In 1961, Sarles et al.1 asked the following question regarding the particular cases of pancreatitis with hypergammaglobulinemia: “Chronic inflammatory sclerosis of the pancreas—an autoimmune pancreatic disease?” As similar cases were rarely observed, a relationship between such pancreatitis and autoimmunity was viewed skeptically during the following several decades. In 1992, Toki et al.2 have reported 4 cases with unusual diffuse irregular narrowing of the main pancreatic duct and diffuse enlargement of the entire pancreas due to lymphocyte infiltration. In 1995, Japanese investigators3 firstly proposed a concept of “autoimmune pancreatitis (AIP)”, in which the patients showed diffusely enlarged pancreas, narrowing pancreatogram, increased serum IgG, presence of autoantibodies, fibrotic changes with lymphocytic infiltration and steroidal efficacy. Thereafter, many AIP cases have been reported from Japan, and AIP has been accepted as a new clinical entity.4,5 The histopathological findings of AIP show massive infiltration of lymphoplasmacytes with fibrosis, which is consistent with lymphoplasmacytic sclerosing pancreatitis (LPSP).6 Many Japanese investigators have paid great attention to AIP, especially with regard to its unique pancreatic images,2 IgG4,7 disease-associated autoantibodies,8 extrapancreatic lesions,6,914 and steroidal efficacy.14,15

Currently in Japan, diagnosis of AIP is based on the “diagnostic criteria 2002 of autoimmune pancreatitis”16 proposed by the Japan Pancreas Society. However, the accumulation of many AIP cases shows that the concept of AIP has changed slightly to include extrapancreatic lesions and associated disorders, which suggests that the current diagnostic criteria are becoming inadequate.

In 2003, the Research Committee of Intractable Diseases of the Pancreas, supported by the Japanese Ministry of Health, Labour and Welfare (Chairman, M. Otsuki), began to review the current diagnostic criteria in light of recently acquired information and knowledge. The team organized a working group (WG), consisting of the team members and researchers specializing in autoimmune pancreatitis, to develop a proposal for the revision of the current diagnostic criteria. On 7 October 2005 and 22 April 2006, the Research Committee of Intractable Diseases of the Pancreas and the Japan Pancreas Society jointly held open forums to discuss the proposed amendments.

This report describes the background of the proposed amendments and the final proposal for the revised version of the clinical diagnostic criteria of AIP.

Background of the amendment of the diagnostic criteria proposed by the working group of the Research Committee of Intractable Diseases of the Pancreas

Table 1 shows the diagnostic criteria 2002 of AIP proposed by the Japan Pancreas Society.16 The members of the WG accumulated 147 cases of AIP and identified the cases that did not fulfill the current diagnostic criteria but were strongly suspected to be AIP. It then evaluated those cases in detail using imaging, laboratory, and pathological findings, and unanimously rediagnosed some of them as AIP. Using the analyzed data, the members then summarized the current status and problems of AIP in Japan, as outlined below. After reviewing the material in an expanded open discussion in October 2004 in Fukuoka City, the Research Committee of Intractable Diseases of the Pancreas amended the current diagnostic criteria for AIP. Major discussions in this open meeting are summarized below.

Table 1 Diagnostic criteria 2002 of autoimmune pancreatitis by the Japan Pancreas Society

Concept and definition of AIP

  1. 1.

    The following extrapancreatic lesions may be associated with AIP: biliary lesions, sialadenitis, retroperitoneal fibrosis, enlarged celiac and hilar lymph nodes, chronic thyroiditis, and interstitial nephritis914 (Table 2). AIP may be a systemic disorder.

  2. 2.

    Sclerosing cholangitis associated with AIP is different from primary sclerosing cholangitis (PSC), because of its effective response to steroid therapy and of the presence of IgG4-positive plasma cell infiltration.914

  3. 3.

    Sialadenitis coexisting with AIP is negative for both anti-SSA and anti-SSB antibodies and shows IgG4-positive plasma cell infiltration, suggesting that it is different from typical Sjögren’s syndrome but is similar to the sclerosing sialadenitis observed in Mikulicz’s disease and Küttner’s tumor.9,10,14

  4. 4.

    In Western countries, ulcerative colitis and the formation of tumors associated with pancreatic lesions are more frequently observed than in Japan.4 Moreover, pancreatic duct lesions with infiltration of leukocytes as well as LPSP are sometimes observed in Western countries17,18 but not in Japan. These findings may thus be somewhat contrary to the definition and concept of the disease adopted in Japan.

  5. 5.

    The biggest problem in diagnosing AIP is how to distinguish it from pancreatic or biliary cancer. With the current diagnostic criteria for AIP, many cases that seem to be AIP are excluded, as the criteria were established to rule out false positive cases but to confidently diagnose definite cases of AIP.4,14

Table 2 Clinicopathological features of autoimmune pancreatitis

Image findings

  1. 1.

    Some cases are consistent with the hematological and histopathological findings of AIP, even though the pancreatic image data show that the lesions are localized to less than one-third of the pancreas.16

  2. 2.

    Some cases fulfill only the image diagnostic criteria for AIP but respond to steroid therapy.14

Laboratory findings

  1. 1.

    Patients with AIP frequently show an increased level of serum IgG4,7 a subclass of IgG, although the pathophysiological significance is still unclear. Serum levels of IgG4 in 147 patients with AIP (602.8 ± 609.1 mg/dl) were significantly higher than those in other, control patients (52.4 ± 57.2 mg/dl) (Fig. 1).

  2. 2.

    Using receiver operating characteristic curves for the 147 cases of AIP and 180 cases of other diseases, the cutoff value for the serum IgG4 was determined to be 128 mg/dl (Fig. 2), which confirmed the validity of the evidenced value of 134 mg/dl.7

Fig. 1
figure 1

Serum levels of IgG4 in 147 patients with autoimmune pancreatitis (AIP) (602.8 ± 609.1 mg/dl) were significantly higher than those (52.4 ± 57.2 mg/dl) in 180 control patients (103 cases of alcoholic chronic pancreatitis, 18 of pancreatic cancer, 13 of primary sclerosing cholangitis, 11 of idiopathic chronic pancreatitis, 5 of cholangiocarcinoma, 2 of Sjögren’s syndrome, and 28 other)

Fig. 2
figure 2

The receiver operating characteristic (ROC) curves. The ROC curves for the 147 cases of AIP and 180 cases of control diseases, the cutoff value for the serum IgG4 was determined to be 128 mg/dl

Pathological findings

  1. 1.

    There is growing evidence that patients with AIP exhibit histopathological symptoms of lymphoplasmacytic sclerosing pancreatitis.4,6,17,18 That is, AIP patients show infiltration of lymphocytes and plasma cells, and obliterative phlebitis. In lymphocyte infiltration, T cells are often predominant, and plasma cells are IgG4-positive.14

  2. 2.

    European and U.S. reports of the destruction of the pancreatic duct epithelium in the presence of predominant neutrophils (idiopathic ductcentric chronic pancreatitis17 or granulocyte epithelial lesion18) have not been confirmed in Japan owing to insufficient study and will be a topic of further study.

  3. 3.

    Pathologically, extrapancreatic lesions are similar to the fibrosis and the lymphoplasmacytic infiltration seen in the pancreatic lesions.


  1. 1.

    Some patients with AIP form pancreatic stones, and the long-term prognosis of AIP is still unclear.14

Final revision based on the discussion in the open forums

In two recently held open forums, the committee members vigorously exchanged opinions about the amendments proposed by the Research Committee of Intractable Diseases of the Pancreas, and unanimously agreed to the finalized amendments (Table 3). The medical treatment guidelines in the current diagnostic criteria have been deleted from the proposed amendments. Those issues that were discussed in the open forums but not included in the proposed amendments are noted below as topics for future consideration.

Table 3 Clinical Diagnostic Criteria of Autoimmune Pancreatitis (revised proposal) (Proposed by the Research Committee of Intractable Diseases of the Pancreas, supported by the Japanese Ministry of Health, Labour and Welfare, and the Japan Pancreas Society)
  1. 1.

    Cases of AIP reported from Western countries are more often associated with ulcerative colitis and the formation of tumors compared with Japanese cases; these associations are somewhat contrary to the definition and concept of the disease adopted in Japan.4,9,17,18 These points were excluded from the Japanese notes, because in Japan, the basic concepts of AIP are generally accepted as pancreatitis featuring abnormal immunity, an enlarged pancreas, and a narrowing of the pancreatic duct. However, these controversial points were considered for inclusion in the introduction to the English notes because they were deemed necessary to clarify the inconsistencies between the findings of foreign and domestic researchers.

  2. 2.

    It was argued that AIP can be diagnosed by imaging data and the effective response to steroid therapy alone. This argument, however, was excluded because of two problems. First, no other autoimmune disorders use steroidal effect for diagnosis except for the scoring system for autoimmune hepatitis, in which the steroidal effect is not used for the differential diagnosis of malignancy. Second, above all, there was a concern that its adoption might encourage the use of facile therapeutic diagnostic techniques just to distinguish AIP from malignant tumors such as pancreatic cancer.

  3. 3.

    There was an argument as to whether the proposal should specify methods for ruling out other pancreatic disorders and pancreatic/biliary cancers. It was decided that each institute may decide the methods at their discretion, because standardization is rather difficult.


The current concept of AIP including extrapancreatic lesions and associated disorders suggests that AIP may be a systemic disorder. As the concept of the disease has undergone changes, a revised version of the clinical diagnostic criteria of AIP in Japan has been proposed. Although it is not possible to establish diagnostic criteria that satisfy everyone, the Japanese criteria are based on the minimum consensus features of AIP in order to avoid the misdiagnosis of malignancy as far as possible, but not to pick up suspicious cases of AIP.