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COPYRIGHT © 2005 JOURNAL OF DRUGS IN DERMATOLOGY

'PHOTOREJUVENATION OF FACIAL SKIN WITH TOPICAL 20%5,AMINOLEVULINIC ACID AND INTENSE PULSED LIGHT

TREATMENT: A SPLIT,FACE COMPARISON STUDYTina S. Alster MD," Elizabeth L. Tanzi MD,b Esperanza C. Welsh, MD,c

a. Director, Washington Institute of Dermatologic Laser Surgeryb. Co-Director, Washington Institute of Dermatologic Laser Surgery

c. Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine

AbstractBackground: Photorejuvenation of facial skin has been reported after intense pulsed light (IPL) therapy alone and in conjunc-tion with topica15-aminolevulinic acid (5-ALA), but no comparative studies between these regimens have been performed.

Objective: To evaluate the safety and effectiveness of combination topica15-ALA and IPL compared to IPL treatment alone.

Methods: Ten patients with mild to moderate photodamage were randomly assigned treatment with 5-ALA + IPL on one facialhalf and IPL alone on the contralateral side. Two treatments were delivered at 4-week intervals. Clinical improvement scoreswere determined by masked evaluations of digital photographs obtained at baseline, prior to each treatment session, and at 1, 3,and 6 months after the final treatment.

Results: High~r clinical improvement scores were noted on the combination 5-ALA + IPL treated areas. Mild edema, erythe-ma, and desquamation Wereobserved on the facial halves where 5-ALA was applied. No scarring or unwanted pigmentary alter-ation was seen.

Conclusions: Photodynamic therapy with combination topica15-ALA + IPL is safe and more effective for facial rejuvenationthan IPL treatment alone.

IntroductionPhotodynamic therapy (PDT) with topical 5-aminole-vulinic acid (5-ALA) is an evolving, non-invasive treat-ment for a variety of dermatologic conditions. Severalreports have documented the successful use of PDT in thetreatment of acne vulgaris, non-melanoma skin cancers,psoriasis, verrucae, sebaceous hyperplasia, and cutaneousT cell lymphoma.':"

PDT involves the application of a photosensitizing chem-ical to a specific cutaneous lesion which, when exposed tovisible light, results in excitation of the photosensitizerand consequent production of a reactive oxygen speciesthat leads to cytotoxicity. Topical application of 20%aminolevulinic acid (ALA) initiates time-dependent accu-mulation of the endogenous photosensitizer protoporphyrinIX (PpIX) in dysplastic and neoplastic dermatologic lesionsand epidermal appendages such as sebaceous glands and hairfollicles. Since hyperproliferative cells are metabolically moreactive than normal cells, they convert more ALA to PpIX.

PpIX has a large absorption peak in the Soret band (400-430 nm) and smaller absorption peaks at longer wave-lengths (509,544,584,630,690 nm), therefore, many dif-ferent light sources can be utilized for 5-ALA PDT.Shorter blue light wavelengths are most effectivelyabsorbed by 5-ALA, but have limited skin penetration.On the other hand, the longer yellow and red wavelengthscan activate 5-ALA deeper in the skin, potentially reduc-ing the number of treatments needed to exert a positiveclinical effect. Treatment discomfort reported during PDTusing blue light may also be diminished with the use oflonger wavelengths.

Intense pulsed light (IPL) therapy, wherein a light sourceemits a broad spectrum (515 -1200 nm) of wavelengths,has been reported to clinically improve rough texture, dys-pigmentation, telangiectasia, and the loss of elasticityassociated with photo damaged skin.":" While its use withtopical 5-ALA also is of apparent benefit for actinic ker-atoses and photodamage, its relative efficacy to IPL treat-

36JOURNAL OF DRUGS IN DERMATOLOGY

JANUARy/FEBRUARY 2005 • VOLUME 4 • ISSUE 1ALA + IPL vs IPL: PHOTOREJUVENATION

"ITable 1. Mean Clinical Improvement.

Treatment 1 Month 3 months 6 Months

1.251PL 1.21 . 1.28

. 1PL + 5-ALA 1.83 1.77 1.65

Quartile grading scale: 1: <25%,2: 25%-50%, 3: 51%-75%, 4: >75% improvement

ment alone has not been studied.":" The purpose of thisstudy was to evaluate the effectiveness and safety of IPLtreatment alone compared to IPL in combination with top-ical 5-ALA in the treatment of facial cutaneous photo-damage.

Materials and MethodsTen patients (2 male, 8 female, age range 38-63, mean 54.6years; SPT I and II) with mild to moderate facial photo-damage were included for study. No patient received anydermatologic facial treatments for 6 months prior to studyentry. Study exclusion criteria included pregnancy or lac-tation, use of photosensitizing drugs, active infectious dis-ease, or history of photosensitivity.

Facial halves were randomly assigned to receive treatmentwith the IPL alone or in combination with topicaI5-ALA.Topical 20% 5-ALA (Levulan" Kerastick", DUSAPharmaceuticals Inc., Wilmington, MA) was uniformlyapplied to one facial half 60 minutes prior to IPL irradia-tion. All patients were treated with an IPL source (IPLQuantum SR, Lumenis Corp., Yokneam, Israel) using a 560 nmcut-off filter at energies ranging from 27 to 30 J/cm2 (mean:29.2 J/cm2) with a double pulse of 2.4 msec and 4.0 msec (10msec delay). All IPL treatments were performed by a singleoperator using identical technique and protocol. Patients wereinstructed to use a mild hypoallergenic cleanser and moisturiz-er, followed by a broad-spectrum sunscreen and strict avoid-ance ofUVA and UVB light for 36 hours after each treatment.Table 2. Side Effects (20 treatments)

Digital photographs (Mirror Image, Canfield) wereobtained using identical camera settings, patient position-ing, and room lighting prior to each IPL treatment sessionand at 1,3, and 6 months after the final treatment. Thedegree of clinical improvement of facial photo damage wasrated by two independent observers using a quartile clini-cal grading scale (1: <25% = minimal improvement; 2:25%-50% = moderate improvement; 3: 51%-75% =marked improvement; 4: >75% = excellent improvement)using comparative photographs to baseline at each treat-ment and follow-upsession.

ResultsGreater clinical improvement was noted in the combina-tion topical 5-ALA + Il'Lrreated facial halves at all post-operative study points (mean clinical grades: 1.82 at 1month, 1.77 at 3 months, 1.65 at 6 months) than in thefacial halves receiving IPL treatment alone (mean clinicalgrades: 1.25, 1.22, and 1.28 at 1,3, and 6 months, respec-tively; Table 1, Figures 1A/B, 2A/B).

Side effects were limited to transient erythema, mildedema, and occasional desquamation, particularly aftercombination 5-ALA + 1PL therapy (Table 2). No scarringor unwanted pigmentary alteration was seen.

DiscussionAs public demand grows for less invasive, yet highly effec-tive modalities to address common cosmetic skin concerns,derma surgeons must continue to explore and develop new

treatment options and combi-nations. Intense pulsed lightphotorej uvenation has beenused successfully to improveskin dyspigmentation, texture,and telangiectasia; however, aseries of treatments (3 to 6 insuccession) are often requiredto affect significant clinicalchange.

o 30% 48 ours

o 65% ays3-4

o 5% NAo NAoScarrin yspigmentation

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JOURNAL OF DRUGS IN DERMATOLOGY ALA + IPL vs IPL: PHOTOREJUVENATIONJANUARy/FEBRUARY 2005 • VOLUME 4 • ISSUE 1

Figure 1. A 33-year-old woman with facial dyschromia on the left cheek, chin, and lip before (A) and after (B) two IPLtreatments (improvement score= 1).

Figure 2. The same woman (as in Figure 1) with facial dyschromia on the contralateral face before (A) and after (B)two combination ALA + IPL treatments (improvement score= 2).

PDT has been used in the treatment of numerous cuta-neous conditions and, more recently, for enhanced pho-torejuvenation.":" This study represents the first split-facecomparison to demonstrate short-incubation, topical 20%5-ALA PDT using an intense pulsed light source as aneffective, well-tolerated method of photorejuvenation thatresults in greater clinical improvement than IPL treatmentalone. More substantive improvement of skin color, tone,and texture was evident within 2 treatment sessions. Theincrease in side effects (erythema, edema, desquamation)observed on the 5-ALA + IPL treated areas may render thecombination procedure less acceptable by some individu-als; therefore, it is essential that the risk of a mild photo-toxic reaction be discussed with patients preoperatively.

The exact mechanism by which the addition of 5-ALAenhances photorejuvenation with IPL has not been fullyelucidated. It is likely that surface texture and pigmenta-tion improved through mild desquamation. Histological

studies have also demonstrated increased fibrosis and newcollagen formation in the dermis several months after 5-ALA-PDT for the treatment of basal-cell and squamouscell carcinomas." The reason for enhanced treatment oftelangiectasia using combined IPL and 5-ALA treatment isunclear. For intravenous or systemic administration of photo-sensitizers, the highest drug concentrations tend to occur neardermal microvasculature." Topical photosensitizers such as 5-ALA, on the other hand, accumulate predominantly inappendageal structures and hyperproliferative cells.

ConclusionThe use of short-incubation topical 5-ALA appears toenhance the effectiveness of IPL treatment for facial pho-todamage, reducing the number of treatments required forsignificant clinical improvement. Further study is warrant-ed to optimize treatment protocols through a better under-standing of the mechanisms of actions.

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ALA +IPL vs IPL: PHOTOREJUVENATION

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ADDRESS FOR CORRESPONDENCETina S. Alster MDDirectorWashington Institute of Dermatologic Laser Surgery2311 M St. NW, Suite 200Washington, DC 20037e-mail: talster®skinlaser.com