Cold atmospheric plasma therapy for Malassezia folliculitis: Laboratory investigations and a randomized clinical trial

Abstract Background Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF. Objectives The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF. Methods We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well‐established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator‐controlled, observer‐blind study was conducted comparing daily CAP therapy versus itraconazole 200 mg/day for 2 weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability. Results In laboratory investigations, CAP time‐dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty‐nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group ( p = 0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group ( p = 0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 ( p = 0.456) or in the GAIS responder rates ( p = 0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs. Conclusion CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF.