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Photodynamic therapy (PDT) is a two-step procedure, involving the topical or systemic administration of a photosensitizer followed by selective illumination of the target lesion with visible light, which triggers the oxidative photodamage and subsequent cell death within the target area. In dermatology, PDT has proven to be a useful treatment for a variety of malignant tumors and selected inflammatory diseases. In addition, PDT of several infective viral or bacterial skin diseases has been investigated. These investigations grew out of the positive findings of studies of another important use of PDT: that of disinfection of blood products. Up to now, little has been published concerning the application of PDT to fungi, probably due to the fact that research funding has been mainly directed towards blood disinfection, and these pathogens show a low risk of transfusion transmission. However, preliminary findings have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro by administering photosensitizers belonging to four chemical groups: phenothiazine dyes, porphyrins and phthalocyanines, as well as aminolevulinic acid, which, while not a photosensitizer in itself, is effectively metabolized into protoporphyrin IX. Besides efficacy, PDT has shown other benefits. First, the sensitizers used are highly selective, i.e., fungi were killed at combinations of drug and light doses much lower than that needed for a similar effect on keratinocytes. Second, all investigated photosensitizers lack genotoxic and mutagenic activity. Finally, the hazard of selection of drug resistant fungal strains was never reported. This paper intends to provide a comprehensive overview of investigative studies about the effects of PDT on yeasts and dermatophytes, and bring attention to this application of PDT which we believe very important in that skin mycosis is so common and PDT is not only cost-effective, but also has the advantages of being highly selective and avoiding the occurrence of drug resistant strains.

We have reviewed the results of clinical investigations into the use of photodynamic therapy (PDT) with intravenous injection of hematoporphyrin derivative (HpD), Photofrin (PF) and Sn-protoporphyrin (Sn-Pp) or oral administration of delta-aminolevulinic acid in the treatment of skin cancers and/or psoriasis. Bowen's disease was highly responsive, provided that adequate light and HpD or PF doses were delivered. In contrast, poor results were shown for squamous cell carcinoma, and the rates of complete response of basal cell carcinoma ranged between 0% and 100%. Treatment failures could be related to the delivery of low drug and/or light doses, but differences in the thickness and pigmentation of the treated lesions may play a relevant role. Good palliation was almost always achieved in patients affected by primary and secondary breast carcinomas, although complete eradication of tumors was very rare. PDT is a very promising treatment modality for both Mediterranean and HIV-related Kaposi's sarcoma, because it appears to be effective, can be repeated and is not associated with immunosuppressive activity or significant systemic toxicity. PDT of psoriasis with low doses of Sn-Pp, HpD or PF plus UVA light and PF plus 630 nm light proved to be effective and was associated with mild, dose-related and reversible photosensitivity.

The photodynamic therapy of cutaneous disease is developing more rapidly than that of other organs due to the accessibility of the skin to photosensitizers and light. The use of hematoporphyrin derivative, with its prolonged photosensitivity of normal skin, is gradually being replaced by a new generation of tetrapyrrolic photosensitizers. These are designed to absorb at longer wavelengths for deeper tissue penetration. Many also feature a greatly reduced photosensitizing potential of uninvolved skin. Another major development is the topical and systemic use of aminolevulinic acid for inducing the formation of endogenous porphyrins in cells which result in photosensitivity. This regimen is currently used quite extensively due to the easy availability of both drug and suitable light sources. However, continued investigation of the underlying mechanisms and their regulation will help to improve this specific photodynamic regimen. Currently, researchers use a whole array of therapeutic regimens and schedules for the evaluation of treatment efficacy. A certain uniformity of both treatment parameters and evaluation criteria will help to improve more rapidly our understanding of photodynamic sensitization in skin disease. This will also help us to define the right place and targeting strategies for photodynamic therapy in dermatology.

Photodynamic therapy (PDT) with topical delta-aminolaevulinic acid (ALA) is considered as a valuable tool for treating non-melanoma skin tumours, but there is no consensus about the methods of treatment, where they should be used and the rates of complete responses. This study reports the treatment of 50 actinic keratoses (AKs), 23 superficial basal cell carcinomas (BCCs), 30 nodular BCCs, 4 pigmented BCCs, 12 superficial squamous cell carcinomas (SCCs), 6 nodular SCCs, 6 Bowen's diseases and 4 keratoacanthomas (KAs). A 20% ALA emulsion was applied under an occlusive dressing for 6-8 h and the skin was then irradiated with 630 nm light from a dye laser. Treatments were delivered every other day until complete clinical disappearance of the lesions was observed. ALA-PDT was interrupted in the case of a partial response if, after two additional treatments, no further improvement was observed. All AKs (50/50), superficial BCCs (23/23), Bowen's diseases (6/6) and KAs (4/4) showed a complete response. In addition, 91.6% (11/12) superficial SCCs, 80.0% (24/30) nodular BCCs and 66.7% (4/6) nodular SCCs responded completely to the treatment. All 4 pigmented BCCs were resistant to the therapy. Some (59) of the treated areas that appeared completely responsive were excised for serial histopathological examination and the remaining 63 were followed-up for 24-36 months (median value, 29 months). Comprehensively, the rates of complete responses decreased after taking into consideration the results of these histological examinations and the long-term follow-up. The final response rates are as follows: 84.0% (42/50) AKs, 86.9% (20/23) superficial BCCs, 50% (15/30) nodular BCCs, 83.3% (10/12) superficial SCCs and 33.3% (2/6) nodular SCCs. The rates of complete responses of Bowen's diseases and KAs remained at 100%.(ABSTRACT TRUNCATED AT 250 WORDS)