Graph II. Correlation between the number of publications and the KA-related actives in the treatment of melasma. 119 Application of Kojic Acid in Treatment of Melasma

120 JOURNAL OF COSMETIC SCIENCE response or quality of life. These data demonstrate the heterogeneity of scientific research in clinical trials or case reports related to aesthetic dysfunctions or dermatology. Even with validated and recommended evaluation instruments, some authors still need to use them to make their results more reliable and comparable. The evaluation of melasma’s clinical response may be correlated with pharmaceutical form, KA concentration, frequency of use, treatment duration, and therapeutic associations. In addition, the occurrence of adverse effects is also linked to the variation of these conditions. Thus, in the studies that used KA in association with other actives or therapeutic resources, it is possible to observe that the lowest concentration of KA (0.75%) occurred when it was used in association with 2.5% vitamin C, presenting only erythema as an adverse effect. The mean reduction in the MASI score was significant from the first week of treatment to the end, in the 12th week (12). The erythema reported in addition to being related to KA may be related to vitamin C, since they are among the expected effects for its application as described since 1999 as ardor, erythema, and dry skin, easily treated with hydration (36). On the other hand, no adverse effects were reported when the concentration of KA was 1% in association with monopolar radio frequency for transdermal administration of the gel formulation with diverse agents associated (uva-ursi, arbutin, antioxidant agents such as pineapple, green tea, Capparis spinosa extract, vitamin C palmitate, papaya, and aloe) and also by the cream formulation of 1% KA, 3% TXA, 5% niacinamide, 5% hydroxyethyl piperazine ethanerazazine (13,25). In the first study, a significant reduction in melasma can be observed where the MASI score decreases after the first month and 6 months after treatment. The same can be observed in the second study with a treatment period of 12 weeks, in which there was a significant reduction in the mMASI score since the beginning of treatment (13,25). When the formulation of 1% KA, 3% TXA, 5% niacinamide, and 5% HEPES serum was used, the following adverse effects were presented: erythema, itching, redness, or burning. The treatment lasted 12 weeks and resulted in a significant reduction in melanin index (MI) scores. It is observed that the same concentration of previous studies and similar associations was used, but with different demonstrations of the occurrence of adverse effects (2). Graph III. Adverse effects related to the use of KA alone in the treatment of melasma.