To the Editor
Autoimmune pancreatitis (AIP), a distinctive type of pancreatitis, is classified to 2 subtypes by the International Consensus of Diagnostic Criteria (ICDC) for AIP1: type 1 related with IgG4 [lymphoplasmacytic sclerosing pancreatitis, (LPSP)], and type 2 with granulocytic epithelial lesion (idiopathic duct-centric pancreatitis). The former one is suspected to be the pancreatic lesions of IgG4-related diseases.2 The patients with both types of AIP should be differed from pancreatic or bile-duct cancer because they often have pancreatic enlargement, mass formation, and obstructive jaundice. However, clinicopathological features of each one are quite different. The patients with type 1 AIP, commonly seen in older men, have frequently elevated serum levels of gammaglobulin, IgG, IgG4, or the presence of positive autoantibodies.1 They are often associated with other organ involvements (OOIs) such as sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis, and so on.1,2 Histopathologic features of LPSP are characterized by prominent infiltration of lymphocytes and IgG4-positive plasmacytes, storiform fibrosis, and obliterative phlebitis. Although treated effectively by steroid therapy, its long-term prognosis of type 1 AIP is not clear, relapse often occurs, and some cases are reported to be associated with pancreatic stones. On the other hand, type 2 AIP lacks abnormal immunological findings, and is seen in both sexes without significant differences, also in relatively young patients, and sometimes associated with inflammatory bowel disease. Steroid therapy is effective, but relapse is rare. Type 2 AIP is more often observed in Europe and United States in 20% to 60% of total AIP cases, but extremely rare in Japan.
Previously, the Japan Pancreas Society (JPS) and the Research Committee for Intractable Pancreatic Disease by the Ministry of Labor, Health and Welfare of Japan (RCIPD-MLHWJ) proposed 2 kinds of Japanese diagnostic criteria for AIP in 20023 and 2006.4 The concepts o Japanese ones were based on being simple as much as possible and easy use for general physicians as well as pancreatologists. The ICDC for AIP1 firstly enable us to diagnose and compare 2 distinctive subtypes, type 1 and type2 AIP, independently. However, the ICDC is somewhat complicated for a general use. Different from western countries, extremely few cases of type 2 AIP have been confirmed in Japan. On the basis of the Japanese conditions, the JPS and RCIPD-MLHWJ revised them as the clinical diagnostic criteria for AIP 2011 (JPS2011), which took the basic concept of the ICDC as much as possible. In 2012, the Japanese version of the amendment for Japanese physicians5 has been published in the official journal of JPS, “Suizo.” To better understand the Japanese situation in the diagnosis of AIP, we, herein, introduce the English version of the JPS2011 (see Table 1, Supplemental Digital Content 1, http://links.lww.com/MPA/A202) in “Pancreas,” the official journal of JPS and American Pancreas Association, with permissions by Professor Takeyama, the editor-in-chief of “Suizo” and Professor Go, that of “Pancreas.”
The concept of the JPS2011 took basic concepts of both the Japanese previous criteria and type 1 in the ICDC as much as possible5: (1) simple for general physicians’ use; (2) diffuse/segmental/focal classification on pancreatic imaging; (3) IgG4 alone as a serological marker; (4) sclerosing cholangitis, sclerosing sialadenitis, and retroperitoneal fibrosis as OOIs; (5) no classifications of level 1/2 in serum IgG4 and OOI; and (6) optional steroid trial only after denying malignancy by endosonography-guided fine needle aspiration (EUS-FNA). Although affiliations available for EUS-FNA have been increasing in Japan, endoscopic retrograde cholangiopancreatography (ERCP) procedures are more commonly performed than EUS-FNA. Therefore, different from the previous Japanese guidelines, the pancreatic parenchyma on computed tomography/magnetic resonance imaging is separated from the ductal image on ERCP. Endoscopic retrograde cholangiopancreatography is basically required in the focal/segmental type, but not in the typical diffuse type of AIP. MRCP is not available in the JPS2011 because of low resonance.
The JPS2011 contains only IgG4 in serological markers, but not gammaglobulinemia, nonspecific autoantibodies such as antinuclear autoantibody.5 We confirmed that the cutoff level of serum IgG4 (<135 mg/dL) using 717 cases of AIP and 577 cases of pancreas cancer was appropriate.5 Histopathologic findings are the same as LPSP, which contains the following 4 histopathologic criteria: (1) prominent infiltration of lymphocytes and plasmacytes and fibrosis, (2) prominent infiltration of IgG4-positive plasma cells and lymphocytes, (3) storiform fibrosis, and (4) obliterative phlebitis. In the histological criterion regarding IgG4-positive cells, the Japanese comprehensive diagnostic criteria (CDC) for IgG4-related disease require both more than 10 IgG4-positive cells /HPF and more than 40% of the ratio of IgG4/IgG-positive cells.2 Different from the Japanese CDC criteria, the JPS2011 requires 1 criterion, more than 10 IgG4-positive cells/HPF by biopsy specimen, which follows the ICDC1 and the Consensus Statement on the Pathology of IgG4-related disease.6
The previous JPS2002 and JPS2006 criteria used in Japan did not contain OOI in diagnosis of AIP.2,3 Among many OOIs previously reported, sclerosing cholangitis, sclerosing sialoadenitis, and retroperitoneal fibrosis are recommended as the typical OOI in JPS2011, which follows the ICDC. As the same as Asian criteria or ICDC, an optional steroid trial was included in diagnostic criterion only after denying malignancy using EUS-FNA by experts. Different from the previous Japanese criteria, the patients with AIP are diagnosed as having definitive, probable, or possible AIP by a combination with criteria described previously, similar to the concept of the ICDC.4 Although the JPS2011 is focused on type 1 AIP, some patients with type 2 AIP, extremely rare in Japan, may be diagnosed as possible AIP. As ERCP is more commonly performed to diagnose AIP or pancreas cancer compared with EUS-FNA in Japan, ERCP is essentially required in the diagnosis of focal/segmental type of AIP. However, to follow the concept of the ICDC as much as possible, the following exceptional case can be acceptable only by an expertise. When a patient with a focal/segmental image of AIP on computed tomography/magnetic resonance imaging without ERCP findings fulfill more than one of III (serum IgG4), IVb (2 of pathological findings), and V(a/b) (OOI), he/she can be diagnosed as possible AIP only after the negative workup for malignancy by EUS-FNA, and confirmed as probable one by an optional steroid response.
The RCIPD-MLHWJ is now studying a nationwide survey of type 2 AIP in Japan as well as type 1 AIP. When the clinical features of the Japanese patients with type 2 AIP are clarified in the near future, the clinical diagnostic guidelines in Japan should be modified.
Kazuichi Okazaki, MD, PhD
Department of Gastroenterology and
Hepatology Kansai Medical University Osaka
Tooru Shimosegawa, MD, PhD
Division of Gastroenterology Tohoku
University Graduate School of Medicine
The working Group Members of the Japan
Pancreas Society and the Research
Committee for Intractable Pancreatic
Disease by the Ministry of Labor, Health and
Welfare of Japan
This study was supported by a grant of Health and Labor Sciences Research Grants for Intractable Diseases, from the Minister of Labor and Welfare of Japan.
The authors declare no conflict of interest.
Supplemental digital content is available in the text.
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