Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial.

BACKGROUND: Melasma is a difficult-to-treat hyperpigmentary disorder. While cysteamine is a known potent depigmenting agent, its efficacy in treating melasma has not been tested. OBJECTIVES: To study the efficacy of cysteamine 5% cream in the treatment of patients with epidermal melasma. METHODS: In this double-blind randomized study, participating patients (n = 50) received either placebo (n = 25) or cysteamine cream (n = 25). Cysteamine cream or placebo were applied on the lesions once a day at bedtime over 4 months. The efficacy of treatments was determined through Mexameter skin colorimetry, Melasma Area Severity Index (MASI) score, Investigator's Global Assessment (IGA) and patients' questionnaires, all performed at baseline and after 2 and 4 months of treatment. RESULTS: At baseline, the mean differences between pigmented and normal skin (calculated by Mexameter) were 75.2 ± 37 and 68.9 ± 31 in the cysteamine and placebo groups, respectively. After 2 and 4 months of application of cysteamine and placebo cream, the mean differences were 39.7 ± 16.6 and 26.2 ± 16 in the cysteamine group, and 63.8 ± 28.6 and 60.7 ± 27.3 in the placebo group, respectively. Statistically significant differences were found between the group outcomes at both points (P = 0.001 and P < 0.001). At the end of the treatment, the MASI scores were significantly lower in the cysteamine group vs. placebo (7.2 ± 5.5 vs. 11.6 ± 7.9, P = 0.02). The IGA and patients' viewpoints indicated significant efficacy of cysteamine cream vs. placebo. CONCLUSIONS: Cysteamine cream showed significant efficacy in the treatment of melasma.

Discrimination between cutaneous pigmentation and erythema: comparison of the skin colorimeters Dermacatch and Mexameter.

BACKGROUND/PURPOSE: Reproducibility and specificity of the present skin colorimeters is still limited as alterations in erythema can bias the measurement of melanin and vice versa. Here, Dermacatch(®) , a new colorimeter covering the visible light spectrum, has been compared with Mexameter(®) , an established narrow-band reflectance spectrophotometer. METHODS: Repeated measurements with both devices were initially collected on colour charts. Then, measures were compared on 12 human volunteers before and after exposure to UVB, and/or modulation of skin erythema. RESULTS: In vitro sensitivity of Dermacatch to erythema/melanin covered a broader wavelength spectrum than Mexameter while in vivo sensitivity of both devices was similar. Interestingly, Mexameter's melanin and erythema values were falsely affected by an increase in erythema or variation in pigmentation respectively. On the contrary, Dermacatch's melanin and erythema values remained constant in the same circumstances. Furthermore, as Mexameter was at least twice less reproducible than Dermacatch, Mexameter showed an increased risk of a confusion over the detection of erythema or melanin fluctuations. CONCLUSION: The analysis of more than 18,000 measures indicated that, Dermacatch has a significantly higher specificity and reproducibility than Mexameter in the measurement of skin pigmentation and erythema.

The potential depigmenting activity of retinaldehyde.

BACKGROUND: Retinoids have been reported to exert depigmenting activity. Unlike most depigmenting agents that target tyrosinase, they are not phenolic agents and may act via different mechanisms. OBJECTIVES: We analysed the properties of retinaldehyde (RAL), a precursor of retinoic acid (RA), as a skin-lightening agent in various models. METHODS: The viability and the depigmenting properties of RAL were assessed in murine melanocytes, in human reconstructed epidermis, and in mice and guinea pigs. The melanin content and cytotoxicity were assessed in melanocytes; in 3-dimensional models, the melanin concentration and the number of active melanocytes were determined. RESULTS: RAL was taken up by melanocytes and mostly metabolised to retinol and retinyl esters, and to a lesser extent to RA. RAL decreased the melanin concentration of guinea pig ears and mouse tails by 54 and 74%, respectively, and decreased the number of active melanocytes by 42 and 77%, respectively. In reconstructed epidermis the melanin concentration was increased by 52%, whereas the number of active melanocytes decreased by 44%. CONCLUSION: RAL exerts a significant depigmenting activity with a mode of action that looks different from that of RA. Our data suggest a skin-lightening effect related to a melanolytic action (i.e. a decrease in melanin concentration, whatever the mechanism) rather than to melanocytotoxicity, besides other still unknown actions of RAL on melanocytes.

The combination of a retinoid, a phenolic agent and an antioxidant improves tolerance while retaining an optimal depigmenting action in reconstructed epidermis.

BACKGROUND: Cutaneous pigmented lesions urge the need to find safe and effective treatments to lighten the skin. OBJECTIVE: The aim of this study was to combine a retinoid (retinaldehyde), a new phenolic agent (4-(1-phenylethyl)-resorcinol) and a proreducing agent (δ-tocopheryl-ß-D-glucopyranoside) to achieve synergistic actions for skin lightening. METHODS: The tolerance profile and the depigmenting properties of these agents were assessed in murine keratinocyte and melanocyte cell lines, as well as in a 3-dimensional model of reconstructed epidermis. RESULTS: Retinaldehyde and 4-(1-phenylethyl)-resorcinol induced a significant decrease of tissue viability in reconstructed epidermis, but this cytotoxicity was prevented by the addition of δ-tocopheryl-ß-D-glucopyranoside. The combination of the three agents was, however, efficient in decreasing the specific melanin content and the density of active melanocytes. CONCLUSION: A combination of various chemicals acting via different mechanisms allows a decrease in the toxicity of each compound alone while retaining optimal skin-lightening properties.

Safety of topical methimazole for the treatment of melasma. Transdermal absorption, the effect on thyroid function and cutaneous adverse effects.

Methimazole is an oral antithyroid compound that exhibits a skin-depigmenting effect when used topically. However, the effect of topical methimazole on thyroid function has not been reported. This study was aimed at assessing the safety of topical methimazole used to treat pigmented lesions, without affecting thyroid hormones due to systemic delivery. The pharmacokinetics of methimazole, either applied in the form of a 5% topical formulation to facial skin or taken orally in the form of a 5-mg tablet by 6 volunteers, were determined. In addition, the effect of long-term topical applications of 5% methimazole on the function of the thyroid gland in 20 patients with epidermal melasma was determined following 6 weeks of once-daily application. Cutaneous adverse effects of topical methimazole were determined. From 15 min up to 24 h after application, methimazole was undetectable in the serum of the individuals receiving single topical methimazole dosing. Methimazole, however, was detected in serum after 15 min of oral administration and remained detectable in serum up to 24 h after administration. Long-term topical methimazole applications in melasma patients did not induce any significant changes in serum TSH, free thyroxine and free triiodothyronine levels. Topical methimazole was well tolerated by the patients and did not induce any significant cutaneous side effects. Present data together with the previously shown non-cytotoxic and non-mutagenic characteristics of methimazole indicate that this agent could be considered as a safe skin-depigmenting compound for topical treatment of skin hyperpigmentary disorders in humans.

The depigmenting effect of RALGA in C57BL/6 mice.

BACKGROUND: It has been known for a long time that the topical use of retinoic acid (RA) produces mild depigmentation of human skin. However, RA has two major disadvantages for its utilisation as a topical depigmenting compound. First, RA can act as an irritant and can produce considerable erythema and exfoliation of skin. Second, RA has a relatively weak depigmenting ability compared to other known depigmenting chemicals. OBJECTIVE: In this study, we show that RALGA, a combination of the less irritant retinoid retinaldehyde (RAL; 0.1%) and glycolic acid (6.4%), has a higher skin-depigmenting potential than RA 0.05% in the tail skin of C57BL/6 mice. This effect was observed in reducing the number of functioning melanocytes and/or in inhibiting their ability to synthesise melanin. In addition, the visually recognisable depigmenting effect of RALGA was evident earlier than that of RA, i.e. only after 1 week of application. RALGA may therefore serve as a depigmenting product for the treatment of skin hyperpigmentary disorders. Postacne hyperpigmented lesions represent a very common pigmentary problem among acne patients. RALGA may thus act as an anti-acne product, due to the presence of RAL--an RA precursor--which could simultaneously remove the postacne hyperpigmented lesions in such patients.