Understanding Melasma-How Can Pharmacology and Cosmetology Procedures and Prevention Help to Achieve Optimal Treatment Results? A Narrative Review.

Melasma is a chronic skin condition that involves the overproduction of melanin in areas exposed to ultraviolet radiation. Melasma treatment is long-term and complicated with recurrence and resistance to treatment. The pathogenesis of melasma is highly complex with multiple pathologies occurring outside of the skin pigment cells. It includes photoaging, excessive melanogenesis, an increased number of mast cells, increased vascularization, and basement membrane damage. In addition, skin lesions related to melasma and their surrounding skin have nearly 300 genes differentially expressed from healthy skin. Traditionally, melasma was treated with topical agents, including hydroquinone, tretinoin, glucocorticosteroids and various formulations; however, the current approach includes the topical application of a variety of substances, chemical peels, laser and light treatments, mesotherapy, microneedling and/or the use of systemic therapy. The treatment plan for patients with melasma begins with the elimination of risk factors, strict protection against ultraviolet radiation, and the topical use of lightening agents. Hyperpigmentation treatment alone can be ineffective unless combined with regenerative methods and photoprotection. In this review, we show that in-depth knowledge associated with proper communication and the establishment of a relationship with the patient help to achieve good adherence and compliance in this long-term, time-consuming and difficult procedure.

Transfersomes improved delivery of ascorbic palmitate into the viable epidermis for enhanced treatment of melasma.

Ascorbic palmitate (AP) is widely used in the topical pharmaceutical or cosmetic formulations for melasma treatment. However, the presence of the skin barriers makes it difficult for the highly lipophilic drug molecules to traverse the stratum corneum (SC) and diffuse into the viable epidermis (EP) to reach the melanocytes, thereby exerting suboptimal antimelasma effects. Herein, AP was encapsulated into the transfersomes (TFs), yielding AP-TFs. AP-TFs utilized the deformability of TFs to squeeze through the skin pores in the SC under the transepidermal hydration gradient forces, leading to 14.1-fold increase in AP accumulation to the EP. AP-TFs could slowly release the encapsulated AP, while whether the released AP or transfersomal AP showed comparable uptake into the melanocytes, thereby exerting similar inhibitory effects on tyrosinase activity and melanogenesis. Ultimately, in the rat melasma model, AP-TFs showed superior antimelasma efficacy to free AP, with effective relief of oxidative stress and inflammation in the skin. Moreover, AP-TFs did not induce skin irritation. Therefore, the study provides a safe and effective approach to elevating the delivery of highly lipophilic drugs to the EP for enhanced treatment of melasma.

Therapeutic efficacy and safety of oral tranexamic acid 250 mg once a day versus 500 mg twice a day: a comparative study.

Oral tranexamic acid (TXA) 250 mg twice daily has been used effectively for 4 weeks to 6 months to treat melasma. As relapses are frequent on discontinuation, a minimum effective dose of TXA that can be used safely for long time remains unknown. We compared the efficacy of oral TXA 250 mg once daily and 500 mg twice daily given for 16 weeks in 132 (m:f 23:109) adults with melasma. 42 patients in Group-A (TXA 250 mg/d) and 46 patients in Group-B (TXA 500 mg twice/d) completed the study. They were followed up at 4-week interval for percentage reduction in baseline Melasma Area Severity Index (MASI) and at 24 and 28 weeks for relapse. Therapeutic response, for both as per-protocol and intention-to-treat analysis, was scored as very good (> 75% reduction), good (51-75% reduction), moderate (25-50% reduction), mild (< 25% reduction) or no improvement. Reduction in mean MASI score at 4 weeks was not statistically significant in Group-A but it decreased significantly 8 weeks onwards and was comparable with that in Group-B. The relapse rate was higher in Group-B (10.8%) than Group-A (4.7%) at the end of 28 weeks. Oligomenorrhoea and abdominal discomfort in few patients did not necessitate treatment discontinuation. TXA 500 mg twice daily showed early reduction in mean MASI score compared to 250 mg given once daily with comparable safety and therapeutic efficacy at 16 weeks. Open-label cross-sectional design, no control arm, small number of patients in each group, MASI score being subjective assessment tool, short duration of treatment and follow-up are study limitations.

Intradermal Tranexamic Acid Injection for the Treatment of Melasma: A Pilot Study with 48-week Follow-up.

BACKGROUND: Despite being an effective treatment for melasma, there have been limited reports on the long-term efficacy of intradermal tranexamic acid (TA) injection. OBJECTIVE: This study sought to evaluate the 48-week efficacy of a 4mg/mL intradermal TA injection for the treatment of melasma. METHODS: Five female patients with melasma participated in the 48-week follow-up after receiving 4-mg/mL intradermal TA injections on the face every two weeks for seven sessions and a sunscreen prescription. Assessments were performed at baseline and Weeks 4, 8, 12, 16, and 48 using the modified Melasma Area Severity Index (mMASI) score, melanin index, and patient satisfaction score. Safety and adverse effects were also evaluated. RESULTS: The mean (standard deviation) age of patients was 53.6 (8.14) years and Fitzpatrick Skin Type IV (60%) and Fitzpatrick Skin Type V (40%) were observed. The mean (standard deviation) duration of melasma was 7.6 (2.51) years and 60 percent of participants reported a family history of melasma. There was a significant decrease in mMASI score and melanin index at 16 weeks, without a statistically significant improvement of mMASI score at 48 weeks. Melasma recurrence was observed in 60 percent of the participants, with higher mMASI scores recorded, but the severity remained less than at baseline. The patient satisfaction score was lower from Week 16 to Week 48. Interestingly, a statistically significant decrease in the melanin index was observed up to Week 48, with no serious adverse effects. CONCLUSION: The 4-mg/mL intradermal TA injection yields significant efficacy at Week 16; however, melasma recurrence occurred during the 48-week follow-up. In addition to tranexamic acid injections, maintenance therapy and sun protection should be considered for patients with melasma.

Intense Pulsed Light and Low-Fluence Q-Switched Nd:YAG Laser Treatment in Melasma Patients.

BACKGROUND: Recently, low fluence collimated Q-switched (QS) Nd:YAG laser has drawn attention for the treatment of melasma. However, it needs a lot of treatment sessions for the substantial results and repetitive laser exposures may end up with unwanted depigmentation. OBJECTIVE: We evaluated the clinical effects and safety of the combinational treatment, using intense pulsed light (IPL) and low fluence QS Nd:YAG laser. METHODS: Retrospective case series of 20 female patients, with mixed type melasma, were analyzed using medical records. They were treated with IPL one time, and 4 times of weekly successive low fluence Nd:YAG laser treatments. At each visit, digital photographs were taken under the same condition. Melanin index (MI) and erythema index (EI) were measured on the highest point on the cheekbones. Modified melasma area and severity index (MASI) scores were calculated by two investigators using digital photographs. RESULTS: The mean values of MI and EI decreased significantly after treatments. The modified MASI score has decreased by 59.35%, on average. Sixty percents of the participants did not require any more treatments, and no clinical aggravations were observed during the follow-up period (mean 5.9 months). CONCLUSION: IPL and low fluence laser may elicit a clinical resolution in the mixed type melasma with long term benefits.

Evaluación de la eficacia de un producto despigmentante en gel en voluntarios diagnosticados con melasma / Evaluation of the efficacy of a skin lightening gel product in volunteer diagnosed with melasma

Introducción: el melasma es una hiperpigmentación común que afecta principalmente a las mujeres, comprometiendo su percepción estética y su autoestima, con un impacto significativo en su entorno psicológico, social y cultural. Se han postulado múltiples tratamientos con aparente eficacia; sin embargo, algunos productos se han asociado con complicaciones cutáneas y sistémicas, que han generado que las regulaciones sean más estrictas para la preparación y la distribución de este tipo de tratamientos. Objetivo:determinar si el uso de un producto despigmentante en gel ayuda en el aclaramiento del melasma. Metodología: mediante un diseño abierto no controlado y no aleatorizado se realizaron evaluaciones instrumentales con ayuda de un mexameter®en un área tratada (con melasma) y otra control (sin melasma) en el día en que se inició la aplicación del producto y a los 15, 30 y 60 días post-aplicación. Resultados: después de 60 días de aplicación del producto bajo condiciones normales de uso en un grupo de 30 voluntarias diagnosticadas con melasma, se evidenció una reducción estadísticamente significativa en las medidas instrumentales del índice de melanina de 340,1 ± 111 al inicio a 288,5 ± 85,4 en la octava semana. En la evaluación de la percepción de las voluntarias, el 72,4 % refirió un efecto despigmentante muy bueno, el 89,7 % notó beneficios adicionales como piel más hidratada, más tersa, más suave, al 82,8 % les gustó mucho el producto y el 96,6 % volvería a usarlo. Conclusión: este estudio permitió determinar la eficacia despigmentante del producto emclarex®puesto que mostró un 57,7 % de disminución del índice de melanina en el 89,7 % de los voluntarios diagnosticados con melasma, después de 60 días de uso.

Introduction: Melasma is a common hyperpigmentation that primarily affects women compromising their aesthetic perception and self-esteem, with a significant impact on their psychological, social and cultural environment. Multiple treatments have been proposed with apparent effectiveness; however, some products have been associated with numerous cutaneous and systemic complications that have generated that are stricter regulations for the preparation and distribution of this type of treatment. Objective: To determine whether the use of a skin lightening gel product helps in clearance of melasma. Methodology: By uncontrolled open design nonrandomized, instrumental evaluations were performed using a Mexameter®in a treated area (with melasma) and other control (without melasma) on day 1 and at 15, 30 and 60 days postapplication started. Results: After 60 days of application of the product under normal conditions of use in a panel of 30 volunteers diagnosed with melasma, it showed a statistically significant reduction in instrumental measurements of melanin index of 340.1 ± 111 at baseline to 288.5 ± 85.4 in the eighth week. In assessing the perception of the volunteers, 72.4 % reported a very good skin lightening effect, 89.7 % saw additional benefits like more hydrated skin, smoother, softer, 82.8 % liked the product and 96.6 % would use it. Conclusion: This study showed the skin-lightening efficacy of the Emclarex®product since it showed a 57.7 % decrease in melanin index in 89.7 % of the volunteers diagnosed with melasma, after 60 days of use.