Facial Melasma Research Articles

Randomized, Double-Blinded, Split-Face Study Comparing the Efficacy and Tolerability of Two Topical Products for Melasma

Background: Melasma is a common disorder of hyperpigmentation that disproportionately affects individuals with skin of color. There is a paucity of studies evaluating non-hydroquinone (HQ) topical therapies for the treatment of melasma in darker skin types. Objective: To compare the safety, efficacy, and tolerability of a HQ-free, retinol-free cosmetic topical brightener (CTB) and HQ 4% in the treatment of moderate symmetric facial melasma in patients with Fitzpatrick skin types (FST) III–VI. Methods & Materials: This was a randomized, double-blinded, split-face clinical trial. Eighteen adult patients with facial melasma were treated with CTB and HQ 4%, each to a different side of the face, twice daily for 12 weeks. Clinical assessments included half-face Melasma Area Severity Index (MASI), Overall Hyperpigmentation scale, and Melasma Severity Rating Scale (MSRS). Patients completed a Melasma Quality of Life (MelasQoL) questionnaire and clinical photographs were taken at each visit. Results: CTB and HQ 4% demonstrated statistically significant improvements in half-face MASI, Overall Hyperpigmentation, MSRS and MelasQol compared to baseline. HQ 4% showed statistically significant improvements in MSRS at week 12 compared to CTB, but was non-superior for all other clinical endpoints. Conclusion: HQ-free, retinol-free CTB and HQ 4% both are effective and well-tolerated in the treatment of moderate facial melasma in FST III–VI. J Drugs Dermatol. 2020;19(9):822-827. doi:10.36849/JDD.2020.5353

Efficacy and safety of oral tranexamic acid as an adjuvant in Indian patients with melasma: a prospective, interventional, single-centre, triple-blind, randomized, placebo-control, parallel group study.

Melasma is a chronic recalcitrant pigmentary disorder whose treatment frustrates physician and patient alike. Tranexamic acid, a plasmin inhibitor, has demonstrated hypopigmenting properties. To compare safety and efficacy of combination of oral tranexamic acid (TXA) and topical fluocinolone-based combination cream (FbTC) with that of topical FbTC alone in melasma. One hundred and eighty patients patients of facial melasma of either sex attending dermatology OPD were screened. Consenting 130 participants were randomized into two blinded groups with 65 patients in each group. Group A patients received oral tranexamic acid 250mg and oral ranitidine 150mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01%, tretinoin 0.05% and hydroquinone 2% once daily, and Group B was asked to take placebo tablets (calcium lactate and multivitamin) and apply the cream only for 12weeks. Response was evaluated using modified melasma area severity index (mMASI) and graded mMASI improvement at 4th, 8th and 12th weeks, and at 24th week for recurrence. Data were analysed using SPSS software. Results were analysed in 120 patients who completed the study with 61 and 59 patients in group A and B, respectively. Demographic profile was equally distributed in both the groups. In group A, 13.1% patients showed marked improvement (>75%) in mMASI as compared to group B (1.7%) at 4th week. By 12th week, 65.6% patients had marked improvement in group A in contrast to only 27.1% in group B. At 24th week, group A (65.6%) had sustained improvement as compared to group B (11.9%) despite stopping treatment; all of which were statistically significant. Recurrence observed was 18.03% in group A vs. 64.4% in group B at 24th week. Oral tranexamic acid is definitely a boon to the armamentarium of melasma management and should be used as an adjuvant to fluocinolone-based triple combination cream for a faster, sustained improvement and to prevent recurrence.

Micro-needling versus fractional carbon dioxide laser for delivery of tranexamic acid in the treatment of melasma: A split-face study.

Tranexamic acid (TXA) in oral, topical, and intra-dermal injection routes showed efficacy in melasma treatment. Micro-needling and fractional carbon dioxide (CO2 ) laser were reported to enhance the drug delivery of TXA. This study aimed at comparing the use of micro-needling and fractional CO2 laser for drug delivery of TXA in the treatment of facial melasma. Thirty female patients with bilateral symmetrical facial melasma were subjected to micro-needling, for one side of the face, and fractional CO2 laser, for the other, followed by an immediate topical application of TXA solution 4mg/mL. Patients received six biweekly sessions. Two weeks after the last session, a significant reduction in baseline modified melasma area and severity index (mMASI) score was observed on both sides. The mean±SD baseline mMASI dropped from 3.43±1.84 to 1.59±1.51 (mean reduction 57.73%,P<.001) and from 3.51±1.84 to 1.78±1.51 (mean reduction 55.82%,P<.001) in the micro-needling-treated side and in the fractional CO2 laser-treated side, respectively. However, no statistically significant differences were found between the two sides (P=.81). Micro-needling and fractional CO2 laser are equally safe and effective for the delivery of TXA in the treatment of facial melasma.

Dermoscopy as a useful tool for evaluating melasma and assessing the response to 1064-nm Q-switched Nd:YAG laser.

Melasma is a hard-to-manage disorder with considerable relapsing behavior. Dermoscopy emerged to help in comprehensive evaluation of pigmentary disorders and melasma. The aim of the study was to evaluate the potential role of dermoscopy in assessing melasma and monitoring the efficacy of 1064-nm low-fluence Q-switched neodymium:yttrium-aluminum-garnet (QS Nd:YAG) laser. A total of 31 patients with facial melasma were included. A total of five laser sessions were performed with 2-week intervals. Patients were evaluated at baseline and 2 weeks after the last session (at the 10th week) by using digital photography, modified melasma area and severity index (mMASI), and colorimetry, as well as dermoscopic score for pigment and vascular elements. Adverse effects were reported. Postlaser sessions, mMASI scores as well as the colorimetric melanin and erythema indices had showed significant improvement. The "dermoscopic score of pigmentary and vascular elements" displayed significant change and confirmed the improvement. Side effects were tolerable. mMASI, colorimetry, and dermoscopy had ascertained the efficacy of low-fluence 1064-nm QS Nd:YAG laser in melasma; however, dermoscopy is superior to other assessments as it can help in the diagnosis of melasma besides the follow-up assessment and can precisely detect the detailed changes in response to treatment.

The efficacy in treatment of facial melasma with thulium 1927-nm fractional laser-assisted topical tranexamic acid delivery: a split-face, double-blind, randomized controlled pilot study.

This split-face, double-blind, randomized controlled study examines the efficacy of fractional thulium laser (FTL)-assisted delivery of topical tranexamic acid (TXA) compared with FTL alone as a treatment option for melasma. Forty-six adults with Fitzpatrick skin types III-V and recalcitrant melasma underwent four weekly treatments with fractional 1927-nm thulium laser on both sides of the face. Immediately after treatment, TXA was applied to one side of the face and normal saline solution (NSS) to the contralateral side as control under occlusion. Melanin index (MI), modified MASI (mMASI), and patients' self-assessed improvement scores were measured at baseline, 1 week, 4 weeks, and 3- and 6 months after the final treatment and were examined statistically with a paired sample t test with significance set at p ≤ 0.05. The majority of the participants (95.7%, n = 44) were female with Fitzpatrick skin type IV (82.6%) and a mean age of 48.0 ± 10.0 years. Twenty-nine individuals were able to be followed up until the 6-month assessment. Significant improvement from baseline was seen in both the MI and mMASI scores for both the TXA and control sides at 3 months, with no statistically significant difference between sides. By the 6th month, significant differences in MI and mMASI scores from baseline were still noted, except in the MI for controls. The patients' self-assessment showed similar patterns. No serious adverse events were reported for either group. A regimen of FTL-assisted delivery of TXA over a 4-week period is a safe and effective treatment option for melasma, producing significant improvement up to 3 months. Results further would suggest a repeat regimen every 3 months could be useful for treatment of recalcitrant melasma.

A clinical and dermatoscopic study of melasma

Melasma is an acquired hypermelanosis that occurs exclusively in sun-exposed area mostly on face and rarely on the neck and forearms. It is more common in women and in Asians. Exact pathogenesis remains elusive, however, genetic predisposition and ultraviolet light exposure seem to play an important role.The aim of this study was to evaluate facial melasma clinically and dermatoscopically and to compare the consistency of the findings with respect to each type of melasma. Dermatoscopy is increasingly being used for diagnosis of pigmentary disorders other than malignancy. Hospital based cross sectional descriptive study. Study was conducted in the Dermatology department of Yenepoya Medical College and Hospital on 110 patients during the period of December 2016 to June 2018.Clinical examination includes standard dermatological examination along with Wood’s lamp and dermatoscopic examination (Detailed format attached).Heine Delta 20 plus Dermatoscope was used for evaluation of the lesions.: A total of 110 patients with clinical diagnosis of melasma attending the Department of dermatology in Yenepoya medical college were studied during a period of 18 months. Maximum number of patients (35.5%) belonged to the age group between 31 and 40 years. Study showed a female preponderance (69.1%) . On the basis of Fitzpatrick skin type, patients with Type IV (90%). With respect to occupation housewives (60%) and manual labourers /farmers (25.5%) formed the majority indicating chronic sunexposure to be a leading cause for melasma. Patients having Centrofacial pattern predominated with 59.1% of the total. In 43.6% of the women cycles were regular, 5.45% had irregular cycles and 20.9% of the women had attained menopause. We found that 66.4% of the patients had a moderate MASI score. Under Wood’s lamp examination patchy enhancement was seen in 56.4% of the patients indicating a mixed pattern. Among the various patterns observed reticuloglobular pattern dominated our study with 85.45% of patients being positive for the pattern. In our study patients presented with some additional features under dermatoscopy namely telangiectasia (36.1%), followed by depigmentation (24.5%). On the basis of dermatoscopy, 64.5% predominantly showed an epidermal pattern.Dermoscopy serves as useful tool in assessing the type of melasma based on the MASI score.

Efficacy and safety of microneedling and oral tranexamic acid in the treatment of facial melasma in women: An open, evaluator-blinded, randomized clinical trial

Efficacy and safety of microneedling and oral tranexamic acid in the treatment of facial melasma in women: An open, evaluator-blinded, randomized clinical trial

Comparative Efficacy of a 35% Glycolic Acid Peel Alone or in Combination With a 10% and 20% Trichloroacetic Acid Spot Peel for Melasma: A Randomized Control Trial

To study and compare the therapeutic efficacy and side effects of a 35% glycolic acid (GA) full face peel alone or in combination with a 10% or 20% trichloroacetic acid (TCA) spot peel for facial melasma. Thirty patients with facial melasma were randomly divided into 3 equal Groups A, B, and C. Group A was treated with a 35% GA full-face peel, Group B and C with 35% GA full-face peel followed by a 10% and 20% TCA spot peel respectively once every 15 days. Four peels were performed once every 15 days. The response to the treatment was evaluated by the percentage reduction in melasma area severity index (MASI) scoring. All 3 groups had significant reduction of MASI, but there was no significant difference between the groups. Group A had minimum side effects. Chemical peels with GA alone or in combination with TCA do result in a significant improvement in melasma, but the combination of the peels in the same sitting does not seem to have any additive or synergistic effect while they may increase the side effects.

Ultrastructural characterization of damage in the basement membrane of facial melasma.

The pathogenesis of melasma is not fully understood, and the role of skin basement membrane zone (BMZ) alterations in disease development and the maintenance of hypermelanogenesis are also poorly known. We performed a comparative study to characterize the ultrastructural alterations that occur in BMZ in melasma and adjacent normal skin, as well as we discuss the implications of these changes in the physiopathology of the disease. Pairs of facial skin biopsies (2 mm) from 10 women with melasma and normal skin (< 2 cm apart) were processed by Transmission Electronic Microscopy or immunohistochemistry for Melan-A counterstained with Periodic acid-Schiff stain. Cytoplasmic organelles (from keratinocyte or melanocyte), BMZ damage were assessed and melanocyte counting (total and pendulous) was done. There was greater amount of cytoplasmic organelles inside basal keratinocytes and melanocytes in melasma, as well as structural damaged areas in the lamina densa (disruptions, gaps, lower density and thinning) and anchoring fibrils (lamina lucida), compared to healthy adjacent skin. Areas with pendulous melanocytes are characterized by discontinuity of BMZ ultrastructure. The prominence of cytoplasmic organelles from melanocytes and keratinocytes evidences the involvement of both cell groups in melasma. The damage in the lamina densa and lamina lucida suggest the role of upper dermis injury/repair process in the pathogenesis of the disease.

Clinical & ultrastructural evaluation of the effect of fractional CO2 laser on facial melasma

ABSTRACTMelasma represents the most obvious and disfiguring change of the face leading to psychological problems especially in females. Ablative lasers have also been used by many professionals to treat melasma, although there is few scientific data supporting this indication. The exact mechanism of action of ablative lasers in melasma is not yet clear enough. We aimed to evaluate the ultrastructural effect of fractional ablative CO2 (FrCo2) laser on facial melasma. Eleven melasma patients evaluated clinically by clinical modified area and severity index (MASI) score, treated by two sessions of fractional CO2 laser one month a part. Two punch biopsies of 2 mm diameter were obtained from all subjects one before and the other 3 months after treatment. All biopsies were analyzed by light and electron microscopy. Clinically, significant improvement of pigmentation and 48% reduction of (MASI) score were observed after two sessions of laser treatments. Light microscopic analysis of specimens revealed significant decrease in melanocyte count after treatment. Electron microscopic analysis of specimens after treatment revealed significant decrease in the number and size of melanocytes and significant decrease or complete absence of melanin granules in the surrounding keratinocytes compared to pre-treatment specimens. No scarring or post inflammatory hyper or hypopigmentation. We concluded that repeated application of Fractional CO2 laser on melasma skin may result in long lasting improvement due to its destructive effect on melanocytes.

Efficacy and Safety of an Oral Nutritional (Dietary) Supplement Containing Pinus pinaster Bark Extract and Grape Seed Extract in Combination with a High SPF Sunscreen in the Treatment of Mild-to-Moderate Melasma: A Prospective Clinical Study

Background: Melasma is a common hyperpigmentation disorder, characterized by light-to-dark brown patches, usually distributed on sun-exposed areas of the body. The objective of this study was to evaluate the efficacy and tolerability of an oral nutritional supplement containing Pinus pinaster and Grape seed extract, vitamins and minerals, used concomitantly with a high SPF sunscreen in 30 women with mild-to-moderate facial melasma. Methods: Efficacy was assessed by measurement of the Melasma Area and Severity Index (MASI), instrumental analysis of the lesions (Mexameter®, VISIA®)) and Patient’s and Physician’s Global Assessment (PGA). Results: The MASI score decreased significantly compared with baseline at days 28, 56, and 84. Mexameter® analysis showed a significant decrease of ∆M (difference in the melanin index between melasma and adjacent area). VISIA® results also showed a reduction in the number and areas of UV pigmented spots and in the areas of melasma overtime. Both the Patient’s and Physician’s Global Assessment showed that the product led to an improvement of the lesions in terms of depigmentation and had positive cosmetic features without adverse events. Conclusion: The oral supplement subject of this study in combination with high SPF sunscreen was effective and well-tolerated for treatment of mild to moderate facial melasma.

Evaluation of oral tranexamic acid in the treatment of melasma.

Melasma is an acquired, chronic, recurrent hypermelanosis that occurs exclusively in areas exposed to the sun. Its treatment can be very challenging. Tranexamic acid (TA) is an inhibitor of plasmin, and it is a synthetic derivative of the amino acid lysine that reversibly blocks binding sites on the plasminogen molecule, inhibiting the plasminogen activator from converting plasminogen to plasmin. This study evaluated the efficacy of oral TA in the treatment of melasma in patients from a philanthropic dermatological clinic. This was a monocentric, randomized, double-blind, controlled clinical trial. Patients with facial melasma were randomly divided into the following two groups: A (TA 250mg orally twice daily) or B (oral placebo twice daily). Evaluations were performed before and after 12weeks of treatment with photographs, colorimetry, MELASQoL, and MASI. All patients were instructed to use tinted sunscreen (SPF 50). Of the 47 patients selected, 37 completed the study, with 20 in group A and 17 in group B; the patients consisted of one male and 36 females, and the mean age was 43.97years old. Based on the four methods of evaluation, the melasma in 50% of patients in group A improved versus only 5.9% of patients in group B (P<0.005). There was an improvement according to all evaluation methods in the treatment group. No patient had severe side effects. We conclude that tranexamic acid was effective in 50% of patients according to four methods of evaluation when compared to the placebo.

Meanings of quality of life for patients with facial melasma

Objective: To exhibit the meanings attributed to quality of life by patients with facial melasma. Methods: Qualitative research using the focal group technique, with 10 people with facial melasma from a public hospital and private clinic of a municipality in the interior of the state of São Paulo. The methodological indicative used was content analysis. Results: In the interviewees’ speech, one perceives the annoyance generated by the opinion of others, with curious and even malicious questions related to the blemish. There is difficulty to hide the injuries and the appearance of skin neglect is also cause for distress for the participants. Conclusion: Because it affects the face, which makes it easily visible, melasma is uncomfortable and has a negative impact on the quality of life, since it affects patients’ psychological and emotional well-being.

Significados da qualidade de vida para pacientes com melasma facial

Objective: To exhibit the meanings attributed to quality of life by patients with facial melasma. Methods: Qualitative research using the focal group technique, with 10 people with facial melasma from a public hospital and private clinic of a municipality in the interior of the state of São Paulo. The methodological indicative used was content analysis. Results: In the interviewees’ speech, one perceives the annoyance generated by the opinion of others, with curious and even malicious questions related to the blemish. There is difficulty to hide the injuries and the appearance of skin neglect is also cause for distress for the participants. Conclusion: Because it affects the face, which makes it easily visible, melasma is uncomfortable and has a negative impact on the quality of life, since it affects patients’ psychological and emotional well-being.

Complex segregation analysis of facial melasma in Brazil: evidence for a genetic susceptibility with a dominant pattern of segregation.

Despite high prevalence, the etiopathology of melasma is not fully understood. Nevertheless, many factors have been associated with the disease, including: sun exposure, sex steroids hormones, drugs, stress, and pregnancy. The high occurrence within familiars (40-60%) suggests a genetic predisposition to the disease. This study explored, through complex segregation analysis (CSA), the inheritance model that best fit the family segregation pattern of facial melasma when accounting for the main epidemiological risk factors. We evaluated 686 subjects from 67 families, and 260 (38%) of them had facial melasma. The CSA model, adjusted for age, skin phototype, sex, sun exposure at work, hormonal oral contraceptive, and pregnancy, evidenced a genetic component that was best fitted to a dominant pattern of segregation. Melasma results from an interaction between exposure factors (e.g. pregnancy, hormones, and sun exposure) over genetically predisposed individuals.

Factors associated with quality of life in facial melasma: a cross-sectional study.

Melasma is a common chronic focal hypermelanosis that affects photexposed areas as face, mainly in women at fertile age. It inflicts a significant impact in quality of life; nevertheless, quality of life scores (e.g. MELASQoL) are not strongly correlated with clinical severity (e.g. MASI) in facial melasma, suggesting that different factors can influence the perception of disease beyond the clinical extension or the intensity of pigmentation. To explore clinical and socio-demographic aspects that influences MELASQoL scores. Cross-sectional study enrolling 155 adults (>18 y.o.) with facial melasma. MELASQoL, MASI, clinical and demographic information were assessed. The associations among factors were explored by multivariable methods. The mean (SD) age of the participants was 39 (8) years, and 134 (86%) were females. The correlation (Spearman's rho) between MELASQoL and MASI was 0.35 (P < 0.05). In a multivariate regression, MELASQoL score was associated (P ≤ 0.05) to MASI score (β = 0.6), lower income (β = 6.8), be single (β = 4.2) and low education level (β = 5.0). At multiple correspondence analysis, MASI, sex, marriage, education and income were associated with MELASQoL, as well as MASI was associated to skin phototypes, income and education level. The perception of life quality impairment in melasma is influenced by low scholarly, low family income, single marital status and greater clinical severity.

α-Viniferin Improves Facial Hyperpigmentation via Accelerating Feedback Termination of cAMP/PKA-Signaled Phosphorylation Circuit in Facultative Melanogenesis.

Rationale: cAMP up-regulates microphthalmia-associated transcription factor subtype M (MITF-M) and tyrosinase (Tyro) in the generation of heavily pigmented melanosomes. Here, we communicate a therapeutic mechanism of hyperpigmented disorder by α-viniferin, an active constituent of Caragana sinica.Methods: We used cAMP-elevated melanocyte cultures or facial hyperpigmented patches for pigmentation assays, and applied immunoprecipitation, immunobloting, RT-PCR or reporter gene for elucidation of the antimelanogenic mechanism.Results: C. sinica or α-viniferin inhibited melanin production in α-melanocyte-stimulating hormone (α-MSH)-, histamine- or cell-permeable cAMP-activated melanocyte cultures. Moreover, topical application with C. sinica containing α-viniferin, a standard in quality control, decreased melanin index on facial melasma and freckles in patients. As a molecular basis, α-viniferin accelerated protein kinase A (PKA) inactivation via the reassociation between catalytic and regulatory subunits in cAMP-elevated melanocytes, a feedback loop in the melanogenic process. α-Viniferin resultantly inhibited cAMP/PKA-signaled phosphorylation of cAMP-responsive element-binding protein (CREB) coupled with dephosphorylation of cAMP-regulated transcriptional co-activator 1 (CRTC1), thus down-regulating expression of MITF-M or Tyro gene with decreased melanin pigmentation.Conclusion: This study assigned PKA inactivation, a feedback termination in cAMP-induced facultative melanogenesis, as a putative target of α-viniferin in the treatment of melanocyte-specific hyperpigmented disorder. Finally, C. sinica containing α-viniferin was approved as an antimelanogenic agent with topical application in skin hyperpigmentation.

Development and validation of a multidimensional questionnaire for evaluating quality of life in melasma (HRQ-melasma)

Background: Melasma has a major impact on quality of life. MELASQoL is the only validated specific psychometric instrument to evaluate melasma QoL.Objective: To develop and validate a multidimensional questionnaire for evaluating quality of life related to facial melasma.Methods: Cross-sectional study performed in 2 institutions (public and private) from Brazil. Two focus groups were carried out: 5 board-certified dermatologists and 10 melasma patients, indicating the dimensions and significant units of melasma QoL. The preliminary questionnaire with 49 itens was applied to 154 facial melasma patients. Item reduction was performed by Rasch analysis. Parallel evaluations of clinical (MASI), demographic, and QoL aspects (MELASQoL, DLQI) were performed. The dimensional structure was assessed by confirmatory factor analysis. Temporal stability was tested in a subgroup of 42 individuals within 7-14 days.Results: The mean (SD) age of the 154 interviewed subjects was 39±8 years, and 87% were females. The median (p25-p75) DLQI and MELASQoL were: 2 (1-6) and 30 (17-44). HRQ-Melasma consisted of 19 items distributed in 4 dimensions: Physical/Appearance, Social/Professional, Psychological, and Treatment. Cronbach’s alpha for HRQ-Melasma was 0.96, and >0.74 for each dimension. There was high correlation between HRQ-Melasma and DLQI and MELASQoL (rho=0.80 and 0.83), but modest with MASI (rho=0.35). Dimensional structure of HRQ-Melasma was stated by confirmatory factor analysis coefficients. Test-retest analysis disclosed an intraclass correlation coefficient of 0.91 (p<0.01).Study limitations: Single-center study.Conclusions: A specific instrument to evaluate QoL in melasma with multidimensional characteristics was developed and validated, with appropriate psychometric performance.

Treatment of facial melasma with robotic microneedling associated to drug delivery of tranexamic acid

Treatment of facial melasma with robotic microneedling associated to drug delivery of tranexamic acid

Assessment of the effects of skin microneedling as adjuvant therapy for facial melasma: a pilot study

BackgroundMelasma is a common chronic and relapsing acquired dyschromia. Skin microneedling was reported resulting sustained long-term improvement of recalcitrant melasma, however, the exact mechanism that promotes this skin lightening is not known. This study aimed to investigate clinical and histologic alterations promoted by skin microneedling in facial melasma.MethodsOpen pilot trial including six women with facial refractory melasma submitted to two sessions of microneedling (1.5 mm) each 30 days followed by daily triple combination and broad-spectrum sunscreen. Comparison of pretreatment (T0) and 15 days after last microneedling procedure (T45) was made by standardized pictures, skin colorimetry, MASI, MELASQoL and histological parameters (haematoxylin-eosin, picrosirius-red, periodic acid Schiff and Fontana-Masson staining).ResultsThe age of the subjects varied from 34 to 46 years-old, the phototypes were III and IV (Fitzpatrick), and age of melasma onset was 20 to 38 years. Improvement of melasma was perceived in all subjects. There was a significant reduction of MASI score (−70%), MELASQoL (−55%) and increase in L* (+13%) colorimetric value (p < 0.03). All cases evidenced epithelium thickening, decrease in melanin pigmentation and densification of upper dermis collagen (p = 0.03). Patients were followed by 6 months under broad-spectrum sunscreen and triple combination without relapse.ConclusionIn addition to classic treatment (broad-spectrum sunscreen and triple combination), skin microneedling promoted clinical and histological improvement of refractory facial melasma.