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PDT for onychomycosis

In this issue, Gilaberte et al. present data on methyl aminolevulinate–photodynamic therapy (MAL-PDT) for onychomycosis. Poor treatment results and evolving drug resistance with the conventional topical and systemic antifungal drugs have initiated a search for alternative treatments, and PDT is such an alternative. There are several reports on successful use of PDT for onychomycosis in the literature. The treatment results with MAL-PDT in Gilaberte et al.’s study are poor, and not different from placebo. Onychomycosis without total dystrophy, however, responded better to MAL-PDT and was associated with a higher microbial cure rate than placebo-PDT and showed a better clinical outcome as measured using the onychomycosis severity index. Twenty-four weeks after initial MAL-PDT, three of nine dermatophyte-infected had achieved microbial cure, but at the end of the study, at week 36, positive dermatophyte cultures had increased to eight. As MAL is not in itself a photosensitizer but needs to be taken up and metabolized to photoactive porphyrins, a necessary capability of a susceptible fungus is that it has uptake capacity and an enzymatic repertoire capable of converting MAL to photoactive porphyrins. This capability was demonstrated for Trichophyton rubrum in laboratory studies, and aminolevulinate–PDT was shown to have growth-inhibiting effect. Gilaberte et al. cultured 10 different species of fungi in their study, and the question arises whether all these species have the same capabilities as shown for Trichophyton rubrum. There might be differences which have considerable influence on their susceptibility to MAL-PDT. Further studies are needed to elucidate this. Treatment of onychomycosis is difficult, and recurrences are the rule rather than the exception. No fungal resistance and genotoxic or mutagenic effect to fungus or human cells have so far been reported using PDT with various photosensitizers. It therefore seems to be a safe therapy option which can be used in selected cases.