|
Jurnal Health Sains: p–ISSN: 2723-4339 e-ISSN: 2548-1398 |
|
Vol. 3, No.11, November
2022 |
EVALUATING
THE EFFICACY AND SAFETY OF TRANEXAMIC ACID TO HYDROQUINONE AND TRIPLE
COMBINATION CREAM IN THE TREATMENT OF MELASMA
A.A. Ayu Adisti Nina Yuniandari, Diana Wijayanti
Department of
Dermatology and Venereology, Cibabat Hospital, Cimahi, Jawa Barat, Indonesia
Email: agungayunina@gmail.com,
adisti.nina@gmail.com
|
INFO
ARTIKEL |
ABSTRACT |
|
Diterima 29 Oktober 2022 Direvisi 14 November 2022 Disetujui 25 November 2022 |
Background: Melasma is an acquired skin condition characterized by
sporadic hyperpigmented macules or patches that affects photo-exposed areas
which occur chronically. Melasma seriously impairs a patient’s quality of
life. Current treatments for melasma include hydroquinone, corticosteroids,
retinoids, natural substances, and triple combination creams (TCC), which
demonstrate variable efficacy and side-effect profiles. Melasma can now be
treated with tranexamic acid (TA), a well-known anti-fibrinolytic drug. Oral,
topically applied, and procedural techniques were used to administer TA.
Purpose: This review evaluates the efficacy and safety of tranexamic acid to
hydroquinone and triple combination cream in the treatment of melasma and
suggests steps that need to be taken to mainstream TA use in clinical
settings. Review: Among the recent melasma treatments are hydroquinone (HQ),
triple combination topicals, and regular use of broad-spectrum sunscreen. .1
Because plasmin has been shown to have melanogenic properties, tranexamic
acid (TA) is an essential therapy option for melasma due to its anti-plasmin
(and consequently anti-fibrinolytic) properties. Recent research has shown
that melasma-affected skin has enhanced vascularity and VEGF expression in
the epidermis, suggesting yet another method by which TA may treat melasma
clinically. Conclusion: The review revealed that a combination of tranexamic
acid and hydroquinone has better efficacy in treating melasma rather than
hydroquinone alone. Oral tranexamic acid combined with TCC can prevent
recurrence and sustain the outcome. |
|
Keywords: Melasma; Tranexamic Acid; Hydroquinone; Triple
Combination Therapy. |
Introduction
Melasma is an acquired skin condition
characterized by sporadic hyperpigmented macules or patches that affects
photo-exposed areas which occur chronically (Espósito et al., 2022);(Zhang et al., 2018). Melasma is a multifactorial disorder in
which several factors have been linked to melasma, including genetic
predisposition, solar radiation, sex hormones, and oxidative status. The
incidence of melasma in first-degree relatives supports the gene hereditary
origin of the melasma. According to a study, genes associated with lipid
metabolism and VEGFA are downregulated whereas those involved in melanogenesis
are upregulated (Espósito et al., 2022). Direct stimulation of melanogenesis in
melanocytes by ultraviolet radiation (UVR). Keratinocytes, mast cells (MC), and
fibroblasts are all impacted by UVR, and these cells also control
melanogenesis. All of those many conditions lead to enhanced melanosome
transfer to keratinocytes and melanosome production in melanocytes (Zhang et al., 2018);(Rajanala et al., 2019).
The clinical manifestation of melasma is
hyperpigmented macules and patches which symmetrically oriented. Another
varying manifestation can present in patients including blotchy, irregular, arcuate,
and polycyclic (Artzi et al., 2021). The pseudo-rete ridges of the skin might
exhibit considerable hyperpigmentation when examined under a dermoscopic examination. When the pigment is epidermal, the
hyperpigmentation can be emphasized with a Wood lamp. However, dermal or mixed melasma
may induce this accentuation to appear (Ogbechie-Godec & Elbuluk, 2017).
Melasma is classified as dermal, epidermal, or
mixed depending on where the melanocytes are located. While the epidermal
subtype displays clinically as brown pigment with well-defined edges, the
dermal subtype appears more gray-brown and has poorly defined margins. It is
referred to be mixed when both epidermal and dermal subtypes coexist (Artzi et al., 2021);(Ogbechie-Godec & Elbuluk, 2017). Based on the pattern of distribution,
melasma is further subdivided into the dentofacial (the most prevalent form),
malar, and mandibular subtypes (Artzi et al., 2021);(Ogbechie-Godec & Elbuluk, 2017).
The forehead, nose, and upper lip are included
in the centrofacial pattern. The mandibular pattern
is restricted to the jawline and chin, whereas the malar pattern is located on
the malar cheeks (Ogbechie-Godec & Elbuluk, 2017).
Therapy for melasma is available in different
routes of administration such as oral, topical, procedural, and combination
therapies. These focus on several melasma pathogenesis factors, including
photodamage, inflammation, vascularity, and pigmentation. Topical treatment as
the first-line treatment of melasma consists of several substances such as
hydroquinone, corticosteroid, retinoid, and natural compounds (Artzi et al., 2021); (Ogbechie-Godec & Elbuluk, 2017). Tyrosinase is inhibited by hydroquinone
(HQ), preventing the conversion of DOPA to melanin. 4% HQ is the most widely
used topical melasma therapy (Artzi et al., 2021);(McKesey et al., 2020). Corticosteroids inhibit melanogenesis by
non-selectively inhibiting the pigmentation process. When administered alone as
monotherapy, corticosteroids are most likely less effective at depigmenting
skin. Topical retinoid, tretinoin 0.1%, has a mechanism of action to induce
keratinocyte turnover. Natural compounds like niacinamide, ascorbic acid, and
kojic acid have a mechanism of action to decrease pigmentation. Niacinamide
prevents the transfer of melanosomes to keratinocytes, which reduces
pigmentation. Tyrosinase activity can be inhibited by both ascorbic acid and
kojic acid. Reactive oxygen species are thought to be reduced by ascorbic acid,
which reduces inflammation in melasma lesions (Ogbechie-Godec & Elbuluk, 2017). Triple combination cream (TCC), which
contains HQ 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%, is another
option for treating melasma topically. Due to its strong and quick whitening
impact, 3-5 TCC is presently regarded as the gold-standard topical therapy for
melasma (Cassiano et al., 2022).
Melasma treatment options other than topical
methods include oral medication. Arachidonic acid production is decreased by
the anti-plasmin drug tranexamic acid (TA), which also lowers
melanocyte-stimulating hormone (MSH) levels and pigmentary synthesis. One study
suggests that TA may also reduce VEGF and endothelin-1, two substances that may
be to blame for the increased vascularity in afflicted lesions. Two
complementary medicines are glutathione and Polypodium leucotomos
(PL). It has been shown that PL decreases ROS production, lowers UV-induced
photodamage, and lessens the T cell-mediated response that increases skin
inflammation and pigmentation (Ogbechie-Godec & Elbuluk, 2017);(Forbat et al., 2020).
Typically, procedural treatment is adjunctive
therapy of melasma. Chemical peeling can increase keratinocyte turnover and
epidermal remodeling. Among the several peels, glycolic acid (GA) has received
the greatest research attention for the treatment of melasma. Microneedling is an additional supplementary treatment that
uses tiny skin channels to administer topical medications intradermally in
small doses. In addition, as compared to traditional resurfacing methods, micro
needling skin punctures might encourage a beneficial wound-healing process.
Using thermal energy, lasers may use certain chromophores in the skin as
targets. Non-ablative lasers are preferred over ablative lasers for the
treatment of melasma because they tend to induce less inflammation and
therefore less post-inflammatory pigment alteration (PIPA) (Ogbechie-Godec & Elbuluk, 2017);(Forbat et al., 2020).
Melasma can now be treated with tranexamic
acid (TA), a well-known anti-fibrinolytic drug. TA was incidentally discovered
and reported by N. Sadako attempted to apply TA to treat severe urticaria in
1979 (Perper et al., 2017);(Parikh & Naik, 2021);(Zhang et al., 2018). Tranexamic acid is used as a hemostatic drug
to treat aberrant fibrinolysis and stop massive bleeding. It is a chemical
lysine precursor that inhibits plasminogen activator (PA) activation by
interfering with its lysine-binding sites in reversible ways. As a result, PA
cannot convert plasminogen into plasmin, which is how it achieves its impact.
It promotes the inhibition of tyrosinase activity by suppressing the
plasminogen/plasmin system, which prevents contact between keratinocytes and
melanocytes. TA also reduces the function of mast cells and blocks fibroblast
growth factors (Cassiano et al., 2022);(Perper et al., 2017);(Fraone & Bartoletti, n.d.). Tranexamic acid is available in three
different drugs administration including oral, topical, and procedural
(intradermal microinjection) (Fraone & Bartoletti, n.d.);(Zhang et al., 2018)
The most common adverse effects of TA are
spinal discomfort, irregular menstruation, muscle ache, headaches, urticaria,
and cramping in the abdomen. TA is contraindicated in cases of renal
impairment, cancer, cardiovascular or respiratory illness, ongoing
anticoagulant medication, a personal or family history of thromboembolic
disease, and pregnancy. TA should be avoided by those who have clotting issues
or a background of thromboembolism, and people who are using hormonal
contraceptives or other pro-coagulants (Cassiano et al., 2022). This review evaluates
the efficacy and safety of tranexamic acid to hydroquinone and triple
combination cream in the treatment of melasma and suggests steps that need to
be taken to mainstream TA use in clinical settings.
Research Methods
Current treatments for melasma
include hydroquinones, corticosteroids, retinoids,
natural ingredients, and triple combination creams (TCC), which show variable
efficacy and side effect profiles. Melasma can now be treated with tranexamic
acid (TA), a well-known antifibrinolytic drug. Oral techniques, topical
applications, and procedures are used to manage TA.
Results and Discussion
Melasma is an acquired skin condition
characterized by sporadic hyperpigmented macules or patches that affects
photo-exposed areas which occur chronically (Espósito et al., 2022);(Zhang et al., 2018). Melasma seriously
impairs a patient's quality of life, leading to psychological distress in many
people, including frustration, embarrassment, and depression (Zhu et al., 2022). Although the specific pathogenesis of
melasma is unknown. It has been hypothesized that several factors have a role
including genetic predisposition, solar radiation, sex hormones, and oxidative
status. According to research, genes associated with lipid metabolism and VEGFA
are downregulated whereas those involved in melanogenesis are upregulated. Direct stimulation of melanogenesis in
melanocytes by ultraviolet radiation (UVR). Keratinocytes, mast cells (MC), and
fibroblasts are all impacted by UVR, and these cells also control melanogenesis
(Espósito et al., 2022);(Rajanala et al., 2019).
Among the recent melasma treatments are hydroquinone (HQ), triple combination topicals, and the regular use of broad-spectrum sunscreen (Espósito et al., 2022). Because plasmin has been shown to have melanogenic properties, tranexamic acid (TA) is an essential therapy option for melasma due to its anti-plasmin (and consequently anti-fibrinolytic) properties. Recent research has shown that melasma-affected skin has enhanced vascularity and VEGF expression in the epidermis, suggesting yet another method by which TA may treat melasma clinically (Pandya et al., 2011). It is also believed that TA competitively inhibits tyrosinase, which would exacerbate the skin-lightening effect (McKesey et al., 2020). TA has become a novel therapeutic option for melasma and has demonstrated encouraging outcomes with all routes of administration including topical, oral or systemic, and intradermal (Fraone & Bartoletti, n.d.);(Zhang et al., 2018).
Based on our literature review we compared the
effectiveness and safety of TA versus hydroquinone (HQ) and triple combination
cream (TCC).
Tranexamic Acid Versus Hydroquinone Cream
Eight studies compared tranexamic acid, in
different routes of administration, with hydroquinone cream. All the studies
used different HQ concentrations making the review quite challenging. Four of
the seventh studies compared hydroquinone cream with oral TA, 1 study compared
topical TA, and three of them evaluated TA intradermally. Several of them
compared hydroquinone with TA as an adjuvant, and others compared hydroquinone
with TA as a single agent.
Table 1
Tranexamic Acid compared to Topical
Hydroquinone
|
Year |
Author |
Study
design |
Sample
Size |
Intervention
Group |
Duration |
Side
Effect |
Conclusion |
|
2016 |
A
single-blinded, randomized controlled trial |
100 |
Group
A: 250 mg of TA oral thrice a day + 4% of HQ cream |
3
months |
10.5% of patients, all of whom were in group
A, had gastrointestinal issues and irregular periods. |
Although
oral TA can increase the effectiveness of hydroquinone 4% cream in the
treatment of melasma, the high rate of recurrence raises the possibility that
therapeutic effects may be transient and calls for more research. |
|
|
Group
B: 4% of HQ cream |
|||||||
|
2019 |
Randomized
Clinical Trial |
30 |
Group
A: oral TA 250 mg twice daily + 2% HQ cream nightly |
12
weeks |
NA |
Oral
TA can increase the efficacy of 2% hydroquinone cream in the treatment of
melasma, although it has a high recurrence rate. |
|
|
Group
B: 2% HQ cream nightly |
|||||||
|
2021 |
Clinical
trial |
80 |
Group
A: topical 4% hydroquinone |
6
months |
Hydroquinone
had mild side effects including local erythema and a burning sensation. |
Hydroquinone
4% topical treatment paired with oral tranexamic acid is more effective than
topical 4% hydroquinone alone for epidermal melasma. |
|
|
Group
B: capsule TA 250 mg twice a day + topical 4% hydroquinone |
|||||||
|
2018 |
Randomized split-face clinical trial |
55 |
TA
intradermal 100 mg/ml every 4 weeks + 4% HQ cream on the right or left side
and topical 4% HQ alone every night on the other side |
12 weeks |
In the TA+ HQ group: erythema (47.3%) and
pruritus at the injection site (10.9%). In the HQ group: erythema occurred in 50.9% of
cases and pruritus in 12.7%. |
The efficiency of the topical treatment can be
increased by adding intradermal tranexamic acid to typical hydroquinone cream
therapy. |
|
|
2017 |
Randomized
Clinical Trial |
140 |
Group
A: topical 2% hydroquinone |
8
weeks |
2
patients presented with nausea, vomiting, and diarrhea, which were
self-limiting |
When
compared to topical hydroquinone 2% cream, oral tranexamic acid 500 mg
offered a superior response and safer safety profile. |
|
|
Group
B: oral TA 500 mg once daily |
|||||||
|
2019 |
Double-blind,
randomized clinical trial |
60 |
Group
A: 3% TA cream |
8
weeks |
Only
two patients in the HQ group had erythema. |
In
epidermal-type melasma, 3% TA cream and 4% of HQ cream are efficient in
lowering the MSI score and Melanin Index (MI). The MSI score and MI in the 3%
TA group were lower by the eighth week than in the 4% HQ group. |
|
|
Group
B: 4% HQ cream |
|||||||
|
2017 |
Randomized
split-faced Controlled Trial |
37 |
TA
intradermal injection on the right or left side and topical HQ every night on
the other side |
3
months |
No
harmful response was noticed on the HQ side. On the TA side: Two people had
acne, and one experienced burning pain during injection. |
The
melanin level was reduced more effectively during the first four weeks by
monthly TA injection than by daily HQ. However, after 20 weeks, there was no
difference in the total changes between the two methods. |
|
|
2022 |
Comparative
clinical trial |
31 |
Group
A: intradermal TA 500 mg/5 ml every 2 weeks + 4% HQ cream every night |
8
weeks |
in
group A, 2 patients had redness, and 1 patient with irritation. Meanwhile, in
group B, 1 had redness, and 1 patient presented with irritation |
In
the treatment of melasma, topical hydroquinone alone is less effective than
topical hydroquinone coupled with intradermal injection of TA. Both forms of
treatment are equally safe and effective. |
Three studies used oral TA combined with
hydroquinone compared with using only hydroquinone was conducted by (Lajevardi et al., 2017). (RIAZ et al., n.d.);(Benhiba et al., 2020); (Lajevardi et al., 2017). used 250 mg TA three times per day orally
and 4% HQ cream, (Benhiba et al., 2020).observed 250 mg TA twice daily and 2% HQ
cream, whilst (RIAZ et al., n.d.). used 250 mg of tranexamic acid twice a day
and 4% HQ cream. Despite different dosage and concentration used in those
studies, nonetheless, the result is similar. The results showed that topical
hydroquinone alone is not as effective as HQ cream combined with oral
tranexamic acid (Lajevardi et al., 2017);(Benhiba et al., 2020).
A study by (Lajevardi et al., 2017) report side
effects including gastrointestinal issues and irregular menstruation in 10.5%
patients where all were from the group given oral TA. Partial recurrence of
melasma was seen over the three-month follow-up period in both groups, as shown
by a rise in mean MASI scores. In the TA + HQ group, MASI scores climbed by 4.3
+ 4.2 points and by 2.7 + 8.8 points in the HQ group, respectively, reflecting
relapse rates of 30% and 26% (Lajevardi et al., 2017). The 30%
recurrence rate in the intervention group in this study may have been caused by
the shorter length of therapy in the trial. As a result, longer-term research may
be suggested while side effects are thoroughly monitored
Figure 1. Melasma patients in TA+HQ group,
before (baseline) and after (3 months in treatment). a) 33-year-old, b)
37-year-old (Lajevardi et al., 2017).
A study by (Samreen et al., 2017), compared oral tranexamic acid alone with HQ
cream. According to a study, oral tranexamic acid 500 mg showed a higher safety
profile and response when compared to topical hydroquinone 2% cream. The oral
usage of TA was shown to have minor and insignificant side effects. A tiny
percentage have diarrhea, nausea, and vomiting, although these symptoms were
self-limiting (Samreen et al., 2017). Four studies were evaluated periodically
using MASI score. When compared to area measurements, the melasma severity
scale, and Mexameter scores, the MASI and mMASI ratings have been proven to be valid and reliable
both within and across raters (Ogbechie-Godec & Elbuluk, 2017);(Pandya et al., 2011). Based on these four trials, we can conclude
that oral tranexamic acid has a high level of safety and effectiveness when
used to treat melasma. It is possible to utilize oral tranexamic acid on its
own with a high level of safety and effectiveness. However, when used in
conjunction with hydroquinone, it produces greater outcomes than hydroquinone
alone (Lajevardi et al., 2017);(Samreen et al., 2017).
A topical TA was another one that was studied (Marpaung et al., 2021),did a double-blind RCT study in epidermal
melasma patients to compare three percent of TA with 4% of hydroquinone cream.
The patients were grouped into two categories, receiving 3% TA cream group and
4% HQ cream group. Side effect of TA cream were not found, but erythema was
found in two of 30 patients which given 4% HQ cream. The baseline mMASI scores for the two groups were identical. The two
groups had different mMASI scores at weeks 4 and 8,
with the TA 3% group having a lower mMASI score and
melanin index than the HQ 4% group. However, 4% HQ cream and 3% TA cream are
equally beneficial in lowering the MASI score and MI in melasma of the
epidermal type.
In addition to oral and topical, there are
also studies comparing hydroquinone with TA in an intradermal form (Taha & Sheer, 2022);(Tehranchinia et al., 2018). conducted study that compare a combination
of intradermal with 4% HQ cream every night and 4% HQ cream only. (Taha & Sheer, 2022) used TA in 500 mg/5 ml every 2 weeks for 8
weeks while (Tehranchinia et al., 2018) used 100 mg/ml in every 4 weeks for 12 weeks.
Both groups in two studies were asked to apply sunscreen of SPF 50 during the
treatment period. Side effect in both
groups (intervention and control group) of two studies showed insignificant
statistically difference, both had erythema and pruritus in certain patients.
During the follow-up period, mean MASI score in intervention group showed
significant improvement. Thus, therapeutic outcome in intervention group (TA +
HQ group) were significantly better than HQ group. In conclusion, the
intradermal injection of TA combined with topical hydroquinone has more
effectiveness than hydroquinone cream alone in the treatment of melasma (Taha & Sheer, 2022);(Tehranchinia et al., 2018). Figures 2 and 3 show, respectively, the clinical
profile of melasma patients in the study performed by (Taha & Sheer, 2022);(Tehranchinia et al., 2018).
Figure 2. Right side before treatment, b)
after 8 weeks of intradermal TA+HQ. c) Left side of face before treatment, d)
after treatment with TA intradermally + HQ. (Minni & Poojary, 2020).
Figure
3. Melasma patient treated with (a) 4% of HQ cream, before treatment (left) and
after 16 weeks of treatment (right); (b) TA intradermal + 4% hydroquinone cream
(Tehranchinia et al., 2018).
Another study about intradermal TA was
performed by (Saki et al., 2018), The study was randomized split-face
controlled trial which compared intradermal tranexamic acid, not in a
combination therapy, and hydroquinone alone. TA was given 20 mg/ml
concentration intradermally to left or right side of the face every month for 2
months and 2% HQ cream on the other side. Patients were instructed to use SPF
50 sunscreen. On the HQ side, there were no indications of a negative reaction,
while three patients reported negative effects after TA injections; one of them
felt burning during the treatment, and the other two had acne. This study
discovered that in order to reduce the melanin value during the initial four
weeks, monthly TA injection was superior to daily HQ. However, after 20 weeks,
there was no difference in the total changes between the two groups (Saki et al., 2018).
According to three studies about intradermal
TA compared to HQ cream. Intradermal TA alone after 20 weeks exhibited
insignificant results when compared to HQ cream alone, while the combination of
intradermal TA and HQ cream has significant outcome.
Tranexamic Acid Versus Triple Combination
Cream
Table 2
Tranexamic Acid compared to
Triple Combination Cream
|
Year |
Author |
Study Design |
Sample Size |
Intervention
Group |
Duration |
Side Effect |
Conclusion |
|
2020 |
Randomized
Clinical Trial |
130 |
Group A received
a triple combination cream (TCC) once daily, as well as oral tranexamic acid
250 mg and ranitidine 150 mg twice a day. |
24 weeks |
The most
frequent side effects during therapy in groups A and B were erythema and
burning, showing that fTCC was mostly to
responsible for both symptoms. |
For a rapid,
more lasting recovery and to avoid recurrence, oral tranexamic acid should be
administered in conjunction with f-TCC. It is unquestionably a benefit to the
arsenal of melasma treatment tools. |
|
|
Group B had only
the cream and was given placebo pills (calcium lactate and multivitamin). |
|||||||
|
2021 |
Randomized
Comparative Trial |
110 |
Group I:
Intradermal TA 4 mg/ml every 15 days |
2 months |
Group I had no
clinically significant side effect Hypertrichosis,
acneiform, erythema, and hypopigmentation were detected by Group II. |
MASI scores in
groups I and II both significantly decreased from baseline (15.4) to 2.4 and
5.6, respectively. Because there were no clinically significant adverse
effects discovered following this therapy and because the MASI score was
significantly reduced, intradermal TA was both safe and effective in the
treatment of melasma. |
|
|
Group II: fbTCC (hydroquinone 4%, tretinoin 0.05%, fluocinolone
acetonide 0.01%) every night for three hours. |
|||||||
|
2021 |
Randomized
Controlled Trial |
60 |
Group A: TCC
cream + oral TA |
8 weeks |
NA |
Oral tranexamic
acid was added to a topical triple regimen, however
this did not appreciably lower the MASI score. As an adjunct to topical
combination treatment, it could be useful. |
|
|
Group B: TCC
cream |
|||||||
|
2022 |
Randomized
Clinical Trial |
44 |
Group A: 325 mg
of TA orally twice a day with fTCC cream. |
8 weeks |
There were no
major negative effects identified. |
Oral TA and
f-TCC are more effective when combined than when used alone for the treatment
of severe melasma. |
|
|
Group B: 325 mg of
TA orally twice daily |
We reviewed four studies comparing tranexamic
acid and triple combination cream. One study used TA administered
intradermally, and three studies were oral TA. (Shahzad et al., n.d.) conducted randomized comparative trial in 110
patients which divided into two groups. First group was given TA 4mg/ml
intradermally every 15 days, and the other group received f-TCC (fluocinolone
acetonide 0.01%, tretinoin 0.05%, hydroquinone 4%) which applied at night on
melasma lesions for 3 hours per day. Baseline MASI score in group I and group II
were 15.4. Side effects were not present in group I, while several patients in
group II experienced hypertrichosis, erythema, acneiform lesions, and
hypopigmentation. During follow-up, MASI score in two groups decreased to 2.4
and 5.6, respectively. The decrease in the MASI score indicates that
intradermal TA has a higher effectiveness than fTCC
alone. Since there were no significant adverse effects discovered following
this treatment and because the MASI score was significantly reduced, the use of
intradermal TA in the treatment of melasma was effective and safe (Shahzad et al., n.d.).
(Minni & Poojary, 2020) performed randomized clinical trial study in
130 patient which were categorized into two groups. Intervention group (group
A) was given 250 mg of TA oral twice daily and applied a fTCC
(0.01% of fluocinolone acetonide 0.01%, 0.05% tretinoin, and 2% of
hydroquinone) once daily, whilst control group (group B) accepted placebo
tablets (contain multivitamin and calcium lactate) and applied fTCC only. The baseline mMASI
score from each group was 10.45 and 9.16, respectively. Measurement mean mMASI score in group A at the end of 4th, 8th and 12th week
were 6.16, 4.32, 2.26, respectively. Similarly, in group B, mMASI
score fell to 7.11, 5.39, and 4.09, respectively. Both groups had topical fTCC side effects. None of the patients receiving oral TA
experienced any systemic side effects. Erythema was the most frequent adverse
effect seen after therapy, followed by burning sensation in both groups,
indicating that fTCC was predominantly responsible
for both conditions. Recurrence of melasma at 24th week in group A was 11
patients (18.03%) and 38 patients (64.4%) in group B. This indicates that oral
TA helps reduce recurrence of melasma (Minni & Poojary, 2020).
The clinical picture of melasma patients in
the study conducted by (Minni & Poojary, 2020) is in Figures 4 and 5. Figure 4 showed a
patient in group A, and the patient in Figure 5 is one of the patients in group
B.
Figure 4. Improvement picture in patient
received 250 mg of TA twice a day + fTCC. (a,b) baseline: mMASI = 15.6; (c,
d) 4th week: 7.5 (51.9%), (e, f) 8th week: 5.1 (67.3%) (Minni & Poojary, 2020).
Figure 5. Improvement
picture in patient treated with placebo + fTCC. a)
baseline: mMASI = 3.6; (b) 4th week: 1.8
(50%); (c) 12th week: 1.2 (67%); (d) 24th week 24: 1.2
(67%) (Minni & Poojary, 2020).
The study conducted by (Basit et al., 2021) was randomized control trial study which
enrolled 63 patients. The patients were classified into group A and group B.
Group A had oral TA + TCC (fluocinolone acetonide 0.01%, tretinoin 0.05%, and
4% of hydroquinone) and group B was given TCC only. The mean decrease of MASI
score in group A and group B was 6.4933±4.38358 and 5.7833±5.04251,
respectively. p-value was 0.56 which mean the difference was insignificant
statistically. TCC was a control in this study. Therefore, the comparative
findings are insignificant, due to the fact that TCC's potential is more
efficient than oral TA. In this instance, oral TA is better combined with TCC (Basit et al., 2021).
Opposite (Martinez‐Rico et al., 2022) studied the efficacy and safety of oral
tranexamic acid as a single therapy and in a combination with TCC for treating
melasma. This study involved 44 patients and was divided into two groups. Group
A was given 325 mg of oral TA twice a day plus f-TCC, and f-TCC only for group
B. Evaluations were made at baseline and Weeks 4, 8, 12, and 16, which include
measurement of MelasQoL, mMASI
score, and melanin index (MI). The highest results on the melanin index level
were consistent with the application of the combination therapy. f-TCC and oral
TA perform better together than they do separately. The greatest improvement in
MASI scores was associated with the use of combination therapy modalities. The
two groups' MelasQoL ratings did not substantially
vary from one another (Martinez‐Rico et al., 2022).
CONCLUSION
BIBLIOGRAFI
Artzi, O., Horovitz, T., Bar‐Ilan, E., Shehadeh, W., Koren, A.,
Zusmanovitch, L., Mehrabi, J. N., Salameh, F., Isman Nelkenbaum, G., & Zur,
E. (2021). The Pathogenesis Of Melasma And Implications For Treatment. Journal
Of Cosmetic Dermatology, 20(11), 3432–3445. Google Scholar
Basit, A., Rahman,
A., & Uddin, R. (2021). Oral Tranexemic Acid With Triple Combination Cream (Flucinolone+
Hydroquinone+ Tretinoin) Versus Triple Combination Cream Alone In Treatment Of
Melasma. Journal Of Ayub Medical College, Abbottabad: JAMC, 33(2),
293–298. Google Scholar
Benhiba, F., Benzekri,
Z., Guenbour, A., Tabyaoui, M., Bellaouchou, A., Boukhris, S., Oudda, H., Warad,
I., & Zarrouk, A. (2020). Combined Electronic/Atomic Level Computational,
Surface (SEM/EDS), Chemical And Electrochemical Studies Of The Mild Steel
Surface By Quinoxalines Derivatives Anti-Corrosion Properties In 1 Mol⋅ L-1 Hcl Solution. Chinese Journal Of Chemical Engineering,
28(5), 1436–1458. Google Scholar
Cassiano, D. P., Espósito,
A. C. C., Da Silva, C. N., Lima, P. B., Dias, J. A. F., Hassun, K., Miot, L. D.
B., Miot, H. A., & Bagatin, E. (2022). Update On Melasma—Part II: Treatment.
Dermatology And Therapy, 1–24. Google Scholar
Espósito, A. C. C.,
Cassiano, D. P., Da Silva, C. N., Lima, P. B., Dias, J. A. F., Hassun, K., Bagatin,
E., Miot, L. D. B., & Miot, H. A. (2022). Update On Melasma—Part I: Pathogenesis.
Dermatology And Therapy, 1–22. Google Scholar
Forbat, E., Al‐Niaimi,
F., & Ali, F. R. (2020). The Emerging Importance Of Tranexamic Acid In
Dermatology. Clinical And Experimental Dermatology, 45(4),
445–449. Google Scholar
Fraone, N., & Bartoletti,
E. (N.D.). Tranexamic Acid And Platelet Rich Plasma In The Treatment Of
Melasma: Efficacy And Safety. Google Scholar
Lajevardi, V., Ghayoumi,
A., Abedini, R., Hosseini, H., Goodarzi, A., Akbari, Z., & Hedayat, K.
(2017). Comparison Of The Therapeutic Efficacy And Safety Of Combined Oral
Tranexamic Acid And Topical Hydroquinone 4% Treatment Vs. Topical Hydroquinone
4% Alone In Melasma: A Parallel‐Group, Assessor‐And Analyst‐Blinded, Randomized
Controlled Trial With A Short. Journal Of Cosmetic Dermatology, 16(2),
235–242. Google Scholar
Marpaung, H. K., Toruan,
T. L., & Kurniawati, Y. (2021). Comparison Of The Effectiveness 3% Tranexamic
Acid Cream Versus 4% Hydroquinone Cream For Treatment Of Epidermal Type Melasma.
Bioscientia Medicina: Journal Of Biomedicine And Translational Research,
5(3), 340–347. Google Scholar
Martinez‐Rico, J. C.,
Chavez‐Alvarez, S., Herz‐Ruelas, M. E., Sosa‐Colunga, S. A., Ocampo‐Candiani, J.,
Suro‐Santos, Y., & Vazquez Martinez, O. (2022). Oral Tranexamic Acid With A
Triple Combination Cream Versus Oral Tranexamic Acid Monotherapy In The
Treatment Of Severe Melasma. Journal Of Cosmetic Dermatology, 21(8),
3451–3457. Google Scholar
Mckesey, J., Tovar-Garza,
A., & Pandya, A. G. (2020). Melasma Treatment: An Evidence-Based Review. American
Journal Of Clinical Dermatology, 21(2), 173–225. Google Scholar
Minni, K., & Poojary,
S. (2020). Efficacy And Safety Of Oral Tranexamic Acid As An Adjuvant In Indian
Patients With Melasma: A Prospective, Interventional, Single‐Centre,
Triple‐Blind, Randomized, Placebo‐Control, Parallel Group Study. Journal Of The
European Academy Of Dermatology And Venereology, 34(11), 2636–2644. Google Scholar
Ogbechie-Godec, O.
A., & Elbuluk, N. (2017). Melasma: An Up-To-Date Comprehensive Review. Dermatology
And Therapy, 7(3), 305–318. Google Scholar
Pandya, A. G., Hynan,
L. S., Bhore, R., Riley, F. C., Guevara, I. L., Grimes, P., Nordlund, J. J., Rendon,
M., Taylor, S., & Gottschalk, R. W. (2011). Reliability Assessment And
Validation Of The Melasma Area And Severity Index (MASI) And A New Modified MASI
Scoring Method. Journal Of The American Academy Of Dermatology, 64(1),
78–83. Google Scholar
Parikh, D., & Naik,
P. P. (2021). A Prospective, Interventional Study Of Oral Tranexamic Acid With
Antioxidants And Local Glycolic Acid For The Treatment Of Resistant Melasma. Journal
Of Dermatology Research Reviews & Reports. SRC/JDMRS-138. DOI: Doi. Org/10.47363/JDMRS/2021
(2), 132, 2–4. Google Scholar
Perper, M., Eber, A.
E., Fayne, R., Verne, S. H., Magno, R. J., Cervantes, J., Alharbi, M., Alomair,
I., Alfuraih, A., & Nouri, K. (2017). Tranexamic Acid In The Treatment Of
Melasma: A Review Of The Literature. American Journal Of Clinical
Dermatology, 18(3), 373–381.Google Scholar
Rajanala, S., Maymone,
M. B. C., & Vashi, N. A. (2019). Melasma Pathogenesis: A Review Of The
Latest Research, Pathological Findings, And Investigational Therapies. Dermatology
Online Journal, 25(10).Google Scholar
Riaz, S., Ahmed,
N., Anwar, A., Tahir, M., Yousaf, F., & Kausar, S. (N.D.). Comparison Of
4% Topical Hydroquinone Versus Combination Of Oral Tranexamic Acid And 4% Topical
Hydroquinone In The Treatment Of Epidermal Melasma.Google Scholar
Saki, N., Darayesh,
M., & Heiran, A. (2018). Comparing The Efficacy Of Topical Hydroquinone 2%
Versus Intradermal Tranexamic Acid Microinjections In Treating Melasma: A
Split-Face Controlled Trial. Journal Of Dermatological Treatment, 29(4),
405–410. Google Scholar
Samreen, R., Usma,
I., Zahida, R., & Ijaz, H. (2017). Comparison Of Efficacy And Safety Of
Topical Hydroquinone 2% And Oral Tranexamic Acid 500 Mg In Patients Of Melasma.
Google Scholar
Shahzad, M. K.,
Tahir, R., Amin, S., Hassan, T., Sattar, F., & Anwar, M. (N.D.). Comparing
Efficacy Of Intradermal Tranexamic Acid (TA) Verses Fluocinolone-Based Triple
Combination (Hydroquinone 4%, Tretinoin 0.05%, Fluocinolone Acetonide 0.01%) Therapy
In The Treatment Of Melasma. Google Scholar
Taha, L. Y., &
Sheer, P. Y. (2022). Intradermal Injection Of Tranexamic Acid Combined With
Topical Hydroquinone Cream Versus Topical Hydroquinone Cream Alone In The
Treatment Of Melasma. Iraqi Journal Of Pharmacy, 19(1), 54–64. Google Scholar
Tehranchinia, Z., Saghi,
B., & Rahimi, H. (2018). Evaluation Of Therapeutic Efficacy And Safety Of
Tranexamic Acid Local Infiltration In Combination With Topical 4% Hydroquinone
Cream Compared To Topical 4% Hydroquinone Cream Alone In Patients With Melasma:
A Split-Face Study. Dermatology Research And Practice, 2018. Google Scholar
Zhang, L., Tan, W.-Q.,
Fang, Q.-Q., Zhao, W.-Y., Zhao, Q.-M., Gao, J., & Wang, X.-W. (2018). Tranexamic
Acid For Adults With Melasma: A Systematic Review And Meta-Analysis. Biomed Research
International, 2018. Google Scholar
Zhu, Y., Zeng, X.,
Ying, J., Cai, Y., Qiu, Y., & Xiang, W. (2022). Evaluating The Quality Of
Life Among Melasma Patients Using The Melasqol Scale: A Systematic Review And
Meta-Analysis. Plos One, 17(1), E0262833. Google Scholar
|
Copyright holder : A.A Ayu Adisti
Nina Yuniandari, Diana Wijayanti (2022) |
|
First publication right : This article
is licensed under: |