治疗目标是淡化现有色素沉着和防止该情况进一步色素沉着。初步意见包括使用广谱紫外线防护以及停止使用可能包含光敏成分的口服避孕药与面部化妆品。
淡化剂(例如,氢醌和维甲酸)[1]Ball Arefiev KL, Hantash BM. Advances in the treatment of melasma: a review of the recent literature. Dermatol Surg. 2012;38:971-984.http://www.ncbi.nlm.nih.gov/pubmed/22583339?tool=bestpractice.com[18]Griffiths CE, Finkel LJ, Ditre CM, et al. Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial. Br J Dermatol. 1993;129:415-421.http://www.ncbi.nlm.nih.gov/pubmed/8217756?tool=bestpractice.com[19]Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al. Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial. Arch Dermatol. 1994;130:727-733.http://www.ncbi.nlm.nih.gov/pubmed/8002642?tool=bestpractice.com仅单独用作一线治疗,或者作为 Kligman 配方(也包含局部皮质类固醇)的一部分。联合治疗可能比单独使用任意单一成分疗效更好。[20]Kang HY, Valerio L, Bahadoran P, et al. The role of topical retinoids in the treatment of pigmentary disorders: an evidence-based review. Am J Clin Dermatol. 2009;10:251-260.http://www.ncbi.nlm.nih.gov/pubmed/19489658?tool=bestpractice.com例如,与单独使用 4% 氢醌相比,联用 0.01% 氟轻松、4% 氢醌和 0.05% 维甲酸(改良后的 Kligman 配方)表明疗效明显更好。[21]Chan R, Park KC, Lee MH, et al. A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma. Br J Dermatol. 2008;159:697-703.http://www.ncbi.nlm.nih.gov/pubmed/18616780?tool=bestpractice.com联合用药与单一用药局部治疗的疗效对比与清除黄褐斑:有高质量的证据显示,使用 4% 氢醌、0.05% 维甲酸和 0.01% 氟轻松三种药物联合治疗对黄褐斑的清除较任意两种单一药物联合治疗更显著。[1]Ball Arefiev KL, Hantash BM. Advances in the treatment of melasma: a review of the recent literature. Dermatol Surg. 2012;38:971-984.http://www.ncbi.nlm.nih.gov/pubmed/22583339?tool=bestpractice.com[22]Taylor SC, Torok H, Jones T, et al. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. Cutis. 2003;72:67-72.http://www.ncbi.nlm.nih.gov/pubmed/12889718?tool=bestpractice.com[21]Chan R, Park KC, Lee MH, et al. A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma. Br J Dermatol. 2008;159:697-703.http://www.ncbi.nlm.nih.gov/pubmed/18616780?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 在初步治疗后,连用三联药物治疗 6 个月进行维持治疗表明能够防止复发。[23]Arellano I, Cestari T, Ocampo-Candiani J, et al. Preventing melasma recurrence: prescribing a maintenance regimen with an effective triple combination cream based on long-standing clinical severity. J Eur Acad Dermatol Venereol. 2012;26:611-618.http://www.ncbi.nlm.nih.gov/pubmed/21623930?tool=bestpractice.com然而,氢醌(尤其是 Fitzpatrick V 型或 VI 型皮肤、长期使用含浓度>3% 的制剂且无防晒措施的患者)可导致称作外源性褐黄病(皮肤中聚合的尿黑酸沉积,导致永久性色素沉着)的疾病。壬二酸也用作淡化剂,浓度为 15%~20%。[24]Prignano F, Ortonne JP, Buggiani G, et al. Therapeutical approaches in melasma. Dermatol Clin. 2007;25:337-342, viii.http://www.ncbi.nlm.nih.gov/pubmed/17662899?tool=bestpractice.com壬二酸与黄褐斑的清除:有高质量的证据表明,20% 壬二酸凝胶比 2% 氢醌凝胶的疗效更好,在治疗黄褐斑方面,其疗效相当于 4% 氢醌。[25]Verallo-Rowell VM, Verallo V, Graupe K, et al. Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma. Acta Derm Venereol Suppl (Stockh). 1989;143:58-61.http://www.ncbi.nlm.nih.gov/pubmed/2528260?tool=bestpractice.com[26]Balina LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol. 1991;30:893-895.http://www.ncbi.nlm.nih.gov/pubmed/1816137?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 替代局部治疗包括对甲氧酚/维甲酸和熊果苷。[27]Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. 2007;20:308-313.http://www.ncbi.nlm.nih.gov/pubmed/18045355?tool=bestpractice.com
由于大多数局部外用药物可导致某些皮肤刺激,因此依从性可能是问题。虽然局部外用皮质类固醇还会导致某些皮肤美白,但是作为联合方案的一部分使用,主要用于降低此类刺激。在面部长期使用皮质类固醇(通常>12 周)可导致皮肤萎缩、毛细血管扩张和/或痤疮样发疹。[28]Gupta AK, Gover MD, Nouri K, et al. The treatment of melasma: a review of clinical trials. J Am Acad Dermatol. 2006;55:1048-1065.http://www.ncbi.nlm.nih.gov/pubmed/17097400?tool=bestpractice.com
难治性病例
化学剥脱法可单独使用或与局部治疗联用。如果患者耐受,则可在难治性病例中将其作为二线治疗。最常用的剥脱剂是乙醇酸,浓度为 50%~70%。乙醇酸和黄褐斑的清除:有中等质量证据表明,在治疗黄褐斑方面,经历乙醇酸、水杨酸或三氯乙酸此一系列化学剥脱术的疗效中等。果酸换肤联合改良Kligman 配方的疗效好于单独使用改良 Kligman 配方的疗效。在一项小型研究中,联合使用果酸换肤和 4% 氢醌似乎并不比单独使用 4% 氢醌更有效。[29]Chun EY, Lee JB, Lee KH. Focal trichloroacetic acid peel method for benign pigmented lesions in dark-skinned patients. Dermatol Surg. 2004;30:512-516.http://www.ncbi.nlm.nih.gov/pubmed/15056140?tool=bestpractice.com[30]Grimes PE. The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol Surg. 1999;25:18-22.http://www.ncbi.nlm.nih.gov/pubmed/9935087?tool=bestpractice.com[31]Javaheri SM, Handa S, Kaur I, et al. Safety and efficacy of glycolic acid facial peel in Indian women with melasma. Int J Dermatol. 2001;40:354-357.http://www.ncbi.nlm.nih.gov/pubmed/11555002?tool=bestpractice.com[32]Soliman MM, Ramadan SA, Bassiouny DA, et al. Combined trichloroacetic acid peel and topical ascorbic acid versus trichloroacetic acid peel alone in the treatment of melasma: a comparative study. J Cosmet Dermatol. 2007;6:89-94.http://www.ncbi.nlm.nih.gov/pubmed/17524124?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。也有三氯乙酸和水杨酸剥脱法有效治疗黄褐斑的报道。化学剥脱剂的不良反应可能包括刺激和炎症后色素沉着。局部疗法可继续联合化学剥脱法应用。
对于局部(± 剥脱性)疗法难治性患者,可使用激光和光照疗法。最常用且最有效的方式包括 Q 开关钕:钇铝石榴石/翠绿宝石激光、二氧化碳激光以及强脉冲光。[24]Prignano F, Ortonne JP, Buggiani G, et al. Therapeutical approaches in melasma. Dermatol Clin. 2007;25:337-342, viii.http://www.ncbi.nlm.nih.gov/pubmed/17662899?tool=bestpractice.comQ 开关翠绿宝石激光和二氧化碳激光联合疗法可能比单独使用 Q 开关翠绿宝石激光的效果更佳。联合使用脉冲二氧化碳激光和 Q 开关翠绿宝石激光可有效治疗真皮型黄褐斑患者:有低质量(可信程度有限)的证据表明,联合使用这 2 种激光比单独使用 Q 开关翠绿宝石激光更有效。[33]Nouri K, Bowes L, Chartier T, et al. Combination treatment of melasma with pulsed CO2 laser followed by Q-switched alexandrite laser: a pilot study. Dermatol Surg. 1999;25:494-497.http://www.ncbi.nlm.nih.gov/pubmed/10469101?tool=bestpractice.com[34]Angsuwarangsee S, Polnikorn N. Combined ultrapulse CO2 laser and Q-switched alexandrite laser compared with Q-switched alexandrite laser alone for refractory melasma: split-face design. Dermatol Surg. 2003;29:59-64.http://www.ncbi.nlm.nih.gov/pubmed/12534514?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。还可使用点阵激光(非剥脱性激光治疗形式)、利用光热分解作用进行有效治疗:有低质量(可信程度有限)的证据表明,60% 的患者使用点阵激光法获得 75%~100% 的清除,而 30% 的患者获得<25% 的改善。[35]Rokhsar CK, Fitzpatrick RE. The treatment of melasma with fractional photothermolysis: a pilot study. Dermatol Surg. 2005;31:1645-1650.http://www.ncbi.nlm.nih.gov/pubmed/16336881?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。皮肤磨削术和冷冻疗法。[36]Kunachak S, Leelaudomlipi P, Wongwaisayawan S. Dermabrasion: a curative treatment for melasma. Aesthetic Plast Surg. 2001;25:114-117.http://www.ncbi.nlm.nih.gov/pubmed/11349301?tool=bestpractice.com点阵激光会降低黑素颗粒浓度和黑素细胞数。[37]Tierney EP, Hanke CW. Review of the literature: Treatment of dyspigmentation with fractionated resurfacing. Dermatol Surg. 2010;36:1499-1508.http://www.ncbi.nlm.nih.gov/pubmed/20698875?tool=bestpractice.com最近,可变方波脉冲 (VSP) Er:YAG 激光已用作受影响患者的治疗方案,导致在 MASI 评分获得显著改善且停机时间更少,无结痂形成,不良反应可能性降低。[38]Wanitphakdeedecha R, Manuskiatti W, Siriphukpong S, et al. Treatment of melasma using variable square pulse Er:YAG laser resurfacing. Dermatol Surg. 2009;35:475-481.http://www.ncbi.nlm.nih.gov/pubmed/19250309?tool=bestpractice.com
在激光治疗后,常见炎症后色素沉着,但该情况通常短暂,并可通过在激光治疗前后使用氢醌疗法进行治疗。[39]Tannous Z. Fractional resurfacing. Clin Dermatol. 2007;25:480-486.http://www.ncbi.nlm.nih.gov/pubmed/17870526?tool=bestpractice.com