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Tranexamic Acid in Melasma Treatment

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Name:  Salman Ahmad

Dermatology in Clinical Practice

of South Wales

of Submission: 2 March 2018


and Introduction:

common pigmentary condition, melasma, is best defined as localized, chronic –
acquired hyper melanosis of the skin characterized by light to dark brown
macules and patches symmetrically involving the sun-exposed areas of the face,
neck and occasionally the forearms. It is commonly observed in reproductive age
group women, rarely in postmenopausal females and males (10% of cases).
Causative factors implicated in the melasma pathogenesis include genetic
susceptibility, ultraviolet (UV) light exposure, pregnancy, sex hormones, oral contraceptive
pills, thyroid dysfunction, cosmetics, phototoxic drugs (e.g., antiseizure
medications).(Grimes PE,1995)(Park et al,2017)

are three clinical patterns of melasma, malar (most
common), centro facial and mandibular. On the basis of visible light,
wood’s light and lesional histology, melasma has been classified as epidermal,
which has increased melanin predominantly in basal and suprabasal layers of the
epidermis with pigment accentuation on Wood’s lamp. The dermal type has
perivascular melanin-laden macrophages in the superficial and deep dermis and
does not accentuate with Wood’s lamp. The mixed variety has elements of both
and appears as deep brown colors with Wood’s lamp accentuation of only the
epidermal component.(Sanchez NP et al,1981)

is well known for treatment resistance and relapses on treatment
discontinuation.Melasma is found to be 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) 

melasma treatment, the introduction of tranexamic acid ( oral, topical or
intralesional) is relatively a novel concept. The skin?whitening effects of
Tranexamic acid were incidentally found when it was used in the treatment of
aneurysmal subarachnoid hemorrhage. Nijor from Japan,1979 first reported
Tranexamic Acid to be effective in melasma treatment.



dissertation proposal seeks to offer therapeutic benefits of the use of
Tranexamic acid (TXA) as an innovative agent, either as an oral, topical or
intralesional method for melasma treatment.


of this Proposal: Tranexamic acid being originally a hemostatic agent. Its use
in treating and gaining clinical benefits in Melasma treatment is not highly
documented and there is scope for establishing and validating Tranexamic acid
with accurate, medically focused perspectives.



Alternative hypothesis: There have been medically documented and validated
evidence that smaller doses use of Tranexamic acid (250 mg BD) has a beneficial
role in Melasma Treatment(Poojary & Minni, 2015). 

Null Hypothesis: There is no medical evidence to even remotely suggest that
smaller doses use of Tranexamic acid (250 mg BD) has a beneficial role in
Melasma Treatment.



Proposal uses the qualitative method of research, to achieve the quantum of
literature, findings, and studies to ascertain research question, as the first
step.  The literature used is secondary sources such as trial proceedings
of peers and data from published papers on the effect of TXA treatment on
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 author will infer from the
research and use the new-found knowledge to address the use of TXA. 

The first phase of the research will investigate literature on the chosen topic
to establish the effects of administering Tranexamic acid on Melasma

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 etiology of melasma has yet to be
established, and the course of treatment continues to be a challenge.

modalities include use of hypo pigmenting agents such as hydroquinone,
tretinoin, topical corticosteroids, 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)

the availability of these therapies, melasma is often recalcitrant to
treatment, melasma poses a great challenge as its treatment can be often
unsatisfactory with high recurrence rates.(Prignano F et al,2007)

the success rates 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 Acid Microinjections’ and
Tranexamic Acid with Microneedling in Patients with Melasma”,

Choi, Cho, and Lee titled “Role of oral tranexamic acid in melasma
patients treated with IPL and low fluence QS ND: Yag laser.

et al, 2012 concluded addition of oral Tranexamic acid to routine treatment
measures provide a rapid and better lightning in patients with melasma. Low
dose oral Tranexamic acid is thus recommended for melasma treatment.

Aamir al, 2014 concluded a rapid and sustained improvement can be provided
with the introduction of tranexamic acid in melasma treatment which none of the
existing treatment modalities for melasma has provided till date.

Ji, et al., titled” Effect of tranexamic acid on melasma- a clinical trial
with Histological evaluation”

Naeini study called “Topical tranexamic acid as a promising treatment for

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 a
lower production of arachidonic acid and thereby lowering prostaglandin levels.
Thus, Tranexamic acid becomes responsible for lowered melanocyte tyrosinase
activity and therefore, useful in treating melasma or UV-induced hyperpigmentation.

AWM Tan et al, 2016 concluded low-dose oral Tranexamic acid
can serve as a safe and useful adjunct in the treatment of refractory melasma.
How Tranexamic acid works in lightening melasma is unknown, but it
is possibly by modulating keratinocyte-melanocyte interactions and by
reducing vascularity in melasma lesions and through its effects on mast cells.


Padhi T et al,2015 concluded oral tranexamic acid can be
used as an adjunct with fluocinolone based triple combination cream for the
faster and sustained improvement in melasma treatment.


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 the treatment
of moderate to severe melasma” treated 250mg 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 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 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:  the study was conducted at a single center where patient demography
was predominantly Hispanic women.

studies which tested the efficacy of oral Tranexamic acid 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. 


therapeutic benefits of the use of Tranexamic acid (TXA), as an innovative
agent, either as an oral, topical or intralesional method for the treatment of


February: Proposal writing create a list of potential studies to review.

Initial review of primary resources with best results on use of TXA for melasma

April: Establish outline by cross-references and secondary data from journal
articles, studies

– July: Propose the best way to arrive at proposal objective 

– August: Submit Thesis



the research studies listed above and literature review, it can be said that
Tranexamic acid as a liposomal topical formulation, Intralesional/Intradermal
Injection of Tranexamic acid and Low-dose oral Tranexamic acid can be a safe
and effective alternative for treating refractory melasma.



the nearly 30 journal articles, books, review articles on the therapeutic
effects of Tranexamic acid in melasma, the conclusion that can be drawn is as
follows: Topical, Intralesional, and low dose oral Tranexamic
Acid is highly useful in treating refractory melasma.


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.




·         Grimes
PE (1995) Melasma. Etiologic and therapeutic considerations.Arch Dermatol 131:


·         Sanchez
NP, Pathak MA, Sato S et al. Melasma: A clinical, light microscopic,
ultrastructural, and immunofluorescence study. J Am Acad Dermatol 1981;4:698-



·         Park,
K.C., and Kim, I.S., 2017. Pathogenesis of Melasma. In Melasma and Vitiligo in
Brown Skin (pp. 21-31). Springer India.


·         Gupta
AK, Gover MD, Nouri K, Taylor S. Treatment of melasma: A review of clinical
trials. J Am Acad Dermatol 2006; 55:1048-65.


·         Prignano
F, Ortonne J, Buggiani G, Lotti T. Therapeutical approaches in melasma.
Dermatol Clin 2007; 25:337– 342.


·         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.


·         Nijor
T. Treatment of melasma with tranexamic acid. Clin Res 1979;13:3129?31.


·         Aamir,
S. and Naseem, R., 2014. The oral tranexamic acid in the treatment of melasma
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·         Wu S,
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·         Atefi,
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·         Ayer,
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·         Veggalam,
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