123 Application of Kojic Acid in Treatment of Melasma Most of the studies described the daily nocturnal application, except for the studies that did not report the frequency of application (15,16,28,30). And when KA was associated with weekly radio frequency or applied as a peeling fortnightly (13,31). The duration of treatment, in general, was 12 weeks 11 studies showed improvement in the reduction of spots by reducing the MASI score at the end of this period. In addition, six studies demonstrated improvement in the MASI score in the first weeks of treatment. Hence, the claims of more significant adverse effects could be directly related to the increase in concentration. Only burning happened when KA was used at 1% reports of redness, burning, and itching occurred when its concentration was increased to 4%. However, it is impossible to confirm this statistically since the included studies have low methodological quality and need to correctly describe the incidence of adverse effects. The improvement of melasma observed by all investigations independent of KA concentration is a crucial feature to take into account. However, more studies should be conducted with more homogeneous or standardized evaluation criteria to establish a proportionality relationship between MASI reduction. STRENGTHS AND LIMITATIONS OF THE STUDY The strengths of this scoping review include the high methodological rigor, the publication of a previous protocol, the use of explicit eligibility criteria, broad and complex research in databases and other records, and the selection and evaluation of studies by independent and standardized reviewers. The studies included are a limiting factor for the results observed due to their methodological quality and heterogeneity in reporting the results of safety and efficacy. It is also worth mentioning that most studies did not consider the patient’s quality of life as an evaluation of the participants, a critical outcome for this clinical condition. The findings related to the safety and efficacy of KA were similar to the previously published studies, suggesting, based on the available emerging evidence, that it may be safe and effective in treating melasma. IMPLICATIONS FOR RESEARCH AND CLINICAL PRACTICE The present scoping review observed the association of KA with several actives, but more was needed concerning its association with aesthetic procedures. Thus, the results gathered in this review can serve as a guide for new publications, generating new research questions and demonstrating where the limitations of studies already published are and, consequently, the knowledge about the clinical application of these formulations in treating melasma. Other reviews available in the literature address the use of KA, but not when specifically used in the in-depth treatment of melasma, or approached through reviews without methodological rigor as a scoping or systematic review (4,7,38,39). This scoping review contributes as a guide to the clinical application of KA by presenting results of several studies published over more than 20 years, which demonstrate that the application of KA alone or in therapeutic association produces significant results in reducing the severity of spots and improving the quality of life associated with melasma. Thus, it can guide the prescription of concentrations, treatment duration, and associations according to the results presented and the adverse effects reported.

124 JOURNAL OF COSMETIC SCIENCE CONCLUSION Using KA alone or in a therapeutic combination significantly reduces the severity of spots and improves the quality of life associated with melasma. Even though it presents good results when used in isolation, the association with GA, arbutin, HQ, and vitamin C generates more promising results. The pharmaceutical form and frequency of application are well elucidated for gel, cream, or serum for nocturnal application. In addition, treatment should be continuous, as melasma tends to go into remission. The KA concentration has not been established because it was reported from 0.75% to 6% for daily application. Further studies should be carefully elaborated using all specific analysis methods for melasma, MASI, mMASI, MI, and MELASQol, generating robustness and comparability among clinical trials. AUTHOR CONTRIBUTIONS Rayane Vieira Brasil: conceptualization, methodology, software, investigation, data curation, writing—original draft preparation, formal analysis, writing—reviewing and editing Jenifer Brasil dos Santos: conceptualization, methodology, software, investigation, data curation, writing—original draft preparation, formal analysis, writing— reviewing and editing Vânia Emerich Bucco de Campos: methodology, investigation, supervision, validation, writing—reviewing and editing Elisabete Pereira dos Santos: conceptualization, investigation, writing—original draft preparation, writing—reviewing and editing Zaida Maria Faria de Freitas: project administration, methodology, investigation, data curation, supervision, validation, formal analysis, writing—reviewing and editing. FUNDING SOURCES None ACKNOWLEDGMENTS We would like to thank University Pharmacy, Federal University of Rio de Janeiro, for their support in development of the paper. REFERENCES (1) Tosti A, Grimes PE, De Padova MP. Color Atlas of Chemical Peels. Springer 2006. Accessed March 6, 2023. DOI: 10.1007/978-3-642-20270-4. (2) Desai S, Ayres E, Bak H, Effect of a tranexamic acid, kojic acid, and niacinamide containing serum on facial dyschromia: A clinical evaluation. J Drugs Dermatol. 2019 18(5):454–459. Accessed March 6, 2023. https://pubmed.ncbi.nlm.nih.gov/31141852/ (3) McKesey J, Tovar-Garza A, Pandya AG. Melasma treatment: An evidence-based review. Am J Clin Dermatol. 2020 21(2):173–225. DOI: 10.1007/s40257-019-00488-w. (4) Austin EBS, Nguyen JKM, Jagdeo JMM. Topical treatments for melasma: A systematic review of randomized controlled trials. J Drugs Dermatol. 2019 18(11):1156. Accessed March 6, 2023. https:// pubmed.ncbi.nlm.nih.gov/31741361/.