Glycolic acid peels in the treatment of melasma among Asian women. Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial. Comparison of 30% salicylic acid with Jessner's solution for superficial chemical peeling in epidermal melasma. The efficacy of a broad-spectrum sunscreen in the treatment of melasma. Safety and efficacy of 4% hydroquinone combined with 10% glycolic acid, antioxidants, and sunscreen in the treatment of melasma. Efficacy of glycolic acid peels in the treatment of melasma. Intense pulsed light for the treatment of refractory melasma in Asian persons. Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma. Topical isotretinoin for melasma in Thai patients: a vehicle-controlled clinical trial. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid. Evaluation of efficacy and safety of rucinol serum in patients with melasma: a randomized controlled trial. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Whitening effect of a dermocosmetic formulation: a randomized double-blind controlled study on melasma. 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.
Melasma is a common disorder of facial hyperpigmentation among Asian women. Many modalities of treatment are available but none is satisfactory.
                This study was undertaken to see if glycolic acid peels are effective and safe in the treatment of melasma and fine facial wrinkling.
                Ten Asian women with moderate to severe melasma were recruited into the study. The women had twice daily applications of a cream containing 10% glycolic acid and 2% hydroquinone (Neostrata AHA Age Spot and Skin Lightening Gel) to both sides of the face, and glycolic acid peels every 3 weeks (20-70%) to one-half of the face using Neostrata Skin Rejuvenation System. All patients had to use a sunblock (SPF 15%). At regular intervals and at the end of 26 weeks (or after eight peels) the degree of improvement of pigmentation and fine facial wrinkling on each side of the face were assessed. Any skin irritation or side effects were also noted. Assessment was by an independent dermatologist, the patients themselves, and the use of the Munsell color chart and photographs. The nonparametric Wilcoxon Rank-Sum test was used for statistical analysis.
                The melasma and fine facial wrinkling improved on both sides of the face. The side that received glycolic acid peels did better but the results were not statistically significant (P > 0.059).
                A cream containing 10% glycolic acid and 2% hydroquinone (Neostrata AHA Age Spot and Skin Lightening Gel) improved melasma and fine facial wrinkling in Asian women. In combination with glycolic acid peels at 3-week intervals the lightening of melasma is subjectively much better. This improvement does not reach statistical significance and the sample size is small (n = 10). Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African-American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically.
                After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild "retinoid dermatitis" occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution.
                This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects. To compare the efficacy and safety of Jessner's solution with 30% salicylic acid as superficial chemical peeling agents in treating epidermal melasma in Asian skin.
                Double blind, randomized, interventional comparative study.
                Department of Dermatology, Combined Military Hospital, Malir Cantt, Karachi, from January to December 2004.
                Sixty consenting patients with epidermal melasma were randomly divided into two groups. Group A was treated with Jessner's solution and Group B with 30% salicylic acid. Baseline Melasma Area Severity Index (MASI) score was noted and peeling started at 2-weekly intervals. Sunscreen in morning and moisturizer at night were prescribed in all patients. MASI score and adverse effects were recorded biweekly. Treatment was stopped at 12 weeks and patients were followed-up at 4 weekly intervals for further 12 weeks. Final MASI score and adverse effects were noted at the end of follow-up period. Mean MASI scores were compared using paired sample t-test and one-way ANOVA.
                Difference in baseline, treatment end and follow-up end MASI scores was not statistically significant between the two groups (p 0.54, 0.26, and 0.55 respectively). On the other hand, within group analysis of difference between pre and posttreatment MASI score was highly significant in both groups (p<0.0001). Adverse effects were mild and comparable in both groups.
                Jessner's solution and 30% salicylic acid are equally effective and safe peeling agents for use in epidermal melasma in Asian skin. A double-blind study comparing a broad-spectrum sunscreen agent with its vehicle in the treatment of melasma was performed in fifty-three patients who were concomitantly using a depigmentating solution. In this study, 96.2 percent of those who used the sunscreen agent showed improvement as compared with 80.7 percent of those who used placebo. These results confirm the positive role of sun protection in the treatment of melasma and also establish hydroquinone as a major therapeutic agent in pigmentary disorders. Melasma, also known as mask of pregnancy, is a common, acquired hypermelanosis seen in women with Fitzpatrick skin types II-V, and is often recalcitrant to treatment with depigmentation agents. Glycolic acid has been added to hydroquinone formulations in the past to enhance their depigmentation effects, but may cause irritation, leading to postinflammatory hyperpigmentation.
                To assess the safety and efficacy of a cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen (Glyquin, ICN Pharmaceuticals, Costa Mesa, USA) vs. a cream containing sunscreen alone in the depigmentation of epidermal melasma of the face.
                Thirty-nine Hispanic women, Fitzpatrick skin types III-V, with bilateral epidermal melasma were enrolled in a randomized controlled trial lasting 12 weeks. Patients underwent twice-daily full-face application with the study cream or with the cream containing sunscreen only. Changes in pigmentation were measured using a mexameter, the melasma area and severity index (MASI), and a global evaluation by the patient and blind investigator. Safety evaluations were performed at each follow-up visit.
                Thirty-five patients completed the trial. Irritation was more common with the study cream, but resolved with temporary cessation of cream application and the addition of moisturizers. Mexameter results demonstrated a significant decrease in the degree of pigmentation using the study cream compared with the cream containing sunscreen alone (P < 0.0001). Fifteen of 20 patients (75%) using the study cream improved, whereas only two of 15 patients (13%) improved using sunscreen alone.
                A cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen is safe and effective in the treatment of melasma. Melasma is an acquired hypermelanosis that is often recalcitrant to treatment with hypopigmenting agents.
                To assess the efficacy of 4% hydroquinone cream vs 4% hydroquinone cream combined with glycolic acid peels as treatment for melasma.
                Twenty-one Hispanic women with bilateral epidermal and mixed melasma were enrolled in a split-faced prospective trial lasting 8 weeks. Patients underwent 20% to 30% glycolic acid peels every 2 weeks to one side of the face only in addition to twice-daily full-face application of 4% hydroquinone cream and sun protective factor 25 UV-B sunscreen each morning. Pigmentation was measured objectively using a mexameter and the Melasma Area and Severity Index and subjectively using a linear analog scale and physician and patient global evaluation.
                Hydroquinone treatment alone and treatment with the combination of hydroquinone and glycolic acid had a significant effect in reducing skin pigmentation compared with baseline (P<.001). However, no significant difference was found using combination therapy compared with hydroquinone alone (P =.75).
                Use of 4% hydroquinone and a daily sunscreen is effective in the treatment of melasma; however, the addition of 4 glycolic acid peels did not enhance the hypopigmenting effect of hydroquinone treatment alone. Patients with dermal or mixed-type melasmas are often refractory to various treatments. Intense pulsed light has been used to treat melanocytic lesions with promising results.
                The purpose of this study was to clarify the effectiveness of intense pulsed light for refractory melasma in Asian persons.
                Seventeen patients were treated with intense pulsed light, during four sessions at 4-week intervals. The patients were also given 4% hydroquinone cream and broad-spectrum sunscreens to prevent and treat postinflammatory hyperpigmentation. Sixteen patients in the control group were treated with hydroquinone cream and sunscreens. The treatment efficacy was evaluated using reflectance spectrophotometer and patient satisfaction questionnaire.
                Patients in the intense pulsed light group achieved an average of 39.8% improvement in relative melanin index, compared to 11.6% improvement in the control group (p<0.05) at Week 16. Six (35%) patients in the intense pulsed light group had more than 50% improvement, compared to two (14%) patients in the control group. Two patients in the intense pulsed light group, however, experienced transient postinflammatory hyperpigmentation, and partial repigmentation was noted 24 weeks after the last treatment session.
                Intense pulsed light is a safe and effective treatment for refractory melasma in Asian persons, with minimal side effects. Further treatment sessions are required for maintenance therapy. Melasma is a common disorder of cutaneous hyperpigmentation predominantly affecting the faces of women. Little is known about the aetiology of melasma, and treatment is frequently disappointing. Topical tretinoin is of benefit in treating other forms of hyperpigmentation, for example liver spots, and we therefore investigated its effectiveness in melasma. Thirty-eight women completed a randomized, vehicle-controlled study, in which they applied 0.1% tretinoin (n = 19) or vehicle cream (n = 19) once daily to the face for 40 weeks. At the end of treatment 13 (68%) of 19 tretinoin-treated patients were clinically rated as improved or much improved, compared with 1 (5%) of 19 in the vehicle group (P = 0.0006). Significant improvement first occurred after 24 weeks of tretinoin treatment. Colorimetry (an objective measure of skin colour) demonstrated a 0.9 unit lightening of tretinoin-treated melasma and a 0.3 unit darkening with vehicle (P = 0.01); these results correlated with clinical lightening (r = 0.55, P = 0.0005). Histologically, epidermal pigment was reduced 36% following tretinoin treatment, compared with a 50% increase with vehicle (P = 0.002). Reduction in epidermal pigment also correlated with clinical lightening (r = -0.41, P = 0.01). Moderate cutaneous side-effects of erythema and desquamation occurred in 88% of tretinoin-treated and 29% of vehicle-treated patients. Topical 0.1% tretinoin produces significant clinical improvement of melasma, mainly due to reduction in epidermal pigment, but improvement is slow. Treatment of melasma, a hyperpigmentation disorder, remains a challenge. The primary objective of two 8-week, multicenter, randomized, investigator-blind studies was to compare the efficacy and safety of a hydrophilic cream formulation containing tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) with the dual-combination agents tretinoin plus hydroquinone (RA+HQ), tretinoin plus fluocinolone acetonide (RA+FA), and hydroquinone plus fluocinolone acetonide (HQ+FA). All agents had the same drug concentration and vehicle. A total of 641 adult patients, predominantly female, with moderate to severe melasma and Fitzpatrick skin types I through IV, were randomized to the various treatment groups. Due to the similarity of the study designs, the results of the 2 studies were combined and are reported here. The primary efficacy analysis involved the proportion of intent-to-treat patients in each treatment group whose condition had completely cleared by week 8. The results of the combined clinical trials demonstrated that significantly more of the patients treated with RA+HQ+FA (26.1%) experienced complete clearing compared with the other treatment groups (4.6%) at the end of week 8 (P<.0001). In addition, at week 8, a 75% reduction in melasma/pigmentation was observed in more than 70% of patients treated with RA+HQ+FA compared with 30% in patients treated with the dual-combination agents. The most common adverse reactions seen with all treatment groups were erythema, skin peeling, burning, and/or stinging sensation. The majority of treatment-related adverse events were of mild severity. Vitamin C is known to both inhibit melanin formation and reduce oxidized melanin. However, vitamin C does not easily penetrate the skin. In this study, vitamin C iontophoresis was employed in order to enhance vitamin C penetration.
                The purpose of this study was to evaluate the efficacy of vitamin C iontophoresis for melasma patients.
                Twenty-nine females with melasma were enrolled. For iontophoresis, a vitamin C solution was applied to one side of the face, while distilled water was applied to the other side as a control. The L (luminance) value was measured by a colorimeter to obtain an objective pigmentation parameter.
                Twelve weeks after iontophoresis, the colorimeter of the treated site showed a significant decrease in the L value (from 4.60 to 2.78, p = 0.002), compared to that of the control site (from 4.45 to 3.87, p = 0.142).
                Vitamin C iontophoresis may be an effective treatment modality for melasma.
                Copyright 2003 S. Karger AG, Basel Melasma is an acquired hyperpigmentary disorder commonly seen in Orientals. Recently it has been demonstrated that tretinoin (all-trans-retinoic acid) can produce significant clinical improvement of melasma. However, moderate cutaneous side effects (retinoid dermatitis) occurred in a number of patients.
                To investigate the efficacy of topical 0.05 per cent isotretinoin gel (Isotrex) in the treatment of melasma in Thai patients.
                Thirty patients with moderate to severe melasma entered a 40-week, randomized, vehicle-controlled clinical trial in which they applied either 0.05 per cent isotretinoin gel, or its vehicle base together with a broad spectrum sunscreen (SPF 28) daily to the entire face. They were evaluated clinically (using Melasma Area and Severity Index), and colorimetrically (using our Melasma Area and Melanin Index).
                After 40 weeks, the average MASI and MAMI scores of the isotretinoin-treated group decreased by 68.2 per cent and 47 per cent respectively, while the corresponding control scores declined 60 per cent and 34 per cent. There was no statistically significant difference between the isotretinoin and vehicle groups. When the MASI and MAMI scores of each visit were compared to their baseline data, a statistically significant reduction of the score was first noted at weeks 4 and 12 respectively. Lightening of melasma, as determined clinically (MASI score), correlated well with pigmentation measurements (MAMI score). Side effects were limited to a mild transient "retinoid dermatitis" occurring in 27 per cent of isotretinoin-treated patients.
                Daily use of broad spectrum sunscreen has a significant lightening effect on melasma in Thai patients. However, there was no statistically significant difference between the isotretinoin and vehicle-treated group. Melasma is an acquired treatment-resistant hyperpigmentation of the skin.
                Sixteen women with idiopathic melasma were included in our trial. After randomization by another clinician, they were instructed to use, at night, 5% ascorbic acid cream on one side of the face and 4% hydroquinone cream on the other side, for 16 weeks. Sunscreen was applied daily throughout the period of observation. They were evaluated every month by colorimetry, digital photography, and regular color slides. Subjective evaluation by each patient was also taken into account.
                The best subjective improvement was observed on the hydroquinone side with 93% good and excellent results, compared with 62.5% on the ascorbic acid side (P < 0.05); however, colorimetric measures showed no statistical differences. Side-effects were present in 68.7% (11/16) with hydroquinone vs. 6.2% (1/16) with ascorbic acid.
                Although hydroquinone showed a better response, ascorbic acid may play a role in the therapy of melasma as it is almost devoid of side-effects; it could be used alone or in combination therapy. Melasma is difficult to clear. Many agents have been used, such as hydroquinone, and glycolic acid and glycolic acid peels, kojic acid, a tyrosinase inhibitor in the fungus Aspergilline oryzae.
                To see if the addition of 2% kojic acid in a gel containing 10% glycolic acid and 2% hydroquinone will improve melasma further.
                Forty Chinese women with epidermal melasma were treated with 2% kojic acid in a gel containing 10% glycolic acid and 2% hydroquinone on one half of the face. The other half was treated with the same application but without kojic acid. The side receiving the kojic acid was randomized. Determination of efficacy was based on clinical evaluation, photographs and self-assessment questionnaires at 4 weekly intervals until the end of the study at 12 weeks. The non-parametric Wilcoxon's rank sum test was used for statistical analysis.
                All patients showed improvement in melasma on both sides of the face. The side receiving the kojic acid did better. More than half of the melasma cleared in 24/40 (60%) patients receiving kojic acid compared to 19/40 (47.5%) patients receiving the gel without kojic acid. In 2 patients, there was complete clearance of melasma, and this was on the side where kojic acid was used. Side effects include redness, stinging, and exfoliation. These were seen on both sides of the face, and they settled by the third week.
                The addition of kojic acid to a gel containing 10% glycolic acid and 2% hydroquinone further improves melasma. Melasma is a hyperpigmentation disorder predominantly affecting sun-exposed areas in women, which is often refractory to treatment. Most commercially available treatments incorporate inhibitors of tyrosinase, a key enzyme in melanin production within the melanocyte. In general, however, the efficacy of these therapies is somewhat limited. Recent studies have identified other enzymes that play an important role in melanogenesis, including tyrosinase-related protein-1 (TRP-1), which catalyses the oxidation of the melanogenetic intermediate 5,6-dihydroxyindole-2-carbolylic acid. Rucinol (4-n-butylresorcinol) has been shown to inhibit the activity of both tyrosinase and TRP-1.
                To assess the efficacy of rucinol serum 0.3% vs. the corresponding vehicle as a treatment for melasma. Secondary objectives were to evaluate local and general tolerability and to assess the skin acceptability of rucinol serum in the target population.
                In this prospective, single-centre, double-blind, randomized, vehicle-controlled, bilateral (split-face) comparative trial, 32 women with melasma were provided with two identical tubes containing rucinol serum 0.3% or vehicle. The products were each applied to one-half of the face, according to the randomization scheme, twice daily for 12 weeks (phase 1). A broad-spectrum sunscreen (sun protection factor 60) was also applied daily. Assessments at baseline, 4, 8 and 12 weeks included clinical evaluations by a dermatologist, chromametry, ultraviolet and standard photography, and assessments of skin acceptability and tolerability. After 12 weeks, patients were given the option of an additional 3-month treatment period of open full-face rucinol treatment, with reviews at 16, 20 and 24 weeks (phase 2).
                Twenty-eight patients completed phase 1 and 26 patients completed phase 2. After 12 weeks, the clinical pigmentation score for rucinol-treated skin was significantly lower than for vehicle-treated skin (P = 0.027). During phase 2, rucinol induced a significant reduction in mean pigmentation score on the half of the face previously treated with vehicle. There was also a further, significant improvement on the rucinol-treated side of the face. Chromametry measurements showed that skin was significantly lighter and less yellow, with a strong trend towards reduced redness, following rucinol therapy compared with vehicle. Rucinol serum showed good tolerability and acceptability and was considered to have good or fair efficacy by 78% of the patient population.
                Rucinol serum was shown to have significant efficacy compared with vehicle alone in improving melasma after 3 months of treatment, according to clinical and objective assessments of skin colour. The efficacy of 20% azelaic acid cream and 4% hydroquinone cream, both used in conjunction with a broad-spectrum sunscreen, against melasma was investigated in a 24-week, double-blind study with 329 women. Over the treatment period the azelaic acid cream yielded 65% good or excellent results; no significant treatment differences were observed with regard to overall rating, reduction in lesion size, and pigmentary intensity. Severe side effects such as allergic sensitization or exogenous ochronosis were not observed with azelaic acid. Melasma is an endocrine-mediated facial hypermelanosis with epidermal and occasionally dermal components. We tested in a randomized double-blind design the effect of a whitening formulation (Thiospot intensive) on this skin disorder. The product containing ethyl linoleate, thioctic acid, octadecenedioic acid, lactic acid and ethylhexyl methoxycinnamate was applied twice daily for 3 months by 20 young women. Another control group of seven women received a non-skin lightening formulation. Clinical assessments were made at 1-month intervals. In addition, objective measurements of the hypermelanosis were performed using narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light reflection (ULEV method) and photodensitometry of the corneomelametry test. A significant lightening effect was evidenced beginning the second month of treatment with the whitening formulation. No significant effect was observed with the control product. Melasma is an acquired, chronic hypermelanosis for which therapy remains a challenge.
                To compare the efficacy and safety of a triple combination [TC: fluocinolone acetonide 0.01%, hydroquinone (HQ) 4%, tretinoin 0.05%] vs. HQ 4% after 8 weeks of treatment of moderate to severe facial melasma in Asian patients.
                This was a multicentre, randomized, controlled, investigator-blinded, parallel comparison study. East and South-East Asian patients aged 18 years or older, with a clinical diagnosis of moderate to severe melasma, were enrolled in this study. Patients were enrolled at baseline and treated daily for 8 weeks with TC cream (one application at bedtime) or HQ cream (twice daily). There were four study visits: at baseline and weeks 2, 4 and 8. The primary efficacy variable was the melasma global severity score (GSS). Other outcome measures included Melasma Area and Severity Index, global improvement and patient satisfaction. Safety was assessed through the reporting of adverse events.
                TC had superior efficacy to HQ for the primary variable: 77/120 patients (64.2%) on TC had GSS 'none' or 'mild' at week 8 vs. 48/122 patients (39.4%) on HQ (P < 0.001). The secondary efficacy variables confirmed these results. Patient satisfaction was in favour of TC (90/127, 70.8%, vs. 64/129, 49.6%; P = 0.005). More patients had related adverse events on TC (63/129, 48.8%) than on HQ (18/131, 13.7%) but most were mild and none was severe.
                Efficacy in Asians and patient satisfaction were superior with the fixed TC than with HQ 4%.
The quality of studies evaluating melasma treatments was generally poor and available treatments inadequate. High-quality randomised controlled trials on well-defined participants with long-term outcomes to determine the duration of response are needed.