Dissertation Proposal Topic: Tranexamic Acid in Melasma TreatmentStudent Name: Salman AhmadMSc Dermatology in Clinical PracticeUniversity oG1 G2 G3 G4 G5 G6 G7 G8 f South G9 G10 G11 G12 G13 WalesDate of Submission: 2 March 2018 Background and Introduction: A common pigmentary condition, melasma, is best defined as localized, chronic- acquired hyper melanosis of skin. The condition is found to be refractory to treatment, with a tendency to recur after treatment phases (Del Rosario E, Florez- Pollack S, Zapata Jr. L, Hernandez K, Tovar-Garza A, Rodrigues M, Hynan LS, Pandya AG, 2017).
Tranexamic Acid, which is a hemostatic drug, has in the past been successfully used in treating hypo pigmentary effects. Further, low-grade melasma patient profiles have demonstrated sufficient results when Tranexamic acid has been administered. G14 Its use has been validated in two conditions – on melasma lesion, and blocking UV-induced pigmentation.
It was successful in risk UV exposures, pregnant women, women in use of sex hormones, birth control pills, increased UV effects and so on.Objective: This dissertation proposal seeks to offer therapeutic, medical and cure-aiding benefits of the use of Tranexamic acid (TXA) as an innovative agent, either as an oral, topical or intralesional method for monitoring, control, and treatment of melasma.G15 G16 G17 G18 Importance of this Proposal: Tranexamic Acid was originally used as hemostatic agent. Its use in treating and gaining clinical benefits in the treatment of MelasmaG19 is not highly documented and there is scope for establishing and validating Tranexamic acid with accurate, medically focused perspectives. Hypothesis: HI: Alternative hypothesis: There have been medically documented and validated evidence that smaller doses use of Tranexamic Acid (250 mg BD) has the beneficial and remedial action against the spread of MelasmaG20 G21 (Poojary & Minni, 2015).
HO: Null Hypothesis: There is no medical evidence to even remotely suggest that smaller doses use of Tranexamic Acid (250 mg BD) has a beneficial and remedial action against the spread of Melasma. Methodology: This Proposal uses the qualitative method of research, to achieve the G22 quantum of literature, findings, and studies to ascertain research question, as the first step. G23 The literature used is secondary sources such as trial proceedings of peers and data from published papers on the effect of TXA treatment on G24 Melasma. All of the referenced publications will be no older than 10 years and will not have a low rating. In the next step, the authoG25 r will infer from the research and use the new-found knowledge to address the use of Tranexamic acid. G26 Methods: The first phase of the research will investigate literature on the chosen topic to establish the effects of administering Tranexamic acid in Melasma treatment. At the outset, it is important to understand Melasma as a disorder and explore the reasons for its occurrence.
Melasma is a pigmentation disorder and is common among women of Hispanic and Asian groups. The pathogens for this condition are yet to be established, and the course of treatment continues to be a challenge. Traditionally, this condition is treated using agents for skin-lightening. However, the successes have varied. When patients are refractory then topical therapy is used. Intense pulsed light, even laser interventions are also used as an alternative treatment method. Additionally, the success rates of all these procedures are considered paradoxical darkening and low, apart from their recognizable side-effect.
Journal paper by Budamakuntla L., et al., titled “A Randomized, Open-label, Comparative Study of Tranexamic Acid Microinjections’ and Tranexamic Acid with MicroneedG27 ling in Patients with Melasma”, Cho, Choi, Cho and Lee titled “Role of oral tranexamic acid in melasma patients treated with IPL and low fluence QS ND:Yag laser. Na Ji, et al., titled” Effect of tranexamic acid on melasma- a clinical trial with Histological evaluation” and Ebrahim Naeini study called “Topical tranexamic acid as a promising treatment for melasma”.
G28 G29 Anju George (2015) review article in Journal Pigment International, established that Tranexamic Acid is an effective depigmenting agent as it is a synthetic derivative of lysine amino acid and useful in arresting the conversion of plasminogen into plasmin (inhibiting plasminogen activator). The result is the lower production of arachidonic acid and thereby lowering prostaglandin levels. Thus, TXA becomes responsible for lowered melanocyte tyrosinase activity and therefore, useful in treating melasma or UV-induced hyperpigmentation. Del Rosario E, Florez- Pollack S, Zapata Jr. L, Hernandez K, Tovar-Garza A, Rodrigues M, Hynan LS, Pandya AG’s (2017), “Randomized, placebo-controlled, double-blind study of oral tranexamic acid in 2 the treatment of moderate to severe melasma” treated 250mg of TA/placebo capsules (2 times a day, for three months) to 44 patients. 39completed the study and the primary outcomes were the Modified Melasma Area and the Severity Index (mMASI) score showing 49% lower mMASI in TA group and 18% in the control group. Severe melasma showed higher rates of improvement G30 over moderate melasma.
Further, after treatment stopped for three months, there was 26% reduction in mMASI in the TA Group, over the baseline results. Additionally, they witnessed 19% reduction in the placebo arm and reported no adverse events in both the groups. Hence, this study established that oral TXA was effective and superior to placebo in patients who had moderate to severe melasma, and thus ideal alternative to standard therapies. The limitations of this group were: G31 the study was conducted at a single center where patient demography was predominantly Hispanic women. G32 G33 G34 Other studies which tested the efficacy of oral TXA vs Triple combination for melasma treatment ( Neerja Puri, 2015) and concluded that recurring melasma is satisfactorily treated with oral TXA in comparison to the combination of other modalities.
Expected OutcomesThe therapeutic, medical and cure-aiding benefits of G35 the use of Tranexamic acid (TXA), as an innovative agent, either as an oral, topical or intralesional method for monitoring, control, and treatment of melasma. Gnat ChartJanuary- February: Proposal writing create a list of potential studies to review. February-March: Initial review of primary resources with best results on use of TXA for melasmaMarch– April: Establish outline by cross-references and secondary data from journal articles, studiesJune – July: Propose the best way to arrive at proposal objective July – August: Submit ThesisRecommendation: From the research studies listed above and literature review, it can be said TXA as a liposomal can be used safely in its topical format. Some of the studies imply that it can be used to lighten melasma and is recommended as a low-dose oral TXA as a safe and useful alternative to treating refractory melasma.
Conclusion: Across the nearly 30 journal articles, books, review articles on the therapeutic effects of TXA on melasma, the conclusion that can be drawn is as follows: The Acid in its liposomal form factor is highly useful in arresting melasma and will continue for a period of 3 months after the treatment has stopped. Thus, as a low-dose TXA is effective in the treatment of refractory melasma. G36 The research objective is achieved by this study as the therapeutic effect is evaluated for oral TXA administration to abate melasma refractory.
Moreover, in conjunction with other related studies in the use of TXA for melasma, it is revealed that there TXA is effective in aiding moderate conditions at a faster rate than average or sub-normal melasma conditions, in the controlled groups that were tested.Limitations of study: The research includes the study of two different demographics – Hispanic and Asians. Therefore, the results of the studies vary in terms of moderate or high rates of success, is subjective to the population where the study was conducted. References: Aamir, S.
and Naseem, R., 2016. The oral tranexamic acid in the treatment of melasma in Pakistani population: a pilot study. G37 G38 Journal of Pakistan Association of Dermatology, 24(3), pp.198-203.
G39 Atefi, N., Dalvand, B., Ghassemi, M., Mehran, G. and Heydarian, A., 2017. Therapeutic Effects of Topical Tranexamic Acid in Comparison with Hydroquinone in Treatment of Women with Melasma.
Dermatology and therapy, 7(3), pp.417-424. Ayer, J., Watson, R., Beck, P.
, Duncan-Parry, E., Ahmed, A. and Griffiths, C.E.M., 2014. British Cosmetic Dermatology Group Orals.
safety, 13, pp.861-2. Banihashemi, M., Zabolinejad, N., Jaafari, M.R., Salehi, M.
and Jabari, A., 2015. Comparison of therapeutic effects of liposomal Tranexamic Acid and conventional Hydroquinone on melasma. Journal of cosmetic dermatology, 14(3), pp.174-177.
Budamakuntla, L., Loganathan, E., Suresh, D.H., Shanmugam, S., Suryanarayan, S., Dongare, A.
, Venkataramiah, L.D. and Prabhu, N.
, 2013. A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with micro needling in patients with melasma. Journal of cutaneous and aesthetic surgery, 6(3), p.139. Dashore, S. and Mishra, K.
, 2017. Tranexamic acid in melasma: Why and how?. Indian Journal of Drugs in Dermatology, 3(2), p.61. Del Rosario, E.
, Florez-Pollack, S., Zapata, L., Hernandez, K.
, Tovar-Garza, A., Rodrigues, M., Hynan, L.S. and Pandya, A.G., 2018. Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma.
Journal of the American Academy of Dermatology, 78(2), pp.363-369. George, A., 2016. Tranexamic acid: An emerging depigmenting agent. Pigment International, 3(2), p.66. Guevara, I.
L. and Pandya, A.G., 2003.
Safety and efficacy of 4% hydroquinone combined with 10% glycolic acid, antioxidants, and sunscreen in the treatment of melasma. International journal of dermatology, 42(12), pp.966-972.
Hurley, M.E., Guevara, I.L., Gonzales, R.
M. and Pandya, A.G., 2002. Efficacy of glycolic acid peels in the treatment of melasma.
Archives of DermatologyG40 , 138(12), pp.1578-1582.G41 Lee, D.
H., Oh, I.Y.
, Koo, K.T., Suk, J.
M., Jung, S.W., Park, J.O.
, Kim, B.J. and Choi, Y.M., 2014. Reduction in facial hyperpigmentation after treatment with a combination of topical niacinamide and tranexamic acid: a randomized, double?blind, vehicle?controlled trial.
Skin Research and Technology, 20(2), pp.208-212. Lee, J.H., Park, J.
G., Lim, S.H.
, Kim, J.Y., Ahn, K.Y., KIM, M.Y. and Park, Y.
M., 2006. Localized intradermal microinjection of tranexamic acid for treatment of melasma in Asian patients: a preliminary clinical trial.
Dermatologic surgery, 32(5), pp.626-631. Karn, D., Kc, S., Amatya, A.
, Razouria, E.A. and Timalsina, M., 2014. Oral tranexamic acid for the treatment of melasma. Kathmandu University Medical Journal, 10(4), pp.
40-43. Kim, H.J., Moon, S.H., Cho, S.
H., Lee, J.D. and Kim, H.
S., 2017. Efficacy and Safety of Tranexamic Acid in Melasma: A Meta-analysis and Systematic Review. Acta Dermatol-venereologicaG42 G43 .G44 Kwon, S.H., Hwang, Y.
J., Lee, S.K. and Park, K.C., 2016. Heterogeneous pathology of melasma and its clinical implications. International journal of molecular sciences, 17(6), p.
824. Machekposhti, S.A., Soltani, M., Najafizadeh, P., Ebrahimi, S.A.
and Chen, P., 2017. Biocompatible polymer microneedle for topical/dermal delivery of tranexamic acid. Journal of Controlled Release, 261, pp.87-92. Manosroi, A., Podjanasoonthon, K.
, and Manosroi, J., 2002. Development of novel topical tranexamic acid liposome formulations. G45 International Journal of PharmaceuticsG46 G47 , 235(1), pp.61-70.G48 G49 Melasma, N.T.M.
, 2014. Pigmentary Disorders. Na, J.I., Choi, S.Y., Yang, S.
H., Choi, H.R.
, Kang, H.Y. and Park, K.
C., 2013. Effect of tranexamic acid on melasma: a clinical trial with histological evaluation. Journal of the European Academy of Dermatology and Venereology, 27(8), pp.1035-1039. Nanda, S., Grover, C.
and Reddy, B.S., 2004. Efficacy of hydroquinone (2%) versus tretinoin (0.025%) as adjunct topical agents for chemical peeling in patients with melasma. G50 Dermatologic surgery, 30(3), pp.385-389.
G51 Park, K.C., and Kim, I.S., 2017.
Pathogenesis of Melasma. In G52 Melasma and Vitiligo in Brown Skin (pp. 21-31). Springer India. Poojary, S. and Minni, K.
, 2015. Tranexamic acid in melasma: A review. Pigmentary Disorders, 2(228), pp.2376-0427. Rai, T., Role of Tranexamic Acid in Management of Melasma.
Rodrigues, M. and Pandya, A.G., 2015.
Melasma: clinical diagnosis and management options. Australasian Journal of Dermatology, 56(3), pp.151-163. Sharma, R., Mahajan, V.K., Mehta, K.S.
, Chauhan, P.S., Rawat, R., and Shiny, T.N., 2017. Therapeutic efficacy and safety of oral tranexamic acid and that of tranexamic acid local infiltration with microinjections in patients with melasma: a comparative study.
G53 Clinical and experimental dermatology, 42(7), pp.728-734. Tan, A.W.M., Sen, P., Chua, S.H.
and Goh, B.K., 2017. Oral tranexamic acid lightens refractory melasma. Australasian Journal of Dermatology, 58(3).
Veggalam, V. and Perumalla, N., 2017.
Intralesional tranexamic acid: Safe and effective way of treatment for melasma. Indian Journal of Drugs in Dermatology, 3(2), p.81. Viyoch, J., Tengamnuay, I.
, Phetdee, K., Tuntijarukorn, P. and Waranuch, N., 2010. Effects of trans-4-(aminomethyl) cyclohexane carboxylic acid/potassium azeloyl diglycinate/niacinamide topical emulsion in Thai adults with melasma: a single-center, randomized, double-blind, controlled study. Current Therapeutic Research, 71(6), pp.345-359. Wu, S.
, Shi, H., Wu, H., Yan, S., Guo, J., Sun, Y. and Pan, L., 2012.
Treatment of melasma with oral administration of tranexamic acid. Aesthetic plastic surgery, 36(4), pp.964-970. Yoo, J., Ahn, H.
, Kim, M.S., Jue, M.
S. and Choi, K.H.
, 2017. Efficacy of Topical Tranexamic Acid in Treatment of Melasma. Korean Journal of Dermatology, 55(5), pp.283-289.