CLINICAL CASE STUDY: ORAL TRANEXAMIC ACID

Consultant dermatologist Dr Rajani Nalluri talks through a new, effective, and safe treatment of melasma.

CLINICAL SCENARIO

A 43-year-old Caucasian air hostess with skin type III presented with centro-facial melasma. There were no triggers such as pregnancy or hormonal contraception. It severely affected her quality of life (QOL), causing embarrassment, and depression, affecting her job and social life. Her routine skin care included sunscreens. She tried multiple courses of triple combination cream (TC) with limited benefit and frequent recurrences; therefore, I considered treatment with oral tranexamic acid (TXA).

Having gone through the checklist and discussion of benefits and risks, I started her on oral TXA 250 mg twice daily for three months, along with regular mineral sunscreens. No other topical treatment was applied. She was advised to avoid hormonal contraception and use barrier methods.

Her modified Melasma Area and Severity Index (mMASI) decreased from 5.2 to 3.6; and her Dermatology Quality of Life Index (DLQI) from 29 to 14 at three-month review, with no major side effects. At follow-up, she had mild recurrence only, for which she was started on a regime of TC for six months and maintenance non-hydroquinone-containing cream for six months, along with mineral sunscreens, to keep her melasma suppressed to a minimum.

BACKGROUND

Melasma is a common cause of facial hyperpigmentation, presenting as symmetrical brown to blue patches with scalloped borders, affecting millions worldwide.1,2Women of Fitzpatrick skin types (ST) III and IV are mostly affected, but both genders and all skin types can be affected as well. The mean age of onset is 29 years but it can occur in postmenopausal women on extra-facial sites such as the neck and arms. 3-5

Although asymptomatic, it causes significant impact on quality of life (QOL), leading to low self-esteem and avoidance of social and outdoor activities.6Treatment is challenging and often unsuccessful, with high relapse rate, causing greater psychosocial impact on QOL; however, when treated successfully, there is huge improvement in QOL. 5,6

Treatment options are topical therapies, physical modalities, systemic agents, and combination treatments. First-line treatment and prevention are with sunscreens offering UVA, UVB and visible light protection. Topical agents include those containing hydroquinone (HQ), retinoids, kojic acid, vitamin C, arbutin, azelaic acid, niacinamide, cysteamine.1,3,5The current gold standard treatment is with triple combination cream (TC) containing 4% hydroquinone, 0.5% tretinoin and fluocinolone acetonide 0.01%, however it is not tolerated by most, with skin irritation, redness and sometimes post inflammatory hyperpigmentation (PIH). 7Physical modalities give mixed and unpredictable results, with risk of PIH, scarring, requiring multiple sessions with significant cost implications for patients. 3,5,7

There has been recent interest and advances in oral treatments for melasma, such as tranexamic acid (TXA), polypodium leucotomos, carotenoids, melanin, and procyanidin.8The best evidence for efficacy and safety so far is for TXA which we will be discussing in further detail. 9

ORAL TRANEXAMIC ACID

TXA is a haemostatic agent which is Food and Drug Administration (FDA) approved for menorrhagia and tooth extractions in hemophiliacs and used off label to control bleeding in trauma and intraoperatively.10When TXA was used to treat a patient with chronic urticaria, it was noted that the patient’s melasma also improved. 11Since this accidental discovery, there have been many studies on TXA for melasma, as topical, intradermal and oral formulations. Oral TXA is not FDA approved for melasma, however following my application, it has been approved by the Greater Manchester Medicines Management Group (GMMMG) for use in melasma.

Oral TXA has demonstrated promising results in melasma, being the most effective form compared to topical and intradermal. It was effective when used alone or as an adjunct to another primary treatment.12It gave superior results compared to placebo and topical HQ with good to excellent improvement in more than 50% of patients. 13When oral TXA was used in conjunction with topical HQ there was a 55% decrease in mMASI compared to a 10.9% decrease with topical HQ alone. 14Oral TXA increased the efficacy of TC with a marked 65.6% improvement in mMASI compared to 27.1% with TC alone. 15Addition of oral TXA to laser (low fluence QS:NdYAG or IPL) resulted in significantly better and faster response with reduction in the number of sessions required, demonstrating that oral TXA enhances the efficacy of laser. 16,17It was found to show good improvement in more than 50% of mixed and refractory melasma as well.

BEFORE ORAL TXA ON SKIN TYPE 3

AFTER ORAL TXA ON SKIN TYPE 3

As melasma is a chronic, relapsing condition, there is recurrence on discontinuation of any treatment; however, the recurrence rate is much lower after TXA compared to other treatments. In an Indian study of 120 patients, there was 18.03% recurrence at six months in the oral TXA + TC group compared to 64.4% in the TC group.15

The hypopigmentary effect of TXA in melasma is by inducing reduced melanocyte tyrosinase activity, melanogenesis and reduced prostaglandin production. It also causes dermal changes of reduced vascularity and mast cells.15

The most effective dose was found to be 250mg TDS for 12 weeks, however 250mg BD is more acceptable due to compliance and provides similar efficacy.18

The side effects were mild, including gastrointestinal disturbances, menstrual irregularities, palpitation, and urticarial rashes. Serious adverse effects such as deep vein thrombosis (DVT) and pulmonary embolism (PE), seizures, infarctions and visual disturbances were not reported in any of the studies, which is attributed to the lower doses used in melasma compared to bleeding.15

However, it is paramount to screen for risk factors to minimize the possibility of serious side effects. The risk factors include history of renal dysfunction, cardiovascular or respiratory disease, malignancy, thrombosis, thrombophilia, DVT, PE, stroke, subarachnoid haemorrhage, more than 2 miscarriages, pregnancy, breastfeeding, acquired disorder of colour vision; concurrent medications (anticoagulation therapy, hormonal contraception, or hormone replacement therapy); smoking or long-distance travel.9,12,15

In conclusion, oral TXA is becoming a promising treatment in the management of this chronic recalcitrant condition, however it requires careful consideration and expertise.

BEFORE ORAL TXA 1

AFTER ORAL TXA 1