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Photodynamic therapy: when and why?

Photodynamic therapy (PDT) is a rapidly evolving treatment modality in dermatology. It involves the application of a photosensitizer, which then accumulates in the lesion to be treated. Subsequently, the lesion is illuminated with visible light at a wavelength corresponding to the specific photosensitizer leading to a photo-oxidative reaction mediating a cytotoxic effect on the tissue. The ideal PDT should include the use of a photosensitizer that selectively accumulates in the cells of the tissue to be treated, thereby avoiding photosensitization of other tissue that does not require treatment. Secondly the photosensitization should be limited in time to avoid the necessity of photoprotection for a longer period of time after the treatment. Thirdly a topical application, as opposed to systemic use, of the photosensitizer facilitate the use. Furthermore, the wavelength of the light should also be adequate to penetrate sufficiently deep into the tissue to be treated. Today PDT in dermatology has developed largely to satisfy the above-mentioned demands. With the introduction of 5-aminolaevulinic acid (5-ALA), and in particular the methylester, methyl-ALA, which is metabolized to the photosensitizer protoporphyrin IX (PpIX), in the cells, PDT took a significant step forward. Methyl-ALA has been shown to be more lesion specific in precancerous and cancerous lesions than 5-ALA,1,2 thus making it an ideal drug for PDT. It is applied as a cream under an occlusive dressing to the lesion, and a dose finding study demonstrated a 3 h application time to give optimal treatment results.3 The light source also plays a significant part in the treatment result. Blue and green light penetrate the skin approximately 0.5 mm to 2 mm, while red light penetrates much deeper, up to 6 mm, thus making it more suitable for optimal treatment results. With methyl-ALA the photosensitization also disappears after the photobleaching, i.e. the illumination, making additional light protection after the treatment unnecessary. The indications for PDT in skin disease are predominantly all precancerous and cancerous lesions, but it has also been used with success in a number of other dermatoses. Excellent results have been obtained in actinic (solar) keratosis, Bowen’s disease, thin spinocellular carcinomas and basocellular carcinomas. Good results have also been obtained in cutaneous T-cell lymphoma, skin metastasis, extramammary Paget’s disease and Kaposi’s sarcoma (see Ceburkov and Gollnick4 and Kalka et al.5). PDT shows overall an excellent cosmetic end result. Particularly in patients with widespread sun-damaged skin with numerous actinic keratosis, PDT is at present the treatment of choice because of its excellent selectivity, efficacy and superior cosmetic results, and in addition because it can be repeated numerous times without any presently known adverse effects. Other dermatoses that have been shown to improve after PDT are psoriasis, common and genital warts and epidermodysplasia verruciformis, acne vulgaris and hypertrophic lichen planus among others (see Ceburkov and Gollnick4 and Kalka et al.5). Further studies are, however, needed to document better the therapeutic effect in these diseases. Taken together, topical PDT is a selective and effective treatment with superior cosmetic results for precancerous and cancerous skin lesions. The photosensitizing drug with the best specificity seems to be the methyl-ester of ALA, with an application time of 3 h under an occlusive dressing, and the illumination should be with red light.