Professional Documents
Culture Documents
Tranexamic Acid For Melasma Treatment
Tranexamic Acid For Melasma Treatment
Face Study
Howyda M. Ebrahim, MD, Ahmed Said Abdelshafy, MD, Fathia Khattab, MD, and
Khaled Gharib, MD*
BACKGROUND Melasma is an acquired hyperpigmented skin disorder. Tranexamic acid (TXA) prevents
ultraviolet radiation induced pigmentation in melasma through interfering with the plasminogen–plasmin
pathway.
OBJECTIVE This study was conducted to evaluate the therapeutic effect and safety of TXA by intradermal
injection versus TXA with microneedling for melasma treatment.
Downloaded from http://journals.lww.com/dermatologicsurgery by BhDMf5ePHKbH4TTImqenVNlUEzghFiXbrD1jgEMpAHBUi3mJZdB0xEw9crmH3Bev on 10/27/2020
METHODS Fifty-six female patients with bilateral symmetrical melasma were recruited in a split-face study.
All patients received an intradermal injection of TXA on one side of the face, and the other side received TXA
with microneedling for 6 sessions at 2 weeks intervals. Clinical efficacy was assessed using a modified Mel-
asma Area Severity Index (mMASI) score at the baseline and after treatment. Global photographs underwent
blinded review by 2 dermatologists. Patient self-assessment and satisfaction were recorded.
RESULTS After the treatment, the mMASI score was significantly reduced compared with the baseline in
both treated sides (p < .001). No significant difference between both treated sides (p > .05). Patient satisfaction
was higher in the microneedling-treated side than the intradermal-injected side (p < .001). No significant
adverse effects were observed in both treated sides.
CONCLUSION Intradermal injection and microneedling of TXA could be safe and effective in melasma
treatment. Microneedling of TXA was significantly more satisfying to the patients.
*All authors are affiliated with the Dermatology, Venereology, and Andrology Department, Faculty of Medicine, Zagazig
University, Zagazig, Egypt
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided
in the HTML and PDF versions of this article on the journal’s Web site (www.dermatologicsurgery.org).
© 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
· ·
ISSN: 1076-0512 Dermatol Surg 2020;46:e102–e107 DOI: 10.1097/DSS.0000000000002449
e102
© 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
EBRAHIM ET AL
© 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
TRANEXAMIC ACID FOR MELASMA TREATMENT
The device used was a battery-powered microneedling The study included 56 female patients with melasma,
pen that has disposable tips which carry 12 needles and their age ranged from 27 to 50 years. Wood’s light
arranged in rows. The needle length was 1.5 mm examination revealed that 30 (53.6%) patients had a
with a diameter of 0.25 mm (Dermapen 3, Avon, mixed type of melasma. The majority of patients
United Kingdom). The penetration depth of the needle (58.9%) had a skin phototype IV. Clinical data of the
was adjusted from 0.25 to 1 mm, according to the patients are summarized in Supplemental Digital Con-
treated area on the face. The speed was adjusted at a tent 1, Table S1, http://links.lww.com/DSS/A425. After
rate of 108 revolutions per second. After gentle the treatment, there was a significant improvement in
cleansing, topical anesthetic cream EMLA (AstraZe- the mMASI score from 13.83 6 7.23 to 3.49 6 2.91 in
neca AB, Sweden) was applied on both sides of the face the injected side and from 13.83 6 7.23 to 3.65 6 2.32
for 30 to 60 minutes. The device was placed perpen- in the microneedling side (p < .001) (See Supplemental
dicular to the skin on the melasma area supported by Digital Content 2, Table S2, http://links.lww.
one hand, with gentle traction of the skin performed by com/DSS/A426 and Figures 1–3). The percent of
the other hand to help the smooth delivery of TXA by change was 74.8% and 73.6% in the injected and
microneedling. The technique was performed in hor- microneedling sides, respectively. There was no statis-
izontal, vertical, and oblique directions over the trea- tically significant difference between both treated sides
ted zone for about 2 to 3 passes. This was followed by (p > .05) (See Supplemental Digital Content 2, Table S2,
application of about 0.5 mL TXA (4 mg/mL) to the http://links.lww.com/DSS/A426). The clinical response
melasma area. Then, an ice pack was applied for of the injected side was excellent in 22 (39.3%) patients,
10 minutes. All patients were advised to regularly use very good in 26 (46.4%) patients, good in 3 (5.4%)
sunscreens. The treatment was conducted by a physi- patients, poor in 3 (5.4%) patients, and 2 (3.6%)
cian every 2 weeks for a maximum of 6 sessions patients had no response. Whereas in the microneedling
(12 weeks). side, it was excellent in 20 (35.7%) patients, very good
in 27 (48.2%) patients, good in 5 (12.5%) patients,
Intradermal Injection of Tranexamic Acid poor in 1(1.8%) patient, and 3 (5.4%) patients had no
response (See Supplemental Digital Content 3, Table
All patients received an intradermal injection of about
S3, http://links.lww.com/DSS/A427). Regarding
0.5 mL of 4 mg/mL TXA on the left side of the face. A
patient self-assessment, there was no significant differ-
1 mL insulin syringe with 30 gauge needle was used for
ence between both treated sides (p > .05). However,
injection. An injection of 0.1 mL per point at 1 cm
patient satisfaction was higher in the microneedling side
intervals was conducted on the melasma area.
than that of the injected side (p < .001) (See Supple-
mental Digital Content 4, Table S4, http://links.lww.
Statistical Analysis
com/DSS/A428).
All analyses were performed with Statistical Package
for Social Sciences (SPSS Inc., Chicago, IL) using Side Effects and Recurrence
program version 18. The Chi-square (x2) test, paired t-
The adverse effects were minimal and well tolerated
test, Mann–Whitney U test, and paired Wilcoxon test
apart from mild erythema and edema that occurred in
were used. For all previous tests, a p-value < .05 was
25 (44.6%) of patients of both treated sides. Pain at the
considered statistically significant.
injection side was reported in 24 (42.9%) patients of
the injected side, whereas mild irritation was noted in
Follow-up
11 (19.6%) patients of the microneedling side. All of
Patients were followed up for 3 months after the final the patients completed the study, and 6 dropped out
session to detect further improvement, any relapse, or during the follow-up period. Recurrence was observed
appearance of adverse effects. in 8 (16%) patients of both treated sides.
© 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
EBRAHIM ET AL
Discussion
Figure 2. (A) A female patient, aged 35 years had dermal
Melasma is characterized by an unpredictable course type of melasma, before treatment, (B) the same patient
after treatment showing excellent improvement (the right
and high relapse rate. Therefore, there is a constant side treated by TXA with microneedling and the left side
need for finding new interventions for melasma treat- by intradermal TXA injection). TXA, tranexamic acid.
ment. It was reported that TXA is an effective agent in
the treatment of melasma.16–18 To the best of authors’ TXA through the microchannels created by it. In this
knowledge, this is the first study that compared 2 dif- study, although there was no significant difference
ferent modalities of TXA application in a split-face between both treated sides, patient satisfaction was
design. The applications of microneedling in derma- higher in the microneedling side because the dermapen
tology have continuously increased. Dermapen is an can help the drug to reach a uniform depth of pene-
electronic pen used for TXA delivery. Dermapen tration with a controlled speed. In addition, the der-
provides a uniform drug delivery without causing mapen can pierce the skin in a vertical manner that
actual epidermal damage; it can overcome the issues of makes it less traumatizing to the skin than the tradi-
pain and epidermal tear that may occur with the tra- tional dermaroller. Moreover, it has a higher speed of
ditional derma rollers. Intradermal injection is a tech- action that can decrease the pain and also save the time.
nique applied with a small needle into the desired area.
It involves a delivery of highly diluted mixture of drugs
without any associated risks of systemic absorption. In
this study, there was an improvement of the mMASI
score in 74.8% of the injected side compared with
73.6% in the microneedling side. No significant dif-
ference was found between both treated sides. The
authors’ study showed a higher improvement in the
mMASI score than that reported by Budamakuntla and
colleagues5 who compared 2 groups of patients with
melasma; one group received TXA by an intradermal
route while the other group was treated with TXA using
microneedling. The result revealed 35.72% improve-
ment in the MASI score in the injected group compared
with 44.41% in the microneedling group. They con-
cluded that there was no significant difference between Figure 3. (A) A female patient, aged 30 years had dermal
both groups. However, a better therapeutic response type of melasma, before treatment, (B) the same patient
after treatment showing very good improvement (the right
was achieved in the microneedling group. They dem- side treated by TXA with microneedling and the left side
onstrated that microneedling helped the delivery of by intradermal TXA injection). TXA, tranexamic acid.
© 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
TRANEXAMIC ACID FOR MELASMA TREATMENT
Lee and colleagues 15 used TXA by intradermal injec- The study was limited by a small number of patients
tion for melasma treatment. The results revealed a sig- and a short follow-up period. A lack of objective tools
nificant decrease in the mMASI score after 12 weeks of for pigment measurement is another limitation. Fur-
treatment (p < .05). They concluded that intradermal ther large-scale studies with longer duration are rec-
injection of TXA could be an alternative therapy for ommended to find out the long-term benefits of TXA
melasma. Another study compared TXA orally versus in this recurrent and recalcitrant disease.
its intradermal injection. A significant reduction of the
MASI score was observed with 77.96 6 9.39 and 79.00
Conclusions
6 9.64 in both the oral and microinjection groups,
respectively. The authors found that both modes of Tranexamic acid seems to be safe and effective therapy
administration were equally effective. However, for the treatment of melasma. Although there was no
microinjection can protect the patients from any sys- significant difference between both treated sides,
temic side effects, such as epigastric discomfort and patient satisfaction was significantly higher in the
hypomenorrhea.18 Several other studies demonstrated microneedling side than that in the intradermal-
that microneedling has favorable results in melasma injected side.
treatment.20–23 Fabbrocini and colleagues compared a
combination of microneedling with a depigmenting
serum composed of rucinol and sophora-alpha com- References
pounds versus the depigmented serum alone in mel-
1. Sarkar R, Chugh S, Garg K. Newer and upcoming therapies for
asma treatment. They evaluated the role of melasma. Indian J Dermatol Venereol Leprol 2012;78:417–28.
microneedling in enhancing transepidermal drug 2. Rathore SP, Gupta S, Gupta V. Pattern and prevalence of physiological
delivery. They observed that the side with combined cutaneous changes in pregnancy: a study of 2000 antenatal women. Ind
J Dermatol Venerol Leprol 2011;77:402–6.
treatment (microneedling and serum) has a significant
3. Chatterjee M, Vasudevan B. Recent advances in melasma. Pigment Int
decrease in the MASI score compared with the other 2014;1:70–80.
side treated with the serum alone.20 By contrast, some 4. Sun YLQ, Fu ZH, He C, He Z, et al. Treatment of melasma with oral
authors stated that microneedling may cause skin irri- administration of compound tranexamic acid: a preliminary clinical
trial. JEADV 2014;28:388–94.
tation that could increase the pigmentation, but when
skin biopsy was obtained after microneedling, the 5. Budamakuntla L, Loganathan E, Suresh DH, Shanmugam S, et al. A
randomized, open-label, comparative study of tranexamic acid
results revealed no change in the epidermal microinjections and tranexamic acid with microneedling in patients
pigmentation.22,23 with melasma. J Cutan Aesthet Surg 2013;6:139–43.
effect in the microinjection group, whereas in the oral 10. Bariya SH, Gohel MC, Mehta TA, Sharma OP. Microneedles: an
emerging transdermal drug delivery system. J Pharm Pharmacol 2012;
group mild epigastric discomfort, hypomenorrhea, 64:11–29.
and headache were reported. Therefore, local appli-
11. Abou-Taleb DA, Ibrahim AK, Youssef EM, Moubasher AE. Reliability,
cation of TXA can bypass many of the side effects that validity, and sensitivity to change over time of the modified Melasma
Area and Severity Index score. Dermatol Surg 2017;43:210–7.
may result from its systemic administration.18 In this
study, 8 (16%) patients were recurrent. Melasma is a 12. Rigopoulos D, Gregoriou S, Katsambas A. Hyper-pigmentation and
melasma. J Cosmet Dermatol 2007;6:195–202.
disease often protracted to treatment; the recurrence of
13. Gupta K, Gover D, Nouri K, Taylor S. The treatment of melasma:
pigment in some patients may be the result of frequent a review of clinical trials. J Am Acad Dermatol 2006;55:1048–65.
sun exposure and presence of some recalcitrant cases 14. Karn D, Kc S, Amatya A, Razouria A, et al. Oral tranexamic acid for
of dermal melasma. the treatment of melasma. Kathmandu Univ Med J 2012;10:40–3.
© 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
EBRAHIM ET AL
15. Lee JH, Park JG, Lim SH, Kim JY, et al. Localized intradermal 20. Fabbrocini G, De Vita V, Fardella N, Pasrore F, et al. Skin needling to
microinjection of tranexamic acid for treatment of melasma in Asian enhance depigmenting serum penetration in the treatment of melasma.
patients: a preliminary clinical trial. Dermatol Surg 2006;32:26–31. Plast Surg Int 2011;2011:158241.
16. Banihashemi M, Zabolinejad N, Jaafari MR, Salehi M, et al. Comparison 21. Alster TN, Graham PM. Microneedling: a review and practical guide.
of therapeutic effects of liposomal tranexamic acid and conventional Dermatol Surg 2018;44:397–404.
hydroquinone on melasma. J Cosmet Dermatol 2015;14:174–7.
22. Aust MC, Reimers K, Repenning C, Stahl F, et al. Percutaneous collagen
17. Kim SJ, Park JY, Shibata T, Fujiwara R, et al. Efficacy and possible induction: minimally invasive skin rejuvenation without risk of
mechanisms of topical tranexamic acid in melasma. J Clin Exp hyperpigmentation-fact or fiction? Plast Reconst Surg 2008;122:1553–63.
Dermatol 2016;41:480–5.
23. Cohen BE, Elbuluk N. Microneedling in skin of color: a review of uses
18. Sharma R, Mahajan VK, Mehta KS, Chauhan PS, et al. Therapeutic and efficacy. J Am Acad Dermatol 2016;74:348–55.
efficacy and safety of oral tranexamic acid and that of tranexamic
acid local infiltration with microinjections in patients with
melasma: a comparative study. Clin Exp Dermatol 2017;42: Address correspondence and reprint requests to: Howyda
728–734.
M. Ebrahim, MD, Department of Dermatology,
19. RAmaut L, Hoeksema H, Pirayesh A, Stillaert F, et al. Microneedling: Venereology, and Andrology, Faculty of Medicine,
where do we stand now? A systematic review of the literature. J Plast Zagazig University, Zagazig, Egypt, or e-mail:
Reconstr Aesthet Surg 2017;17:30250–4. howyda1968@gmail.com
© 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.