局部用药和一些患者采用的系统性用药可轻松治疗花斑癣。PV 很少自发消退,如果不予治疗,则该病可能持续数年。[13]Gupta AK, Kogan N, Batra R. Pityriasis versicolor: a review of pharmacological treatment options. Expert Opin Pharmacother. 2005;6:165-178.http://www.ncbi.nlm.nih.gov/pubmed/15757415?tool=bestpractice.com仅 2 周抗菌疗法后,显微镜下就可见马拉色菌的真菌碎片。[6]Gupta AK, Bluhm R, Summerbell R. Pityriasis versicolor. J Eur Acad Dermatol Venereol. 2002;16:19-33.http://www.ncbi.nlm.nih.gov/pubmed/11952286?tool=bestpractice.com然而,即使治疗成功,患者和临床医生也必须记住,PV 引起的色素异常可能需要 6 周才会恢复,这并非治疗失败的表现。[32]El-Gothamy Z, Abdel-Fattah A, Ghaly AF. Tinea versicolor hypopigmentation: histochemical and therapeutic studies. Int J Dermatol. 1975;14:510-515.http://www.ncbi.nlm.nih.gov/pubmed/1099036?tool=bestpractice.com尤其是色素减退性皮损可能需要更长时间恢复。[19]Thoma W, Kramer HJ, Mayser P. Pityriasis versicolor alba. J Eur Acad Dermatol Venereol. 2005;19:147-152.http://www.ncbi.nlm.nih.gov/pubmed/15752280?tool=bestpractice.com因此,治疗效果通常根据皮屑 KOH 处理后的检查结果来评估,而不是色素异常的恢复。此外,由于在许多病例中都普遍认为是内源性宿主因素导致马拉色菌酵母相转化成病理性菌丝相,因此往往有高达 60% 的患者会在治疗后第 1 年内出现复发,且 2 年后复发率高达 80%。[6]Gupta AK, Bluhm R, Summerbell R. Pityriasis versicolor. J Eur Acad Dermatol Venereol. 2002;16:19-33.http://www.ncbi.nlm.nih.gov/pubmed/11952286?tool=bestpractice.com[33]Faergemann J. Pityrosporum species as a cause of allergy and infection. Allergy. 1999;54:413-419.http://onlinelibrary.wiley.com/doi/10.1034/j.1398-9995.1999.00089.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/10380771?tool=bestpractice.com因此,临床医生应考虑对反复发病的患者使用预防药治疗。[6]Gupta AK, Bluhm R, Summerbell R. Pityriasis versicolor. J Eur Acad Dermatol Venereol. 2002;16:19-33.http://www.ncbi.nlm.nih.gov/pubmed/11952286?tool=bestpractice.com
局部治疗
局部疗法是所有患者(尤其是儿童和孕妇)的一线治疗方案。[34]Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for superficial mycotic infections of the skin: pityriasis (tinea) versicolor. Guidelines/Outcomes Committee. American Academy of Dermatology. J Am Acad Dermatol. 1996;34:287-289.http://www.ncbi.nlm.nih.gov/pubmed/8642095?tool=bestpractice.com多种局部治疗可供使用,效果大致类似。局部药物的选择最终取决于患者的偏好。当使用任何局部治疗时,即使病变仅累及很少区域,患者也应治疗整个颈部、躯干、臂部和膝盖以上的腿部。[24]Faergemann J. Management of seborrheic dermatitis and pityriasis versicolor. Am J Clin Dermatol. 2000;1:75-80.http://www.ncbi.nlm.nih.gov/pubmed/11702314?tool=bestpractice.com
非特异性局部治疗是较旧的方法,且相对便宜。这些药剂包括吡硫嗡锌、丙二醇和硫化硒。特异性局部疗法是使用较新型药物,包括唑类抗真菌药,例如酮康唑、克霉唑和咪康唑。[24]Faergemann J. Management of seborrheic dermatitis and pityriasis versicolor. Am J Clin Dermatol. 2000;1:75-80.http://www.ncbi.nlm.nih.gov/pubmed/11702314?tool=bestpractice.com[35]Croxtall JD, Plosker GL. Sertaconazole: a review of its use in the management of superficial mycoses in dermatology and gynaecology. Drugs. 2009;69:339-359.http://www.ncbi.nlm.nih.gov/pubmed/19275277?tool=bestpractice.com特比萘芬和环吡酮胺同样有效。[24]Faergemann J. Management of seborrheic dermatitis and pityriasis versicolor. Am J Clin Dermatol. 2000;1:75-80.http://www.ncbi.nlm.nih.gov/pubmed/11702314?tool=bestpractice.com还可以局部使用维 A 酸类软膏(例如,维 A 酸、阿达帕林)。[36]Mills OH Jr, Kligman AM. Letter: Tretinoin in tinea versicolor. Arch Dermatol. 1974;110:638.http://www.ncbi.nlm.nih.gov/pubmed/4414455?tool=bestpractice.com[37]Shi TW, Ren XK, Yu HX, et al. Roles of adapalene in the treatment of pityriasis versicolor. Dermatology. 2012;224:184-188.http://www.ncbi.nlm.nih.gov/pubmed/22572567?tool=bestpractice.com各种特异性局部治疗的疗效类似,但选择合适的剂型很重要,(例如选择洗剂、洗发露和溶液来治疗有毛发的病变皮肤,疗效要优于霜剂)。
妊娠期可局部用特比萘芬和环吡酮胺。妊娠期不应使用硫化硒和唑类抗真菌药。然而,有些临床医生仍在妊娠期局部用硫化硒。吡硫嗡锌和丙二醇的安全性尚未在孕妇中充分证实。然而,动物实验中使用吡硫嗡锌后,其后代中未观察到致畸性或胚胎毒性。[38]Wedig JH, Kennedy GL Jr, Jenkins DH, et al. Teratologic evaluation of dermally applied zinc pyrithione on swine. Toxicol Appl Pharmacol. 1976;36:255-259.http://www.ncbi.nlm.nih.gov/pubmed/1273846?tool=bestpractice.com[39]Nolen GA, Patrick LF, Dierckman TA. A percutaneous teratology study of zinc pyrithione in rabbits. Toxicol Appl Pharmacol. 1975;31:430-433.http://www.ncbi.nlm.nih.gov/pubmed/1145628?tool=bestpractice.com孕妇禁用局部维 A 酸类药物。
系统治疗
系统治疗主要用于皮损广泛者、对前期局部治疗产生耐受者,免疫功能低下的患者、局部治疗依从性差者以及病情频繁复发的患者。在 PV 治疗中,仅需短期进行系统治疗,从而限制其副作用。[24]Faergemann J. Management of seborrheic dermatitis and pityriasis versicolor. Am J Clin Dermatol. 2000;1:75-80.http://www.ncbi.nlm.nih.gov/pubmed/11702314?tool=bestpractice.com口服药的优势是患者依从性增加,因为口服比局部治疗更方便且耗时更少。[13]Gupta AK, Kogan N, Batra R. Pityriasis versicolor: a review of pharmacological treatment options. Expert Opin Pharmacother. 2005;6:165-178.http://www.ncbi.nlm.nih.gov/pubmed/15757415?tool=bestpractice.com口服唑类抗真菌药(例如,酮康唑、氟康唑、伊曲康唑)为首选药物。[6]Gupta AK, Bluhm R, Summerbell R. Pityriasis versicolor. J Eur Acad Dermatol Venereol. 2002;16:19-33.http://www.ncbi.nlm.nih.gov/pubmed/11952286?tool=bestpractice.com[12]Gupta AK, Batra R, Bluhm R, et al. Skin diseases associated with Malassezia species. J Am Acad Dermatol. 2004;51:785-798.http://www.ncbi.nlm.nih.gov/pubmed/15523360?tool=bestpractice.com[13]Gupta AK, Kogan N, Batra R. Pityriasis versicolor: a review of pharmacological treatment options. Expert Opin Pharmacother. 2005;6:165-178.http://www.ncbi.nlm.nih.gov/pubmed/15757415?tool=bestpractice.com[19]Thoma W, Kramer HJ, Mayser P. Pityriasis versicolor alba. J Eur Acad Dermatol Venereol. 2005;19:147-152.http://www.ncbi.nlm.nih.gov/pubmed/15752280?tool=bestpractice.com[40]Kokturk A, Kaya TI, Ikizoglu G, et al. Efficacy of three short-term regimens of itraconazole in the treatment of pityriasis versicolor. J Dermatolog Treat. 2002;13:185-187.http://www.ncbi.nlm.nih.gov/pubmed/19753739?tool=bestpractice.com虽然研究未能一致证明单剂量伊曲康唑在 PV 治疗中的作用,但仍有一些证据提示伊曲康唑短疗程使用疗效可能与多天疗程相同。[40]Kokturk A, Kaya TI, Ikizoglu G, et al. Efficacy of three short-term regimens of itraconazole in the treatment of pityriasis versicolor. J Dermatolog Treat. 2002;13:185-187.http://www.ncbi.nlm.nih.gov/pubmed/19753739?tool=bestpractice.com[41]Köse O, Bülent Taştan H, Riza Gür A, et al. Comparison of a single 400 mg
dose versus a 7-day 200 mg daily dose of itraconazole in the treatment of tinea
versicolor. J Dermatolog Treat. 2002;13:77-79.http://www.ncbi.nlm.nih.gov/pubmed/12060506?tool=bestpractice.com[42]Wahab MA, Ali ME, Rahman MH, et al. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial. Mymensingh Med J. 2010;19:72-76.http://www.ncbi.nlm.nih.gov/pubmed/20046175?tool=bestpractice.com系统性唑类抗真菌药在酸性环境中的吸收最佳。因此,患者应使用碳酸饮料服药。另外,通常让患者在工作出汗前 45 分钟用药,出汗后等待数小时后再沐浴,以使更多药物能够到达角质层。
以上所列药物在疗效相差无几。[6]Gupta AK, Bluhm R, Summerbell R. Pityriasis versicolor. J Eur Acad Dermatol Venereol. 2002;16:19-33.http://www.ncbi.nlm.nih.gov/pubmed/11952286?tool=bestpractice.com少见的不良反应包括恶心、呕吐并且所有的唑类药物(尤其是酮康唑)均可引发肝炎。[28]Borelli D, Jacobs PH, Nall L. Tinea versicolor: epidemiologic, clinical, and therapeutic aspects. J Am Acad Dermatol. 1991;25:300-305.http://www.ncbi.nlm.nih.gov/pubmed/1918469?tool=bestpractice.com然而,考虑到治疗PV时,治疗疗程短,这些不良反应并不常见。酮康唑可能导致重度肝损伤和肾上腺功能不全。2013 年 7 月,欧洲药品管理局人类药品委员会 (CHMP) 不建议使用口服酮康唑治疗真菌感染,因为治疗效果不再大于其带来的风险。所以,一些国家可能已限制或不再使用口服酮康唑。这个提议并没有限制局部使用酮康唑。[43]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 30 July 2017).http://webarchive.nationalarchives.gov.uk/20141205150130/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON297530[44]European Medicines Agency. European Medicines Agency recommends suspension of marketing authorisations for oral ketoconazole. July 2013. http://www.ema.europa.eu/ema/ (last accessed 30 July 2017).http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/07/news_detail_001855.jsp&mid=WC0b01ac058004d5c1美国食品药品监督管理局 (FDA) 建议,在危及生命的真菌感染时,如果没有替代治疗或替代治疗无法耐受时,且潜在疗效超过风险时,才推荐使用口服酮康唑。伴有肝脏疾病的患者禁用酮康唑。如果使用,则应在治疗之前和治疗期间监测肝和肾上腺功能。[45]US Food and Drug Administration. FDA drug safety communication: FDA limits usage of Nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal gland problems. May 2016. http://www.fda.gov/ (last accessed 30 July 2017).http://www.fda.gov/Drugs/DrugSafety/ucm362415.htm已有对传统的系统性药物(例如伊曲康唑和氟康唑)耐药的报道,这就可能需要更高剂量和延长疗程,或者以传统的局部治疗为主,例如使用硫化硒和吡硫嗡锌。[46]Helou J, Obeid G, Moutran R, et al. Pityriasis versicolor: a case of resistance to treatment. Int J Dermatol. 2014;53:e114-e116.http://www.ncbi.nlm.nih.gov/pubmed/23432729?tool=bestpractice.com
口服特比萘芬和灰黄霉素对于治疗 PV 无效。[6]Gupta AK, Bluhm R, Summerbell R. Pityriasis versicolor. J Eur Acad Dermatol Venereol. 2002;16:19-33.http://www.ncbi.nlm.nih.gov/pubmed/11952286?tool=bestpractice.com
预防
对于复发患者,在成功治疗后,进行预防性治疗可能是必要的。一线预防治疗是硫化硒(尤其对于儿童)。[1]Schwartz RA. Superficial fungal infections. Lancet. 2004;364:1173-1182.http://www.ncbi.nlm.nih.gov/pubmed/15451228?tool=bestpractice.com如果局部预防性治疗无效,则可使用包括口服唑类抗真菌药冲击治疗在内的二线疗法。[47]Faergemann J, Djarv L. Tinea versicolor: treatment and prophylaxis with ketoconazole. Cutis. 1982;30:542-545;550.http://www.ncbi.nlm.nih.gov/pubmed/6291861?tool=bestpractice.com[48]Rausch LJ, Jacobs PH. Tinea versicolor: treatment and prophylaxis with monthly administration of ketoconazole. Cutis. 1984;34:470-471.http://www.ncbi.nlm.nih.gov/pubmed/6094116?tool=bestpractice.com[49]Faergemann J, Gupta AK, Al Mofadi A, et al. Efficacy of itraconazole in the prophylactic treatment of pityriasis (tinea) versicolor. Arch Dermatol. 2002;138:69-73.http://archderm.ama-assn.org/cgi/content/full/138/1/69http://www.ncbi.nlm.nih.gov/pubmed/11790169?tool=bestpractice.com
辅助措施
即使在成功消除病原体后,皮肤色素异常也会长期存在,尤其是色素减少型患者。对于色素减退明显的患者,应在完全消除真菌后( 皮屑KOH处理后镜检阴性)后,考虑每周 3 次 UV-B 紫外线光疗。在开始紫外线治疗后,可在 3 周内见到色素重新生成。[50]Jung EG, Bohnert E. Mechanism of depigmentation on pityriasis versicolor alba. Arch Dermatol Res. 1976;256:333-334.http://www.ncbi.nlm.nih.gov/pubmed/825051?tool=bestpractice.com