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).

A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face: Clinical evidence and mechanistic understanding by computational biology and optical biopsy.

Topicals and chemical peels are the standard of care for management of facial hyperpigmentation. However, traditional therapies have come under recent scrutiny, such as topical hydroquinone (HQ) has some regulatory restrictions, and high concentration trichloroacetic acid (TCA) peel pose a risk in patients with skin of colour. The objective of our research was to identify, investigate and elucidate the mechanism of action of a novel TCA- and HQ-free professional-use chemical peel to manage common types of facial hyperpigmentation. Using computational modelling and in vitro assays on tyrosinase, we identified proprietary multi-acid synergistic technology (MAST). After a single application on human skin explants, MAST peel was found to be more effective than a commercial HQ peel in inhibiting melanin (histochemical imaging and gene expression). All participants completed the case study (N = 9) without any adverse events. After administration of the MAST peel by a dermatologist, the scoring and VISIA photography reported improvements in hyperpigmentation, texture and erythema, which could be linked to underlying pathophysiological changes in skin after peeling, visualized by non-invasive optical biopsy of face. Using reflectance confocal microscopy (VivaScope®) and multiphoton tomography (MPTflex™), we observed reduction in melanin, increase in metabolic activity of keratinocytes, and no signs of inflammatory cells after peeling. Subsequent swabbing of the cheek skin found no microbiota dysbiosis resulting from the chemical peel. The strong efficacy with minimum downtime and no adverse events could be linked to the synergistic action of the ingredients in the novel HQ- and TCA-free professional peel technology.

Topical isoniazid as a novel treatment for melasma: A randomized, double-blind, vehicle-controlled clinical trial.

INTRODUCTION: Melasma is a chronic hyperpigmentation disorder, and its treatment poses a challenge to dermatologists due to its chronicity and resistance to conventional therapies. Oral isoniazid is used for the treatment of tuberculosis. One of us had previously showed that topical isoniazid exerts a strong depigmenting action in animal models. In this clinical trial, we assessed the therapeutic effect of topical isoniazid on melasma. METHODS: Twenty female patients suffering from epidermal melasma were enrolled and divided equally into two groups. The treatment group received topical isoniazid 10%, and the control group received the cold cream vehicle as the placebo. All participants were advised to avoid sunlight and used SPF 50 sunscreen. Patients applied topical agents once daily at night for 3 months. The melanin and erythema indices were measured by colorimetric evaluations at baseline and after 4, 8, and 12 weeks of treatment. At these time points, the (mMASI) score was also determined, as was the subjective evaluation through Melasma Quality of Life Scale (MELASQOL) scores. Blood tests were performed to evaluate CBC and the liver enzymes. RESULTS: All patients completed the 12-week study. In the treatment group, a significant decrease in melanin index from 63.77 ± 6.27 at baseline to 55.92 ± 5.79 was recorded (p = 0.001). Very minimal clinical changes were also seen in the control group and melanin index was decreased from 62.65 ± 2.23 to 61.25 ± 2.34 (p = 0.004). Clinically significant differences were observed in the rate of changes between both groups. These findings indicate that topical isoniazid has significant depigmenting effects compared to the placebo (p = 0.001). The erythema index remained unchanged in both groups. In the treatment group, the mMASI score was 5.63 ± 3.28 at baseline and 2.13 ± 1.71 at the last follow-up, significantly reduced compared to the control group (p = 0.002). The MELASQOL score indicated a significant improvement in the quality of life in the treatment group. CONCLUSION: This clinical trial shows for the first time that topical isoniazid is effective in treating melasma. Further clinical trials are necessary to confirm the efficacy and tolerability of topical isoniazid in comparison with other skin-depigmenting compounds.

Different therapeutic approaches in melasma: advances and limitations.

Melasma is a chronic hyperpigmentation skin disorder that is more common in the female gender. Although melasma is a multifactorial skin disorder, however, sun-exposure and genetic predisposition are considered as the main etiologic factors in melasma occurrence. Although numerous topical and systemic therapeutic agents and also non-pharmacologic procedural treatments have been considered in melasma management, however, the commonly available therapeutic options have several limitations including the lack of sufficient clinical effectiveness, risk of relapse, and high rate of unwanted adverse drug reactions. Recruitment of nanotechnology for topical drug delivery in melasma management can lead to enhanced skin penetration, targeted drug delivery to the site of action, longer deposition at the targeted area, and limit systemic absorption and therefore systemic availability and adverse drug reactions. In the current review, first of all, the etiology, pathophysiology, and severity classification of melasma have been considered. Then, various pharmacologic and procedural therapeutic options in melasma treatment have been discussed. Afterward, the usage of various types of nanoparticles for the purpose of topical drug delivery for melasma management was considered. In the end, numerous clinical studies and controlled clinical trials on the assessment of the effectiveness of these novel topical formulations in melasma management are summarized.

Management of Melasma: Laser and Other Therapies-Review Study.

Melasma is a commonly occurring pigmented skin condition that can significantly affect one's appearance, described as symmetric hyperpigmentation that presents as irregular brown to gray-brown macules on various facial areas, such as the cheeks, forehead, nasal bridge, and upper lip, along with the mandible and upper arms. Due to its complex pathogenesis and recurrent nature, melasma management is challenging and the outcomes following treatment are not always deemed satisfactory. Solely treating hyperpigmentation may prove ineffective unless paired with regenerative techniques and photoprotection, since one of the main reasons for recurrence is sun exposure. Hence, the treatment protocol starts with addressing risk factors, implementing stringent UV protection, and then treatment using different strategies, like applying topical treatments, employing chemical peels, laser and light therapies, microneedling, and systemic therapy. This review aims to provide a summary of the effectiveness and safety of the frequently employed laser and light therapies for treating melasma, focusing on laser therapy as a treatment for melasma.

Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway.

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis.

Melasma and reflectance confocal microscopy: from baseline to treatment monitoring.

Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non-invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring.

Efficacy and safety of adjuvant topical application of botanicals in the treatment of melasma: A systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy and safety of topical application of botanical (TAB) adjuvants in the treatment of melasma and provide evidence-based medical evidence for their clinical application. Methods: Medline, Web of Science, EMBASE, Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, databases were searched to identify all randomized controlled clinical trials on TAB adjuvant treatment for melasma from inception to May 2023. The primary outcomes included clinical efficacy, adverse effects, recurrence rate, and melanin index. Subgroup analyses were performed using the Melasma Area Severity Index (MASI) scores. Results: This study included 16 randomized trials with 1386 participants. Eligible trials demonstrated that topical phytomedicine adjuvant treatment for melasma increased clinical effectiveness (RR = 1.14, 95% CI (1.10, 1.19), P ＜0.00001), decreased recurrence rate (RR = 0.28, 95% CI (0.13, 0.59), P = 0.0009), and decreased melanin index (MI) (MD = -22.2,95% CI (-31.79, -12.61), P < 0.00001). In addition, subgroup analysis showed that topical phytomedicines reduced MASI scores (I2 = 0%, MDI = -0.95, 95% CI (-1.23,0.67), P < 0.00001), but when scored as the rate of decrease in MASI, topical phytomedicines had high MASI scores (I2 = 15%, MD = 0.3, 95% CI (0, 0.59), P = 0.05), indicating a slower rate of melasma mitigation when botanicals were applied topically. Although burning pain, redness and other mild adverse reactions may occur during the treatment period, they can be recovered on their own, and there is no statistical significance in the comparison of the two groups (RR = 0.95, 95% CI (0.42, 2.51), P = 0.91). Conclusion: TAB for melasma has a clear adjuvant clinical efficacy, a low recurrence rate, and does not cause serious adverse effects. An appropriate administration method may achieve better efficacy; however, this requires further verification.

Efficacy and tolerability of a depigmenting gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that targets the biological processes regulating skin melanogenesis.

BACKGROUND: The diverse causes of hyperpigmentation and complex nature of melanogenesis make it a challenge to manage. Current approaches either fail to deliver effective pigmentation control or have undesirable safety profiles that preclude their long-term use. AIMS: To evaluate the capacity of a cosmetic gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that was designed to target the biological processes regulating skin melanogenesis to attenuate melanin production in vitro and reduce hyperpigmentation clinically. METHODS: Capacity to reduce melanin production in vitro was determined in melanocyte-containing reconstructed human epidermis (RHEm). Clinical efficacy and skin tolerability following twice daily application were assessed in 35 subjects with slight to moderate facial hyperpigmentation by instrumental (VISIA®-CR, Mexameter®) and clinical (mMASI, clinical score, IGA for hyperpigmentation) evaluation on D14, D28, D56, and D84. Maintenance of pigmentation control was followed up 1 month after cessation of treatment on D112. RESULTS: In RHEm in vitro, melanin production was reduced by 50.0% from baseline (D0) on D14 (p < 0.001) and by 67.0% on D21 (p < 0.001). Clinical reductions from baseline in brown spots count (-9.0%; p < 0.05), brown spots area (-16.7%; p < 0.001), and the melanin index (-11.4%; p < 0.001) were observed within 14 days of use. Statistically significant improvements in all clinical parameters were achieved by D28. By the end of treatment on D84, the number and surface area of brown spots were reduced by 28.4% and 40.3% compared to D0, respectively (p < 0.001, both), the melanin index was reduced by 31.1% (p < 0.001), mMASI was reduced by 63.0% (p < 0.001), and skin luminosity was increased by 79.0% (p < 0.001). IGA was reduced from 2.3 on D0 to 1.3 on D84 (p < 0.001). Improvements to all these parameters were maintained until D112, 1 month after termination of treatment. The product also demonstrated very good skin tolerability. CONCLUSION: A gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, and hydroxy acids, designed to target the biological processes regulating skin melanogenesis, demonstrates rapid, robust, and sustained pigmentation control in this cohort.

Enhancing Tranexamic Acid Penetration through AQP-3 Protein Triggering via ZIF-8 Encapsulation for Melasma and Rosacea Therapy.

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches ≈25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration.

Comparison of the efficacy of Hydroquinone cream versus Hydroquinone cream plus Danggui Shaoyao powder in the treatment of melasma.

Introduction: Melasma is an acquired hypermelanosis and occurs in areas exposed to sunlight. Aim: To investigate the effectiveness of Danggui Shaoyao powder (DSP) as a complementary drug in the treatment of melasma. Material and methods: A total of 40 melasma patients over the age of 18 who met the inclusion criteria entered the study randomly in two DSP + Hydroquinone (DSP + H) and Hydroquinone (H) groups. Results: At the beginning of the study, the average MASI score of the two groups of patients had no statistical difference (DSP + H: 15.79 ±1.01 vs. H: 15.37 ±1.17, p = 0.23). But from the eighth week of treatment, the MASI score of the patients decreased significantly and in the DSP + H group it decreased statistically significantly compared to the H group (DSP + H: 5.83 ±0.97 vs. H: 8.29 ±2.23, p < 0.001 for the eighth week and DSP + H: 3.60 ±0.58 vs. H: 5.52 ±1.73, p < 0.001 for the twelfth week of the treatment). It means after 12 weeks of treatment, the average MASI score of patients in the DSP + H group decreased by 77.26 ±2.70%, but in the grroup H, it decreased by 64.31 ±9.68% (p < 0.001). Dynamic PGA showed that excellent treatment occurred in 65% of the + H group H, but only 20% of the H group (p = 0.01). Conclusions: Oral DSP for 12 weeks along with hydroquinone cream can significantly reduce the MASI score of melasma patients and increase the patients' recovery and satisfaction.

Carotenoids in red fruit (Pandanus conoideus Lam.) have a potential role as an anti­pigmentation agent (Review).

Melasma is a persistent condition characterized by excessive melanin production in the skin. The management of melasma necessitates a protracted treatment duration, which is associated with diminished levels of patient satisfaction. One effective strategy for mitigating occurrence of melasma is consumption of nutricosmetics with depigmentation properties. The present review aimed to investigate the potential of red fruit as a depigmentation agent. Carotenoids serve a crucial role in human nutrition as a precursor to vitamin A. Carotenoids serve as scavengers of reactive oxygen species generated by ultraviolet radiation. Carotenoids promote skin health. Red fruit, a fruit originating from Papua (Indonesia) has anti-pigmentation properties associated with its ability to block melanogenesis through various protein pathways such as PKA, ERK, and AKT signaling pathways. The consumption of food rich in carotenoids, such as red fruit, has advantageous properties to reduce hyperpigmentation and skin brightening.

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.

Combination of 5% cysteamine and 4% nicotinamide in melasma: Efficacy, tolerability, and safety.

BACKGROUND: Melasma is a chronic dermatosis that impacts the patient's quality of life and can present considerable challenges in terms of effective treatment. OBJECTIVE: To evaluate the effectiveness, tolerability, and safety of 5% cysteamine combined with 4% nicotinamide in female subjects with melasma. METHODS: This single-center, single-arm, prospective, open-label study evaluated patients with melasma using a combination cream of 5% cysteamine and 4% nicotinamide in a progressive regimen (60 min in the first month, 120 min in the second month, and 180 min in the third month). RESULTS: Overall, 35 treated subjects exhibited reduced modified Melasma Area and Severity Index (mMASI) (p < 0.001) and decreased MelasQoL scores (p < 0.001), accompanied by improved brightness, luminosity, homogeneity, and spot intensity (p < 0.001). Photographic and colorimetric analysis revealed smaller spots and improved homogeneity. LIMITATIONS: Adherence to progressive daily treatment could not be evaluated long-term. CONCLUSION: A combination cream comprising 5% cysteamine and 4% nicotinamide was effective, tolerable, and safe for treating melasma.