Effect of Intense Pulsed Light versus Intradermal Tranexamic Acid for the Management of Melasma.

OBJECTIVE: To compare the effectiveness of intense pulsed light (IPL) and intradermal tranexamic acid (TXA) in treating melasma. STUDY DESIGN: A cross-sectional analytical study. Place and Duration of the Study: Department of Dermatology, Dow International Medical College, Dow University Hospital, Karachi, Pakistan, from 15th January to 15th July 2023. METHODOLOGY: A total of 62 patients with melasma, aged 20-50 years, were divided into two groups. Group A (32 patients) received IPL (560 nm filter was used) treatment, and Group B (30 patients) received intradermal TXA. Each group underwent four treatment sessions with varying intervals. Melasma area and severity index (MASI) scores were used to compare the effects of treatment. RESULTS: After a 3-month treatment period, both groups showed reduced mMASI scores compared to baseline with a significant initial difference between Group A (8.6 ± 4.2) and Group B (5.4 ± 2.7, p <0.001). However, post-treatment, there was no significant difference in mMASI scores (Group A: 3.8 ± 2.6; Group B: 3.2 ± 2.0, p = 0.29). IPL treatment (Group A) demonstrated a significant reduction in mMASI scores (57.1 ± 19.7) compared to intradermal TXA treatment (Group B, 42.2 ± 18.8, p = 0.0034). CONCLUSION: Both IPL and intradermal TXA treatments effectively reduced melasma, with IPL exhibiting superior results. However, post-treatment outcomes converged, emphasising the need for personalised approaches considering the unique characteristics of South East Asian skin. KEY WORDS: Intense pulsed light, Melasma, Intradermal tranexamic acid.

Definition of refractory melasma and its treatment: a review.

Although patients with refractory melasma have been treated using various methods, there is still no precise definition or summary of the therapies. To define refractory melasma and conduct a review of the treatments, we searched for relevant publications in PubMed, Web of Science, and the Cochrane Library, and a total of 35 references were obtained. Refractory melasma can be roughly defined as an ineffective treatment for melasma, including topical bleaching agents, chemical peels, laser therapy, microdermabrasion for more than six months, or chemical peels treated more than six times. Meanwhile, physicians should be careful when treating patients with darker skin and dermal or mixed types of melasma since these individuals do not respond well to treatment. Lasers combined with other methods, especially different types of lasers or topical agents, are considered more effective than monotherapy. Oral tranexamic acid (TXA) is a prospective cure for refractory melasma. Other methods include a combination of chemical peels, microneedling, or injections with additional therapies. In conclusion, we were able to provide a rough definition of refractory melasma and list the available therapies. According to the literature, the most prevalent treatment is laser combination therapy. However, laser treatment should be considered only after topical agents and chemical peeling have failed. Considering its side effects, efficacy, and safety, oral TXA may be a better option, but more research is needed to make a firm conclusion. Moreover, maintenance therapy is required after treatment.

755-nm picosecond laser plus topical 20% azelaic acid compared to topical 20% azelaic acid alone for the treatment of melasma: a randomized, split-face and controlled trial.

PURPOSE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients. METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient's satisfaction assessments (PSA). RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period. CONCLUSION: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).

Efficacy and safety of the combination of oral tranexamic acid and intense pulsed light versus oral tranexamic acid alone in the treatment of refractory Riehl's melanosis: A prospective, comparative study.

BACKGROUND: There is no standardized and effective treatment modality for Riehl's melanosis. AIMS: To compare the efficacy and safety of oral tranexamic acid (TXA) combined with intense pulsed light (IPL) versus TXA alone in the treatment of refractory Riehl's melanosis. METHODS: A prospective study of 28 subjects with refractory Riehl's melanosis and Fitzpatrick Skin Types III or IV was conducted. All subjects received oral TXA 500 mg daily and 11 of them were treated in combination with monthly IPL therapy for 6 months. The primary outcome measure was mean melanin index (MI), erythema index (EI) and acquired dermal macular hyperpigmentation area and severity index (DPASI). The Physician Global Assessment (PGA) and patient satisfaction scale were documented. RESULTS: After treatment, DPASI, mean MI, and EI were significantly reduced in both groups. The group treated with combination therapy showed better improvement according to MI (p = 0.0032) and DPASI (p = 0.00468). PGA and patient satisfaction scale showed superior efficacy in the combination group. No significant difference was observed in treatment-related side effects. CONCLUSION: The combination of oral TXA and IPL proves to be a safe and satisfactory treatment strategy for refractory Riehl's melanosis.

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.

Review of Fractional Nonablative Lasers for the Treatment of Dermatologic Conditions in Darker Skin Phototypes.

BACKGROUND: Fractional nonablative lasers (NAFLs) have demonstrated efficacy and safety for treating dermatologic conditions in patients with darker skin phototypes. Nonablative lasers are preferred in darker skin tones due to lower risk of postinflammatory hyperpigmentation. OBJECTIVE: This review aims to identify the ideal laser options and parameters for treating common dermatologic conditions in patients with skin types IV-VI. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed in May 2023. Of 1,065 articles were identified, and 40 articles met the inclusion criteria. The studies were classified based on design, dermatologic condition, and skin phototype of patients, and assigned levels of evidence according to the Modified Criteria of the Oxford Center of Evidence Based Medicine. RESULTS: Strong level 1 evidence supports the treatment of melasma and atrophic scars using NAFL. Moderate level 2 evidence was found for using NAFL in acne vulgaris, striae, and skin rejuvenation; 45% of the studies examined skin types III-IV, 20% III-V, 7.5% II-IV, 5% II-V, 5% IV alone, and 2.5% I-IV. CONCLUSION: Further research is needed to determine the optimal treatment modalities and parameters for skin types V and VI. Appropriate device selection and conservative treatment settings are crucial for optimizing outcomes and minimizing adverse events.

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).

Efficacy and safety of novel topical pigment-correcting regimen with biweekly diamond tip microdermabrasion procedures on facial hyperpigmentation.

BACKGROUND: Facial hyperpigmentation can negatively affect an individual's emotional and psychosocial well-being. AIMS: Assess safety and tolerability of a combination of microdermabrasion (DG) procedures using a novel brightening pro-infusion serum (EC-DG) with a targeted at-home treatment regimen in subjects with mild to severe facial hyperpigmentation, including melasma, post-inflammatory hyperpigmentation, and dark spots. PATIENTS/METHODS: This 12-week, open-label study enrolled 18 subjects (Fitzpatrick skin types I-IV) who underwent 6 in-office DG procedures with EC-DG (one procedure administered biweekly), along with daily topical application of a brightening treatment serum and dark spot cream. End points included change from baseline across multiple skin quality attributes and the Melasma Area and Severity Index (MASI), self-assessment questionnaires, and tolerability assessments. RESULTS: The combination treatment was well tolerated and resulted in significant (p ≤ 0.05) improvements from baseline in radiance, tactile roughness, and moisturization/hydration immediately after the first treatment, in MASI score at day 3, and in overall hyperpigmentation at week 4. Most (94.1%) subjects were satisfied with treatment. CONCLUSIONS: DG procedures using EC-DG combined with a targeted at-home skincare regimen are effective and tolerable for treating facial hyperpigmentation across a broad range of skin types.

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.

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/ .

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.

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.