## 4 Discussion
30 volunteers had one side of their face treated with BioPlasma once per week for four weeks [38]. A sebum reduction in up to 80% of cases was measured by a sebumeter. The effect of oil reduction lasted until four weeks after treatment cessation, which could explain why, in our study, the number of acne lesions further decreased up to four weeks after treatment cessation. However, the study from Thailand did not report any further details about patients, methodology and results. [PERSON] et al. treated 2 patients with mild to moderate facial acne with CAP, using a plasma torch producing argon plasma (SteriPlas, Adtec Healthcare), which resulted in a reduction in acne lesions after treatment [39]. Sebumexcretion parameters, as measured by sebometry and trans-epidermal water loss, also improved as compared to base values. These preliminary studies together with the results of our study confirm the potential of different CAP devices for this new indication. The cold plasma device used in this study was the BioWeld1 System, which is CE-marked for surgical wound closure. Treatment with the BioWeld1 system included CAP-exposure of each skin segment for no more than 20 s per day including a minimal UV-exposure well below the maximum exposure according to the American Conference of Governmental Industrial Hygienists (ACGIH) guidelines. Thus, no UV-induced side effects such as eye damage or sun burn had to be expected. The application of CAP was quick and comfortable for the patients. Patients tolerated the treatment very well, and only two mild AEs relating to pain and no SAE were documented. In comparison with other topical and systemic treatment modalities for acne, there is no other conventional therapy with such a favourable spectrum of side effects. For moderate acne, guidelines recommend therapies combining benzoyl peroxide (BPO), retinoids and topical or systemic antibiotics [1, 40]. Although oral antibiotics remain one of the main options for treating moderate to severe acne, current guidelines strongly advocate limiting their use due to rising concerns of antibiotic resistance [40, 41]. In this context, CAP could become a new therapeutic alternative with a completely different and mainly physical mode of action that warrants to be further explored in larger studies that also include patients of younger age. In our study, CAP treatment led to a continuous reduction in acne lesions with the maximal decrease of about \(-50\%\) in inflammatory acne lesions and \(-36\%\) in non-inflammatory acne lesions (as compared to \(-41\%\) and \(-23\%\) on the untreated side, differences not significant) at the four-week follow-up. Interestingly, the lesion counts continued to show a decrease in lesions after the last CAP treatment until the four-week follow-up, indicating that CAP continues to be efficacious beyond treatment cessation. Efficacy of CAP was superior for inflammatory lesions than for non-inflammatory lesion, as is also known for most other acne therapies. A meta-analysis of placebo-controlled trials indicated that oral minocycline was more active than placebo against inflammatory acne lesions, producing a \(-45.5\%\) reduction compared to \(-32.0\%\) for placebo after twelve weeks of therapy [42]. The effect against non-inflammatory acne lesions was smaller with \(-14.9\%\) versus \(-6.3\%\) after placebo. For topical acne treatments, the reduction in inflammatory lesions after twelve weeks of therapy ranges from \(-44\%\) to \(-72\%\) for BPO, from \(-46\) to \(-57\%\) for adapalene, and from \(-62\%\) to \(-70\%\) for a combination of BPO and adapalene [43]. With a mean reduction in inflammatory acne lesions of about \(-50\%\) after a study period of ten to twelve weeks, CAP seems to be slightly less effective than conventional topical treatments but shows much better skin tolerability. An obvious limitation of this study is the non-achievement of the recruitment goal due to the sponsor's decision to close the study prematurely.