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Oral tranexamic acid for the treatment of melasma

Melasma is a common acquired disorder of pigmentation, typically presenting in a symmetrical fashion on photoexposed areas. It tends to respect orbital and mandibular margins, and often occurs in a centrifacial or malar distribution. Although the aetiology remains poorly understood, aberrant activation of melanocytes and underlying angiogenesis are thought to play a role. Predisposing factors include hormonal factors (including oral contraceptives, hormone replacement therapy, pregnancy), female sex and genetic susceptibility. Treatment of melasma can be challenging for clinicians and frustrating for patients. Historically, this has comprised stringent photoprotection, topical agents (including hydroquinone, retinoids, corticosteroids, azelaic acid or combinations thereof) with a limited evidence base for lasers and chemical peels. Recent attention has focussed on the usefulness of oral tranexamic acid (TA) in reducing the appearance of melasma. TA is an antifibrinolytic agent, used for the management of menorrhagia and to reduce bleeding post-trauma. TA has several reported uses in dermatology, notably for physical urticaria and hereditary angio-oedema. In melasma, postulated mechanisms of action of TA include reduction of angiogenesis, including reduced expression of vascular endothelial growth factor and endothelin-1, and inhibition of the plasminogen/plasmin pathway, which in turn interferes with the interaction of keratinocytes and melanocytes, inhibiting melanin synthesis. While there have been several case reports and exploratory case series of the use of oral TA for melasma, Lee et al. in 2014 took the highly informative step of publishing their experience in the largest retrospective case series to date of 561 cases with clinical melasma treated with oral TA in the National Skin Centre, Singapore, a tertiary referral dermatology centre. Of note, the dose of TA used (250 mg twice daily, equalling 15 g/month) is less than the cumulative monthly dose of TA recommended for menorrhagia (up to 4 g for 4 days, equalling 16 g/month), suggesting that the proposed TA doses have been used safely for some time for other indications. In that study, 1081 patients were identified as having been treated with oral TA (250 mg twice daily) for clinical melasma, of whom 561 had adequate assessment and follow-up documentation to be included in the case series. Extent of disease and response to treatment was gauged by Physician Global Assessment (PGA), undertaken at each visit. Of the 561 patients reported, 91% were female and 9% were male. Median age of onset was 40 years (range 15–62 years) and median time between onset and seeking treatment was 7 months (range 0– 40 months). Of the 561 patients, 530 completed the full course of prescribed treatment. Median duration of treatment was 4 months and median time to show improvement was 2 months. The majority of patients (503; 89.7%) showed clinical improvement, irrespective of whether concomitant topical therapies were used, while 56 (10.0%) had no improvement and 2 (0.4%) had worsened diesase. More favourable responses to TA treatment were seen in patients with no family history of melasma and in patients with an older age of onset of melasma. On discontinuing treatment, 27.2% patients relapsed. Adverse effects (AEs) were reported by 40 patients (7%), with the most common being abdominal pain (n = 12), headache (n = 6), menstrual irregularities (n = 4), tinnitus (n = 3), paraesthesia (n = 3) and nausea/vomiting (n = 2). One patient developed deep vein thrombosis: on later questioning, it emerged that Correspondence: Dr Faisal R Ali, Dermatological Surgery and Laser Unit, Guy’s Cancer Centre, Guy’s and St Thomas’ NHS Foundation Trust, Great Maze Pond, London, SE1 9RT, UK E-mail: f.r.ali.01@cantab.net