Malassezia-related diseases

Abstract

The purpose of this thesis is to investigate whether the new taxonomy of Malassezia may have important clinical implications. In particular, the studies look at pityriasis versicolor and other dermatological disorders associated with Malassezia yeasts to see whether there is a clear association between the yeast species and body site colonized and/or disease state. The papers in this thesis also use laboratory work to supplement these clinical investigations. One of the papers tests the in vitro efficacy of several antifungal agents (ketoconazole, itraconazole, voriconazole and terbinafine) against various strains of the seven Malassezia species. The Malassezia species are sensitive to the azoles; however, the in vitro susceptibility of different strains of Malassezia to terbinafine is varied. The second paper describes molecular techniques to distinguish between the Malassezia species. Using PCR and restriction enzyme analysis of four regions of the Malassezia genome, we were able to distinguish between the seven Malassezia species. The next two papers are concerned with the relationship between the new taxonomy of Malassezia and various dermatological disorders. The purpose of the third paper was to determine whether or not one or more of the Malassezia species were more commonly associated with pityriasis versicolor lesions than any of the other species. We also investigated possible species differences in other diseases related, or possibly related, to Malassezia species. These diseases were seborrheic dermatitis, psoriasis and atopic dermatitis. In addition to the relationship between the species and the diseases, the relationship between body site and species was also investigated. The fifth paper in this thesis is a randomized, placebo-controlled, multicentre, international study that investigates the potential use of itraconazole as prophylactic treatment for this condition. It was found that itraconazole is significantly more effective than placebo in both therapy of the active disease and as a prophylactic against recurring pityriasis versicolor. Overall, the studies presented in this thesis investigate the relationship between Malassezia yeasts and various dermatological disorders, primarily pityriasis versicolor. The new taxonomy of Malassezia may have clinical implications. Our work suggests that some pharmacological agents have varying efficacy against some strains and species of Malassezia. If it is, in fact, the case that certain species are reliably associated with particular disorders, species differences may ultimately become important in the development of new interventions against Malassezia-related disorders.