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Efficacy of cysteamine cream in the treatment of epidermal melasma,

evaluating by Dermacatch as a new measurement method: A randomized
double blind placebo controlled study

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DOI: 10.1080/09546634.2017.1351608

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 Journal of Dermatological Treatment

ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20

Efficacy of cysteamine cream in the treatment of

epidermal melasma, evaluating by Dermacatch
as a new measurement method: a randomized
double blind placebo controlled study

Susan Farshi, Parvin Mansouri & Behrooz Kasraee

To cite this article: Susan Farshi, Parvin Mansouri & Behrooz Kasraee (2018) Efficacy of
cysteamine cream in the treatment of epidermal melasma, evaluating by Dermacatch as a
new measurement method: a randomized double blind placebo controlled study, Journal of
Dermatological Treatment, 29:2, 182-189, DOI: 10.1080/09546634.2017.1351608

To link to this article: https://doi.org/10.1080/09546634.2017.1351608

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JOURNAL OF DERMATOLOGICAL TREATMENT, 2018
VOL. 29, NO. 2, 182–189
https://doi.org/10.1080/09546634.2017.1351608

ORIGINAL ARTICLE

Efficacy of cysteamine cream in the treatment of epidermal melasma, evaluating

by Dermacatch as a new measurement method: a randomized double blind
placebo controlled study
Susan Farshia, Parvin Mansouria and Behrooz Kasraeeb
a
Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran; bScientis Pharma SA, Geneva, Switzerland

ABSTRACT ARTICLE HISTORY

Background: Melasma is a difficult-to-treat hyperpigmentary disorder. Very few studies have been per- Received 21 March 2017
formed regarding the efficacy of cysteamine in the treatment of melasma. Revised 5 June 2017
Objective: To determine the efficacy of cysteamine cream in the treatment of patients with epidermal Accepted 5 June 2017
melasma using DermacatchV as a more accurate skin colorimetric measurement tool.
R

Methods: Participating patients (n ¼ 40) received either placebo (n ¼ 20) or cysteamine cream (n ¼ 20) in KEYWORDS
a double-blind placebo controlled study. Cysteamine cream or placebo was applied on the lesions once a Epidermal melasma;
day at bedtime throughout the four-month study period. Treatment efficacy was determined through cysteamine hydrochloride;
DermacatchV and MexameterV skin colorimetry, MASI scores, Investigator Global Assessments (IGAs), and
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MexameterV; DermacatchV;
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patient questionnaires, all performed at baseline, 2-month, and 4-month examinations. depigmenting agent;
Results: Prior to the start of the protocol, the mean difference between pigmented and normal skin was hydroquinone
calculated for cysteamine and placebo groups using both DermacatchV (72.3 ± 27.8 and 52.9 ± 16.4,
R

respectively) and MexameterV (93.6 ± 42.6 and 65.4 ± 22.6, respectively). At 2 months, the mean differences
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were 38.1 ± 15.3 (DermacatchV) and 49.9 ± 19 (MexameterV) in the cysteamine group and 64.9 ± 25.3
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(DermacatchV) and 68 ± 26.2 (MexameterV) in the placebo group. At 4 months, the mean differences were
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23.8 ± 12.9 (DermacatchV) and 35.5 ± 16.1 (MexameterV) in the cysteamine group, and 50 ± 18
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(DermacatchV) and 51.2 ± 16.8 (MexameterV) in the placebo group. Statistically significant differences were
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found between the cysteamine and placebo group outcomes at both time points (p ¼ .01, p ¼ .02). At the
end of the treatment period, MASI scores were significantly lower in the cysteamine group versus placebo
(8.03 ± 5.2 vs. 12.2 ± 7.4, p ¼ .04). IGA scores and patient viewpoints indicated significant efficacy of cyste-
amine cream versus placebo.
Conclusion: Cysteamine cream showed significant efficacy in decreasing melanin content of the lesions,
as established by DermacatchV as a new measuring method.
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Introduction To date, the depigmenting effect of cysteamine has been

shown in guinea pigs, and was confirmed by dermatoscopal and
Melasma is an acquired skin disorder characterized by bilateral,
chromametric evaluations, as well as through histological studies
hyperpigmented, irregularly shaped macules on the malar regions,
(3). A considerable efficacy of cysteamine in the treatment of epi-
forehead, upper lip, and mandible of the face, occurring
dermal melasma was confirmed by all evaluation methods (3,7).
commonly on sun-exposed areas and predominantly affecting
In our previous study, we have successfully demonstrated the
women (1,2).
efficacy of cysteamine cream in reducing and eliminating melasma
Cysteamine hydrochloride (b-mercaptoethylamine hydrochlor-
in humans (7). However, in that study, the melanin content of the
ide) is the simplest stable aminothiol that has been known to be
lesions was evaluated by MexameterV only. In a more recent
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a potent depigmenting molecule for over five decades (3). This study, MexameterV and DermacatchV were compared, revealing
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molecule is naturally produced in the human body and is a deg- that DermacatchV has a significantly higher specificity and repro-
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radation product of the amino acid L-cysteine. At high L-cysteine ducibility than MexameterV in the measurement of skin pigmenta-
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concentrations, melanocytes exhibit reduced tyrosinase activity tion and erythema (8). The key advantage of DermacatchV
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and produce notably greater amounts of pheomelanin (4). (Colorix, Neuchatel, Switzerland) stems from its use of the entire
Previous cell culture studies have confirmed that cysteamine acts visible-spectrum reflectance. Thus, MexameterV might be signifi-
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through inhibition of melanogenesis, rather than melanocytotoxic-
ity, to depigment cultured melanocytes.
However, at present, empirical evidence supporting the
depigmenting effects of cysteamine in animal models is
limited (5,6).
cantly less reliable, owing to its potential for providing false
results for melanin values in cases of skin erythema. Dermacatch
is shown to be more effective for discriminating between melanin
and erythema (8). Therefore, we conducted a second clinical trial
using DermacatchV as the skin colorimeter alongside MexameterV.
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CONTACT Susan Farshi farshi_s@yahoo.com, sfarshi@razi.tums.ac.ir Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
ß 2017 Informa UK Limited, trading as Taylor & Francis Group

Methods
A randomized, double-blind, placebo-controlled parallel group
study was conducted at a general hospital and a research center.
The study protocol conformed to the guidelines of the 1975 First
Revision of the Declaration of Helsinki, and was approved by the
Medical Ethics Committee of the Tehran University of Medical
Sciences. This study was a continuation of our previous research,
which had been registered in the Iranian Registry of Clinical Trials
(IRCT201212059800N2). After completing patient recruitment in
our previous study, the trial was continued using the same crite-
ria, with the only alteration being the introduction of
DermacatchV for assessing skin pigmentation, alongside the previ-
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ously employed use of MexameterV and Melasma Area and
R
Severity Index (MASI) scores.
Written informed consent was obtained from all patients prior
to enrolment. The study started in April 2014 (the first visit of the
first patient) and ended in June 2015 (the last visit of the last
patient). Patients with facial melasma were recruited from the
Dermatology Clinic of Imam Hospital (Tehran University of Medical
Sciences) and the Skin and Stem Cell Research Center.
The treatment period was four months. Female and male
patients aged 18–50 years with Fitzpatrick skin types III, IV, and V
were eligible to take part in the study. The inclusion criteria were
the diagnosis of epidermal melasma, as confirmed by Wood's
lamp examination, and minimum disease duration of six months.
None of the patients received any treatment for at least two
months prior to the start of the study.
The exclusion criteria were as follows: dermal and mixed-type
melasma, use of oral contraceptives at the time of the study or
during the three months prior to its commencement, topical or
oral corticosteroid therapy, suffering from other pigmentation dis-
orders, a history of endocrine disorders, and pregnancy and
lactation.
Clinical assessment
Melasma severity was determined at the beginning of the study,
and was categorized into four groups: (0) Minimal residual pig-
mentation (clear); (1) Mild, slightly darker than the surrounding
area; (2) Moderate, darker than the surrounding area; and (3)
Severe, darker than the surrounding area (9). The melasma sever-
ity scores were also determined at the end of the study, i.e. at
4-month follow-up.
MASI scores were determined at baseline, as well as at
2-month and 4-month follow-ups. The MASI score is a reliable
index used to quantify the severity of melasma and any changes
during therapy. According to the MASI scoring system, the face is
divided into four areas: forehead (F), right malar (RM), left malar
(LM), and chin (C), which correspond to 30, 30, 30, and 10% of
the total facial area, respectively. The melasma in each of these
areas was graded in terms of three variables. First, the percentage
of total area involved in each of these was given a numerical
value from 0 to 6: 0 denoted no involvement, and 1–6 denoted
0–9%, 10–29%, 30–49%, 50–69%, 70–89%, and 90–100% total area
involved, respectively. The remaining two parameters were dark-
ness (D) and homogeneity (H), both measured on a scale from 0
(absent) to 4 (maximum). The MASI score was calculated by apply-
ing the following equation, in accordance with the formulation by
Kimbrough-Green et al. (2):
MASI ¼ 0:3ðDF þ HF ÞAF þ 0:3ðDRM þ HRM Þ þ 0:3ðDLM þ HLM Þ
þ 0:1ðDc þ HC Þ
where, D denotes darkness, H is homogeneity, A represents area,
JOURNAL OF DERMATOLOGICAL TREATMENT 183
F is forehead, RM stands for right malar, LM is left malar, C per-
tains to chin, and the values 0.3, 0.3, 0.3, and 0.1 are the respect-
ive percentages of the total facial area. The MASI score thus
ranges from 0 to 48. A mean of the MASI scores obtained by each
investigator was calculated.
High-resolution images were taken using a camera, as well as
Visioface 1000D (CK Electronic GmbH, Cologne, Germany).
DermacatchV (Colorix, Neuchatel, Switzerland) is the most
R
advanced high-tech Swiss-made portable visible-spectrum reflect-
ance skin colorimeter, and was specifically developed to instantly
display measuring results, including melanin and erythema values
(with arbitrary units that differ from those used by the
MexameterV) that benefits from whole visible-spectrum reflect-
R
ance. The measured area covers a disk of 5.5 mm in diameter, i.e.
24 mm2 (8).
The differences in pigment (melanin) content between lesions
and normal skin area were used in statistical analysis.
The melanin content and erythema level were also calculated
using a MexameterV (MexameterV MX 18, MPA 9, Courage þ
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Khazaka Electronic, GmbH, Germany) in lesions and surrounding
normal skin areas in each part of the face at the baseline examin-
ation, as well as at 2-month and 4-month follow-ups. The
MexameterV MX 18 is a convenient tool, allowing the user to
R
quickly measure the two components that are primary contribu-
tors to skin color: melanin and hemoglobin (erythema). The differ-
ences in melanin content in each lesion and the surrounding
normal skin were calculated and the mean of the differences in
each part of the face was used for statistical analysis.
The Investigator's Global Assessment (IGA) was grouped into
four categories, according to Lee et al. (10): (1) no effect (no vis-
ible changes of pigmentation), (2) mild (decrease in visible pig-
mentation with some visible borders), (3) moderate (marked
decrease in visible pigmentation with some visible borders), and
(4) excellent (a complete loss of visible abnormal pigmentation).
Patient feedback regarding efficacy was grouped similarly to
the IGA scores. However, the questionnaire required patients to
select specific items related to the effects of the cream they
believed were most influential in reducing their lesion color.
Adverse events, including erythema, dryness, itching, burning
sensation, irritation, and dyspigmentation (hypo and hyperpig-
mentation), were monitored during the study and were rated on a
scale from 0 (none) to 3 (severe).
Patients were instructed to wash their face in the evening
using the prescribed syndet bar and apply a thin layer of the
cream (placebo or cysteamine) on their lesions 30 min later. They
were also advised to wash their face with tepid water 3 h after
the application of the cream. All patients were provided with a
broad-spectrum standard sunscreen with SPF 50þ and were
instructed to apply it on their entire face and to repeat the appli-
cation every 3 h during the day throughout the study period.
Neither the investigator nor the patients were aware of the treat-
ment type provided to individual participants.
Cysteamine cream and the placebo (containing all ingredients
except cysteamine hydrochloride) were kindly provided by
Scientis Pharma SA and Sharaje SA (Geneva, Switzerland). The
product contained 5% cysteamine.
The creams were sent to an independent investigator who was
not involved in the assessment of trial outcomes.
A consecutive sampling method was used. The randomization
sequences were computer generated, where blocked randomiza-
tion, with four in each block, was used to encoding cream tubes.
The sequences of the blocks were also computer generated. In
order to decrease the possibility of disclosure, four labels for the
creams were provided, two for the placebo and two for the drug.
184 S. FARSHI ET AL.

Sampling and randomization were performed by an independ-
ent investigator. The investigators who assessed primary and sec-
ondary outcomes did not participate in randomization and
allocation.
In order to assess patient compliance, at each visit, the patients
brought their cream tubes, which were weighed at each follow-up
appointment.
Statistical analysis
All analyses were performed using SPSS (Statistical Package for
dropout rate of <10%, as well as for analysis following the intent-
to-treat principle, 20 patients per group were required.
Descriptive statistics were used to summarize the overall char-
acteristics of the study population.
A p value of 0.05 or less was considered to indicate statistical
significance. For the comparison of MASI scores, DermacatchV,
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and MexameterV measurements in each drug group, an independ-
R
ent t-test was used, as the data were found to be normally distrib-
uted. Normality was verified through the Kolmogorov–Smirnov
test and the grades in objective assessment were compared using
the Mann–Whitney test.
The correlation of measurements using MexameterV and
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Social Sciences) software (version 16, Chicago, IL). Sample size was
DermacatchV was assessed by Pearson’s correlation.
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calculated using the expression below, where the one-sided Type

I error was set to a ¼ 5% and b was equal to 0.2.
2ðz1a þ z1b Þ2 pð1  pÞ
n¼
ðp1  p2 Þ2
The study was designed to detect a difference of 40% between
an active treatment group (cysteamine) and the placebo group in
the proportion of patients achieving a response. Assuming propor-
tions of 50% responders in the active treatment groups and 10%
in the placebo group, a sample size of 18 patients per group was
required to reach a power of 80%. After further accounting for a
Results
Following the evaluation of 60 patients for inclusion, 45 were
invited to take part in this study, but 5 declined to participate
(Figure 1). While two individuals did not state any specific reasons
for refusal, the remaining three cited impracticality, as they
resided in other cities.
The remaining 40 patients (20 of whom were treated with cys-
teamine cream and 20 with placebo) completed the 4-month
treatment protocol and attended all follow-up appointments.

Study Design

Enrollment 60 Assessed for eligibility

20 Excluded
♦ 15 Not meeting inclusion criteria
♦ 5 Declined to participate

40 Randomized
Cysteamine Placebo

Allocation

20 Allocated to intervention 20 Allocated to intervention

♦ 20 Received allocated intervention ♦ 20 Received allocated intervention
(cysteamine cream) (placebo cream)

Follow-Up

0 Lost to follow-up 0 Lost to follow-up

0 Discontinued intervention 0 Discontinued intervention

Analysis

20 Analysed 20 Analysed
♦0 Excluded from analysis ♦0 Excluded from analysis

Figure 1. Flow diagram according to CONSORT guidelines showing the flow of participants in the trial, including dropouts.
 JOURNAL OF DERMATOLOGICAL TREATMENT 185

Table 1. Baseline patient characteristics. Upon completion of the treatment period, a statistician was given
Variable Cysteamine (n ¼ 28) Placebo (n ¼ 25) the data for analysis. In order to ensure the double-blind design,
Age (years), mean ± SD 39.9 ± 6.9 39.7 ± 6.3 the data were encoded by another independent statistician.
Sex, n (%) Among the 40 patients, 6 (15%) were male and 34 (85%) were
Male 4 (20) 2 (10) female. The mean disease duration was 5.6 ± 4.4 years. The base-
Female 16 (80) 18 (90)
Skin Type line characteristics of the full sample cohort are provided in
III 14 (70) 15 (75) Table 1.
IV 6 (30) 5 (25) Melasma severity assessments indicated that 9 patients (22.5%)
Duration of melasma (years), mean ± SD 5.97 ± 4.4 5.2 ± 4.5 had mild melasma, 27 (67.5%) had moderate melasma, and 4
MSS
Minimal residual pigmentation 0 0 (10%) had severe melasma, as shown in Table 2. Statistically sig-
Mild 3 (15) 6 (30) nificant differences were noted between the placebo and cyste-
Moderate 14 (70) 13 (65) amine groups at the 4-month follow-up (Mann–Whitney, p ¼ .01).
Severe 3 (15) 1 (5) IGA and patient feedback on efficacy at the end of the study
MASI Scores (mean ± SD) 18.1 ± 8.2 13.2 ± 7.4
Dermacatch findings (mean ± SD) 65.4 ± 22.6 52.9 ± 16.4 are summarized in Table 3. Significant differences were found
Mexameter findings (mean ± SD) 93.7 ± 42.4 72.3 ± 27.8 between the placebo and cysteamine groups in both investigator
MSS: Melasma Severity Score; MASI: Melasma Area Severity Index. and patient assessments (Mann–Whitney, p ¼ .0001 and .001,
Mean: mean difference between lesion and surrounding normal skin. respectively).
The mean MASI scores in the placebo and cysteamine groups
prior to treatment, after 2 months of treatment, and at the 4-
Table 2. Melasma severity scales before and after treatment in placebo and cys-
teamine groups. month follow-up are shown in Table 4. Statistically significant dif-
Placebo Cysteamine Placebo Cysteamine
ferences were noted between the placebo and cysteamine groups
before before after after only at the completion of four months of treatment.
Melasma treatment treatment treatment treatment The mean difference in melanin content between the lesions
Severity
scales No % No % No % No % and the surrounding normal areas in the placebo and cysteamine
groups were calculated using DermacatchV and MexameterV
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Clear 0 0 0 0 0 0 0 0
Mild 6 30 3 15 8 40 17 85 before treatment, and at months 2 and 4 after treatment.
Moderate 13 65 14 70 11 55 3 15 Statistically significant differences were found between the pla-
Severe 1 5 3 15 1 5 0 0 cebo and cysteamine groups at the 2- and 4-month follow-ups
Total 20 100 20 100 20 100 20 100
using both measurement methods (Table 4).
Statistically significant differences was found between placebo and cysteamine
The correlation between DermacatchV and MexameterV prior
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in Melasma Severity Scale (MSS) after 4 months treatment (Mann–Whitney,

p ¼ .01). to treatment and at months 2 and 4 was 0.82, 0.74, and 0.76,
respectively (Pearson correlation). These results indicate a good
correlation between DermacatchV and MexameterV scores.
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Figure 2 shows a good clinical response in a melasma patient.

Table 3. Hypopigmentation grading in placebo and cysteamine groups assessed
by investigators and by the patients. According to this patient, she had already received several topical
Investigator’s global Patient’s viewpoint
treatments (hydroquinone, as well as hydroquinone-free topical
assessment on efficacy depigmenting creams) for her melasma without any improve-
ments. Figure 3 depicts a 38-year-old woman before treatment
Cysteamine Placebo Cysteamine
Hypopigmentation Placebo and after 2 and 4 months of cysteamine cream application, who
Grading No. % No. % No. % No. % experienced a good clinical response. Figure 4 shows the error
bars of MASI scores, MexameterV readings, and DermacatchV read-
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1 12 60 0 0 7 35 2 10 ings at baseline, after two months, and after four months of top-
2 8 40 9 45 13 65 8 40
3 0 4 11 55 0 0 10 50 ical treatment with cysteamine cream and placebo.
4 0 0 0 0 0 0 0 0 Overall, seven patients in the cysteamine group reported some
Total 20 100 20 100 20 100 20 100 adverse effects. The degree of these effects was rather mild and
(1) no effect (no visible changes of pigmentation); (2) mild (decrease of visible tolerable in these patients and was resolved by continuing the
pigmentation, but there is still some visible border); (3) moderate (marked treatment. In the placebo group, no patient complained of any
decrease of visible pigmentation, but there is still some visible border); and (4)
excellent (a complete loss of visible abnormal pigmentation). A significant dif- adverse events.
ference was found between placebo and cysteamine groups by investigator's Table 5 shows the adverse events in the placebo and cyste-
global assessment and also by patient's viewpoint on efficacy (Mann–Whitney, amine group, indicating no significant differences in erythema,
p ¼ .0001, p ¼ .001). dryness, itching, burning sensation, and irritation as reported in

Table 4. Mean MASI scores, mean differences of pigment content of the lesions and normal skin using MmexameterV and DermacatchV before, after 2 months and
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at the end of the study at month 4.

MASI Scores Mexameter Dermacatch
Before T After 2 M After 4 M Before T After 2 M After 4 M Before T After 2 M After 4 M
Placebo 13.2 ± 7.4 12.5 ± 7.4 12.2 ± 7.4 72.3 ± 27.8 68 ± 26.2 64.9 ± 25.3 52.9 ± 16.4 51.2 ± 16.8 50 ± 18
Cysteamine 18.1 ± 8.1 11.2 ± 6.2 8.03 ± 5.2 93.6 ± 42.4 49.9 ± 19 38.1 ± 15.3 65.4 ± 22.6 33.5 ± 16.1 23.8 ± 12.9
p Value 0.06 0.55 0.04 0.07 0.01 0.0001 0.055 0.002 0.0001
CI 95% 9.9 to 0.1 3.4 to 5.67 0.06 to 8.24 44.5 to 1.7 3.4 to 32.79 13.39 to 40.3 25.2 to 0.2 7.1 to 28.2 16.1 to 36.3
T: treatment; M: month.
186 S. FARSHI ET AL.
Figure 2. A 39 years old woman with 8 years melasma duration, (A) before treatment, (B) after 4 months treatment by topical cysteamine cream.
Figure 3. A 38 years old woman with 6 years melasma, (A) before treatment, (B) after 2 months, (C) after 4 months treatment by cysteamine cream.
the two groups (Mann–Whitney, p ¼ .06, p ¼ .3, p ¼ .2, p ¼ .2, and
p ¼ .3, respectively).
Discussion
The currently available information is insufficient to identify the
most effective or standardized melasma treatment. Moreover, the
effectiveness of the wide range of treatments presently in use is
highly variable (11–24). Not only are some of these treatments
associated with significant side effects, but the chronic and relaps-
ing nature of melasma makes maintaining any positive response
achieved challenging (12).
The most commonly used depigmenting agent, hydroquinone
(HQ), as a member of the phenol group of chemicals, was origin-
ally claimed to act as a tyrosinase inhibitor, capable of inhibiting
the conversion of tyrosine to dihydroxyphenylalanine (DOPA) and
of DOPA to dopaquinone (23,25,26). However, in 1981, Passi and
Nazzaro-Porro demonstrated that, rather than as an inhibitor of
tyrosinase, HQ in fact behaved as an oxidizable substrate for the
enzyme, with the oxidation product being the highly toxic metab-
olite 1,4-benzoquinone (27). Subsequent studies revealed that the
depigmenting activity of HQ stems from its potent cytotoxic effect
against melanocytes (28), mediated via its enzymatic oxidation to
quinones (26).
Melanogenesis is based on the enzymatic conversion of the
amino acid tyrosine, through a series of intermediates, to mel-
anin pigments. The type of the enzymes implicit in the differ-
ent melanogenesis stages has been a subject of an intense
debate. However, there is a growing consensus that tyrosinase
is responsible for the conversion of tyrosine to DOPA, as well
as that of DOPA to dopaquinone. Moreover, it is widely
accepted that peroxidase is responsible for the oxidative poly-
merization of the subsequently formed indoles to eumelanin
pigments (26).

Figure 4. Error bar of MASI scores before (A), after 2 months therapy (B), and after 4 months treatment (C); Mexameter differences before (D), after 2 months (E), and
after 4 months treatment (F); Dermacatch differences before (G), after 2 months (H), and after 4 months treatment (I).
The dose-dependent inhibition of tyrosinase by cystamine and
cysteamine was the subject of several extant studies (29,30). The
available evidence indicates that cystamine and linoleic acid are
capable of hindering melanin synthesis both in vitro and in vivo
(29). The authors further reported that cysteamine, a reduced
monomer of cystamine, decreased the formation of dopachrome,
the immediate precursor of eumelanin (29).
Cysteamine is a radioprotector, as it provides protection
against the mutagenic and potentially lethal consequences of ion-
izing radiation. It can also inactivate a mutagen independently of
a biological system. The well-known radioprotective role of amino-
thiols is directly analogous to their antimutagenic effects, i.e. the
direct scavenging of hydroxyl radicals produced by the radiolysis
of water and/or oxygen depletion (31–33).
Extant studies indicate that cysteamine can inhibit DNA poly-
merases and cell cycle progression (34,35).
DermacatchV is a visible-spectrum reflectance colorimeter that
R
utilizes a diode emitting light in the full visible spectrum. The
photodetector detects the globally reflected light, which is subse-
quently measured in order to compute both erythema and mel-
anin values expressed in different units than MexameterV.
R
DermacatchV has been reported to yield more reproducible
R
results, and is also a more specific colorimeter, owing to its
JOURNAL OF DERMATOLOGICAL TREATMENT 187
greater ability to discriminate pigmentation from cutaneous ery-
thema (8).
In the present study, both DermacatchV and MexameterV were
R R
used for measuring the melanin content of melasma lesions. The
results yielded by the two methods were highly correlated, sug-
gesting that DermacatchV could be used as an alternative to
R
MexameterV, as it is a more reliable measuring method in terms
R
of evaluating melasma.
In both our previous and current study, none of our patients
reached a MASI of zero (100% clearance of melasma lesions) as
measured by DermacatchV or MexameterV despite the high clin-
R R
ical efficacy of cysteamine. This could be due to the presence of
recalcitrant and resistant forms of melasma in patients recruited
for this study.
In our previous study, a few of our patients complained about
the sulfur-like odor of the cream, which interfered with the blind-
ness of the investigators. However, in the present study, no
patients complained about the odor.
Although transient redness was sometimes observed immedi-
ately after the first application of cysteamine, the issue did
not persist. Overall, the product was found to be more
tolerable than in our first study and caused fewer adverse
events (7).
188 S. FARSHI ET AL.

Table 5. Adverse events reported in the placebo and cysteamine groups. 3. Chavin W, Schlesinger W. Some potent melanin depigmen-
Placebo Cysteamine tary agents in the black goldfish. Naturwissenschaften.
1966;53:413–414.
Grade N % N %
4. Smit NP, Van der Meulen H, Koerten HK, et al.
Erythema
0 2 100 13 65 Melanogenesis in cultured melanocytes can be substantially
1 0 0 4 20 influenced by L-tyrosine and L-cysteine. J Invest Dermatol.
2 0 0 3 15 1997;109:796–800.
3 0 0 0 0 5. Frenk E, Pathak MA, Szabo  G, et al. Selective action of mer-
Dryness
captoethylamines on melanocytes in mammalian skin:
0 20 100 16 80
1 0 0 4 20 experimental depigmentation. Arch Dermatol. 1968;97:
2 0 0 0 0 465–477.
3 0 0 0 6. Bleehen S, Pathak MA, Hori Y, et al. Depigmentation of skin
Itching with 4-Isopropylcatechol, mercaptoamines, and other com-
0 20 100 15 75
1 0 0 5 25 pounds. J Invest Dermatol. 1968;50:103–117.
2 0 0 0 0 7. Mansouri P, Farshi S, Hashemi Z, et al. Evaluation of the effi-
3 0 0 0 0 cacy of cysteamine 5% cream in the treatment of epidermal
Burning melasma: a randomized double-blind placebo-controlled
0 20 100 15 75
trial. Br J Dermatol. 2015;173:209–217.
1 0 0 3 15
2 0 0 2 10 8. Baquie M, Kasraee B. Discrimination between cutaneous pig-
3 0 0 0 0 mentation and erythema: comparison of the skin colorime-
Irritation ters Dermacatch and Mexameter. Skin Res Technol.
0 20 100 16 80 2014;20:218–227.
1 0 0 3 15
2 0 0 1 5 9. Pandya A, Berneburg M, Ortonne JP, et al. Guidelines for
3 0 0 0 0 clinical trials in melasma. Pigmentation Disorders Academy.
Dyspigmentation Br J Dermatol. 2006;156 Suppl 1:21–28.
0 25 100 25 100 10. Lee MH, Kim HJ, Ha DJ, et al. Therapeutic effect of topical
1 0 0 0 0
application of linoleic acid and lincomycin in combination
2 0 0 0 0
3 0 0 0 0 with betamethasone valerate in melasma patients. J Korean
Med Sci. 2002;17:518–523.
11. Gupta AK, Gover MD, Nouri K, et al. The treatment of mel-
asma: a review of clinical trials. J Am Acad Dermatol.
2006;55:1048–1065.
The main limitations of the present study stem from the omis- 12. Rajaratnam R, Halpern J, Salim A, et al. Interventions for
sion of histological assessments and not determining the systemic melasma. In: Cochrane Database of Systematic Reviews.
absorption of cysteamine. Cochrane Collaboration. John Wiley & Sons, Ltd; 2010. p. 7.
The results yielded by the present study, in which the melanin 13. Jutley GS, Rajaratnam R, Halpern J, et al. Systematic review
content of melasma lesions was measured using DermacatchV as of randomized controlled trials on interventions for mel-
R

well as MexameterV, show that cysteamine is effective in reducing asma: an abridged Cochrane review. J Am Acad Dermatol.
R

and treating epidermal melasma. 2014;70:369–373.

The cysteamine and placebo creams have been kindly offered
by Scientis Pharma SA & Sharaje SA.
Acknowledgements
The authors would like to thank the derma lab personnel of “Skin
and Stem Cell Research Center” for their cooperation in this study.
Disclosure statement
Dr Behrooz Kasraee works at Scientis Pharma SA, but he did not
have a role in data collection and analysis.
References
1. Rivas S, Pandya AG. Treatment of melasma with topical
agents, peels and lasers: an evidence-based review. Am J
Clin Dermatol. 2013;14:359–376.
2. 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.
14. Kang HY, Valerio L, Bahadoran P, et al. The role of topical
retinoids in the treatment of pigmentary disorders: an evi-
dence-based review. Am J Clin Dermatol. 2009;10:251–260.
15. Farshi S. Comparative study of therapeutic effects of 20%
azelaic acid and hydroquinone 4% cream in the treatment
of melasma. J Cosmet Dermatol. 2011;10:282–287.
16. Kasraee B, Handjani F, Parhizgar A, et al. Topical methima-
zole as a new treatment for postinflammatory hyperpigmen-
tation: report of the first case. Dermatology (Basel).
2005;211:360–362.
17. Kasraee B, Hugin A, Tran C, et al. Methimazole is an inhibitor
of melanin synthesis in cultured B16 melanocytes. J Invest
Dermatol. 2004;122:1338–1341.
18. Kasraee B, Nikolic DS, Salomon D, et al. Ebselen is a
new skin depigmenting agent that inhibits melanin biosyn-
thesis and melanosomal transfer. Exp Dermatol.
2012;21:19–24.
19. Erbil H, Sezer E, Tastan B, et al. Efficacy and safety of serial
glycolic acid peels and a topical regimen in the treatment
of recalcitrant melasma. J Dermatol. 2007;34:25–30.
20. Deo KS, Dash KN, Sharma YK, et al. Kojic acid vis-a-vis its
combinations with hydroquinone and betamethasone valer-
ate in melasma: a randomized, single blind, comparative
study of efficacy and safety. Indian J Dermatol. 2013;58:
281–285.

21. Khunger N, Sarkar R, Jain RK. Tretinoin peels versus glycolic
acid peels in the treatment of melasma in dark-skinned
patients. Dermatol Surg. 2004;30:756–760.
22. Goldman MP, Gold MH, Palm MD, et al. Sequential treat-
ment with triple combination cream and intense pulsed
light is more efficacious than sequential treatment with an
inactive (control) cream and intense pulsed light in patients
with moderate to severe melasma. Dermatol Surg. 2011;37:
224–233.
23. Jimbow K. N-acetyl-4-S-cysteaminylphenol as a new type of
depigmenting agent for the melanoderma of patients with
melasma. Arch Dermatol. 1991;127:1528–1534.
24. Berardesca E, Cameli N, Primavera G, et al. Clinical and
instrumental evaluation of skin improvement after treatment
with a new 50% pyruvic acid peel. Dermatol Surg.
2006;32:526–531.
25. Subrahmanyam VV, Kolachana P, Smith MT. Metabolism of
hydroquinone by human myeloperoxidase: mechanisms of
stimulation by other phenolic compounds. Arch Biochem
Biophys. 1991;286:76–84.
26. Kasraee B. Peroxidase-mediated mechanisms are involved in
the melanocytotoxic and melanogenesis-inhibiting effects of
chemical agents. Dermatology (Basel). 2002;205:329–339.
27. Passi S, Nazzaro-Porro M. Molecular basis of substrate and
inhibitory specificity of tyrosinase: phenolic compounds. Br J
Dermatol. 1981;104:659–665.
View publication stats
JOURNAL OF DERMATOLOGICAL TREATMENT 189
28. Ito Y, Jimbow K, Ito S. Depigmentation of black guinea pig
skin by topical application of cysteaminylphenol, cysteinyl-
phenol, and related compounds. J Invest Dermatol.
1987;88:77–82.
29. Hwang JS, Choi H, Rho HS, et al. Pigment-lightening effect
of N,N'-dilinoleylcystamine on human melanoma cells. Br J
Dermatol. 2004;150:39–46.
30. Qiu L, Zhang M, Sturm RA, et al. Inhibition of melanin syn-
thesis by cystamine in human melanoma cells. J Invest
Dermatol. 2000;114:21–27.
31. Hoffmann GR, Shorter RA, Quaranta JL, et al. Two mecha-
nisms of antimutagenicity of the aminothiols cysteamine
and WR-1065 in Saccharomycescerevisiae. Toxicol In Vitro.
1999;13:1–9.
32. Clarke CH, Shankel DM. Antimutagenesis in microbial sys-
tems. Bacteriol Rev. 1975;39:33–53.
33. Gebhart E. Antimutagens. Data and problems. Humangenetik.
1974;24:1–32.
34. Tatsuta M, Iishi H, Baba M, et al. Tissue norepinephrine
depletion as a mechanism for cysteamine inhibition of colon
carcinogenesis induced by azoxymethane in Wistar rats. Int
J Cancer. 1989;44:1008–1011.
35. Tatsuta M, Iishi H, Baba M, et al. Enhancement by sulpiride
of the inhibitory effects of cysteamine on gastric carcino-
genesis induced by N-methyl-N0 -nitro-N-nitrosoguanidine in
Wistar rats. Int J Cancer. 1991;47:54–59.