103 Application of Kojic Acid in Treatment of Melasma The selection steps of the studies included in this review were performed according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation (9). A previously developed protocol was made available under open access in the Open Science Framework repository (DOI 10.17605/OSF. IO/P7G6R https://osf.io/f5dhk ),as well as complete data from the included studies. INVOLVEMENT OF STAKEHOLDERS This scoping review had the direct participation of a pharmaceutical aesthete (J.B.S.) and three specialists in cosmetology (V.E.B.C., E.P.S., Z.M.F.F.) in the refinement of the protocol and screening of the studies. RESEARCH QUESTION This scoping review was guided by the following question: How is the clinical application of KA in the treatment of melasma performed? To describe the pharmaceutical forms of delivery of KA, concentration, treatment duration time, frequency of application and associations, reduction of the severity of melasma spots, improvement of the quality of life of carriers, and adverse effects were reported. The research question followed the acronym Population, Concept, and Context (PCC): Population: Studies involving participants of both sexes, of any age, and with melasma who received melasma treatment through topical application of KA alone or in association with other actives or therapies. Studies involving participants with other pigmentation disorders were excluded. Concept: This scoping review was based on the following main concepts: KA and melasma: • KA, whose IUPAC name is 5-hydroxy-2-hydroxymethyl-4-pyrone, which is a substance of natural origin that is obtained from the fermentation of carbohydrates by fungi such as Aspergillus and Penicillium. Its function is to lighten the skin by being able to inhibit the enzyme tyrosinase, which is responsible for melanin production (5). • Melasma, which is a dysfunction of the pigmentary system known as acquired and chronic symmetrical cutaneous hyper melanosis. It is characterized by macules or irregular spots of light brown to dark brown coloration in skin areas exposed to the sun. It is distributed symmetrically on areas of the face, such as the forehead, lips, cheeks, and chin. It may affect other body areas more rarely, such as the neck and chest (1). Context: This review has no restrictions regarding the year of publication of the studies, country of origin, or place where these treatments were investigated. The complete strategy for each database is described in Complementary File 1 (https:// osf.io/54nkw ).This was elaborated using the following terms: Medical Subject Headings (MeSH), Health Descriptors (DeCS), alternative terms, and keywords: • MeSH: KA, Melanose, Adverse Effects • DeCS: Portuguese (Melanose, efeitos colaterais e reações adversas relacionadas a medicamentos) and English (Melanosis, Drug-Related Side Effects, and Adverse Reactions) • Alternative terms for DeCS: Chloasma, Melasma, Adverse Effects, Adverse Event, Adverse Events • Keywords: KA, Melasma, Adverse Effects.

104 JOURNAL OF COSMETIC SCIENCE ELECTRONIC DATABASE FOR STUDY IDENTIFICATION The following databases were consulted: MEDLINE (PubMed), Embase, VHL, Scopus, Cochrane Library, and Web of Science, without restricting year and language, through December 2022. OTHER RESEARCH RESOURCES FOR IDENTIFYING STUDIES The search strategy has been adapted to grey literature, including Google Scholar, Open Gray, the ISRCTN registry, ClinicalTrials, the Australian New Zealand Clinical Trials Registry, the International Clinical Trials Registry Platform operated by the World Health Organization, the EU Clinical Trials Register, the American Academy of Dermatology, the British Association of Dermatologists, the Annual Meeting of European Academy of Dermatology and Venereology, and the Annual Scientific Meeting of the Australasian College of Dermatologists. Manual searches were also performed in the references of the included studies to find as much material as possible for this review. ELIGIBILITY CRITERIA The clinical application of KA either alone or in combination with the treatment of melasma in both primary and secondary studies. EXCLUSION CRITERIA Studies that included participants with pigmentation disorders other than melasma or who did not use KA as one of the therapies were excluded. In addition, in vivo and in vitro studies, literature reviews, and charts were excluded. ELIGIBILITY DETERMINATION References were managed and selected by Rayyan software (10), where duplicates were automatically removed. Two reviewers (R.V.B. and J.B.S.) independently evaluated the titles and abstracts to verify whether they met the eligibility criteria. Subsequently, a complete reading of the article was performed by the same reviewers, also independently, to confirm eligibility within the guidelines described above. Discrepancies were resolved by consensus by a third reviewer when necessary. Notably, the reviewers underwent a calibration process before determining eligibility. DATA EXTRACTION The data from the included studies were extracted independently by two reviewers (R.V.B. and J.B.S.). The information was organized in Microsoft Excel. The same reviewers performed the extraction of data independently. The discrepancies were resolved through