ReviewA comprehensive overview of photodynamic therapy in the treatment of superficial fungal infections of the skin
Introduction
Photodynamic therapy (PDT) combines the topical or systemic administration of a photosensitizer with the selective illumination of the target lesion with visible light, which results in localized oxidative photodamage and subsequent cell death. This technique is now routinely used in dermatology. The FDA has recently approved 5-aminolevulinic acid (ALA) for the photodynamic treatment of actinic keratosis while the European regulatory authorities have approved methyl-aminolevulinate (MAL) for actinic keratosis and basal cell carcinoma. In addition, PDT with these and other sensitizers has been proven, in worldwide laboratory and clinical studies, to be a promising tool for a wide variety of other skin tumors including squamous cell carcinoma, Bowen’ s disease and cutaneous T-cell lymphoma, and selected inflammatory and infective diseases. This last application grew out of the positive results of research studies concerning photo-induced viral or bacterial inactivation that were conducted with the aim of disinfecting blood products [1], [2]. Up to now these blood disinfection studies pay little or no attention to possible applications of PDT to fungi due to the low risk of transfusion transmission of such pathogens [3].
However, superficial skin mycosis, either caused by Candida species or dermatophytes, is one of the most frequent diseases in human beings and animals and the search for new therapeutic approaches is stimulated by the fact that standard drug treatments are prolonged and expensive and the appearance of drug resistant strains is more and more frequent in high risk groups such as HIV+ patients and cancer patients undergoing chemotherapy [4]. The present paper aims to provide a comprehensive overview of investigative in vitro and in vivo studies of anti-fungal PDT that have been reported so far.
Section snippets
General principles of photosensitization of fungi
Several photosensitizers, mainly belonging to three chemical groups (phenothiazine dyes, porphyrins and phthalocyanines), have been investigated. As a general rule, sensitizers which are medically interesting, are those without dark toxicity, i.e., are devoid of toxicity in the absence of light activation, and, upon irradiation, lack genotoxicity and mutagenicity [5]. The hazard of DNA damages in eukaryotic fungi is furtherly reduced by the presence of a membrane that envelopes the nucleus and
Conclusions and perspectives
Results of experimental investigations have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro by several dyes belonging to three chemical groups: phenotiazinum, Pp and Pc. In addition, they can effectively metabolize ALA to PpIX. Besides being effective, antifungal PDT is selective because fungi can be killed at dose rates much lower than that which kills keratinocytes. Absence of genotoxic and mutagenic effects on both fungal cells and keratinocytes seems a
Abbreviations
- PDT
photodynamic therapy
- ALA
5-aminolevulinic acid
- MAL
methyl-aminolevulinate
- MB
methylene blue
- TBO
toluidine blue
- HpD
hematoporphyrin derivative
- Pp
porphyrin
- PpIX
protoporphyrin IX
- Pc
phthalocyanine
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