Received: 22 January 2019 Revised: 3 May 2019 Accepted: 26 August 2019 DOI: 10.1111/jocd.13157
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: email@example.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.
wileyonlinelibrary.com/journal/jocd © 2019 Wiley Periodicals, Inc. | 1321
SIRITHANABADEEKUL et al.
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
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
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
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
SIRITHANABADEEKUL et al.
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.
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
SIRITHANABADEEKUL et al.
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
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
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‐
blinded, and placebo‐controlled trials with greater statistical power
SIRITHANABADEEKUL et al.
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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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