今日の臨床サポート

自己免疫性膵炎

著者: 神澤輝実 都立駒込病院 内科

監修: 下瀬川徹 みやぎ県南中核病院企業団

著者校正/監修レビュー済:2021/11/02
参考ガイドライン:
  1. 厚生労働省難治性膵疾患調査研究班・日本膵臓学会:自己免疫性膵炎診療ガイドライン2013
  1. 日本膵臓学会・厚生労働省IgG4関連疾患の診断基準並びに治療指針を目指す研究班:自己免疫性膵炎診療ガイドライン2020
患者向け説明資料

概要・推奨   

  1. 閉塞性黄疸で膵腫大を認めた患者には、自己免疫性膵炎も疑い、検査することが勧められる(推奨度2
  1. 涙腺腫大、唾液腺腫大のある患者は、自己免疫性膵炎の併発を疑い、検査する必要がある(推奨度2)
  1. びまん性膵腫大は膵臓癌より自己免疫性膵炎を示唆する所見である(推奨度1)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
神澤輝実 : 特に申告事項無し[2021年]
監修:下瀬川徹 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 自己免疫性膵炎診療ガイドライン2020に基づき確認を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 自己免疫性膵炎は発症機序に何らかの自己免疫現象の関与が示唆される膵炎である。
  1. 膵腫大(<図表>,<図表>)と膵管狭細像(<図表>,<図表>)、血中IgG4値の上昇(<図表>)、リンパ球とIgG4陽性形質細胞の密な浸潤と線維化、多彩な膵外病変、ステロイドの反応性(<図表>,<図表>)などを特徴とする。
  1. 自己免疫性膵炎の診断においては、膵癌との鑑別がきわめて重要である。
  1. 診断は「自己免疫性膵炎臨床診断基準2018」(<図表>)によって行われる。
  1. 国際的に自己免疫性膵炎は、IgG4が関連する1型と好中球病変を有する2型に大別される。
  1. わが国の自己免疫性膵炎のほとんどは1型であり、IgG4が関連した全身性疾患(IgG4関連疾患)の膵病変であると考えられている。
  1. 治療はステロイドが奏効するが、しばしば再燃する。
 
  1. 自己免疫性膵炎はしばしば再燃する。
  1. まとめ:自己免疫性膵炎のステロイド治療後の再発率は54%と報告され、再発率は治療法に関係なく肝門部胆管狭窄がある例(64%)で、下部胆管狭窄のみの例(32%)より高かった(p<0.05)[1]。自己免疫性膵炎のステロイド治療後の再発率は、ステロイド治療後に血中IgG4値の上昇が持続した例(30%、34/115)で、血中IgG4値が正常化した例(10%、7/69)より明らかに高かった(p<0.01)[2]
  1. 結論:自己免疫性膵炎はしばしば再燃し、肝門部胆管狭窄例とステロイド治療後も血中IgG4高値が持続する例で再燃しやすい。
問診・診察のポイント  
  1. 年齢、性別を確認する。

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文献 

著者: Amaar Ghazale, Suresh T Chari, Lizhi Zhang, Thomas C Smyrk, Naoki Takahashi, Michael J Levy, Mark D Topazian, Jonathan E Clain, Randall K Pearson, Bret T Petersen, Santhi Swaroop Vege, Keith Lindor, Michael B Farnell
雑誌名: Gastroenterology. 2008 Mar;134(3):706-15. doi: 10.1053/j.gastro.2007.12.009. Epub 2007 Dec 7.
Abstract/Text BACKGROUND & AIMS: Immunoglobulin (Ig)G4-associated cholangitis (IAC) is the biliary manifestation of a steroid-responsive multisystem fibroinflammatory disorder in which affected organs have a characteristic lymphoplasmacytic infiltrate rich in IgG4-positive cells. We describe clinical features, treatment response, and predictors of relapse in IAC and compare relapse rates in IAC with intrapancreatic vs proximal bile duct strictures.
METHODS: We reviewed clinical, serologic, and imaging characteristics and treatment response in 53 IAC patients.
RESULTS: IAC patients generally were older (mean age, 62 y) men (85%), presenting with obstructive jaundice (77%) associated with autoimmune pancreatitis (92%), increased serum IgG4 levels (74%), and abundant IgG4-positive cells in bile duct biopsy specimens (88%). At presentation, biliary strictures were confined to the intrapancreatic bile duct in 51%; the proximal extrahepatic/intrahepatic ducts were involved in 49%. Initial presentation was treated with steroids (n = 30; median follow-up period, 29.5 months), surgical resection (n = 18; median follow-up period, 58 months), or was conservative (n = 5; median follow-up period, 35 months). Relapses occurred in 53% after steroid withdrawal; 44% relapsed after surgery and were treated with steroids. The presence of proximal extrahepatic/intrahepatic strictures was predictive of relapse. Steroid therapy normalized liver enzyme levels in 61%; biliary stents could be removed in 17 of 18 patients. Fifteen patients treated with steroids for relapse after steroid withdrawal responded; 7 patients on additional immunomodulatory drugs remain in steroid-free remission (median follow-up period, 6 months).
CONCLUSIONS: IAC should be suspected in unexplained biliary strictures associated with increased serum IgG4 and unexplained pancreatic disease. Relapses are common after steroid withdrawal, especially with proximal strictures. The role of immunomodulatory drugs for relapses needs further study.

PMID 18222442  Gastroenterology. 2008 Mar;134(3):706-15. doi: 10.1053/・・・
著者: T Kamisawa, T Shimosegawa, K Okazaki, T Nishino, H Watanabe, A Kanno, F Okumura, T Nishikawa, K Kobayashi, T Ichiya, H Takatori, K Yamakita, K Kubota, H Hamano, K Okamura, K Hirano, T Ito, S B H Ko, M Omata
雑誌名: Gut. 2009 Nov;58(11):1504-7. doi: 10.1136/gut.2008.172908. Epub 2009 Apr 26.
Abstract/Text OBJECTIVE: To establish an appropriate steroid treatment regimen for autoimmune pancreatitis (AIP).
METHODS: A retrospective survey of AIP treatment was conducted in 17 centres in Japan. The main outcome measures were rate of remission and relapse.
RESULTS: Of 563 patients with AIP, 459 (82%) received steroid treatment. The remission rate of steroid-treated AIP was 98%, which was significantly higher than that of patients without steroid treatment (74%, 77/104; p<0.001). Steroid treatment was given for obstructive jaundice (60%), abdominal pain (11%), associated extrapancreatic lesions except the biliary duct (11%), and diffuse enlargement of the pancreas (10%). There was no relationship between the period necessary to achieve remission and the initial dose (30 mg/day vs 40 mg/day) of prednisolone. Maintenance steroid treatment was given in 377 (82%) of 459 steroid-treated patients, and steroid treatment was stopped in 104 patients. The relapse rate of patients with AIP on maintenance treatment was 23% (63/273), which was significantly lower than that of patients who stopped maintenance treatment (34%, 35/104; p = 0.048). From the start of steroid treatment, 56% (55/99) relapsed within 1 year and 92% (91/99) relapsed within 3 years. Of the 89 relapsed patients, 83 (93%) received steroid re-treatment, and steroid re-treatment was effective in 97% of them.
CONCLUSIONS: The major indication for steroid treatment in AIP is the presence of symptoms. An initial prednisolone dose of 0.6 mg/kg/day, is recommend, which is then reduced to a maintenance dose over a period of 3-6 months. Maintenance treatment with low-dose steroid reduces but dose not eliminate relapses.

PMID 19398440  Gut. 2009 Nov;58(11):1504-7. doi: 10.1136/gut.2008.1729・・・
著者: Suresh T Chari, Naoki Takahashi, Michael J Levy, Thomas C Smyrk, Jonathan E Clain, Randall K Pearson, Bret T Petersen, Mark A Topazian, Santhi S Vege
雑誌名: Clin Gastroenterol Hepatol. 2009 Oct;7(10):1097-103. doi: 10.1016/j.cgh.2009.04.020. Epub 2009 May 4.
Abstract/Text BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) and pancreatic cancer (PaC) have similar presentations; a diagnostic strategy is needed to distinguish the 2 diseases.
METHODS: We compared computed tomography images (for pancreas and other organ involvement), serum IgG4 levels, histology data, and the response to steroids between patients with AIP (n = 48) and those with PaC (n = 100).
RESULTS: Pancreatic imaging findings stratified patients into 3 groups. Group 1 was highly suggestive of AIP, with diffuse pancreatic enlargement without group 3 features (n = 25, 100% AIP). Group 2 was indeterminate, with normal-sized pancreas or focal pancreatic enlargement without group 3 features (n = 20, 75% AIP). Group 3 was highly suggestive of PaC, with presence of >1 low-density mass, pancreatic duct cutoff, or upstream pancreatic atrophy (n = 103, 92% PaC). Although all patients in group 1 had AIP, only 20 of the 25 patients had increased serum IgG4 levels and/or other organ involvement. Of the patients in groups 2 and 3 who did not have cancer, all those with serum IgG4 levels >2-fold the upper limit of normal or a combination of increased serum IgG4 levels and other organ involvement (n = 15) had AIP. In AIP subjects without supportive serologic evidence or other organ involvement (n = 14), diagnosis required pancreatic core biopsy (n = 7), steroid trial (n = 5), or resection (n = 2).
CONCLUSIONS: PaC can be distinguished from AIP by pancreatic imaging, measurement of serum IgG4 levels, and determination of other organ involvement. However, a pancreatic core biopsy, steroid trial, or surgery is required for diagnosis in approximately 30% of patients with AIP.

PMID 19410017  Clin Gastroenterol Hepatol. 2009 Oct;7(10):1097-103. do・・・
著者: Terumi Kamisawa, Mitsuho Imai, Pong Yui Chen, Yuyang Tu, Naoto Egawa, Kouji Tsuruta, Atsutake Okamoto, Mizuka Suzuki, Noriko Kamata
雑誌名: Pancreas. 2008 Oct;37(3):e62-7. doi: 10.1097/MPA.0b013e318175e3a0.
Abstract/Text OBJECTIVES: It is of utmost importance that autoimmune pancreatitis (AIP) be differentiated from pancreatic cancer (PC) because some AIP cases undergo unnecessary laparotomy or pancreatic resection on suspicion of PC. This study aimed to develop an appropriate strategy for differentiating between AIP and PC.
METHODS: Clinical, serological, and radiological features of 17 AIP patients forming a masslike lesion on pancreas head and 70 patients with pancreatic head cancer were compared.
RESULTS: Numerous findings can be used to distinguish between AIP and PC, and the following are more likely in AIP: fluctuating jaundice; elevated serum IgG4 levels; delayed enhancement of the enlarged pancreas and a capsule-like low-density rim on computed tomography; long or skipped narrowed portion with side branches of the main pancreatic duct without upstream dilatation on endoscopic retrograde pancreatography, extrapancreatic lesions, such as stenosis of the intrahepatic bile duct, salivary gland swelling, and retroperitoneal mass; and responsiveness to steroid therapy.
CONCLUSIONS: In elderly male patients presenting with obstructive jaundice and a pancreatic mass, AIP should be considered in the differential diagnosis. Based on a combination of clinical, serological, and radiological findings, AIP can be differentiated from PC. An algorithm for management of patients with a masslike lesion on pancreas head is presented.

PMID 18815540  Pancreas. 2008 Oct;37(3):e62-7. doi: 10.1097/MPA.0b013e・・・
著者: Yayoi Ozaki, Kazuhiro Oguchi, Hideaki Hamano, Norikazu Arakura, Takashi Muraki, Kendo Kiyosawa, Mitsuhiro Momose, Masumi Kadoya, Kazunobu Miyata, Takao Aizawa, Shigeyuki Kawa
雑誌名: J Gastroenterol. 2008;43(2):144-51. doi: 10.1007/s00535-007-2132-y. Epub 2008 Feb 29.
Abstract/Text BACKGROUND: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions.
METHODS: We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG.
RESULTS: FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis.
CONCLUSIONS: FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis.

PMID 18306988  J Gastroenterol. 2008;43(2):144-51. doi: 10.1007/s00535・・・
著者: Jian Zhang, Guorong Jia, Changjing Zuo, Ningyang Jia, Hui Wang
雑誌名: BMC Cancer. 2017 Oct 23;17(1):695. doi: 10.1186/s12885-017-3665-y. Epub 2017 Oct 23.
Abstract/Text BACKGROUND: 18F-FDG PET/CT could satisfactorily show pancreatic and extra-pancreatic lesions in AIP, which can be mistaken for pancreatic cancer (PC). This study aimed to identify 18F-FDG PET/CT findings that might differentiate AIP from PC.
METHODS: FDG-PET/CT findings of 26 AIP and 40 PC patients were reviewed. Pancreatic and extra-pancreatic lesions related findings, including maximum standardized uptake values (SUVmax) and patterns of FDG uptake, were identified and compared.
RESULTS: All 26 patients with AIP had increased pancreatic FDG uptake. Focal abnormal pancreatic FDG activities were found in 38/40 (95.00%) PC patients, while longitudinal were found in 18/26 (69.23%) AIP patients. SUVmax was significantly different between AIP and PC, both in early and delayed PET/CT scans (p < 0.05). AUCs were 0.700 (early SUVmax), 0.687 (delayed SUVmax), 0.683 (early lesions/liver SUVmax), and 0.715 (delayed lesion/liver SUVmax). Bile duct related abnormalities were found in 12/26 (46.15%) AIP and 10/40 (25.00%) PC patients, respectively. Incidentally, salivary and prostate gland SUVmax in AIP patients were higher compared with those of PC patients (p < 0.05). In males,an inverted "V" shaped high FDG uptake in the prostate was more frequent in AIP than PC patients (56.00%, 14/25 vs. 5.71%, 2/35). Increased FDG activity in extra-pancreatic bile duct was present in 4/26 of AIP patients, while was observed in none of the PC patients. Only in AIP patients, both diffuse pancreatic FDG accumulation and increased inverted "V" shaped FDG uptake in the prostate could be found simultaneously.
CONCLUSIONS: 18F-FDG PET/CT findings might help differentiate AIP from PC.

PMID 29061130  BMC Cancer. 2017 Oct 23;17(1):695. doi: 10.1186/s12885-・・・
著者: Taku Tabata, Terumi Kamisawa, Kensuke Takuma, Hajime Anjiki, Naoto Egawa, Masanao Kurata, Gorou Honda, Kouji Tsuruta, Keigo Setoguchi, Taminori Obayashi, Tsuneo Sasaki
雑誌名: Clin Chim Acta. 2009 Oct;408(1-2):25-8. doi: 10.1016/j.cca.2009.06.036. Epub 2009 Jul 4.
Abstract/Text BACKGROUND: Based on histological and immunohistochemical examinations of various organs of patients with autoimmune pancreatitis (AIP), a new clinicopathological entity, IgG4-related systemic disease, was proposed. This study aimed to clarify clinical utility of serum IgG4 levels in differentiating AIP from other pancreatobiliary diseases, clinical utility of serum IgG4 levels in differentiating Mikulicz's disease from other salivary gland disorders, as well as in identifying other IgG4-related diseases.
METHODS: Serum IgG4 levels were measured in 468 patients.
RESULTS: The median serum IgG4 level was significantly greater in AIP (301.5mg/dl) than in other pancreatobiliary diseases (p<0.01). Using the cutoff value of 119 mg/dl that was determined on the basis of this study's ROC curve data, the sensitivity and specificity to distinguish AIP from pancreatic cancer were 82.1% and 94.8%, respectively. The median serum IgG4 level was significantly greater in Mikulicz's disease (357.0mg/dl) than in other salivary gland diseases (p<0.01). Of 75 patients with elevated serum IgG4 levels, 15 had diseases other than pancreatobiliary and salivary gland diseases.
CONCLUSIONS: Serum IgG4 levels were useful for diagnosing AIP and Mikulicz's disease. Some diseases with serum IgG4 level elevations may be lesions of IgG4-related systemic disease without manifestations of AIP and Mikulicz's disease.

PMID 19580797  Clin Chim Acta. 2009 Oct;408(1-2):25-8. doi: 10.1016/j.・・・
著者: Atsushi Kanno, Kazuyuki Ishida, Shin Hamada, Fumiyoshi Fujishima, Jun Unno, Kiyoshi Kume, Kazuhiro Kikuta, Morihisa Hirota, Atsushi Masamune, Kennichi Satoh, Kenji Notohara, Tooru Shimosegawa
雑誌名: Gastrointest Endosc. 2012 Sep;76(3):594-602. doi: 10.1016/j.gie.2012.05.014.
Abstract/Text BACKGROUND: It is controversial whether EUS-guided FNA by using 22-gauge (G) needles is useful for the diagnosis or evaluation of autoimmune pancreatitis (AIP).
OBJECTIVE: To evaluate the usefulness of EUS-FNA by 22-G needles for the histopathological diagnosis of AIP.
DESIGN: A retrospective study.
SETTING: Single academic center.
PATIENTS: A total of 273 patients, including 25 with AIP, underwent EUS-FNA and histological examinations.
RESULTS: EUS-FNA by using 22-G needles provided adequate tissue samples for histopathological evaluation because more than 10 high-power fields were available for evaluation in 20 of 25 patients (80%). The mean immunoglobulin G4-positive plasma cell count was 13.7/high-power field. Obliterative phlebitis was observed in 10 of 25 patients (40%). In the context of the International Consensus Diagnostic Criteria for AIP, 14 and 6 of 25 patients were judged to have level 1 (positive for 3 or 4 items) and level 2 (positive for 2 items) histological findings, respectively, meaning that 20 of 25 patients were suggested to have lymphoplasmacytic sclerosing pancreatitis based on the International Consensus Diagnostic Criteria. The diagnosis in 1 patient was type 2 AIP because a granulocytic epithelial lesion was identified in this patient.
LIMITATIONS: A retrospective study with a small number of patients.
CONCLUSIONS: The results of this study suggest that EUS-FNA by using 22-G needles provides tissue samples adequate for histopathological evaluation and greatly contributes to the histological diagnosis of AIP.

Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.
PMID 22898417  Gastrointest Endosc. 2012 Sep;76(3):594-602. doi: 10.10・・・
著者: Atsushi Masamune, Isao Nishimori, Kazuhiro Kikuta, Ichiro Tsuji, Nobumasa Mizuno, Tatsuo Iiyama, Atsushi Kanno, Yuichi Tachibana, Tetsuhide Ito, Terumi Kamisawa, Kazushige Uchida, Hideaki Hamano, Hiroaki Yasuda, Junichi Sakagami, Akira Mitoro, Masashi Taguchi, Yasuyuki Kihara, Hiroyuki Sugimoto, Yoshiki Hirooka, Satoshi Yamamoto, Kazuo Inui, Osamu Inatomi, Akira Andoh, Kazuyuki Nakahara, Hiroyuki Miyakawa, Shin Hamada, Shigeyuki Kawa, Kazuichi Okazaki, Tooru Shimosegawa, Research Committee of Intractable Pancreas Diseases in Japan
雑誌名: Gut. 2017 Mar;66(3):487-494. doi: 10.1136/gutjnl-2016-312049. Epub 2016 Aug 19.
Abstract/Text OBJECTIVE: Corticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP.
DESIGN: We conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5-7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis.
RESULTS: Between April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed.
CONCLUSIONS: Maintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks.
TRIAL REGISTRATION NUMBER: UMIN000001818; Results.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
PMID 27543430  Gut. 2017 Mar;66(3):487-494. doi: 10.1136/gutjnl-2016-3・・・

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(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから