Treatment of Melasma in Asian Skin Using a Fractional H S

Treatment of Melasma in Asian Skin Using a Fractional
1,550-nm Laser: An Open Clinical Study
HYOUN SEUNG LEE, MD, CHONG HYUN WON, MD,y DONG HUN LEE, MD,zyz JEE SOO AN, MD,zyz
HANG WOOK CHANG, MD,J JONG HEE LEE, MD, KYU HAN KIM, MD,zyz SOYUN CHO, MD, AND
JIN HO CHUNG, MDzyz
BACKGROUND Melasma is a common hyperpigmentation disorder that can cause refractory cosmetic
disfigurement, especially in Asians. Fractional photothermolysis (FP) has been reported to be effective
for the treatment of melasma, despite small study populations and short follow-up periods.
OBJECTIVE
To evaluate the efficacy and safety of FP for the treatment of melasma in Asians.
PATIENTS AND METHODS Twenty-five patients with melasma received four monthly FP sessions and
were followed up to 24 weeks after treatment completion. Efficacy was evaluated using objective and
subjective ratings, Melasma Area and Severity Index (MASI), melanin index tracking, and skin elasticity
measurements.
RESULTS Investigators observed clinical improvements in 60% and patients in 44% at 4 weeks after
treatment, but the figures decreased to 52% and 35%, respectively, at 24 weeks after treatment. Mean
MASI scores decreased significantly from 7.6 to 6.2. Mean melanin index decreased significantly after
the first two sessions, but it relapsed slightly in subsequent follow-ups. The treatment did not alter skin
elasticity. Hyperpigmentation was observed in three of 23 subjects (13%).
CONCLUSION Treatment of melasma with FP led to some clinical improvements, but it was not as
efficacious as previously reported at 6-month follow-up. We recommend judicious use of FP for the
treatment of melasma in Asian skin because of its limited efficacy.
The authors have indicated no significant interest with commercial supporters.
M
elasma is a common acquired hypermelanosis
characterized by irregular light- to darkbrown macules and patches on sun-exposed areas of
the skin. It is common in Asian and Hispanic
women.1 In spite of its high prevalence, its pathogenesis has not been clearly defined. Numerous
treatment options, including topical agents such as
hydroquinone, retinoic acid, and chemical peels,
have been tried, but most of them have therapeutic
limitations.2–6 A few kinds of ablative laser resurfacing, including pulsed carbon dioxide laser and
erbium-doped yttrium aluminum garnet laser resurfacing, have been reported successful, but these
require significant downtime and have risks of significant complications.7–9
Fractional resurfacing laser devices have recently
been introduced for the treatment of various skin
conditions such as melasma, freckles, pigmentation,
facial rhytides, surgical scars, and acne scars.10–12
Fraxel laser (Solta Medical, Inc., Hayward, CA)
treatment is one of the mostly widely used fractional
photothermolysis (FP) techniques in Korea and has
been applied effectively for the treatment of wrinkles, photodamaged skin, acne scars, and dyschromia.13–15 Some pilot studies have showed the
Gowoonsesang Dermatology Clinic, Seoul, Korea; yDepartment of Dermatology, Asan Medical Centre, College of
Medicine, University of Ulsan, Ulsan; zDepartment of Dermatology and yLaboratory of Cutaneous Aging Research,
Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; zInstitute of Dermatological Science, Seoul
National University, Seoul, Korea; JAmi Clinic, Seoul, Korea; Department of Dermatology, Boramae Hospital, Seoul
National University College of Medicine, Seoul, Korea
& 2009 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2009;35:1499–1504 DOI: 10.1111/j.1524-4725.2009.01264.x
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effectiveness of FP in melasma, but the study populations were small, and the follow-up periods were
short.16,17 Thus, its therapeutic efficacy and safety
for larger populations with Asian skin have not been
well investigated. We postulated that FP could be a
treatment modality for melasma, especially in patients with darker skin. The aim of this study was to
evaluate the efficacy and safety of fractional photothermolysis for the treatment of melasma in Asian
patients.
Patients and Methods
Outcome measures included objective and subjective
ratings and quantitative determination of melanin
indices (MIs) and erythema indices (EI) using a narrow-band reflectance spectrophotometer (DermaSpectrometer, Cortex Technology, Hadsund,
Denmark) and of skin elasticity using a noninvasive
in vivo suction skin elasticity meter (Cutometer MPA
580, CK Electronics, Ko¨ln, Germany). To quantify
the changes in pigmentation after treatment, the
Melasma Area and Severity Index (MASI) was used
for clinical assessment. According to the MASI score
determined by Kimbrough-Green and colleagues,18
the whole face is divided into four areas: the forehead, right malar, left malar, and chin, corresponding
to 30, 30, 30, and 10% of the total face area,
respectively. The grade of melasma severity was
determined according to three variables: the percentages 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 (maximum);
and the homogeneity of hyperpigmentation, on a
scale of 0 (minimal) to 4 (maximum). The MASI was
then calculated according to the following equation:
Twenty-five women with clinical diagnosis of melasma were recruited for the 36-week prospective
open study. Exclusion criteria included pregnant or
nursing women, the use of hydroquinone, topical or
systemic treatment with vitamin A analog including
tretinoin, the use of a topical bleaching agent within
2 months before the study, a history of laser treatment or chemical peeling on facial lesion within
6 months before the study, and the use of contraceptive pills at the time of the study or in the preMASI = 0.3 (DF 1 HF)AF 1 0.3 (DMR 1 HMR)AMR
vious 6 months. This clinical study was performed in
10.3 (DML1HML)AML 1 0.1(DC 1 HC) AC, where
accordance with the Declaration of Helsinki (1975)
D is darkness, H is homogeneity, A is area, F is
and was approved by the Institutional Review Board
forehead, MR is right malar, ML is left malar, and
of Seoul National University Hospital. We explained
C is chin.
the procedures, risks, benefits, potential complications, and side effects of the procedure to all subjects,
A high MASI score correlates with severe hyperpigand written informed consent was obtained from
mentation. Safety evaluations were performed at
each patient before commencement of this study.
each follow-up visit, and any reported adverse effects
Four sessions of FP treatment were performed on
were recorded.
each subject. After 1 hour of occlusive application of
topical anesthetic cream (eutectic mixture of lidoFor statistical analysis, data obtained at each visit
caine and prilocaine, AstraZeneca, Wilmington,
were compared with baseline data using the WilDE), the involved area of the cheeks was irradiated
coxon signed rank test in SPSS software (version
with a 1,550-nm erbium-doped FP laser (Fraxel la12.0, SPSS Inc., Chicago, IL). Data are expressed as
ser) at a fluence of 15 mJ/microthermal zone (MTZ)
means 7 standard errors, and po.05 was considered
and a density of 125 MTZ/pass with eight passes.
to be statistically significant.
Follow-up evaluations were made at 4-week intervals during the 12-week treatment period and
Results
at 4 weeks and 24 weeks after the final session
Twenty-five subjects with facial melasma (Fitzpat(total study duration, 36 weeks from treatment
rick skin type III or IV) were enrolled in this study.
commencement).
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LEE ET AL
Figure 1. Clinical appearance of a 49-year-old patient with melasma during the study.
Their ages ranged from 32 to 53 years (mean 7 SD
age was 40.6 7 6.3). All patients completed the
16-week follow-up (4 weeks after the final session),
but two subjects were lost to follow-up by the
24-week posttreatment follow-up.
Figure 1 shows serial photographs of a representative patient with melasma during the study.
Four weeks after the final treatment session, the
global assessment of melasma improvement by
dermatologists was as follows; of 25 patients,
six (24%) were evaluated as definitely improved,
15 (60%) as improved, nine (36%) as slightly
improved, 10 (40%) as no change, and none
(0%) as aggravated. Twenty-four weeks after
treatment completion, four of 23 patients
(17.4%) were assessed as definitely improved,
eight (34.8%) as slightly improved, eight (34.8%)
as stationary, and three (13%) as aggravated
(Figure 2).
Figure 2. Investigators’ global assessment of changes in
melasma severity.
The patients’ subjective global assessment of
melasma improvement at 4 weeks after the final
session was as follows; of 25 patients, two (8%)
graded their skin lesion as definitely improved, nine
(36%) as slightly improved, 11 (44%) as stationary,
and three (12%) as aggravated. At 24 weeks after
treatment completion, eight of 23 patients (34.8%)
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increase subsequently (Figure 4). FP-induced
decreases in EI and MI scores as a function
of time indicate laser-induced improvement in
vascularity and melanin turnover.19 Skin elasticity
as measured using the Cutometer showed no remarkable changes during or after FP treatment
(data not shown).
Figure 3. Patients’ subjective global assessment of changes
in melasma severity.
rated their skin lesion as slightly improved,
11 (47.8%) as stationary, and 4 (17.4%) as aggravated because of postinflammatory hyperpigmentation (Figure 3). Mean MASI scores decreased
from 7.6 7 0.7 (range 3.2–14.7) at baseline to
6.2 7 0.5 (range 1.8–10.2) at 36 weeks (p = .03,
Wilcoxon signed rank test), concurring with the
improvement of melasma rated by physicians
and patients.
FP-treated melasma lesions showed a significant
decrease in mean MI after the first two sessions
(p = .02 and p = .01, respectively, vs baseline)
but a slight increase afterwards in MI (Figure 4).
EI also decreased significantly after the first
session (p = .004 vs baseline) but showed a gradual
Treatment-related pain was well tolerated with
topical anesthesia. Transient local swelling on the
treated area, long-lasting (44 weeks) erythema, and
hyperpigmentation were reported as adverse events,
but no patient dropped out of the study because of
these adverse events. At the end of the study, hyperpigmentation was partially observed in three of 23
subjects (13%).
Discussion
Melasma is a common dermatologic condition in
dark-skinned women, but currently available conventional treatments have limited value.20 Given the
high incidence of postinflammatory hyperpigmentation and unpredictable efficacy, laser treatment for
the treatment of melasma has not been recommended routinely.21 Recently developed FP techniques have been known to be used effectively for the
treatment of wrinkles, photodamaged skin, acne
scars, and dyschromia.13–15 There are preliminary
Figure 4. Changes in melanin indices and erythema indices during the study. (A) Mean melanin index showed a significant
decrease from baseline to week 8 (4 weeks after 2nd session) but a slight increase afterwards. (B) Mean erythema index also
exhibited a temporary but significant decrease at week 4. a.u., arbitrary unit. Error bars indicate standard errors of the
means. po.05 versus baseline.
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LEE ET AL
reports on the effectiveness of FP on melasma as
well.16,17 Rokhsar and Fitzpatrick16 treated 10 female patients with recalcitrant melasma using 1,535nm and 1,550-nm Fraxel lasers (6–12 mJ/MTZ with
2,000–3,500 MTZ/cm2) at 1- to 2-week intervals.
The physicians’ assessment at 3-month follow-up
revealed that six patients achieved 75% to 100%
clearing and three had less than 25% improvement.
Patients’ evaluations were in good agreement with
physicians’.
In the present study, we demonstrated the efficacy
and safety of FP for the treatment of melasma
in Asian women. At 4 weeks after treatment
completion, a physician assessed 60% of patients
as improved, and 44% of subjects assessed themselves as improved, although these improvements
showed a slight decline subsequently, which
resulted in 52.2% and 34.8%, respectively,
assessed as improved 24 weeks after treatment.
In addition, although MI revealed a significant improvement after the first two sessions, it deteriorated
after the third session (12 weeks after commencement of the study) and plateaued in subsequent
follow-ups.
Recently, new insights into the pathogenesis of melasma have been suggested, based on the comparison
of histological characteristics between lesional and
nonlesional skin.22–24 These studies indicate that
pathologic dermal changes such as altered fibroblasts
or greater vascularity are implicated in the pathogenesis of melasma.22–24
The so-called ‘‘melanin shuttle function’’ and remodeling of the underlying pathologic dermis below
melasma lesions suggested the possible mechanism
of FP for the treatment of pigmentation.25 Melanin
shuttle was proposed based on the observation that
some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the
epidermis to be exfoliated through the stratum
corneum after FP treatment.25 Some positive clinical
results after FP on pigmentation16,17 might favor this
suggested mechanism.
In this respect, the results of our study suggest that,
in some patients, the depth affected by FP appeared
not to be deep enough to cause dermal remodeling to
suppress the activation of melanocytes, and the
elimination of melanin pigment by melanin shuttle
occurred temporarily, leading to reappearance of
melanin after the third treatment. The rebound of
MI during and after the treatment period supports
these assumptions.
In conclusion, FP affords a new treatment modality
for melasma, but the therapeutic efficacy of FP in our
study did not differ significantly from that of conventional treatments,4,8,20,21 in contrast to previously published overly optimistic results. More
studies are needed to define the exact place of FP in
the treatment of melasma.
References
1. Sanchez NP, Pathak MA, Sato S, et al. Melasma: a clinical, light
microscopic, ultrastructural, and immunofluorescence study. J Am
Acad Dermatol 1981;4:698–710.
2. Griffiths CE, Finkel LJ, Ditre CM, et al. Topical tretinoin (retinoic
acid) improves melasma. A vehicle-controlled, clinical trial. Br J
Dermatol 1993;129:415–21.
3. Grimes PE. The safety and efficacy of salicylic acid chemical peels
in darker racial-ethnic groups. Dermatol Surg 1999;25:18–22.
4. Haddad AL, Matos LF, Brunstein F, et al. A clinical, prospective,
randomized, double-blind trial comparing skin whitening complex with hydroquinone vs. placebo in the treatment of melasma.
Int J Dermatol 2003;42:153–6.
5. Khunger N, Sarkar R, Jain RK. Tretinoin peels versus glycolic acid
peels in the treatment of melasma in dark-skinned patients.
Dermatol Surg 2004;30:756–60; discussion 60.
6. Sarkar R, Kaur C, Bhalla M, et al. The combination of glycolic
acid peels with a topical regimen in the treatment of melasma in
dark-skinned patients: a comparative study. Dermatol Surg
2002;28:828–32; discussion 32.
7. Goldberg DJ. Benign pigmented lesions of the skin. Treatment
with the Q-switched ruby laser. J Dermatol Surg Oncol
1993;19:376–9.
8. Manaloto RM, Alster T. Erbium:YAG laser resurfacing for refractory melasma. Dermatol Surg 1999;25:121–3.
9. Nouri K, Bowes L, Chartier T, et al. Combination treatment of
melasma with pulsed CO2 laser followed by Q-switched alexandrite laser: a pilot study. Dermatol Surg 1999;25:494–7.
10. Geronemus RG. Fractional photothermolysis: current and future
applications. Lasers Surg Med 2006;38:169–76.
35:10:OCTOBER 2009
1503
F R A C T I O N A L P H O T O T H E R M O LY S I S F O R M E L A S M A
11. Manstein D, Herron GS, Sink RK, et al. Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med
2004;34:426–38.
12. Narurkar VA. Skin rejuvenation with microthermal fractional
photothermolysis. Dermatol Ther 2007;20Suppl 1:S10–3.
13. Chiu RJ, Kridel RW. Fractionated photothermolysis: the Fraxel
1,550-nm glass fiber laser treatment. Facial Plast Surg Clin North
Am 2007;15:229–37, vii.
14. Lee HS, Lee JH, Ahn GY, et al. Fractional photothermolysis
for the treatment of acne scars: a report of 27 Korean patients.
J Dermatol Treat 2008;19:45–9.
15. Wanner M, Tanzi EL, Alster TS. Fractional photothermolysis:
treatment of facial and nonfacial cutaneous photodamage
with a 1,550-nm erbium-doped fiber laser. Dermatol Surg
2007;33:23–8.
16. Rokhsar CK, Fitzpatrick RE. The treatment of melasma with
fractional photothermolysis: a pilot study. Dermatol Surg
2005;31:1645–50.
19. Kim BJ, Lee DH, Kim MN, et al. Fractional photothermolysis for
the treatment of striae distensae in Asian skin. Am J Clin
Dermatol 2008;9:33–7.
20. Rendon M, Berneburg M, Arellano I, et al. Treatment of melasma.
J Am Acad Dermatol 2006;54:S272–81.
21. Briganti S, Camera E, Picardo M. Chemical and instrumental
approaches to treat hyperpigmentation. Pigment Cell Res
2003;16:101–10.
22. Kang HY, Hwang JS, Lee JY, et al. The dermal stem cell factor
and c-kit are overexpressed in melasma. Br J Dermatol
2006;154:1094–9.
23. Kang WH, Yoon KH, Lee ES, et al. Melasma: histopathological
characteristics in 56 Korean patients. Br J Dermatol
2002;146:228–37.
24. Kim EH, Kim YC, Lee ES, et al. The vascular characteristics of
melasma. J Dermatol Sci 2007;46:111–6.
25. Hantash BM, Bedi VP, Sudireddy V, et al. Laser-induced transepidermal elimination of dermal content by fractional photothermolysis. J Biomed Opt 2006;11:041115.
17. Tannous ZS, Astner S. Utilizing fractional resurfacing in the
treatment of therapy-resistant melasma. J Cosmet Laser Ther
2005;7:39–43.
18. 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:
727–33.
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Address correspondence and reprint requests to: Jin Ho
Chung, MD, Department of Dermatology, Seoul National
University Hospital, 28, Yongon-dong, Chongno-Gu,
Seoul 110-744, Korea, or e-mail: jhchung@snu.ac.kr