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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 46-50

Comparative study of efficacy of intradermal tranexamic acid microinjections versus intradermal glutathione microinjections for treatment of facial melasma


1 Department of Dermatology, Venereology and Leprosy, Sri Aurobindo Medical College and Post-graduate Institute, Indore, Madhya Pradesh, India
2 Sarin Skin Solutions, New Delhi, India
3 Department of Dermatology and STD, Lady Hardinge Medical College and ASS Hospitals, New Delhi, India

Date of Submission05-Mar-2020
Date of Decision13-Jan-2021
Date of Acceptance07-Jun-2021
Date of Web Publication16-May-2022

Correspondence Address:
Dr. Jushya Bhatia
D-396 (Basement), Defence Colony, New Delhi 110024
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/Pigmentinternational.Pigmentinternational_

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  Abstract 


Background Melasma is a hypermelanotic disorder, which poses therapeutic challenge. Tranexamic acid (TA) and glutathione are novel therapies for the treatment of melasma.
Aim To compare the therapeutic efficacy of localized intradermal microinjections (mesotherapy) of TA versus microinjections of glutathione for the treatment of melasma.
Methods This prospective, comparative study was carried out to assess the therapeutic efficacy of TA and glutathione in 64 patients with dermal melasma after obtaining written informed consent, over a period of 12 weeks. Face of the patient was divided into two halves (split face); right cheek was injected with TA and the left with glutathione, at baseline (zero), 4th, 8th, and 12th weeks. The treatment response was assessed by using visual analog scale (VAS); photographs were taken to ascertain the improvement and its percentage was calculated. A parametric test, Student t test, and Z test were applied wherever applicable. P-value of <0.05 was considered statistically significant.
Results Out of 64 enrolled, 50 patients completed the study and it was found that the reduction in VAS score from baseline to 8th week and baseline to 12th week was significant in both the groups (P < 0.05). However, the mean difference in improvement percentage between baseline and 8th week and baseline and 12th week with TA was found to be more significant than glutathione.
Conclusion This study revealed that both TA and glutathione intradermal microinjections are effective in the treatment of melasma but TA is more effective.

Keywords: Glutathione, intradermal microinjection, melasma, mesotherapy, tranexamic acid


How to cite this article:
Kumawat K, Bhatia K, Bhatia J, Kataria R, Namdeo C, Sarin A. Comparative study of efficacy of intradermal tranexamic acid microinjections versus intradermal glutathione microinjections for treatment of facial melasma. Pigment Int 2022;9:46-50

How to cite this URL:
Kumawat K, Bhatia K, Bhatia J, Kataria R, Namdeo C, Sarin A. Comparative study of efficacy of intradermal tranexamic acid microinjections versus intradermal glutathione microinjections for treatment of facial melasma. Pigment Int [serial online] 2022 [cited 2022 Jul 1];9:46-50. Available from: https://www.pigmentinternational.com/text.asp?2022/9/1/46/345294




  Introduction Top


Melasma is an acquired, chronic, and recurrent form of hypermelanosis, which is characterized by symmetrical brown macules and patches of variable darkness on sun exposed areas of the body, typically occurring on the face (lower cheeks, forehead, nose, and upper lip).[1] Though the pathogenesis of melasma is unclear, factors such as genetic makeup, ultraviolet (UV) radiation, pregnancy, and hormonal therapy are known to influence the development of melasma. Apart from these, other factors are also implicated such as phototoxic drugs, anticonvulsant medications, and certain cosmetics.[2]

Melasma is resistant to treatment and has a high rate of recurrence. Some of the most promising available treatments for the melasma are: elimination of causative factors, protection from UV radiations (with sunscreen application), and use of triple combination (hydroquinone, tretinoin, fluocinolone). Azelaic acid, ascorbic acid, kojic acid, arbutin, chemical peels, and laser therapy also offer benefit but none of these therapies have shown uniformly satisfactory results.

Pistor from France first introduced the term “mesotherapy,” a widely used technique of drug delivery in dermatology. The mesotherapy technique comprises of localized intradermal or subcutaneous microinjections of 0.05 to 0.1 ml of diluted drug mixture or a single drug at the site of medical or aesthetic lesion.[3]

The treatment of melasma by tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid; TA) is a novel concept. This drug is widely used as an antifibrinolytic agent and has been found to inhibit plasminogen–keratinocyte interaction leading to decrease in activity of tyrosinase, thereby resulting in decreased synthesis of melanin from the melanocytes.[4],[5],[6] Human keratinocytes secrete the urokinase-type plasminogen activator, which increases the activity of melanocytes leading to increased synthesis of melanin and the blockade of this effect may be the mechanism behind therapeutic effect of TA for the treatment of melasma.[7],[8]

Glutathione is an anti-oxidant tri-peptide, which is normally present in humans and has also been tried successfully as a treatment modality for melasma. It reduces the activity of tyrosinase by three different mechanisms: (i) chelation of the copper site by its thiol group, (ii) interfering with the cellular transfer of tyrosinase to premelanosomes which is a prerequisite for melanin synthesis, and (iii) indirectly via its antioxidant effect.[9] Glutathione shifts melanogenesis from eumelanin to phaeomelanin synthesis by reactions between thiol groups and dopa-quinone leading to the formation of sulfhydryl-dopa conjugates.[10] It has also been found to be scavenger of UV radiation-induced reactive oxygen species generated in epidermal cells.[11]


  Methods Top


This was a prospective comparative study to assess and compare the therapeutic efficacy of localized TA and glutathione for treatment of facial melasma over a period of 18 months (December 2017 to May 2019) conducted in department of dermatology on OPD basis in a tertiary care center. This was a self-financed project and institutional ethical clearance (SAIMS/RC/IEC/45 dated: December 28, 2017) was taken.

After obtaining written informed consent, 64 patients of dermal type of malar melasma, examined by wood’s lamp and dermoscopy, were included. Pregnant/lactating females, patients on hormone replacement therapy or oral contraceptive pills, bleeding disorders, concomitant use of anticoagulants and any known drug allergy especially to TA, associated medical illness, and history of any other depigmenting treatment in the past 3 months were excluded.

The sociodemographic parameters, detailed history, and clinical examination were carried out and recorded in proforma. After gentle facial cleansing, a topical eutectic mixture of local anesthetic cream application was applied over the area to be treated and left for about 45 to 60 minutes. TA (500 mg/5 ml, ready to use ampule) was injected intradermally in the lesions on right cheek, 0.05 ml (5 mg)-1 cm apart using a 29G, 40 IU/ml insulin syringe, whereas glutathione (600 mg vial in powder formulation) was prepared by dissolving in 5 ml of distilled water and injected intradermally on left cheek, 0.05 ml1 cm apart using a 29G, 40 IU/ml insulin syringe. The dose and strength of TA and glutathione were chosen arbitrarily. The procedure was carried out three times, 4 weeks apart (baseline, i.e., day 0, 4th and 8th weeks). All patients were given the same sunscreen lotion (Sun Protection Factor 50, Encube ethicals Pvt. Ltd. Madkaim, Post Mardol, Ponda, Goa, India) for application over the cheeks during entire treatment duration.

Assessment and analysis

To assess the clinical response photographs were taken at the beginning of the therapy (baseline, i.e., day 0, at each sitting [4th and 8th weeks], and after 4 weeks of last therapy, i.e., at 12th week. Visual analog scale (VAS) score was recorded subjectively for each patient on a scale of 1 to 10 at baseline, 4 th, 8th, and 12th weeks, where 10 denotes maximum pigmentation and 1 denotes minimum pigmentation. Difference between the two consecutive (baseline and 4th week, 4th week and 8th week, 8th week and 12th week), VAS scores of same patient was converted into percentage with respect to initial VAS score using the formula [|(VAS score at initial stage ‒ VAS score at later stage)|]/VAS score at initial stage. The clinical improvement was assessed by using Z test to identify significance of mean difference of VAS score and its percentage on both cheeks with the assumption that the distribution of the collected VAS scores is normal. The results were evaluated only for those patients who completed the study.

Statistical software SPSS version 17.0 (SPSS inc., 233 South Wacker Drive, 11th floor, Chicago, IL, USA) trial was used for analysis. Z test was used to identify the significance of mean differences of VAS scoring, its percentage, and difference of mean between patients treated using TA and glutathione over right and left cheeks, respectively, at baseline (0 day), at 4th, 8th, and 12th weeks. Student t test, a parametric test was used to identify the significance of mean difference in age of patients with facial melasma with respect to their gender to confirm the nonbias which is further treated by Z test due to large sample size (n > 30). The probability value from P < 0.05 to P < 0.02 was considered as statistically significant, whereas from P < 0.01 to P < 0.001 was considered strongly significant.


  Results Top


A total of 64 patients were enrolled, out of which 50 completed the study and 14 dropped out due to their personal reasons. The sociodemographic characteristics and clinical features of patients are summarized in [Table 1]. The improvement in facial melasma over recipient’s cheek after TA (right cheek) and glutathione (left cheek) was analyzed and VAS score was calculated. It was noted that there was no significant difference in VAS scores over right and left cheeks of patients before start of treatment (at baseline [0 day], P > 0.05). The mean difference on VAS score showed significant improvement in both cheeks from baseline to 8th and 12th weeks (P < 0.0001). The analysis of results showed that the improvement of right cheek was significant over the left cheek depicted on the VAS score at 8th week (P < 0.011) and 12th week (P < 0.001) [Table 2].
Table 1 Patient’s sociodemographical characteristics and clinical features

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Table 2 Assessment of mean difference and comparison of improvement of facial melasma over individual cheek before and after intradermal microinjections of tranexamic acid (right cheek) and glutathione (left cheek) on VAS scoring

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The assessment of improvement/difference of the right and left cheeks for the TA versus glutathione on VAS scoring is summarized in [Table 3]. It was noted that two patients did not respond to treatment and consequently their score was noted in negative and hence the standard deviation was found to be high. The overall results after 12 weeks of therapy indicated that there was significant improvement in melasma over right cheek (TA) when compared with left cheek (glutathione)[Figure 1] and [Figure 2].
Table 3 Assessment of percentage difference in improvement in facial melasma over recipient cheeks before and after TA (right cheek) and glutathione (left cheek) intradermal microinjections on VAS scoring.

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Figure 1 Clinical photograph of patient showing melasma on cheeks and improvement after therapy on 12th week (patient 1).

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Figure 2 Clinical photograph of patient showing melasma on cheeks and improvement after therapy on 12th week (patient 2).

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  Discussion Top


In the present study, the numbers of patients of facial melasma were 50 and the maximum patients belonged to age group of 30 to 39 years. The mean age of the study patients was found to be 32.90 ± 7.92 years which was similar to the studies by Kumar et al.,[12] Garg et al.,[13] and Achar and Rathi.[14] The disease duration of melasma in majority of patients (56.0%) was between 1 to 3 years, which is in concordance with the study by Kumar et al.[12] Similar to the study by Khurana et al., majority of patients (78%) in our study were found to be of Fitzpatrick skin type IV, followed by Fitzpatrick skin type V and type III.[15]

The assessment of mean difference in VAS over both cheeks before and after TA (right cheek) and glutathione (left cheek) revealed that both the treatment options were effective [Table 2]. Khurana et al.[15] studied the therapeutic effect of oral and intradermal microinjections of TA in patients of facial melasma (n = 32 in each arm) and found that undoubtedly oral TA treatment is more efficacious; however, they concluded that by either increasing the frequency or concentration of TA microinjections, the results may be encouraging. In our study, we used higher concentration of TA (500 mg/5 ml) and observed that on right cheek, there was significant reduction in VAS score from baseline to 8th week and baseline to 12th week, suggesting that TA was more effective in treatment of facial melasma. There is very limited literature available about glutathione in facial melasma,[16] but its probable benefit in the treatment of melasma is claimed to be good. In our study, on left cheek, there was significant reduction in VAS score from baseline to 8th week and baseline to 12th week, which supports that glutathione is also effective for the treatment of facial melasma. On comparing, the results of therapeutic effect of both drugs on VAS from baseline to 8th and 12th weeks, it was found that the average score (mean ± standard deviation) with TA (right cheek) was significantly lesser when compared with glutathione (left cheek) [Table 2]. It was also observed that the mean difference in improvement (%) on VAS between baseline to 8th and 12th weeks over right cheek (TA) was found to be higher when compared with left glutathione [Table 3].

On observing adverse effects, pain and erythema were noted in both cheeks in all patients after intradermal injections but subsided in 1 to 2 days and did not need any intervention. This observation was also made by Budanmakuntla et al.[17]

Our study has thus demonstrated that although both the novel interventions are effective in the treatment of facial melasma, TA intradermal microinjections are more effective for the treatment of facial melasma than glutathione. We also noticed that there is a scarcity of literature focusing on the comparative efficacy of intradermal microinjections of TA and glutathione in the treatment of melasma and to the best of our knowledge and literature search, no such study comparing between these two modalities have been carried out in India. Thus, more studies need to be conducted using both TA and glutathione intradermal microinjections on a larger number of patients for better understanding the therapeutic effects of the two modalities.


  Conclusion Top


Both TA and glutathione intradermal microinjections were effective in the treatment of facial melasma. However, TA was found to be more effective when compared with glutathione.

Limitations

This study could not assess melasma area severity index score as mesotherapy was applied only on cheeks of the patients.

Declaration of patient consent

The authors certify that they have obtained written informed consent from all the patients. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
Sheth VM, Pandya AG. Melasma: a comprehensive update Part I, II. J Am Acad Dermatol 2011;65:689-97.  Back to cited text no. 2
    
3.
Pistor M. Un defi Therapeutiche: la Mesotherapie. 3rd ed. Paris: Maloine; 1979. p. 1-50.  Back to cited text no. 3
    
4.
Lee JH, Park JG, Lim SH et al. Localized IDM of tranexamic acid for treatment of melasma in Asian patients: A preliminary clinical trial. Dermatol Surg 2006;32:626-31.  Back to cited text no. 4
    
5.
Maeda K, Tomita Y. Mechanism of the inhibitory effect of tranexamic acid on melanogenesis in cultured human melanocytes in the presence of keratinocyte-conditioned medium. J Health Sci 2007; 53:389–96.  Back to cited text no. 5
    
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Wang N, Zhang L, Miles L, Hoover-Plow J. Plasminogen regulates pro-opiomelanocortin processing. J Thromb Haemost 2004; 2:785-96.  Back to cited text no. 6
    
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Tse TW, Hui E. Tranexamic acid: and important adjuvant in the treatment of melasma. J Cosmet Dermatol 2013;12:57-66.  Back to cited text no. 7
    
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Kim HJ, Moon SH, Cho SH, Lee JD, Kim HS. Efficacy and safety of tranexamic acid in melasma: a meta-analysis and systematic review. Acta Derm Venereol 2017;97:776-81.  Back to cited text no. 8
    
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Zhang XY, Yang XH, Yang H, Yang YP. Study of inhibitory effect of acidum tranexamicum on melanin synthesis. Chin J Dermatovenerol Int Tradit West Med 2003;2:227-9.  Back to cited text no. 9
    
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Yamamura T, Onishi J, Nishiyama T. Antimelanogenic activity of hydrocoumarins in cultured normal human melanocytes by stimulating intracelllar glutathione synthesis. Arch Dermatol Res 2002;294:349-54.  Back to cited text no. 10
    
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Maeda K, Hatao M. Involvement of photooxidation of melanogenic precursors in prolonged pigmentation induced by ultraviolet A. J Invest Dermatol 2004;122:503-9.  Back to cited text no. 11
    
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Kumar S, Mahajan BB, Kamra N. Melasma in North Indians: a clinical, epidemiological, and etiological study. Pigment Int 2014;1:95-9.  Back to cited text no. 12
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Garg VK, Sarkar R, Agarwal R. Comparative evaluation of beneficiary effects of priming agents (2% hydroquinone and 0.025% retinoic acid) in the treatment of melasma with glycolic acid peels. Dermatol Surg 2008;34:1032-40.  Back to cited text no. 13
    
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Achar A, Rathi KS. Melasma: a clinic-epidemiological study of 312 cases. Indian J Dermatol 2011;56:380-2.  Back to cited text no. 14
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Khurana VK, Misri RR, Agarwal S, Thole AV, Kumar S, Anand T. A randomized, open-label, comparative study of oral tranexamic acid and tranexamic acid microinjections in patients with melasma. Indian J Dermatol Venereol Leprol 2019;85:39-43.  Back to cited text no. 15
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Sonthalia S, Daulatabad D, Sarkar R. Glutathione as a skin whitening agent: Facts, myths, evidence and controversies. Indian J Dermatol Venereol Leprol 2016;82:262-72.  Back to cited text no. 16
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Budanmakuntla L, Loganathan E, Suresh DH et al. A randomized, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma. J Cutan Aesthet Surg 2013;6:139-43.  Back to cited text no. 17
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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