawa S, Kamisawa T, et al. Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol. 2006;41:626–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38:982–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Kamisawa T, Okamoto A. Autoimmune pancreatitis. Proposal of IgG4-related sclerosing disease. J Gastroenterol. 2006;41:613–25.PubMedCrossRefGoogle Scholar
  5. 5.
    Kamisawa T, Takuma K, Egawa N, et al. Autoimmune pancreatitis and IgG4-related sclerosing disease. Nat Rev Gastroenterol Hepatol. 2010;7:401–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Kawaguchi K, Koike M, Tsuruta K, et al. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol. 1991;22:387–95.PubMedCrossRefGoogle Scholar
  7. 7.
    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. Virchow Arch. 2004;445:552–63.CrossRefGoogle Scholar
  8. 8.
    Kamisawa T, Chari ST, Giday SA, et al. Clinical profile of autoimmune pancreatitis and its histological subtypes. An international multicenter study. Pancreas. 2011;40:809–14.PubMedCrossRefGoogle Scholar
  9. 9.
    Notohara K, Burgart LJ, Yadav D, Chari S, Smyrk TC. Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration. Clinicopathologic features of 35 cases. Am J Surg Pathol. 2004;27:1119–27.CrossRefGoogle Scholar
  10. 10.
    Kamisawa T, Wakabayashi T, Sawabu N. Autoimmune pancreatitis in young patients. J Clin Gastroenterol. 2006;40:847–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Sah RP, Chari ST, Pannala R, et al. Differences in clinical profile and relapse rate of type 1 vs type 2 autoimmune pancreatitis. Gastroenterology. 2010;139:140–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Kamisawa T, Notohara K, Shimosegawa T. Two clinicopathologic subtypes of autoimmune pancreatitis: LPSP and IDCP. Gastroenterology. 2010;139:22–5.PubMedCrossRefGoogle Scholar
  13. 13.
    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: 352–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Kamisawa T, Takuma K, Tabata T, et al. Serum IgG4-negative autoimmune pancreatitis. J Gastroenterol. 2011;46:108–16.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Seiichi Hara
    • 1
  • Terumi Kamisawa
    • 1
  • Taku Tabata
    • 1
  • Sawako Kuruma
    • 1
  • Kazuro Chiba
    • 1
  • Satomi Koizumi
    • 1
  1. 1.Department of Internal MedicineTokyo Metropolitan Komagome HospitalTokyoJapan

Personalised recommendations