Melasma is a complex, long-lasting, acquired dermatologic pigmentation disorder resulting in grey-brown patches that last for more than 3 months. Sun-exposed areas including the nose, cheeks, forehead, and forearms are most likely to be affected.1 In Southeast Asia, 0.25% to 4% of the population affected by melasma is aged 30 to 40 years.2 In particular, melasma is a concern among pregnant women due to increased levels of melanocyte-stimulating hormones (MSHs) and is impacted by genetics, hormonal influence, and exposure to UV light.3,4 In Pakistan, approximately 46% of women are affected by melasma during pregnancy.2,5 Although few studies have focused on the clinical approaches to melasma in darker skin types, it continues to disproportionately affect the skin of color population.4
The areas of hyperpigmentation seen in melasma exhibit increased deposition of melanin in the epidermis and dermis, but melanocytes are not elevated. However, in areas of hyperpigmentation, the melanocytes are larger and more dendritic and demonstrate an increased level of melanogenesis.6 During pregnancy, especially in the third trimester, elevated levels of estrogen, progesterone, and MSH often are found in association with melasma.7 Tyrosinase (TYR) activity increases and cellular proliferation is reduced after treatment of melanocytes in culture with β-estradiol.8 Sex steroids increase transcription of genes encoding melanogenic enzymes in normal human melanocytes, especially TYR.9 These results are consistent with the notable increases in melanin synthesis and TYR activity reported for normal human melanocytes under similar conditions in culture.10 Because melanocytes contain both cytosolic and nuclear estrogen receptors, melanocytes in patients with melasma may be inherently more sensitive to the stimulatory effects of estrogens and possibly other steroid hormones.11
The current treatment options for melasma have varying levels of success and include topical depigmenting agents such as hydroquinone, tretinoin, azelaic acid, kojic acid, and corticosteroids; dermabrasion; and chemical peels.12-14 Chemical peels with glycolic acid, salicylic acid, lactic acid, trichloroacetic acid, and phenol, as well as laser therapy, are reliable management options.13,14 Traditionally, melasma has been treated with a combination of modalities along with photoprotection and trigger avoidance.12
The efficacy and safety of the available therapies for melasma are still controversial and require further exploration. In recent years, off-label tranexamic acid (TA) has emerged as a potential therapy for melasma. Although the mechanism of action remains unclear, TA may inhibit melanin synthesis by blocking the interaction between melanocytes and keratinocytes.15 Tranexamic acid also may reverse the abnormal dermal changes associated with melasma by inhibiting melanogenesis and angiogenesis.16
Although various therapeutic options exist for melasma, the search for a reliable option in patients with darker skin types continues.13 We sought to evaluate the efficacy of TA solution 5% in reducing the severity of melasma in South Asian patients, thereby improving patient outcomes and maximizing patient satisfaction. Topical TA is inexpensive and readily accessible and does not cause systemic side effects. These qualities make it a promising treatment compared to traditional therapies.
Methods
We conducted a randomized controlled trial at Rawalpindi Medical Institute (Punjab, Pakistan). The researchers obtained informed consent for all enrolled patients. Cases were sampled from the original patient population seen at the office using nonprobability consecutive sampling. The sample size was calculated with a 95% CI, margin of error of 9%, and expected percentage of efficacy of 86.1% by using TA solution 5%. South Asian male and female patients aged 20 to 45 years with melasma were included in the analysis. Patients were excluded if they were already taking TA, oral contraceptive pills, or photosensitizing drugs (eg, nonsteroidal anti-inflammatory drugs, tetracyclines, phenytoin, carbamazepine); were pregnant; had chronic kidney disease (creatinine >2.0 mg/dL); had cardiac abnormalities (abnormal electrocardiogram); had hematologic disorders (international normalized ratio >2); or had received another melasma treatment within the last 3 to 6 months.
All enrolled patients underwent a detailed history and physical examination. Patient demographics were subsequently noted, including age, sex, history of diabetes mellitus or hypertension, and duration of melasma. The melasma area and severity index (MASI) score of each patient was calculated at baseline, and a corresponding photograph was taken.