INTRODUCTION
Melasma, characterized by hyperpigmented macules and patches on the face, is a common disorder affecting millions of people across the globe.1 While it provides no direct health concern, it does pose a considerable cosmetic concern, which can lower self-esteem and overall quality of life.2
The exact pathophysiology of melasma is unknown, however, certain triggers have been identified. These triggers include sun exposure, pregnancy, use of oral contraceptives/hormone replacement, certain foods, ovarian tumors, photosensitizing drugs, inflammatory processes of the skin, and stressful life events. Familial predisposition has been reported but no Mendelian pattern has been identified.3 Among the inciting triggers, sun exposure is considered the most important factor.3
A variety of treatment options exist for melasma. First-line therapies generally consist of topical skin-lightening agents. These agents include but are not limited to hydroquinone, azelaic acid, mequinol, kojic acid, tranexamic acid (TXA), retinoids, and a variety of combination creams. (ie, hydroquinone combined with a topical retinoid and a low potency topical corticosteroid).4 Second-line therapies include a variety of chemical peels and laser therapy.5 Treatment with these first and second line treatments have often led to suboptimal results, therefore, novel treatments such as oral formulations of TXA have emerged. No consensus guidelines on the dosing of oral TXA exist.
Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine. Its mechanism of action regarding melasma is the inhibition of ultraviolet radiation (UVR)-induced plasmin activity in keratinocytes. Normally, prostaglandins are responsible for stimulating tyrosinase; by blocking the binding of plasminogen, TXA decreases free arachidonic acid, and therefore prostaglandins.6 As well documented in many dermatologic conditions, tyrosinase is the essential enzyme in melanogenesis and enzymatic browning.7 Additionally, plasmin is responsible for indirectly leading to angiogenesis, as it converts matrix-bound vascular endothelial growth factor (VEGF) into freely diffusible forms.6
Oral TXA, therefore, targets melasma by reducing melanin production and decreasing erythema (Figure 1).6 Oral TXA is currently FDA approved for cyclic heavy menstrual bleeding (1300 mg PO TID), hemoptysis (500 mg inhalation TID), and tooth extraction in patients with hemophilia (PO or injection 650 mg). Off-label uses include but are not limited to long-term prophylaxis in hereditary angioedema, hip fracture, operative blood conservation, and non-traumatic subarachnoid hemorrhage.8-11 Treatment for refractory melasma with oral TXA is an off-label indication, yet it has shown promising safety and efficacy data in the limited studies available to date. Our case series demonstrates the efficacy and safety profile of utilizing oral TXA to treat recalcitrant melasma, while also outlining a novel dosing regimen that can be used for this condition.
The exact pathophysiology of melasma is unknown, however, certain triggers have been identified. These triggers include sun exposure, pregnancy, use of oral contraceptives/hormone replacement, certain foods, ovarian tumors, photosensitizing drugs, inflammatory processes of the skin, and stressful life events. Familial predisposition has been reported but no Mendelian pattern has been identified.3 Among the inciting triggers, sun exposure is considered the most important factor.3
A variety of treatment options exist for melasma. First-line therapies generally consist of topical skin-lightening agents. These agents include but are not limited to hydroquinone, azelaic acid, mequinol, kojic acid, tranexamic acid (TXA), retinoids, and a variety of combination creams. (ie, hydroquinone combined with a topical retinoid and a low potency topical corticosteroid).4 Second-line therapies include a variety of chemical peels and laser therapy.5 Treatment with these first and second line treatments have often led to suboptimal results, therefore, novel treatments such as oral formulations of TXA have emerged. No consensus guidelines on the dosing of oral TXA exist.
Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine. Its mechanism of action regarding melasma is the inhibition of ultraviolet radiation (UVR)-induced plasmin activity in keratinocytes. Normally, prostaglandins are responsible for stimulating tyrosinase; by blocking the binding of plasminogen, TXA decreases free arachidonic acid, and therefore prostaglandins.6 As well documented in many dermatologic conditions, tyrosinase is the essential enzyme in melanogenesis and enzymatic browning.7 Additionally, plasmin is responsible for indirectly leading to angiogenesis, as it converts matrix-bound vascular endothelial growth factor (VEGF) into freely diffusible forms.6
Oral TXA, therefore, targets melasma by reducing melanin production and decreasing erythema (Figure 1).6 Oral TXA is currently FDA approved for cyclic heavy menstrual bleeding (1300 mg PO TID), hemoptysis (500 mg inhalation TID), and tooth extraction in patients with hemophilia (PO or injection 650 mg). Off-label uses include but are not limited to long-term prophylaxis in hereditary angioedema, hip fracture, operative blood conservation, and non-traumatic subarachnoid hemorrhage.8-11 Treatment for refractory melasma with oral TXA is an off-label indication, yet it has shown promising safety and efficacy data in the limited studies available to date. Our case series demonstrates the efficacy and safety profile of utilizing oral TXA to treat recalcitrant melasma, while also outlining a novel dosing regimen that can be used for this condition.
