Effect of Retinoid Pretreatment on Outcomes of Patients Treated by Photodynamic Therapy for Actinic Keratosis of the Hand and Forearm

October 2011 | Volume 10 | Issue 10 | Original Article | 1124 | Copyright © 2011

Barry I. Galitzer MD

Abstract

Background/Objective: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been shown to be useful in both spot and field treatments of actinic keratoses (AK). This study evaluates the safety and efficacy of pretreatment of AK lesions on the dorsal hands and forearms with tazarotene gel (0.1%) twice a day for one week before broad-area ALA PDT.
Methods: Ten subjects aged 75.4 ± 11.6 years (mean ± SD) with at least four AK lesions on their dorsal forearm or hand were randomized so that one dorsal hand or forearm was pretreated with tazarotene gel (0.1%) twice daily for one week before ALA PDT with blue light. The other hand or forearm (control) was not pretreated. After seven days, ALA was applied to both sides and incubated 60 minutes before irradiation with blue light. ALA was applied first only to the AK lesions and then to the entire treatment area (defined as the extensor surface of the hand or forearm between the elbow and the base of the fingers) before 60-minute incubation. The ALA area on the control side was occluded during the 60-minute incubation. Efficacy and adverse effects were evaluated within 48 hours and eight weeks later.
Results: For both the pretreated and control group, lesion counts of the target areas decreased significantly from baseline to eight weeks after ALA PDT. Reduction percentages of the target area, however, did not differ significantly between the two groups. When reduction percentages of the entire treatment area for both groups were compared the difference between the two groups was of borderline significance (P=0.0547). When the entire treatment area was analyzed, lesion counts of the tazarotene group differed significantly from baseline at eight weeks (P=0.0002), but this was not the case with the control group (P=0.0365). Adverse events were limited to those expected after ALA PDT. Erythema was significantly more severe (P=0.0029) in the pretreated arm five minutes after ALA PDT.
Conclusion: Pretreatment of AK lesions on the dorsal hand and forearm with tazarotene gel (0.1%) may enhance the therapeutic effect of ALA PDT without serious side effects.

J Drugs Dermatol. 2011;10(10):1124-1132.

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INTRODUCTION

Actinic keratoses (AK) comprise 14 percent of visits to dermatologists in the United States.1 Since AK lesions may evolve into invasive squamous cell carcinoma (SCC), it is prudent to treat AK lesions promptly. Treatment options include cryosurgery, curettage, dermabrasion, excision, chemical peels, 5-fluorouracil (5-FU), laser resurfacing, and topical agents such as retinoids, diclofenac and imiquimod. The choice of treatment depends on lesion thickness, number and anatomic location of lesions, skin type, patient preferences, reimbursement issues, cosmesis and physician experience.2

Photodynamic therapy (PDT) with either 5-aminolevulinic acid (ALA) or methylaminolevulinate (MAL) has been shown to be selective, useful in both spot and field treatments, and cosmetically beneficial for the treatment of AK.2 ALA PDT is based on the use of a topical photosensitizing agent (ALA) that penetrates the stratum corneum of actinically damaged cells where it undergoes conversion to protoporphyrin IX (PpIX), a photosensitive compound which, when irradiated with light energy of the appropriate wavelength, undergoes degradation to cytotoxic reactive oxygen species.3

Topical treatments are useful in treating multiple lesions over a large area whereas destructive procedures such as cyrotherapy are effective against thick, hyperkeratotic, and isolated lesions.4 Retinoids have strong antiproliferative and differentiation-inducing effects.5 A well-known example is topical tretinoin (all-trans-retinoic acid) which improves the appearance of photodamaged skin.6,7 Tretinoin (0.1%) also reduces AK lesions in the forearms and hands.5,8-10 Isotretinoin has shown efficacy in reducing AK lesions of the face, but not the scalp or extremities.11 Tazarotene cream has been shown to reduce the severity

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