###### Abstract  
The increase in antibiotic resistance requires effective non-antibiotic therapies for acne. Cold atmospheric plasma (CAP) inactivates bacteria and improves wound healing, but its effect on acne has not been investigated. The objective of this controlled split-face study was to assess safety and efficacy of CAP in moderate acne. One side of the face received 8-10 treatments with cold helium plasma within 4-6 weeks; follow-up was two and four weeks thereafter. Acne lesions were counted, followed by global acne severity ratings. Of the 34 patients included, 29 completed the study. No serious adverse events occurred. The two facial sides did not significantly differ in the number of inflammatory and non-inflammatory lesions. An interaction effect of number and type of treatment was found for inflammatory lesions. Lesion reduction after 10 treatments was significantly higher on the treated than on the untreated side. Percentage of patients reporting improved aesthetics was higher for the treated than for the untreated side after treatment completion (79% vs. 45%) and at the two- (72% vs. 45%) and four-week follow-up (79% vs. 52%). In conclusion, CAP was safe with excellent tolerability, showed moderate reduction in acne lesions and led to higher patient-based ratings of aesthetics than non-treatment.  
acne; antibiotic resistance; CAP; cold plasma Article  
Trial to Assess the Safety and the Efficacy of Cold Atmospheric Plasma in the Treatment of Acne Vulgaris  
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depending on the different plasma technologies available, the ionization processes, the density and temperature, and the gas used [8]. CAP has been shown to be very effective not only against all types of bacteria including multi-resistant germs but also against biofilm-forming bacteria, viruses, fungi and spores [9; 10; 11; 12]. The suggested mechanisms for the antimicrobial effects include lysis of microorganisms due to accumulation of charged particles and oxidative damage to cytoplasmic membranes, bacterial proteins and DNA [13]. Treatment with CAP may therefore constitute an effective alternative to antiseptides and antibiotics for the eradication of pathogens. In dermatology, CAP is being used for treating chronic leg ulcers [14; 15; 16; 17; 18; 19], acute wounds [20], shingles [21], skin aging [22] and actinic keratosis [23]. In wounds, CAP has been found to not only significantly reduce the bacterial load but also to accelerate wound healing [14; 15; 16; 17; 18; 19]. So far, no serious adverse events have been described after CAP treatment; furthermore, no mutagenic potential has been found [24; 25; 26]. The advantage of CAP is its pain-free, non-invasive, easy and fast application. Bacterial resistance and allergic or toxic reactions are very unlikely because of its physical mode of action.  
Because of its gaseous form, CAP can penetrate into hair follicles [27], in which inflammation is triggered by _Cutibacterium acnes_ in patients with acne [2; 3]. We hypothesised that the antibacterial and anti-inflammatory properties of CAP have the potential to improve skin affected by acne. Therefore, we conducted a controlled, randomised, split-face study to investigate the safety and efficacy of CAP in patients with moderate acne vulgaris.