Laser-mediated photodynamic therapy of actinic cheilitis

Journal of Drugs in Dermatology, Sept-Oct, 2004 by Macrene R. Alexiades-Armenakas, Roy G. Geronemus

Abstract

Actinic cheilitis (AC) is a common precancerous condition for which a safe, effective, rapid, and cosmetically favorable treatment is needed. The objective of this study was to assess the safety and efficacy of the long-pulsed pulsed dye laser (LP PDL) (595 nm) with photodynamic therapy (PDT) for the treatment of AC. This study was designed to be a prospective, proof-of concept pilot study to assess safety and efficacy of LP PDL in conjunction with topical 20% 5-aminolevulinic acid solution PDT for the treatment of AC. Control patients received LP PDL alone. The setting was an outpatient clinical research center. A volunteer sample of 21 patients with biopsy-proven AC was enrolled (age range, 42-86 years; skin types I-III). All patients were refractory to prior therapies.

Patients with a history of herpes labialis were pre-treated with famcyclovir. Nineteen patients received one-to-three treatments of topical 20% 5-aminolevulinic acid for 2-3 hours, followed by LP PDL (595 nm) at monthly intervals. Two control patients received one treatment with LP PDL alone. Patients in the ALA-LP PDL group were followed at 1, 2, 3, 6, 9, and 12 months. Clearance of AC was assessed by clinical evaluation. Control patients were followed to the one month interval.

We observed none-to-mild pain: slight-to-moderate erythema; no crusting, purpura, or scarring; treatment time of less than one minute: and complete resolution of post-operative erythema by day three. Complete clearance was achieved in 13/19 (68%) of patients following a mean of 1.8 treatments (7/13 (37%) after one, 2/13 (11%) after two, and 1/13 (21%) after three treatments). Patients were followed for a mean of 4.1 (range 1-12) months. Among the remaining cases, partial clearing was achieved in two patients, recurrence during the follow-up interval was observed in one patient, and failure to follow-up occurred in three patients. Post-operative impetiginization occurred in three patients with erosive AC, which resolved with dicloxacillin therapy. Among the control patients, no clearing was observed.

Treatment of AC using LP PDL (595 nm) at nonpurpuric parameters following topical application of 5-aminolevulinic acid at short incubation times is safe and effective. It may offer the advantages of rapid incubation, treatment, and recovery times, minimal discomfort, excellent cosmetic outcome, and good efficacy rates. Patients with erosive AC should receive antibacterial prophylaxis. Multiple treatments may be required for complete clearing.

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Introduction

Actinic cheilitis (AC) is a precancerous condition affecting the lips, prevalent in an estimated 5% of individuals over the age of 40, which progresses to squamous cell carcinoma. Once SCC of the lower lip has occurred, metastasis rates are high at 17-25% (1-3). Multiple therapies of AC have been reported: however, they carry disadvantages such as prolonged treatment and recovery times, poor cosmetic outcomes, or questionable efficacy. Ablative treatments for AC include cryotherapy, electrodessication (ED), and carbon dioxide resurfacing. Cryotherapy and ED are appropriate for focal AC, but less favorable for extensive AC due to the disadvantages of hypopigmented scarring and delayed (approximate three weeks) recovery times (4-5). Carbon dioxide resurfacing is utilized for extensive AC; however, disadvantages include hypopigmented scarring and an approximate two week recovery time (4-5). Topical chemotherapy or immunomodulators, such as topical 5-fluorouracil and imiquimod have been used to treat extensive AC; however, they bear the disadvantages of prolonged multiple weeks' treatment and recovery times, poor post-treatment cosmesis, and questionable efficacy (4,6). High treatment failure rates of up to 60% have been reported due to patient non-compliance with this approach (7). The treatment of AC by surgical excision or vermillionectomy involves the routine risks of surgery and includes a high incidence of scarring and poor cosmetic outcome (4). Thus, an effective therapy with little-to-no down-time is needed.

We have previously shown that photodynamic therapy (PDT) in conjunction with short incubation topical 5-aminolevulinic acid (ALA) solution and the long-pulsed pulsed dye laser (LP PDL) at non-purpuric parameters is safe and effective in the treatment of actinic keratoses (AK) (8). This therapeutic approach has provided the advantages of minimal discomfort. rapid incubation, treatment, and recovery times, excellent cosmetic outcome, and high efficacy rates for head lesions. The objective of this study was to evaluate the safety and efficacy of laser-mediated PDT in the treatment of the closely related condition of AC.

Patients and Methods

This was a prospective, proof-of-concept pilot study. Twenty-one patients with biopsy-proven and/or a clinical diagnosis of AC were enrolled and informed written consent was obtained. All patients were refractory to prior therapies (Table 1). Mean age was 59 (range: 45-75) and skin phototypes I-III. Patients with a history of herpes labialis were pre-treated with oral famcyclovir 250 mg bid starting one day prior to the procedure. The lips were cleansed, and then topical 5-ALA 20% solution was applied as per the manufacturer's instructions (Levulan, DUSA pharmaceuticals). Following an incubation time of 2-3 hours, the lips were irradiated with the LP PDL (595 nm, V beam, Candela) at 7.5 J/cm2 fluence, 10 ms pulse duration, 10 mm spot size, and dynamic cooling spray at 30 ms cryogen spray and a 30 ms delay. Two-to-three passes of minimally overlapping pulses were administered to each lip. The area was cleansed and aquaphor healing ointment applied. This procedure was repeated as necessary at 1-month intervals or until complete clearing for up to three treatment sessions. Patients were followed at one, three, six, nine, and 12 months post-treatment. Two control patients were treated with the LP PDL alone and followed at the one month interval.