Hypopigmentation as a side effect of melasma treatment with tranexamic acid intradermal microinjections

Dear Editor, Melasma is a chronic pigmentary disorder occurring commonly in women with dark skin types. It is a chronic often-relapsing condition that affects patient's quality of life. Its treatment is challenging. The use of tranexamic acid (TXA), an antifibrinolytic agent, as a treatment of melasma was first reported in 1979. Then, several studies have assessed its efficacy and safety. Oral TXA has proved to be an efficacious treatment for melasma. Side effects related to oral TXA were rarely reported and ranged from mild (gastrointestinal discomfort, skin rash, and drowsiness) to serious hypersensitivity reactions. Therefore, local infiltration with microinjections of TXA was introduced and proved to be as efficacious as oral TXA. The treatment regimen that is most commonly used is monthly intradermal microinjections of TXA 4 mg/mL at the site of melasma, keeping a distance of around 1 cm from each injection. Reported side effects are mild and include irritation, erythema, scaling, and xerosis. Hypopigmentation was reported as a side effect of oral TXA treatment but evidence of its association with intradermal TXA microinjections is lacking. We describe herein two cases. Case 1 involved a 31-year-old otherwise healthy female patient who presented with a 2-year history of centrofacial melasma. Treatment consisted of photoprotection and monthly intradermal injections of TXA (5 mg/mL) using a 0.5 mL insulin syringe. Three months after treatment initiation, a marked improvement of the Melasma Area and Severity Index (MASI) score was noted, but with no complete clearance. Due to the relapsing nature of melasma, maintenance therapy was indicated (every 6 weeks). Following the tenth session, multiple hypopigmented asymptomatic macules appeared on both arms and forearms (Figure 1). There were no scales or erythema. We decided to stop TXA microinjections. A slight repigmentation was observed after 2 months. Case 2 involved a 57-year-old woman who presented with a 7-year history of melasma. She had no relevant medical or family history, especially autoimmune disorder, thromboembolic event, miscarriage, or vitiligo. On physical examination, there were multiple brown-gray patches with irregular borders, distributed in a centrofacial pattern. Monthly intradermal injections of TXA was initiated. After 4 months, a well-demarcated depigmented macule appeared on the upper lip (Figure 2). TXA injections were stopped. After 2 months of follow-up, there was no repigmentation. We described two patterns of hypopigmentation appearing after TXA intradermal microinjections. In the first case, hypopigmented macules appeared distant to treated areas after several monthly microinjections of TXA. In this case, maintenance therapy was motivated by previous studies reporting greater recurrence rates with microinjections of TXA as compared to oral TA 250 mg twice daily, thus suggesting that intradermal TA injections should be administered frequently to achieve equivalent efficacy to oral TA. We F IGURE 1 Multiple hypopigmented asymptomatic macules on both hands and forearms