暴露后预防性治疗
暴露后单次使用多西环素预防性治疗,推荐用于符合下列条件的明显暴露患者:
吸饱血的肩突硬蜱已经叮咬至少约 36 个小时才被清除掉。
应在清除蜱虫 72 小时内开始预防性治疗。
已知当地蜱虫的伯氏疏螺旋体感染率在 20% 以上。
无多西环素禁忌证。禁忌证包括年龄<8 岁的儿童(在某些国家/地区)、妊娠期或哺乳期;在英国,不推荐年龄<12 岁的儿童使用多西环素。在美国,美国儿科学会 (American Academy of Pediatrics, AAP) 认可年龄<8 岁的儿童短期应用(<21 天)多西环素治疗莱姆病。[25]American Academy of Pediatrics. Lyme disease. In: Kimberlin DW, Brady MT, Jackson MA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018: 515-23. 以前,多西环素仅限用于 8 岁及以上的人群,但最近的比较数据表明,在年龄较小的儿童中,该药不太可能引起明显的牙齿染色或牙釉质发育不全,因此已对该推荐内容进行了修订。[26]American Academy of Pediatrics. Tetracyclines. In: Kimberlin DW, Brady MT, Jackson MA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018: 905-6.
不能使用多西环素的患者,如果出现早期症状,即开始治疗。
游走性红斑
有游走性红斑,但是没有心血管和神经系统症状的莱姆病患者,治疗方法如下:[2]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134.http://cid.oxfordjournals.org/content/43/9/1089.fullhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com[27]Steere AC, Malawista SE, Newman JH, et al. Antibiotic therapy in Lyme disease. Ann Intern Med. 1980 Jul;93(1):1-8.http://www.ncbi.nlm.nih.gov/pubmed/6967272?tool=bestpractice.com[28]Steere AC, Hutchinson GJ, Rahn DW, et al. Treatment of early manifestations of Lyme disease. Ann Intern Med. 1983 Jul;99(1):22-6.http://www.ncbi.nlm.nih.gov/pubmed/6407378?tool=bestpractice.com[29]Massarotti EM, Luger SW, Rahn DW, et al. Treatment of early Lyme disease. Am J Med. 1992 Apr;92(4):396-403.http://www.ncbi.nlm.nih.gov/pubmed/1313637?tool=bestpractice.com[30]Nadelman RB, Luger SW, Frank E, et al. Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann Intern Med. 1992 Aug 15;117(4):273-80.http://www.ncbi.nlm.nih.gov/pubmed/1637021?tool=bestpractice.com[31]Luger SW, Paparone P, Wormser GP, et al. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents Chemother. 1995 Mar;39(3):661-7.http://aac.asm.org/cgi/reprint/39/3/661http://www.ncbi.nlm.nih.gov/pubmed/7793869?tool=bestpractice.com[32]Nowakowski J, Nadelman RB, Forseter G, et al. Doxycycline versus tetracycline therapy for Lyme disease associated with erythema migrans. J Am Acad Dermatol. 1995 Feb;32(2 Pt 1):223-7.http://www.ncbi.nlm.nih.gov/pubmed/7829706?tool=bestpractice.com[33]Eppes SC, Childs JA. Comparative study of cefuroxime axetil versus amoxicillin in children with early Lyme disease. Pediatrics. 2002 Jun;109(6):1173-7.http://www.ncbi.nlm.nih.gov/pubmed/12042561?tool=bestpractice.com[34]Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003 May 6;138(9):697-704.http://www.ncbi.nlm.nih.gov/pubmed/12729423?tool=bestpractice.com
阿莫西林或者头孢呋辛,疗程为 14~21 天。多西环素,疗程为 10-21天。
孕妇和哺乳期女性的治疗方式相同,但应避免使用多西环素。
大环内酯类不推荐作为一线治疗药物,但对于不能耐受上述三种一线药物的患者,可选用大环内酯类。
当无法鉴别游走性红斑与社区获得性蜂窝织炎时,由于头孢呋辛、阿莫西林/克拉维酸对上述两种疾病均有效,故推荐使用。
心脏受累
莱姆病患者出现心脏并发症,但不伴高度心脏传导阻滞时,可以选用口服抗生素治疗。[2]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134.http://cid.oxfordjournals.org/content/43/9/1089.fullhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com 出现胸痛、晕厥、呼吸困难、2 度或者 3 度房室 (atrioventricular, AV) 传导阻滞或者 1 度阻滞伴 PR 间期 ≥300 毫秒的患者应住院治疗、接受静脉输注抗生素治疗和持续监护。对于存在重度房室传导阻滞的患者,推荐使用临时起搏器。[2]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134.http://cid.oxfordjournals.org/content/43/9/1089.fullhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com[35]Sigal LH. Early disseminated Lyme disease: cardiac manifestations. Am J Med. 1995 Apr 24;98(4A):25S-28S;discussion 28S-29S.http://www.ncbi.nlm.nih.gov/pubmed/7726189?tool=bestpractice.com
莱姆关节炎
治疗方法取决于感染的类型和严重程度:[2]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134.http://cid.oxfordjournals.org/content/43/9/1089.fullhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com
已经成功使用关节镜下滑膜切除术治疗抗生素耐药的莱姆关节炎。现据报道,偶用关节腔内注射皮质类固醇、全身性非甾体抗炎药或使用改善疾病的抗风湿药物(例如羟氯喹)也有助于治疗抗生素耐药性莱姆关节炎。上述治疗必须在医生的监督指导下进行。
神经系统莱姆病(神经疏螺旋体病)
虽然静脉抗生素通常用于神经系统并发症患者,口服多西环素已被证明同样有效。
对于早期神经系统症状局限于脑膜、颅神经、神经根、周围神经(Bannwarth 综合征)的莱姆病患者,可以进行疗程为期 2 周的口服抗生素(多西环素)或静脉抗生素(头孢曲松、头孢噻肟或苄青霉素)治疗。[23]Mygland A, Ljøstad U, Fingerle V, et al; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16;e1-4.http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2009.02862.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19930447?tool=bestpractice.com 然而,基于现有的小规模研究结果,有脊髓炎、脑炎和血管炎的早期神经莱姆病患者,需要静脉注射抗生素 2 周。[23]Mygland A, Ljøstad U, Fingerle V, et al; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16;e1-4.http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2009.02862.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19930447?tool=bestpractice.com 一项 Cochrane 评价发现有低质量到极低质量的证据显示,在欧洲,青霉素 G、多西环素、头孢曲松和头孢噻肟对于早期神经莱姆病的治疗可带来相似的良好结局;在美国没有发现针对神经莱姆病进行的临床试验。[36]Cadavid D, Auwaerter PG, Rumbaugh J, et al. Antibiotics for the neurological complications of Lyme disease. Cochrane Database Syst Rev. 2016;(12):CD006978.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006978.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27931077?tool=bestpractice.com
对于合并周围神经病变和慢性萎缩性肢端皮炎的晚期莱姆病,欧洲神经科学协会联盟 (European Federation of Neurological Societies) 指南推荐口服多西环素或静脉注射头孢曲松进行治疗。[23]Mygland A, Ljøstad U, Fingerle V, et al; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16;e1-4.http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2009.02862.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19930447?tool=bestpractice.com 然而,如果这些患者有中枢神经系统表现,如脊髓炎、脑炎和血管炎,则需要静脉注射头孢曲松。
面瘫的治疗方法仍有争议。尚没有确凿的数据表明,是应当按照神经并发症治疗,还是按照不伴有中枢神经系统表现的急性莱姆病进行治疗。[37]Halperin JJ, Shapiro ED, Logigian E, et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2007 Jul 3;69(1):91-102.http://n.neurology.org/content/69/1/91http://www.ncbi.nlm.nih.gov/pubmed/17522387?tool=bestpractice.com 本专著的作者治疗莱姆病患者的孤立性面瘫时,按照早期神经疏螺旋体病合并颅神经受累进行治疗。
根据患者的自身情况,对存在关节和神经系统受累的患者选择适合的治疗方案,并应在医生的监督指导下完成。