Melanoma of the central nervous system based on neurocutaneous melanocytosis in childhood: A rare but fatal condition.

BACKGROUND: Melanomas of the central nervous system (CNS) based on neurocutaneous melanocytosis (NCM) are exceptionally rare in childhood and have been described only sporadically. Rapidly progressive disease may represent a major challenge for treating physicians, especially given the limited knowledge about this condition. This analysis aimed to increase knowledge about the occurrence and treatment of these malignancies. PROCEDURE: Data on diagnosis, treatment, and outcome of patients aged 0-18 years with CNS melanoma based on NCM recorded in the German Registry for Rare Pediatric Tumors (STEP registry) were analyzed. Additionally, published case reports on this condition were analyzed. RESULTS: In STEP, five patients with leptomeningeal melanoma based on NCM were identified, with a median age at melanoma diagnosis of 3.7 years. Various multimodal treatments were performed: (partial) resection (n = 4), irradiation (n = 2), trametinib (n = 3), different cytostatics (n = 2), and anti-GD2 immunotherapy (n = 1). All patients died between 0.3 and 0.8 years after diagnosis. Including published case reports, 27 patients were identified with a median age of 2.8 years at melanoma diagnosis (range: 0.2-16.6). Fourteen of 16 cases with reported data had a NRAS alteration (88%), particularly NRAS p.Q61K (85%). In the expanded cohort, no patient survived longer than 1 year after diagnosis despite multimodal therapy (including trametinib; n = 9), with a median survival of 0.4 years (range 0.1-0.9). CONCLUSIONS: CNS melanomas based on NCM in childhood are aggressive malignancies without curative treatment to date. Therapeutic approaches must be individualized. Genetic tumor sequencing is essential to improve understanding of tumorigenesis and potentially identify new therapeutic targets.

Evaluation of systemic oxidative stress in patients with melasma.

BACKGROUND: The significance of oxidative stress has been assessed and proven in the etiopathogenesis of many cutaneous disorders, but there are few studies that evaluated the role of only some factors involved in oxidative stress in patients with melasma. OBJECTIVE: This study aimed to examine the role of oxidative stress in melasma and assess the relationship between systemic oxidative stress and the severity and extension of this disease. METHODS: In this study, the serum levels of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), malondialdehyde (MDA), protein carbonyl (PC), selenium (Se), vitamin E (vit E), and vitamin C (vit C) of fifty patients with melasma were compared with those of fifty controls. RESULTS: The serum level of MDA was significantly higher in the melasma group (3.08 vs. 2.35 U/mL; p < 0.05), and it was positively correlated with the severity (r = 0.4; p < 0.001) and extension (r = 0.3; p < 0.05) of the disease. Furthermore, the serum level of vit C was significantly lower in melasma patients (2.16 vs. 2.57 µg/mL; p < 0.001). CONCLUSION: Systemic oxidative stress has a key role in the etiopathogenesis of melasma. Serum concentrations of MDA and vitamin C are indicators of this impairment.

Effect of dual-optical pulses with temporal energy distribution on laser ablation performance in in vivo zebrafish model.

A Q-switched laser system has been used in a single-pulse mode for skin melasma treatments because of instant heat deposition in the target. Despite the efficient ablation of the melanophores in the skin, the single, high-fluence pulse often causes undesirable damage to the surrounding tissue, leading to high recurrence rates. This study aims to investigate the feasibility of dual-optical pulses with a temporal energy distribution on the melasma treatment in in vivo zebrafish models in comparison to that of the single optical pulse. Based on the optical detection, the dual-optical pulses had a temporal energy distribution ratio of 4:1 and an interval of 61 µs between the two consecutive pulses. According to the histological analysis, the dual pulses removed melanophores and induced a few apoptotic nuclei with minimal recurrence. This study demonstrated that the feasibility of dual-optical pulses (energy ratio = 4:1) could enhance the laser ablation performance in vivo.

Microneedling with glutathione versus microneedling alone in treatment of facial melasma: Split-face comparative study.

BACKGROUND: Melasma is a distressing disfiguring acquired pigmentary disorder especially affecting females and it is of high tendency of recurrence. Up till now, treatment of melasma is a challenging problem. OBJECTIVES: We evaluated the effectiveness of microneedling with glutathione versus microneedling alone in treatment of melasma. PATIENTS AND METHODS: In this study, 29 adult females with epidermal type of melasma (confirmed with Wood's light examination) were enrolled. The affected area was subjected to microneedling using dermapen followed by application of glutathione solution on the right side only. This session was performed every 2 weeks for 3 months (six sessions for every patient). The response to therapy was measured using modified melasma area and severity index (m MASI) that were calculated on each side of the face (Hemi- m MASI) before treatment sessions. RESULTS: There was statistically significant reduction in the mean of Hemi- m MASI score over the sessions on both sides of the face but the right side (microneedling with glutathione) showed more reduction and earlier response to therapy than the left side (microneedling alone). On the left side, mean of Hemi- m MASI score before and after sessions was (4.06 ± 1.91, 2.31 ± 1.450) and on the right side, it was (4.21 ± 2.08, 1.96 ± 1.30), respectively and this was statistically significant. Percentage of improvement on the left side was 46.92 ± 16.30 (%) while on the right side was 55.17 ± 15.50 (%) and this was statistically significant. CONCLUSIONS: Microneedling is an effective promising tool in treatment of melasma and its combination with glutathione as a whitening agent, increases and accelerates its efficacy. So, combined therapy is more preferred than monotherapy in treatment of facial melasma.

Efficacy and Safety of Picosecond Laser in the Treatment of Melasma: A Network Meta-analysis.

BACKGROUND: The role of lasers in the treatment of melasma and acquired hyperpigmentation disease of the skin has been suggested by clinicians. However, there is no consensus on the most efficient and safe treatment method. OBJECTIVE: To systematically evaluate the efficacy and safety of picosecond laser in the treatment of melasma. METHODS AND MATERIALS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese scientific journal database, and Wanfang database were searched. The data for therapeutic efficacy, melasma area and severity score, and incidence rate of adverse reactions were extracted from the included studies. RESULTS: A total of 20 studies involving 1,182 patients were included in this network meta-analysis. Combined therapy with carbamic acid and 1064-nm picosecond laser was the best measure. Melasma area and severity index score of patients after low-power fractional CO2 laser treatment was higher than that of patients after the treatment with 1064-nm picosecond laser. CONCLUSION: Aminomethyl cyclic acid combined with 1064-nm picosecond laser may have the highest effective rate after treatment. Low-power fractional CO2 laser provided the lowest melasma area and severity index score after treatment, and the incidence rate of adverse reactions after treatment, was highest when intense pulsed light was used.

Comparative effectiveness and safety of topical methimazole 5% monotherapy versus combination of Q-Switched Nd: YAG Laser and topical methimazole 5% in patients with refractory melasma.

INTRODUCTION: Melasma is an acquired pigmentary disorder which currently has no definitive treatment. Although topical drugs containing hydroquinone are the basis of treatments, they are usually associated with recurrence. We aimed to evaluate the effectiveness and safety of monotherapy with topical methimazole 5% versus combination of Q-Switched Nd: YAG Laser and topical methimazole 5% in patients with refractory melasma. METHODS: A total of 27 women with refractory melasma were included. We applied topical methimazole 5% (once a day) with three passes of QSNd: YAG laser (Wavelength: 1064 nm, pulse energy: 750 mJ, fluence: 1.50  J/cm2 , spot size: 4 × 4 mm, hand piece: fractional, JEISYS company) for six sessions on the right half of the face, and topical methimazole 5% (once a day) on the left half of the face, for each patient. The treatment course was 12 weeks. Evaluation of effectiveness was done with the Physician Global Assessment (PGA), Patient Global Assessment (PtGA), Physician satisfaction (PS), Patients satisfaction (PtS), and mMASI score. RESULTS: PGA, PtGA, and PtS were not significantly different between the two groups at any time (p > 0.05). PS in the laser plus methimazole group was significantly better than methimazole group at 4th, 8th, and 12th weeks (p < 0.05). The rate of PGA improvement in the combination group was significantly better than the monotherapy over time (p < 0.001). The changes of mMASI score between the two groups did not significantly differ at any time (p > 0.05). There was no significant difference in the adverse events between the two groups. CONCLUSION: Combination therapy with topical methimazole 5% and QSNY laser can be considered as an effective way to treat refractory melasma.

Perspectives of topical formulations for melasma.

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.

Trichloroacetic Acid With Microneedling Versus Trichloroacetic Acid Alone for Treating Melasma.

BACKGROUND: Melasma is a common acquired disorder of hyperpigmentation which is difficult to treat. OBJECTIVE: We aim to evaluate the efficacy and safety of combined microneedling with trichloroacetic acid in the treatment of melasma. PATIENTS AND METHODS: Forty women with facial melasma were included and randomly classified into 2 groups. Group A included 20 patients treated with bimonthly session of trichloroacetic acid 25% peeling (8 sessions) combined with a monthly session of microneedling (4 sessions). Group B included the other 20 patients that were treated by bimonthly trichloroacetic acid 25% peeling session (8 sessions) alone. RESULTS: After 1 and 3 months of treatment, the mean melasma area and severity index, modified melasma area and severity index, and melasma severity index scores showed significant improvement in each group (p < .05 for each). At 1 and 3 months, the mean percentages of change of all scores were significantly higher in group A than group B (p < .05). CONCLUSION: Combined trichloroacetic acid peel with microneedling is effective and a safe option for treating melasma.

Treatment of melasma by a combination of intense pulsed light with advanced optimal pulse technology and human-like collagen repair dressing: A case series study.

To observe the efficacy and safety of a combination of intense pulsed light (IPL) with advanced optimal pulse technology (AOPT) and human-like collagen repair dressing in the treatment of melasma. Ten patients with melasma were treated using IPL with AOPT once a month for a total of 8 times, and received the treatment of external human-like collagen repair dressing after each operation. The efficacy was evaluated with the modified Melasma Area Severity Index (mMASI) score and satisfaction score, respectively, before treatment, after each treatment and at 4 months after the end of the whole treatment course. The melasma was significantly lightened in all 10 patients after 8 times of treatments. The mMASI score before treatment was (8.6 ± 3.8) points, which decreased significantly to (5.1 ± 2.7) points after 8 times of treatments, and there was a significant difference in mMASI score between before and after 8 times of treatments (P = .001). The mMASI score was (3.3 ± 2.2) points at 4 months after the end of whole treatment course, and there was no significant difference in mMASI score between after 8 times of treatments and 4 months after the end of whole treatment course (P > .05). The satisfaction score was (7.2 ± 1.4) points after 8 times of treatments and (7.1 ± 1.4) points at 4 months after the end of whole treatment course, there was no significant difference in satisfaction score between after 8 times of treatments and 4 months after the end of whole treatment course (P > .05). A combination of IPL with AOPT and human-like collagen repair dressing can effectively decrease the severity of melasma, and is associated with a higher patient satisfaction score and a lower risk of relapse after discontinuation of treatment.

Single and combined 1064 nm Q-switched Nd: YAG laser therapy in melasma: A meta-analysis.

PURPOSE: This article attempted to describe the efficacy and safety of 1064QNYL in combination with other treatments for refractory melasma. METHODS: Two researchers independently retrieved randomized controlled trials (RCTs) according to inclusion and exclusion criteria. Primary outcome was evaluated with MASI and mMASI scores in control group and experiment group. The secondary outcome was evaluated with MI scores. We calculated 95% CI of standardized mean difference (SMD) and heterogeneity of the included literature by Higgins I2 test, and assessed publication bias by Funnel plots, Egger's, and Begg's tests. RESULTS: A total of 12 articles including 322 subjects were analyzed. Experiment group was treated with 1064QNYL combined with single treatment (e.g., PDL, IPL, RF, and TA). Control group was treated with 1064QNYL alone. A greater reduction of Melasma Area and Severity Index (MASI)/modified Melasma Area and Severity Index (mMASI) scores were shown in experiment group than that in control group at the end of the treatment (SMD, -0.37; 95% CI -0.70 to -0.04, p = 0.03, I2  = 33%). The SMD of MI scores further supported this conclusion by -0.32 (95% CI -0.63 to -0.02, p = 0.04, I2  = 27%). As for adverse events (AEs), combined treatment gave rise to more mild burning, stinging, and erythema that resolved spontaneously. Several studies reported focal purpura, punctate leukoderma, hyperpigmentation, hypopigmentation, and so on. CONCLUSION: Combined 1064QNYL treatment was better than single laser treatment, with the highest short-term benefit and long-term follow-up to maintain the effect in favor of combined treatment.

Medical therapies for melasma.

Melasma is a common malady affecting all races with a higher incidence in Hispanics, Middle Eastern, Asians, and African origin females (Fitzpatrick skin phototypes III-V). Women are affected much more often than men. Melasma remains a significant cause of cosmetic morbidity and psychosocial embarrassment affecting quality of life necessitating effective and reliable treatment. Unfortunately, treatment remains unsatisfactory due to limited efficacy, adverse effects, and relapses after stopping treatment. Although chemical peels, laser and light therapies and dermabrasion may have utility, the evidence available for their efficacy is limited and they often cause post-inflammatory hyperpigmentation, particularly in individuals with darker skin types. Medical therapies remain mainstay in the management of melasma. The triple combination, hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% (Triluma, Galderma, Ft. Worth Texas, often modified incorporating different corticosteroids) remains the only US FDA-approved treatment for melasma and is the gold standard due its demonstrated efficacy across ethnicities. Oral tranexamic acid alone or in combination with other modalities has also shown significant efficacy. Several cosmeceuticals and botanical extracts used as skin lightening agents have been demonstrated to be useful. Physical sunscreens containing zinc oxide, iron oxide, titanium dioxide, and silicones provide photoprotective and camouflage effect. We propose that a multimodality approach to the treatment of melasma is the most effective treatment approach. This review is focused on the medical therapies for melasma.

Bilirubin as a new antioxidant in melasma.

BACKGROUND: Oxidative stress and its role in the pathogenesis of cutaneous diseases have been widely investigated. However, there are few studies that have solely assessed the contribution of intracellular antioxidants in the etiopathology of melasma. Furthermore, there are convincing reports about antioxidant properties of bilirubin (Bil) and uric acid (UA) in some skin disorders but not melasma. OBJECTIVE: This study aimed to determine serum levels of two major extracellular antioxidants (Bil and UA) levels in patients with melasma and their correlation with the severity and extent of the disease. METHODS: In this case-control study, the serum levels of bilirubin and uric acid of 50 melasma patients were compared with 50 healthy controls. Moreover, the correlation of serum concentrations of these antioxidants with the extent and severity of the disease were assessed. RESULTS: The serum concentration of Bil was significantly higher in the case group (p < 0.05). Furthermore, serum Bil level had a positive correlation with the extent of the melasma (correlation coefficient, +0.3; p < 0.05). No significant difference was found between the serum concentrations of UA between the study and control group. Neither Bil nor UA had a significant correlation with the severity of the disease. CONCLUSION: Oxidative stress may play a major role in the etiopathology of melasma and bilirubin, as an antioxidant, could be involved in the process of oxidative stress.