Does Systemic Metformin Have a Role in Treating Melasma?

BACKGROUND: Melasma is a common pigmentary condition that affects the patients' quality of life and all the prescribed treatment options till now are not satisfactory, especially in dark-skinned patients. OBJECTIVE: To evaluate the efficacy and safety of systemic metformin (1,000 mg and 500 mg) combined with trichloroacetic acid (TCA) peeling versus TCA alone in the treatment of melasma. PATIENTS AND METHODS: The study included 60 melasma patients divided into 3 groups: Group A received systemic metformin (1000 mg/d), Group B received systemic metformin (500 mg/d) and Group C received placebo. The 3 treatment groups were treated by TCA 25% over the whole face bimonthly for a total of 6 sessions. Melasma area and severity index (MASI), and Melasma impact Quality of life Scale (MELASQOL) were used to assess the outcome. RESULTS: There was a statistically significant decrease in the MASI, and the MELASQOL in the 3 studied groups after treatment with significantly better improvement in Group (A) than Group (C) ( p = .045). CONCLUSION: Systemic metformin is a safe and promising therapeutic option for treating melasma.

Characteristics of dermal vascularity in melasma and solar lentigo.

BACKGROUND /PURPOSE: Melasma and solar lentigo (SL) are major benign hyperpigmented lesions, and both have been shown to involve the dermal vasculature. This review discusses current knowledge regarding the clinical characteristics of dermal vascularity in melasma and SL, as well as the results of relevant molecular biological investigations. METHODS: PubMed and Google Scholar were searched in December 2023 to identify articles related to melasma, SL, and the dermal vasculature in these lesions. RESULTS: Vascular morphologies in melasma and SL have been detected by histological and non-invasive methods, including modalities such as optical coherence tomography. Biological studies have indicated that factors secreted from vascular endothelial cells, such as stem cell factor and endothelin-1, can promote melanogenesis. With respect to phototherapy, blood vessel-targeting laser treatments are expected to provide long-term suppression of pigmentation, but this regimen is only effective when dilated capillaries are visible. CONCLUSION: In both melasma and SL, clinical and experimental investigations are revealing the contributions of dermal vascularity to hyperpigmentation. More effective treatment may require identification of hyperpigmentation subtypes. In the future, knowledge of treatment (including phototherapy) is expected to accumulate through reliable and validated non-invasive measurements.

Targeting the dermis for melasma maintenance treatment.

Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma, emphasize the dermal targeting therapy. We investigated maintenance effect of microneedling radiofrequency (RF) for melasma treatment. Subjects with melasma were administered oral tranexamic acid and triple combination cream for 2 months and a randomly assigned half face was treated with RF. After discontinuation of conventional therapy, the half face RF continued monthly over 6 months. Modified melasma area severity index (mMASI) score and L* value by a chromameter were collected monthly. Fifteen subjects were enrolled and eleven completed the 8-month study. At 2nd month of conventional therapy, all subjects showed improvement with a 64% reduction in mMASI score. With continuous RF treatment, the improvement was well maintained; whereas in untreated side, the Δ L* gradually decreased, returning to the baseline after the conventional therapy ended. The continuous microneedling RF therapy is beneficial in maintaining the conventional therapy of melasma suggesting the protective effect of dermal targeting therapy in melasma development.(Clinical Trial registration number: NCT05710068, date of first registration: 02/02/2023).

The efficacy and safety of microneedling with topical tranexamic acid for melasma treatment: A systematic review and meta-analysis.

OBJECTIVE: Microneedling with topical tranexamic acid (TXA) is a novel treatment option for melasma; however, the efficacy and safety of this combined administration therapy is in controversial. This study is conducted to address this issue of this technique in melasma. METHODS: An extensive literature review was performed to identify relevant trials, including randomized split-face studies, randomized controlled trials and prospective non-randomized split-face studies, comparing microneedling plus topical TXA to routine treatments or placebo. The primary outcomes were changes of the Melasma Area Severity Index (MASI)/modified MASI (mMASI)/hemi MASI between before and after treatment, as well as the changes between a particular treatment and microneedling plus TXA. The mean differences (MDs) and 95% confidence intervals (CIs) were calculated for the reduction of melasma severity scores from baseline to each time point. In contrast, the standard mean differences (SMDs) and 95% CIs were calculated for the differences in reduction in melasma severity scores between the experimental and control groups at each time point. RESULTS: A total of 16 trials were included in the systematic review and data synthesis. The pooled analysis demonstrated that MASI, mMASI, and hemiMASI scores decreased significantly at 4 weeks (MD = 1.85; 95% CI = 1.15-2.54), 8 weeks (MD = 3.28; 95% CI = 2.31-4.24), 12 weeks (MD = 4.73; 95% CI = 2.79-6.50), 16 weeks (MD = 3.18; 95% CI = 1.50-4.85), and 20 weeks (MD = 3.20; 95% CI = 1.95-4.46) after treatment when compared with baseline. The reduction in melasma severity scores of microneedling with TXA group at 4 weeks was more significant than the routine treatment group (SMD = 0.97; 95% CI = 0.09-1.86), while insignificant at 8 weeks (SMD = 1.21; 95% CI = -0.17 to 2.59), 12 weeks (SMD = 0.63; 95% CI = -0.03 to 1.29), 16 weeks (SMD = 0.61; 95% CI = -2.85 to 4.07), or 20 weeks (SMD = 1.04; 95% CI = -1.28 to 3.36). CONCLUSION: Despite the high heterogeneity across these studies, the current findings indicated that microneedling with topical TXA is an alternative treatment option for melasma treatment; and more well-designed studies are needed to confirm it.

The role of reflectance confocal microscopy in the diagnosis and management of pigmentary disorders: A review.

BACKGROUND: Reflectance confocal microscopy (RCM) has quickly transitioned from a research tool to an adjunct diagnostic bedside tool, providing the opportunity for noninvasive evaluation of skin lesions with histologic resolution. RCM is an optical imaging technique that uses near-infrared excitation wavelengths and safe low-power lasers. En-face images of different skin layers (up to the superficial dermis) are acquired in grayscale based on the reflective indices of tissue components. Melanin has the highest reflective index (contrast) and appears bright on RCM. AIMS: We present a review of the current literature on the use of RCM in the diagnosis and management of pigmentary disorders. METHODS: We reviewed PubMed and Ovid Medline databases from January 2000 to June 2021, using MeSH key terms: "reflectance confocal microscopy, confocal laser scanning microscopy, pigmentary disorders, treatment, melasma, vitiligo, freckles, solar lentigo, lentigo, tattoo, complications, melanoma, skin cancers, pigmented lesions, post inflammatory, melanin, photoaging" to identify studies and review articles discussing the use of RCM in the diagnosis and management of pigmentary disorders. RESULTS: RCM findings of pigmentary disorders were divided into the following categories: (1) disorders of increased pigmentation (post-inflammatory hyperpigmentation, melasma, Riehl's melanosis, solar lentigines, ephelides, hori nevus, naevus of Ota, café-au-lait macules, melanocytic nevus, melanoma, nevus spilus, labial mucosal melanosis, and mucosal melanoma), (2) disorders of decreased pigmentation or depigmentation (post-inflammatory hypopigmentation, vitiligo, nevus depigmentosus, halo nevus), and (3) exogenous pigmentation (tattoo, ochronosis). CONCLUSION: RCM has been explored and proven valuable for the evaluation and management of pigmentary disorders including melasma, vitiligo, solar lentigines, tattoo, and tattoo-related complications.

The 675-nm wavelength for treating facial melasma.

BACKGROUND: Melasma is an acquired skin problem. It characterises sun-exposed areas, particularly on the face, with irregular borders and bilateral distribution. With this study, we want to strengthen the scientific literature regarding the use of a 675-nm laser device for the treatment of women and men with facial melasma pigmentary and vascular symptoms. MATERIALS AND METHODS: Eighteen patients were treated for facial melasma. A total of three sessions at 30-day intervals were performed with a 675-nm laser device. A five-point Global Aesthetic Improvement Scale was used to separately assess the improvement of the patient's skin 3 months after the last treatment (T1) compared to baseline (T0). The pain during treatment was measured using a Visual Analog Scale of 10 points. The non-ablative laser system used emits red light with a wavelength of 675 nm through a 13 × 13 mm scanning system. RESULTS: At T1 , a consistent improvement in the pigmentary and vascular components was visible. This is always combined with a considerable reduction in vascular expression. CONCLUSION: Our research shows that individuals with Fitzpatrick phototypes II to III can treat facial melasma with the 675-nm laser source system without risk. Due to its interaction with melanin, collagen and haemoglobin chromophores, as well as its excellent capacity to penetrate tissues with less heating, this system is promising in the treatment of pigmentary and vascular illnesses such as melasma. The great success of the technology we used came from the reduced levels of inflammation produced after the treatments and the low energy level implied.

A novel treatment for Riehl's melanosis targeting both dermal melanin and vessels.

BACKGROUND/PURPOSE: Riehl's melanosis is a difficult-to-treat condition characterized by persisting dermal hyperpigmentation. This study aimed to evaluate the efficacy of a histology-specific targeted therapy for Riehl's melanosis. METHODS: Skin biopsy samples of Riehl's melanosis were assessed to identify histology-specific targets for treatment. Subsequently, the efficacy of a combination involving a fractional picosecond laser and a pulsed dye laser (PDL) targeting the dermal melanin and vessels, respectively, was evaluated. Clinical improvement was assessed using the dermal pigmentation area and severity index (DPASI). The treatment outcomes were compared to those of a control, in this case a single laser treatment solely targeting pigmentation. RESULTS: Histological and immunohistochemical analyses identified dermal melanin pigment and dilated vessels as treatment targets for Riehl's melanosis. The combined treatment of the fractional picosecond laser and PDL showed a significant reduction of the DPASI scores, which was significantly better than the control group. Patients who underwent the combined laser treatment indicated high levels of satisfaction with no adverse events except of transient erythema and oedema. CONCLUSION: The combined treatment of a fractional picosecond laser and a PDL was more effective for Riehl's melanosis compared to single laser treatment. The treatment targets both dermal pigmentation and dilated vessels, offering promising results for those working to manage Riehl's melanosis.

Melasma in people with darker skin types: a scoping review protocol on prevalence, treatment options for melasma and impact on quality of life.

BACKGROUND: Melasma is one of the most encountered dermatoses in dermatology and skin care clinics. It is a challenging chronic, recurrent condition associated with hyperpigmentation. Its aetiology is poorly understood. Melasma affects all races and gender but is more prevalent in women with darker skin types. Being a facial lesion, melasma has a severe impact on quality of life due to its disfigurement. While many modalities of treatment for melasma exists, unfortunately, effectiveness and safety remain a huge concern. Treatment modalities are variable and often unsatisfactory. The objective of this scoping review is to systemically map available evidence from literature regarding melasma on people with darker skin types, garner insight as to how melasma affects the quality of life and begin to investigate and gain understanding on effectiveness of different treatments used for melasma. METHODS: A scoping review guided by Arksey and O'Malley's framework, the enhancements and recommendations of Levac, Colquhoun and O'Brien, Daudt and associates and the 2015 Johanna Briggs Institute's guidelines will be conducted. Systematic electronic searches of databases and search engines will include Scopus, PubMed, CINAHL Complete, Cochrane, Science Direct, and Web of Science which will be conducted to attain published peer-reviewed articles of all study designs excluding reviews and grey literature. All literature that meets the inclusion criteria, research question and sub-question will be included in this review. All the retrieved literature will be exported to an Endnote X20 library. Quality appraisal of the included articles will be conducted using the mixed methods appraisal tool (MMAT) 2018 version. DISCUSSION: We anticipate mapping relevant literature on the melasma, investigating the effectiveness of treatment options of melasma as well as evaluating its association with quality of life in people with darker skin types. This study is likely to reveal research gaps, which could guide future implementation research on melasma treatment interventions. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered a priori with OSF and is accessible on this link: https://osf.io/ru3jc/ .

Unveiling the mystery of Riehl's melanosis: An update from pathogenesis, diagnosis to treatment.

Riehl's melanosis is a hyperpigmentation disorder that has a significant psychological and social impact on individuals. In the past 10 years, new categories have been developed, raising questions about how to classify Riehl's melanosis. The mechanism of this disease remains unclear, although the type IV hypersensitivity response caused by allergic sensitization, as well as genetic, ultraviolet radiation, and autoimmune factors, is to blame. Clinical manifestation, dermoscopy, reflectance confocal microscopy, patch/photopatch testing, histopathology, and a novel multimodality skin imaging system have been used for the diagnosis. A variety of therapies including topical skin-lightening agents, oral tranexamic acid, glycyrrhizin compound, chemical peels, and lasers and light therapies (intense pulsed light, 1064-nm Q-Switched Nd: YAG laser, 755-nm PicoWay laser, nonablative 1927-nm fractional thulium fiber laser, new pulsed-type microneedling radiofrequency), with improved effectiveness. The latest findings on possible biomarkers and their relationship to other autoimmune diseases were also summarized.

Skin hyperpigmentation index in melasma: A complementary method to classic scoring systems.

BACKGROUND: Due to relapsing nature of melasma with significant impact on quality of life, an objective measurement score is warranted, especially to follow-up the patients with melasma and their therapy response in a quantitative and precise manner. AIMS: To prove concordance of skin hyperpigmentation index (SHI) with well-established scores in melasma and demonstrate its superiority regarding inter-rater reliability. Development of SHI mapping for its integration in common scores. METHODS: Calculation of SHI and common melasma scores by five dermatologists. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) and concordance by Kendall correlation coefficient. RESULTS: Strong concordance of SHI with melasma area and severity index (MASI)-Darkness (0.48; 95% CI: 0.32, 0.63), melasma severity index (MSI)-Pigmentation (0.45; 95% CI: 0.26, 0.61), and melasma severity scale (MSS) (0.6; 95% CI: 0.42, 0.74). Using step function for mapping SHI into pigmentation scores showed an improvement of inter-rater reliability with a difference in (ICC of 0.22 for MASI-Darkness and 0.19 for MSI-Pigmentation), leading to an excellent agreement. CONCLUSION: Skin hyperpigmentation index could be an important additional cost-and time-conserving assessment method, to follow-up the patients with melasma undergoing brightening therapies in clinical studies, as well as in routine clinical practice. It is in strong concordance with well-established scores but superior regarding inter-rater reliability.

Efficacy of topical vitamin C in melasma and photoaging: A systematic review.

BACKGROUND: Vitamin C is a micronutrient present in high concentrations in normal skin and a highly prescribed cosmeceutical, well known for protecting against ultraviolet-induced pigmentation and regulating collagen production. However, there is a lack of studies evaluating the efficacy of topical vitamin C in photoaging and melasma, with this systematic review being the first to assess the existing evidence. AIM: This systematic review aims to assess whether topical vitamin C could be effective in reversing photoaging signs and treating melasma. METHODS: Prospective, randomized controlled trials assessing protocols with topically applied vitamin C in patients with melasma or photodamage were searched in Medline, CENTRAL, and Scopus databases until the 12th of May 2022. Risk of bias was conducted in accordance with Cochrane Collaboration's tool for assessing the risk of bias in randomized trials, using RevMan 5.0. RESULTS: Seven publications were included, with 139 volunteers in total. Studies that evaluated the topography of skin indicated that the treated skin appeared smoother and less wrinkled, which was supported by biopsies data. On objective assessments of pigmentation, there was a significant lightening of the skin treated. Hydration improved equally in the vitamin C and placebo-treated sites. CONCLUSIONS: This study revealed that vitamin C is effective in treating uneven, wrinkled skin and has depigmenting properties, but long-term use may be needed to achieve noticeable changes. Q-switched Nd:YAG laser-associated protocols appear beneficial in enhancing vitamin C effects. Topical vitamin C may be a suitable alternative for melasma and photoaging, but more studies are needed to confirm these results and assess the ideal vitamin C concentration.

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.

Efficacy and safety of picosecond laser for the treatment of melasma: a systematic review and meta-analysis.

Multiple laser modalities have been used for melasma treatment. However, the effectiveness of picosecond laser in treating melasma remains unclear. This meta-analysis investigated the effectiveness and safety of picosecond laser for melasma treatment. Randomized controlled trials (RCTs) comparing picosecond laser with conventional treatment for melasma were searched through five databases. The melasma area severity index (MASI)/modified MASI (mMASI) was used to quantify the degree of melasma improvement. Standardized mean differences and 95% confidence intervals were calculated using Review Manager for result standardization. Six RCTs, which used picosecond laser at 1064, 755, 595, and 532 nm wavelengths, were included herein. Picosecond laser significantly reduced the MASI/mMASI, but the results were highly heterogeneous (P = 0.008, I2 = 70%). In the subgroup analysis of 1064 and 755 nm picosecond lasers, 1064 nm picosecond laser significantly reduced the MASI/mMASI with no significant side effects (P = 0.04). Meanwhile, 755 nm picosecond laser did not significantly improve the MASI/mMASI compared with topical hypopigmentation agents (P = 0.08) and caused post-inflammatory hyperpigmentation. Other laser wavelengths could not be used in the subgroup analysis owing to an insufficient sample size. Picosecond laser at 1064 nm is safe and effective for melasma treatment. Picosecond laser at 755 nm is not superior to topical hypopigmentation agents in treating melasma. The exact efficacy of other wavelengths of picosecond laser for melasma treatment remains to be verified in large-scale RCTs.

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.

Safety and efficacy of superficial micro-focused ultrasound with visualization for melasma in Asians: An uncontrolled pilot study.

BACKGROUND: The pathophysiology of melasma is multifactorial, resulting in treatment resistance and a high recurrence rate. Recent research suggests that focused ultrasound might treat melasma effectively. OBJECTIVES: To investigate the efficacy and safety of superficial micro-focused ultrasound with visualization (MFU-V) for melasma in Asians. METHODS: Patients (n = 20) with mixed melasma on both cheeks received 2 MFU-V treatments spaced 1 month apart. At monthly visits over 5 months, treatment efficacy and safety were evaluated. Standardized photographs were clinically assessed using the modified Melasma Area and Severity Index (mMASI), and 6-point grading scales for melasma lightening and area of involvement. Patients provided pain, global aesthetic improvement scale (GAIS), and satisfaction assessments. RESULTS: In 40 cheeks, the mean mMASI score was significantly reduced from 13.2 at baseline to 2.4 at month 4, and 2.8 at month 5. Twenty-nine cheeks (72.5%) showed lightening of melasma at month 4 that persisted until month 5, with improvements up to 75% compared to baseline. Melasma area decreased overall, with sites containing >30% melasma involvement decreasing from 55% to 20% by month 5, and none with 70%-89% involvement. Melasma lightening and area improved visibly in 40% and 20% of cheeks, respectively, as early as 1 month after index MFU-V treatment. Improvements continued after the second treatment and persisted until study closure, correlating with patient GAIS and satisfaction scores. Procedure was well tolerated with only mild-to-moderate pain reported in 92.5% of treatments. CONCLUSION: Superficial MFU-V is a safe and effective treatment for melasma.

Disorders of hyperpigmentation. Part II. Review of management and treatment options for hyperpigmentation.

Key challenges in the management of pigmentary disorders such as melasma and postinflammatory hyperpigmentation are their resistance to treatment, tendency to recur after treatment, and the risk of exacerbating hyperpigmentation with many treatment modalities. The second article in this 2-part continuing medical education series on pigmentary disorders focuses on the evidence behind medical and procedural treatments of dyschromias, including photoprotection, topical lightening agents, oral agents, chemical peels, and laser therapy.

Efficacy and Safety of Low Fluence Nd:YAG Laser Treatment in Melasma: A Meta-Analysis and Systematic Review.

BACKGROUND: Low-fluence, multisession therapy of Nd:YAG laser has been widely used for treating melasma. OBJECTIVE: To evaluate the efficacy and safety of low-fluence Nd:YAG laser toning for melasma using a systematic review and meta-analysis. METHODS: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched till December 2020. A total of 50 studies (1,772 patients) and 66 studies were selected for the evaluation of the efficacy and complications, retrospectively. RESULTS: The mean Melasma Area and Severity Index/modified Melasma Area and Severity Index scores for laser toning as monotherapy at <4, 4 to <8, 8 to <12, 12 to <24, and ≥24 weeks after treatment compared with that at pretreatment were -0.51, -0.91, -0.97, -0.92, 0.01 SD, whereas those as combination therapy were -1.64, -1.26, -0.94, not available, -1.45 SD, respectively. An increase in light value and a decrease in relative lightness index have remained up to 8 weeks after laser toning. Complications including hypopigmentation/leukoderma, postinflammatory hyperpigmentation, and recurrence were noted. The incidence of hypopigmentation/leukoderma correlated with the number of laser sessions (p = .036). CONCLUSION: Low-fluence Nd:YAG laser toning as combination therapy has shown better efficacy than monotherapy and the efficacy seems to diminish with time. This study suggests the positive correlation of hypopigmentation/leukoderma with the number of laser sessions.