今日の臨床サポート

腸管ベーチェット病

著者: 長沼 誠 慶應義塾大学医学部 内科学(消化器内科)

監修: 上村直実 国立国際医療研究センター 国府台病院

著者校正/監修レビュー済:2020/02/14
参考ガイドライン:
  1. 日本ベーチェット病学会:ベーチェット病診療ガイドライン2020
患者向け説明資料

概要・推奨   

  1. 腸管ベーチェット病の臨床症状には特徴的な症状はないが、腹痛、下血・血便、腹部腫瘤、下痢、体重減少などが見られるとき、腸管ベーチェット病を考慮する。
  1. 臨床検査所見として、炎症反応高値・低タンパク血症・貧血が認められる。骨髄異形成症候群に合併する腸管ベーチェット病ではトリソミー8を高率に認めており、臨床上に加えて、これらの臨床検査所見が認められた場合、腸管ベーチェット病を考慮する。
  1. 典型的には回盲部を中心に円形または類円形の深掘れの潰瘍を呈することが特徴であるが、クローン病・腸結核・非ステロイド系抗炎症薬による小腸潰瘍を鑑別することが推奨される。
  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
  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。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  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。閲覧にはご契約が必要とな
  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。閲覧にはご契約が必要となります。閲覧にはご
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:
長沼 誠 : 未申告[2021年]
監修:上村直実 : 未申告[2021年]

改訂のポイント:
  1. 日本ベーチェット病学会が監修したベーチェット病診療ガイドライン2020が公表されたことを踏まえ、診断・治療のアリゴリズムを掲載した。またガイドラインのGQの一部内容を本コンテンツに反映させた。
  1. インフリキシマブ(レミケード)が腸管ベーチェット病に対する治療法として保険収載されたことを踏まえ、抗TNF抗体製剤の治療法としてインフリキシマブを追記した。
  1. 骨髄異形成症候群(MDS)に合併するベーチェット病において、腸管病変を高率に合併すること、MDSに合併する腸管ベーチェット病ではトリソミー8を高率に認めており(54~86%)、難治例が多いとされていることを記載した。

病態・疫学・診察

疾患(疫学・病態)  
  1. ベーチェット病とは、口腔粘膜の再発性アフタ性潰瘍、眼病変、皮膚病変、陰部潰瘍を主症状とする原因不明の難治性疾患である。腸管ベーチェット病とは、ベーチェット病のなかで回盲部に特徴的な潰瘍を有する特殊型と位置づけられている。腸管ベーチェット病は、腹痛、体重減少、下痢、発熱などを主訴とし、重症例では穿孔・腹膜炎を来し、手術になる例も存在する。
  1. 東アジア、中央アジアなどに多く、欧米ではまれな疾患である。遺伝学的にHLA-B51の関与が示唆されているが、腸管ベーチェット病では頻度は高くない。
  1. 典型的には回盲部を中心に円形または類円形の深掘れの潰瘍を呈することが特徴である。
  1. なお、回盲部の潰瘍の中で、ベーチェト病診断基準の完全型あるいは不全型の条件を満たすものを腸管ベーチェット病、それ以外で回盲部の潰瘍のみを有するものを単純性潰瘍と定義しているが、両者の病因・病態・定義については明確ではない。
  1. 治療法はエビデンスの高い治療法はほとんどなく、経験的に栄養療法、5-アミノサリチル酸(5-ASA)製剤、ステロイド、コルヒチンなどが使用されている。
  1. 近年わが国で、ベーチェット病に対する抗TNFα抗体製剤の有用性が治験にて確認され、難治例を中心に実際の現場で使用可能となっている。
  1. ベーチェット病は、指定難病であり、重症度基準Ⅱ度以上の場合などでは、申請し認定されると保険料の自己負担分の一部が公費負担として助成される ([平成27年1月施行])。ただし現在、特殊型である腸管ベーチェト病のみでは認定されないことが多い。
  1.  難病法に基づく医療費助成制度 
問診・診察のポイント  
  1. まずベーチェット病の主症状の有無について確認する。口内炎の出現時期、繰り返しているかどうかについて確認する。口内炎は腹部症状に先行して発症している場合が多い。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Tadakazu Hisamatsu, Fumiaki Ueno, Takayuki Matsumoto, Kiyonori Kobayashi, Kazutaka Koganei, Reiko Kunisaki, Fumihito Hirai, Masakazu Nagahori, Mitsunobu Matsushita, Kenji Kobayashi, Mitsumasa Kishimoto, Mitsuhiro Takeno, Masanori Tanaka, Nagamu Inoue, Toshifumi Hibi
雑誌名: J Gastroenterol. 2014 Jan;49(1):156-62. doi: 10.1007/s00535-013-0872-4. Epub 2013 Aug 18.
Abstract/Text BACKGROUND: Clinical evidence regarding intestinal Behçet's disease (BD) management is lacking and intestinal lesions are a poor prognostic factor. In 2007, the Japan consensus statement for diagnosis and management of intestinal BD was developed. Recently, the efficacy of anti-tumor necrosis factor (TNF)α monoclonal antibodies (mAbs), and infliximab (IFX) was reported and adalimumab (ADA) was approved for intestinal BD in Japan. This study renewed consensus-based practice guidelines for diagnosis and treatment of intestinal BD focusing on the indication of anti-TNFα mAbs.
METHODS: An expert panel of Japanese gastroenterology and rheumatology specialists was involved. Clinical statements for ratings were extracted from the literature, a professional group survey, and by an expert panel discussion, which rated clinical statements on a nine-point scale. After the first round of ratings, a panelist meeting discussed areas of disagreement and clarified areas of uncertainty. The list of clinical statements was revised after the panelist meeting and a second round of ratings was conducted.
RESULTS: Fifteen relevant articles were selected. Based on the first edition consensus statement, improved clinical statements regarding indications for anti-TNFα mAbs use were developed. After a two-round modified Delphi approach, the second edition of consensus statements was finalized.
CONCLUSIONS: In addition to standard therapies in the first edition, anti-TNFα mAbs (ADA and IFX) should be considered as a standard therapy for intestinal BD. Colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and leukocytapheresis were deemed experimental therapies.

PMID 23955155  J Gastroenterol. 2014 Jan;49(1):156-62. doi: 10.1007/s0・・・
著者: M Naganuma, Y Iwao, N Inoue, T Hisamatsu, H Imaeda, H Ishii, T Kanai, M Watanabe, T Hibi
雑誌名: Am J Gastroenterol. 2000 Oct;95(10):2848-51. doi: 10.1111/j.1572-0241.2000.03198.x.
Abstract/Text OBJECTIVE: Much remains unknown about the pathogenesis of intestinal Behçet's disease. The majority of these patients are treated with surgical intervention, although it has been recently reported that a number of medical treatments are sometimes effective. Only few studies, however, have ever been undertaken to analyze the long-term prognosis of this disease. In this study, we analyzed the clinical course and the recurrences after initial therapy in patients with intestinal Behçet's disease.
METHODS: We investigated 20 patients (surgical group, n = 8; nonsurgical group, n = 12) for whom the clinical courses were known for > or = 2 yr (2-23 yr).
RESULTS: The surgical group tended to have higher rates of complications such as ocular and ileal lesions than the nonsurgical group. In the surgical group, 75% of the patients recurred (and were readmitted) within 2 yr, and 37.5% of the patients required reoperation for intestinal obstruction because of ulcer at the anastomosis. The percentage of peripheral CD8+ DR+ lymphocytes in the recurrent group (10.4% +/- 2.5%) was significantly higher than that in the nonrecurrent group (4.3% +/- 1.2%, p < 0.05).
CONCLUSIONS: Our results indicate that more extensive disease involving the ileum and ocular lesions are markers of severity and progression to surgical crisis, and that patients requiring surgery suffer more frequent recurrences. Furthermore, an increased percentage of peripheral CD8+ DR+ lymphocytes may be a risk factor for disease recurrence.

PMID 11051358  Am J Gastroenterol. 2000 Oct;95(10):2848-51. doi: 10.11・・・
著者: Yoon Suk Jung, Jae Hee Cheon, Sung Pil Hong, Tae Il Kim, Won Ho Kim
雑誌名: Inflamm Bowel Dis. 2012 Apr;18(4):750-7. doi: 10.1002/ibd.21757. Epub 2011 May 25.
Abstract/Text BACKGROUND: To date, there have been no studies focusing on the efficacy of thiopurine therapy in intestinal Behcet's disease (BD). We conducted this study to investigate clinical outcomes and predictors of clinical relapse in intestinal BD patients receiving thiopurine maintenance therapy.
METHODS: We reviewed the medical records of all patients with intestinal BD who received thiopurine therapy in a single tertiary academic medical center between March 1986 and October 2010. The cumulative probabilities of clinical relapse after remission were calculated using the Kaplan-Meier method. Predictors of clinical relapse were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models.
RESULTS: Of a total of 272 patients with intestinal BD, 67 (24.6%) received their first course of thiopurine therapy at our center. Thirty-nine (58.2%) of the 67 patients constantly received thiopurines for maintaining medically or surgically induced remission. The cumulative relapse rates at 1 year, 2 years, 3 years, and 5 years after remission were 5.8%, 28.7%, 43.7%, and 51.7%, respectively. On multivariate analysis, a younger age (<25 years) at diagnosis and a lower hemoglobin level (<11 g/dL) were independent predictive factors for relapse in intestinal BD patients receiving thiopurine maintenance therapy.
CONCLUSIONS: Thiopurine therapy showed a relatively good effect for maintenance of remission in intestinal BD patients. However, a younger age at diagnosis and a lower hemoglobin level were associated with a poor response to thiopurines, necessitating early adoption of effective alternative therapeutic options in these risk groups.

Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
PMID 21618352  Inflamm Bowel Dis. 2012 Apr;18(4):750-7. doi: 10.1002/i・・・
著者: I J Choi, J S Kim, S D Cha, H C Jung, J G Park, I S Song, C Y Kim
雑誌名: Dis Colon Rectum. 2000 May;43(5):692-700.
Abstract/Text PURPOSE: The present study was aimed at evaluating the long-term course of intestinal Behçet's disease and determining predictive factors of prognosis.
METHODS: This report is a retrospective study based on the records of 43 patients with intestinal Behçet's disease. The mean follow-up duration was 73 +/- 60 months. We evaluated the efficacy of medical treatment for the intestinal lesion at initial eight weeks. The cumulative probabilities were calculated by using Kaplan-Meier method, and the results were compared by using the log-rank test.
RESULTS: Sixteen patients (38 percent) achieved a complete remission of intestinal lesions eight weeks after medical treatment had begun. The patients who achieved a complete remission had a lower probability of receiving an operation than those who had not (13 percent at 2 and 5 years vs. 36 and 43 percent, respectively; P = 0.028). The recurrence probability of intestinal lesions was 25 percent at two years and 49 percent at five years after complete remission with medical treatment. Patients who had a history of intestinal perforation or fistula had a higher probability of recurrence after operation than those without such history (59 vs. 33 percent at 2 years; 88 vs. 57 percent at 5 years; P = 0.020). Patients who had taken azathioprine had a lower probability of receiving reoperation than those who did not (7 vs. 25 percent at 2 years; 25 vs. 47 percent at 5 years; P = 0.035). The length of ileal resection and whether hemicolectomy was performed had no significant effect on the recurrence or reoperation rate.
CONCLUSIONS: Intestinal Behçet's disease frequently requires a surgical treatment and has a high recurrence rate. The patients who achieved a complete remission with medical treatment, who had no history of intestinal perforation, and who received azathioprine after operation showed better clinical courses. Resection of a short segment of bowel would be a more appropriate surgical procedure.

PMID 10826433  Dis Colon Rectum. 2000 May;43(5):692-700.
著者: Satoshi Tanida, Nagamu Inoue, Kiyonori Kobayashi, Makoto Naganuma, Fumihito Hirai, Bunei Iizuka, Kenji Watanabe, Keiichi Mitsuyama, Takuya Inoue, Yoshiaki Ishigatsubo, Yasuo Suzuki, Masakazu Nagahori, Satoshi Motoya, Shiro Nakamura, Vipin Arora, Anne M Robinson, Roopal B Thakkar, Toshifumi Hibi
雑誌名: Clin Gastroenterol Hepatol. 2015 May;13(5):940-8.e3. doi: 10.1016/j.cgh.2014.08.042. Epub 2014 Sep 19.
Abstract/Text BACKGROUND & AIMS: Behçet's disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçet's disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor α, in patients with intestinal Behçet's disease who were refractory to corticosteroid and/or immunomodulator therapies.
METHODS: The study was conducted at 12 sites in Japan, from November 2010 through October 2012. Twenty patients were given 160 mg adalimumab at the start of the study and 80 mg 2 weeks later, followed by 40 mg every other week for 52 weeks; for some patients, the dose was increased to 80 mg every other week. A composite efficacy index, combining GI symptom and endoscopic assessments, was used to evaluate efficacy. The primary efficacy end point was the percentage of patients with scores of 1 or lower for GI symptom and endoscopic assessments at week 24. Secondary end points included complete remission and resolution of non-GI Behçet's-related symptoms.
RESULTS: Nine patients (45%) had GI symptom and endoscopic assessment scores of 1 or lower at week 24 of treatment, and 12 patients (60%) had these scores by week 52. Four patients (20%) achieved complete remission at weeks 24 and 52. Individual global GI symptom and endoscopic scores improved for most patients at weeks 24 and 52. Two thirds of patients with oral aphthous ulcers, skin symptoms, and genital ulcers, and 88% of patients with erythema nodosum had complete resolution of these conditions at week 52. A total of 9 of 13 patients (69%) taking steroids at baseline were able to taper (n = 1) or completely discontinue steroids (n = 8) during the study. No new safety signals were observed.
CONCLUSIONS: Adalimumab is a potentially effective treatment for intestinal Behçet's disease in Japanese patients who are refractory to conventional treatments. ClinicalTrials.gov number: NCT01243671.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 25245624  Clin Gastroenterol Hepatol. 2015 May;13(5):940-8.e3. do・・・
著者: Makoto Naganuma, Atsushi Sakuraba, Tadakazu Hisamatsu, Hiroki Ochiai, Hirotoshi Hasegawa, Haruhiko Ogata, Yasushi Iwao, Toshifumi Hibi
雑誌名: Inflamm Bowel Dis. 2008 Sep;14(9):1259-64. doi: 10.1002/ibd.20457.
Abstract/Text BACKGROUND: Intestinal Behçet disease (BD) is characterized by intestinal inflammation with round and oval ulcers associated with gastrointestinal symptoms. Although several cases have been reported that infliximab is effective for induction of remission, the efficacy of infliximab for maintaining remission is unknown.
METHODS: Six cases with fulminant intestinal BD were treated with infliximab. All patients were steroid-dependent and refractory to immunosuppressants; 3 patients were treated with 6-mercaptopurine, 1 patient with azathioprine, 1 patient with cyclosporine A, and 1 patient with methotrexate.
RESULTS: Four patients achieved remission by infliximab and all of these patients maintained remission with scheduled treatments of infliximab, with the longest duration of remission being about 3 years. Another 2 patients with ileal ulceration required surgery; however, 1 patient has maintained remission by scheduled treatment of infliximab for 2 years after surgery.
CONCLUSIONS: Infliximab appears to offer an option for fulminant intestinal BD to induce and maintain remission, although a randomized control trial is needed.

PMID 18393375  Inflamm Bowel Dis. 2008 Sep;14(9):1259-64. doi: 10.1002・・・
著者: Shigeru Iwata, Kazuyoshi Saito, Kunihiro Yamaoka, Shizuyo Tsujimura, Masao Nawata, Katsunori Suzuki, Yoshiya Tanaka
雑誌名: Rheumatology (Oxford). 2009 Aug;48(8):1012-3. doi: 10.1093/rheumatology/kep126. Epub 2009 May 22.
Abstract/Text
PMID 19465589  Rheumatology (Oxford). 2009 Aug;48(8):1012-3. doi: 10.1・・・
著者: Toshifumi Hibi, Shunsei Hirohata, Hirotoshi Kikuchi, Ukihide Tateishi, Noriko Sato, Kunihiko Ozaki, Kazuoki Kondo, Yoshiaki Ishigatsubo
雑誌名: Medicine (Baltimore). 2016 Jun;95(24):e3863. doi: 10.1097/MD.0000000000003863.
Abstract/Text Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy.IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint).The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3 intestinal BD patients, resulting in the improvement of clinical symptoms, CRP levels, and visual analogue scale score. Safety and pharmacokinetics profiles were comparable to those in patients with rheumatoid arthritis or Crohn disease. These findings support IFX as a new therapeutic option for patients with intestinal BD, NBD, or VBD.

PMID 27310969  Medicine (Baltimore). 2016 Jun;95(24):e3863. doi: 10.10・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※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