Project benefits of the use of Tranexamic acid (TXA)

Project Summary/ProposalTopic: Tranexamic Acid inMelasma Treatment Student Name:  Salman AhmadMSc Dermatology in ClinicalPracticeUniversity of South WalesDate of Submission: 2 March2018 Background and Introduction:  A common pigmentary condition, melasma, isbest defined as localized, chronic – acquired hyper melanosis of the skincharacterized by light to dark brown macules and patches symmetricallyinvolving the sun-exposed areas of the face, neck and occasionally theforearms. It is commonly observed in reproductive age group women, rarely inpostmenopausal females and males (10% of cases). Causative factors implicatedin the melisma pathogenesis include genetic susceptibility, ultraviolet (UV)light exposure, pregnancy, sex hormones, contraceptive pills, thyroid disease,cosmetics, phototoxic drugs (e.g., antiseizure medications).(Grimes PE,1995)(Parket al,2017)There are three clinicalpatterns of melasma, malar (most common), centro facial and mandibular.

On thebasis of visible light, wood’s light and lesional histology, melasma has beenclassified as epidermal, which has increased melanin predominantly in basal andsuprabasal layers of the epidermis with pigment accentuation on Wood’s lamp.The dermal type has perivascular melanin-laden macrophages in the superficialand deep dermis and does not accentuate with Wood’s lamp. The mixed variety haselements of both and appears as deep brown colors with Wood’s lamp accentuationof only the epidermal component.(Sanchez NP et al,1981)Melasma is well known for treatment resistance and relapseson treatment discontinuation.Melasma is found tobe refractory to treatment, with a tendency to recur after treatment.There is not a single satisfactory treatment modality to date.(Del Rosario E., et al, 2018)  In melasma treatment, theintroduction of tranexamic acid ( oral, topical or intralesional) is relativelya novel concept.

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The skin?whiteningeffects of Tranexamic acid were incidentally found when it was used in thetreatment of aneurysmal subarachnoid hemorrhage. Nijor from Japan,1979 firstreported Tranexamic Acid to be effective in melasma treatment.Objective: This dissertation proposal seeks to offertherapeutic benefits of the use of Tranexamic acid (TXA) as an innovativeagent, either as an oral, topical or intralesional method for melasmatreatment. Importance of this Proposal:Tranexamic acid being originally a hemostatic agent. Its use in treating andgaining clinical benefits in Melasma treatment is not highly documented andthere 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 dosesuse of Tranexamic acid (250 mg BD) has a beneficial role in MelasmaTreatment(Poojary & Minni, 2015).

   HO: Null Hypothesis: There is no medicalevidence to even remotely suggest that smaller doses use of Tranexamic acid(250 mg BD) has a beneficial role in Melasma Treatment.Methodology: This Proposal uses the qualitative method ofresearch, to achieve the quantum of literature, findings, and studies toascertain research question, as the first step. The literature used is secondary sources such as trial proceedings of peersand data from published papers on the effect of TXA treatment on Melasma. Allof the referenced publications will be no older than 10 years and will not havea low rating. In the next step, the author will infeG1 r from the research and use the new-foundknowledge to address the use of TXA. G2  Methods: The first phase of the research willinvestigate literature on the chosen topic to establish the effects ofadministering Tranexamic acid on Melasma treatment.

   At the outset, it is important to understandMelasma as a disorder and explore the reasons for its occurrence. Melasma is apigmentation disorder and is common among women of Hispanic and Asian groups.The etiology of melasma has yet to be established, and the course of treatmentcontinues to be a challenge.

Treatment modalities includeuse of hypo pigmenting agents such as hydroquinone, tretinoin, topicalcorticosteroids, superficial peeling (lactic acid, glycolic acid,trichloroacetic acid and kojic acid), LASERS (including Q-switched ruby laser,Q-switched Alexandrite laser, erbium: yttrium-aluminum-garnet (Er: YAG) laser,Fraxel laser, and intense pulsed light.(Gupta AK et al,2006)Despite the availability of these therapies, melasma isoften recalcitrant to treatment, melasma posesa great challenge as its treatment can be often unsatisfactory with highrecurrence rates.(Prignano F et al,2007)Additionally, the successrates of all these procedures are considered paradoxical darkening and low,apart from their recognizable side-effects.  Journal paper by Budamakuntla L., et al.,titled “A Randomized, Open-label, Comparative Study of Tranexamic AcidMicroinjections’ and Tranexamic Acid with Microneedling in Patients withMelasma”, Cho, Choi, Cho, and Lee titled”Role of oral tranexamic acid in melasma patients treated with IPL and lowfluence QS ND: Yag laser.G3 Karn et al, 2012 concluded addition of oral Tranexamic acid to routinetreatment measures provide a rapid and better lightning in patients withmelasma.

Low dose oral Tranexamic acid is thus recommended for melasmatreatment.G4 G5 G6 G7 al, 2014G8  concludeda rapid and sustained improvement can be provided with the introduction of tranexamicacid in melasma treatment which none of the existing treatment modalities formelasma has provided till date. G9 G10 G11 Na Ji, et al., titled”Effect of tranexamic acid on melasma- a clinical trial with Histologicalevaluation”Ebrahim Naeini study called”Topical tranexamic acid as a promising treatment for melasma”.

 Anju George (2015) review article in JournalPigment International, established that Tranexamic acid is an effectivedepigmenting agent as it is a synthetic derivative of lysine amino acid anduseful in arresting the conversion of plasminogen into plasmin (inhibitingplasminogen activator). The result is a lower production of arachidonic acidand thereby lowering prostaglandin levels. Thus, Tranexamic acid becomesresponsible for lowered melanocyte tyrosinase activity and therefore, useful intreating melasma or UV-induced hyperpigmentation.AWM Tan et al, 2016 concluded low-doseoral Tranexamic acid can serve as a safe and useful adjunct in the treatment ofrefractory melasma. How Tranexamic acid works in lightening melasma is unknown,but it is possibly by modulating keratinocyte-melanocyte interactions and byreducing vascularity in melasma lesions and through its effects on mast cells. Padhi T et al,2015 concluded oral tranexamic acid can beused as an adjunct with fluocinolone based triple combination cream for thefaster and sustained improvement in melasma treatment.G12 G13  Del Rosario E, Florez- PollackS, Zapata Jr. L, Hernandez K, Tovar-Garza A, Rodrigues M, Hynan LS, Pandya AG’s(2017), “Randomized, placebo-controlled, double-blind study of oraltranexamic acid in the treatment of moderate to severe melasma” treated250mg of TA/placebo capsules (2 times a day, for three months) to 44 patients.

39 completed the study and the primary outcomes were the Modified Melasma Areaand the Severity Index (mMASI) score showing 49% lower mMASI in TA group and18% in the control group. Severe melasma showed higher rates of improvementover moderate melasma. Further, after treatment stopped for three months, therewas 26% reduction in mMASI in the TA Group, over the baseline results.Additionally, they witnessed 19% reduction in the placebo arm and reported noadverse events in both the groups. Hence, this study established that oral TXAwas effective and superior to placebo in patients who had moderate to severemelasma, and thus ideal alternative to standard therapies. The limitations ofthis group were:  the study was conductedat a single center where patient demography was predominantly Hispanic women.  Other studies which tested the efficacy oforal Tranexamic acid vs Triple combination for melasma treatment ( Neerja Puri,2015) and concluded that recurring melasma is satisfactorily treated with oralTXA in comparison to the combination of other modalities.  Expected OutcomesThe therapeutic benefits ofthe use of Tranexamic acid (TXA), as an innovative agent, either as an oral,topical or intralesional method for the treatment of melasma Gnat ChartJanuary- February: Proposalwriting create a list of potential studies to review.

February-March: Initial reviewof primary resources with best results on use of TXA for melasmaMarch– April: Establishoutline by cross-references and secondary data from journal articles, studiesJune – July: Propose the bestway to arrive at proposal objective  July – August: Submit Thesis Recommendation: From the research studieslisted above and literature review, it can be said that Tranexamic acid as aliposomal topical formulation, Intralesional/Intradermal Injection ofTranexamic acid and Low-dose oral Tranexamic acid can be a safe and effectivealternative for treating refractory melasma. Conclusion: Across the nearly 30 journalarticles, books, review articles on the therapeutic effects of Tranexamic acidin melasma, the conclusion that can be drawn is as follows: Topical ,Intralesional and low dose oral Tranexamic Acid is highly useful in treating refractorymelasma.  Limitations of study: Theresearch includes the study of two different demographics – Hispanic andAsians.

Therefore, the results of the studies vary in terms of moderate or highrates of success, is subjective to the population where the study wasconducted. References:  ·        Grimes PE (1995) Melasma. Etiologic and therapeutic considerations.ArchDermatol 131: 1453-1457. ·        Sanchez NP, Pathak MA, Sato S et al. Melasma: A clinical, lightmicroscopic, ultrastructural, and immunofluorescence study. J Am Acad Dermatol1981;4:698- 710.  ·        Park, K.

C., and Kim, I.S.

, 2017. Pathogenesis of Melasma. In Melasma andVitiligo in Brown Skin (pp.

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S. and Pandya, A.G., 2018. Randomized,placebo-controlled, double-blind study of oral tranexamic acid in the treatmentof moderate-to-severe melasma. Journal of the American Academy of Dermatology,78(2), pp.

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