Topical Methyl Aminolevulinate-Photodynamic Therapy for the Treatment of Actinic Keratoses and Photorejuvenation

Abstract

Background: Fair-skinned individuals exposed to ultraviolet radiation in sunlight age prematurely (photoaging) and develop actinic (solar) keratoses (AKs). Photoaging is characterized by fine lines, wrinkles, uneven or mottled pigmentation, sallow complexion, tactile roughness, erythema, and telangiectasia. The risk of malignant transformation of AKs is still debated, but as there is as yet no means to distinguish those that will transform or progress and those that will not, the ILDS (International League of Dermatological Societies) guidelines recommend adequate treatment. Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is now an established treatment for AKs that has proven efficacy and resulted in excellent cosmetic outcomes. Not only the absence of scarring or pigment changes after PDT, but also the coincidental improvement in signs of skin aging, has prompted a closer examination of the aesthetic benefits/effects (and the characterization of the mode of action) in specific targeted clinical studies. In addition, a major approved variation in MAL-PDT has been the introduction of daylight PDT utilizing visible wavelengths in sunlight to activate the protoporphyrins produced intracellularly in response to MAL exposure. The objective of this chapter is to report the efficacy of topical MAL-PDT for AK, its cosmetic outcomes and side effects. Multiple electronic databases were searched for studies involving MAL-PDT, AK, and photoaging. The Cochrane Central Register of Controlled Trials was also searched. Additionally, cited references of all trials identified and key review articles were assessed. A total of 18 studies which studied MAL-PDT to treat AKs were included in this review. Four studies compared MAL-PDT and cryotherapy; 3 other studies compared MAL-PDT with placebo cream. Only 1 study compared MAL-PDT with both cryotherapy and placebo, while 1 report examined proprietary MAL-PDT in comparison with compounded aminolevulinic acid (ALA) PDT. Two studies compared differences in treatment regimens; dose, and treatment interval. One study compared MAL-PDT with imiquimod 5% cream, 1 with diclofenac in hyaluronic acid gel, and 2 with new ALA formulations. Three studies examined daylight MAL-PDT for AKs. MAL-PDT is effective as a treatment for AK lesions, especially on the face and scalp. The cosmetic outcome is excellent and superior to cryotherapy in terms of minimum skin discoloration and scarring. The side effects, including skin ‘burning', pain, and erythema, have been reported as tolerable. The introduction of daylight MAL-PDT has removed pain, a potential barrier to utilization of the procedure, from the decision-making process. Further work is required to explore the application of MAL-PDT as a photorejuvenation technique.