今日の臨床サポート

帯状疱疹(感染症科)

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. 内服薬や既往歴(特に免疫状態に影響をもたらすもの)は帯状疱疹の診断・治療を行ううえで重要な情報であり、必ず聴取される必要がある(推奨度1)
  1. アシクロビル・バラシクロビル・ファムシクロビルは共に帯状疱疹に対して有効な薬剤であり、特に皮疹の出現後72時間以内に開始することが重要だと考えられている(推奨度1)
  1. 三環系抗うつ薬やガバペンチンは帯状疱疹の痛みに対して有効であったという報告もあり、症状が強く他に禁忌が存在しない場合には考慮してもよい(推奨度2)
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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:
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、フォローアップおよび予防接種の項目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. 帯状疱疹とは、脊髄後根神経節に潜伏感染した水痘・帯状疱疹ウイルス(VZV)の再活性化により、デルマトームに沿った痛みを伴う水疱を発症する皮膚疾患である。
  1. 帯状疱疹の診断は、デルマトームに沿った特徴的な皮疹と痛みを確認することにより行う。
  1. 疾患の頻度は高く、特に65歳以上の年齢では頻度が3倍以上に上昇することが知られている。
  1. 眼窩に及ぶ帯状疱疹は、重篤な眼科的合併症を来す頻度が高く、緊急に眼科コンサルトを要する。
  1. 若年者で他にリスクの見当たらない患者が帯状疱疹を発症した場合、HIV感染症や自己免疫疾患などの存在を疑う必要がある。
  1. 免疫抑制患者では、非定型的な分布で発症することや、皮疹を伴わずに発症すること(zoster sine herpete)、肺炎・脳炎・網膜炎などの合併症を来すこともある。
問診・診察のポイント  
  1. ごく初期の帯状疱疹は痛みから発症して皮疹を後から発症することもあり、特定のデルマトームに限局した急性痛をみた場合には帯状疱疹も鑑別に挙げる必要がある。

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。

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文献 

著者: M J Wood, R Kay, R H Dworkin, S J Soong, R J Whitley
雑誌名: Clin Infect Dis. 1996 Feb;22(2):341-7.
Abstract/Text Meta-analysis of four double-blind, randomized, placebo-controlled trials of oral acyclovir (800 mg five times daily) for the treatment of herpes zoster was conducted to provide definitive assessments of the effect of acyclovir on the resolution of zoster-associated pain. The studies involved a total of 691 patients, and the analysis was performed on an intent-to-treat basis. A range of milestones of pain cessation were evaluated by means of Cox regression models with adjustment for relevant prognostic factors. The proportion of patients with postherpetic neuralgia at 3 and 6 months was also determined. Advancing age and more severe pain at presentation were associated with more prolonged pain. Acyclovir was clearly shown to accelerate pain resolution by all of the measures employed. Benefit was especially evident in patients 50 years of age or older. Fewer acyclovir recipients had postherpetic neuralgia at 3 or 6 months. Overall, the reductions of pain duration and prevalence were approximately twofold.

PMID 8838194  Clin Infect Dis. 1996 Feb;22(2):341-7.
著者: D Bowsher
雑誌名: J Pain Symptom Manage. 1997 Jun;13(6):327-31.
Abstract/Text Seventy-two patients older than 60 years of age who received a diagnosis of herpes zoster (HZ) were entered into a randomized, double-blind, placebo-controlled trial of daily amitriptyline 25 mg. Treatment with either amitriptyline or placebo continued for 90 days after diagnosis. Pain prevalence at 6 months was the primary outcome. Results showed that early treatment with low-dose amitriptyline reduced pain prevalence by more than one-half (p < 0.05; odds ratio, 2.9:1) This finding makes a strong case for the pre-emptive administration of amitriptyline, in combination with an antiviral drug, to elderly patients with acute herpes zoster.

PMID 9204652  J Pain Symptom Manage. 1997 Jun;13(6):327-31.
著者: James D Berry, Karin Lottrup Petersen
雑誌名: Neurology. 2005 Aug 9;65(3):444-7. doi: 10.1212/01.wnl.0000168259.94991.8a.
Abstract/Text This randomized, double-blind, placebo-controlled crossover study measured the effect of a single dose of oral gabapentin (900 mg) on pain and allodynia associated with herpes zoster. Pain severity decreased by 66% with gabapentin compared to 33% with placebo. Reductions in allodynia area and severity, and overall pain relief, were also greater with gabapentin.

PMID 16087911  Neurology. 2005 Aug 9;65(3):444-7. doi: 10.1212/01.wnl.・・・
著者: L He, D Zhang, M Zhou, C Zhu
雑誌名: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005582. doi: 10.1002/14651858.CD005582.pub2. Epub 2008 Jan 23.
Abstract/Text BACKGROUND: Postherpetic neuralgia is a common serious complication of herpes zoster. Corticosteroids are anti-inflammatory and might be beneficial.
OBJECTIVES: To examine the efficacy of corticosteroids in preventing postherpetic neuralgia.
SEARCH STRATEGY: Search for randomised or quasi-randomised controlled trials for corticosteroids for preventing postherpetic neuralgia in MEDLINE (1950 to 2006), EMBASE (1980 to 2006), LILACS (1982 to 2005), the Chinese Biomedical Retrieval System (1978 to 2006) and the Cochrane Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 3, 2006). Date of most recent search: September 2006.
SELECTION CRITERIA: Types of studies: quasi-randomised or randomised controlled trials.
TYPES OF PARTICIPANTS: people of all ages with herpes zoster of all degrees of severity within seven days after onset. Types of interventions: all kinds of corticosteroids given by oral, intramuscular or intravenous routes during the acute stage (starting within one week of onset of the rash) compared with no treatment or placebo, but not with other treatments. We also included trials which compared corticosteroids plus routine treatment with placebo plus routine treatment. Types of outcome measures: Primary: the presence of postherpetic neuralgia six months after the onset of the acute herpetic rash. Secondary: pain severity measured by a validated visual analogue scale or numerical descriptive scale after three, six and 12 months; quality of life measured with the short form 36 questionnaire after six months; adverse events during or within two weeks after stopping treatment.
DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers.
MAIN RESULTS: Five trials were included with altogether 787 participants. All were randomised, double-blind, placebo-controlled parallel group studies. Our primary outcome measure was the presence of postherpetic neuralgia six months after the onset of the acute herpetic rash. There was no significant difference between the corticosteroid and control groups for the primary outcome (RR 1.27, 95% CI 0.20 to 7.97). There was also no significant difference between the corticosteroid plus antiviral agents and placebo plus antiviral agents groups for the primary outcome (RR 0.90, 95% CI 0.40 to 2.03). No included trials evaluated pain severity with a validated visual analogue scale or numerical descriptive scale and also no trials measured quality of life with the Short Form 36 questionnaire. Adverse events during or within two weeks after stopping treatment were reported by all five included trials, but after meta-analysis, there was no significant difference in any serious adverse event (death, acute cardiac insufficiency, rash dissemination, bacterial pneumonia or haematemesis) or non serious adverse event (dizziness, nausea, vomiting, hypertension or hyperglycaemia).
AUTHORS' CONCLUSIONS: There was insufficient evidence to conclude that corticosteroids are safe or effective in the prevention of postherpetic neuralgia. More randomised controlled trials with a greater number of participants are needed to determine reliably whether there is real benefit (or harm) from the use of corticosteroid therapy to prevent postherpetic neuralgia. Future trials should measure function and quality of life.

PMID 18254083  Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005582. d・・・
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: 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・・・

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