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Clinical Experience

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Whitening Efficacy of Tranexamic Acid Cataplasm on Melasma in Chinese Women

Lu J. · Yang L. · Xu P. · Bian F. · Zhang H.

Author affiliations

Department of Dermatology, Shu-guang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China

Corresponding Author

Huimin Zhang

Department of Dermatology, Shu-guang Hospital Affiliated to Shanghai

University of Traditional Chinese Medicine

185 Pu'an Road, Shanghai 200021 (China)

E-Mail happy2003_1@msn.com

Related Articles for ""

Integr Med Int 2017;4:154-160

Abstract

Background/Aims: Oral tranexamic acid (TXA) has been reported to be effective for treating melasma. However, the effect of topical TXA on melasma remains controversial. The aim of this study was to assess the effects of topical TXA cataplasm on melasma. Methods: Eighty-four patients with melasma were randomly assigned to a treatment group or a separate control group. They were instructed to apply 2 pieces of cataplasm with or without TXA. The melasma area severity index (MASI), skin color tone scale (SCTS), and area score were evaluated by dermatologists blinded to the treatment. Results: A significant decrease in the MASI and SCTS was observed on either or both sides of the face by the end of 8 weeks compared to the control group (p < 0.05). The area score was also significantly reduced on both tested sides compared to the control group (p < 0.05). Conclusion: Based on these results, we believe that localized cataplasm of TXA may be used as a potentially new, effective, and safe therapeutic modality for treating melasma.

© 2017 The Author(s) Published by S. Karger AG, Basel


Introduction

Melasma is a common acquired pigmentary disorder that occurs usually in women, especially in Asia. The prevalence of melasma is around 13% and can seriously affect the appearance and quality of life of the women it affects [1]. Oral tranexamic acid (TXA) treatment is regarded as the preferred method for curing melasma in some countries [2]. However, oral TXA treatment of melasma, which requires a long treatment period, has the side effect of menstrual reduction in some patients [3]. Therefore, topical TXA treatment of melasma has received much more attention. Nowadays, TXA is added to some cosmetics, but there is no consensus on the clinical effect yet.

Cataplasm is also called gel patch or poultice and has a special hydrophilic polymer structure. It was suggested that cataplasm can improve the transdermal absorption rate. Cataplasm, as a remarkable drug carrier, has been used for a long time in Japan and China [4].

The present study was conducted in Chinese females with melasma to investigate the efficacy and safety of topical TXA treatment.

Materials and Methods

Materials

Cataplasm (containing 2.5% TXA or no TXA) was produced by Anssure Pharmaceutical Co., Ltd. (Tianjin, China). Cataplasm forms a special hydrophilic polymer structure through sodium and aluminum ion-connecting technology. The drug (TXA) is then mixed with a hydrophilic polymer matrix coated on a backing material. The polymer structure contains 50-60% of water and can increase the concentration of drugs and release drugs into the skin more quickly than other drug delivery routes, retaining a sufficient amount of moisture for more than 12 h [5] (Fig. 1).

Fig. 1

Photos of one pair of cataplasm (a) and the diagram of cataplasm (b).

/WebMaterial/ShowPic/912377

The skin color tone scale (SCTS) bars were obtained from Inforward, Inc. (Tokyo, Japan). The planimetry was purchased from Xinan Science Instrument Co., Ltd. (Jiangsu, China).

Methods

Study Design

The study was a simple randomized trial (with computer-generated random numbers), and patients and dermatologists were blinded to the treatment. A total of 84 patients with melasma were recruited for the study. The study was carried out according to the principles of the Declaration of Helsinki and was approved by the Shanghai University of Traditional Chinese Medicine Ethics Committee. Informed consent was obtained from all patients. All patients with Fitzpatrick skin types III or IV and with moderate to severe facial melasma were enrolled based on guidelines for clinical trials in melasma [6]. Patients' age ranged from 23 to 58 years (median, 43 years), and the duration of melasma varied from 1 to 7 years (median, 4 years). They were randomly assigned to a treatment group and a separate control group. Pregnant or nursing women, patients taking whitening drugs and being treated within 3 months prior to enrolment, and patients with a history of thrombosis, thrombophilia, serious liver and kidney dysfunction, or cardiovascular or respiratory disease were excluded. The therapeutic process was as follows: 2 pieces of cataplasm containing TXA or no TXA were applied to the treatment group or the control group for approximately 7 h per day. During this 8-week period, all patients were asked to visit the hospital in weeks 2, 4, 6, and 8. The patients were advised to avoid excessive sun exposure and to apply the same broad-spectrum sunscreen with a sun protection factor 30.

Evaluation of Efficacy

As mentioned in the guidelines for clinical trials on melasma [6], a blinded dermatologist quantified the melasma area and severity index (MASI) [7]. As objective evaluation techniques, SCTS score [8] and area score were assessed in this study. Skin pigment was measured by SCTS according to Konishi et al. [8]. Briefly, the SCTS bar is composed of 5 different-hue plastic bars. Nineteen kinds of value color charts from 4.0 to 8.5 with increments of 0.25 were attached to each bar. The value (V) was recorded before treatment and after treatment. The difference in V from pretreatment (ΔV) was calculated. The difference in V in the SCTS compared to pretreatment was rated as follows: marked improvement (ΔV ≥1.5), general improvement (ΔV ≥0.75), slight change (ΔV ≥0.26), unchanged (ΔV 0-0.25), and deterioration (ΔV <0). The areas of the pigmented patches were depicted by a piece of transparent paper. The area scores were measured by planimetry to calculate the total pigmented area.

Statistical Analysis

The values (MASI, SCTS, and area score) were recorded before treatment and at 2, 4, 6, and 8 weeks after treatment. The data were analyzed using analysis of variance and the Student t test. A p value of <0.05 was considered significant. Data are presented as means ± standard deviations.

Results

Of the 84 patients, 81 completed the study, while the remaining 3 patients failed to finish the study. One lost patient belonged to the treatment group, and the other 2 were from the control group. A 48-year-old woman in the treatment arm failed to complete the trial because of moving to another city during the treatment. In the control group, a 42-year-old woman and a patient aged 52 years lost touch with us before the end of the treatment. The means of the MASI, SCTS, and area scores before treatment were not statistically different between the 2 groups (data not shown).

MASI of Patients with Melasma before and after Treatment

Clinical manifestations revealed that the color and area of the skin lesions had improved significantly after treatment (Fig. 2). In weeks 4, 6, and 8, the mean MASI of the treatment group was significantly decreased (p < 0.01) (Table 1). However, the mean MASI scores of the control group were virtually unchanged (p > 0.05) (Fig. 3a).

Table 1

Melasma area and severity index of patients with melasma

/WebMaterial/ShowPic/912380

Fig. 2

Photo of a melasma patient before (a) and after (b) treatment with tranexamic acid cataplasm.

/WebMaterial/ShowPic/912376

Fig. 3

The effects of topical tranexamic acid cataplasm on melasma. a Melasma area severity index (MASI) of patients with melasma before and after treatment. The mean MASI of the control group (open square) was almost unchanged before and after treatment (p > 0.05). The mean MASI score of the treatment group (solid square) decreased starting from week 2 (p < 0.05). In weeks 4, 6, and 8, the mean MASI was significantly decreased (* p < 0.01). b Skin color tone scale of patients with melasma before and after treatment. The mean ΔV of the treatment group (solid triangle) started to decrease in week 2. After 8 weeks, the mean ΔV of the treatment group shown marked improvement (* p < 0.05). There was no change in the control group (open triangle). c Area score of patients with melasma before and after treatment. The area score of the treatment group (solid circle) was significantly decreased compared to the control group (open circle) (* p < 0.05). ΔV, difference in value from pretreatment.

/WebMaterial/ShowPic/912375

SCTS of Patients with Melasma before and after Treatment

The mean ΔV of the treatment group changed obviously from the 2nd week (p < 0.05) (Table 2). After 8 weeks of treatment, the mean ΔV of the treatment group was 0.76 ± 0.27, indicating moderate to marked improvement (p < 0.05) (Fig. 3b).

Table 2

Skin color tone scale score of patients with melasma

/WebMaterial/ShowPic/912379

Area Score of Patients with Melasma before and after Treatment

The area score of the treatment group decreased after 8 weeks of treatment compared to the control group (p < 0.05) (Fig. 3c). Patients in the treatment group exhibited a 60-70% improvement after treatment (Table 3).

Table 3

Area score (mm2) of patients with melasma

/WebMaterial/ShowPic/912378

Relationship between Lesion Location and Efficacy

With respect to the distribution of lesions, malar melasma was the most common (43 cases, 54%) in our study. Eyelid, perioral, and cheek melasma were present in 16, 9, and 21% of the patients, respectively. No difference in the improvement rate (%) of MASI (63.2 vs. 67.5%), SCTS (17.1 vs. 15.6%), and area score (61.7 vs. 65.4%) was observed between malar melasma and nonmalar melasma (p > 0.05).

Safety

No side effects, such as allergy symptoms, erythema, papula, or pruritus, were observed.

Discussion

Integrative medicine (IM) is a patient-centered, healing-oriented clinical paradigm that explicitly includes all appropriate therapeutic approaches whether they originate in conventional or complementary medicine. While there is some evidence for the clinical and cost-effectiveness of IM practice models, the existing evidence base for IM depends largely on studies of individual complementary medicine therapies. Topical TXA cataplasm on melasma is a good example of IM [9].

TXA was discovered in 1962 by Utako Okamoto [10]; it is a synthetic derivative of the amino acid lysine and has been used to prevent abnormal fibrinolysis to reduce blood loss. The side effects of TXA include changes in color vision, blood clots, and allergic reactions. Nijo [11] (1970) first reported on the efficacy of oral TXA in the treatment of melasma in Japan. It inhibits UV-induced plasmin activity in keratinocytes and decreases melanocyte tyrosinase activity. In recent years, in order to avoid the side effects of oral TXA, researchers began to use TXA topically in the treatment of melasma. TXA cataplasm is a promising alternative among topical preparations.

Cataplasm is a special transdermal drug carrier. Kanikkannan et al. [12] reported that the concentrations of drugs in the serum and tissue (skin and muscle) after application of the cataplasm in rats also increased with an increase in the content of the drug. Drugs can be absorbed in proportion to its contents. Our results of the present study suggested significant improvements in MASI, SCTS score, and area score in the treatment group, which may be closely related to the high absorption rate of drugs by cataplasm. By the way, the oral dosage of treatment for melasma is usually 0.75-1.0 g per day [13]. Only 0.1 g of topical TXA cataplasm was used per day in our study. Therefore, the risk associated with TXA, which can cause some side effects, is probably reduced.

A recent study reported that TXA can accelerate skin barrier recovery and upregulate occludin induced by physicochemical damage to human skin [14]. It stimulates antioxidant activity, eliminates pigmentation disorder, protects the skin from the environment, slows down aging, makes the skin more elastic, and promotes moisture retention. This is of great importance for the treatment of melasma.

In conclusion, our preliminary study indicates that TXA cataplasm seems to be a potentially new and promising therapeutic option. However, a large-scale and multicenter study will be needed to define its long-term benefits and any potential additional adverse effects.


References

  1. Budamakuntla L, Loganathan E, Suresh DH, et al: A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma. J Cutan Aesthet Surg 2013;6:139-143.
  2. Karn D, Kc S, Amatya A, Razouria EA, et al: Oral tranexamic acid for the treatment of melasma. Kathmandu Univ Med J 2012;10:40-43.
    External Resources
  3. Li Y, Sun Q, He Z, et al: Treatment of melasma with oral administration of compound tranexamic acid: a preliminary clinical trial. J Eur Acad Dermatol Venereol 2014;28:393-394.
  4. Kanikkannan N, Jayaswal SB, Singh J: Transdermal delivery of indomethacin: II. Effect of penetration enhancers on the in vitro percutaneous absorption from patch formulations. Pharmazie 1994;49:619-620.
    External Resources
  5. Miyazaki M, Arimori K, Nakano M: Pharmaceutical evaluation of cataplasms. J Nippon Hosp Pharm Assoc 1988;14:192-197.
  6. Pandya A, Berneburg M,Ortonne P, et al: Guidelines for clinical trials in melasma. Br J Dermatol 2007;156:21-28.
  7. Pandya AG, Hynan LS, Bhore R, et al: Reliability assessment and validation of the melasma area and severity index (MASI) and a new modified MASI scoring method. J Am Acad Dermatol 2011;64:78-83.
  8. Konishi N, Kawada A, Morimoto Y, et al: New approach to the evaluation of skin color of pigmentary lesions using skin tone color scale. J Dermatol 2007;34:441-446.
  9. Herman PM, Dodds SE, Logue MD, et al: IMPACT - Integrative Medicine PrimAry Care Trial: protocol for a comparative effectiveness study of the clinical and cost outcomes of an integrative primary care clinic model. BMC Complement Altern Med 2014;14:132-144.
  10. Watts G: Obituary Utako Okamoto. Lancet 2016;387:2286.
  11. Nijo S: Effect of tranexamic acid on melasma. Clin Rep 1979;13:3129-3131.
  12. Kanikkannan N, Jayaswal SB, Singh J: Transdermal delivery of indomethacin: II. Effect of penetration enhancers on the in vitro percutaneous absorption from patch formulations. Pharmazie 1994;49:619-620.
    External Resources
  13. Kato H, Araki J, Eto H, et al: A prospective randomized controlled study of oral tranexamic acid for preventing postinflammatory hyperpigmentation after Q-switched ruby laser. Dermatol Surg 2011;37:605-610.
  14. Yuan C, Wang XM, Yang LJ, et al: Tranexamic acid accelerates skin barrier recovery and upregulates occludin in damaged skin. Int J Dermatol 2013;53:959-965.

Author Contacts

Huimin Zhang

Department of Dermatology, Shu-guang Hospital Affiliated to Shanghai

University of Traditional Chinese Medicine

185 Pu'an Road, Shanghai 200021 (China)

E-Mail happy2003_1@msn.com


Article / Publication Details

First-Page Preview
Abstract of Clinical Experience

Received: August 03, 2017
Accepted: November 08, 2017
Published online: December 21, 2017
Issue release date: Published online first (Issue-in-Progress)

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 3


eISSN: 2296-7362 (Online)

For additional information: https://www.karger.com/IMI


Open Access License / Drug Dosage / Disclaimer

This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Budamakuntla L, Loganathan E, Suresh DH, et al: A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma. J Cutan Aesthet Surg 2013;6:139-143.
  2. Karn D, Kc S, Amatya A, Razouria EA, et al: Oral tranexamic acid for the treatment of melasma. Kathmandu Univ Med J 2012;10:40-43.
    External Resources
  3. Li Y, Sun Q, He Z, et al: Treatment of melasma with oral administration of compound tranexamic acid: a preliminary clinical trial. J Eur Acad Dermatol Venereol 2014;28:393-394.
  4. Kanikkannan N, Jayaswal SB, Singh J: Transdermal delivery of indomethacin: II. Effect of penetration enhancers on the in vitro percutaneous absorption from patch formulations. Pharmazie 1994;49:619-620.
    External Resources
  5. Miyazaki M, Arimori K, Nakano M: Pharmaceutical evaluation of cataplasms. J Nippon Hosp Pharm Assoc 1988;14:192-197.
  6. Pandya A, Berneburg M,Ortonne P, et al: Guidelines for clinical trials in melasma. Br J Dermatol 2007;156:21-28.
  7. Pandya AG, Hynan LS, Bhore R, et al: Reliability assessment and validation of the melasma area and severity index (MASI) and a new modified MASI scoring method. J Am Acad Dermatol 2011;64:78-83.
  8. Konishi N, Kawada A, Morimoto Y, et al: New approach to the evaluation of skin color of pigmentary lesions using skin tone color scale. J Dermatol 2007;34:441-446.
  9. Herman PM, Dodds SE, Logue MD, et al: IMPACT - Integrative Medicine PrimAry Care Trial: protocol for a comparative effectiveness study of the clinical and cost outcomes of an integrative primary care clinic model. BMC Complement Altern Med 2014;14:132-144.
  10. Watts G: Obituary Utako Okamoto. Lancet 2016;387:2286.
  11. Nijo S: Effect of tranexamic acid on melasma. Clin Rep 1979;13:3129-3131.
  12. Kanikkannan N, Jayaswal SB, Singh J: Transdermal delivery of indomethacin: II. Effect of penetration enhancers on the in vitro percutaneous absorption from patch formulations. Pharmazie 1994;49:619-620.
    External Resources
  13. Kato H, Araki J, Eto H, et al: A prospective randomized controlled study of oral tranexamic acid for preventing postinflammatory hyperpigmentation after Q-switched ruby laser. Dermatol Surg 2011;37:605-610.
  14. Yuan C, Wang XM, Yang LJ, et al: Tranexamic acid accelerates skin barrier recovery and upregulates occludin in damaged skin. Int J Dermatol 2013;53:959-965.
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