Cold Atmospheric Plasma for Moderate-to-severe Acne Vulgaris Study

Acne vulgaris is one of the most prevalent chronic inflammatory skin diseases worldwide, with a complex and multifactorial pathogenesis. The main contributing factors include excessive proliferation of follicular keratinocytes leading to follicular plugging, dysregulated sebum production, and the overgrowth and hyperactivity of Cutibacterium acnes (formerly Propionibacterium acnes). Clinically, acne vulgaris is characterised by both non-inflammatory lesions (open and closed comedones) and inflammatory lesions (papules, pustules, and nodules), with severity ranging from mild to severe.

Current therapeutic strategies primarily target reduction of inflammation, sebum production, and microbial load. The mainstays of topical therapy are antibiotics, benzoyl peroxide, and retinoids. For moderate-to-severe cases, oral antibiotics such as minocycline and doxycycline are widely used, and oral isotretinoin remains the cornerstone for severe and refractory disease. In patients with underlying hormonal disturbances, combined oestrogen/progestin therapy may be beneficial. Nevertheless, the long-term use of systemic antibiotics is associated with potential side effects, increasing antimicrobial resistance, and limited efficacy in some patients. Isotretinoin, while highly effective, can be contraindicated or poorly tolerated due to its teratogenicity and adverse effect profile. These challenges underscore the need for innovative and alternative therapeutic approaches, particularly for patients with moderate-to-severe disease, contraindications, or treatment resistance.

Cold atmospheric plasma (CAP) has recently emerged as a novel technology in wound healing and aesthetic dermatology. CAP generates a range of reactive oxygen and nitrogen species (RONS) via glow discharge at atmospheric pressure, producing strong oxidative effects that can denature and coagulate bacterial proteins, disrupt cell membranes, and induce apoptosis of pathogenic microorganisms. In addition to its antimicrobial properties, CAP stimulates local microcirculation, enhances nutrient absorption, accelerates collagen synthesis, and promotes tissue regeneration and wound healing. CAP has been approved by the US FDA since 2008 for use in a variety of dermatological indications, including acne scars, wrinkles, superficial skin lesions, actinic keratosis, viral warts, and seborrheic keratosis. Its broad-spectrum effects offer both anti-inflammatory and skin-rejuvenating benefits, with a favourable safety profile and good patient tolerability.

Although CAP holds promise as a therapeutic modality, its application in the management of acne vulgaris, particularly moderate-to-severe cases, remains underexplored. The high cost of CAP devices and limited availability in specialised dermatology centres have restricted its widespread adoption, and robust clinical data are still lacking. In a prospective study by Wasinee et al. (Mae Fah Luang University, Thailand), weekly CAP-assisted treatment over six weeks in 31 volunteers with mild-to-moderate acne led to approximately 75% reduction in lesion count, with the greatest improvement observed in inflammatory lesions. Most adverse events were mild, including transient dryness and superficial exfoliation. Arisi et al. also reported improvements in two young patients with mild-to-moderate facial acne following CAP treatment, as assessed by lesion count, sebum output, and transepidermal water loss, with no reported adverse effects. However, data on the use of CAP for moderate-to-severe acne vulgaris-where clinical management is most challenging-are particularly scarce. To date, there have been no large, randomised controlled trials specifically evaluating CAP in this population.

Given these gaps, CAP represents a potentially innovative and adjunctive therapeutic approach for moderate-to-severe acne vulgaris, particularly in cases refractory to or unsuitable for standard treatments. In this study, we combine two self-developed CAP devices to capitalise on their respective advantages, enabling personalised and precise coverage of diverse lesion sites. This strategy aims to maximise CAP's antimicrobial and wound-healing mechanisms, and to provide robust evidence regarding its safety and efficacy in the management of moderate-to-severe acne vulgaris.