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2008 j clin gastroenterol diagnostic criteria for autoimmune pancreatitis

2008 j clin gastroenterol diagnostic criteria for autoimmune pancreatitis






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    2008 j clin gastroenterol diagnostic criteria for autoimmune pancreatitis 2008 j clin gastroenterol diagnostic criteria for autoimmune pancreatitis Document Transcript

    • CLINICAL REVIEW Diagnostic Criteria for Autoimmune Pancreatitis Terumi Kamisawa, MD, PhD In North America, about 2.5% of pancreatoduode-Abstract: Autoimmune pancreatitis (AIP), a particular type of nectomies are performed in AIP cases that have beenpancreatitis, is thought to have an autoimmune etiology; it is incorrectly diagnosed as pancreatic cancer2; between 21%recognized as a distinct entity worldwide. AIP has many and 23% of pancreatoduodenectomies performed forcharacteristic clinical, serologic, morphologic, and histopatho- benign conditions are done for AIP.2,3 As there islogic features. In the absence of a diagnostic serologic marker currently no diagnostic serologic marker for AIP, AIPfor AIP, AIP should be diagnosed on the basis of combination should be diagnosed on the basis of presence of aof characteristic findings. AIP responds dramatically to steroid combination of abnormalities unique to AIP. In 2002, thetherapy; thus, accurate diagnosis of AIP can avoid unnecessary Japan Pancreas Society established the ‘‘Diagnosticlaparotomy or resection. It is important not to misdiagnose Criteria for Autoimmune Pancreatitis,’’4,5 which werepancreatic cancer as AIP, and not to misdiagnose AIP as revised in 2006.6 In 2006, 2 new sets of diagnostic criteriapancreatic cancer. Currently, 3 sets of major diagnostic criteria for AIP were proposed, 1 in Korea7 and 1 in the Unitedfor AIP have been proposed in Japan, Korea, and the United States.8 Thus, at present, there are 3 major sets ofStates. The Japanese criteria are based on the minimum diagnostic criteria for AIP. This review discusses andconsensus features of AIP and aim to avoid misdiagnosis of compares the potential limitations of these 3 sets ofmalignancy. When response to steroid therapy is added to the diagnostic criteria for AIP on the basis of our recentcriteria, the diagnostic sensitivity is increased. However, the use treatment of AIP cases and suggests an improved set ofof a steroid trial in cases where differentiation from malignancy diagnostic criteria.is an issue may result in delaying pancreatic cancer surgery,which could lead to cancer progression in several cases. Thus,given that AIP is an IgG4-related systemic disease, an additional JAPANESE DIAGNOSTIC CRITERIAcriterion can be recommended to the Japanese diagnostic During the past decade, many AIP cases have beencriteria: IgG4-immunostaining of biopsied extrapancreatic reported in Japan. These cases were found to have manylesions such as the major duodenal papilla, the bile duct, or common clinicopathologic features. On the basis of thesethe minor salivary gland. It is also time for an international data, the Japan Pancreas Society published the ‘‘Diag-consensus on AIP. nostic Criteria for Autoimmune Pancreatitis, 2002,’’Key Words: autoimmune pancreatitis, diagnostic criteria, steroid which included 3 items: (1) radiologic imaging showingtherapy, IgG4 diffuse enlargement of the pancreas and diffuse irregular narrowing of the main pancreatic duct (more than one(J Clin Gastroenterol 2008;42:404–407) third the length of the entire pancreas); (2) laboratory data demonstrating abnormally elevated levels of serum gammaglobulin or IgG, or the presence of autoantibo-A utoimmune pancreatitis (AIP) is a particular type of pancreatitis that is thought to have an autoimmuneetiology. Since Yoshida et al1 proposed AIP as a dies; and (3) histologic examination of the pancreas showing lymphoplasmacytic infiltration and fibrosis.4,5 The diagnosis of AIP is made when either all 3 criteria arediagnostic entity in 1995, many cases of AIP have been present or criterion 1 together with either criterion 2 orreported in Western countries, and also in Japan. During criterion 3 is present. The presence of the imagingthe past 10 years, a number of new clinicopathologic criterion is essential to make the diagnosis of AIP. Theseaspects of AIP have been clarified, and AIP is now criteria are based on the minimum consensus features ofconsidered to be a discrete entity worldwide. It is AIP to minimize the risk of misdiagnosing pancreaticimportant not to misdiagnose AIP as pancreatic cancer. cancer. With the accumulation of more AIP cases, it hasFrom the Department of Internal Medicine, Tokyo Metropolitan become clear that, in several cases strongly suspected of Komagome Hospital, Tokyo, Japan. having AIP, the degree of narrowing of the mainThe author declares no conflict of interest. pancreatic duct is less than one third of the entireSupported by Research for Intractable Disease of the Pancreas, Ministry pancreas. Furthermore, serum IgG4 levels are rather of Health, Labour and Welfare of Japan. significantly and specifically elevated in AIP patients.Reprints: Terumi Kamisawa, MD, PhD, Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Thus, the 2002 criteria were revised in 2006.6 The 2006 Bunkyo-ku, Tokyo 113-8677, Japan (e-mail: kamisawa@cick.jp). criteria deleted the requirement that ‘‘more than one thirdCopyright r 2008 by Lippincott Williams & Wilkins of the entire pancreas’’ be involved, allowing segmental404 J Clin Gastroenterol  Volume 42, Number 4, April 2008
    • J Clin Gastroenterol  Volume 42, Number 4, April 2008 Diagnostic Criteria for Autoimmune PancreatitisTABLE 1. Clinical Diagnostic Criteria for AIP (2006) in Japan6 TABLE 2. Diagnostic criteria for AIP in Asan Medical Center71. Diffuse or segmental narrowing of the main pancreatic duct with Criterion I. Pancreatic imaging (essential) irregular wall and diffuse or localized enlargement of the pancreas by (1) CT: Diffuse enlargement (swelling) of the pancreas and imaging studies, such as abdominal ultrasonography, CT, and (2) ERCP: Diffuse or segmental irregular narrowing of the main magnetic resonance imaging pancreatic duct2. High serum g-globulin, IgG or IgG4, or the presence of Criterion II. Laboratory findings autoantibodies, such as antinuclear antibodies and rheumatoid factor (1) Elevated levels of IgG and/or IgG4, or3. Marked interlobular fibrosis and prominent infiltration of (2) Detected autoantibodies lymphocytes and plasma cells in the periductal area, occasionally with Criterion III. Histopathologic findings lymphoid follicles in the pancreas Fibrosis and lymphoplasmacytic infiltration Criterion IV. Association of other postulated autoimmune disease Proposed by the Research Committee of Intractable Diseases of the Pancreas Definite: I+II+III+IV orsupported by the Japanese Ministry of Health, Labour, and Welfare, and Japan I+II+III or I+IIIPancreas Society. Diagnosis of AIP is established when criterion 1, together with criterion 2 and/ Probable: I+IV Rediagnosed as definite if response toor 3, are fulfilled. the steroid is present. However, it is necessary to exclude malignant diseases such as pancreatic or Possible: I only Rediagnosed as definite if response tobiliary cancers. the steroid is present Patients are stratified by evidence strength for AIP into (1) definite, (2) probable, and (3) possible AIP.AIP cases to be diagnosed. Furthermore, the 2006 criteriaincluded elevation of the serum IgG4 level as a diagnosticfactor. Finally, the 2006 criteria stressed the need to be the gold standard for diagnosing AIP; many AIPexclude malignant diseases such as pancreatic or biliary patients at Mayo Clinic are diagnosed using the histologiccancers, before making the diagnosis of AIP (Table 1). criteria (Table 3). KOREAN DIAGNOSTIC CRITERIA OUR CASES 7 During the past 8 years, we clinically diagnosed 27 The Korean diagnostic criteria proposed by Asan patients (21 males, 6 females) as having AIP who haveMedical Center in 2006 stratified the strength of the been followed long-term. The patients’ average age wasevidence for AIP into ‘‘definite,’’ ‘‘probable,’’ and‘‘possible.’’ In addition to the Japanese criteria, theKorean criteria include the patient’s response to steroid TABLE 3. Diagnostic Criteria for AIP (The HISORt Criteria,therapy and the presence of extrapancreatic lesions as Mayo Clinic)8diagnostic criteria. The definite AIP category includes Category Criteriaalmost the same criteria as the Japanese criteria, whereas Histology At least one of the following:patients who have only typical features of AIP on (1) Periductal lymphoplasmacytic infiltrate withdiagnostic imaging are diagnosed as possible AIP. AIP obliterative phlebitis and storiform fibrosispatients frequently have various extrapancreatic lesions, (LPSP)including sclerosing cholangitis, sialadenitis, or retro- (2) Lymphoplasmacytic infiltrate with storiform fibrosis showing abundant (^10 cells/HPF)peritoneal fibrosis. When extrapancreatic lesions occur IgG4-positive cellsalong with typical pancreatic imaging findings of AIP, the Pancreatic Typical: diffusely enlarged gland with delayed (rim)index of suspicion becomes higher, and the patients are imaging enhancement; diffusely irregular, attenuated maindesignated as possible AIP. The diagnosis of AIP is pancreatic ductconfirmed by the patient’s response to steroid therapy, Others*: Focal pancreatic mass/enlargement; focal pancreatic duct stricture; pancreatic atrophy;which involves dramatic resolution of narrowing of the pancreatic calcification; or pancreatitispancreatic duct; such patients are then reassigned to the Serology Elevated serum IgG4 level (normal, 8-140 mg/dL)definite AIP category (Table 2). Other organ Hilar/intrahepatic biliary strictures, persistent distal involvementw biliary stricture, parotid/lacrimal gland involvement, mediastinal lymphadenopathy, USA DIAGNOSTIC CRITERIA retroperitoneal fibrosis In the United States, diagnostic criteria were Response to Resolution/marked improvement of pancreatic/ steroid extrapancreatic manifestation with steroidproposed by Mayo Clinic in 2006.8 On the basis of these therapyz therapycriteria, AIP can be diagnosed in patients with Z1 of thefollowing criteria: (1) diagnostic histology showing *With negative work-up for known etiologies for pancreatic disease, especially pancreatic/biliary cancer.lymphoplasmacytic sclerosing pancreatitis or abundant wRadiologic evidence of organ involvement can be confirmed by biopsyIgG4-positive cell infiltration of pancreatic lymphoplas- showing lymphoplasmacytic infiltrate with abundant IgG4-positive cells or itsmacytic infiltrate; (2) characteristic imaging on computed resolution/improvement with steroid therapy. zSteroid therapy should be given only to patients with negative work-up fortomography (CT) and pancreatography with elevated known etiologies for pancreatic disease and only to those in whom response can beserum IgG4 levels; (3) response to steroid therapy of objectively assessed. It should not be used as a substitute for a thorough search for etiology.pancreatic and/or extrapancreatic lesions of AIP. The LPSP indicates lymphoplasmacytic sclerosing pancreatitis.Mayo Clinic criteria stress that histologic criteria shouldr 2008 Lippincott Williams & Wilkins 405
    • Kamisawa J Clin Gastroenterol  Volume 42, Number 4, April 200865.5 years (range, 29 to 83 y). Symptoms on presentation COMPARISON OF THE 3 SETS OF CRITERIAincluded: painless obstructive jaundice in 22 (81%) The revised Japanese criteria4,5 require that thepatients; exacerbation of preexisting diabetes mellitus in characteristic imaging findings of AIP be present, and3; pancreatic swelling on screening ultrasound in 2; and that at least 1 of the laboratory criterion or thegeneral malaise in 1. Mild abdominal pain was present at histopathologic criterion be present. The Korean criter-onset in 6 patients, and 14 patients (52%) had diabetes ia,6 in addition to the Japanese criteria, include themellitus. The diagnoses of diabetes mellitus and AIP were response to steroid therapy and the presence of extra-made simultaneously in 9 patients, and 5 patients pancreatic lesions. Using the Mayo Clinic criteria,7 AIPdeveloped an exacerbation of their preexisting diabetes can be diagnosed: solely on the basis of diagnosticmellitus at the onset of AIP. On CT and ultrasonography, pancreatic histology; by the presence of both the imagingswelling of the pancreas was noted in 27 patients. On criteria and serum IgG4 level elevation; or by response toendoscopic retrograde cholangiopancreatography, 19 steroid therapy with elevated serum IgG4 levels and/orpatients had diffuse narrowing of the main pancreatic other organ involvement. In the 27 AIP cases that weduct, and 9 patients had segmental narrowing of the main recently diagnosed based on the overall clinical picture,pancreatic duct (head: n = 6, body: n = 1, tail: n = 2). the sensitivity of the Japanese, Korean, and Mayo ClinicTwo patients had a segmental change of the pancreatic criteria was 78% (21/27), 96% (26/27), and 85% (23/27),tail at first, which progressed to diffuse pancreatic respectively. On the basis of the Japanese criteria,4,5 5changes, 6 and 12 months later, respectively. Serum seronegative cases fulfilling the imaging criterion withoutgammaglobulin, IgG, and IgG4 levels were elevated in histologic examination, and 1 case without pancreatic50% (13/26), 44% (12/27), and 80% (20/25) of patients, enlargement could not be diagnosed. On the basis ofrespectively. Autoantibodies were present in 35% Korean criteria,6 only 1 case without pancreatic enlarge-(9/26) of patients including antinuclear antigen (7/26) ment could not be diagnosed. On the basis of the Mayoand rheumatoid factor (5/26). Histologic findings of the Clinic criteria,7 2 seronegative cases with other organpancreas biopsied under abdominal ultrasound guidance involvement who responded to steroid therapy could beincluded lymphoplasmacytic infiltration with fibrosis, diagnosed in addition to the cases that fulfilled thecompatible with AIP (2/2). Stenosis of the lower bile Japanese criteria.duct was detected in 23 cases. Extrapancreatic lesions In the absence of a diagnostic serologic marker forwere found in 12 cases (44%): swelling of the AIP, AIP must be diagnosed on the basis of the presencesalivary glands (n = 5), retroperitoneal fibrosis (n = 4), of a combination of abnormalities unique to AIP. It isthickening of the gallbladder wall (n = 4), swelling important not to misdiagnose pancreatic cancer as AIP,of the cervical or mediastinal lymph nodes (n = 3), and also not to misdiagnose AIP as pancreatic cancer.stenosis of the intrahepatic bile duct (n = 3), swelling The Japanese criteria are based on the minimumof the lacrimal glands (n = 1), pulmonary pseudotumor consensus features of AIP to minimize the risk of(n = 1), and hypophysitis (n = 1). Abundant infiltration misdiagnosing malignancy. When response to steroidof IgG4-positive plasma cell and fibrosis were detected therapy is added to the criteria, the diagnostic sensitivityin swollen salivary glands, a retroperitoneal mass, and is increased. Korean investigators recommend a diagnos-a pulmonary pseudotumor. Swollen cervical lymph tic trial of steroid therapy in cases that do not fulfill thenodes were also infiltrated by many IgG4-positive plasma Japanese criteria.6 As relief of narrowing of the pancreaticcells. duct with steroid administration can be seen as early as 2 A total of 26 patients received steroid therapy. weeks after steroid therapy in AIP cases, and it does notIndications for steroid therapy included: stenosis of the occur in pancreatic cancer cases, the Korean investigatorsbile duct (n = 23), diffuse enlargement of the pancreas advocate a short trial of steroid therapy to differentiate(n = 2), and associated retroperitoneal fibrosis (n = 2). AIP from pancreatic cancer.6 We also agree that a trial ofThe most common regimen involved induction with oral steroid therapy can be used to assist in making theprednisolone 30 mg/d for 2 weeks, followed by tapering diagnosis when it is used appropriately. However, asof the dose (5 mg every 1 to 2 wk). Medication was generalist physicians who are not pancreatologists use thediscontinued in 4 patients, but the other 22 patients criteria, it is possible that the facile use of steroid trialsrequired continued maintenance therapy with predniso- will result in delaying pancreatic cancer surgery, whichlone 2.5 to 5 mg/d. All patients had resolution or could lead to cancer progression in some cases.improvement clinically, morphologically, and serologi- AIP has characteristic histologic findings in thecally in the extrapancreatic involvement and also in the pancreas.9,10 Thus, histology may be a gold standard forpancreatic lesion. One patient relapsed during mainte- diagnosis,11 especially in association with IgG4-immu-nance therapy, but the biliary stenosis improved with a nostaining. However, an adequate pancreatic core biopsytemporary dose increase. On follow-up, the prognosis was can be obtained in only limited number of institutes. Onfound to be good except in one 83-year-old male who died the other hand, rather specific pancreatic imaging on CT,of esophageal cancer 3 years after developing AIP. Two ultrasonography, and endoscopic retrograde cholangio-patients developed pancreatic stones during follow-up, pancreatography is widely available and more clinicallybut pancreatic exocrine function did not deteriorate in applicable. Thus, the importance of characteristic pan-any of the patients. creatic imaging findings, as diagnostic criteria should be406 r 2008 Lippincott Williams & Wilkins
    • J Clin Gastroenterol  Volume 42, Number 4, April 2008 Diagnostic Criteria for Autoimmune Pancreatitisstressed. It has become clear that some patients develop REFERENCESpancreatic calcification or stone formation during follow- 1. Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis causedup.12 Some AIP patients in the postacute phase may be by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995;40:1561–1568.found to have an atrophic pancreas or pancreatic 2. Hardacre JM, Iacobuzio-Donahue CA, Sohn TA, et al. Results ofcalcification, which are characteristics that are seen in pancreaticoduodenectomy for lymphoplasmacytic sclerosing pan-patients with ordinary chronic pancreatitis. It will be creatitis. Ann Surg. 2003;237:853–859.necessary in the future to incorporate atypical imaging 3. Abraham SC, Wilentz RE, Yeo CJ, et al. Pancreaticoduodenectomycases, as in the Mayo Clinic criteria. 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Kamisawa T, Yu Y, Nakajima H, et al. Usefulness of biopsyinggland, as an additional criterion for the Japanese the major duodenal papilla to diagnose autoimmune pancreatitis:diagnostic criteria. Furthermore, it is time for interna- a prospective study using IgG4-immunostaining. World J Gastro-tional consensus on AIP. enterol. 2006;12:2031–2033.r 2008 Lippincott Williams & Wilkins 407