感染通常为自限性的;但是,应考虑对所有患者(尤其是存在严重疾病、年龄>50 岁和/或免疫功能受损的患者)进行抗病毒治疗。治疗目标为减少病毒复制、治疗疼痛和减轻带状疱疹后遗神经痛。妊娠期带状疱疹的治疗与任何其他带状疱疹患者的治疗一样。在所有抗病毒药物中,阿昔洛韦已在妊娠女性中经过最广泛的研究,并且是最常使用的。
病毒复制减少
应对所有患者(尤其是存在严重疾病、年龄>50 岁、免疫功能受损和/或三叉神经受累证据的患者)进行抗病毒治疗,以减少病毒复制。抗病毒治疗可缩短病毒排出时长,阻止新病灶形成,防止眼部并发症,并减轻疼痛的严重程度。[40]Pavan-Langston D. Herpes zoster antivirals and pain management. Opthalmology. 2008;115:S13-S20.http://www.ncbi.nlm.nih.gov/pubmed/18243927?tool=bestpractice.com[41]Huff JC, Bean B, Balfour HH Jr, et al. Therapy of herpes zoster with oral acyclovir. Am J Med. 1988;85:84-88.http://www.ncbi.nlm.nih.gov/pubmed/3044099?tool=bestpractice.com[42]Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:89-96.http://www.ncbi.nlm.nih.gov/pubmed/7778840?tool=bestpractice.com[43]Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000;9:863-869.http://www.ncbi.nlm.nih.gov/pubmed/11031393?tool=bestpractice.com[44]Severson EA, Baratz KH, Hodge DO, et al. Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003;121:386-390.http://archopht.ama-assn.org/cgi/content/full/121/3/386http://www.ncbi.nlm.nih.gov/pubmed/12617710?tool=bestpractice.com 治疗通常为口服抗病毒药物,例如阿昔洛韦、泛昔洛韦和伐昔洛韦,在皮疹发作后 72 小时内开始使用通常最有效。对无法耐受口服药物的患者,静脉给予阿昔洛韦。不推荐使用外用抗病毒药物。
比较泛昔洛韦与伐昔洛韦对皮损和疼痛效果(研究终点)的研究发现,两者的效果无差异。[43]Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000;9:863-869.http://www.ncbi.nlm.nih.gov/pubmed/11031393?tool=bestpractice.com[45]Wassilew SW. Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study. J Eur Acad Dermatol Venereol 2005; 19:47-55.http://www.ncbi.nlm.nih.gov/pubmed/15649191?tool=bestpractice.com 关于高质量临床试验的一项系统评价发现,在降低迁延性疼痛的可能性方面,泛昔洛韦和伐昔洛韦优于阿昔洛韦。[46]McDonald EM, de Kock J, Ram FS. Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials. Antivir Ther. 2012;17:255-264.http://www.ncbi.nlm.nih.gov/pubmed/22300753?tool=bestpractice.com
一些关于随机对照试验的 meta 分析发现,使用抗病毒疗法治疗带状疱疹患者可减少迁延性疼痛的持续时间或发生率。[42]Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:89-96.http://www.ncbi.nlm.nih.gov/pubmed/7778840?tool=bestpractice.com[45]Wassilew SW. Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study. J Eur Acad Dermatol Venereol 2005; 19:47-55.http://www.ncbi.nlm.nih.gov/pubmed/15649191?tool=bestpractice.com[47]Degreef H; Famciclovir Herpes Zoster Clinical Study Group. Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocompetent patients. Int J Antimicrob Agents. 1994;4:241-246.http://www.ncbi.nlm.nih.gov/pubmed/18611615?tool=bestpractice.com[48]Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39:1546-1553.http://www.ncbi.nlm.nih.gov/pubmed/7492102?tool=bestpractice.com[49]Wassilew SW, Wutzler P. Oral brivudin in comparison with acyclovir for herpes zoster: a survey study on postherpetic neuralgia. Antiviral Res. 2003;59:57-60.http://www.ncbi.nlm.nih.gov/pubmed/12834861?tool=bestpractice.com[50]Huff JC, Drucker JL, Clemmer A, et al. Effect of oral acyclovir on pain resolution in herpes zoster: a reanalysis. J Med Virol. 1993;Suppl 1:93-96.http://www.ncbi.nlm.nih.gov/pubmed/8245901?tool=bestpractice.com[51]Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J. 1989;102:93-95.http://www.ncbi.nlm.nih.gov/pubmed/2648213?tool=bestpractice.com 然而,其他研究却发现结果相反。[52]McKendrick MW, McGill JI, White JE, et al. Oral acyclovir in acute herpes zoster. BMJ. 1986;293:1529-1532.http://www.ncbi.nlm.nih.gov/pubmed/3099943?tool=bestpractice.com[53]McKendrick MW, McGill JI, Wood MJ. Lack of effect of acyclovir on postherpetic neuralgia. BMJ. 1989;298:431.http://www.ncbi.nlm.nih.gov/pubmed/2495051?tool=bestpractice.com[54]Wood MJ, Ogan PH, McKendrick MW, et al. Efficacy of oral acyclovir treatment of acute herpes zoster. Am J Med 1988; 85(Suppl 2A):79-83.http://www.ncbi.nlm.nih.gov/pubmed/3044098?tool=bestpractice.com 研究已经表明,在缩短至疼痛完全停止的时间方面,泛昔洛韦、伐昔洛韦和阿昔洛韦优于安慰剂。[42]Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:89-96.http://www.ncbi.nlm.nih.gov/pubmed/7778840?tool=bestpractice.com[48]Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39:1546-1553.http://www.ncbi.nlm.nih.gov/pubmed/7492102?tool=bestpractice.com[55]Wood MJ, Kay R, Dworkin RH, et al. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. Clin Infect Dis. 1996;22:341-347.http://www.ncbi.nlm.nih.gov/pubmed/8838194?tool=bestpractice.com[56]Jackson JL, Gibbons R, Meyer G, et al. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia: a meta-analysis. Arch Intern Med. 1997;157:909-912.http://www.ncbi.nlm.nih.gov/pubmed/9129551?tool=bestpractice.com 然而,在其他临床试验中,阿昔洛韦对慢性疼痛作用不太明确。[57]Whitley RJ, Weiss H, Gnann JW Jr, et al. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Ann Intern Med. 1996;125:376-383.http://www.ncbi.nlm.nih.gov/pubmed/8702088?tool=bestpractice.com[53]McKendrick MW, McGill JI, Wood MJ. Lack of effect of acyclovir on postherpetic neuralgia. BMJ. 1989;298:431.http://www.ncbi.nlm.nih.gov/pubmed/2495051?tool=bestpractice.com
免疫功能低下的患者
带状疱疹感染在免疫功能受损患者中更常见,且通常更复杂。对这些患者的主要治疗目标是降低病毒在皮肤和内脏中传播的发生率,因其可导致危及生命的并发症。因此推荐免疫功能受损患者应在皮疹发作 1 周内或在病变全部结痂前的任何时间立即接受抗病毒治疗。使用口服伐昔洛韦、泛昔洛韦或阿昔洛韦治疗局部疾病,并密切进行门诊随访。通过静脉给予阿昔洛韦疗法治疗播散性水痘带状疱疹病毒感染、眼部受累、极重度免疫抑制或无法口服药物的患者。
疼痛处理
对于所有患者,使用镇痛药是为了减少急性期疼痛以及带状疱疹后遗神经痛,给药的类型根据严重程度而定。对于轻度疼痛,适合使用对乙酰氨基酚和布洛芬等镇痛药。对于严重疼痛,可选择阿片类镇痛药。已有报告指出,局部用利多卡因和神经阻滞剂有效。[58]Opstelten W, Zaal MJ. Managing ophthalmic herpes zoster in primary care. BMJ. 2005;331:147-151.http://www.ncbi.nlm.nih.gov/pubmed/16020856?tool=bestpractice.com[59]Kumar V, Krone K, Mathieu A. Neuraxial and sympathetic blocks in herpes zoster and postherpetic neuralgia: an appraisal of current evidence. Reg Anesth Pain Med. 2004;29:454-461.http://www.ncbi.nlm.nih.gov/pubmed/15372391?tool=bestpractice.com[60]Wolff RF, Bala MM, Westwood M, et al. 5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review. Acta Neurol Scand. 2011;123:295-309.http://www.ncbi.nlm.nih.gov/pubmed/21039364?tool=bestpractice.com 也可对开放性皮损处使用含炉甘石的洗剂,以减轻疼痛和瘙痒。
带状疱疹后遗神经痛
皮疹发作或皮损愈合后,疼痛持续>30 天,应怀疑带状疱疹后遗神经痛,这是最常见的并发症。此疼痛通常表现为烧灼感或瘙痒。严重程度的范围从轻度到使人虚弱。[2]Roxas M. Herpes zoster and postherpetic neuralgia: diagnosis and therapeutic considerations. Altern Med Rev. 2006;11:102-113.http://www.ncbi.nlm.nih.gov/pubmed/16813460?tool=bestpractice.com 至少 50 岁的患者发生并发症和严重疼痛的风险增加。[61]Choo PW, Galil K, Donahue JG, et al. Risk factors for postherpetic neuralgia. Arch Intern Med. 1997;157:1217-1224.http://www.ncbi.nlm.nih.gov/pubmed/9183233?tool=bestpractice.com症状通常在 6 个月内消退;但是,70 岁以上患者出现更长时间疼痛的风险更高。
治疗主要是控制疼痛。对于轻度至中度疼痛的患者,可单独使用非甾体抗炎药/对乙酰氨基酚或者与一种弱效阿片类药物进行联合治疗。[62]Wu CL, Marsh A, Dworkin RH. The role of sympathetic nerve blocks in herpes zoster and postherpetic neuralgia. Pain. 2000;87:121-129.http://www.ncbi.nlm.nih.gov/pubmed/10924805?tool=bestpractice.com[63]Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. 1998;280:1837-1842.http://jama.ama-assn.org/cgi/content/full/280/21/1837http://www.ncbi.nlm.nih.gov/pubmed/9846778?tool=bestpractice.com[64]Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology. 1998;50:1837-1841.http://www.ncbi.nlm.nih.gov/pubmed/9633737?tool=bestpractice.com[65]Bernstein JE, Korman NJ, Bickers DR, et al. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol. 1989;21:265-270.http://www.ncbi.nlm.nih.gov/pubmed/2768576?tool=bestpractice.com[66]Galer BS, Rowbotham MC, Perander J, et al. Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain. 1999;80:533-538.http://www.ncbi.nlm.nih.gov/pubmed/10342414?tool=bestpractice.com 已经表明外用辣椒素也可缓解疼痛。[67]Backonja M, Wallace MS, Blonsky ER, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7:1106-1112.http://www.ncbi.nlm.nih.gov/pubmed/18977178?tool=bestpractice.com[68]Derry S, Rice AS, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017 Jan 13;1:CD007393.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007393.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28085183?tool=bestpractice.com[69]Irving GA, Backonja MM, Dunteman E, et al. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2011;12:99-109.http://www.ncbi.nlm.nih.gov/pubmed/21087403?tool=bestpractice.com[70]Webster LR, Malan TP, Tuchman MM, et al. A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. J Pain. 2010;11:972-982.http://www.ncbi.nlm.nih.gov/pubmed/20655809?tool=bestpractice.com 对于中度至重度疼痛的患者,应使用强效阿片类镇痛药进行治疗。如果患者对阿片类镇痛药无反应,应给予三环类抗抑郁药(例如阿米替林)[71]Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry. 2010;(81):1372-1373.http://www.ncbi.nlm.nih.gov/pubmed/20543189?tool=bestpractice.com 或抗惊厥药(例如加巴喷丁或普瑞巴林)。[72]Roth TV, van Seventer R, Murphy TK. The effect of pregabalin on pain-related sleep interference in diabetic peripheral neuropathy or postherpetic neuralgia: a review of nine clinical trials. Cur Med Res Op. 2010;26:2411-2419.http://www.ncbi.nlm.nih.gov/pubmed/20812792?tool=bestpractice.com[73]Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017 Jun 9;6:CD007938.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007938.pub4/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/28597471?tool=bestpractice.com[74]Semel D, Murphy TK, Zlateva G, et al. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies. BMC Fam Pract. 2010;11:85.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988717/http://www.ncbi.nlm.nih.gov/pubmed/21054853?tool=bestpractice.com 一项 meta 分析显示,加巴喷丁和三环类抗抑郁药在缓解疼痛方面没有差异。[75]Chou R, Carson S, Chan BK. Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials. J Gen Intern Med. 2009;24:178-188.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628998/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/19089502?tool=bestpractice.com 对于不能耐受阿片类药物的患者,单用或联用抗惊厥药物、三环类抗抑郁剂或皮质类固醇均合适。
关于最初使用何种药物进行治疗,无标准指南。[76]Edelsberg JS, Lord C, Oster G. Systematic review and meta-analysis of efficacy, safety, and tolerability data from randomized controlled trials of drugs used to treat postherpetic neuralgia. Ann Pharmacother. 2011;45:1483-1490.http://www.ncbi.nlm.nih.gov/pubmed/22085778?tool=bestpractice.com 进行单药治疗还是联合治疗取决于疼痛的严重程度和对治疗的反应。
眼部受累
治疗包括使用抗病毒药物(例如使用阿昔洛韦、泛昔洛韦或伐昔洛韦)7-10 天,最好在皮疹出现后 72 小时内开始使用药物。对视网膜炎患者需要进行阿昔洛韦静脉给药。口服抗病毒药物可使急性病消退,并抑制晚期炎症复发。[44]Severson EA, Baratz KH, Hodge DO, et al. Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003;121:386-390.http://archopht.ama-assn.org/cgi/content/full/121/3/386http://www.ncbi.nlm.nih.gov/pubmed/12617710?tool=bestpractice.com[77]Tyring S, Engst R, Corriveau C, et al. Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study. Br J Ophthalmol. 2001;85:576-581.http://www.ncbi.nlm.nih.gov/pubmed/11316720?tool=bestpractice.com 其他治疗包括镇痛药、保护眼表的抗生素眼药膏和局部用皮质类固醇。需要立即将有眼部症状的所有患者转诊给眼科医生。在转诊前尽快开始抗病毒治疗。[3]Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(Suppl 1):S1-S26.https://academic.oup.com/cid/article-lookup/doi/10.1086/510206http://www.ncbi.nlm.nih.gov/pubmed/17143845?tool=bestpractice.com
慢性疾病的治疗包括以下方面:[3]Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(Suppl 1):S1-S26.https://academic.oup.com/cid/article-lookup/doi/10.1086/510206http://www.ncbi.nlm.nih.gov/pubmed/17143845?tool=bestpractice.com
起润滑作用、不含防腐剂的人工泪液凝胶或泪液
抗生素软膏
横向睑裂缝合术,以保护角膜,避免破裂(通常由神经元损伤造成感觉减退/麻木)
持续佩戴治疗性软性接触镜和使用抗生素滴眼液
使用外用皮质类固醇和抗生素治疗炎症疾病(虹膜炎、表层巩膜炎、巩膜炎和免疫性角膜炎)
对虹膜炎进行扩张治疗
根据需要治疗青光眼
根据需要进行手术处理:例如,羊膜移植、粘连组织以闭合溃疡、人工角膜和青光眼小梁切除术。
慢性疼痛的处理一般与带状疱疹后遗神经痛的类似。