Acta Dermato-Venerelogica Issue No 7, 2017 97-7CompleteContent | Page 8

SPECIAL REPORT Efficacy and Safety of Tranexamic Acid in Melasma: A Meta-analysis and Systematic Review Hyun Jung KIM 1# , Seok Hoon MOON 2# , Sang Hyun CHO 2 , Jeong Deuk LEE 2 and Hei Sung KIM 2 Department of Preventive Medicine, Korea University College of Medicine, Seoul, and 2 Department of Dermatology, Incheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea # These authors contributed equally to this work. Tranexamic acid is a novel treatment option for me- lasma; however, there is no consensus on its use. This systematic review searched major databases for relevant publications to March 2016. Eleven studies with 667 participants were included. Pooled data from tranexamic acid-only observational studies with pre- and post-treatment Melasma Area and Severity Index (MASI) showed a decrease of 1.60 in MASI (95% con- fidence interval (CI), 1.20–2.00; p  < 0.001) after treat­ ment with tranexamic acid. The addition of tranexa- mic acid to routine treatment modalities resulted in a further decrease in MASI of 0.94 (95% CI 0.10–1.79; p  = 0.03). Side-effects were minor, with a few cases re- porting hypo­menorrhoea, mild abdominal discomfort, and transient skin irritation. These results support the efficacy and safety of tranexamic acid, either alone or as an adjuvant to routine treatment modalities for me- lasma. Key words: tranexamic acid; melasma: systematic review; meta-analysis. 1 776 Accepted Apr 3, 2017; Epub ahead of print Apr 4, 2017 Acta Derm Venereol 2017; 97: 776–781. Corr: Hei Sung Kim, Department of Dermatology, Incheon St Mary’s Hospital, The Catholic University of Korea, 56 Dongsuro, Bupyeong-gu, 150-713, Incheon, Korea. E-mail: [email protected] M elasma is a common acquired disorder of facial pigmentation with predominance in the Asian po- pulation. Various treatment modalities have been used, but with inconsistent results (1, 2). Topical bleaching agents are the mainstay of treatment, but are often insufficient. Intense pulsed light (IPL) or laser-based treatments have conflicting outcomes with significant side-effects, such as mottled hypopigmentation and paradoxical darkening of melasma (3). Increased pigmentation is the main feature of me- lasma. Although the exact pathogenesis is unknown, it has been hypothesized that melasma is induced by bio- logically active melanocytes (4). Increased vascularity in the affected skin and elevated expression of angio­ genic factors in the epidermis have been found. These factors may play an important role in the development of melasma (4–6). Tranexamic acid (TA), a synthetic derivative of lysine, is a well-known haemostatic agent. TA is anti-fibrinolytic. It can inhibit plasminogen activation through the revers­ doi: 10.2340/00015555-2668 Acta Derm Venereol 2017; 97: 776–781 ible blockade of lysine-binding sites on plasminogen molecules (7). In recent years, off-label TA has emerged as potential treatment for melasma (5, 8). Although the mechanism of action remains unclear, it is thought that TA may inhibit melanin synthesis by blocking the interaction between melanocytes and keratinocytes. TA may also reverse the abnormal dermal changes associated with melasma, such as the aforementioned increased vasculature (9). While different forms of TA (i.e. oral, topical and loca- lized microinjections) have shown promising results (7, 9–11), there is a lack of support for its efficacy and safety in melasma due to the absence of sufficiently powered randomized controlled trials (RCTs). Through a systematic review of the literature, we aimed to investigate the ef- fectiveness and safety of TA, alone, or as an adjuvant, in patients with melasma. MATERIALS AND METHODS A systematic review and meta-analysis were conducted and reported in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) statement (12). Search strategy A systematic review of studies of the effect of TA in melasma was carried out. In order to collect all available evidence, EMBASE (1988 to present), MEDLINE (1946 to present), Web of Science (1975 to present), Scopus (1996 to present), and the Cochrane Central register of Controlled Trials (CENTRAL) (1991 to pre- sent) databases were searched on 4 March 2016, without limita- tion as to dates or language. To search for studies of TA, the fol- lowing keywords were used: “tranexamic acid’, “antifibrinolytic agents” and ‘tranexamic”. To search for melasma, the following keywords were used: “melanosis”, “chloasma”, “chloasmas”, “melasma”, and “melasmas”. The full search strategy, shown in Appendix S1 1 , was developed for MEDLINE and tailored to the other electronic databases. Study selection Inclusion criteria were: original reports (study, case series, item of correspondence, posters and meeting abstracts) describing treatment with any form of TA, alone or as an adjunct in melasma (human). According to the pre-defined criteria, 2 authors (H.J.K. and H.S.K.) independently selected reports based on the title and abstracts. Any discrepancies were resolved in consultation with a https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2668 1 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.