ORIGINAL ARTICLE

Intense Pulsed Light for the Treatment of RefractoryMelasma in Asian PersonsCHIA-CHEN WANG, MD,n CHUNG-YEE HUI, MD,w YUH-MOU SUE, MD,z

WEN-ROU WONG, MD,w§ AND HONG-SHANG HONG, MD, PHDw

nDepartment of Dermatology, Cardinal Tien Hospital, Hsintien, Taipei, Taiwan; §Graduate Institute of Clinical Sciencesand wDepartment of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan; and zDepartment of InternalMedicine, Taipei Medical University, Taipei, Taiwan

BACKGROUND. Patients with dermal or mixed-type melasmas areoften refractory to various treatments. Intense pulsed light has

been used to treat melanocytic lesions with promising results.

OBJECTIVE. The purpose of this study was to clarify the effec-tiveness of intense pulsed light for refractory melasma in Asian

persons.

METHODS. Seventeen patients were treated with intense pulsedlight, during four sessions at 4-week intervals. The patients

were also given 4% hydroquinone cream and broad-spectrumsunscreens to prevent and treat postinflammatory hyperpig-mentation. Sixteen patients in the control group were treated

with hydroquinone cream and sunscreens. The treatment effi-cacy was evaluated using reflectance spectrophotometer andpatient satisfaction questionnaire.

RESULTS. Patients in the intense pulsed light group achievedan average of 39.8% improvement in relative melanin index,

compared to 11.6% improvement in the control group(po0.05) at Week 16. Six (35%) patients in the intensepulsed light group had more than 50% improvement, comparedto two (14%) patients in the control group. Two patients

in the intense pulsed light group, however, experienced tran-sient postinflammatory hyperpigmentation, and partial re-pigmentation was noted 24 weeks after the last treatment

session.

CONCLUSION. Intense pulsed light is a safe and effective treat-ment for refractory melasma in Asian persons, with minimal

side effects. Further treatment sessions are required for main-tenance therapy.

CHIA-CHEN WANG, MD, CHUNG-YEE HUI, MD, YUH-MOU SUE, MD, WEN-ROU WONG, MD, AND HONG-SHANGHONG, MD, PHD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.

MELASMA IS an acquired masklike facial hyperpig-mentation and is commonly observed in Asian middle-aged women. Genetics, ultraviolet radiation, pregnan-cy, hormone therapies, and phototoxic drugs havebeen implicated in the pathogenesis of melasma.1,2 Inaddition to routine usage of broad-spectrum sunscreens,bleaching agents, such as hydroquinone, tretinoin,2–4

and chemical peels,5,6 have shown satisfactory resultsfor the patients with epidermal melasma. Nevertheless,patients with dermal or mixed-type melasma are ther-apeutically challenging.

In the past, attempts to treat melasma with lasersthat targeted melanin, such as Q-switched ruby laserand Q-switched Nd:YAG laser, yielded disappointingresults.7,8 Meanwhile, Er:YAG laser resurfacing, de-rmabrasion, and a combined ultrapulse CO2 laser withQ-switched alexandrite laser have been reported totreat refractory melasma successfully. Side effects, suchas postinflammatory hyperpigmentation and hypertro-

phic scars, may develop, especially in patients withdarker skin.9–11

Intense pulsed light is a noncoherent, broad-spec-trum light, ranging from 500 to 1200 nm.The pulselength, mode, delay between pulses, and fluence can allbe varied. This flexibility in choice of parameters al-lows performance of different treatments, such asphotocoagulation of vascular lesions,12 photoepilat-ion,13 photorejuvenation,14 improvement of striaedistensae,15 and removal of melanocytic lesions.16–18

For pigment disorders, intense pulsed light is associ-ated with fewer photothermal injuries and fewer sideeffects, such as postinflammatory hyperpigmentationcompared with Q-switched lasers.17,18 We conducted aprospective, case-control study among Asian womento clarify whether intense pulsed light is a safe andeffective treatment for melasma that is refractory totopical bleaching agents.

Materials and Methods

Thirty-three Taiwanese women with melasma unre-sponsive to hydroquinone cream for at least 3 monthswere enrolled in the study. Some patients had also used

r 2004 by the American Society for Dermatologic Surgery, Inc. � Published by Blackwell Publishing, Inc.ISSN: 1076-0512/04/$15.00/0 � Dermatol Surg 2004;30:1196–1200

Address correspondence and reprint requests to: Wen-Rou Wong, MD,

Department of Dermatology, Chang Gung Memorial Hospital, 199

Tung-Hwa North Road, Taipei, Taiwan, or e-mail: wongw@adm.cgmh.

org.tw.

topical tretinoin, azelaic acid, l-ascorbic acid, and/orglycolic acid without apparent clinical improvement.Patients with pregnancy, lactation, oral pills, hormonereplacement therapy, and major outdoor activitieswere excluded. One month before enrolling in thestudy, the patients stopped using bleaching agents, butcontinued to use sunscreen. An ultraviolet camera wasused to determine the type of melasma. Histories re-garding age of onset and duration of melasma, Fitz-patrick skin types, and risk factors of pregnancy ororal contraceptives were taken. The study was ap-proved by the Medical Ethics and Human ResearchCommittee of Chang Gung Memorial Hospital. Writ-ten informed consent was obtained from each patientbefore enrollment.

Patients were randomly divided into two groups.Seventeen patients were treated with a light emissionapparatus of the intense pulsed light family (Vascu-light, ESC/Sharplan, Yokneam, Israel), during foursessions at 4-week intervals. A 570-nm cutoff filter wasused in the first session, and 590 to 615 filters wereused during subsequent sessions in an attempt to treatresidual deeper pigment. During all sessions, patientswere treated with fluences of 26 to 33 J/cm2; doublemode; and pulse lengths of 3 to 4 and 4 to 5 ms, re-spectively, with a delay of 30 to 35 ms between pulses.During the procedure, chilled, colorless gel was used toprotect the epidermis and to aid in delivering the lightuniformly onto the skin surface. Mild perilesional ery-thema and graying of skin lesions indicated the end-point of each treatment. No local anesthesia wasrequired. Four percent hydroquinone cream andbroad-spectrum sunscreens were used throughout thestudy to prevent possible postinflammatory hyperpig-mentation. Any other bleaching agents were prohibit-ed. Sixteen patients were in the control group,receiving only hydroquinone cream and broad-spec-trum sunscreens.

Clinical and instrumental evaluations for the im-provement in pigmentation were conducted every 4weeks for 16 weeks in both groups. In the intensepulsed light group, patients were also followed up atWeek 36 to assess the persistence of improvement.Digital photography documentation under the samecondition (light source, room, and camera) was takenat baseline and every visit. A reflectance spectropho-tometer (Mexameter 18, Courage1Khazaka Electron-ic GmbH, Koln, Germany) was used to quantifychanges in melanin level.19 Absolute melanin index ofmelasma was obtained by taking the mean of fivemeasurements from a fixed spot within the area ofpigmentation at each visit. The spot was recorded asthe distance in centimeters either from the upper earpole on line A1, A2, A3, or A4 or from the earlobe online B1, B2, B3, or B4 on the left or right side of the

face, depending on the location of melasma (Figure 1).Relative melanin index was calculated from the dif-ference of the absolute melanin index between me-lasma and normal skin.

Relative melanin index (RMI)5Absolute melaninindex of melasma�Absolute melanin index of normalskin

Improvement rate ¼ ½ðRMIpretreatment�RMIposttreatmentÞ=

RMIpretreatment� � 100%:

An objective assessment of the improvement ratewas documented as follows: excellent, 76% to 100%;good, 51% to 75%; fair, 26% to 50%; poor, 0 to 25%or darker. In addition, all patients completed a ques-tionnaire using a grading system to assess their sub-jective satisfaction with the treatment as follows: verysatisfied, satisfied, slightly satisfied, and unsatisfied. Inthe intense pulsed light group, the degree of pain, ery-thema, and blistering was assessed immediately aftereach treatment as mild, moderate, or severe. Statisticalanalysis was performed by using t test, paired t test,and simple linear regression. A p value of less than0.05 defined statistical significance. All values wereexpressed as means � standard deviation.

Results

Thirty-one patients completed the study at Week 16.Two patients in the control group dropped out atWeek 8 because of poor compliance. One patient inthe intense pulsed light group failed to complete theWeek 36 follow-up because she moved away. All pa-tients were women with skin phototypes III or IV andwere determined as mixed melasma by ultravioletcamera. There were no significant differences inany variables such as age, duration of melasma, skin

Figure 1. The definitions of the lines used to locate the fixed spot forthe measurement of melanin index. Line A1, from upper ear pole toeyebrow; line A2, from upper ear pole to lateral canthus; line A3, fromupper ear pole to nose angle; line A4, from upper ear pole to mouthangle. Line B1, from earlobe to eyebrow; line B2, from earlobe tolateral canthus; line B3, from earlobe to nose angle; line B4, fromearlobe to mouth angle.

Dermatol Surg 30:9:September 2004 WANG ET AL.: INTENSE PULSED LIGHT FOR REFRACTORY MELASMA 1197

phototypes, and baseline relative melanin index scoresbetween the two groups (p40.05) (Table 1).

In the intense pulsed light group, the mean relativemelanin index score decreased from 66.1 � 24.7 atbaseline to 49.7 � 18.3 after only one session of in-tense pulsed light treatment at Week 4, representing a24.8% change in pigmentation, which is statisticallysignificant (po0.05). Patients had further improve-ment in pigmentation with subsequent treatment ses-sions. After four sessions of intense pulsed lighttreatment, the mean relative melanin index score de-creased to 39.8 � 22.6 at Week 16, representing a39.8% improvement compared to that of the baseline(po0.005). The excellent/good (51%–100%) level inimprovement was achieved for 35% of the patients.The treatment efficacy did not correlate with any var-iables, such as age, duration of melasma, or skin pho-totypes. In the control group, the mean relativemelanin index score decreased from 67.2 � 46.5 atbaseline to 59.4 � 44.8 at Week 16, representing a11.6% change in pigment intensity (p40.05). Only14% of the patients achieved the good (51%–75%)level at the end of treatment. The difference in im-provement rate between the two groups was alsofound to be significant (po0.05), with a better re-sponse in the intense pulsed light group. At Week 36(24 weeks after the last treatment session), the meanrelative melanin index score for the intense pulsed lightgroup returned to 50.1 � 18.7, representing a per-centage change of 24.2% compared to baseline(po0.05). These results suggested that additionaltreatments were necessary to maintain the results(Tables 1 and 2; Figures 2–4). In the intense pulsedlight group, 23.5% of the patients assessed their im-provement as satisfied, 53% as slightly satisfied, and23.5% as unsatisfied. In the control group, 64% of thepatients assessed their improvement as slightly satisfiedand 36% as unsatisfied.

Few side effects were associated with intense pulsedlight treatment. Erythema and pain during and aftertreatment were mild and disappeared within 1 day. Inmost patients, microcrust formation was noted, butthese disappeared after 1 to 2 weeks. Patients coulduse makeup immediately after treatment and did notneed any wound care. No wound infection or scarringformation was noted. Two patients, however, experi-enced transient postinflammatory hyperpigmentationpossibly because of higher fluence energy. The hyper-pigmentation gradually resolved using hydroquinone

Table 1. Characteristics of Both Groups of the MelasmaPatients

General Data

Group

Intense Pulsed Light Control

Age (years) 45.0 � 4.9 47.3 � 6.7

Duration (years) 10.1 � 5.8 10.7 � 7.0

Skin phototypes III, 3; IV, 14 III, 3; IV, 13

Relative melanin index score

Baseline 66.1 � 24.7 (n517) 67.2 � 46.5 (n5 16)

16 weeks 39.8 � 22.6 (n517)nw 59.4 � 44.8 (n5 14)w

36 weeks 50.1 � 18.7 (n516)z Not done

nStatistically significant improvement within the group (paired t test), po0.005.wStatistically significant difference between the intense pulsed light and controlgroup (t test), po0.05.zStatistically significant improvement within the group (paired t test), po0.05.

Figure 2. Mean relative melanin index (RMI) score for the intensepulsed light and control groups at different posttreatment intervals.

Figure 3. Standard digital photography at baseline (A) and Week 16(B) of a 41-year-old woman in the intense pulsed light group.

Table 2. Improvement Rate at Week 16 Assessed by Re-flectance Spectrophotometer

Improvement

Rate Assessment

Group

Intense Pulsed

Light (n517)

Control

(n5 14)

76%–100% (excellent) 2 (12%) 0 (0%)

51%–75% (good) 4 (23%) 2 (14%)

26%–50% (fair) 6 (35%) 1 (7%)

0%–25% or darker (poor) 5 (30%) 11 (79%)

1198 WANG ET AL.: INTENSE PULSED LIGHT FOR REFRACTORY MELASMA Dermatol Surg 30:9:September 2004

cream and further intense pulsed light treatment. Inaddition, most patients’ skin appeared to be brighterafter intense pulsed light treatment. Two patients inthe intense pulsed light group who had freckles andlentigines intermingled with melasma also experiencedexcellent improvement.

Discussion

Intense pulsed light is a noncoherent, broad-spectrumlight, ranging from 500 to 1200 nm.Variation of pulselength, mode, delay between pulses, and fluence can bechosen. Intense pulsed light has been used to treatmelanocytic lesions with promising results. Regardingwavelengths, intense pulsed light sources can be usedwith lower cutoff filters to treat superficial pigmenta-tion, such as freckles, and higher cutoff filters fordeeper lesions, such as nevus spilus.16–18 In this study,we demonstrated that intense pulsed light is a safe andeffective treatment for refractory melasma in Asianpersons.

Successful treatment of melasma by intense pulsedlight has been reported in studies with small sample inHispanic and Asian persons. Moreno Arias and Fer-rando16 treated two patients with epidermal melasmausing a 590-nm filter, a fluence energy of 34 J/cm2, apulse width of 3.8 ms, double mode, and a delay of20 ms. A clearance rate of 76% to 100% was achievedafter two sessions of treatment. Three patients withmixed melasma were treated using a 615-nm filter, afluence energy of 38 J/cm2, a pulse width of 4.5 ms,double mode, and a delay of 20 ms. Nevertheless, theskin lesions showed less than 25% clearance withpostinflammatory hyperpigmentation after four ses-sions of treatment. Negishi et al.20 treated 97 patientswith photoaging, including 4 cases with melasma, us-ing 550- to 570-nm filters, a fluence energy of 28 to32 J/cm2, a pulse width of 2.5 to 4 and 4 to 5 ms,

double mode, and a delay of 20 to 40 ms, three to sixsessions at 2- to 3-week intervals. Topical bleachingagents were used after the third treatment session. Skintexture as well as pigmentation improved. The authorsdid not mention, however, the type of melasma, andthere was no control group in the study.

In our experience, patients with epidermal melasmausually had better results than those with mixed-typemelasma. Most epidermal melasmas respond well totopical bleaching agents,2–4 a simpler and less expen-sive treatment. Chemical peels also show more benefitsfor epidermal melasma than mixed type.5,6 Patientswith mixed melasma are more refractory to traditionaltherapies and need alternative methods. In this study,all enrolled patients had mixed melasma and were re-fractory to many kinds of bleaching agents, includinghydroquinone cream. We used intense pulsed lightwith low fluence and long delay between pulses astreatment modality. Sun protection was advised and4% hydroquinone cream was applied throughout thestudy to prevent postinflammatory hyperpigmentationrather than treat melasma per se. An improvement rateof 39.8% was achieved after four sessions of treatmentand was significantly better than the 11.6% improve-ment rate of the control group (po0.05). Twenty-fourweeks after the last session, partial repigmentation wasnoted despite the use of hydroquinone cream andbroad-spectrum sunscreens, indicating further treat-ment sessions are required for maintenance therapy.

Reflectance spectrophotometer is quite useful forestimating accurately the intensity of pigmentation.Both absolute melanin index and relative melanin in-dex had been used in some studies.11,19 Absolute mel-anin index of normal skin in people with darker skintype may be higher than which of melasma in peoplewith lighter skin type and hence cannot reflect thegenuine severity of melasma. We used relative melaninindex because it indicates the difference in pigmenta-tion between melasma and normal skin and truly re-veals the severity of melasma. We did not conduct aside-by-side comparison, a method to avoid individualbias of treatment response, for reasons of ethics andesthetics. Most of our patients refused to receive split-face treatment. The unevenness of pigmentation be-tween two sides of the face lasted up to 36 weekswould be extremely embarrassing and annoying.

Er:YAG laser resurfacing, dermabrasion, and com-bined ultrapulse CO2 laser with Q-switched alexand-rite laser were also reported to show benefits forrefractory melasma.9–11 Nevertheless, these methodsare more invasive and wound care is necessary. In ad-dition, prolonged erythema, hyperpigmentation, hypo-pigmentation, infection, and hypertrophic scarring arepotential side effects. Asian skin is prone to hyperpig-mentation after laser therapy.21 Intense pulsed light

Figure4. Standard digital photography at baseline (A) and Week 16(B) of a 42-year-old woman in the intense pulsed light group.

Dermatol Surg 30:9:September 2004 WANG ET AL.: INTENSE PULSED LIGHT FOR REFRACTORY MELASMA 1199

therapy using the variables used in this study hadminimal adverse effects and is safe to treat pigmentedlesions in Asian persons. Although no correlation be-tween the skin phototypes and treatment efficacy wasnoted, both patients with transient postinflammatoryhyperpigmentation had darker skin color. For darkerskin, a lower fluence should be used with caution.

Other superficial pigmentary anomalies, such asfreckles or lentigines, intermingled with melasma iscommon in Asian women. Prolonged postinflammato-ry hyperpigmentation, especially in Asian women withmelasma, decreases the efficacy of laser treatment. in-tense pulsed light can improve the irregularity ofdyschromia without the possibility of postinflamma-tory hyperpigmentation. Two patients in our intensepulsed light group had superimposed pigmentary le-sions in addition to melasma and both had excellentimprovement after the treatment. Furthermore, mostpatients in our intense pulsed light group also had ad-ditional benefits of brighter skin color, smoother skintexture, and uniform pigmentation. These findingssupported the safety of photorejuvenation using in-tense pulsed light, even in patients with melasma.

Based on videomicroscopic and histopathologicfindings, Kawada et al.22 proposed that the light en-ergy of intense pulsed light induced the injury of mel-anin-containing epidermal cells via photothermaleffects. Clinical improvement of pigmented lesionswas seen when microcrusts were formed and droppedoff with melanin pigment. The effects of intense pulsedlight for melasma may be associated with a similarmechanism, including the destruction of dermal mel-anin. More than half of our patients experienced mi-crocrusts, which appeared 2 to 3 days after irradiationand disappeared within 1 to 2 weeks. The crustsformed on pigmented areas, not on normal skin, in-dicating that intense pulsed light was specific for mel-anin under our conditions. Intense pulsed light mayachieve selective photothermolysis of pigmented le-sions even though the pulse duration is longer than thethermal relaxation time of melanosome (70–250 ns).The disappearance of the crusts led to the clinical im-provement of the melasma. The pigments graduallyreappeared, however, possibly because deeper pigmentremained or repigmentation was induced by persistenttrigger factors.

Conclusion

Intense pulsed light is a safe and effective treatment forrefractory melasma in Asian persons, with minimalside effects under our conditions. Partial repigmenta-tion is noted in the long-term follow-up, indicatingthat additional treatment sessions are required for

maintenance therapy. Additional studies are needed toestablish the optimal treatment parameters and to de-termine the biologic mechanisms of the treatment.

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