Recent Advances in Autoimmune Pancreatitis

doi:10.1053/j.gastro.2015.03.010

Gastroenterology

Volume 149, Issue 1, July 2015, Pages 39-51

https://doi.org/10.1053/j.gastro.2015.03.010 Get rights and content

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is characterized clinically by frequent presentation with obstructive jaundice, histologically by a dense lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to corticosteroid therapy. Two distinct diseases, type 1 and type 2 AIP, share these features. However, these 2 diseases have unique pancreatic histopathologic patterns and differ significantly in their demographic profiles, clinical presentation, and natural history. Recognizing the popular and long-standing association of the term “AIP” with what is now called “type 1 AIP,” we suggest using “AIP” solely for type 1 AIP and to acknowledge its own distinct disease status by using “idiopathic duct-centric chronic pancreatitis” (IDCP) for type 2 AIP. AIP is the pancreatic manifestation of immunoglobulin G4–related disease (IgG4-RD). The etiopathogenesis of AIP and IgG4-RD is largely unknown. However, the remarkable effectiveness of B-cell depletion therapy with rituximab in patients with AIP and IgG4-RD highlights the crucial role of B cells in its pathogenesis. IDCP is less commonly recognized, and little is known about its pathogenesis. IDCP has no biomarker but is associated with inflammatory bowel disease in ∼25% of patients. Recently, the international consensus diagnostic criteria for AIP identified combinations of features that are diagnostic of both diseases. Both AIP and IDCP are corticosteroid responsive; however, relapses are common in AIP and rare in IDCP. Therefore, maintenance therapy with either an immunomodulator (eg, azathioprine, 6-mercaptopurine, or mycophenolate mofetil) or rituximab is often necessary for patients with AIP. Long-term survival is excellent for both patients with AIP and patients with IDCP.

Section snippets

Subtypes of AIP: History and Nomenclature

The term “AIP” was used by Yoshida et al to describe a corticosteroid-responsive disease associated with features of autoimmunity.³ The association of AIP and elevated serum immunoglobulin (Ig) G4 levels was recognized by Hamano et al.⁴ The observation by Kamisawa et al that not only the pancreas but also the extrapancreatic organs involved in AIP had abundant infiltration with IgG4⁺ plasma cells led to the notion that AIP was part of a multiorgan disease, recently named IgG4-related disease

Conclusions

AIP and IDCP are two distinct steroid-responsive pancreatitides. AIP is a unique form of chronic pancreatitis defined by characteristic histological features. Despite the frequent association with elevated levels of IgG4 in the serum and IgG4⁺ plasma cells in tissue, IgG4 is not believed to play a critical role in its pathogenesis. The initial triggering events and predisposing factors to AIP remain elusive and require additional exploration. A diagnosis of AIP requires a high index of clinical

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