Wu Bing-Qi, Wang Yen-Jen, Chang Chang-Cheng, Juang Tzong-Yuan, Huang Yung-Hsueh, Hsu Ying-Chuan
Department of Education, China Medical University Hospital, Taichung 404327, Taiwan.
School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
J Clin Med. 2024 Dec 9;13(23):7483. doi: 10.3390/jcm13237483.
Melasma is a challenging, acquired hyperpigmentary disorder. The gold standard treatment is Kligman's formulation, which contains hydroquinone, tretinoin, and dexamethasone, but its long-term use is limited by the risk of exogenous ochronosis. Cysteamine, a tyrosinase inhibitor, reduces melanocyte activity and melanin production, showing strong depigmenting effects in patients resistant to Kligman's formulation. Nonetheless, clinical studies have yielded inconsistent efficacy results. This meta-analysis aimed to assess the efficacy of cysteamine in treating melasma and to identify potential factors that may impact its therapeutic outcomes. A systematic search of PubMed, Embase, Web of Science, and CENTRAL, from the earliest record until August 2024, was conducted. Randomized controlled trials and quasi-randomized design studies related to topical cysteamine on melasma patients were included. The primary outcome was MASI or mMASI assessment after treatments. The current meta-analysis was conducted with a random-effects model. Subgroup analyses and meta-regressions were performed based on baseline MASI, disease duration of melasma, patient age, and sample size of the included studies. Funnel plots and Duval and Tweedie's trim and fill method were adopted to assess the publication bias. Eight studies were included for quantitative analysis. The analysis of MASI after topical cysteamine demonstrated a significant decrease compared to the placebo ( = 0.002). Compared to other melasma treatments, cysteamine did not show superior efficacy in mMASI ( = 0.277). The treatment efficacy of hydroquinone, modified Kligman's formula, and tranexamic acid mesotherapy for melasma was not statistically different when compared to cysteamine ( = 0.434). Further analyses showed no benefit when allowing extended cysteamine application time ( < 0.0001). The meta-regression revealed the efficacy of cysteamine decreased as the duration of melasma increased (coefficient = 0.38, = 0.0001, R = 0.99). The funnel plot displayed some asymmetry. The trim and fill method suggested the adjusted effect size was 0.607 (95% CI = -0.720 to 1.935). Cysteamine exhibited efficacy in treating melasma patients; however, its depigmentation effect was comparable to hydroquinone-based regimens, tranexamic acid mesotherapy, and modified Kligman's formula. Using cysteamine in patients with a short duration of melasma may result in better efficacy.
黄褐斑是一种具有挑战性的获得性色素沉着障碍性疾病。金标准治疗方法是Kligman配方，其含有氢醌、维甲酸和地塞米松，但长期使用会受到外源性褐黄病风险的限制。半胱胺是一种酪氨酸酶抑制剂，可降低黑素细胞活性和黑色素生成，对Kligman配方耐药的患者显示出强大的色素减退作用。尽管如此，临床研究的疗效结果并不一致。这项荟萃分析旨在评估半胱胺治疗黄褐斑的疗效，并确定可能影响其治疗效果的潜在因素。我们对PubMed、Embase、Web of Science和CENTRAL进行了系统检索，检索时间从最早记录到2024年8月。纳入了与外用半胱胺治疗黄褐斑患者相关的随机对照试验和半随机设计研究。主要结局是治疗后的MASI或mMASI评估结果。本荟萃分析采用随机效应模型进行。基于纳入研究的基线MASI、黄褐斑病程、患者年龄和样本量进行亚组分析和荟萃回归分析。采用漏斗图以及Duval和Tweedie的修剪和填充方法评估发表偏倚。纳入八项研究进行定量分析。外用半胱胺后MASI分析显示与安慰剂相比有显著下降（P = 0.002）。与其他黄褐斑治疗方法相比，半胱胺在mMASI方面未显示出更高的疗效（P = 0.277）。与半胱胺相比，氢醌、改良Kligman配方和氨甲环酸中胚层疗法治疗黄褐斑的疗效在统计学上无差异（P = 0.434）。进一步分析表明延长半胱胺使用时间并无益处（P < 0.0001）。荟萃回归分析显示，随着黄褐斑病程延长，半胱胺的疗效降低（系数 = −0.38，P = 0.0001，R = 0.99）。漏斗图显示存在一定不对称性。修剪和填充方法提示调整后的效应大小为0.607（95%CI = −0.720至1.935）。半胱胺在治疗黄褐斑患者方面显示出疗效；然而，其色素减退效果与基于氢醌的治疗方案、氨甲环酸中胚层疗法和改良Kligman配方相当。在黄褐斑病程较短的患者中使用半胱胺可能会产生更好的疗效。
