Letters to the Editor
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DOI: 10.1111/jdv.12200
Treatment of melasma with oral
administration of compound
tranexamic acid: a preliminary
clinical trial
Editor
Melasma is a relatively common, acquired facial skin disorder of
hyperpigmentation. It occurs in both sexes, although nearly 90%
of the patients are female.1 Hydroquinone has been considered as
the gold standard for treatment.2 Other treatments include me-
quinol, tretinoin, kojic acid, glycolic acid, ascorbic acid, or vari-
ous combinations of these medications. Although a variety of
therapeutic options are currently available, no treatment has been
proved to be consistently satisfactory. More recent studies show
that trans-4-aminomethylcyclohexanecarboxylic acid (tranexa-
mic acid), one of plasmin inhibitors, can prevent UV-induced
(a)
Figure 1 Change in the lesions of a
melasma patient before (a) and after (b)
treatment with tranexamic acid. The brown
patches almost completely disappeared
after treatment for 16 weeks (b).
JEADV 2014, 28, 388–394
393
pigmentation in guinea pigs.3 Topical trans-AMCHA (tranexa-
mic acid) inhibits UV-induced plasmin activity in keratinocytes
by preventing the binding of plasminogen to the keratinocytes,
which ultimately results in less free arachidonic acids and dimin-
ished ability to produce prostaglandins, and decreases melano-
cyte tyrosinase activity. The goal of our preliminary study was to
evaluate the efficacy and side-effects of a novel method using
compound tranexamic acid as a novel therapy for melasma.
As a prospective open-label study, all melasma patients
recruited for the study were from the dermatology clinic in the
Peking Union Medical College Hospital in Beijing, China. Before
the study, we carefully explained the procedures, risks, benefits,
potential complications, and side-effects to all patients, and all
written informed consents were obtained. The exclusion criteria
included: pregnant or nursing women; patients who took drugs
containing whitening drugs, and treatment within 3 months prior
to enrolment; patients with a history of thrombosis or thrombo-
philia or serious liver and kidney dysfunction or cardiovascular or
respiratory disease. A total of 35 patients with melasma were
enrolled between 2011 and 2012. The total duration of the study
was 16 weeks. After evaluation of the testing results, patients were
ready to take two tablets of compound tranexamic acid (Dai-ichi
Sankyo Healthcare, Tokyo, Japan) after meal, three times daily for
16 weeks [Correction added on 26 August 2013, after first online
publication: manufacturer name was changed.]. The patients were
advised to avoid excessive sun exposure and to apply the same
broad-spectrum sunscreen with a sun protection factor 30.
We used a 5-point scoring system to evaluate the severity of
melasma at baseline, 4, 8, 12, 16 weeks; significant improve-
ment, moderate improvement, no change, minor deterioration,
deterioration in VISIA Photos (Version 5; Canfield Scientific
Inc., Fairfield, NJ, USA); significant improvement (The differ-
ence of V from pretreatment (ΔV ≥ 1.0), improvement (0.75),
(b)
© 2013 European Academy of Dermatology and Venereology
394 Letters to the Editor

Table 1 Patient characteristics and change of clinical assessments general improvement (0.5), unchanged ( 0.25 to 0.25), deteri-
Total number of patients (n) 35 oration (< 0.25) in Skin Tone Color Scale.4 The nonlesional
Age(years), mean 24 to 54.41 (normal) skin on the cheek and the most representative
Gender male/female, n 2/33 pigmented lesions of the face were used for the evaluation.
Severity of melasma At the end of our study, patient self-assessment questionnaire
Mild melasma (involved <1/3 of the 11 (31.43%) was provided. The patients were followed up once a month,
entire cheek), n (%) and any side-effect during the study was recorded. Data were
Moderate melasma (involved 1/3 to 2/3 24 (68.57%) analysed with Statistical Package Program (SPSS 17.0, China).
of the entire cheek), n (%)
Statistical significance was assumed at P < 0.05.
Skin Colour (Hue on the Skin Tone Color Scale), n
Of 35 patients, 32 completed the trail. The mean age was
1YR* normal skin/melasma, n 0/0
41-years old. All the 33 women were Fitzpatrick skin types III or
3YR* 2/2
5YR* 4/5
IV, two men type IV. They were all mild or moderate melasma.
7YR* 11/12
The mean ΔV and SD of melasma was 0.86  0.57 in patients
9YR* 18/16 with moderate to marked improvement, normal skin was
V Value of the Skin Tone Color Scale mean  SD 0.49  0.41 with moderate improvement. Clinical manifesta-
Baseline normal skin/melasma (7.16  0.42)/(6.21  0.54) tions revealed the colour and size of skin lesions had significantly
mean  SD improved (Fig. 1). From the doctors’ evaluation results, we
4 weeks (7.44  0.32)/(6.77  0.37) found that the improved patients accounted for 85% in 4 weeks,
8 weeks (7.47  0.24)/(6.79  0.31) 97% in 8 and 12 weeks, and 100% in 16 weeks. Lesions signifi-
12 weeks (7.60  0.22)/(7.01  0.28) cantly improved early during the treatment and remained stabi-
16 weeks (7.67  0.28)/(7.10  0.36) lized later (Table 1). Significant improvements of the quality of
The difference of V from pretreatment (ΔV) mean  SD life were observed in patients’ self-assessment. All patients were
4 weeks normal skin/melasma (0.29  0.40)/(0.55  0.50) asked in details of any discomfort, but no serious adverse effects
mean  SD
except some possible slightly adverse effects were documented
8 weeks (0.30  0.39)/(0.56  0.47)
(Table 1). Yet, none of them stop taking this medication.
12 weeks (0.45  0.36)/(0.82  0.51)
In conclusion, our preliminary study indicates that oral
16 weeks (0.49  0.41)/(0.86  0.57)
Doctor’s assessment
compound tranexamic acid seems to be a potentially new and
Marked improvement 4 weeks/ 8/15/24/24
promising therapeutic option. But a large-scale and multicentre
8 weeks/12 weeks/16 weeks study will be needed to define its long-term benefits and any
Moderate improvement 20/16/7/8 potential additional adverse effect. In addition, further trials
No change 4/1/1/0 might be required to evaluate the effect of combining this drug
Slight deterioration 0/0/0/0 with other treatments such as the topical drugs, chemical peel-
Marked deterioration 0/0/0/0 ing, laser, or phototherapy, to identify any additive effect in the
Patient’s self-assessment completed/ 23/30 search for better treatments for melasma.
all, n
Feel facial pigmentation faded, n (%) 23 (100%) Y. Li, Q. Sun,* Z. He, L. Fu, C. He, Y. Yan
Feel the skin became brighter 22 (96%) Dermatology Department, Peking Union Medical College Hospital, Beijing,
No longer disturbed by the presence 20 (87%) China
of facial pigmentation and emotional
*Correspondence: Q. Sun. E-mail: sunqnzhy@yahoo.com
stress
Satisfied with the medication 23 (100%)
Reference
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getting better
treatments. Coll Antropol 2011; 35 (Suppl 2): 315–318.
Others tell them the skin was getting 18 (78%) 2 Piamphogsant T. Treatment of melasma: a review with personal experi-
whiter ence. Int J Dermatol 1998; 37: 897–903.
Drug safety, n (%) 3 Maeda K, Naganuma M. Topical trans-4-aminomethylcyclohexanecarb-
Slightly elevated ALT 1 (3%) oxylic acid prevents ultraviolet radiation induced pigmentation. J Photo-
chem Photobiol B 1998; 47: 130–141.
Gastrointestinal discomfort such as 3 (12.5%)
nausea and vomiting 4 Konishi Natsuko, Kawada Akira, Morimoto Yoshinobu, Watake Asami,
Matsuda Hiromasa, Oiso Naoki. Shigeru kawaranew approach to the eval-
Menstruation in advance 1 (3%)
uation of skin color of pigmentary lesions using skin tone color scale.
Menstruation postponed 1 (3%) J Invest Dermatol 2007; 34: 441–446.
Drowsiness 1 (3%)
DOI: 10.1111/jdv.12209
*[Correction added on 22 July 2013, after first online publication: Skin
Colour values that were wrong due to a typesetting error have been
amended to ‘YR’.]

JEADV 2014, 28, 388–394 © 2013 European Academy of Dermatology and Venereology