|Year : 2019 | Volume
| Issue : 2 | Page : 100-103
Comparison of effectiveness of oral tranexamic acid with that of the topical modified Kligman's formula in the treatment of melasma
Aditi Bansal, Vidyadhar R Sardesai
Department of Dermatology, Venereology and Leprosy, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Maharashtra, India
|Date of Web Publication||16-Dec-2019|
Dr. Vidyadhar R Sardesai
102 Alliance Nakshatra, 48 Tulshibagwale Colony, Sahakar Nagar 2, Pune - 411 009, Maharashtra
Source of Support: None, Conflict of Interest: None
Context: Melasma is an acquired disorder of hyperpigmentation presenting over the face. Modified Kligman's formula is used most commonly as treatment modality. Considering the various side effects of individual components of topical modified Kligman's formula, the use of oral tranexamic acid might be a better and safer alternative for the treatment of melasma. Aims: This study aims to compare the efficacy of oral tranexamic acid with that of topical modified Kligman's formula in the treatment of melasma. To assess the degree of improvement in pigmentation objectively using Melasma Area and Severity Index at baseline and after 4 weeks of treatment with oral tranexamic acid and topical modified Kligman's formula and to compare the side effects, if any, associated with both the modalities. Settings and Design: This was randomized, comparative, prospective, open-labeled study. Methods: This study was done in a tertiary care hospital from September 2018 to June 2019. Overall, 40 patients with clinical diagnosis of melasma were included in the study. Statistical Analysis Used: Paired t-test and unpaired t-test. Results: Improvement was noted in patients belonging to both the groups. After applying paired t-test, it was found that results were statistically significant in both the treatment groups. When both the groups were compared statistically using unpaired t-test, both the groups showed statistically equivalent results. Conclusions: Both oral tranexamic acid and modified Kligman's formula were equally effective in the treatment of melasma. Oral tranexamic acid is a better and safer alternative than the modified Kligman's formula to initiate the treatment in melasma.
Keywords: Melasma, modified Kligman's formula, oral tranexamic acid
|How to cite this article:|
Bansal A, Sardesai VR. Comparison of effectiveness of oral tranexamic acid with that of the topical modified Kligman's formula in the treatment of melasma. Indian J Drugs Dermatol 2019;5:100-3
|How to cite this URL:|
Bansal A, Sardesai VR. Comparison of effectiveness of oral tranexamic acid with that of the topical modified Kligman's formula in the treatment of melasma. Indian J Drugs Dermatol [serial online] 2019 [cited 2020 Sep 20];5:100-3. Available from: http://www.ijdd.in/text.asp?2019/5/2/100/272990
| Introduction|| |
Melasma is an acquired disorder of hyperpigmentation presenting over the face. The modified Kligman's formula is one of the most effective topical therapies, hence used more commonly. However, the topical corticosteroid component can promote undesirable and at times, irreversible side effects due to prolonged use. Easy over-the-counter availability of topical preparations in our country has resulted in prolonged self-use of this preparation by the patients. Oral tranexamic acid is known to have skin-lightening effect and is used for the treatment of melasma.
Considering the atrophogenic and other side effects of individual components of modified Kligman's formula, oral tranexamic acid may be a safer treatment option if its efficacy matches that of the modified Kligman's formula. Hence, this study was undertaken to compare the efficacy and safety of both the treatment options.
The aim of the study is to compare the efficacy of oral tranexamic acid with that of topical modified Kligman's formula in melasma.
- To assess the degree of improvement in pigmentation objectively using Melasma Area and Severity Index (MASI) at baseline and after 4 weeks of treatment with oral tranexamic acid and topical modified Kligman's formula
- To compare the side effects associated with both the above modalities.
| Methods|| |
This study was done in a tertiary care hospital in Maharashtra after ethics committee permission was obtained. A total of 40 newly diagnosed cases of melasma were included in the study and randomly allotted into one of the two groups.
- Group A patients were given oral tranexamic acid 250 mg twice daily for 4 weeks
- Group B patients were asked to apply modified Kligman's formula (combination of a topical formulation containing mometasone furoate 0.1%, tretinoin 0.025%, and hydroquinone 2%) topically once daily at night for 4 weeks. Patients of both groups were given broad-spectrum sunscreens with a sun protection factor of 30 to apply over face. Pre- and post-treatment evaluation was done with detailed history, clinical examination, MASI scoring, and color photographs after 4 weeks. Paired t-test was used to calculate P value in each group (intragroup), whereas unpaired t-test was used to calculate the P value while comparing the two groups (intergroup).
| Results|| |
A total of 40 newly diagnosed patients, all females with melasma belonging to the age group of 25–45 years, were included in the study. Twenty patients were prescribed conventional modified Kligman's formula while the remaining 20 were given oral tranexamic acid. The mean age was 31.93 years in modified Kligman's formula group and was 35.19 years in the oral tranexamic acid group. Improvement was noted in patients belonging to both the groups [Figure 1] and [Figure 2]. The MASI scores also were reduced in both the groups. After applying paired t-test, it was found that P < 0.05. Hence, results were statistically significant in both the treatment groups [Table 1] and [Table 2]. When both the groups were compared statistically using unpaired t-test, both the groups showed statistically equivalent results [Table 3]. This study showed that both topical Kligman's formula as well as oral tranexamic acid were effective for treating melasma, which was objectively seen by reduced MASI scores. Furthermore, when the efficacy between the two was compared, it showed to be equally effective.
| Discussion|| |
Melasma is an acquired disorder of hyperpigmentation presenting over the face. Females in their reproductive age group are commonly affected, with cheek, nose, upper lip, and forehead being the predominant areas of involvement. However, it can occur over areas other than the face and also in men. It is classically known to affect females of Asian or Hispanic origin with Fitzpatrick skin Type III-V  Clinically, when the area of involvement is taken into consideration, it can be centrofacial, malar or mandibular. Based on histological and Wood's lamp examination, it can be of epidermal, dermal, or mixed type. From an etiological point of view, it is related to high-intensity ultraviolet ray exposure, pregnancy, contraceptives, drugs, hormone therapy, and genetic abnormality. A predilection for facial skin and relative refractoriness to treatment makes patients cosmetically disfigured, along with putting them through intense psychological distress. It imparts a poor quality of life with adversely affected social interaction, recreation, and emotional wellbeing.
A variety of treatment options have been proposed and used in melasma. Topical modalities include modified Kligman's formula, hydroquinone, azelaic acid, kojic acid, and glycolic acid. Oral modality includes tranexamic acid. Procedure based modalities include chemical peels, microdermabrasion, and lasers.
Modified Kligman's formula is one of the most commonly used topical therapies. Kligman had originally used dexamethasone 0.1% along with tretinoin 0.1% and hydroquinone 5% in a cream base  However, there have been many modifications where dexamethasone has been substituted with other topical corticosteroids such as hydrocortisone, mometasone, fluocinolone and fluticasone, and the strength of tretinoin and hydroquinone have also been altered. Any topical corticosteroid should ideally not be used on the face for a longer duration as it can promote unpleasant side effects such as telangiectasia, hypertrichosis, atrophy, and acneiform eruptions. Tranexamic acid is known to have skin-lightening effect and has been used topically, intralesionally as microinjections and very recently, orally.,,
Sun exposure of the skin leads to the synthesis of plasmin activator, which thereby increases plasmin activity in keratinocytes. Plasmin leads to the release of arachidonic acid (AA). AA promotes prostaglandin E2 synthesis, which in turn, stimulates melanogenesis. In addition, increased plasmin elevates α-melanocyte-stimulating hormone and fibroblast growth factor which are both potent melanocyte stimulators. Plasmin also plays a role in angiogenesis by increasing the release of free vascular endothelial growth factor.
Tranexamic acid prevents ultraviolet-induced pigmentation by interfering with the plasminogen binding to the keratinocyte. Side effects include gastrointestinal problems, reversible hypomenorrhea, and color vision disturbances. Rare side effects reported are deep vein thrombosis, myocardial infarction, and pulmonary embolism. Contraindications include defective color vision, coagulopathy, hypersensitivity, cardiovascular disease, stroke, and anticoagulant medications. Before starting tranexamic acid, it is important to get prothrombin time, activated partial thromboplastin time, and other blood clotting parameters. Oral tranexamic acid for melasma is given in a dose of 250 mg twice a day. This is a much lower dose than that given to treat menorrhagia, i.e. 500 mg thrice a day. Apart from the oral formulation, tranexamic acid is also available in 2% emulsion, 3% cream, and 5% solution form. It can also be administered through intradermal injections in the concentration of 4 mg/ml.
Several studies show oral tranexamic acid to have a considerable impact on melasma with few side effects.
In 2012, Wu et al. showed a significant improvement in 96% of the 74 women who received tranexamic acid tablets in the dose of 250 mg twice daily for 6 months for melasma. 5.4% of the study population had some sort of gastrointestinal discomfort, and 8.1% developed hypomenorrhea. No serious complications were encountered. They also noted that women with multiple pigmented lesions along with melasma, such as freckles and lentigines, showed improvement only in melasma and not in any other lesion. This indicated different pathogenetic actions of tranexamic acid in melasma. Improvement started to appear at 4–8 weeks.
In 2013, Cho et al. compared the efficacy of IPL and Q-switched Nd: YAG laser treatment for melasma with and without oral TXA. They found oral TXA at 500 mg/day to improve the clinical efficacy of lasers and IPL in melasma. This is especially true during the relatively high sun exposure months.
Among the currently available topical modalities for the treatment of melasma, the best response is seen to the modified Kligman's formula; hence, it is used most commonly to initiate the therapy. However, it may be continued for a prolonged period by patients in spite of instructions from the dermatologist. In our country, topical preparations can be procured easily without prescription and so may be misused by the patients. In contrast, oral preparations are less easily procured without prescription.
Relapses are known to occur in melasma irrespective of the treatment modality used, and hence, a safer modality, which could be used repeatedly, is always desirable.
Considering the atrophogenic and other side effects of individual components of the triple combination regimen, it would be worthwhile to see how effective and safe is the use of oral tranexamic acid for reducing pigmentation of melasma.
Our study objectively shows both methods to treat melasma are equally effective by reduction in their respective MASI scores.
| Conclusion|| |
Keeping in mind the potential of misuse by patients of modified Kligman's formula, a phenomenon widely seen by dermatologists, perhaps it is time to consider oral tranexamic acid as a safe and effective therapy to initiate the treatment in this condition of widespread cosmetic concern.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]