治疗的主要目标是消除头皮、胡须、皮肤或甲的皮肤真菌感染。
皮肤感染的治疗通常基于临床外观,使用氢氧化钾 (KOH) 镜检寻找可疑病例中的确定性证据。建议对甲癣和头癣进行确定性检测(KOH 镜检、真菌培养、或甲碎片过碘酸希夫染色 [PAS])。
外用或口服治疗取决于感染部位。目前,没有首选抗真菌药,故需要进一步研究。[11]Rotta I, Sanchez A, Gonçalves PR, et al. Efficacy and safety of topical antifungals in the treatment of dermatomycosis: a systematic review. Br J Dermatol. 2012;166:927-933.http://www.ncbi.nlm.nih.gov/pubmed/22233283?tool=bestpractice.com口服抗真菌药需考虑其安全性,在免疫正常人群药物不良事件发生率较低。[12]Chang, CH, Young-Xu Y, Kurth T, et al. The safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis: a meta-analysis. Am J Med. 2007;120:791-798.http://www.ncbi.nlm.nih.gov/pubmed/17765049?tool=bestpractice.com
建议患者常换鞋,用粉末除汗剂,避免在公共洗浴区赤脚和共用衣服、发刷/梳子。
头癣
系统性抗真菌药物是主要治疗方式,最佳治疗方案根据所涉及的皮肤癣菌而定。治疗时间为 2-8 周,取决于所选药物。选择药物时需考虑其安全性、成本和在治疗时间。 [
]How do different systemic antifungals compare with each other for treating children with tinea capitis?http://cochraneclinicalanswers.com/doi/10.1002/cca.1398/full显示答案
最早使用的口服药物灰黄霉素,[13]Gupta AK, Cooper EA, Bowen JE, et al. Meta-analysis: griseofulvin efficacy in the treatment of tinea capitis. J Drugs Dermatol. 2008;7:369-372.http://www.ncbi.nlm.nih.gov/pubmed/18459518?tool=bestpractice.com和治疗所需时间较短的较新药物(例如特比萘芬),均为一线用药。灰黄霉素被认为是治疗小孢子菌感染的黄金标准,特比萘芬则被认为是治疗发癣菌感染的黄金标准。[7]Fuller LC, Barton RC, Mohd Mustapa MF, et al. British Association of Dermatologists’ guidelines for the management of tinea capitis 2014. Br J Dermatol. 2014;171:454-463.http://www.bad.org.uk/library-media/documents/Tinea%20capitis%20guidelines%202014.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/25234064?tool=bestpractice.comMeta 分析表明,对于发癣菌引起的头癣,特比萘芬比灰黄霉素更有效,但灰黄霉素对于小孢子菌引起的头癣更有效。[14]Tey HL, Tan AS, Chan YC. Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis. J Am Acad Dermatol. 2011;64:663-670.http://www.ncbi.nlm.nih.gov/pubmed/21334096?tool=bestpractice.com[15]Chen X, Jiang X, Yang M, et al. Systemic antifungal therapy for tinea capitis in children. Cochrane Database Syst Rev. 2016;(5):CD004685.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004685.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27169520?tool=bestpractice.com
经研究,伊曲康唑、酮康唑和氟康唑对头癣均有效。然而,氟康唑未获批准用于该适应证,酮康唑则因具有肝脏毒性不被推荐使用。[7]Fuller LC, Barton RC, Mohd Mustapa MF, et al. British Association of Dermatologists’ guidelines for the management of tinea capitis 2014. Br J Dermatol. 2014;171:454-463.http://www.bad.org.uk/library-media/documents/Tinea%20capitis%20guidelines%202014.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/25234064?tool=bestpractice.com酮康唑可引起严重肝损伤和肾上腺皮质功能不全。2013 年 7 月,欧洲药品管理局建议,口服酮康唑不应用于治疗真菌感染,因为治疗的获益已不及风险。因此,一些国家已限制使用或禁用口服酮康唑。但不包括外用酮康唑。[16]Medicines and Healthcare Products Regulatory Agency. Press release: Oral ketoconazole-containing medicines should no longer be used for fungal infections. July 2013. http://www.mhra.gov.uk/ (last accessed 25 October 2015).http://webarchive.nationalarchives.gov.uk/20141205150130/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON297530[17]European Medicines Agency. European Medicines Agency recommends suspension of marketing authorisations for oral ketoconazole. July 2013. http://www.ema.europa.eu/ema/ (last accessed 25 October 2015).http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/07/news_detail_001855.jsp&mid=WC0b01ac058004d5c1美国食品和药物管理局(FDA)建议口服酮康唑仅用于其余治疗不耐受、治疗的获益大于风险的严重至威胁生命的真菌感染。肝病患者禁忌使用。使用前和使用中,需监测肝和肾上腺功能。[18]US Food & Drug Administration. FDA drug safety communication: FDA warns that prescribing of Nizoral (ketoconazole) oral tablets for unapproved uses including skin and nail infections continues; linked to patient death. May 2016. www.fda.gov (last accessed 6 December 2016).http://www.fda.gov/Drugs/DrugSafety/ucm500597.htm
外用抗真菌洗发水不会加快缓解速度,但可降低真菌扩散和直接、间接传染的风险。
若诊断正确,治疗失败较少见。头皮病变若不缓解,需考虑是否已使用合适药物、治疗时间是否足够、患者依从性是否好、是否存在免疫抑制,可请皮肤科会诊。
须癣、手癣、Majocchi肉芽肿和广泛股癣
这些感染都侵及更深层的皮肤结构,需要全身而非局部的抗真菌药物治疗。特比萘芬、伊曲康唑和氟康唑是较好的一线选择。酮康唑可能引起严重的肝损害和肾上腺功能不全,因此不推荐使用。
若诊断正确,治疗失败较少见。 病变若不缓解,需考虑是否使用合适药物、治疗时间是否足够、依从性是否好、是否免疫抑制及需要皮肤科会诊。
面癣、体癣、股癣或足癣
此类皮肤癣菌病多发病于皮肤浅表结构,局部治疗有效。虽然近期的研究未发现各类局部抗真菌药在疗效上的显著差异,[11]Rotta I, Sanchez A, Gonçalves PR, et al. Efficacy and safety of topical antifungals in the treatment of dermatomycosis: a systematic review. Br J Dermatol. 2012;166:927-933.http://www.ncbi.nlm.nih.gov/pubmed/22233283?tool=bestpractice.com但有限的证据支持烯丙胺基类(如萘替芬、特比萘芬、布替萘芬)用于局部治疗。[19]Crawford F, Hollis S. Topical treatments for fungal infections of the skin and nails of the foot. Cochrane Database Syst Rev. 2007;(3):CD001434.http://www.ncbi.nlm.nih.gov/pubmed/17636672?tool=bestpractice.com外用唑类、环吡酮类或托萘酯类较少使用,为二线用药。高浓度萘替芬可用于股癣和足癣。[20]Parish LC, Parish JL, Routh HB, et al. A double-blind, randomized, vehicle-controlled study evaluating the efficacy and safety of naftifine 2% cream in tinea cruris. J Drugs Dermatol. 2011;10:1142-1147.http://www.ncbi.nlm.nih.gov/pubmed/21968664?tool=bestpractice.com[21]Parish LC, Parish JL, Routh HB, et al. A randomized, double-blind, vehicle-controlled efficacy and safety study of naftifine 2% cream in the treatment of tinea pedis. J Drugs Dermatol. 2011;10:1282-1288.http://www.ncbi.nlm.nih.gov/pubmed/22052309?tool=bestpractice.com使用2%浓度治疗足癣2周与1%浓度治疗4周的效果一致。[21]Parish LC, Parish JL, Routh HB, et al. A randomized, double-blind, vehicle-controlled efficacy and safety study of naftifine 2% cream in the treatment of tinea pedis. J Drugs Dermatol. 2011;10:1282-1288.http://www.ncbi.nlm.nih.gov/pubmed/22052309?tool=bestpractice.com[22]El-Gohary M, van Zuuren EJ, Fedorowicz Z, et al. Topical antifungal treatments for tinea cruris and tinea corporis. Cochrane Database Syst Rev. 2014;(8):CD009992.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009992.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25090020?tool=bestpractice.com
足癣较难根除,若趾感染清除不净、抗真菌药物使用未充分覆盖整个足表明或平底鹿皮鞋样分布的足癣皮损,极易复发。治疗足癣时消毒或及时更换鞋也可减少复发。
若患者患水疱型足癣,推荐局部醋酸铝浸泡辅助治疗。
平底靴足癣也需在足底、足侧缘应用局部外用抗真菌药,还可能需要系统性抗真菌治疗,特别是在有广泛足癣的免疫抑制患者中。
面癣、股癣或足癣治疗失败多由于患者依从性差、误诊和/或免疫抑制。治疗失败需考虑上述原因,必要时请皮肤科会诊。
甲癣
建议使用系统抗真菌治疗。口服特比萘芬可能提高临床治愈率。特比萘芬治疗皮肤甲癣较伊曲康唑有效,故考虑作为一线治疗选择。[23]de Sá DC, Lamas AP, Tosti A. Oral therapy for onychomycosis: an evidence-based review. Am J Clin Dermatol. 2014;15:17-36.http://www.ncbi.nlm.nih.gov/pubmed/24352873?tool=bestpractice.com[24]Yin Z, Xu J, Luo D. A meta-analysis comparing long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole. J Dermatolog Treat. 2012;23:449-452.http://www.ncbi.nlm.nih.gov/pubmed/21801094?tool=bestpractice.com伊曲康唑和氟康唑也有效,但较特比萘芬效果差。考虑药物不良反应和价格时,可使用二线药物。[6]Ameen M, Lear JT, Madan V, et al. British Association of Dermatologists' guidelines for the management of onychomycosis 2014. Br J Dermatol. 2014;171:937-958.http://www.bad.org.uk/shared/get-file.ashx?id=2125&itemtype=documenthttp://www.ncbi.nlm.nih.gov/pubmed/25409999?tool=bestpractice.com酮康唑可能引起严重的肝损害和肾上腺功能不全,因此不推荐使用。
治疗失败和复发较常见;需再次明确诊断以确保无甲癣不能解释的甲病变。只有在确诊后,才应考虑第二疗程的口服治疗。应重复教育患者,应经常换鞋、避免在公共洗浴区赤脚及避免感染的指(趾)甲受伤。[6]Ameen M, Lear JT, Madan V, et al. British Association of Dermatologists' guidelines for the management of onychomycosis 2014. Br J Dermatol. 2014;171:937-958.http://www.bad.org.uk/shared/get-file.ashx?id=2125&itemtype=documenthttp://www.ncbi.nlm.nih.gov/pubmed/25409999?tool=bestpractice.com
环吡酮甲油是一种低治愈率的局部疗法;也需要清除过度角化甲板以获得最优效果。[25]Gupta AK, Fleckman P, Baran R. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Am Acad Dermatol. 2000;43(suppl 4):S70-S80.http://www.ncbi.nlm.nih.gov/pubmed/11051136?tool=bestpractice.com目前较多试验研究环吡酮甲油的改良剂型,如水溶性生物聚合物,以提高疗效,但治疗时间不变。[26]Baran R, Tosti A, Hartmane I, et al. An innovative water-soluble biopolymer improves efficacy of ciclopirox nail lacquer in the management of onychomycosis. J Eur Acad Dermatol Venereol. 2009;23:773-781.http://www.ncbi.nlm.nih.gov/pubmed/19453778?tool=bestpractice.com
艾菲康唑 (Efinaconazole) 和 tavaborole 局部用溶液在一些国家/地区被批准用于治疗红色毛癣菌或须癣毛癣菌引起的趾甲远端甲下真菌病。对两项 3 期随机试验的合并分析表明,对于评估的所有主要和次要结局指标,艾菲康唑 10% 甲溶液均优于赋形剂对照品。完全治愈率为 18.5% vs 4.7% (P<0.001),真菌学治愈率为 56.3% vs 16.6% (P<0.001)。完全或几乎完全治愈率和治疗成功率达到了 27.7% 和 47.2%,使用赋形剂的完全或几乎完全治愈率和治疗成功率则分别为 7.9% 和 18.2% (P<0.001)。[27]Elewski BE, Rich P, Pollak R, et al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol. 2013;68:600-608.http://www.ncbi.nlm.nih.gov/pubmed/23177180?tool=bestpractice.com两项赋形剂对照双盲随机 3 期试验评估了 5% tavaborole 局部用溶液治疗轻度至中度(目标大趾趾甲)远端甲下真菌病患者的疗效与安全性。每项研究中 tavaborole 组的完全治愈率和真菌学阴性率分别为 6.5% 和 9.1%(对于每个研究组,与安慰剂对比 P<0.001),同时分别在 31.1% 和 35.9% 的患者中实现真菌学阴性(对于每个研究组,与安慰剂对比 P<0.001)。[28]Elewski BE, Aly R, Baldwin SL, et al. Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-III studies. J Am Acad Dermatol. 2015;73:62-69.http://www.jaad.org/article/S0190-9622%2815%2901512-1/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25956661?tool=bestpractice.com