Comparative study of oral tranexamic acid and triple combination versus tranexamic acid through microneedling in patients of melisma

Abstract

p class="abstract"> Background: Melasma can be difficult to treat due to the refractory and recurrent nature of condition. The aim of this study is to compare and evaluate the efficacy of oral tranexamic acid and triple combination versus tranexamic acid through microneedling in patients of melisma.
Methods: This is a prospective study with a sample size of 20, 10 in each treatment arm.10 patients (group-A) were given topical triple combination to apply daily at night and along with oral tranexamic acid 250 mg twice a day, while in the other arm (group-B), 10 patients were given procedural treatment of microneedling with tranexamic acid (4 mg/ml). Patients were followed up for 3 consecutive months. Clinical photograph was taken after each visit, and a modified melasma area and severity index was performed at the beginning and end of the treatment.
Results: According to melasma area and severity index, improvement in group-A was 65% as compared to 33% in group-B.
Conclusions: Triple combination is known as gold standard treatment in melasma, but because of its long term steroidal and tretinoin side effects we can consider microneedling with TXA as an adjuvant treatment.

</p

Full text

International Journal of Research in Dermatology | July-September 2019 | Vol 5 | Issue 3 Page 537
International Journal of Research in Dermatology
Wali V et al. Int J Res Dermatol. 2019 Aug;5(3):537-541
http://www.ijord.com
Original Research Article
Comparative study of oral tranexamic acid and triple combination
versus tranexamic acid through microneedling in patients of melisma
Vishal Wali, Hemangi Parwani*
INTRODUCTION
Melasma is the most common cause of facial melanosis
and is manifested by hyperpigmented macules on the face
which become more pronounced after sun exposure. It
accounts for 2.5%-4% of patients seen in dermatology
clinic in South East Asia.1,2 Increased pigmentation is
almost invariable in pregnancy and is most marked in
brunettes. Melasma is frequently seen in women on oral
contraceptives. Mostly starts between the ages of 20 and
40 years. Up to 10% of cases of melasma occur in men.
More common in light brown skin types, particularly
latin Americans and those from the Middle East or Asia.
Several factors have been linked to melasma, among
them UV exposure and hormonal factors appear to be the
most significant. Local or diffuse hyperpigmentation can
be seen in a subset of women, probably due to these
hormonal factors. Pregnancy and oral contraceptives have
been linked to increased skin pigmentation. It has been
speculated that this is due to increased levels of oestrogen
and progesterone stimulating the activity of melanocytes.
In the context of pregnancy, melasma is regarded as a
normal physiological change, along with darkening of the
nipples and linea nigra. Treatment of melasma can be
difficult due to the refractory and recurrent nature of the
condition. Different skin depigmentation formulations
can be used and contain one or several active compounds.
However, there are many ongoing studies aiming to find
more effective and safe treatment.
ABSTRACT
Background:
Melasma can be difficult to treat due to the refractory and recurrent nature of condition. The aim of this
study is to compare and evaluate the efficacy of oral tranexamic acid and triple combination versus tranexamic acid
through microneedling in patients of melisma.
Methods:
This is a prospective study with a sample size of 20, 10 in each treatment arm.10 patients (group-A) were
given topical triple combination to apply daily at night and along with oral tranexamic acid 250 mg twice a day, while
in the other arm (group-B), 10 patients were given procedural treatment of microneedling with tranexamic acid (4
mg/ml). Patients were followed up for 3 consecutive months. Clinical photograph was taken after each visit, and a
modified melasma area and severity index was performed at the beginning and end of the treatment.
Results:
According to melasma area and severity index, improvement in group-A was 65% as compared to 33% in
group-B.
Conclusions:
Triple combination is known as gold standard treatment in melasma, but because of its long term
steroidal and tretinoin side effects we can consider microneedling with TXA as an adjuvant treatment.
Keywords: Camparative study, Melasma, Microneedling, Tranexamic acid
Department of Dermatology, Venereology and Leprology, Basaveshwara Teaching and General Hospital, Kalaburagi,
Karnataka, India
Received: 04 February 2019
Revised: 28 March 2019
Accepted: 02 April 2019
*Correspondence:
Dr. Hemangi Parwani,
E-mail: hemangi.parwani903@gmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: http://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20193226

Wali V et al. Int J Res Dermatol. 2019 Aug;5(3):537-541
International Journal of Research in Dermatology | July-September 2019 | Vol 5 | Issue 3 Page 538
METHODS
A prospective, randomized study was conducted on 20
clinically diagnosed melasma patients, with 10 patients in
each group of the study. Patients were selected among
those coming for treatment of various dermatoses in
outpatient department of DVL, Basaveshwara Teaching
and General Hosiptal during period of September 2017 to
September 2018, after obtaining approval from
institutional ethical committee. In this study patients with
facial melasma belonging to both sexes between age
group 20-45 years were selected. Pregnant, lactating
females and patients with a history of hypertrophic scars,
keloids, bleeding disorder, use of anticoagulant, oral
contraceptives pills and patient who refuse to come for
follow up were excluded from the study.
After taking complete history, bed site examination and
baseline investigations, patients were randomly included
in each group of the study. Bed site examination includes
Woods lamp examination to classify the type of melasma.
Modified melasma area and severity index (MASI) was
recorded to assess the severity of melisma (Table 1) in
the patient and to compare the improvement on every
visit. Three parameters are considered in calculating the
MASI score and i.e., darkness (D), homogenecity (H) and
area (A) of the pigmentation. Multiplication factor for
forehead, chin and cheeks are 0.3, 0.3 and 0.1
respectively. Therefore total MASI score is calculated by
using the following formula i.e.,
0.3(D+H)A+0.3(D+H)A+0.3(D+H)A+0.1(D+H)A. The
baseline investigations like liver function test, renal
function test, coagulation profile were done before
initiation of the study.
Patient on group A were given oral tranexamic acid 250
mg twice a day with daily application of topical triple
combination at night.
Patient on group B requires pre-procedure preparation
and that includes, gentle cleansing of the skin and then
application of topical EMLA cream over the area to be
treated for 45 to 60 minutes. Meanwhile 4 mg/ml of
tranexamic acid was prepared as it is available as 5 ml
ampoule containing 500mg of the drug. About 1 ml of the
tranexamic acid was withdrawn from the ampoule and
was diluted with 25ml of distilled water to make it a
concentrate of 4mg/ml. Prepared tranexamic acid
(4mg/ml) was applied over the pigmented area with the
peeling brush, then skin was stretched and microneedling
was carried out in vertical, horizontal and both diagonal
directions for about 4-5 times in above said directions.
Ice packs were applied over the treated areas. The patient
was instructed to follow the strict photo-protective
measures.
Mironeedling was done with dermaroller with needle
length of 2.5 mm and diameter of 0.25 mm. It was
studded with 192 fine needles of medical graded stainless
steel. This procedure was done three times at monthly
interval (0, 4 and 8 weeks) and followed up for further 3
months at monthly interval. To assess the clinical
response, clinical photographs were taken at the
beginning of the therapy and then serially. MASI score
was performed at monthly intervals. Any complications
and side effects were also noted during these follow ups.
Statistical analysis was done with t-test using SPSS
version 20.0 and p value <0.05 was taken as significant.
Table 1: Grading of the melasma area and severity
index with its three parameters.
Area
(A)
0=No involvement;
1=<10% involvement;
2=11-29% involvement;
3=30-49% involvement;
4=50-69% involvement;
5=70-89% involvement; and
6=90-100% involvement.
Darkness
(D)
0=normal skin color;
1=barely visible hyperpigmentation;
2=mild hyperpigmentation;
3=moderate hyperpigmentation;
4=severe hyperpigmentation.
Homogenity
(H)
0=normal without evidence of
hyperpigmentation;
1=specks of involvement;
2=small patchy areas of involvement
<1.5 cm diameter;
3=patches of involvement >2 cm
diameter;
4=uniform skin involvement without
any clear areas.
RESULTS
The study with 10 patients in each group, 62% of male
patient belonged to the age group of 25-30 years, while
58% of female patients were between 25-35 years age
group (Figure 1A). The number of women was more
compared to men in group A i.e., 70% female patients
while in group B there were equal distribution of female
and male patients (Figure 1B). All patients had
Fitzpatrick skin type 4 or 5. Patients had mixed pattern of
melasma, the distribution of melasma was either
centrofacial or malar. None of the patients were on drugs.
Mean melasma area and severity index score of the
patients at the beginning and end of the trial with
percentage improvement is shown in (Figure 2). Mean
decrease in melasma area and severity index score in
group A was significantly higher than in group B. Figure
3 and 4 shows example of clinical improvement in some
of the patients.
No major side effects were observed except for mild pain
and erythema in microneedling with tranexamic acid
group patients, which lasted for 2-3 days. In group A, no
side effects were noted. There was no change in
coagulation profile at the end of 3 months. At 3 months

Wali V et al. Int J Res Dermatol. 2019 Aug;5(3):537-541
International Journal of Research in Dermatology | July-September 2019 | Vol 5 | Issue 3 Page 539
of follow up, 4 patients in group A and 3 patients in
group B complaint of repigmentation. There was also the
history of not using any kind of photo protection which
was adviced.
 Average MASI before treatment: Group A– 12.38%;
Group B– 15.32%.
 Average decrease in MASI at the end of treatment:
Group A– 4.07%; Group B– 10.35%.
 Percentage decrease in MASI at the end of treatment:
Group A– 67.12%; Group B– 32.44%.
Figure 1: Percentage of female (A) and male (B)
patients in different age groups.
Figure 2: Mean MASI score of the patient before and
after treatment in both the groups.
Figure 3 (A and B): Group A patient (clinical
improvement in pigmentation after 12 weeks).
Figure 4 (A and B): Group B patient (clinical
improvement in pigmentation after 12 weeks).
Female
20-25
25-30
30-35
35-40
40-45
Age group
0
62%
38%
Male
20-25
25-30
30-35
35-40
40-45
Age Group
0
2
4
6
8
10
12
14
16
18
MASI SCORE
Group A
Group B
B
A
B
A
A
B

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International Journal of Research in Dermatology | July-September 2019 | Vol 5 | Issue 3 Page 540
DISCUSSION
One of the most popular topical therapy for melasma
worldwide is the triple combination regimen known as
Kligmans formula. And considering its side effects
tranexamic acid can be used as potentially a safe,
effective, and promising therapeutic agent for the
treatment of melasma. Tranexamic acid is possibly the
only treatment of melasma that can prevent the activation
of melanocyte by sunlight, hormonal influence, and
injured keratinocyte (after UV radiation, chemical
peeling, IPL, laser) through the inhibition of the plasmin
activator system by preventing the binding of
plasminogen to the keratinocytes, which ultimately
results in decreased free arachidonic acid and a
diminished ability to produce prostaglandins, which in
turn decrease melanocyte tyrosinase activity.3-8 Thus
tranexamic acid has been demonstrated with
depigmenting properties and combining this novel agent
(oral, microneedling) with other modalities of treatment
has shown promising results. In addition to this action,
tranexamic acid exhibits antiallergic and anti-
inflammatory effects on various skin diseases such as
angioedema.11
Microneedling technology offers a minimal invasive and
painless route of drug delivery.9 This technology involves
the creation of channels in the skin with micron-sized
dimensions, thereby enabling the delivery of broad range
of therapeutic molecules including proteins which would
not otherwise cross intact skin.
Triple combination therapy, comprise of hydroquinone,
retinoid and a corticosteroid, is a highly effective and safe
treatment for melasma. A corticosteroid was introduced
to this treatment to reduce the inflammation as it is a side
effect of both hydroquinone and tretinion, in addition to
this advantage, it also inhibits the melanocyte
metabolism.10,11 This combination of hydroquinone 5%,
tretinion 0.1% and dexamethasone 0.1% was first
introduced in 1975 and termed the Kliegman formula
after its invention. Recently, the US food and drug
approach has approved a modified combination of
Kligman formulation, containing 4% hydroquinone,
0.05% tretinoin, and 0.01% fluocinolone acetonide. This
association has proved its efficacy without significant
side effects. But still considering the atrophogenic and
other side effects of individual component of triple
combination regimen, concomitant use of oral tranexamic
acid would help in decreasing the duration of topical
steroid based treatment. Since both group A and group B
study showed 67.12% and 32.44% reduction in MASI
score respectively, and simultaneously we also know the
long-time side effects of use of any one treatment as
disease has recalcitrant characteristics, therefore we can
consider microneedling with tranexamic acid as an
adjuvant treatment or as a sequential therapy and triple
combination and oral tranexamic acid 250 mg twice a day
being the mainstay of therapy.11 With this approach long
term side effects of individual drug can be prevented,
duration of treatment taken can be decreased and patient
satisfaction can also be achieved.
In the study conducted by Karn et al from Nepal, clinical
effect of oral tranexamic acid combined with triple
combination was compared with triple combination
alone. Statistical analysis was done between the groups.
Fall in MASI was significant at 8 weeks in patient
receiving both oral tranexamic acid and treatment. Seong
et al used neonatal foreskin cultured melanocytes to
demonstrate effects of tranexamic acid after UVB
irradiation and showed a significant inhibition of
multiplication of melanocyte, decrease in tyrosinase
activity, tyrosinase related peptide trp1/2, and melanin
content. Zhu et al. reported that increasing the treatment
duration was more effective than increasing the dose of
txa.12,13 The duration of therapy has varied in different
studies ranging from 6 weeks to a maximum 6 months. In
2008 Mafune et al used 750 mg oral tranexamic acid two
tablets three times a daily.14
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: The study was approved by the
institutional ethics committee
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Cite this article as: Wali V, Parwani H. Comparative
study of oral tranexamic acid and triple combination
versus tranexamic acid through microneedling in patients
of melisma. Int J Res Dermatol 2019;5:537-41.