Photodynamic therapy comes of age

Journal of Drugs in Dermatology, Jan-Feb, 2004 by Mitchel P. Goldman

Photodynamic therapy (PDT), utilizing the topical administration of 20% 5-aminolevulinic acid (ALA), has generated widespread interest in the past several years among dermatologists. Numerous dermatologic conditions ranging from actinic keratosis to acne vulgaris have been successfully treated with the combination of ALA-PDT and newer applications with this therapy are emerging making ALA-PDT an exciting therapeutic modality for dermatologists.

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This special supplement to the Journal of Drugs in Dermatology contains four important articles on photodynamic therapy. The review article, "Photodynamic Therapy in Dermatology: History and Horizons" by Amy Taub, MD examines the historical roots of PDT from the early 1900's to the introduction of less sensitizing 5-ALA in the 1970's and the cutaneous form of 5-ALA introduced recently by DUSA (Levulan Kerastick). Dr. Taub's exhaustive review details the various cutaneous diseases that have benefited from the use of topical 5-ALA. She then reviews the pros and cons of various light sources (laser and non-laser) in activating 5-ALA and concludes her review with an evaluation of recent applications of PDT in acne and photorejuvenation, and new uses of PDT in dermatology and other areas of medicine.

Bissonnette, Bergeron and Liu present their experience in, "Large Surface Photodynamic Therapy with Aminolevulinic Acid: Treatment of Actinic Keratoses and Beyond." Their article reviews the safety and efficacy of large surface ALA-PDT for the treatment of actinic keratoses and photodamage. They review most of the present literature in this regard with the exception of Goldman and Atkin (1) who studied 32 patients with moderate photodamage and multiple actinic keratoses utilizing short contact, full face ALA and blue light therapy. At the end of the clinical trial, lesion counts revealed a 90% clearance of the actinic keratoses. There was also an improvement in skin texture in 72% and skin pigmentation in 59%. Of note, 62.5% of his patients found this therapy less painful than cryotherapy.

Bissonnette et al. treated nude hairless mice with weekly topical ALA-PDT and demonstrated no episodes of skin tumor formation after 10 weeks. Their hypothesis, based on previous animal studies (2,3) is that large surface ALA-PDT for patients with multiple actinic keratoses and photodamage could theoretically prevent skin cancer appearance by inducing a phototoxic reaction in non-visible lesions. These animal studies suggest that large surface ALA-PDT could be used in patients at high risk of developing skin cancer in order to prevent the development of AKs and SCCs.

Avram and Goldman present the first paper on the use of the Lumenis Intense Pulse Light (IPL) with Levulan[TM], "Effectiveness and Safety of ALA-IPL in Treating Actinic Keratoses and Photodamage." They performed a retrospective trial on 17 patients treated with ALA-IPL. Patients were evaluated for improvement of telangiectasias, blotchy pigment, fine wrinkles, coarseness of skin, and number of actinic keratoses. All side effects were recorded. Sixty-eight percent of actinic keratoses resolved after one treatment. There was a 55% improvement in telangiectasias, a 48% improvement in pigmentary irregularities, and a 25% improvement in coarseness of skin texture. There was minimal change in fine wrinkle appearance. Side effects were minimal including almost no pain, mild erythema, and edema for 3-5 days on average. Of interest was that one treatment with a 1 hour application of 5-ALA followed by standard IPL treatment produced clinical "photorejuvenation" results similar to 3-5 monthly treatments with IPL alone. In addition to photorejuvenation, with the IPL, the combined use of 5-ALA also treated a substantial number of actinic keratoses which do not resolve with IPL treatment alone.

The final article in this issue by Michael Gold, one of the most active dermatologist's researching new and improved uses for photodynamic therapy, describes "ALA-PDT and Blue Light Therapy for Hidradenitis Suppurativa." Gold identified four individuals with chronic hidradenitis suppurativa who had not responded to traditional therapy with a variety of topical and systemic agents, as well as intralesional corticosteroid therapy. These patients elected to use ALA-PDT therapy as a last resort prior to contemplating a major surgical procedure or C[O.sub.2] laser therapy. All of the patients tolerated the treatments well. There were no adverse effects noted during these treatments. These therapies were pain-free and not associated with any downtime for these patients. While the exact mechanism of action on how this process works in hidradenitis suppurativa still needs to be determined, patients described in this report achieved clearance rates from 75-100% which were able to be maintained at a three month follow-up period.

The future of ALA-PDT appears bright. For many years, dermatologists have hoped that ALA-PDT would leave the laboratory setting and become part of our everyday practices. Cosmetic improvements have been shown in a variety of cutaneous concerns including photorejuvenation and acne vulgaris. Short-contact, full face/broad area ALA-PDT treatments make this therapy more appropriate for the dermatologic community; trials have shown it is safe, efficacious, relatively pain-free, and without significant adverse effects. Clinicians should be ready for these new therapeutic approaches to common skin concerns and may rethink how dermatologists treat photodamage, sebaceous hyperplasia, and acne vulgaris, bridging closer the worlds of medical dermatology and cosmetic dermatologic surgery.