Autoimmune pancreatitis and IgG4-related sclerosing disease

Abstract

Autoimmune pancreatitis (AIP) is a unique form of pancreatitis in which the pathogenesis is suspected to involve autoimmune mechanisms. AIP sometimes mimics pancreatic cancer in its presentation, but as AIP responds dramatically to steroid therapy, accurate diagnosis is necessary. AIP is currently diagnosed on the basis of a combination of characteristic clinical, serological, morphological and histopathological features. However, its diagnosis remains a clinical challenge and there are no internationally agreed diagnostic criteria. Another type of AIP called 'idiopathic duct-centric chronic pancreatitis' or 'AIP with granulocytic epithelial lesion' has been reported in Western countries. IgG4-related sclerosing disease is a systemic disease in which IgG4-positive plasma cells and T lymphocytes extensively infiltrate various organs. Organs with tissue fibrosis and obliterative phlebitis, such as the pancreas, salivary gland and retroperitoneum, show clinical manifestations; AIP seems to represent one manifestation of IgG4-related sclerosing disease. As a mass is formed in most cases of IgG4-related sclerosing disease, a malignant tumor is frequently suspected on initial presentation. Clinicians should consider IgG4-related sclerosing disease in the differential diagnosis to avoid unnecessary surgery.

Autoimmune Pancreatitis-What is Known, What Needs to be Known

“…Similar infiltration is observed near the pancreatic veins leading to obliterative phlebitis [4]. This type of AIP often presents in men in the [5][6] th decade of life as painless jaundice mimicking pancreatic cancer and patients experience frequent relapses despite treatment. Very soon, patients diagnosed with AIP were being reported with extra-pancreatic manifestations such as biliary, retroperitoneal, renal, and salivary gland disease.…”

“…This eventually leads to upregulation of Th2 cells and memory T-reg cells during the "progression" phase inducing the maturation and proliferation of local B cells. During this phase, the overproduction of IL-10 leads to expansion of IgG 4 -producing plasma cells and the elevated levels of transforming growth factor beta induce fibrosis [6]. As Th2 and T-reg cells are known to contribute to pathogenesis of allergic disorders, this would explain the elevated serum IgE and peripheral eosinophilia often observed in these patients [6].…”

“…Histologically, there is neutrophilic infiltration and granulocytic lesions that damage the duct epithelium itself, but no obliterative phlebitis or IgG 4 -positive plasma cells. It tends to be associated with inflammatory bowel disease, but no other extra-pancreatic manifestations have been observed with this type of AIP [6].…”

“…It has been observed that T helper 1 (Th1) cells predominate over T helper 2 (Th2) cells in the peripheral blood while Th2 cells dominate over Th1 within the involved organs, and circulating levels of regulatory T cells (T-regs) are increased while naïve T-reg cells are decreased. This has led some researchers to suggest a biphasic mechanism by which cytokines produced by Th1 cells induce AIP, and Th2 cytokines contribute to disease progression [6]. The initial "induction" phase involves response to self-antigens induced by decreased levels of naive T-reg cells which causes a Th1 type immune response and release of pro-inflammatory cytokines.…”

“…During this phase, the overproduction of IL-10 leads to expansion of IgG 4 -producing plasma cells and the elevated levels of transforming growth factor beta induce fibrosis [6]. As Th2 and T-reg cells are known to contribute to pathogenesis of allergic disorders, this would explain the elevated serum IgE and peripheral eosinophilia often observed in these patients [6]. It has also been observed that increased peripheral inducible memory T-reg cells correlate with serum levels of IgG 4 , suggesting that the elevated IgG 4 level does not act as a pathogenic factor in this disease but rather as an anti-inflammatory factor.…”