Lasers in Surgery and Medicine 43:108–113 (2011)

A Comparison of Q-Switched and Long-Pulsed AlexandriteLaser for the Treatment of Freckles and Lentigines inOriental Patients

S.G.Y. Ho,1 C.K. Yeung,1 N.P.Y. Chan, MD,1�S.Y. Shek,1 and H.H.L. Chan1,2

1Division of Dermatology, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China2Visiting Scientist, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School,Boston, Massachusetts

Background: Q-switched (QS) lasers are effective in thetreatment of freckles and lentigines in Type I and II skin,with minimal adverse effects. Long pulsed (LP) lasers havebeen proposed to be more suitable for treatment of darkerskin types.Objectives: To investigate the efficacy and adverse effectsof using QS or LP Alexandrite laser for the treatment offreckles and lentigines in Oriental patients.Methods: A prospective split-face study of 20 Chinesepatients who were randomly assigned to undergo a singleQS (50 nanosecond) or LP (100 microseconds) laser treat-ment to either side of their face was carried out. Two blindedphysicians assessed clinical efficacy using visual analoguescales of pre- and post-treatment photographs. Subjectiveassessment was evaluated using questionnaires whichdetailed the degree of pain, erythema and edema sustainedduring treatment, and improvement and satisfaction levelsat 4, 8, and 12 weeks.Results:Therewasstatisticallysignificantimprovementinpigmentation (P < 0.05) in both groups throughout thestudy, with no statistical difference found between thegroups. Postinflammatory hyperpigmentation was morefrequently found after QS treatment (22%), compared toLP treatment (6%). Majority of patients reported moderateto marked improvement in pigmentation throughout thestudy with both pulse widths, and correspondingly highlevels of satisfaction rates. More severe pain, erythemaand edema were experienced during QS Alexandritetreatment.Conclusion: LP Alexandrite is quick and effective, andcarries a lower risk of adverse effects than QS Alexandrite,for the removal of freckles and lentigines in darker skintypes. Lasers Surg. Med. 43:108–113, 2011.� 2011 Wiley-Liss, Inc.

Key words: Q-switched; long pulsed; Alexandrite laser;freckles and lentigines; postinflammatory hyperpigmenta-tion; Chinese; Oriental; Asian; lasers

INTRODUCTION

The principle of laser treatment of freckles and lentigineshas been studied extensively during the last 20 years dueto wide use of this technology. Anderson et al. [1] were the

first to demonstrate the effectiveness of Q-switched (QS)Nd:YAG laser in the treatment of cutaneous pigmentation.Since then, several lasers with wavelengths stronglyabsorbed by melanin and nanosecond pulse durations havebeen shown to treat pigmented lesions effectively andquickly. However, studies using QS Nd:YAG, QS Rubyand QS Alexandrite laser for pigmented lesions in darkerskin types have reported a PIH risk of 10–25% [2–4]. Chanet al. [4] later compared the use of different types of 532 nmNd:YAG lasers in the treatment of facial lentigines inChinese patients and found similar efficacy between QSNd:YAG and long pulsed (LP) Nd:YAG, with a higher riskof postoperative hyperpigmentation with the QS device. Itwas explained that unlike LP lasers that cause tissuedestruction purely by photothermolysis, QS lasers, withtheir short burst of high energy nanosecond radiation,exhibit both photothermal and photomechanical effects.The undesirable photomechanical effect induces damageto surrounding oxyhaemoglobin and melanin, resulting ininflammation of superficial vessels, altered activity of mel-anocytes, and subsequent PIH [5]. Other studies are also insupport of the theory that long pulsed devices are moresuitable for darker skin types in reducing the risk of PIH[2,6].

Studies using the LP 755 nm Alexandrite laser in thetreatment of superficial pigmented lesions have reportedit to be effective with minimal adverse effects [7,8]. Thesestudies were carried out predominantly on lighter-skinnedType II patients, who have a lower risk of postinflammatoryhyperpigmentation (PIH), compared to darker skin types.Large spot sizes of 7 or 10 mm were used without anyadverse effects.

Laser units with multiple modalities that are capable ofemitting beams of different spot sizes, wavelengths andpulse durations are increasingly developed in order to opti-mize functionality of each system. These laser units are

Conflict of interest: Dr. H.H.L. Chan has conducted research,received grants and free equipment from Candela.

*Corresponding to:N.P.Y. Chan,MD,13/F, ClubLusitano,16 IceHouseStreet,Central,HongKong,China.E-mail:hhlchan@hku.hk

Accepted 30 December 2010Published online 15 February 2011 in Wiley Online Library(wileyonlinelibrary.com).DOI 10.1002/lsm.21045

� 2011 Wiley-Liss, Inc.

multi-functional and saves space, and are increasinglyfavored in the clinical setting. The Candela Alex TriVant-age1 (ATV) system (Candela Corporation, Wayland, MA) isonesuchsystemcapableofproviding532,755,and1,064 nmoutput wavelengths. At the 755 nm wavelength, nominalpulse widths of either 50 nanoseconds or 100 microsecondscan be selected. Beam spot sizes of 3 or 4 mm are alsoavailable.

Our current study aims to investigate the efficacy of usinglong microsecond pulse duration or Q-switched nanosecondpulse duration of the 755 nm wavelength for the treatmentof freckles and lentigines in Oriental patients. Based onpreviousstudies,wehypothesizethatefficacywillbesimilarusing either pulse duration, but the risk of adverse effectswill be lower in the lesions treated using the long micro-second pulse duration.

METHOD

This is a prospective split-face study of 20 Chinesepatients who were randomly assigned to undergo a singleQS or LP laser treatment to either side of their face using a755 nm Alexandrite laser.

This is a FDA approved device for the treatment of super-ficial pigmentation, and all patients gave written informedconsent to participate.

Patient Selection

Twenty Chinese volunteers with a clinical diagnosis offreckles or/and lentigines were recruited. Eligible patientswerehealthymalesor females21yearsofageorolder,andofFitzpatrick skin type III–V. Pregnant and lactating womenwere excluded, as well as patients with known photosensi-tivity, recent tan, poor wound healing, significant skin con-dition or scarring in treatment area, history of keloidformation, active infection, immunosuppression or otherserious concomitant illness. All patients could not be takingphotosensitizing medications or isotretinoin in the preced-ing 6 months. They also could not have received any treat-ment with laser or other devices in the treated area duringthe preceding 6 months. All patients agreed to avoid anyother facial treatment or creams other than that prescribedby us during the study period.

All patients were randomized to have one side of the facetreated by long microsecond pulse duration (100 micro-seconds), and the other side by QS nanosecond pulseduration (50 nanosecond). The process of randomizationinvolved each patient picking one out of an initial total of20 envelopes. Each envelope contained a paper statingwhich pulse duration would be used on the left and rightside of the face.

Laser Treatment

Each patient received one session of 755 nm Alexandritelaser treatment, with each half of the face treated by either50 nanoseconds or 100 microseconds pulsewidth. Topicalanesthetic (lidocaine 2.5% and prilocaine 2.5%, EMLA1)under cling-film occlusion was applied to the whole facefor 1 hour prior to treatment. Lead eyeshields were insertedafter application of lignocaine eye drops for eye protection

during laser treatment. The device utilizes a flat beam toensure uniform delivery of treatment energy. When usingthe 100 microsecond pulse duration, a spot size of 4 mm andenergyof11–13 J/cm2 wereused.Theclinical end-pointwasdefined as an ashen-gray appearance without purpura.When treating with the 50 nanoseconds pulse duration, a3 mm spot size and 5–6.5 J/cm2 of energy were employed.The desired end point for the Q-switched treatment isimmediate whitening without bleeding. Immediately aftertreatment, a thin layer of potent topical steroid cream(mometasone furoate 0.1% cream, Schering-Plough) wasapplied to the treated areas for up to 3 days. Patients werewarnedtoavoiddirectsunlightandregularuseofsunscreenwas advised.

Subjective Assessment

Patients were assessed post-treatment to evaluate thedegree of pain sustained during treatment, and also at 4,8, and 12 weeks after. During each follow-up, patients wereasked to fill out a questionnaire detailing the degree ofclearing, erythema, edema, and satisfaction level. A visualanalogue scale was used, with ‘‘0’’ representing the mini-mum score and ‘‘10’’ representing the maximum score.Patients were asked to mark the scales accordingly.

Objective Assessment

Frontal and lateral clinical photographs were taken atbaseline and at 4, 8, and 12 weeks post-treatment using theCanfield Visia CR System1 (Canfield, NJ). This systemallows for consistent positioning of the patient’s head andimages taken had a 10-megapixel resolution. The photo-graphs were assessed by two non-treating, blinded phys-icians. Clinical efficacy was assessed using a 0–10 visualanalogue scale (VAS) to represent the degree of improve-ment. The Wilcoxon Signed Ranks test and Mann–Whitneytest were used to analyze the data. In addition, an investi-gator global assessment (IGA) was recorded, where thedegreeof improvementwasfurthercategorizedintoworsen-ing, no change, mild, moderate, or marked improvement.Adverse effects such as hyperpigmentation, hypopigmenta-tion, erythema, edema, blistering and scarring were gradedas absent, mild, moderate, or severe.

RESULTS

The patient demographics are shown in Table 1. All 20patients were female and had a clinical diagnosis of frecklesor/and lentigines. Their ages ranged from 26 to 52 years,with a mean of 39 years. Nine patients had Fitzpatrick skintype III, and 11 patients had skin type IV. Twenty patientswere treated, and 1 was lost to follow up by week 4. She wasexcluded from our data analysis. There was a patient whomissed the week 8 follow up, and another who missed theweek 12 follow up. The mean length of follow up was 3months.

Degree of Clearing

The mean scores for the degree of clearing achieved atfollow up using the microsecond and nanosecond pulse

Q-SWITCHED OR LONG PULSED ALEXANDRITE LASER IN THE MANAGEMENT OF FRECKLES AND LENTIGINES 109

widthareshowninTable2.Therewasmeanimprovementinthe degree of pigmentation for all patients at 4, 8, and12 weeks post-treatment, regardless of pulse width used.This improvement was statistically significant for themicrosecond pulse width treatment at 4, 8, and 12 weeks(P ¼ 0.001, P < 0.05, P < 0.05 respectively). Statisticalimprovement was also seen with the nanosecond pulsewidth treatment at 4, 8 and 12 weeks (P ¼ 0.001,P < 0.05, P < 0.05 respectively). However, no statisticaldifference was found when comparing the two groups toeach other (P > 0.05). Representative clinical responsesto the two lasers are shown in Figure 1.

Postinflammatory Hyperpigmentation

Mild postinflammatory hyperpigmentation (PIH) wasa common postoperative complication, affecting 1 (6%)patient treated with the microsecond pulse width, and 5(22%) patients treated with the nanosecond pulse widthat 12 weeks. No statistical difference in the rates of PIHwas found between the two pulse widths.

Hypopigmentation

Hypopigmentation was also seen postoperatively, with 1(6%) patient noted to have severe hypopigmentation atweek 4 after LP laser treatment; this gradually improvedto mild hypopigmentation at week 12. There were also 2(11%) patients with mild hypopigmentation noted at week 8after QS laser treatment; these resolved spontaneouslyby week 12. There was no statistical difference in the ratesof postinflammatory hypopigmentation between the twodifferent pulse widths employed.

Other Adverse Effects

There were no other long term adverse effects, such aserythema,edema,blistering, orscarringnotedatweeks4,8,or 12 in any of the patients treated.

Investigator Global Assessment (IGA)

The IGA assessing the overall efficacy of treatment atweek 12 is shown in Figure 2. Fifty six percent of patientsin the LP treated group were noted to have improvement insuperficial pigmentation at week 12, compared to 72% ofpatients in the nanosecond treated group. Two patients inthe LP treated group had worsening of global facial pigmen-tation;1hadPIH andtheotherhadpostinflammatory hypo-pigmentation. Although five patients were noted to havePIH at week 12 in the QS treated group, there was improve-ment in their overall facial pigmentation. Hence no patientsdemonstratedworseningofoverallpigmentationatweek12in the QS group.

Subjective Improvement

Patients’ perceptions of efficacymirrored thatof thephys-icians, with the majority of patients reporting moderate tomarked improvement in the degree of pigmentation at 4, 8,and12weekspost-treatmentwhentreatedwitheitherpulsewidth.Figure3showsthesubjectiveassessmentof improve-ment in pigmentation at week 12. Overall satisfaction rateswere also very high, with majority of patients reporting thatthey were ‘‘satisfied’’ or ‘‘very satisfied’’ during all follow upappointments. Five (27.8%) patients reported being unsa-tisfied in the LP treated group, compared to 3 (16.7%)patients in the QS treated group at the 12 weeks follow

TABLE 2. Mean Improvement of VAS for Microsecond and Nanosecond Treatment

Treatment Mean of baseline (SD) Mean of endpoint (SD) Improvement in VAS

Microsecond pulse width

4 weeks follow up 4.7 (1.1) 4.0 (0.9) 0.7

8 weeks follow up 4.7 (1.1) 3.9 (0.9) 0.8

12 weeks follow up 4.8 (1.0) 4.1 (1.0) 0.7

Nanosecond pulse width

4 weeks follow up 4.5 (1.3) 3.3 (0.9) 1.28 weeks follow up 4.4 (1.3) 3.5 (0.9) 0.9

12 weeks follow up 4.5 (1.3) 3.4 (0.9) 1.1

TABLE 1. Patient Demographics

100 Microseconds 50 Microseconds

No. of patients 19

Sex, N (%) Female, 19 (100%)

Age Range 26–52

Mean (SD) 38.5 (7.0)

Fitzpatrick skin type III: 9 (47.3%)

IV: 10 (52.6%)

Candela ATV system laser parameters Energy: 11–13 J/cm2 Energy: 5–6.5 J/cm2

Laser parameters Spot size: 4 mm Spot size: 3 mm

Mean duration of follow up in months (SD) 3.1 (0.2)

Follow up in months (SD)

110 HO ET AL.

up. Of the five patients in the LP group who reported dis-satisfaction, two did not notice any improvement in facialpigmentation and three reported worsening of pigmenta-tion. In the QS treated patients, two did not notice anyimprovement and one noticed worsening of pigmentation.

Adverse Effects Immediately Post-Treatment

Despite topical anesthetic application for 1 hour prior tolaser treatment, almost all patients reported some discom-fortduringtreatment(Fig.4),with89%ofpatientsreportingmild to moderate pain during treatment with the LP laser.During treatment with the QS laser, 58% reported mild tomoderate pain, and 37% reported severe pain.

Mild to moderate erythema and edema was seen immedi-ately post-treatment in the majority (84% and 90% respect-ively) of LP treated patients. Moderate to severe erythemaand edema was seen in all (100%) of QS treated patients.There were so signs of blistering, erosions or ulcerationimmediately post-treatment in any of the patients.

Fig. 1. Representative clinical responses to the two laser treatments.

Fig. 2. Objective assessment of improvement in pigmenta-

tion at week 12.

Q-SWITCHED OR LONG PULSED ALEXANDRITE LASER IN THE MANAGEMENT OF FRECKLES AND LENTIGINES 111

DISCUSSION

Thisprospectivesplit-facestudywasdesignedtoprovideagoodcomparisonoftheefficacyandadverseeffectsofQSandLP Alexandrite laser for the management of freckles andlentigines in Oreintal patients. Using either treatment inthis study, all patients achieved significant improvementthroughout the 12 weeks of follow up. PIH was more fre-

quently found after QS Alexandrite laser for freckles andlentigines. No severe adverse effects such as blistering orscarring were noted in any of the patients.

Patients’ subjective perception of efficacy was consistentwith physicians’ objective assessments, with majorityreporting moderate to marked improvement throughoutthe study. Satisfaction rates among patients were also cor-respondingly high. More severe pain was experiencedduring QS Alexandrite treatment, and moderate to severeerythema and edema was noted in all patients immediatelypost-QS laser treatment.

Among Alexandrite lasers, the QS Alexandrite hastraditionally been successfully used to treat benign epider-mal pigmentation such as freckles and lentigines [2,9,10].Whenusedinlightskinnedpatients,minimalcomplicationsare encountered. However in darker skinned individualswith melanin rich epidermis, the risk of PIH is recognized tobe greater [2–4]. Similar findings are found in our currentstudy, highlighting the efficacy of QS Alexandrite in target-ing superficial pigmentation, and also its limitation ofincreased PIH in Oriental skin. This is thought to be dueto the combination of photothermal and photomechanicaleffects from its short burst of high energy nanosecond radi-ation, which not only targets melanin, but induce damage tosurrounding oxyhaemoglobin and melanin as well, result-ing in inflammation of superficial vessels, altered activity ofmelanocytes, and subsequent PIH [5].

Longer wavelengths, such as that found in Alexandritelasers(755 nm),result inmoreabsorptionbytargetmelaninand minimal absorption by competing chromophores suchas oxyhemoglobin, restricting damage to the pigment ladenskin structures [11]. With its longer pulse width of100 microseconds, the LP Alexandrite also employs a gen-tler heating approach, and shows convincing results in ourcurrent study to be both effective at targeting melanin richepidermal lesions as well as minimizing any photomechan-ical effects that can result in PIH. This has been shownpreviously in skin type II patients [7,8] butnot patientswithskin type III/IV. Recent work that is due to be published byour group have noted that when using LP Alexandrite (Gen-tlelase, Candela Corporation) with a large spot size (10 mm,20–35 J/cm2,pulsewidth1.5 milliseconds,nocooling) inthetreatment of epidermal pigmentation in Oriental skin, sig-nificant improvement in epidermal pigmentation was notfound,andwasassociatedwithaveryhighriskofPIH(38%).Fromthesefindings,wehighlighted the importanceofbeamspotsize in influencingtheriskofPIH.Whenlargespotsizesare utilized, it can lead to inadvertent treatment of sur-roundingunaffectedskin,whenthe lesiontreated issmallerthan the spot size available, especially when contrastbetween the lesional and non-lesional skin is low. Our cur-rent study lends further support to this theory.

It is worth noting that patients in this study underwentjust a single treatment with either QS or LP Alexandritelaser and achieved significant improvement in their epider-malpigmentation,resultinginhighorveryhighsatisfactionlevels in the majority of patients. It can be expected thatfurther treatments will result in even better clearance ofsuch lesions. Such effective results have been shown in

Fig. 3. Subjective assessment of improvement in pigmenta-

tion at 12 weeks.

Fig. 4. Adverse events during and immediately post-treatment.

112 HO ET AL.

Asians with the QS Alexandrite in previous studies [2,10],but not the LP Alexandrite laser. Despite successful results,high rates of PIH can limit the use of QS Alexandrite, andindeed other QS devices, on Oriental skin [2,4].

Oneoftheconcernsregardingtheuseof longpulsed lasersforthetreatmentofsuperficialpigmentation isthepotentialfor thermal diffusion from the epidermis to the dermis, andthe subsequent risk of scar formation. In a previous studywhere a 514 nm argon laser was used to treat epidermalpigmented lesions, a pulse duration of 200 milliseconds wasused, and there was little evidence of histological damage totheskinadjacenttothetreatmentsites [12].Similarly inourstudy,despitetheuseofa755 nmwavelengthandlongpulsewidth of 100 milliseconds, the relatively low fluence usedensured that any thermal diffusion was minimal, and scar-ring was not found in any of our patients.

Patients’ experience during laser treatment is an import-ant consideration. Although almost all patients appeared tobe satisfied with the results, considerable discomfort duringthe procedure, and more severe erythema and swellingimmediately post-treatment, were noted with the QStreated group. LP Alexandrite, in its ability to deliver effec-tive results with less discomfort and adverse effects duringand after treatment, should therefore be recommended inthe management of freckles and lentigines in darker skintypes.

In conclusion, LP Alexandrite with a small spot size andlow fluence is a highly effective and quick modality for theremoval of freckles and lentigines in darker skin types. QSAlexandrite, although effective, causes more discomfortduring treatment, and poses a higher risk of erythema,edema, and PIH. The use of a daily broad-spectrumsunscreen, photoprotective clothing andhats, together withregulartopicalbleachingagentscanserveasusefuladjunctsto prevent any appearance or recurrence of unwanted epi-dermal pigmentation.

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