Objective To assess the efficacy and safety of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women. Topical 5% cysteamine is an antioxidant and tyrosinase inhibitor that has been shown to be effective in the treatment of melasma. However, to date, no study has compared the performance of topical cysteamine to hydroquinone for facial melasma. Methods A quasi-randomized, multicenter, evaluator-blinded clinical trial was conducted on 40 women with facial melasma who were submitted to the nightly application of 5% cysteamine (CYS) or 4% hydroquinone (HQ) on hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were assessed at the inclusion and after 60 and 120 days of treatment for mMASI, MELASQoL, and the difference in colorimetric luminosity between melasma and the adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in the appearance of the skin through standardized photographs. Results The mean reduction of the mMASI scores was 24% for CYS and 41% for HQ (P = 0.015) at 60 days, and 38% for CYS and 53% for HQ (P = 0.017) at 120 days. The photographic evaluation revealed up to 74% improvement for both groups, without statistically significant difference between them (P = 0.087). The MELASQoL score showed a progressive decrease for both groups over time, despite the greater reduction for HQ after 120 days (P = 0.018). Colorimetric assessment disclosed progressive depigmenting in both groups, without statistically significant difference between them (P > 0.160). No severe adverse effects were identified in either group. Erythema and burning were the most important local adverse effects with cysteamine, although their frequency did not differ between groups (P > 0.170). Conclusion Cysteamine proved to be safe, well-tolerated, and effective, despite its inferior performance to hydroquinone in decreasing mMASI and MELASQoL in the treatment of melasma.

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Melasma is a multifactorial dyschromia that results from exposure to external factors (such as solar radiation) and hormonal factors (such as sex hormones and pregnancy), as well as skin inflammation (such as contact dermatitis and esthetic procedures), in genetically predisposed individuals. Beyond hyperfunctional melanocytes, skin with melasma exhibits a series of structural and functional alterations in the epidermis, basement membrane, and upper dermis that interact to elicit and sustain a focal hypermelanogenic phenotype. Evolution in the knowledge of the genetic basis of melasma and the cutaneous response to solar radiation, as well as the roles of endocrine factors, antioxidant system, endothelium proliferation, fibroblast senescence, mast cell degranulation, autophagy deficits of the melanocyte, and the paracrine regulation of melanogenesis, will lead to the development of new treatments and preventive strategies. This review presents current knowledge on these aspects of the pathogenesis of melasma and discusses the effects of specific treatments and future research on these issues.

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Background Melasma can be refractory to treatment, and relapses are frequent. Thiamidol is a new potent tyrosinase inhibitor that has been found effective as a cosmeceutical for the depigmenting of melasma.Objective This study compared the efficacy and tolerability of topical 0.2% Thiamidol vs. 4% hydroquinone for facial melasma.Methods Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomly assigned to apply a double layer of 0.2% Thiamidol twice a day or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Seve:rity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life [Melasma Quality of Life Index (MELAS-QoL)], colourimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation.Results One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III-IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35-50%) for Thiamidol and 33% (23-42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colourimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67-97%) for participants in the Thiamidol group and 74% (CI: 95% 61-93%) for those in the hydroquinone group. There were only mild adverse effects in the Thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. ConclusionThe melasma improvement achieved using 0.2% Thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone.