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Received: 22 January 2019    Revised: 3 May 2019    Accepted: 26 August 2019 DOI: 10.1111/jocd.13157

ORIGINAL CONTRIBUTION

Platelet‐rich plasma treatment for melasma: A pilot study Punyaphat Sirithanabadeekul MD1

 | Arada Dannarongchai MD1 |

Atchima Suwanchinda MD2 1 Department of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand 2

Department of Dermatology, School of AntiAging and Regenerative Medicine, Mae Fah Luang University, Bangkok, Thailand Correspondence Punyaphat Sirithanabadeekul, Department of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand Email: punyaphats.cicm@gmail.com

Abstract Background: Melasma treatments have varying success and are associated with some complications. Aims: To assess the effectiveness of platelet‐rich plasma (PRP) treatment for melasma. Methods: Ten female patients with bilateral mixed‐type melasma were enrolled in our randomized, split‐face, single‐blinded prospective trial. Over 4 treatment ses‐ sions that each took place every 2 weeks, PRP was injected intradermally on one side of the face (PRP condition) and normal saline on the other (control condition). PRP was prepared by using the YCELLBIO Kit®. Outcomes were evaluated with the modified Melasma Area and Severity Index (mMASI), Mexameter®, and Antera® 3D. Patient satisfaction was also assessed at baseline, at 2, 4, and 6 weeks, and 1 month after treatment completion. Results: mMASI score and Antera® 3D‐assessed melanin levels show significant im‐ provement in the PRP condition than control condition between baseline and week 6, while patient satisfaction significantly increased over time. However, Mexameter®‐ assessed erythema and melanin indices did not significantly differ between the con‐ trol and PRP conditions, though there was a trend toward reduced pigmentation in the latter. Finally, side effects of treatment were mild and resolved spontaneously within a few days. Conclusion: This is the first randomized, placebo‐controlled trial study using PRP for treatment of melasma. PRP injection significantly improved melasma within 6 weeks of treatment in terms of mMASI scores, patient satisfaction, and Antera®‐assessed melanin levels. Hence, intradermal PRP injection could be used as an alternative or adjuvant therapy for melasma. However, additional trials are needed for more rigor‐ ous evaluation of its long‐term efficacy and safety. KEYWORDS

hyperpigment, intradermal, melasma, platelet‐rich plasma, treatment

1 |  I NTRO D U C TI O N

people with darker skin (Fitzpatrick type IV‐VI). Although its pathogenesis remains unknown, common risk factors for melasma

Melasma is an acquired skin pigmentation disorder characterized

include genetics, UV light exposure, pregnancy, and use of oral

by symmetrical hyperpigmented macules and patches in sun‐ex‐

contraceptives and drugs such as phenytoin. Recently, there has

posed areas of the face such as the forehead, cheeks, lips, and

also been evidence that dermal factors, including increased mast

nose. It occurs commonly and is found especially in women and

cell numbers, vascular growth factor levels, solar elastosis, and

J Cosmet Dermatol. 2020;19:1321–1327.

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basement membrane disruption, may be involved in the pathogen‐ esis of melasma.1 Furthermore, histopathological findings show

2.3 | Platelet‐rich plasma preparation

increased melanin deposition and melanocyte numbers in me‐

The anticoagulant citrate dextrose A (1.5 mL) and 13.5 mL of blood

lasma‐affected skin. 2

were drawn into a 20‐mL syringe using a butterfly cannula. The sy‐

Although there are several treatment options for melasma, in‐

ringe was then shaken slowly for 15 seconds to allow the liquids

cluding topical agents, chemical peels, and laser and light therapies,

to mix. The cannula was then swapped with an 18‐gauge needle

these treatments have varying success and can cause complications

before the blood was processed using the YCELLBIO Kit ® (Ycellbio

such as irritation, postinflammatory hyperpigmentation (PIH), and

Medical Co., Ltd) following manufacturer guidelines. Specifically,

rebound hyperpigmentation.3 In light of these limitations, platelet‐

the anticoagulant‐blood mixture was transferred to the device pro‐

rich plasma (PRP) is beginning to receive attention in aesthetic med‐

vided with the YCELLBIO Kit® and then centrifuged at 3200 revolu‐

icine as an alternative or adjuvant treatment option.

tions per minute for 4 minutes at room temperature. The resultant

Platelet‐rich plasma is plasma containing higher‐than‐normal

buffy coat and plasma at the neck of the device were then extracted

platelet concentrations and is prepared by whole blood centrifu‐

with a 3‐mL syringe, and an 18‐gauge needle before the needle was

gation. PRP has been shown to have rejuvenating effects, with the

removed slowly.

alpha granules of platelets containing an abundance of cytokines and growth factors involved in wound healing, collagen production, and the control of homeostasis. Indeed, previous case studies have

2.4 | Clinical evaluation

demonstrated its efficacy in reducing hyperpigmented lesions in‐

To objectively measure cosmetic outcomes, melanin index (MI) and

cluding melasma, though this has yet to be shown in a controlled

erythema index (EI) at baseline, at 2, 4, and 6 weeks, and 1 month

trial. Hence, we aimed to investigate the effectiveness of PRP in‐

after treatment completion (ie, at 10 weeks) were measured using

jection for melasma treatment in a randomized, split‐face, single‐

the narrow‐band reflectance spectrophotometer (Mexameter®

blinded prospective trial.

MX18; Courage + Khazaka electronic GmbH). At the same time‐ points, melanin levels, hemoglobin levels, wrinkle levels, and skin

2 |  M E TH O DS 2.1 | Patient selection

textures were assessed using the Antera® 3D Analysis equipment (Miravex Limited). Subjective measures included evaluation of modified Melasma Area and Severity Index (mMASI) scores by two blinded dermatol‐

This study was performed with 10 female patients from November

ogists at the timepoints above. Patient satisfaction scores (ranging

2016 to February 2017. We aimed to recruit patients with bilateral

from 0% = no change in melasma to 100% = completely resolved

mixed‐type melasma of the face who were 18‐65 years of age. Those

melasma) were also assessed at 2, 4, 6, and 10 weeks.

who were pregnant, lactating, had bleeding tendencies, were con‐ comitantly using isotretinoin or hormonal therapy, any concurrent melasma treatments, any bleaching or whitening cream, any laser

2.5 | Statistical analysis

treatment in last 6 months or had any skin diseases affecting the

Data are expressed as mean ± standard deviation. Paired t tests

areas to be treated with PRP were excluded. The study protocol was

were used to analyze differences in outcomes between the PRP and

approved by the Human Ethics Committee of Thammasat University

control conditions, and between different timepoints in the same

and all patients provided informed consent.

condition. SPSS software version 21 (SPSS) was used for all analyses. P values <.05 were considered statistically significant.

2.2 | Patient preparation Patients were asked to remove all makeup and clean their faces

3 | R E S U LT S

before treatment. A preoperative topical analgesic cream (2.5% li‐ docaine and 2.5% prilocaine, EMLA®) was applied onto lesions and

Ten female patients with mixed‐type melasma were enrolled in this

occluded 45 minutes before treatment and subsequently washed off

study. All completed the treatment protocol, and their average age

to leave the skin surface completely dry. PRP (0.1 mL/cm2) was then

was 46.2 years (range, 33‐58  years). Among these 10 patients, 2

injected intradermally into melasma‐affected areas on one side of

(20%) had skin type III and 8 (80%) had skin type IV.

the face in a random manner (PRP condition), and normal saline was

Mean melanin levels as assessed by the Antera® (Figure 1A)

injected intradermally on the other (control condition). This treat‐

were significantly reduced in the PRP condition from 0.61 ±  0.02

ment was administered over a total of 4 sessions that each took

at baseline to 0.57 ± 0.03 at week 6 (P = .038). The relative mela‐

place every 2 weeks. Patients were also instructed to apply broad‐

nin improvement compared to baseline also shows significant im‐

spectrum SPF50 sunscreen and avoid sun exposure, to use only a

provement on PRP condition at week 6(Figure 1B) Moreover, mean

specific moisturizer and cleanser, and to not use any other topical

wrinkle levels, again as assessed by the Antera® (Figure 2), were sig‐

preparations on the lesions during the study period.

nificantly reduced in the PRP condition from 10.47 ± 1.26 at baseline


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SIRITHANABADEEKUL et al.

F I G U R E 1   A, Mean Antera®‐assessed melanin levels at baseline and at weeks 2, 4, 6, and 10 in the platelet‐rich plasma (PRP) and control conditions. *P < .05. B, Mean Antera®‐assessed relative melanin improvement compare between baseline and weeks 2, 4, 6, and 10 in the PRP and control conditions. *P < .05

(A)

(B)

F I G U R E 2   Mean Antera®‐assessed wrinkle levels at baseline and at weeks 2, 4, 6, and 10 in the platelet‐rich plasma and control conditions. *P < .05

to 7.63 ±  1.06 at week 4 (P = .040). Neither melanin nor wrinkle

(Figure 4) also improved significantly at every visit from baseline to

levels significantly changed in the control condition.

the end of treatment and were unchanged in the control condition.

There was a mean mMASI score improvement of 1.03 ± 0.44 be‐

Melanin index values (Figure 5) as measured by the Mexameter®

tween baseline and week 10 in the PRP condition (Figure 3), which

fell from a mean score of 256.73 ± 17.68 at baseline to 238.63 ± 16.4

was significantly greater than the improvement seen in the control

at week 10 in the PRP condition, though this change was not sig‐

condition (P = .042). Patient satisfaction scores in the PRP condition

nificant (P = .334). In the control condition, melanin index values


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SIRITHANABADEEKUL et al.

1324      

F I G U R E 3   Mean mMASI scores at baseline and at weeks 2, 4, 6, and 10 in the platelet‐rich plasma and control conditions. *P < .05

instead increased from a mean score of 246.57 ± 22.88 at baseline to

hyperpigmentation. Recently, PRP has garnered attention in aes‐

249.47 ± 21.36 at week 10, though this change was also not significant

thetic medicine as a possible alternative or adjuvant therapy. As a

(P = .849). Furthermore, neither melanin index nor hemoglobin level

concentrated source of autologous platelets, PRP contains several

changes were significant between any of the measurement timepoints

different growth factors and other cytokines that can stimulate

in either of the 2 conditions, though there was a trend toward gradual

various soft tissue functions such as wound healing and collagen

improvement in terms of melanin index in the PRP condition.

production. Hence, PRP has promise as an effective treatment with

®

fewer side effects and less rebound hyperpigmentation than other

Erythema index values as measured by the Mexameter (Figure 6) increased nonsignificantly from a mean score of 320.6 ±  13.75 at

melasma treatments. We therefore aimed to assess the effective‐

baseline to 322.02 ± 13.27 at week 10 in the PRP condition (P = .938).

ness of PRP injection as a treatment for melasma.

Erythema index values in the control condition also increased non‐

In 2014, Çayırlı et al studied the effects of PRP injection in one

significantly from 322.3 ± 18.94 at baseline to 327.0 ± 13.99 at

patient by giving a total of 3 injections, each 2 weeks apart, to the

weeks 10 (P = .802). They also did not change significantly between

whole face. At the end of the treatment, a reduction in epidermal

any of the measurement timepoints in either of the 2 conditions.

hyperpigmentation of over 80% was observed with no recurrence

Finally, all side effects were mild such as bruising and resolved

in 6 months.4 Similarly, Yew et al reported 2 cases for which mean

spontaneously within a few days of symptom onset. Figure 7 demon‐

mMASI scores were significantly reduced from 33.5% to 20% after

strates the PRP‐induced changes seen in one of our patients.

intradermal administration of PRP with Q‐switched Nd:YAG laser treatment over 2 sessions a month apart, along with daily topical ap‐ plication of alpha arbutin. 5 Our trial adds to this body of evidence by

4 | D I S CU S S I O N

being, to our knowledge, the first randomized, controlled, split‐face

Melasma is an acquired skin hyperpigmentation disorder that com‐

teers with melasma were randomly treated with an intradermal PRP

monly occurs in Thailand. Although there are several treatment

injection to one side of the face and an intradermal normal saline

options for melasma, they have varying success and are associ‐

injection (control) to the other side over 4 sessions each 2 weeks

ated with some complications such as irritation, PIH, and rebound

apart. They were then followed up 1 month after the last treatment.

trial of PRP injection for melasma treatment. Specifically, 10 volun‐


SIRITHANABADEEKUL et al.

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F I G U R E 4   Mean patient satisfaction scores at weeks 2, 4, 6, and 10 in the platelet‐rich plasma and control conditions. *P < .05

F I G U R E 5   Mean Mexameter®‐ measured melanin index values at baseline and at weeks 2, 4, 6, and 10 in the platelet‐rich plasma and control conditions. *P < .05

The most notable finding of our study was that mean mMASI

These results demonstrate that PRP can partially improve me‐

scores in the PRP condition were significantly reduced from

lasma lesions, though this improvement is not as drastic as that in

4.92 ±  0.96 to 3.5  ±  0.67, an improvement of 28.9%. On the

previous studies.4,5 This discrepancy could be due to subjects being

other hand, scores were reduced from 4.98 ± 0.86 at baseline to

younger in previous studies, as well as the use of different antico‐

4.53 ± 0.96 at week 10 in the control condition, an improvement

agulants and PRP preparation methods between studies. However,

of only 9%. Importantly, the decrease in mMASI scores signifi‐

regarding redness in terms of Mexameter®‐assessed erythema index

cantly differed between these 2 conditions (P = .042). In addition,

values and Antera®‐assessed hemoglobin levels, both treatment reg‐

mean melanin levels as assessed by the Antera® were significantly

imens did not result in an improvement from baseline. This suggests

reduced from 0.61 ±  0.02 at baseline to 0.57  ±  0.03 at week 6

that PRP does not affect the mechanism by which redness of the

(P = .038) in the PRP condition. Even though melanin index and

skin develops. In contrast, wrinkle levels as measured by the Antera®

melanin levels did not significantly differ between the 2 conditions

were significantly lower in the PRP than control condition at week

at any timepoint, there was a trend toward a gradual reduction of

4 (P = .018). This is likely attributable to the rejuvenating effect of

melanin in the PRP condition. Accordingly, patient satisfaction sig‐

PRP that has been demonstrated in many studies, whereby fibro‐

nificantly improved between weeks 2 and 10 in the PRP condition

blast and collagen proliferation are stimulated and hyaluronic acid

but did not change in the control condition. Any improvements

synthesis is enhanced.6,7 The main growth factors with extracellular

seen in the control condition were likely largely due to the daily

matrix production properties involved in these effects are epidermal

use of SPF50 sunscreen.

growth factor, platelet‐derived growth factor, transforming growth


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SIRITHANABADEEKUL et al.

1326      

F I G U R E 6   Mean Mexameter®‐ measured erythema index at baseline and at weeks 2, 4, 6, and 10 in the platelet‐rich plasma and control conditions. *P < .05

F I G U R E 7   Skin appearance at (A) the 2nd week of treatment and (B) the 6th week of treatment (platelet‐rich plasma at right side, control at left side)

factor‐beta 1, and fibroblast growth factor. Finally, all side effects

are needed for more rigorous evaluation of its long‐term efficacy

of treatment were mild and were resolved within a few days. The

and safety.

limitations of this study design include its small sample size and the relatively short follow‐up period of 1 month. Further studies in other growth factor expression according to melanogenesis reduction

AC K N OW L E D G M E N T S

which will benefit in providing further information on hyperpigmen‐

We acknowledge the assistance of Achara Phumyen, PhD for PRP

tation improvement.

preparation.

In conclusion, this is the first randomized, placebo‐controlled trial of PRP for the treatment of melasma. We found that PRP injec‐ tion significantly improved melasma within 6 weeks of treatment, as indicated by improved mMASI scores, reduced Antera®‐as‐

C O N FL I C T O F I N T E R E S T No conflict of interest.

sessed melanin levels, and increased patient satisfaction. We also observed a trend toward a gradual reduction of pigmentation in terms of melanin index in the PRP condition. Therefore, PRP injec‐ tion may be an effective alternative or adjuvant treatment option

ORCID Punyaphat Sirithanabadeekul

for melasma. However, larger and longer randomized, double‐

org/0000-0002-5107-8153

blinded, and placebo‐controlled trials with greater statistical power

Atchima Suwanchinda

https://orcid.

https://orcid.org/0000-0002-3432-7090


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SIRITHANABADEEKUL et al.

REFERENCES 1. Sarkar R, Arora P, Garg VK, Sonthalia S, Gokhale N. Melasma update. Indian Dermatol Online J. 2014;5(4):426‐435. 2. Sehgal VN, Verma P, Srivastava G, Aggarwa AK, Verma S. Melasma: treatment strategy. J Cosmet Laser Ther. 2011;13(6):265‐279. 3. Rivas S, Pandya A. Treatment of melasma with topical agents, peels and lasers: an evidence‐based review. Am J Clin Dermatol. 2013;14(5):359‐376. 4. Çayırlı M, Çalışkan E, Açıkgöz G, Erbil AH, Ertürk G. Regression of melasma with platelet‐rich plasma treatment. Ann Dermatol. 2014;26(3):401‐402. 5. Yew CH, Ramasamy TS, Amini F. Response to intradermal autologous platelet rich plasma injection in refractory dermal melasma: report of two cases. JUMMEC. 2015;18(2):1‐6.

6. Law Jia X, Chowdhury SR, Saim AB, Hj Idrus RB. Concentration‐de‐ pendent effect of platelet‐rich plasma on keratinocyte and fibroblast wound healing. Cytotherapy. 2015;17(3):293‐300. 7. Shin MK, Lee JH, Lee SJ, Kim NI. Platelet‐rich plasma combined with fractional laser therapy for skin rejuvenation. Dermatol Surg. 2012;38(4):623‐630.

How to cite this article: Sirithanabadeekul P, Dannarongchai A, Suwanchinda A. Platelet‐rich plasma treatment for melasma: A pilot study. J Cosmet Dermatol. 2020;19:1321– 1327. https​://doi.org/10.1111/jocd.13157​

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