Treatment of Actinic Cheilitis by Photodynamic Therapy With 5-Aminolevulinic Acid and Blue Light Activation

November 2011 | Volume 10 | Issue 11 | Original Article | 1240 | Copyright © November 2011


Martin Zaiac MD and Annabelle Clement MMS PA-C

Abstract
Actinic cheilitis (AC), a common disorder of the lower lip, should be treated early to prevent progression to invasive squamous cell carcinoma. This study evaluated the safety and efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) activated by blue light for the treatment of AC. Fifteen patients with clinically evident or biopsy-proven AC received two treatments with ALA PDT with blue light activation. Treatments were spaced three to five weeks apart. Most patients achieved 65% to 75% clearance three to five weeks after the first treatment and all achieved more than 75% clearance one month after the second treatment. Three patients achieved complete clearance. Pain and burning during irradiation were absent or mild. All patients said they would repeat the procedure. ALA PDT with 417 nm blue light is a promising option for the treatment of AC of the lower lip.

J Drugs Dermatol. 2011;10(11):1240-1245.

INTRODUCTION

Actinic cheilitis (AC) is a precancerous malformation, usually of the lower lip. The condition is especially common among fair-skinned men frequently exposed to the UV radiation of sunlight.1 Early treatment is recommended because approximately 17 percent of AC lesions may develop into invasive squamous cell carcinoma (SCC) of the lower lip, whose rates of metastasis are four times that of cutaneous SCC.2-4 Early stage AC is marked by erythema and edema, followed by scaling and in some cases leukoplakia. Erythroplasia and linear fissures perpendicular to the lip may also develop.5
Current treatment options for AC are presented in Table 1. Ablative methods, though effective, require skill, are expensive, and carry the risk of scarring and long recovery times. Topical therapies are inexpensive but have limited efficacy and are often associated with noncompliance and side effects that may cause patients to discontinue treatment.
Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) may be a superior alternative. The photosensitizing agent, ALA, when absorbed by cells, enters into the heme biosynthesis pathway, causing buildup of photosensitive porphyrins, particularly protoporphyrin IX (PpIX). When irradiated with wavelengths of light in PpIX's absorption spectrum, PpIX is activated to produce cytotoxic singlet oxygen. Abnormal keratin more readily absorbs ALA than normal keratin, conferring specificity. ALA PDT has been used to treat epithelial skin tumors such as actinic keratosis and superficial basal cell carcinoma, 12-14 as well as acne, sebaceous skin, and photodamage.15 This prospective study assessed the efficacy, safety, and tolerability of ALA PDT with 417-nm blue light for the treatment of AC.

METHODS

Sixteen patients (skin types I–III, nine women, seven men, 28–73 years of age) with AC untreated during the previous three months were enrolled. The study was conducted in a private office setting. Diagnosis of AC was by histopathological evaluation of biopsy specimen (n=5) or clinical presentation (n=11). Two patients had a history of squamous cell carcinoma. Patients had failed cryotherapy with liquid nitrogen or could not tolerate imiquimod. None had a history of herpes labialis. All patients provided signed informed consent to treatment.
Patients received two ALA PDT treatments separated by three to five weeks. For the first, the lower lip of each subject was cleansed with mild soap and water and then alcohol. When the lip was dry, ALA (Levulan ® Kerastick,® Dusa Pharmaceuticals, Wilmington, MA) was applied liberally as recommended by the manufacturer and allowed to incubate 60 minutes. The ALAtreated area was exposed to 417 nm blue light (BLU-U, Dusa Pharmaceuticals) for 16 min, 40s. After irradiation, the area was cleaned with mild cleanser and coated with occlusive sunblock. Patients were instructed to keep the treated areas clean, avoid scratching, and apply sunblock daily until the study was completed. The procedure for the second ALA-PDT treatment was identical to the first, except that ALA was incubated for 90 rather than 60 minutes to increase the intensity of the reaction with blue light.