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 Iraji et al. ,2014 (15) 2% KA cream The treatment lasted 3 months. Patients were evaluated every month. Frequency of unreported application. In total, 79% of patients were cured after 3 months. According to Friedman’s test, regarding the time of pigment healing, there was a significant difference between the groups (=0.008). The two groups had a significant difference regarding pigment tone changes at the end of the second and third months. It does not apply It was not reported Sheikh et al. ,2021 (16) Group A: oral TXA capsules +KA cream Group B: KA cream The study lasted 3 months. The patients were followed up in the eighth and 12th weeks. Frequency of unreported application Group A: there was a significant decrease in the MASI score from 12.08 ± 2.8 to 9.1 ± 2.2 in the eighth week and from 8.2 ± 2.0 in the 12th week (0.05 for both). Group B: MASI score decreased from 12.6 ± 2.4 to 10.9 ± 2.4 in the eighth week and then 10.3 ± 2.9 in the 12th week. In this group, the decrease in the MASI was significant in the eighth week, p 0.05, and was insignificant in the 12th week, p 0.05. It does not apply Group A: abdominal cramps and oligomenorrhea Group B: erythema and dryness Mesquita- Guimarães et al.2005 ,(17) 10% GA, 3% KA, 2% arbutin, 2% depigmenting factor 174J/276-D, 2% octyl methoxycinnamate, 1% butyl methoxydibenzoylmethane, 0,3% titanium dioxide, 0,5% disodium EDTA, 0,15% vitamin E, and 0,2% alpha-bisabolol cream Daily use in the morning and night for 12 weeks. The evaluations were performed in the fourth, eighth, and 12th weeks. The extent of lesions decreased significantly from first to last consultations (=0.001), with 68.8% of patients having affected areas greater than 20 cm². Decrease in melasma area between consultations, predominantly in patients with initial area greater than 50cm². Only 3 patients (18.7%) still had their original area at week 12. It does not apply Local irritation, contact dermatitis, itching, erythema, shilling, and flaking ()113 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 Azzam et al. ,2009 (18) 2% HQ and 2% KA cream Daily use, at night, for 2 months. The MASI score before treatment (mean ± SD =14,500 ± 2.107) decreased significantly (0.001) after treatment (mean ± SD =8.327 ± 2.172) and at the end of the follow-up period (10.813 ± 1.778) It does not apply It was not reported Costa et al. ,2012 (19) KA, arbutin, Sepiwhite, ® and Achromaxylcream ® Daily use twice a day for 90 days. The evaluations took place every 30 days. The initial mean MASI was 12.73 (D0), which went to 10.89 (D30) and 9.65 (D60), finishing the study with 8.63 (D90) The mean MELASQol in D0 was 45.62 in D90 it was 27.09 (0.001) A: erythema, flaking, pinching, ardor, and flaking. Berardesca et al.2019 ,(20) KA and vitamin A cream (day)+KA and glycolic cream (ight) Daily use twice a day, morning and evening, for 90 days. The evaluations were made in the first week, then 45 days and 90 days after the start of treatment. At 90 days, the mean MASI score for all patients was significantly lower than at baseline (2.1 1.128 ± 0.129 versus 3.29 ± 0.267, p 0.00001). It is important to note that a statistically significant reduction in the mean score of the mMASI was also observed at 45 days (2.193 ± 0.181 versus 3.29 ± 0.267, p 0.0001). It does not apply It has no adverse effects Desai et al. ,2019 (2) 3% TXA, 1% KA, 5% niacinamide, and 5% HEPES sérum Daily use twice a day, morning and evening, for 12 weeks. The evaluations were made in weeks 2, 4, 8, and 12. At 4 weeks, there was a considerable decline in the melanin index (MI) scores of the lesional melasma skin. At week 8, the skin of lesional melasma showed a decrease in MI by up to 9%. The normal skin perilesional (control site) also showed an MI decrease at week 4. It does not apply Erythema or redness, itching, or burning ()114 JOURNAL OF COSMETIC SCIENCE