| |

Received: 29 October 2019    Revised: 6 February 2020    Accepted: 24 February 2020

DOI: 10.1111/jocd.13369

ORIGINAL CONTRIBUTION

Study of efficacy of microneedling and mesoneedling in the

treatment of epidermal melasma: A pilot trial

Susan Farshi MD, MPH1  | Parvin Mansouri MD2

1
Tehran University of Medical Sciences,
Tehran, Iran Abstract
2
Skin and Stem Cell Research Center, Tehran Background: Melasma is a difficult to treat pigmentation disorder. However, some
University of Medical Sciences, Tehran, Iran
successes have been attained by microneedling. The aim of the present study was
Correspondence to evaluate the efficacy of microneedling using meso-depigmentation solution (me-
Susan Farshi, Tehran University of Medical
soneedling) in comparison with standard microneedling, over a 4-month treatment
Sciences, Tehran, Iran.
Email: farshi_s@yahoo.com period.
Parvin Mansouri, Skin and Stem Cell Methods: As a part of this pilot study, 20 patients received microneedling on one
Research Center, Tehran University of side and mesoneedling on another side of their face. Treatment was repeated on a
Medical Sciences, Tehran, Iran.
Email: mansouripr@yahoo.com monthly basis for 4 months. Treatment efficacy was defined through Dermacatch®
colorimetry, modified Melasma Area and Severity (mMASI) score determination,
Investigator's Global Assessment (IGA), and patient questionnaires, whereby all as-
sessments were conducted at the baseline, as well after 2 and 4 months of treatment.
Results: Before treatments, mean difference between pigmented and normal skin
calculated by Dermacatch® was 43.7 ± 20.12 and 44.6 ± 20.72 in microneedling sides
and mesoneedling sides, respectively. After two and four sessions, these values de-
clined to 34.5  ±  16.26 and 28.05  ±  13.79 on the side subjected to microneedling,
while 29.75  ±  15.07 and 20.45  ±  10.58 were measured on the mesoneedling side.
Statistically significant differences have been observed between microneedling and
mesoneedling treatments at both time points (P = .0001, P  =  .0001). The mMASI
scores obtained upon treatment completion were significantly lower on both the mi-
croneedling and the mesoneedling side. The IGA and patients' self-assessment scores
further confirmed that both treatments were effective in treating melasma, without
producing any notable side-effects or complications.
Conclusion: In sum, both microneedling and mesoneedling are effective in decreas-
ing melanin content in the epidermal melasma lesions.

KEYWORDS

Dermacatch®, melasma, mesoneedling, microneedling

1 |  I NTRO D U C TI O N
Melasma is an acquired symmetrical brownish pigmentation, ap-
pearing mainly on the face, which is more prevalent in females and in
Author Susan Farshi, and Parvin Mansouri, are both the first author.
individuals with darker skin types, and is predominantly attributed to
ultraviolet (UV) exposure and hormonal influences.1
Skin microneedling, which is known as percutaneous collagen in-
duction therapy, is a minimally invasive procedure as a part of which a
barrel covered with sterilized short fine needles (typically 0.5-1.5 mm
in length) is rolled across the skin to puncture the outer layer and

J Cosmet Dermatol. 2020;00:1–6. wileyonlinelibrary.com/journal/jocd© 2020 Wiley Periodicals, Inc.     1 |

 |
2       FARSHI and MANSOURI
penetrate into the stratum corneum and papillary dermis. This pro-
duces small holes known as micro-conduits, with minimal damage to
the epidermis, allowing migration of epithelial and endothelial cells.
The procedure has been shown to promote growth factor release
and thus stimulate fibroblast proliferation, while also enhancing col-
lagen and elastin production in the papillary layer of the epidermis,
inducing beneficial wound healing with a few side-effects. 2-6
Addressed technique is also utilized to augment transdermal
drug delivery (TDD) through several methods, including creation of
pores and channels with micron-sized dimensions in the stratum cor-
neum, followed by topical drug application and direct drug injection
through hollow microneedles.4,5,7-10
Localized intradermal or subcutaneous microinjections of di-
luted injectable drugs, called “mesotherapy,” were first introduced
by Pistor.11
In the context of the present study, the term “mesoneedling” re-
fers to the combined treatment involving both microneedling and
infusion of injectable meso-depigmentation solution.
Microneedling applied with 1.5 mm needle length, without add-
ing any active medication, has been shown to lighten skin stains in
patients with recalcitrant melasma.12
However, the exact mechanism behind this beneficial effect is
presently insufficiently understood.12 Some authors posit that im-
proved skin hydration and induction of collagen and elastin synthesis
diminishes the visibility of dermal pigment.13
In the present study, microneedling and mesoneedling efficacy
in the treatment of epidermal melasma was assessed as a part of an
open pilot trial.
2 |  M E TH O DS
The inclusion criteria for this open pilot trial were age in the
18-50 years range, and Fitzpatrick skin type III, IV, or V. Both males
and females were eligible and were required to provide a written
informed consent. The study was approved by the Ethics Committee
of Tehran University of Medical Sciences within IRB protocol num-
ber 91031519422.
The study commenced in January 2017 (the first visit of
the first patient) and ended in November 2018 (the last visit of
the last patient), and the participants were recruited from the
Dermatology Clinic of the Skin and Stem Cell Research Center.
The diagnosis of epidermal melasma which confirmed by Wood's
lamp and minimum disease duration of 6 months was considered
as inclusion criteria. Pregnant/lactating females and patients on
hormone replacement therapy or oral contraceptives were ex-
cluded from the study, as were individuals with any known drug
allergies, Koebner phenomenon, infection at the treatment sites,
associated medical illnesses or malignancy, and history of any
other depigmenting treatment in at least 2 months preceding the
study. In patients with history of herpes simplex, prophylaxis was
provided by prescribing acyclovir 400  mg every 8  hours 1  day
prior to procedure for 5 days.
The four monthly treatments given to all patients comprised of
microneedling on one side and mesoneedling on another side of their
face. Amiea Med (MT.DERM GmbH) was utilized for microneedling,
while mesoneedling was performed by mesoestetic depigmentation
solution (C proof 210, Mesoestetic Pharma Group). Mesoestetic C
proof 210 contains a combination of active antioxidant ingredients
including tranexamic acid, N-Acetyl Glucosamine, vitamin C, and
idebenone.
Both procedures were performed under topical anesthesia,
which contained 2.5% lidocaine and 2.5% Prilocaine (Xyla-P cream)
applied 45 minutes before the intervention after gentle cleaning of
the face.
The needle was of 1.5 mm length and 0.25 mm diameter.
According to the pressure applied, the needles penetrate 0.1-1.3 mm
into the skin.
The treatment involved rolling the barrel back and forth approxi-
mately four times in all four directions (right-left and horizontal-ver-
tical), resulting in a diffuse erythema and mild, discrete punctuated
bleeding. The procedure applied on melasma areas and a little
around the lesion.
For the duration of the study, participants were instructed to
apply a standard sunscreen cream with sun protection factor ≥50
(Skincode) to their entire face and repeat the application at 3-hour
intervals during the day.
Clinical evaluations were performed by the same investigators
at baseline, at month 2, and at the end of the study (month 4). Skin
surface analyzer (Visioface 1000D; CK Electronic GmbH) was ap-
plied for taking standard facial images at baseline and at the 2- and
4-month visits.
A Dermacatch® (Colorix) was utilized for calculating melanin
content and erythema level. For statistical analyses, the differences
in pigment (melanin) content between lesions and normal skin was
used.
MASI score was first used by Kimbrough-Green et al14 to quan-
tify the pigmentation area, darkness and homogeneity in melasma
patients with the following equation:
( ) ( ) ( )
MASI score = 0.3AF D + H + 0.3ARM D + H + 0.3ALM D + H
( )
+ 0.1AC D + H
D is darkness, H is homogeneity, A is area, F is forehead, MR is right
malar, ML is left malar, and C is chin. The value 0.3, 0.3, 0.3, and 0.1 are
respective percentage of the total facial area.
In this study, modified MASI score (mMASI) was calculated for
both sides of the face, by the same equation without considering
the percentage of involved area because each patient serving as his/
her control.
Evaluation of mMASI was performed at baseline and at month
2 and 4.
The Investigator's Global Assessment (IGA) was defined into
seven categories, according to Pandya et al15: (0) Clear, except for
possible residual discoloration; (1) Almost clear, very significant
clearance (approx. 90%), only minor evidence of hyperpigmentation
FARSHI and MANSOURI
remains; (2) Marked improvement, significant improvement (c. 75%),
some disease evidence of hyperpigmentation remains; (3) Moderate
improvement, intermediate between slight and marked improve-
ment (c. 50%), improvement in appearance of hyperpigmentation;
(4) Slight improvement, some improvement (c. 25%), significant ev-
idence of hyperpigmentation remains; (5) No improvement, hyper-
pigmented condition unchanged; and (6) Worse, condition worse
than at week 0.
Patient feedback was obtained using a questionnaire com-
prising of items related to the effects of the microneedling and
mesoneedling. Their responses were defined similarly to the IGA
scores.
Erythema, itching, burning sensation, dryness, irritation, and
dyspigmentation (hypo and hyperpigmentation) were monitored as
adverse events during the study and were rated on a scale from 0
(none) to 3 (severe).
Statistical analyses were performed using IBM Statistics SPSS
(Statistical Package for Social Sciences) software (version 24,
Chicago, IL), and P ≤ .05 was considered to indicate statistical signif-
icance. Paired t test was used for the comparison of mMASI scores
and the Dermacatch® measurements in each group, as the data
were found to be normally distributed. Testing for normality of the
distribution was determined through the Kolmogorov-Smirnov test
and Wilcoxon signed-rank test compared the grades in objective as-
sessment. Repeated measure analysis was conducted for evaluating
the effect of both microneedling and mesoneedling, from baseline to
the end of the study.
3 | R E S U LT S
The study sample comprised of 20 patients (1 male and 19 females)
with facial epidermal melasma who met the study inclusion crite-
ria. All recruited patients completed the four courses of treatment.
Table 1 shows the baseline characteristics of the participants.
Table 2 shows the IGA scores and treatment efficacy in both mi-
croneedling and mesoneedling side based on patients' self-assess-
ment. The difference between the microneedling and mesoneedling
sides was statistically significant (Wilcoxon signed-rank test, P = .04,
P = .04).
The mMASI scores pertaining to the microneedling and me-
soneedling sides, at baseline, and after two and four microneedling
TA B L E 1   Baseline patient characteristics
Age (y), mean ± SD 39.4 ± 7.2
Sex, n (%)
Male 1 (5)
Female 19 (95)
Skin type
III 14 (70)
IV 6 (30)
Duration of melasma (y), mean ± SD 5.6 ± 4.5
|
      3
and mesoneedling sessions are shown in Table 3. Normal distribution
of the mMASI scores was confirmed by Kolmogorov-Smirnov test
(P  =  .2). Paired t test confirmed statistically significant differences
between the microneedling and mesoneedling sides (P = .001). The
mean difference in melanin content between the lesions and the sur-
rounding normal areas on the microneedling and mesoneedling sides
were calculated at baseline, and after two and four sessions using
Dermacatch®, and statistically significant differences were found
between the microneedling and mesoneedling sides after two and
four sessions (Table 3). Repeated measure analysis showed that both
microneedling alone and microneedling using depigmentation solu-
tion (mesoneedling) yielded a significant reduction in the melanin
content of melasma lesions, as measured by Dermacatch® instru-
ment (P  =  .0001). Following both treatment styles, mMASI scores
were also significantly decreased (Repeated Measure, P = .0001).
Figure 1 represents a valuable clinical response in a patient, who
received microneedling on the right side of her face, while melasma
was treated through mesoneedling on her left side.
Regarding the side-effects, six patients reported mild erythema
on both sides of their face. Moreover, three individuals complained
of mild skin dryness, four noted mild itching, and five experienced
mild burning sensation for a few hours after the procedure on both
sides. There was no significant difference between the micronee-
dling and mesoneedling sides regarding the adverse effects, which
were rather mild, transient, and tolerable in all affected patients.
4 | D I S CU S S I O N
Most existing therapies for melasma have been unsatisfactory and,
due to the chronic and relapsing nature of melasma, research aimed
at developing efficacious and optimal therapeutic options is urgently
needed.16-18 Microneedling is a minimally invasive procedure involv-
ing repetitive puncturing of the skin with sterilized microneedles to
treat numerous dermatologic conditions. The created microwounds
stimulate the release of growth factors and induce collagen produc-
tion, while limiting adverse events, including risk of infection and
scarring. The procedure also decreases downtime and hastens re-
covery because the epidermis remains relatively intact.3-5
Microneedling may offer a more advantageous safety profile,
particularly in the skin-of-color population (Fitzpatrick skin types
IV-VI).5
Overall, the efficacy and safety of microneedling, as well as ease
of use, make this technique a favorable therapeutic alternative to
consider.4
In an open trial, Lima et al2 reported a significant reduction of
MASI score from 37.1 to 11.0 (70% mean decrease in MASI) after
two sessions of microneedling.
In a randomized clinical trial conducted by Budamakuntla
et al,11 microneedling with tranexamic acid was found effective
in treating melasma. In another randomized trial, Lee et al16 re-
ported that intradermal localized microinjection of tranexamic
acid was also effective in the treatment of melasma. Similarly,
 |
4       FARSHI and MANSOURI

TA B L E 2   Hypopigmentation grading
Investigator's global assessment Patient's self-assessment
in microneedling and mesoneedling sides
Microneedling Mesoneedling* Microneedling Mesoneedling* assessed by investigators and by the
Hypopigmentation patients
grading No. % No. % No. % No. %

0 0 0 0 0 0 0 0 0
1 1 5 2 10 3 15 3 15
2 7 35 8 40 3 15 6 30
3 9 45 8 40 11 55 9 45
4 3 15 2 10 3 15 2 10
5 0 0 0 0 0 0 0 0
6 0 0 0 0 0 0 0 0
Total 20 100 20 100 20 100 20 100

Note: (0) clear, except for possible residual discoloration, (1) almost clear, very significant clearance
(c. 90%); only minor evidence of hyperpigmentation remains, (2) Marked improvement, significant
improvement (c. 75%); some disease evidence of hyperpigmentation remains, (3) Moderate
improvement, intermediate between slight and marked improvement; (c. 50%) improvement in
appearance of hyperpigmentation, (4) slight improvement, some improvement (c. 25%), significant
evidence of hyperpigmentation remains (5) no improvement, hyperpigmented condition unchanged
(6) Worse, condition worse than at week 0.
*Statistically significant difference was found between microneedling and mesoneedling sides by
investigator's global assessment and also by patient's self-assessment (Wilcoxon signed-rank test,
P = .04, P = .04).

TA B L E 3   MASI scores and mean differences of pigment content of the lesions and normal skin using Dermacatch before, after 2 mo and
at the end of the study at month 4 in Microneedling alone and Mesoneedling sides of the patients' face

MASI scores Dermacatch

  N Before T After 2 M After 4 M Before T After 2 M After 4 M

Microneedling 20 11.37 ± 3.23 8.92 ± 3.28 8.05 ± 3.17 43.7 ± 20.12 34.5 ± 16.26 28.05 ± 13.79

Mesoneedling 20 11.43 ± 3.23 8.44 ± 3.26 6.86 ± 3.17 44.6 ± 20.72 29.75 ± 15.07 20.45 ± 10.58
P value   .38 .001 .0001 .33 .0001 .0001
CI 95%   −0.2 to 0.81 0.26 to 0.68 0.86 to 1.48 −2.81 to 1.01 3.26 to 6.23 4.71 to 10.48

Abbreviations: M, Month; N, Number of patients; T, Treatment.

microneedling along with an infusion of a serum containing light-
ening compounds has been successfully used in a patient with
13
periorbital melanosis.
In a pilot study involving 20 patients diagnosed with melasma,
microneedling combined with topical depigmenting agents was
shown to be more effective than monotherapy with topical de-
pigmenting agents. In this trial, in hemi-faces which micronee-
dling plus depigmenting serum applied, the mean MASI score
decreased significantly more than the other sides which depig-
menting serum used alone. In addition to that, mean MASI score
of 19.1 reached to 9.2 two months after therapy in microneedling
sides in contrast the other sides which mean MASI score of 20.4
decreased to 13.3.7
This finding is similar to our study based on MASI score but in
present study we applied microneedling in both sides and meso-de-
pigmentation solution only in one side.
In our study, mMASI scores of 11.37 in microneedling sides reached
to 8.05 after 4 months and from 11.43 to 6.86 in mesoneedling sides.
It seems that the lower MASI reduction in our study is due to the fact
that we calculated modified MASI score on each side.
The adverse events in our study were mild and transient and also
very similar to adverse effects of most other studies which applying
microneedling for the treatment of melasma, other melanosis, and
acne scars. Although in some studies post inflammatory hyperpig-
mentation was reported but we did not face such complication.5
The present investigation demonstrated that 2-4 sessions as
a part of which melasma was treated by microneedling with me-
so-depigmentation solution (mesoneedling) were significantly
more efficacious than microneedling alone (based on mMASI
scores and Darmacatch® colorimetry). However, microneedling
alone was also effective in reducing melanin content of the me-
lasma lesions after two and four sessions. The investigators' global
assessment and patients' self-assessment confirmed the statisti-
cally significant difference between microneedling and mesonee-
dling effectiveness, although both treatments yielded significant
improvements.
FARSHI and MANSOURI
F I G U R E 1   A 39 y old woman with 3 y
duration of melasma on right and left sides
of her face before treatment (A, B), and
4 mo after 4 sessions Microneedling alone
(C) and after 4 sessions Mesoneedling (D)
The main limitations of the present study are its nonrandomized
nature and absence of blinding. Thus, continued research involving
larger randomized samples is needed to provide more reliable evi-
dence on the effectiveness of microneedling for melasma treatment
in different skin types.
C O N FL I C T O F I N T E R E S T
None.
ORCID
Susan Farshi  https://orcid.org/0000-0003-0575-4381
REFERENCES
1. Ogbechie-Godec OA, Elbuluk N. Melasma: an up-to-date compre-
hensive review. Dermatol Ther. 2017;7:305-318.
2. Lima EVA, Lima M, Paixao MP, Miot HA. Assessment of the effects
of skin microneedling as adjuvant therapy for facial melasma: a pilot
study. BMC Dermatol. 2017;17:14.
3. Iriarte C, Awosika O, Rengifo-Pardo M, Ehrlich A. Review of ap-
plications of microneedling in dermatology. Clin Cosmet Investig
Dermatol. 2017;10:289-298.
4. Hou A, Cohen B, Haimovic A, Elbuluk N. Microneedling: a compre-
hensive review. Dermatol Surg. 2017;43:321-339.
5. Cohen BE, Elbuluk N. Microneedling in skin of color: a review of
uses and efficacy. J Am Acad Dermatol. 2016;74:348-355.
6. Arenas-Soto CM. Microneedles: a therapeutic alternative in me-
lasma. J Dermat Cosmetol. 2018;2:207-210.
|
      5
7. Fabbrocini G, De Vita V, Fardella N, et al. Skin needling to enhance
depigmenting serum penetration in the treatment of melasma. Plast
Surg Int. 2011;2011:158241.
8. Prausnitz MR. Microneedles for transdermal drug delivery. Adv
Drug Deliv Rev. 2004;56:581-587.
9. Park JH, Choi SO, Seo S, Choy YB, Prausnitz MR. A micronee-
dle roller for transdermal drug delivery. Eur J Pharm Biopharm.
2010;76:282-289.
10. Li K, Yoo KH, Byun HJ, et al. The microneedle roller is an effec-
tive device for enhancing transdermal drug delivery. Int J Dermatol.
2012;51:1137-1139.
11. 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.
12. Lima EA. Microneedling in facial recalcitrant melasma: report of a
series of 22 cases. An Bras Dermatol. 2015;90:919-921.
13. Sahni K, Kassir M. Dermafrac: an innovative new treatment for
periorbital melanosis in a dark-skinned male patient. J Cutan Aesthet
Surg. 2013;6:158-160.
14. Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al. Topical retinoic
acid (tretinoin) for melasma in black patients. A vehicle-controlled
clinical trial. Arch Dermatol. 1994;130:727-733.
15. Pandya A, Berneburg M, Ortonne JP, Picardo M. Guidelines for clin-
ical trials in melasma. Pigmentation Disorders Academy. Br J Dermatol.
2006;156(Suppl 1):21-28.
16. Lee JH, Park JG, Lim SH, et al. Localized intradermal micro-
injection of tranexamic acid for treatment of melasma in
Asian patients: a preliminary clinical trial. Dermatol Surg.
2006;32:626-631.
 |
6       FARSHI and MANSOURI

17. Rivas S, Pandya AG. Treatment of melasma with topical agents,

peels and lasers: an evidence-based review. Am J Clin Dermatol. How to cite this article: Farshi S, Mansouri P. Study of
2013;14:359-376. efficacy of microneedling and mesoneedling in the treatment
18. Jutley GS, Rajaratnam R, Halpern J, Salim A, Emmett C. Systematic
of epidermal melasma: A pilot trial. J Cosmet Dermatol.
review of randomized controlled trials on interventions for
melasma: an abridged Cochrane review. J Am Acad Dermatol. 2020;00:1–6. https://doi.org/10.1111/jocd.13369
2014;70:369-373.