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 Table of Contents  
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 188-196

Comparison of therapeutic efficacy of intralesional platelet-rich plasma and topical alpha-glucoside derivative of trihydroxy benzoic acid in melasma: a randomized controlled study

Department of Dermatology, Government Medical College, Bhavnagar, Gujarat, India

Date of Submission06-Nov-2020
Date of Decision09-Aug-2021
Date of Acceptance09-Oct-2021
Date of Web Publication30-Nov-2022

Correspondence Address:
Dr. Hita Mehta
Department of Dermatology, 201 Golden Arc Apartment, Atabhai Chowk, Bhavnagar 364001, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pigmentinternational.pigmentinternational_

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Background: Melasma is the most common cause of facial melanosis and presents with a complex therapeutic problem. Intralesional platelet-rich plasma (PRP) has shown promising results in hyperpigmentation, whereas alpha-glucoside derivative of trihydroxy benzoic acid (THBG) is a newer molecule for the management of pigmentation. Aims and objective: To compare therapeutic effects of PRP and THBG in facial melasma, note any untoward side effects of therapy and evaluate dermoscope as a tool for therapeutic prognosis. Methods: A total of 60 patients were enrolled based on inclusion and exclusion criteria after due written informed consent. After clinical, dermoscopic, and Wood lamp examination with relevant blood investigations, group P was treated by three sittings of intralesional injection of PRP at monthly interval, whereas group B was subjected to local application of THBG twice a day. Intergroup as well as intragroup comparative analyses were performed by subjective scores and dermoscope. Results: The mean of difference between modified melasma area and severity index (mMASI) score at the end of the study (i.e., difference mMASI at 12 and 0 weeks) was 2.21 for group P and 0.18 for group B and on comparison, the P-value was <0.0001 which is considered statistically significant. The average %mMASI improvement in group P was 35.05%, whereas in group B, it was 3.18%. On analysis of other parameters, physician global assessment, patient global assessment, and melasma quality of life scale patients of group P showed higher and significant improvements in comparison with group B. Changes in dermoscopic parameters could be appreciated in patients with significant improvement only. Conclusion: There is mild–moderate improvement in melasma (average 35.05%) with PRP with no untoward side effects, whereas THBG did not show any promising result in the treatment of melasma in FT grade IV/V.

Keywords: Melasma, PRP, THBG

How to cite this article:
Jhavar M, Mehta H, Somani S, Agrawal N. Comparison of therapeutic efficacy of intralesional platelet-rich plasma and topical alpha-glucoside derivative of trihydroxy benzoic acid in melasma: a randomized controlled study. Pigment Int 2022;9:188-96

How to cite this URL:
Jhavar M, Mehta H, Somani S, Agrawal N. Comparison of therapeutic efficacy of intralesional platelet-rich plasma and topical alpha-glucoside derivative of trihydroxy benzoic acid in melasma: a randomized controlled study. Pigment Int [serial online] 2022 [cited 2023 Mar 27];9:188-96. Available from: https://www.pigmentinternational.com/text.asp?2022/9/3/188/362396

  Introduction Top

Melasma is the most common cause of facial melanosis. Triple combination therapy with hydroquinone, tretinoin, and corticosteroid is preferred topical therapy but already there is extensive literature available about the many side effects as exogenous ochronosis, confetti-like leukoderma, milia, irritation, telangiectasia, and atrophy.

Intralesional platelet-rich plasma (PRP) injections have shown promising results in hyperpigmented lesions. Yew et al. reported a significant reduction of melasma area and severity index (MASI) score in two patients with refractory melasma when using intradermal PRP injection as an adjunct to Q-switched Nd:YAG laser and topical alpha arbutin.[1],[2],[3] PRP contains higher-than-normal platelet concentration, prepared by whole blood centrifugation. In alpha granules of platelets, cytokines and growth factors are abundant. Kim et al. used mouse melanocyte cell line to study the effect of transforming growth factor-beta 1 (TGF-β1); a growth factor present in PRP, their study showed that TGF-β1 reduces the activity of tyrosinase, melanocyte-inducing transcription factor promoter, decreases tyrosinase-related protein production, and can inhibit the expression of the paired-box homeotic gene (PAX3), which is a key regulator of UV-induced melanogenesis.[4]

Alpha-glucoside derivative of trihydroxy benzoic acid (THBG) is a new nonsteroidal preparation that decreases melanogenesis by controlling the nuclear factor kappa B pathway, reducing PGE2 expression, preventing melanin transfer to keratinocytes, and inhibiting tyrosinase. Chajra et al. in their study performed siascope analysis for melanin content quantification and noted THBG cream induced 7.5% decrease of skin melanin content on 84 days of daily use.[5]

Hence, in this study, we compared the therapeutic efficacy of PRP and a new molecule THBG in the treatment of melasma, both clinically and dermoscopically.

  Methods Top

The study was a double arm, parallel-group, prospective, interventional, open-labeled randomized controlled trial with an allocation ratio of 1:1.

The study was carried out in outpatient department of DVL of Sir T Hospital and Government Medical College, Bhavnagar, a tertiary care hospital located in Gujarat, India.

After ethical clearance from Institutional Review Board, a total of 60 patients clinically diagnosed with facial melasma, above 18 years irrespective of their gender, were enrolled after written informed consent explaining the risks, benefits, and potential complications. Patients with a history of any treatment taken for melasma in the past 6 months, patients on oral contraceptive pills, oral tretinoin, hormonal therapy, anticoagulant drugs, pregnant/lactating female, patients with the tendency of keloid, hypertrophic scar, bleeding disorder, platelet abnormality, chronic liver disease, hepatitis B/HIV positive, known allergy to components of topical anesthetic used in this trial (prilocaine) and who refused for photographs or follow-up were excluded.

The sample size was calculated by using openEpi software version 3 which came out to be 60 with 30 in each group.

Simple random sampling was performed using an android application “random number generator” for the sample size of 60, which generated two sets of random lists of 30 numbers in each group. Patients were allocated numbers based on the sequence of their arrival to outpatient department (OPD) and randomized according to the generated list.

After the detailed personal history, medical history, and Wood lamp examination, clinical and dermoscopic photographs (interception of vertical line from lateral canthus of the eye and horizontal line from ala of nose) were stored and modified MASI (mMASI) score [Figure 1][6] and melasma quality of life (MelasQOL) scale were calculated at baseline.[7]
Figure 1 Illustration representing calculation mMASI score.

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Topical anesthesia Prilox (2.5% lidocaine + 2.5% Prilocaine) was applied under occlusion for 45 minutes to patients of group P, meanwhile 15 to 20 mL of blood was withdrawn from the patient and a standard protocol for the formation of PRP was followed.[3]. Platelets in PRP are estimated to be three to four times more concentrated than whole blood. Approximately 4 to 5 mL of PRP was obtained at the end of the process.

This prepared PRP was filled into 1-mL insulin syringes. Under aseptic precautions, the site was cleaned with povidone-iodine and spirit. PRP was administered by superficial microinjections via mesotherapy technique using a 32-G needle into the papillary dermis (1.5–2.0 mm deep) about 0.05 mL at 1 cm interval over the site of melasma. The operative site was covered with sterilized gauze pieces, left till dry, and removed by the patient after 1 hour. This protocol was followed for a total of three sittings at monthly intervals.

Patients of group B applied THBG twice a day for the study period.

Patients were advised photoprotection, refrain from using any cosmetic products other than sunscreen and visit OPD to report any side effects.

For assessment, the baseline parameters (i.e., at 0 weeks) namely the mMASI score, MelasQOL, clinical and dermoscopic photographs were compared with that of at the end of the study, that is, 12 weeks. The patient global assessment (PtGA) score and physician global assessment (PGA) score were calculated at end of the study.

For statistical analysis, data entry was carried out in MS Excel and data analysis was carried out using Graph pad Instat 3, quantitative variables were compared using unpaired t test and Mann–Whitney test and for correlation Pearson r, and Spearman r (Gaussian distribution non-Gaussian distribution, respectively) were used. Any P-value <0.05 was considered significant.

  Results Top

The age of patients ranged from 25 to 49 years, and the majority of the study participants were in the age group of 31 to 40 years (61.66%). There were 7 (11.66%) males and 53 (88.33%) females in the study. Thirty-five (58.33%) patients had centrofacial type of melasma and 25 (41.66%) had malar pattern. No patient had mandibular melasma. There was no significant difference between age, gender, and pattern distribution of melasma between the two groups (P-value 0.12, 0.82, 0.82, respectively, which is statistically not significant), ensuring that patients were randomly distributed among two groups [Table 1].
Table 1 Demographic details of study participant

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In our study, all patients belonged to Fitzpatrick (FT) skin types 3, 4, and 5, and majority that is 35 (58.3%) patients belonged to FT skin type 4. All patients had intermittent sun exposure with none using sunscreen before enrolment in the study and interestingly no patient had a positive family history. Findings of baseline Wood lamp examination are represented in [Table 2].
Table 2 Wood lamp examination in two groups at baseline

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On intragroup comparison of mMASI score in group P mean mMASI score decreased from 6.47 at 0 weeks to 4.35 at the end of 12th week which was statistically significant with P-value 0.0011 [Figure 2] and [Figure 3]. On the other hand, in group B, the mean mMASI decreased from 4.82 to 4.64, which was not statistically significant with a P-value of 0.77.
Figure 2 Dermoscopic and clinical improvement in a patient of group P. (2A) Pretreatment dermoscopy. (2B) mMASI score 7.0. (2C) Posttreatment dermoscopy showing partial clearance of reticuloglobular pattern and arciform structures. (2D) mMASI score improved to 4.8.

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Figure 3 Comparison of pre- and posttreatment clinical image in patient X of group P. (A&B) Pretreatment mMASI score 7.2. (C&D) Posttreatment mMASI score 2.4 at 12 weeks.

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Only 3 (10%) patients in group P showed improvement between 61% and 100%, and the majority of patients (73.3%) showed improvement between 31% and 60%, whereas in group B, all patients showed improvement between 0% and 31%. The average mMASI % improvement in group P was 35.05%, whereas in group B, it was 3.18% [Table 3].
Table 3 Percentage mMASI improvement in both groups

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For intergroup comparison, we analyzed the mMASI-12 (mMASI at 12th week) and mMASI-0 differences between the two groups and found improvement was significantly higher for group P (P < 0.0001).

On reviewing the association between age and mMASI % improvement, the correlation coefficient (r) was −0.036 and 0.008 for groups P and B, respectively, stating that in group P, there was mild negative correlation, that is, in patients receiving PRP as the age increases the therapeutic improvement decreases; whereas no such correlation was present in group B.

There was no statistical significant association of mMASI score improvement with FT skin type and appearance on Wood lamp in any group [Table 4] and [Table 5].
Table 4 Association between mMASI % improvement and Fitzpatrick skin type

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Table 5 Association of mMASI % improvement and Wood lamp examination

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We performed dermoscopic examination pre- and posttreatment in both the groups. [Table 6] shows pretreatment dermoscopic findings. Incomplete dark brown reticulate pattern was the most common finding (68.3%). To note, in our study, dermoscopic findings were similar pre- and posttreatment, except one patient of group P showed improvement in telangiectasias (decrease in red streaks), whereas in two patients of group P, we observed partial clearance of reticuloglobular and arciform patterns (depicted in [Figure 4]). This lesser frequency of dermoscopic improvement could be attributed to less average improvement in mMASI score by both treatment modalities.
Table 6 Pretreatment dermoscopic examination in both groups

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Figure 4 Dermoscopic image of patient X showing mild decrease in intensity of brown pigment and reticuloglobular pattern. (A) Pretreatment dermoscopy. (B) Posttreatment dermoscopy.

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On assessing PtGA majority of patients in group P showed near clearance of pigmentation, whereas most of the patients of group B showed persistence of significant hyperpigmentation. PtGA for group P was significantly improved than group B (P = 0.0014) [Figure 5], whereas evaluating PGA at 12 weeks, complete improvement was observed in none of the two groups. In group P, 3.3% of patients showed almost clearance, 10% showed marked improvement, 26.6% showed moderate improvement, a slight improvement was reported in 46.6% and only 13.3% showed no improvement. In group B, none of the patients showed almost clearance, 33.3% showed marked improvement, moderate and slight improvement was observed in 3.3% and 26.6%, respectively, and 66.6% showed no improvement. The improvement in PGA in group P was statistically significant (P < 0.001) [Figure 6].
Figure 5 Bar graph showing intragroup comparison of patient global assessment scale. PtGA, patient global assessment.

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Figure 6 Bar graph showing intragroup comparison physician global assessment scale. PGA, physician global assessment.

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The mean of MelasQOL of group P was 46.06 and group B was 39.60 at 0 weeks. The mean percentage improvement of MelasQOL of the two groups at the end of 12 weeks was 23.6% and 6.5%, respectively, for groups P and B [Table 7]. There was no correlation noted between mMASI and MelasQOL (correlation coefficient r = 0.012).
Table 7 Mean MelasQOL percentage improvement in both groups

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  Discussion Top

Melasma is a common acquired condition of symmetric hyperpigmentation, typically occurring on the face. In the present study of 60 patients of melasma, the most notable finding was that group P showed 32.7% improvement in mMASI score after three sessions of treatment by PRP (P-value 0.011 which was statistically significant). This is consistent with the findings of Yew et al.[3] On the other hand, in a case reported by Cayırlı et al., more than 80% reduction in epidermal hyperpigmentation was noted on intradermal injection of PRP.[8]

Dannarongchai et al. conducted a split-faced prospective trial, with PRP at one and normal saline at the other side. In their study, mMASI score showed a statistically significant reduction, with no difference between the two groups. They found no significant difference between the PRP and the normal saline groups using melanin index, erythema index, hemoglobin, and textures at any visits.[9]

Chajra et al. in their study conducted quantitative and qualitative analysis of (brightness), chromaticity coordinates, individual typology angle, using Chroma-Meter (CM2600d TMKonica Minolta, Toulouse, France) tool, VISIA-CR™ (Canfield Scientific Inc., Fairfield, NJ, USA), and SIAscope™ MedX Company (searched through google). They demonstrated that THBG can significantly modify skin color and concluded THBG controls skin tone via the inhibition of melanin synthesis.[5] On the other hand, in our study, group B showed only 3.73% improvement at week 12 that was statistically not significant (P = 0.77).

Also to note study conducted by Chajra et al. was on Korean population FT 2/3 and this study was on Indian population with FT 4/5, this lack of significant response can be attributed to higher FT grade of the study population.

In this study, in group P, there was a negative correlation of age and mMASI % improvement, that is, it was observed that as the age increases the improvement in mMASI decreases (r = −0.03), whereas no such correlation was noted in group B. This is probably attributing to a higher amount of growth factors in the plasma of younger age group.

Our study shows there was no relation between therapeutic response in terms of mMASI score improvement and appearance of melasma on Wood lamp in both groups. Studies by Sarvjot et al. and Grimes et al. also noted Wood light examination may not be accurate in determining the depth of pigment. And they found a poor correlation between the classification based on Wood light examination and histopathology.[10],[11],[12]

The dermoscopic findings were similar to that of studies performed by Sonthalia et al. and Neema et al.[13],[14] Interestingly, we observed whether the follicular opening was spared periosteal hyperpigmentation surrounding the follicle in majority of patients. Motive behind including pre- and postdermoscopy in our study was to diagnose melasma and differentiate it from exogenous ochronosis, lichen planus pigmentosus, reihls melanosis, and other facial pigmentary mimics; in addition to evaluate it as a tool for prognosis. But it occurred that dermoscopic findings were mostly similar at pre- and posttreatment. This lesser frequency of dermoscopic improvement could be attributed to less average improvement in mMASI score by both the modalities. Hence, it would be premature to comment on the usefulness of dermoscopy in the therapeutic prognosis of melasma. On extensive literature search, we could not find any study using dermoscope for prognosis of melasma.

An additional finding was that we found no correlation between Wood lamp and dermoscopic findings, that is, it is said epidermal melasma enhances on Wood lamp and shows complete reticular pattern. On the other hand, in our study, we found 41 patients showed enhancement on Wood lamp, whereas 13 showed complete reticular pattern on dermoscope. But newer literature describes melasma as more or less mixed.[10] Therefore, we did not attempt to classify melasma in epidermal and dermal on basis of dermoscope; instead, we noted individual characteristic features pre- and posttreatment.

Quality of life is often adversely affected in patients of melasma and in today’s digital world where selfies and profile pictures are the usual trend, this adds to the suffering faced by patients. The mean percentage improvement of MelasQOL of two groups at the end of 12 weeks was 23.6% and 6.5%, respectively, for groups P and B.In addition, on comparing the baseline mMASI and MelasQOL, we found that patients with minimal clinical involvement may be highly distressed and patients with extensive involvement may not be bothered at all, so we did not find any correlation between MelasQOL and disease severity in contrary to Balkrishnan et al., as they reported moderate correlation.[15]

None of the study participants of any group showed any major adverse effects. Mild erythema was noted by all patients of group P which subsided in average 2 to 3 days similar to many other studies conducted in relation to injecting PRP on face for purpose as facial rejuvenation, periorbital pigmentation.[1],[16]

  Conclusion Top

There is mild‒moderate improvement in melasma with PRP (35.05% mMASI % average improvement), whereas THBG did not show any promising result in FT grade IV/V. It would be premature to comment on the usefulness of dermoscopy for therapeutic prognosis in melasma due to overall noted fewer efficacies of the treatment modalities compared in this study which paves the road toward more such studies utilizing dermoscopic examination.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Al-shami SH. Treatment of periorbital hyperpigmentation using platelet-rich plasma injections. 2014;3:87-94.  Back to cited text no. 1
Yun WJ, Bang SH, Min KH, Kim SW, Lee MW, Chang SE. Epidermal growth factor and epidermal growth factor signaling attenuate laser-induced melanogenesis. Dermatologic Surg 2013;39:1903-11.  Back to cited text no. 2
Yew CH, Ramasamy TS, Amini F. Response to intradermal autologous platelet rich plasma injection in refractory dermal melasma: report of two cases. J Health Transl Med 2015;18:6-7.  Back to cited text no. 3
Kim DS, Park SH, Park KC. Transforming growth factor-β1 decreases melanin synthesis via delayed extracellular signal-regulated kinase activation. Int J Biochem Cell Biol 2004;10:1482-91.  Back to cited text no. 4
Chajra H, Redziniak G, Auriol D, Schweikert K, Lefevre F. Trihydroxybenzoic acid glucoside as a global skin color modulator and photo-protectant. Clin Cosmet Investig Dermatol 2015;8:579-89.  Back to cited text no. 5
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.  Back to cited text no. 6
Sarkar R, Garg S, Dominguez A, Balkrishnan R, Jain RK, Pandya AG. Development and validation of a Hindi language health-related quality of life questionnaire for melasma in Indian patients. Indian J Dermatol Venereol Leprol 2016;82:16-22.  Back to cited text no. 7
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Cayırlı M, Calışkan E, Açıkgöz G, Erbil AH, Ertürk G. Regression of melasma with platelet-rich plasma treatment. Ann Dermatol 2014;26:401-2.  Back to cited text no. 8
Dannarongchai A, Luplertlop N, Deeanandlarp S. Thai Journal of Pharmaceutical Sciences (TJPS) the potential role of platelet-rich plasma in melasma treatment. 2017;41:233-6.  Back to cited text no. 9
Grimes PE, Yamada N, Bhawan J. Light microscopic, immunohistochemical, and ultrastructural alterations in patients with melasma. Am J Dermatopathol 2005;27:96-101.  Back to cited text no. 10
Manjunath KG, Kiran C, Sonakshi S, Agrawal R. Melasma: through the eye of a dermoscope. Int J Res Dematol 2016;2:113-7.  Back to cited text no. 11
Sarvjot V, Sharma S, Mishra S, Singh A. Melasma: a clinicopathological study of 43 cases. Indian J Pathol Microbiol 2009;52:357-9.  Back to cited text no. 12
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Sonthalia S, Jha AK, Langar S. Through the dermoscope dermoscopy of melasma. Indian Dermatol Online J 2017;8:525-6.  Back to cited text no. 13
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Neema S, Chatterjee M. Dermoscopic characteristic of melasma in Indians: A cross sectional study. Int J Dermoscop 2017;6-10.  Back to cited text no. 14
Balkrishnan R, McMichael AJ, Camacho FT et al. Development and validation of a health-related quality of life instruments for women with melasma. Br J Dermatol 2003;149:572-7.  Back to cited text no. 15
Le ADK, Enweze L, DeBaun MR, Dragoo JL. Current clinical recommendations for use of platelet-rich plasma. Curr Rev Musculoskelet Med 2018;11:624-34.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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