Received: 7 March 2018 | Revised: 1 December 2018 | Accepted: 3 January 2019

DOI: 10.1111/jocd.12878

ORIGINAL CONTRIBUTION

Efficacy of microneedling with topical vitamin C in the

treatment of melasma

Esraa Salah Ali Ismail MSc1 | Aikaterini Patsatsi MD, PhD2 | Wafaa Mohammed Abd
el‐Maged MD1 | Essam El‐Din Abd el‐Aziz Nada MD1

1
Faculty of Medicine, Department of
Dermatology, Sohag University, Sohag Summary
University Hospital, Sohag, Egypt Background: Despite the wide therapeutic options available for the treatment of me‐
2
Faculty of Medicine, 2nd Department
lasma, including many active topical medications, technologies with lights and peel‐
of Dermatology, Aristotle University,
Papageorgiou General Hospital, ings, clinical control of this disorder is extremely challenging.
Thessaloniki, Greece
Objectives: To evaluate the effect of microneedling with topical vitamin C in the
Correspondence treatment of melasma.
Esraa Salah Ali Ismail, Faculty of Medicine,
Methods: Thirty female patients with melasma received six sessions of micronee‐
Department of Dermatology, Sohag
University, Sohag University Hospital, dling with addition of topical vitamin C every two weeks. At each session, photos
Sohag, Egypt.
were taken and Melasma Area and Severity Index (MASI) score was calculated to
Email: esraasalah123@yahoo.com
assess the clinical improvement.
Funding information
Results: Mean age of the eligible patients was 33.2 ± 5.77 years. About 50% of cases
Sohag university hospital
were of Fitzpatrick skin type III. All patients showed improvement at the end of the
sessions. Mean MASI score in the first session was 8.61 ± 4.45 and there was a grad‐
ual decline in its value till it reached a mean of 5.75 ± 4.16 in the last session
(P < 0.0001).
Conclusion: Microneedling with topical vitamin C is an effective and safe treatment
option for epidermal melasma especially in Fitzpatrick skin phototypes I‐III.

KEYWORDS
dermaroller, melasma, microneedling, vitamin C

1 | I NTRO D U C TI O N however, men are sometimes affected representing approximately

Melasma (from the Greek word “melas” that means black) is a com‐
mon acquired and circumscribed hypermelanosis of sun‐exposed
skin. It presents as symmetric and hyperpigmented macules having
irregular, serrated, and geographic borders. The most common af‐
fected areas are the cheeks, upper lips, chin, and forehead, but other
1
sun‐exposed areas may be involved. The prevalence of melasma
varies between 1.5% and 33.3% among different ethnicities. 2 For
example, among paddy field workers in India, melasma prevalence
was reported to be 41%3 while in Assiut governorate, it was 3.23%.4
Although melasma affects any race, it is more common in darker and
light brown skin types, especially in people of East Asian, Southeast
Asian, and Hispanic origin.5 Women are predominantly affected;
10% of the cases.5
Several factors have been implicated in the etiology of melasma
such as genetic predisposition, hormonal influences, pregnancy, oral
contraceptive pills (OCPs), UV radiation, thyroid disease, and drugs
such as phenytoin.6
Wood's light examination is used to categorize melasma accord‐
ing to the depth of melanin pigment into epidermal, dermal, mixed,
or indeterminate.7 Although Wood's light examination may not be
accurate in determining the depth of melanin pigment,8 this classifi‐
cation helps in predicting the therapeutic outcome.
Many therapeutic options are available for melasma such as
chemical peelings, light‐based therapies (laser or intense pulse light),
and topical agents, which are more effective in the epidermal type

J Cosmet Dermatol. 2019;1–6. wileyonlinelibrary.com/journal/jocd

© 2019 Wiley Periodicals, Inc. | 1
2 |
of melasma.7 Topical agents include hydroquinone, azelaic acid,
kojic acid, retinoids, steroids, vitamin C (ascorbic acid), alpha‐to‐
copherylferulate, flavonoids, niacinamide, liquorice derivatives,
and n‐acetyl‐4scysteaminylphenol.9 Lasers, especially nonablative
fractional laser (NAFL) has been used for treatment of melasma.10-13
Positive effects of laser treatments may be equivalent to topical in‐
terventions. A cost‐benefit assessment is usually applied, despite
their effectiveness.11 Furthermore, nonablative lasers have common
side effects like postinflammatory hyperpigmentation,10 edema, and
erythema.11 Thus, there is no universally effective therapy for this
disease.14
One of the new topical agents is vitamin C which interacts with
copper ions at the tyrosinase‐active site that leads to inhibition of
9
tyrosinase enzyme. This action decreases melanin formation, par‐
ticularly the perifollicular one.15 Vitamin C is an unstable compound,
so it needs to be combined with other depigmenting agents such as
soy and liquorice for a better depigmenting effect.16
A recent minimally invasive and painless approach of drug de‐
livery to the skin is microneedling technology.17 The micro‐wounds
created stimulate the release of growth factors and induce colla‐
gen production.18 The epidermis remains relatively intact there‐
fore, helping to limit adverse events.18 Microneedling may offer
a more advantageous safety profile, particularly in Fitzpatrick
skin types IV‐VI, compared with more conventional resurfacing
modalities.19
Literature search revealed few studies that reported mi‐
croneedling in the treatment of melasma, one study of which
using microneedling with tranexamic acid (TA)20 and the other,
microneedling with depigmentation formula (0.05% tretinoin +
21
4% hydroquinone + 1% fluocinoloneacetonide). Another study
compared the therapeutic efficacy and safety of tranexamic acid
microinjections versus tranexamic acid with microneedling in me‐
lasma. 20 To our knowledge, this is the first study investigating
the effect of microneedling with topical vitamin C in treatment
of melasma.
1.1 | Aim
This study aimed to evaluate the effect of microneedling with topical
vitamin C in treatment of melasma.
2 | M ATE R I A L S A N D M E TH O DS
2.1 | Study type
A prospective clinical trial was conducted from January 2015 to
January 2016.
2.2 | Ethics
All patients provided informed consent for participating in this study,
and the research project was approved by Research and Ethical com‐
mittee of our hospital.
ISMAIL et al.
2.3 | Patient population
2.3.1 | Inclusion criteria
Women, aged 20‐40 years with any disease duration regardless of
marital status. Diagnosis of melasma was based on clinical evaluation
by two consultants of dermatology.
2.3.2 | Exclusion criteria
Patients with dark brown pigmentation (dermal melasma), those
with history of any other depigmenting treatment in the past
three months, pregnant/lactating females, patients on hormone
replacement therapy or oral contraceptives, patients with a his‐
tory of bleeding disorders, patients with any known allergy to vi‐
tamin C, patients with history of scarring or keloid formation and
patients with history of medical illness as renal, hepatic or endo‐
crinal disorders.
2.4 | Study design
After obtaining detailed personal, medical, and family history,
history of present illness was also taken. Melasma severity was
scored before and after each session using the Melasma Area and
Severity Index (MASI) score. The MASI score is an index used to
quantify the severity of melasma and changes observed during
therapy. According to the MASI score, the face is divided into four
areas: the forehead, the right malar, the left malar, and the chin,
which correspond to 30, 30, 30, and 10% of the total face area,
respectively. The melasma in each of these areas was graded on
three variables: percentage of total area involved, on a scale of
0 (no involvement) to 6 (90%‐100% involvement); darkness, on a
scale of 0 (absent) to 4 (severe); and homogeneity, on a scale of
0 (absent) to 4 (maximum). The MASI score was then calculated
using the following equation:
( ) ( )
MASI = 0.3 DF + HF AF + 0.3 DMR + HMR AMR
( ) ( )
+0.3 DML + HML AML + 0.1 DC + Hc AC
where D is darkness, H is homogeneity, A is area, F is forehead, MR is
right malar, ML is left malar, C is chin, and the values 0.3, 0.3, 0.3, and
0.1 are the respective percentages of total facial area. 22 Follow‐up
was done for all patients after three months from the last session
and MASI score was calculated.
2.4.1 | The microneedling procedure
After gentle cleansing, topical anesthetic lidocaine cream was ap‐
plied over the area to be treated for about 45 to 60 min. A der‐
maroller was used (from Medical Cure Company). It was studded
with 540 fine needles of titanium. The needle length was 1.5 mm.
The skin was stretched and microneedling was carried out in verti‐
cal, horizontal, and both diagonal directions for about ten passes
in each direction or till pin point bleeding occur. 21 Pure L‐Ascorbic
ISMAIL et al. | 3

acid 20% (Fusion Mesotherapy Company, Cairo, Egypt) was applied TA B L E 1 Demographic data of the studied population
over all affected areas. Ice packs were applied over the treated
Characteristics Summary statistics
areas if bleeding persisted. Patients were instructed to follow strict
Age (Mean ± SD) 33.2 ± 5.77
photo‐protective measures such as avoidance of sun exposure as
possible, especially from 10 am to 4 pm , and to use sunscreen with Marital status (%)

sun protection factor (SPF) 50+, even at home. They were advised Single 4 (13.33)

also to repeat the application every two hours. Microneedling pro‐ Married 24 (80.00)
cedures were performed every two weeks for three months. Divorced 2 (6.67)
Pregnancy (%)
No 4 (13.33)
2.5 | Outcome measures
1‐4 20 (66.67)
The main outcome measures were changes in clinical appearance.
≥5 6 (20.00)
Photographs of the right and left profiles and full face were taken for
Occupation (%)
each patient to assess the response to treatment. MASI score was
Outdoor workers 20 (66.67)
calculated at each visit.
Indoor workers 10 (33.33)
Predisposing factors (%)
2.6 | Statistical analysis Sun exposure 20 (66.67)

Group sample sizes of 30 females with epidermal melasma achieve Pregnancy 12 (40)

80% power to detect a difference of 2.86 in mean MASI score be‐ Pregnancy + Hormonal Contraception 14 (46.67)
tween the null hypothesis that both group means are 8.61 and the Family history (%)
alternative hypothesis that the mean of group 2 is 5.75 with known Yes 17 (56.67)
group standard deviations of 4.45 and 4.16 and with a significance No 13 (43.33)
level (α) of 0.05 using a two‐sided Mann‐Whitney test assuming that Fitzpatrick skin type (%)
the actual distribution is double exponential. Statistical analysis was Type 2 2 (6.67)
performed using STATA v12.1(Stata Statistical Software, College
Type 3 15 (50.00)
Station, TX, USA), a P‐value of <0.05 was considered significant.
Type 4 9 (30.00)
Type 5 4 (13.33)
3 | R E S U LT S
TA B L E 2 Characteristics and duration of melasma
3.1 | MASI score
Characteristics Summary statistics
To evaluate the effect of microneedling with topical vitamin C in
Duration in years (Mean ± SD) 5.83 ± 4.82
treatment of melasma, MASI score was calculated for 30 female pa‐
Duration (%)
tients with epidermal melasma every two weeks.
1 year 4 (13.33)
Mean age of the eligible patients was 33.2 ± 5.77 years, 80% of
cases were married (n = 24), while 66.7% of the cases were outdoor 1‐4 years 12 (40.00)

workers (n = 20) in whom sun exposure was a main risk factor. Fifty per‐ ≥5 years 14 (46.67)

cent of cases were of Fitzpatrick skin type III (n = 15) (Table 1). Melasma Affected area (%)
was diagnosed since more than five years in 46.67% (n = 14) of the Malar 4 (13.33)
cases (Table 2). Mean MASI score in the first session was 8.61 ± 4.45, Malar & Centro facial 26 (85.67)
and there was a gradual decline in its value till it reached a mean of
5.75 ± 4.16 in the last session (P < 0.0001; Table 3; Figure 1). The
percentage of improvement in the studied cases was 36.87 ± 19.85% TA B L E 3 MASI of the studied population

(P < 0.0001; Figures 2 and 3). Nonsignificant improvement was de‐ Characteristics Summary statistics P value
tected in indoor than outdoors workers (P = 0.19). In patients with
MASI 1 (Mean ± SD) 8.61 ± 4.45 —
melasma, the duration of disease had no significant effect on the thera‐
MASI 2 (Mean ± SD) 8.46 ± 4.47 0.89
peutic outcome. Nonsignificant improvement was observed in patients
MASI 3 (Mean ± SD) 7.53 ± 4.30 <0.0001
of malar melasma (P = 0.50). History of use of hormonal contraceptives
MASI 4 (Mean ± SD) 6.88 ± 4.25 <0.0001
had no significant effect in the improvement of melasma (P = 0.53).
MASI 5 (Mean ± SD) 6.02 ± 4.11 <0.0001
Improvement was more pronounced in lighter Fitzpatrick skin types
than in darker ones. Pairwise comparison of Fitzpatrick skin type II MASI 6 (Mean ± SD) 5.75 ± 4.16 <0.0001

and V was statistically significant (P = 0.04). Patients were evaluated P value was calculated compared to MASI1 using Wilcoxon ranked sum test.
4 |
FIGURE 1 Melasma Area and Severity Index of studied
population
for recurrence after three months of the last session. Recurrence was
observed in five cases (16.67%), While, twenty‐five cases showed no
recurrence (83.33%). The improvement in MASI score was persistent
in twenty‐five patients for three months after stopping the treatment,
while in five cases it returned to the pretreatment session. Recurrence
occurred in patients who presented with melasma since more than five
years (Table 4), especially those with skin phototypes (III‐V; Table 5).
Other incidental findings were noticed after microneedling with
topical vitamin C in three patients, such as skin texture improvement
and skin brightness. Also, improvement in acne scars was noted in
one patient indicating an effect of this procedure in dermal collagen
synthesis. No significant side effects were observed in the current
study except for tolerable pain during the microneedling procedure
and mild erythema that resolved shortly after the procedure.
4 | D I S CU S S I O N
Despite the wide therapeutic options available for treatment of me‐
lasma, including many active topical medications, technologies with
ISMAIL et al.
lights and peelings, clinical control of this melanoderma is extremely
challenging. The proposed application of active medication with de‐
pigmentation action has been used, but little is mentioned about the
action of microneedling in melasma.16
Up to our knowledge, this is the first study evaluating the ef‐
ficacy of microneedling with topical vitamin C in the treatment of
melasma. Vitamin C is initially unstable compound that needs to be
combined with other depigmenting agents such as soy and liquorice
in order to have a better depigmenting effect. 23 There is a marked
interest to find methods for efficient transepidermal delivery of vita‐
min C,9 because of its hydrophilic nature that eliminates this process.
The dermal reservoir of vitamin C which is a protective antioxidant
could be increased and photo protection might be enhanced,9 if vi‐
tamin C could be delivered in high concentration through the stra‐
tum corneum barrier. Extensive research was done to investigate
microspheres, nanoparticles, and multi‐layered micro‐emulsions for
graded topical delivery. Both electroporation and iontophoresis have
been used to enhance penetration of vitamin C into the dermis. 24-27
Our study included thirty adult females with epidermal melasma.
They received six sessions of microneedling with topical vitamin C
20% with two weeks interval between sessions. The majority of
cases were of Fitzpatrick skin type III and IV and this was consistent
with several studies. 28 More than half of our cases had positive fam‐
ily history and were outdoor workers. This was due to sun exposure
and correlated with the epidemiologic studies which suggest that
sun exposure alone or sun exposure during pregnancy may trigger or
aggravate melasma. 28 Improvement was observed in all cases.
Our results were comparable to a previous study that com‐
pared tranexamic acid microinjections versus tranexamic acid with
microneedling in patients with melasma. 20 Moreover, the results
of the current study were better than previous study evaluating
the in vitro and in vivo effect of magnesium lascorbyl‐2‐phosphate
(VC‐PMG) on melanogenesis. 29 Furthermore, the results of the
current study were comparable to those of a previous study that
used microneedling to enhance the penetration of a depigment‐
ing serum in the treatment of melasma. 21 In the current study,
F I G U R E 2 Clinical improvement in the
comparative photographs
ISMAIL et al. | 5

F I G U R E 3 Clinical improvement in the

comparative photographs

TA B L E 4 Comparison between patients without and with negative therapeutic outcome in such patients. 30 Patients with
recurrence as regards characteristics and duration of Melasma darker Fitzpatrick skin phototypes showed less improvement than
those with lighter one and similar findings were reported also in
Recurrence No recurrence
Characteristics (n = 5) (n = 25) P value the study by Moin et al, 6 who stated skin phototypes III‐VI as a
risk factor with negative therapeutic outcome in the treatment of
Duration in years, 8.2 ± 4.87 5.46 ± 4.84 0.01*
Mean ± SD
melasma.
Patients were followed up for 3 months after the last session
Duration (%)
and about (83.33%) of cases showed no recurrence, while in remain‐
1y 0 4 (16.00) 0.03#
ing cases recurrence was either due to pregnancy, use of hormonal
1‐4 y 0 12 (48.00)
contraception or lack of use of sunscreen. This was consistent with
≥5 y 5 (100) 9 (36.00)
another prospective study that evaluated aggravating factors of me‐
Affected area (%)
lasma.31 It should be mentioned that recurrence rate in the current
Malar 0 4 (16.00) 1.00 ## study was less than other studies evaluating other treatment modal‐
Malar & Centro 5 (100) 20 (84.00) ities. 22,32 This might be explained by microneedling which allowed
facial
the delivery of sufficient concentrations of vitamin C into the skin,
*
Mann Whitney test was used. that enforced the depigmenting effect of vitamin C and decreased
#
Chi square test was used. the recurrence rate. In the current study, four out of five patients
##
Fisher exact test was used.
who showed recurrence were outdoor workers and this can be ex‐
plained by the role of ultraviolet rays and heat exposure in induc‐
TA B L E 5 Comparison between patients without and with
ing and worsening of melasma. 28 All patients with recurrence were
recurrence as regards Fitzpatrick skin type
Fitzpatrick skin phototype III‐V and were suffering from melasma for
Recurrence No recurrence more than five years which is consistent with the literature that pro‐
Characteristics (n = 5) (n = 25) P value posed dark skin phototypes and long‐term melasma for more than
Fitzpatrick skin type (%) two years as poor prognostic factors in melasma.6
a
Type 2 0 2 (8.00) 0.02
Type 3 1 (20.00) 14 (56.00)
5 | CO N C LU S I O N
Type 4 2 (40.00) 7 (28.00)
Type 5 2 (40.00) 2 (8.00)
We can conclude that microneedling with topical vitamin C is an
*
Chi‐square test for trend was used. effective treatment option for epidermal melasma especially in
Fitzpatrick skin phototypes I‐III. It is a safe treatment modality with
the percentage of improvement of MASI score was not related to no side effects except for, minimal pain of microneedling and post‐
patient age, occupation, marital status, family history, or duration procedure erythema. Microneedling with topical vitamin C can be
of melasma. However, in other studies, it was found that long du‐ used as a maintenance therapy without the known side effects
ration of melasma and familial predisposition was associated with of classical treatments of melasma specially the classical triple
6 | ISMAIL et al.

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