Cold Atmospheric Plasma (CAP) and Skin Health: A Scientific Overview with Focus on Eczema & Topical Steroid Withdrawal
Introduction
Skin conditions such as Atopic Dermatitis (AD, commonly known as eczema) and Topical Steroid Withdrawal (TSW, also referred to as red‐skin syndrome) pose significant therapeutic challenges. Both involve impaired skin barrier function, chronic inflammation, and predisposition to microbial colonisation or infection.
An emerging modality in dermatological therapy is cold atmospheric plasma (CAP) - a non‐thermal, ionised gas produced at or near ambient temperature and atmospheric pressure. Over the past decade, CAP has been investigated for wound healing, disinfection, and now inflammatory skin diseases. This article summarizes the science behind CAP, its mechanisms relevant to skin health, and its application evidence in eczema and TSW.
What is Cold Atmospheric Plasma?
Plasma is often termed the “fourth state of matter” (solid, liquid, gas, plasma). In plasma, a gas is partially ionised: electrons are freed, and reactive species (ions, radicals) are generated.
Cold atmospheric plasma (CAP) refers to plasma generated at ambient or near-ambient temperature (typically < 40 °C) and atmospheric pressure, making it safe for direct skin contact. Medical News Today+2PMC+2
Key features of CAP relevant to dermatology:
Generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which can act on microbes, cells, and tissue. PMC+1
Mild electric fields, UV emissions, charged particles, and electromagnetic effects all acting synergistically. MDPI+1
Ability to promote tissue regeneration, influence microcirculation, modulate immunity, and improve barrier properties. PMC+2Karger Publishers+2
Because CAP is non‐thermal, it avoids tissue‐damage risks of traditional (hot) plasma, enabling safe use on skin and open wounds.
Pathophysiology of Eczema (Atopic Dermatitis) and TSW: Why CAP Might Help
Eczema / Atopic Dermatitis (AD)
Major pathophysiological features:
Skin barrier dysfunction: Increased transepidermal water loss (TEWL), altered lipids, impaired repair. Medical Journals+1
Chronic inflammation: Cytokine dysregulation (Th2/Th22/Th17 pathways) leading to erythema, pruritus, lichenification.
Microbial dysbiosis / colonization: Especially Staphylococcus aureus colonisation correlates with severity. PubMed+1
Because AD involves barrier weakness + inflammation + microbial burden, a therapy that simultaneously addresses all three could be particularly valuable.
Topical Steroid Withdrawal (TSW)
TSW is a condition that can follow cessation of long‐term or high‐potency topical corticosteroids. Typical features include burning or stinging skin, intense redness, flaking, sometimes oozing/crusting, and prolonged healing. PubMed+1
Pathophysiology is less clearly defined, but proposed mechanisms include:
Altered barrier repair processes due to chronic steroid use (glucocorticoid‐related suppression of skin regeneration)
Microbial overgrowth on compromised barrier
Dysregulated immune responses and rebound inflammation
Because TSW involves a severely compromised barrier, inflammatio, possible microbial complications, the same rationale (as with AD) applies for considering CAP.
Mechanisms by Which CAP May Benefit Skin Conditions
The following mechanism categories summarise how CAP could exert positive effects in eczema and TSW.
1. Antimicrobial / Microbial Modulation
CAP generates ROS/RNS that have bactericidal and fungicidal effects; studies show CAP reduces numbers of pathogens (including S. aureus) on skin. PMC+2PMC+2
In a pilot human AD trial, lesion microbiome analysis revealed a statistically significant reduction in the proportion of S. aureus after CAP treatment. PubMed+1
By reducing microbial load and biofilm, CAP decreases a common trigger of flares (especially in AD) and may reduce secondary infection risk in TSW.
2. Anti-inflammatory & Oxidative Stress Modulation
CAP has been shown in animal AD models to reduce inflammatory cytokine expression, reduce endoplasmic reticulum (ER) stress and oxidative stress. For example, in a dinitrofluorobenzene (DNFB) mouse AD model, CAP upregulated HIF-1α which then increased mesencephalic astrocyte-derived neurotrophic factor (MANF), thereby reducing apoptosis, inflammation and oxidative stress. Frontiers+1
A review noted that CAP can regulate reactive oxygen/ nitrogen species both inside and outside cells, thereby improving immunocompetence of skin cells. Karger Publishers+1
3. Barrier Repair / Tissue Regeneration
CAP can stimulate keratinocyte and fibroblast proliferation and migration, enhance angiogenesis and microcirculation, thus promoting tissue repair. PMC+1
CAP has been shown to alter skin lipid content: for example changes in carbon/oxygen/nitrogen composition of lipids have been observed post‐CAP, which may reflect improved barrier lipid organisation. Karger Publishers
In a wound healing study of various superficial skin wounds (including one chronic eczema case), all patients achieved complete healing after several rounds of CAP (2–8 sessions) with no adverse effect. PMC
4. Enhancement of Topical Treatment Penetration
CAP can temporarily increase skin permeability, thereby potentially enhancing penetration of moisturizers and other topical therapies. This is relevant because in eczema/TSW, barrier creams are mainstay care and improved penetration may boost their effect. Karger Publishers
Evidence in Eczema (Atopic Dermatitis)
Clinical Human Data
A key study:
Kim YJ et al. (2021), “Prospective, comparative clinical pilot study of cold atmospheric plasma device in the treatment of atopic dermatitis.”. In this study: 22 adult patients with mild to moderate AD (symmetric lesions) were randomised to CAP vs sham on matched lesions. Treatment sessions occurred at week 0, 1 and 2; assessments at weeks 0,1,2,4. PMC+1
Key results: EASI (Eczema Area and Severity Index) and modified antecubital severity (ADAS) scores were significantly decreased in CAP‐treated lesions compared to sham. Pruritic visual analogue scale (VAS) improved significantly. Microbiome analysis: reduced S. aureus proportion in treated group. No safety issues reported. PubMed
Mechanistic Animal Data
Sun et al. (2022), “Cold plasma irradiation attenuates atopic dermatitis via enhancing HIF-1α-induced MANF transcription expression” (Front. Immunol.). In a DNFB‐induced AD mouse model, CAP decreased apoptosis of skin cells, relieved skin inflammation, ER stress and oxidative stress, mediated via HIF-1α → MANF pathway. Frontiers+1
Other preclinical studies show CAP inhibits mast cell activation and ameliorates allergic skin inflammatory diseases in NC/Nga mice. BioMed Central+1
Reviews & Systematic/Scoping Evidence
Zhang/et al. (2023) review: “Cold atmospheric plasma: a promising and safe therapeutic strategy for atopic dermatitis.” (Int Archives Allergy Immunol) summarised the potential mechanistic and clinical evidence. BioMed Central
A scoping review: Cespedes Zablah et al. (2025), “Cold Atmospheric Plasma in Inflammatory and Infectious Dermatology: A Scoping Review” found that CAP appears more effective in inflammatory than infectious dermatoses, though human study numbers remain limited. Journal of Integrative Dermatology+1
Implications for Eczema Patients
From the above:
CAP offers a multi‐modal mechanism: antimicrobial, anti‐inflammatory, barrier repair, addressing many of the drivers of eczema.
The pilot human study in AD shows statistically significant clinical improvements (severity indices, itch) in mild–moderate AD.
CAP appears to have a favourable safety profile in these contexts.
However: sample sizes are modest, follow‐up short, devices/protocols vary, long‐term efficacy and comparative effectiveness vs standard therapies remain to be established.
Evidence in Topical Steroid Withdrawal (TSW)
TSW is less well‐studied in the context of CAP. There are currently no large randomized trials specifically in TSW published in peer‐reviewed journals as of this writing. The evidence consists mostly of mechanism plausibility, clinic‐based case series, and emerging interest.
Rationale for CAP in TSW
Because TSW involves:
severely impaired barrier leading to increased TEWL, susceptibility to infection
chronic/rebound inflammation
microbial colonisation/infection risk
The multifunctional actions of CAP (barrier repair, inflammation modulation, antimicrobial) make it a plausible adjunctive therapy.
Published Evidence
Though not a full clinical trial, there is a summary “Cold plasma therapy for TSW” article; however, this is from a non‐peer‐reviewed source and does not provide rigorous quantitative data. drkateaesthetics.co.uk+1
One wound healing study of superficial skin diseases (including one chronic eczema case) treated by CAP reported successful healing. This provides indirect relevance to TSW (since TSW skin has features akin to chronic wound/irritated barrier) but is not specific to TSW. PMC
The systematic/scoping review note that while CAP shows promise in inflammatory skin disease, the number of human studies remains small and TSW is not yet specifically addressed in the literature. Journal of Integrative Dermatology+1
Summary & Caution
CAP for TSW is biologically plausible and anecdotally reported in clinical practices (such as ours).
However, rigorous human trials in TSW are lacking (no large RCTs with published data as of current literature).
Therefore, CAP should be considered experimental/adjunctive in TSW rather than an established standard of care.
Practical Considerations & Key Points for Clinicians/Patients
Device/Protocol Variability: Different CAP devices (jet vs dielectric barrier discharge, different gas compositions, treatment durations) exist. Protocols in studies vary (e.g., 3 sessions in the AD pilot at weeks 0,1,2). PubMed
Safety Profile: The AD pilot reported no safety issues. Reviews note CAP appears safe for dermatologic use when applied appropriately. Karger Publishers+1
Adjunctive Use: Because CAP addresses multiple mechanistic pathways (microbial, inflammation, barrier), it is best viewed as an adjunct to established treatments rather than a replacement.
Patient Selection: Mild-to-moderate eczema appears the most studied; severely damaged/eroded skin may require careful clinical oversight. In TSW, given the paucity of RCTs, careful risk/benefit discussion is warranted.
Expectation Setting: CAP is not a “magic cure,” clinical improvement in eczema has been modest but statistically significant; for TSW, improvement may be slower and variable.
Cost & Access: CAP treatment may not yet be widely available in all dermatologic settings, and reimbursement/insurance coverage may be limited.
Research Gaps: More large‐scale RCTs (especially in TSW), long‐term outcomes, comparisons versus standard therapies, cost‐effectiveness analyses, and standardization of device/protocol are needed.
Summary
Cold atmospheric plasma (CAP) is a promising therapeutic adjunct in dermatology, particularly for inflammatory skin conditions such as atopic dermatitis (eczema). The evidence to date shows:
In mild to moderate AD, CAP has been shown to reduce clinical severity scores, itch symptoms, and microbial (S. aureus) burden in a pilot human trial.
Mechanistically, CAP addresses key pathophysiologic components: microbial colonization, inflammation/oxidative stress, and barrier repair.
The application of CAP in topical steroid withdrawal (TSW) is plausible and clinically promising, but the evidence base remains limited and largely anecdotal.
CAP appears safe in studied contexts, but device/protocol heterogeneity and small study sizes mean caution should be warranted.
Clinically, CAP should currently be considered as an adjunctive therapy until more robust data are available.
With further research and standardization, CAP could become an important tool in the dermatologic arsenal for barrier-compromised, inflamed skin conditions, offering a multi‐modal, non‐pharmacologic approach.
References
Kim YJ, Lim DJ, Lee MY, Lee WJ, Chang SE, Won CH. Prospective, comparative clinical pilot study of cold atmospheric plasma device in the treatment of atopic dermatitis. Scientific Reports. 2021;11(1):14461. PubMed+1
Sun L, Zhang Y, Hou C, Yu S, Zhai Y, Yu Z, et al. Cold plasma irradiation attenuates atopic dermatitis via enhancing HIF-1α-induced MANF transcription expression. Frontiers in Immunology. 2022;13:941219. Frontiers+1
Bai F, Ran Y, Zhai S, Xia Y. Cold atmospheric plasma: a promising and safe therapeutic strategy for atopic dermatitis. International Archives of Allergy and Immunology. 2023;184(2):1184-1197. BioMed Central
Cespedes Zablah A, Griffin T, Lio P. Cold Atmospheric Plasma in Inflammatory and Infectious Dermatology: A Scoping Review. Journal of Integrative Dermatology. 2025. Journal of Integrative Dermatology+1
Review: Cold Atmospheric Plasma: A Promising and Safe Therapeutic … (Karger). Karger Publishers
Ma et al. Cold atmospheric plasma promotes different types of superficial skin wounds. PLoS ONE/PMC. 2021. PMC
Review: Cold atmospheric plasma applications in dermatology: A systematic review. (PubMed). PubMed
On TSW: Topical steroid withdrawal: an emerging clinical problem. PubMed
