今日の臨床サポート

帯状疱疹後神経痛

著者: 篠原 浩 京都大学大学院医学研究科 臨床病態検査学/京都市立病院 感染症内科(非常勤)

監修: 山本舜悟 京都市立病院 感染症科/京都大学 医療疫学(非常勤講師) 

著者校正/監修レビュー済:2021/07/14
患者向け説明資料

概要・推奨   

  1. 三環系抗うつ薬・ガバペンチン・プレガバリンはいずれもRCTで有効性が証明された薬剤であり、帯状疱疹後神経痛の患者においては使用を考慮する(推奨度2)
  1. 帯状疱疹後神経痛の長期にわたる重篤な痛みは、オピオイド系鎮痛薬を必要とすることも少なくない。副作用のコントロールや有害事象に注意しつつ使用する(推奨度2)
  1. 弱毒生水痘ワクチンもしくは組換え帯状疱疹ワクチンの接種により、帯状疱疹・帯状疱疹後神経痛の頻度はともに低下することが証明されている。特に、帯状疱疹後神経痛の発症率も67~90%低下させる(推奨度1)いずれも、50歳以上で帯状疱疹予防目的での使用が承認されている。
  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。閲覧にはご契約が必要となります。閲覧にはご
  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。閲覧にはご契約が必要となります。閲覧に
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:
篠原 浩 : 未申告[2021年]
監修:山本舜悟 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、予防接種および難治例の治療について加筆修正した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 帯状疱疹後神経痛とは、帯状疱疹の皮疹消失後にも1カ月以上その部位に持続する疼痛と定義され、帯状疱疹の最も多い合併症である。
  1. 帯状疱疹の患者の約20%で発症するとされ、若年者での頻度は10%以下であるが、60歳以上の高齢者では40%前後まで頻度が上昇する。
  1. 疼痛は長期にわたって持続することも少なくなく、QOLを低下させる大きな要因となる。
  1. 帯状疱疹を発症したすべての患者において帯状疱疹後神経痛を発症する可能性があるが、特に高齢者で頻度が高い。
 
  1. 弱毒生水痘ワクチン組換え帯状疱疹ワクチンの接種により、帯状疱疹・帯状疱疹後神経痛の頻度はともに低下することが証明されている。特に、帯状疱疹後神経痛の発症率も67~90%低下させる(推奨度1)
  1. 弱毒生水痘ワクチンの接種により、帯状疱疹・帯状疱疹後神経痛の頻度はともに低下することが証明されている。特に、帯状疱疹後神経痛の発症率も67%低下させる[1][2]
  1. 海外では従来60歳以上に適応が認められていたが、2012年に発表された50~59歳を対象にした臨床試験で有効性が認められ、適応を拡大する流れにある[3]
  1. このことを踏まえ、国産水痘ワクチン(乾燥弱毒生水痘ワクチン「ビケン」、国際的に使用されているものとほぼ同じ株)に対し、わが国でも2016年3月に50歳以上の帯状疱疹予防目的での使用が承認された。
  1. また、組換え帯状疱疹ワクチンも海外において実施された臨床試験で、帯状疱疹発症・帯状疱疹後神経痛の予防において有効性が証明された。
  1. 帯状疱疹後神経痛の発症予防効果は50歳以上で91.2%、70歳以上で88.8%であった[4][5]
  1. 組換え帯状疱疹ワクチン(シングリックス®)についても、50歳以上の帯状疱疹予防目的に承認され、2020年1月から販売開始された。
病歴・診察のポイント  
  1. (帯状疱疹の問診・診察のポイントに関しては 帯状疱疹 を参照)

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: M N Oxman, M J Levin, G R Johnson, K E Schmader, S E Straus, L D Gelb, R D Arbeit, M S Simberkoff, A A Gershon, L E Davis, A Weinberg, K D Boardman, H M Williams, J Hongyuan Zhang, P N Peduzzi, C E Beisel, V A Morrison, J C Guatelli, P A Brooks, C A Kauffman, C T Pachucki, K M Neuzil, R F Betts, P F Wright, M R Griffin, P Brunell, N E Soto, A R Marques, S K Keay, R P Goodman, D J Cotton, J W Gnann, J Loutit, M Holodniy, W A Keitel, G E Crawford, S-S Yeh, Z Lobo, J F Toney, R N Greenberg, P M Keller, R Harbecke, A R Hayward, M R Irwin, T C Kyriakides, C Y Chan, I S F Chan, W W B Wang, P W Annunziato, J L Silber, Shingles Prevention Study Group
雑誌名: N Engl J Med. 2005 Jun 2;352(22):2271-84. doi: 10.1056/NEJMoa051016.
Abstract/Text BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults.
METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia.
RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild.
CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Copyright 2005 Massachusetts Medical Society.
PMID 15930418  N Engl J Med. 2005 Jun 2;352(22):2271-84. doi: 10.1056/・・・
著者: Michael N Oxman, Myron J Levin, Shingles Prevention Study Group
雑誌名: J Infect Dis. 2008 Mar 1;197 Suppl 2:S228-36. doi: 10.1086/522159.
Abstract/Text BACKGROUND: Herpes zoster (HZ) and postherpetic neuralgia (PHN) cause significant morbidity in older adults. The incidence and severity of HZ and PHN increase with age in association with an age-related decline in varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI). VZV vaccines can boost VZV-CMI. Therefore, we tested the hypothesis that VZV vaccination would protect older adults against HZ and PHN.
METHODS: We enrolled 38,546 adults > or =60 years of age in a randomized, double-blind, placebo-controlled trial of an investigational HZ vaccine and actively followed subjects for the development of HZ. The primary end point was the burden of illness due to HZ (HZ BOI), a composite measure of the incidence, severity, and duration of pain and discomfort caused by HZ. The secondary end point was the incidence of PHN.
RESULTS: Subject retention was >95%. HZ vaccine reduced the HZ BOI by 61.1% (95% confidence interval [CI], 51.1%-69.1%; P<.001) and reduced the incidence of PHN by 66.5% (95% CI, 47.5%-79.2%; P<.001). The incidence of HZ was also reduced by 51.3% (95% CI, 44.2%-57.6%; P<.001). HZ vaccine was well tolerated; injection site reactions were generally mild. HZ vaccine neither caused nor induced HZ.
CONCLUSION: The Shingles Prevention Study demonstrated that HZ vaccine significantly reduced the morbidity due to HZ and PHN in older adults.

PMID 18419402  J Infect Dis. 2008 Mar 1;197 Suppl 2:S228-36. doi: 10.1・・・
著者: Kenneth E Schmader, Myron J Levin, John W Gnann, Shelly A McNeil, Timo Vesikari, Robert F Betts, Susan Keay, Jon E Stek, Nickoya D Bundick, Shu-Chih Su, Yanli Zhao, Xiaoming Li, Ivan S F Chan, Paula W Annunziato, Janie Parrino
雑誌名: Clin Infect Dis. 2012 Apr;54(7):922-8. doi: 10.1093/cid/cir970. Epub 2012 Jan 30.
Abstract/Text BACKGROUND: Herpes zoster (HZ) adversely affects individuals aged 50-59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50-59 years.
METHODS: This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50-59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for ≥1 year (mean, 1.3 years) postvaccination until accrual of ≥96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination.
RESULTS: The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups.
CONCLUSIONS: In subjects aged 50-59 years, the ZV significantly reduced the incidence of HZ and was well tolerated.
CLINICAL TRIALS REGISTRATION: NCT00534248.

PMID 22291101  Clin Infect Dis. 2012 Apr;54(7):922-8. doi: 10.1093/cid・・・
著者: Himal Lal, Anthony L Cunningham, Olivier Godeaux, Roman Chlibek, Javier Diez-Domingo, Shinn-Jang Hwang, Myron J Levin, Janet E McElhaney, Airi Poder, Joan Puig-Barberà, Timo Vesikari, Daisuke Watanabe, Lily Weckx, Toufik Zahaf, Thomas C Heineman, ZOE-50 Study Group
雑誌名: N Engl J Med. 2015 May 28;372(22):2087-96. doi: 10.1056/NEJMoa1501184. Epub 2015 Apr 28.
Abstract/Text BACKGROUND: In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.
METHODS: We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.
RESULTS: A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.
CONCLUSIONS: The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).

PMID 25916341  N Engl J Med. 2015 May 28;372(22):2087-96. doi: 10.1056・・・
著者: Anthony L Cunningham, Himal Lal, Martina Kovac, Roman Chlibek, Shinn-Jang Hwang, Javier Díez-Domingo, Olivier Godeaux, Myron J Levin, Janet E McElhaney, Joan Puig-Barberà, Carline Vanden Abeele, Timo Vesikari, Daisuke Watanabe, Toufik Zahaf, Anitta Ahonen, Eugene Athan, Jose F Barba-Gomez, Laura Campora, Ferdinandus de Looze, H Jackson Downey, Wayne Ghesquiere, Iris Gorfinkel, Tiina Korhonen, Edward Leung, Shelly A McNeil, Lidia Oostvogels, Lars Rombo, Jan Smetana, Lily Weckx, Wilfred Yeo, Thomas C Heineman, ZOE-70 Study Group
雑誌名: N Engl J Med. 2016 Sep 15;375(11):1019-32. doi: 10.1056/NEJMoa1603800.
Abstract/Text BACKGROUND: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70).
METHODS: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50.
RESULTS: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups.
CONCLUSIONS: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).

PMID 27626517  N Engl J Med. 2016 Sep 15;375(11):1019-32. doi: 10.1056・・・
著者: N Kotani, T Kushikata, H Hashimoto, F Kimura, M Muraoka, M Yodono, M Asai, A Matsuki
雑誌名: N Engl J Med. 2000 Nov 23;343(21):1514-9. doi: 10.1056/NEJM200011233432102.
Abstract/Text BACKGROUND: There is no effective treatment for intractable postherpetic neuralgia. Because there is evidence that postherpetic neuralgia has an inflammatory component, we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder.
METHODS: We enrolled 277 patients who had had intractable postherpetic neuralgia for at least one year, 270 of whom were followed for two years. The patients were randomly assigned to receive intrathecal methylprednisolone and lidocaine (3 ml of 3 percent lidocaine with 60 mg of methylprednisolone acetate, 89 patients), lidocaine alone (3 ml of 3 percent lidocaine, 91 patients), or no treatment (90 patients) once per week for up to four weeks. Each weekly dose was injected into the lumbar intrathecal space. Pain was evaluated before randomization, at the end of the treatment period, and then four weeks, one year, and two years later. Samples of cerebrospinal fluid were obtained for measurement of interleukin-8 before and at the end of the treatment period.
RESULTS: There was minimal change in the degree of pain in the lidocaine-only and control groups during and after the treatment period. In the methylprednisolone-lidocaine group, the intensity and area of pain decreased, and the use of the nonsteroidal antiinflammatory drug diclofenac declined by more than 70 percent four weeks after the end of treatment. No complications related to intrathecal methylprednisolone were observed. Before treatment, the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients (r=-0.49, P<0.001). In the patients who received methylprednisolone, interleukin-8 concentrations decreased by 50 percent, and this decrease correlated with the duration of neuralgia and with the extent of global pain relief (P<0.001 for both comparisons).
CONCLUSIONS: The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.

PMID 11087880  N Engl J Med. 2000 Nov 23;343(21):1514-9. doi: 10.1056/・・・

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