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 Table of Contents  
Year : 2017  |  Volume : 3  |  Issue : 2  |  Page : 61-63

Tranexamic acid in melasma: Why and how?

1 Consultant Dermatologist, Dr Dashore's DHL Clinic, Indore, Madhya Pradesh, India
2 Consultant Dermatologist, Ujjain, Madhya Pradesh, India

Date of Web Publication28-Dec-2017

Correspondence Address:
Dr. Shuken Dashore
Dr Dashore's DHL Clinic, 11-C Sneh Nagar Main Road, Indore, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijdd.ijdd_37_17

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How to cite this article:
Dashore S, Mishra K. Tranexamic acid in melasma: Why and how?. Indian J Drugs Dermatol 2017;3:61-3

How to cite this URL:
Dashore S, Mishra K. Tranexamic acid in melasma: Why and how?. Indian J Drugs Dermatol [serial online] 2017 [cited 2024 Mar 2];3:61-3. Available from: https://www.ijdd.in/text.asp?2017/3/2/61/221751

Melasma is a chronic, acquired symmetrical pigmentary disorder characterized by gray-brown macules and patches affecting photodistributed part of the face such as the bridge of the nose, cheek, upper lip, forehead, and mandible. It is seen mostly in women of reproductive age group and has an onset usually after pregnancy. However, in around 10% of the cases, males are also affected. Causative factors that have been implicated in aggravating or precipitating melasma include sex hormones, genetic susceptibility, ultraviolet (UV) light exposure, oral contraceptive pills, cosmetics, and phototoxic drugs.[1] Epidemiologically, melasma is found in all geographical and ethnic groups but occurs more commonly in Asians and Middle Easterners.[2]

Treatment is mostly unsatisfactory. Various modalities include hydroquinone (HQ), tretinoin, and corticosteroid triple combinations, nonsteroidal demelanizing creams, superficial chemical peels (glycolic acid, trichloroacetic acid, kojic acid, and lactic acid), lasers (Q-switched Nd:YAG laser, ruby laser, Alexandrite laser, Er:YAG laser, and Fraxel laser), and intense pulsed light (IPL).

Despite the plethora of treatment modalities, the results of these treatments in melasma are poor. Treatment is often incomplete and there is a high rate of recurrence.

Tranexamic acid (TXA) has been recently recommended for the use in melasma.[3] It can be given as an oral preparation, a topical preparation, or an intralesional agent. It is probably the first oral medication that has proven efficacy in the treatment of melasma. Other oral medications are Polypodium leucotomos which has indirect effect, and glutathione which has unproven efficacy.

  Tranexamic Acid Top

TXA (trans-4-aminomethyl cyclohexane carboxylic acid) is an antifibrinolytic agent which blocks lysine-binding sites on plasminogen molecules.[4]

TXA is not a new molecule. It has been extensively used in the treatment of menorrhagia since the 70s. Dosages up to 2–4 g/day for 4–7 days have been used safely during cycles.[5] TXA has also been used prophylactically in hereditary angioedema in the duration of 8–34 months.[6]

For melasma, it has been used in low doses of 250 mg BD. Contraindications include defective color vision, coagulopathy, hypersensitivity, cardiovascular disease, stroke, and anticoagulant medications. Before starting TXA, it is important to get prothrombin time, activated partial thromboplastin time, and other blood clotting parameters. Common adverse effects include gastrointestinal side effects and reversible hypomenorrhea. Other reported adverse effects include deep vein thrombosis (DVT), myocardial infarction, and pulmonary embolism.[7]

  Use of Tranexamic Acid in Melasma Top

The use of TXA in melasma was first reported by Nijo in 1979.[8] It was an accidental discovery in a patient of melasma who was receiving TXA for chronic urticaria. Sun exposure of the skin leads to synthesis of plasmin activator, which thereby increases plasmin activity in keratinocytes. This plasmin leads to release of arachidonic acid (AA) via phospholipase A2.[9] Prostaglandin E2 synthesis promoted by AA stimulates melanogenesis. Increased plasmin elevates α-melanocyte-stimulating hormone and fibroblast growth factor which are both potent melanocyte stimulators.[7] Plasmin also plays a role in angiogenesis by increasing the release of free vascular endothelial growth factor (VEGF).

Repeated UV damage leads to increased production of mast cell tryptase which weakens and damages the basement membrane, a condition seen in melasma.[10] Contraceptive pills and pregnancy have also shown to increase serum plasminogen activator that can activate the melanogenesis process. Other dermal changes also seen in melasma include disruption of basement membrane, increased blood vessels, and solar elastosis. Number of mast cells may also be increased in the lesional dermis. These dermal factors may be the cause behind the refractory nature of melasma.[10]

TXA prevents UV-induced pigmentation by interfering with the plasminogen binding to the keratinocyte.[7] This reduces free AA and thereby reduces prostaglandins in the melanocytes. It also prevents angiogenesis by blocking the action of plasmin. It also reduces VEGF and endothelin 1 (ET)-1; both may be responsible for increased vascularity in melasma.[11]

Apart from the oral formulation, TXA is also available in 2% emulsion, 3% cream, and 5% solution form. It can also be administered via intradermal injections in the concentration of 4 mg/ml. There are various reports and studies to authenticate safety and usefulness of TXA in melasma. Some of these studies are mentioned here.

In a study by Seo et al., a significant inhibition of multiplication of melanocytes was seen following TXA application to neonatal foreskin-cultured melanocytes before UVB irradiation. They also observed decreased tyrosinase activity, decreased tyrosine-related protein 1 and 2 expression, and decreased melanin content. However, no change in number of all length of dendrites of melanocyte was seen.[12] A study by Hongjin and Xihui reported that the treatment duration was more important parameter than the dose of TXA.[13] Hence, the consensus arrived at a dose of 500 mg a day instead of 1.5 g/day used for menstrual disorders.

Histological analysis by Na et al. showed a significant reduction in epidermal melanin pigmentation, vessel numbers, and mast cell counts.[14] A significant reduction in lesional melanin index was also seen. Lee et al. showed a significant reduction in melasma area severity index (MASI) score at 8 and 12 weeks as compared to baseline following weekly intradermal injection of TXA (4 mg/ml).[15] Injections were given 1 cm apart, and 0.05 ml of TXA was injected at each site.

Wu et al. showed a significant improvement in 96% of the 74 women who received TXA 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 TXA in melasma. Improvement started to appear at 4–8 weeks.[3]

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.[16]

In a study by Kim et al., 2% topical TXA was applied in 23 melasma patients for 12 weeks. Significant improvement in modified MASI score was observed in 22 of 23 participants. Fontana-Masson staining showed a significant reduction in melanin content of epidermis. ET-1 was also found to be downregulated.[11] In a large study by Lee et al. in 2016, oral TXA was given to 561 patients of melasma. 89.7% showed improvement while 10% did not show any improvement. Among those cases who responded, improvement was seen in 2 months. A relapse rate of 27.2% was seen. One patient developed DVT and required discontinuation of therapy. She was later found to be a case of familial protein S deficiency.[7]

A recent split face study by Saki et al. comparing monthly intradermal TXA and daily 2% HQ cream showed a significant reduction in melanin value in each side. Monthly TXA showed better improvement at the end of 4 weeks, but the results were comparable at the end of 20 weeks.[17]

In another recent study by Atefi et al. comparing the 5% TXA cream and 2% HQ cream in two groups of people, they found significant improvement in MASI scores in both groups but no significant difference between the groups. A higher level of patient satisfaction was seen in TXA group (33.3% vs. 6.7% in HQ group). HQ group also suffered higher incidence of adverse effects such as skin irritation and erythema (10% vs. no major side effect in TXA group).[18]

We feel that TXA with microneedling using 2-mm dermaroller gives significant improvement in melasma. Treatment session is repeated monthly for 4 months. In our practice, we use a higher dose of TXA, i.e. 40 mg/ml. An important point missed by various studies is the frequency of maintenance sessions. In other words, how frequently the sessions have to be repeated to maintain the improvement. If the sessions required are too frequent, for example monthly, then it becomes too inconvenient for the patient. In our protocol, maintenance sittings are required every 6 months. This time gap is long enough for the patient to follow and thus prevent recurrence of melasma.

  Conclusion Top

Oral TXA at the dose of 250 mg twice daily is found to be a promising modality for the treatment of melasma. It is the only agent that acts by inhibiting UV light-induced melanocyte activation, hormone-induced melanocyte proliferation, VEGF-induced neovascularization, and mast cell-induced basement membrane damage.[19] It can be used both as a standalone therapy and in conjunction with other modalities. It can improve the results achieved by lasers and IPL.[16]

Considering effects of TXA at various levels of melanogenesis in melasma, it has a definite place in the treatment of this frustrating condition. Further studies are required to standardize the dose and duration of oral TXA in melasma. Large studies need to be done in various ethnic groups. In addition, studies need to be done for the ideal dose, concentration, and frequency of intradermal TXA injections. In conclusion, TXA has proven to be an essential tool in the armamentarium against melasma.

  References Top

Grimes PE. Melasma. Etiologic and therapeutic considerations. Arch Dermatol 1995;131:1453-7.  Back to cited text no. 1
Halder RM, Grimes PE, McLaurin CI, Kress MA, Kenney JA Jr. Incidence of common dermatoses in a predominantly black dermatologic practice. Cutis 1983;32:388, 390.  Back to cited text no. 2
Wu S, Shi H, Wu H, Yan S, Guo J, Sun Y, et al. Treatment of melasma with oral administration of tranexamic acid. Aesthetic Plast Surg 2012;36:964-70.  Back to cited text no. 3
Dunn CJ, Goa KL. Tranexamic acid: A review of its use in surgery and other indications. Drugs 1999;57:1005-32.  Back to cited text no. 4
Wellington K, Wagstaff AJ. Tranexamic acid: A review of its use in the management of menorrhagia. Drugs 2003;63:1417-33.  Back to cited text no. 5
Agostoni A, Marasini B, Cicardi M, Martignoni G, Uziel L, Pietrogrande M, et al. Hepatic function and fibrinolysis in patients with hereditary angioedema undergoing long-term treatment with tranexamic acid. Allergy 1978;33:216-21.  Back to cited text no. 6
Lee HC, Thng TG, Goh CL. Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis. J Am Acad Dermatol 2016;75:385-92.  Back to cited text no. 7
Nijo T. Treatment of melasma with tranexamic acid. Clin Res 1979;13:3129-31.  Back to cited text no. 8
Maeda K, Naganuma M. Topical trans-4-aminomethylcyclohexane carboxylic acid prevents ultraviolet radiation-induced pigmentation. J Photochem Photobiol B 1998;47:136-41.  Back to cited text no. 9
Hernández-Barrera R, Torres-Alvarez B, Castanedo-Cazares JP, Oros-Ovalle C, Moncada B. Solar elastosis and presence of mast cells as key features in the pathogenesis of melasma. Clin Exp Dermatol 2008;33:305-8.  Back to cited text no. 10
Kim SJ, Park JY, Shibata T, Fujiwara R, Kang HY. Efficacy and possible mechanisms of topical tranexamic acid in melasma. Clin Exp Dermatol 2016;41:480-5.  Back to cited text no. 11
Seo SJ, Cho SH, Cho WI, Jung MS, Ro SW, Kim MN, et al. Effect of trans-4-aminomethylcyclohexanecarboxylic acid on the proliferation and melanization in cultured normal human melanocytes. Ann Dermatol 2007;19:60-7.  Back to cited text no. 12
Hongjin ZH, Xihui Y. The clinical study of acidum tranexamicum on melasma. Prog Pharm Sci 2001;25:178-81.  Back to cited text no. 13
Na JI, Choi SY, Yang SH, Choi HR, Kang HY, Park KC, et al. Effect of tranexamic acid on melasma: A clinical trial with histological evaluation. J Eur Acad Dermatol Venereol 2013;27:1035-9.  Back to cited text no. 14
Lee JH, Park JG, Lim SH, Kim JY, Ahn KY, Kim MY, et al. Localized intradermal microinjection of tranexamic acid for treatment of melasma in Asian patients: A preliminary clinical trial. Dermatol Surg 2006;32:626-31.  Back to cited text no. 15
Cho HH, Choi M, Cho S, Lee JH. Role of oral tranexamic acid in melasma patients treated with IPL and low fluence QS nd: YAG laser. J Dermatolog Treat 2013;24:292-6.  Back to cited text no. 16
Saki N, Darayesh M, Heiran A. Comparing the efficacy of topical hydroquinone 2% versus intradermal tranexamic acid microinjections in treating melasma: A split-face controlled trial. J Dermatolog Treat 2017;Nov 9:1-6.  Back to cited text no. 17
Atefi N, Dalvand B, Ghassemi M, Mehran G, Heydarian A. Therapeutic effects of topical tranexamic acid in comparison with hydroquinone in treatment of women with melasma. Dermatol Ther (Heidelb) 2017;7:417-24.  Back to cited text no. 18
Tse TW, Hui E. Tranexamic acid: An important adjuvant in the treatment of melasma. J Cosmet Dermatol 2013;12:57-66.  Back to cited text no. 19

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