The topical solution was prepared with 5 g of TA dissolved in 10 cc of ethanol at 96 °F, 10 cc of 1,3-butanediol, and distilled water up to 100 cc. The TA solution was applied to the affected areas once daily by the patient for 12 weeks. Each application covered the affected areas completely. Patients were instructed to apply sunscreen with sun protection factor 60 to those same areas for UV protection after 15 minutes of TA application. Biweekly follow-ups were scheduled during the trial, and the MASI score was recorded at these visits. If the mean MASI score was reduced by half after 12 weeks of treatment, then the treatment was considered efficacious with a 95% CI.
The percentage reduction from baseline was calculated as follows: percentage reduction=(baseline score– follow-up score)/baseline score×100.
Statistical Analysis—Data were analyzed in SPSS Statistics 25 (IBM). The quantitative variables of age, duration of melasma, and body mass index were presented as mean (SD). Qualitative variables such as sex, history of diabetes mellitus or hypertension, site of melasma, and efficacy were presented as frequencies and percentages. Mean MASI scores at baseline and 12 weeks posttreatment were compared using a paired t test (P≤.05). Data were stratified for age, sex, history of diabetes mellitus or hypertension, site of melasma, and duration of melasma, and a χ2 test was applied to compare efficacy in stratified groups (P≤.05).
Results
Sixty patients were enrolled in the study. Of them, 17 (28.33%) were male, and 43 (71.67%) were female (2:5 ratio). They ranged in age from 20 to 45 years (mean [SD], 31.93 [6.26] years). Thirty-seven patients (61.67%) were aged 31 to 45 years of age (Table 1). The mean (SD) duration of disease was 10.18 (2.10) months. The response to TA was recorded based on patient distribution according to the site of melasma as well as history of diabetes mellitus and hypertension.
Topical TA was found to be efficacious for melasma in 50 (83.33%) patients. The mean (SD) baseline and week 12 MASI scores were 23.15 (5.02) and 12.71 (4.10)(P<.0001), respectively (Table 2). The stratification of efficacy with respect to age, sex, duration of melasma, site of melasma, and history of diabetes mellitus or hypertension is shown in the eTable. The site of melasma was significant with respect to stratification of efficacy. On the forehead, TA was found to be efficacious in 11 patients and nonefficacious in 0 patients (P=.036). In the malar region, it was efficacious in 16 patients and nonefficacious in 1 patient (P=.036). Finally, on the chin, it was efficacious in 23 patients and nonefficacious in 9 patients (P=.036).
Comment
Melasma Presentation and Development—Melasma is a chronic skin condition that more often affects patients with darker skin types. This condition is characterized by hyperpigmentation of skin that is directly exposed to the sun, such as the cheek, nose, forehead, and above the upper lip.17 Although the mechanism behind how melasma develops is unknown, one theory suggests that UV light can lead to increased plasmin in keratinocytes.18 This increased plasmin will thereby increase the arachidonic acid and α-MSH, leading to the observed uneven hyperpigmentation that is notable in melasma. Melasma is common in patients using oral contraceptives or expired cosmetic drugs; in those who are pregnant; and in those with liver dysfunction.18 Melasma has a negative impact on patients’ quality of life because of substantial psychological and social distress. Thus, finding an accessible treatment is imperative.19
Melasma Management—The most common treatments for melasma have been topical bleaching agents and photoprotection. Combination therapy options include chemical peels, dermabrasion, and laser treatments, though they present with limited efficacy.17,20 Because melasma focuses on pigmentation correction, topical treatments work to disturb melanocyte pigment production at the enzymatic level.21 Tyrosinase is rate limiting in melanin production, as it converts L-tyrosinase to L-3,4-dihydroxyphenylalanine, using copper to interact with L-3,4-dihydroxyphenylalanine as a cofactor in the active site.22 Therefore, tyrosine is a major target for many drugs that have been developed for melasma to decrease melaninization.21