Table II Characteristics of the Intervention Regarding Pharmaceutical Forms of KA Delivery, Concentration, Treatment Time, and Frequency of Application Author/year Association/pharmaceutical form/concentration Frequency of application/ treatment duration Reduced severity of stains Improving the quality of life Adverse effect Bhagwat et al.2016 ,(21) 2% KA, octinoxate, and allantoin gel Daily use, at night, for 3 months. The evaluations were performed every month for 3 months. Initial mean (MASI0) MASI score of 10.02 ± 5.81. After completion of treatment, i.e., after 3 follow-ups (MASI3), the mean MASI score was 3.35 ± 4.25. The mean reduction in the MASI score was 6.67 (66.5%) at the end of treatment. The reduction in MASI was statistically highly significant (0.0001). It does not apply It was not reported Chowdhury et al.2012 ,(22) HQ, KA, and GA Daily use, at night, for 12 weeks. The MASI score decreased by 24.20%, indicating a decrease in melasma severity according to the scale: 0 =no reduction up to 25% =mild 26–50% =moderate above 50% =remarkable reduction It does not apply Itching, burning, flaking, and erythema Fragoso- Covarrubias et al.2015 ,(23) 5% arbutine, 10% GA, and 2% KA cream Daily use, at night, for 3 months. At the beginning of the study, the MASI index was 10.68 ± 5.19 (limits: 4.6 and 21.7). It found an average reduction in the MASI index of 7.2 ± 4.22 (limits: 2.3 and 15). The initial and final MASI indexes had a significant difference (=0.001). The mean MELASQoL score in patients was 40.18 ± 21.15 (limits: 7 and 67). The MELASQoL score until the end of the study was 33.12 ± 17.79 (limits: 2.3 and 56). When comparing the points of the MELASQoL indicator at the beginning and end of treatment, there was a significant reduction in treatment (=0.001). Erythema, burning, and irritation ()115 Application of Kojic Acid in Treatment of Melasma

Table II Characteristics of the Intervention Regarding Pharmaceutical Forms of KA Delivery, Concentration, Treatment Time, and Frequency of Application Author/year Association/pharmaceutical form/concentration Frequency of application/ treatment duration Reduced severity of stains Improving the quality of life Adverse effect Tsilika et al. ,2011 (24) Azelaic acid, KA, alpha arbutin, Glycyrrhiza glabra extract, and ascorbic acid cream Daily use for 12 weeks. Patients were evaluated in the week that started, weeks 4, 8, 12, and at week 12 +4. Before treatment, the mean MASI score was 22. After completion of treatment, the MASI decreased to 11 (=0.008). Decrease in MASI after 1 month of treatment maintained up to 1 month after the end of the treatment. It does not apply Mild irritation Xing et al. ,2021 (25) 3% TXA, 5% niacinamide, 1% KA, and 5% HEPES sérum Daily use, twice a day, for 12 weeks. Patients were evaluated in the following weeks: 0.2, 4, 8, and 12. Two weeks after treatment, mMASI scores decreased significantly (=0.044, which was very close to the cutoff value for significance of 0.05). At 4, 8, and 12 weeks, mMASI scores decreased significantly, indicating gradual improvement of melasma: 4 weeks (0.01) 8 weeks (0.001) 12 weeks (0.001). It does not apply It was not reported Draelos et al. ,2010 (26) KA, emblica extract, and GA cream Daily use, twice a day, for 12 weeks. Patients were evaluated at weeks 4, 8, and 12. At week 8, a statistically significant improvement was observed for uniform tone (=0.003) and hyperpigmentation (=0.007). At week 12, a highly statistically significant improvement was observed for skin texture/softness, clarity, uniform tone, hyperpigmentation, brightness, and general appearance (=0.001) and the size of dark spots (=0.021) and in the intensity of dark spots (=0.001). It does not apply It was not reported ()116 JOURNAL OF COSMETIC SCIENCE