Diagnostic Criteria For Autoimmune Pancreatitis Research Articles

Autoimmune Pancreatitis (AIP) Type 1 and Type 2

To develop and validate histologic diagnostic criteria for autoimmune pancreatitis (AIP) and its types. Thirteen pathologists participated in this 2-phase study to develop diagnostic criteria for AIP types 1 and 2 (phase 1) and validate them (phase 2). A virtual library of 40 resected pancreata with AIP and other forms of chronic pancreatitis (CP) was constructed. Readers reviewed the slides online and filled out a questionnaire for histopathologic findings and diagnosis. Diagnostic criteria for AIP and its types were proposed according to the results from the top 5 reviewers in phase 1. The interobserver agreement was significantly improved in phase 2 by applying the proposed diagnostic criteria. Features distinguishing AIP from alcoholic and obstructive forms of CP were periductal lymphoplasmacytic infiltrate, inflamed cellular stroma with storiform fibrosis, obliterative phlebitis, and granulocytic epithelial lesions. Although there was overlap, 2 types of AIP were recognized. Type 1 had dense lymphoplasmacytic infiltrate with storiform fibrosis and obliterative phlebitis, whereas type 2 was distinguished from type 1 by the presence of granulocytic epithelial lesions. Autoimmune pancreatitis can be distinguished from other forms of CP with substantial interobserver agreement. The 2 types of AIP can be distinguished by the proposed consensus histopathologic diagnostic criteria.

Proposal for diagnostic criteria for IgG4-related kidney disease

IgG4-related disease has attracted wide attention recently. It is characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive plasma cells into multiple organs, with the kidney being one representative target. Although several sets of diagnostic criteria for autoimmune pancreatitis (AIP) are available and renal lesion is recognized as an extra-pancreatic manifestation of AIP, it is difficult to differentiate IgG4-related tubulointerstitial nephritis (TIN) without AIP from other types of TIN. To clarify the entity of IgG4-related kidney disease (IgG4-RKD) and support in-depth studies, the Japanese Society of Nephrology has established a working group to prepare diagnostic criteria for IgG4-RKD. The working group analyzed 41 patients with IgG4-RKD, and collected the following data to devise a diagnostic algorithm and diagnostic criteria for IgG4-RKD: clinical features including extra-renal organ involvement, urinalysis and serological features including serum IgG4 levels, imaging findings demonstrated by computed tomography (CT), renal histology with IgG4 immunostaining, and response to steroid therapy. The conditions for criteria are as follows. (1) Presence of some kidney damage, as manifested by abnormal urinalysis or urine marker(s) and/or decreased kidney function with either elevated serum IgG level, hypocomplementemia, or elevated serum IgE level. (2) Kidney imaging studies showing abnormal renal imaging findings, i.e., multiple low density lesions on enhanced CT, diffuse kidney enlargement, hypovascular solitary mass in the kidney, and hypertrophic lesion of the renal pelvic wall without irregularity of the renal pelvic surface. (3) Serum IgG4 level exceeding 135mg/dl. (4) Renal histology showing two abnormal findings: (a) dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/high power field (HPF) and/or ratio of IgG4-positive plasma cells/IgG positive plasma cells >40%. (b) Characteristic 'storiform' fibrosis surrounding nests of lymphocytes and/or plasma cells. (5) Extra-renal histology showing dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/HPF and/or ratio of IgG4-positive plasma cells/IgG-positive plasma cells >40%. The diagnosis is classified into 3 stages of definite, probable and possible according to the combinations of the above conditions. Thirty-nine cases (95.1%) were diagnosed with IgG4-RKD according to the criteria. The provisional criteria and algorithm appear to be useful for clarifying the entity of IgG4-RKD and seeking underlying IgG4-RKD cases; however, further experience is needed to confirm the validity of these criteria.

Recent advances in diagnosis and treatment of autoimmune pancreatitis

Autoimmune pancreatitis (AIP), which is always associated with autoimmune manifestations, was introduced in 1995 and has been recognized as a type of chronic pancreatitis. Despite numerous studies in Japan, Europe and the United States in recent years, no consensus has been reached about the diagnostic criteria for AIP that may be difficult to distinguish from pancreatic cancer(PC). Nevertheless, the results find it dramatically responds to steroid therapy. Key words: Pancreatitis; Autoimmune diseases; Diagnostic, differential; Therapy

Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease

Recent studies have suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1 AIP, related to IgG4 (lymphoplasmacytic sclerosing pancreatitis); and type 2 AIP, related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Compared with type 2 AIP, the clinicopathological features of type 1 AIP, with increased serum IgG4/IgE levels, abundant infiltration of IgG4 + plasmacytes and lymphocytes, autoantibodies, and steroid responsiveness, are more suggestive of abnormal immunity such as allergy or autoimmunity. Moreover, patients with type 1 AIP often have extrapancreatic lesions, such as sclerosing cholangitis, sclerosing sialadenitis, or retroperitoneal fibrosis, showing pathological features similar to those of the pancreatic lesions. Based on these findings, an international concept of and diagnostic criteria for AIP have been proposed recently. Of interest, many synonyms have been proposed for the conditions of AIP and extrapancreatic lesions associated with IgG4, such as "multifocal idiopathic fibrosclerosis," "IgG4-related autoimmune disease," "IgG4-related sclerosing disease," "systemic IgG4-related plasmacytic syndrome (SIPS)," and "IgG4-related multiorgan lymphoproliferative syndrome," all of which may refer to the same conditions. Therefore, the Japanese Research Committee for "Systemic IgG4-Related Sclerosing Disease" proposed a disease concept and clinical diagnostic criteria based on the concept of multifocal fibrosclerosing disease, in 2009, in which the term "IgG4-related disease" was agreed upon as a minimal consensus to cover these conditions. Although the significance of IgG4 in the development of "IgG4-related disease" remains unclear, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-related diseases. The concept and diagnostic criteria of "IgG4-related disease" will be changed in accordance with future studies.

Comparative Evaluation of the Japanese Diagnostic Criteria for Autoimmune Pancreatitis

The aim of the study was to clarify the problems of the Japanese criteria for autoimmune pancreatitis (AIP) in comparison with the other criteria. We retrospectively investigated the clinical, imaging, serological, and histopathogic features, together with other organ involvement and response to steroid, in 50 patients with AIP diagnosed on the basis of the Japanese, Korean, HISORt, and Asian criteria. Thirty-five patients with pancreatic cancer were enrolled as a control group. Forty (80%) of 50 patients received a diagnosis of AIP on the basis of the Japanese criteria. Imaging findings and serological parameters fulfilled the Japanese criteria in 40 (80%) and 50 (100%) of the patients. Pathological findings fulfilled the Japanese criteria in 6 (43%) of 14 patients. All of the 10 patients who did not have a diagnosis of AIP did not fulfill the imaging criteria. Serological parameters fulfilled the Japanese criteria in 8 (23%) of 35 patients with pancreatic cancer. The sensitivities of the Japanese, Korean, HISORt, and Asian criteria for AIP were 80%, 86%, 92%, and 82%, respectively. The specificities of those 4 criteria were 89%, 89%, 97%, and 89%, respectively. The low sensitivity of imaging criteria and low specificity of serological criteria were the problems in the Japanese criteria.

Comparison of the Mannheim Diagnostic Criteria of autoimmune pancreatitis with other diagnosic criteria systems

Introduction: Different diagnostic criteria for autoimmune pancreatitis (AiP) have been developed in various centers from Europe, USA and Asia. We recently developed the Mannheim AiP Diagnostic Criteria. A consensus about the different diagnostic systems has not been reached.

Relapsing Autoimmune Pancreatitis in a 14-Year-Old Girl

We present a case of acute pancreatitis in a 14-year-old girl which fulfilled the diagnostic criteria of autoimmune pancreatitis (AIP) and responded to corticosteroid therapy. Imaging studies revealed that the main pancreatic duct was narrow in the head of the pancreas but had been dilated in the body at an earlier stage. The pancreatitis recurred twice when the prednisolone dose was reduced to 10 mg or less but responded each time to an increased dose and has been kept under control with low-dose prednisolone therapy for 3 years since onset. Repeated magnetic resonance cholangiopancreatography during steroid therapy revealed an improvement of the narrowing of the main pancreatic duct in the head and dilation of the duct in the body. AIP in younger patients has distinct clinical features, such as presentation with epigastralgia, back pain without jaundice, and elevated serum amylase levels. The serum level of IgG4 is rarely increased in young patients, indicating a different disease mechanism than for cases in elderly patients. Given the excellent response of this condition to steroid therapy, AIP should be considered even in young children and adolescents when the diagnosis of idiopathic pancreatitis is suggested.

The Combined Measurement of Total Serum IgG and IgG4 May Increase Diagnostic Sensitivity for Autoimmune Pancreatitis Without Sacrificing Specificity, Compared With IgG4 Alone

Until now, there was no international consensus on the diagnostic criteria for autoimmune pancreatitis (AIP). As for serologic criteria, the HISORt criteria use elevated immunoglobulin (Ig) G4 alone, whereas the Asian diagnostic criteria include elevations of total IgG or IgG4, or the presence of autoantibodies. This study was mainly aimed at determining whether the combined measurement of total IgG and IgG4 could increase the diagnostic sensitivity for AIP while maintaining specificity, compared with IgG4 alone. Another aim was to determine the utility of autoantibodies to diagnose AIP. We prospectively measured total serum IgG and IgG4 together in 82 consecutive patients with AIP, and seropositivity was defined as elevation of either total IgG or IgG4. To evaluate specificity in the differentiation of AIP from pancreatic cancer, total serum IgG and IgG4 were prospectively measured in 110 patients with pancreatic cancer. Also, the detection rates of antinuclear antibody (ANA) and rheumatoid factor (RF) were retrospectively reviewed in patients with AIP. In patients with AIP, the sensitivity of IgG4 (> or = 135 mg/dl) was 52.5% (43/82), significantly higher than that (46.3%, 38/82) of total IgG (> or = 1,800 mg/dl) (P<0.05). The sensitivity of combined measurement of total IgG and IgG4 for AIP was 68.3% (56/82), significantly higher than that of IgG4 alone (P<0.05). The specificity of total IgG and IgG4 in the differentiation of AIP from pancreatic cancer was 96.4 and 99.1%, respectively. The specificity of combined measurement of total IgG and IgG4 was 95.5%, and it was not significantly different from that of IgG4 alone (P=0.125). The sensitivity of ANA (> or = 1:80) and RF was 24.4% (19/78) and 20.3% (13/64), respectively. All but one patient who had positive results for ANA or RF also showed elevations of either total IgG or IgG4, respectively. The combined measurement of total serum IgG and IgG4 may increase diagnostic sensitivity without sacrificing specificity, compared with IgG4 alone. However, the measurement of ANA or RF may show no additional benefit when combined with total serum IgG and IgG4.

Autoimmune Pancreatitis: Pathologic Subtypes and Their Implications for Its Diagnosis

Autoimmune pancreatitis (AIP) is a rare but treatable form of pancreatic disease that is being increasingly recognized worldwide. The diagnosis of AIP remains a clinical challenge and the difficulty is compounded by the fact that there are no internationally agreed on diagnostic criteria for AIP. One of the reasons for the lack of consensus on diagnostic criteria could be that the term "AIP" likely refers to more than one distinct disease or subtype. This may explain the divide between European and other diagnostic criteria. Recent insights into AIP subtypes should help develop an evidence-based consensus on diagnostic criteria for the disease.

A variant form of autoimmune pancreatitis successfully treated by steroid therapy, accompanied by von Meyenburg complex

Diagnostic criteria for autoimmune pancreatitis (AIP) have been proposed and used clinically because, despite its unique clinicopathological features, AIP does not have disease-specific serological tests for confirmation. However, diagnosis of a patient with pancreatic lesions mimicking cancer who deviates from these diagnostic criteria is still difficult. We present herein a patient with a variant form of AIP successfully diagnosed by fine-needle biopsy, whose response to steroid therapy was excellent. A 55-year-old Japanese man was admitted to hospital because of jaundice and pancreatic head mass. AIP was considered as one of the differential diagnoses; however, as the patient showed neither pancreatic duct narrowing nor immunological abnormalities, he did not meet the Japanese diagnostic criteria for AIP. Histopathology of the pancreatic mass demonstrated abundant infiltration by lymphocytes and interstitial fibrosis, which suggested AIP. Immunoreaction to IgG4, which is supposed to be specific to AIP, was not observed; however, response to subsequent prednisolone therapy was good, with dramatic pancreatic head mass regression. Aside from the pancreatic head mass, diffusely spreading small lesions were observed throughout the liver. The likelihood of a potential association with extrapancreatic lesions of AIP was considered and led us to carry out a liver biopsy, which revealed biliary hamartoma, also called von Meyenburg complex (VMC). As IgG4-positive plasma cell infiltration was not demonstrated in the hamartomatous regions, the hepatic condition was thought to have occurred incidentally; however, to the best of our knowledge, this is the first report in which the association between AIP and VMC was investigated and discussed.

Review of 67 Patients With Autoimmune Pancreatitis in Korea

The ideal diagnostic criteria of autoimmune pancreatitis (AIP) are still challenging. Therefore, we investigated the clinical features of AIP in Korea and assessed the clinical use of new Korean diagnostic criteria. We reviewed 67 patients with AIP enrolled in 16 hospitals via a multicenter study. The diagnosis was confirmed according to the Korean diagnostic criteria that included pancreatic imaging, laboratory findings, histopathology, and response to steroid. Mean age of the patients was 56 years, and 73% were men. Obstructive jaundice (52%) was the most common symptom, and 14 patients (21%) had other organ involvement. Fifty-four patients (81%) revealed diffuse swelling of the pancreas. Either immunoglobulin (Ig)G or IgG4 was elevated in 76%. According to the Korean criteria, 65 patients had definite diagnostic criteria, and 2 patients had probable criteria. Fifteen patients were fulfilled with image, serological, and histopathologic criteria, and 4 patients could be diagnosed with image and steroid responsiveness. Ten patients experienced recurrent attacks of AIP during the mean 20-month follow-up. Among 67 cases of AIP, either IgG or IgG4 was elevated in 76% of patients, and 14 patients (21%) had other organ involvement. New Korean diagnostic criteria are useful for diagnosis of AIP.

US, CT AND MRI FINDINGS OF AUTOIMMUNE PANCREATITIS BASED ON "CLINICAL DIAGNOSTIC CRITERIA OF AUTOIMMUNE PANCREATITIS 2006"

US, CT and MRI findings of autoimmune pancreatitis (AIP) were described based on "Clinical diagnostic criteria of autoimmune pancreatitis 2006". Evaluation of the enlargement of the pancreas, either diffuse or localized, is the essential point by imaging studies. However, other characteristic imaging findings are also required in order to obtain a correct diagnosis. On US, hypoechoic pancreatic enlargement is characteristic to AIP. On dynamic study, either on CT or on MRI, AIP usually shows a delayed enhancement pattern. Signal intensity on T1-weighted MRI usually decreased, however it varies on T2-weighted image. Attention should be paid to the fact that there are various imaging findings of AIP, probably due to the disease condition. At present, MRCP cannot be used in evaluating main pancreatic duct narrowing; however, it might be used in the near feature based on advances in image quality.

Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan-Korea Symposium on Autoimmune Pancreatitis

In 2002, the Japan Pancreas Society (JPS) was the first in the world to propose diagnostic criteria for autoimmune pancreatitis (AIP). Since the concept of AIP has changed with the accumulation of AIP cases, the Research Committee of Intractable Pancreatic Diseases (RCIPD) provided by the Ministry of Health, Labour and Welfare of Japan and the JPS issued revised clinical diagnostic criteria of AIP in 2006. The Asan Medical Center of Korea also proposed diagnostic criteria for AIP in 2006. However, there are subtle but clinically challenging differences between the Japanese and Korean criteria. This inconsistency makes it difficult to compare data in studies from different centers and elucidate the characteristics of AIP. To reach a consensus on AIP, the RCIPD and the Korean Society of Pancreatobiliary Diseases established the following Asian criteria for the diagnosis of AIP: I-1. Imaging studies of pancreatic parenchyma show a diffuse/segmental/focally enlarged gland, occasionally with a mass and/or a hypoattenuation rim. I-2. Imaging studies of pancreaticobiliary ducts show diffuse/segmental/focal pancreatic ductal narrowing, often with stenosis of the bile duct. (Both I-1 and I-2 are required for diagnosis). II. Elevated level of serum IgG or IgG4, and detection of autoantibodies. III. Common lymphoplasmacytic infiltration and fibrosis, with abundant IgG4-positive cell infiltration. AIP should be diagnosed when criterion I and one of the other two criteria are satisfied, or when histology shows the presence of lymphoplasmacytic sclerosing pancreatitis in the resected pancreas. A diagnostic trial of steroid therapy can be applied carefully by expert pancreatologists only in patients fulfilling criterion I alone with negative diagnostic work-up results for pancreatobiliary cancer.

Autoimmune pancreatitis: with special reference to a localized variant.

In 2006, the Japan Pancreas Society revised the diagnostic criteria for autoimmune pancreatitis (AIP) so as to more clearly define its morphological, pathological, and immunological features, as follows: (1) diffuse or segmental narrowing of the main pancreatic duct with an irregular wall and diffuse or localized enlargement of the pancreas recognized by imaging studies; (2) high serum gamma globulin, IgG, or IgG4 levels, or the presence of autoantibodies; and (3) marked interlobular fibrosis and prominent infiltration of lymphocytes and plasma cells in the periductal area, occasionally with lymphoid follicles in the pancreas. Establishing a diagnosis of AIP has become easier with knowledge of its immunological abnormalities, including serum IgG4 levels. However, the localized form of AIP sometimes mimics pancreatic cancer. The rate of focal mass formation in patients with AIP is reportedly 24%-43%; however, there have been few reports on the histological findings of localized AIP, in contrast to mass-forming pancreatitis (MFP). Our review of patients who had undergone resection due to a preoperative diagnosis of MFP with possible cancer revealed 72% to be patients with localized AIP. For the discrimination of these conditions, it is important to recognize the characteristic ultrasonographic findings of AIP, i.e., (1) diffuse or localized enlargement and hypoechogenicity of the pancreas; (2) rarity of calcification, cystic lesions, and peripancreatic fluid collection; (3) thickened layer structure of the bile duct wall; (4) iso/hypervascularity in the swollen portion of the pancreas; (5) attenuation of pancreatic swelling and bile duct wall thickening after steroid therapy; and (6) multiple hypoechoic masses in various organs, including the pancreas. Contrast-enhanced endoscopic ultrasonography is potentially a useful tool in the differential diagnosis and for assessment of the efficacy of steroid therapy by enabling evaluation of the vascularity of the lesions. Along with the presence of IgG4-positive plasma cells, verification of obliterative phlebitis is highly specific for the histological diagnosis of AIP.

Review of diagnostic criteria for autoimmune pancreatitis; for establishment of international criteria.

Along with worldwide expansion of the disease concept of autoimmune pancreatitis (AIP), the necessity of international diagnostic criteria for the disease is increasing. Since the first diagnostic criteria for AIP by the Japan Pancreas Society was proposed in 2002, certain groups in several countries have reported criteria for AIP. We reviewed the criteria proposed to date. Among three systematic criteria from Japan, the Mayo Clinic and Korea, there is no fundamental difference in the three major diagnostic categories: findings on pancreatic imaging, laboratory and histological studies. Notable differences are that typical imaging findings are essential for the diagnosis in Japanese and Korean criteria, but not in the Mayo criteria, while, the Mayo criteria emphasize the histological findings as a gold standard for the diagnosis. The critical differences between the Japanese and the other two criteria are the use of the diagnostic factors "other organ involvement" and "steroid responsiveness." Employment of these factors in clinical diagnostic criteria for general physicians possibly confuses the disease concept and definitely increases the risk for treating patients with pancreatic or biliary malignancies with steroids. Even if the sensitivity of criteria goes down, their use might be limited to certain kinds of specific criteria, such as that for epidemiological study, patient selection for research purposes, or use in expert hospitals. The disease entity of AIP postulated in Europe includes two histological types of pancreatitis with different clinical phenotypes, suggesting two syndromic spectra of autoimmune-related chronic pancreatitis.

Autoimmune pancreatitis

Autoimmune pancreatitis is a form of chronic pancreatitis of presumed autoimmune aetiology. The disease is characterised with clinical, serological, histomorphological and imaging features. Autoimmune pancreatitis is recognised as a T-cell-mediated specific disease with lymphoplasmatic infiltration of pancreatic tissue and pancreatic parenchyma fibrosis. Serum immunoglobulin IgG or IgG4 and antibodies (rheumatoid factor, lactoferrin antibodies, carbonic anhydrase II, etc) are usually increased. But the lack of specific biochemical markers is a major drawback in the diagnosis of autoimmune pancreatitis. The Japan Pancreas Society proposed diagnostic criteria for autoimmune pancreatitis as the presence antibodies, pancreas enlargement and pancreatic duct narrowing, lymphoplasmatic infiltration, response to corticosteroid therapy, and association with other autoimmune diseases such as autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, sialoadenitis, inflammatory bowel disease and Sjögren syndrome. New criteria (HISORt Criteria) incorporate imaging changes, organ involvement, specific elevation of IgG4 subclass and histopathological markers. Autoimmune pancreatitis could be associated with diabetes mellitus and exocrine pancreatic dysfunction. Clinically, autoimmune pancreatitis is a disease with mild symptoms; severe attacks of abdominal pain are not typical. Typically, pancreatic calcifications and pseudocyst are absent; on the other hand jaundice and/or pancreatic mass are frequent signs, and both make differential diagnosis with pancreatic cancer difficult. From a practical point of view, in an elderly male presenting with obstructive jaundice and pancreatic mass, autoimmune pancreatitis is one of the differential diagnoses to avoid unnecessary surgical therapy.

Therapeutic strategy for autoimmune pancreatitis

Autoimmune pancreatitis (AIP) is a particular type of pancreatitis that is thought to have an autoimmune etiology. Before therapy for AIP is begun, accurate diagnosis of AIP is necessary. It is important to distinguish AIP from pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, AIP should be diagnosed on the basis of a combination of abnormalities unique to AIP. The Japanese "Diagnostic Criteria for Autoimmune Pancreatitis 2006" require the characteristic imaging findings of AIP and that at least one of the laboratory criteria or histopathological criteria have to be present. Unlike in patients with usual chronic pancreatitis, corticosteroid therapy is frequently effective in resolving the morphological findings and the symptoms of AIP patients. Therefore, administration of oral steroid therapy has become standard therapy for AIP. Indications for steroid therapy for AIP are thought to include obstructive jaundice due to stenosis of the bile duct, associated extrapancreatic sclerosing lesions, and diabetes mellitus coincidental with AIP. Oral prednisolone is usually started at 30 mg/day and tapered by 5 mg every 1-2 weeks. Serological and imaging tests are followed periodically after commencement of steroid therapy. Patients in whom complete radiological improvement is documented can stop their medication. To prevent relapses, continued maintenance therapy with prednisolone 2.5-5 mg/day is sometimes required. Patients who relapse should be re-treated with high-dose steroid therapy. A poor response to steroid therapy should raise the possibility of pancreatic cancer and the need for further examination, including laparotomy.

Diagnostic criteria for autoimmune pancreatitis in Japan

Autoimmune pancreatitis (AIP) is a particular type of pancreatitis of presumed autoimmune etiology. Currently, AIP should be diagnosed based on combination of clinical, serological, morphological, and histopathological features. When diagnosing AIP, it is most important to differentiate it from pancreatic cancer. Diagnostic criteria for AIP, proposed by the Japan Pancreas Society in 2002 first in the world, were revised in 2006. The criteria are based on the minimum consensus of AIP and aim to avoid misdiagnosing pancreatic cancer as far as possible, but not for screening AIP. The criteria consist of the following radiological, serological, and histopathological items: (1) radiological imaging showing narrowing of the main pancreatic duct and enlargement of the pancreas, which are characteristic of the disease; (2) laboratory data showing abnormally elevated levels of serum gamma-globulin, IgG or IgG4, or the presence of autoantibodies; (3) histopathological examination of the pancreas demonstrating marked fibrosis and prominent infiltration of lymphocytes and plasma cells, which is called lymphoplasmacytic sclerosing pancreatitis (LPSP). For a diagnosis of AIP, criterion 1 must be present, together with criterion 2 and/or criterion 3. However, it is necessary to exclude malignant diseases such as pancreatic or biliary cancer.

Substitution of Aspartic Acid at Position 57 of the DQβ1 Affects Relapse of Autoimmune Pancreatitis

Although autoimmune pancreatitis (AIP) responds well to corticosteroid therapy, relapse during maintenance corticosteroid therapy or after the withdrawal of corticosteroid treatment is not uncommon. To date, the factors related to relapse of AIP have not been fully explored. To determine the clinical and genetic predictors relating to the relapse of AIP, we evaluated clinical factors, HLA polymorphisms, and the amino acid sequences in 40 patients with AIP. At a median follow-up period of 40 months (range, 12-67 months), relapse developed in 13 of 40 patients with AIP (33%), in whom complete remission was achieved with oral corticosteroid therapy. Among demographics, clinical characteristics in the initial diagnosis of AIP, we could not find any clinical predictor for relapse of AIP; however, in amino acid sequence analysis for relapse of AIP, the substitution of aspartic acid to nonaspartic acid at residue 57 of DQbeta1 showed a significant association with relapse of AIP (nonrelapse group, 29.6%; relapse group, 100%; P = .00003; odds ratio, 3.38; 95% confidence interval, 1.9-6.0). There was a significant difference in the timing of relapse of AIP, according to density of the nonaspartic acid residue at DQbeta1 57 (nonaspartic acid homozygosity: mean +/- SD, 6.7 +/- 4.2 months; nonaspartic acid heterozygosity: mean +/- SD, 33 +/- 11 months; P < .001). Substitution of aspartic acid to nonaspartic acid at DQbeta1 57 appears to represent a key genetic factor for relapse of AIP (ClinicalTrials.gov number, NCT00444444).

Prevalence of autoimmune pancreatitis in Japan from a nationwide survey in 2002

Because autoimmune pancreatitis is a new disease entity, there are no data with regard to its prevalence. To estimate the number of patients with autoimmune pancreatitis in Japan, we randomly selected hospitals using stratification and asked them how many patients they had with pancreatitis in 2002 who fulfilled the diagnostic criteria for autoimmune pancreatitis as proposed by the Japan Pancreas Society. The number of patients with autoimmune pancreatitis who visited hospitals in Japan in 2002 was approximately 900 (95% confidence interval; range 670-1100). The male : female ratio was 2.85 : 1, and the age of disease onset in 95% of the patients was over 45 years. The prevalence of patients with autoimmune pancreatitis in Japan was estimated to be 0.82 per 100,000. Autoimmune pancreatitis was predominantly seen in men past middle age (over the age of 45 years).