Author:
Joel L. Cohen, MD, Director, AboutSkin Dermatology and DermSurgery, Englewood and Lone Tree, Colorado

Introduction

While the current FDA approval for topical photodynamic therapy (PDT) remains the treatment of actinic keratoses, the spectrum of clinical conditions that have reports of efficacy with PDT continues to grow.

In early 2008, there have already been several important meetings where experts have expanded on their clinical use and research regarding this exciting and evolving therapy in cutaneous medicine (American Academy of Dermatology, South Beach Symposium and Maui Derm). This column will include content from the updates by Mark Nestor, Michael Gold, Bill Hanke and Amy Taub at the February, South Beach Symposium in Miami. At relevant points, I will also interject my extensive personal experience using PDT in my own clinical practice which focuses on cutaneous oncology and aesthetic dermatology. As a matter of disclosure of potential conflict of interest, I want to indicate that I am currently a consultant to DUSA Pharmaceuticals (Wilmington, MA), the makers of the Levulan^® (aminolevulinic acid HCl, ALA) Kerastick^® and the BLU-U^®.

Overview of PDT

The effects of PDT for the treatment of cutaneous conditions appears to be largely due to a cytotoxic effect achieved through the production of singlet oxygen. First, ALA diffuses thru the stratum corneum to the epidermis and dermis. Second, cells of epidermal origin actively take up ALA via an amino acid transport pathway and then convert ALA to protoporphyrin IX (PpIX), which accumulates within target cells. Last, light source irradiation of the appropriate wavelength and energy activates PpIX, which then transfers the energy to molecular oxygen, leading to the formation of singlet oxygen which remains in the cell in which it is made. This creates perforations in the mitochondrial and cell membranes, leading to cell death via direct cytotoxicity as well as by triggering apoptosis. The release of cell contents into the stroma triggers an inflammatory response generally peaking within 24 hours of the PDT procedure.

In 1999, PDT using the Levulan^® Kerastick^® together with blue light received FDA clearance for the treatment of non-hypertrophic actinic keratoses (AK) of the face and scalp. Levulan^® Kerastick^® remains the only available form of ALA in the US, though a second PDT photosensitizer, methyl aminolevulinate Metvix^® (Galderma Laboratories, Paris, France and PhotoCure AS, Oslo, Norway) has been FDA approved as second-line therapy for the treatment of non-hyperkeratotic AKs of the face and scalp not amenable to conventional therapy. Despite FDA approval, however, Metvix^® has not yet been launched in the US market. This review will thus focus on the use of Levulan^® Kerastick^® in clinical dermatologic practice.

As with many procedures in our field, it is not only the actual in-office treatment session but also the pre-treatment and post-treatment time periods that can be quite important in determining the level of response with this type of therapy. These three variables of pre-treatment preparation of the skin, light source factors during the actual office procedure, and post-treatment patient instruction are the key elements in the efficacy and safety of this procedure for dermatologic conditions. As AK's have the actual FDA indication for PDT, I will review these parameters in reference to their treatment but later highlight some areas of relevance to the treatment of other conditions, particularly photodamage and acne.