The Diagnosis of Autoimmune Pancreatitis

要旨

The new Japanese clinical guidelines for autoimmune pancreatitis (JCGAIP) presented in this issue1 reflect a careful, consensus-building effort to guide and standardize the diagnosis and treatment of patients with autoimmune pancreatitis (AIP) in Japan. These guidelines are based on the extensive and carefully documented experience of Japanese clinicians and pathologists with AIP-a disease that is increasingly recognized worldwide. The guidelines provide an effective review of AIP and merit attention and careful consideration regarding their application internationally. We wish to focus on 2 issues that arise because of differences in experience and practice among clinicians and pathologists in Western nations: (a) recognition of histological and clinical subtypes of AIP and (b) diagnostic criteria for AIP. The most basic issue is the question of whether there is more than 1 form of AIP in regard to pancreatic pathology, clinical features, and pathogenetic mechanisms. The JCGAIP focus on patients with the histopathologic changes called lymphoplasmacytic sclerosing pancreatitis (LPSP), most of whom have elevations of plasma immunoglobulins, and specifically of IgG4. It has been proposed that AIP is a manifestation of a systemic IgG4-related autoimmune disease.2,3 These patients are typically older than 50 years and male. Large series reported from Europe and the United States consistently identify a second set of patients with slightly different histopathologic changes that have been called idiopathic duct-centric chronic pancreatitis (IDCP)4 or AIP with granulocytic epithelial lesions (GELs).5 This subgroup of patients is more diverse in age, includes a higher fraction of female patients, and characteristically does not have elevated plasma IgG4.5 These patients may have chronic inflammatory bowel disease such as ulcerative colitis, but typically lack evidence of extrapancreatic involvement of the organs typical of IgG4-related autoimmune disease.4,5 More recently, these 2 patterns have been designated as AIP types 1 and 2.6 In the United States and Europe, type 1 AIP (LPSP) is more common than type 2 (IDCP/AIP with GELs) in series that identify both types.4,5 The JCGAIP specifically deal with type 1 AIP and leave open the question as to whether the type 2 pattern is an autoimmune disease. In turn, this raises the question of what evidence suggests an autoimmune origin for IDCP/AIP with GELs. The following observations provide support. Both types of AIP share a number of histopathologic features-most notably a periductal lymphoplasmacytic infiltrate and a phlebitis. Only the concomitant duct infiltration by neutrophilic granulocytes, the GEL, and a less marked phlebitis distinguish the histological changes of type 2 from type 1 AIP. A fraction of patients with type 2 AIP also has inflammatory bowel disease, and one had multiple sclerosis4,5 (some forms of multiple sclerosis are considered to be of autoimmune origin). Type 2 AIP patients may also show biliary involvement similar to that seen in type 1 AIP (G.K., personal observations). A recent report provides evidence that type 2 AIP is found in association with other autoimmune diseases, such as Evans syndrome and Hashimoto thyroiditis, and responds to steroid therapy.7 Finally, both types 1 and 2 AIP cases reveal a similar increase in the numbers of CD4 and CD8 lymphocytes that infiltrate the pancreas.8 In aggregate, these observations provide a significant support for an autoimmune mechanism in the pathogenesis of type 2 AIP. The second issue is more clinical-the question of how to establish the diagnosis of AIP. Let us first discuss the diagnosis of type 1 AIP, which is the focus of Japanese (JCGAIP), Asian,9 and American10 criteria. It is clear from the discussion above that type 1 AIP has a distinct pancreatic histology, that is, LPSP. The Japanese diagnostic criteria, however, do not include diagnostic histology as being a valid independent criterion for diagnosis of AI

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