A Case Series: Exploring the Role of “Shock-Free Plasma” Therapy on Dermatophyte Infection of the Skin

Sir, “Difficult-to-treat” dermatophyte skin infection is currently emerging as a significant health problem in our country. Injudicious use of corticosteroids, poor compliance to long-term systemic antifungal therapy, doubtful bioavailability of oral antifungals, and drug hyporesponsive dermatophytes are among the important causes. High cost for long duration of therapy often becomes a problem. This results in frequent discontinuation of therapy, followed by recurrence. Systemic comorbidities such as hepatic and cardiac diseases act as barriers for long-term antifungal therapy. Plasma jet therapy for cutaneous dermatophyte infection is an innovation. Plasma is basically an ionized gas and a collection of charged particles. It is generated through the dielectric barrier discharge phenomenon using argon (Ar) gas as a carrier. The plasma jet consists of a two-electrode configuration; the positive electrode is at the center of the tube, and the negative (ground) electrode is just the outer side of the quartz tube. The outer aluminum foil is surrounded and placed near the orifice of the quartz tube. When the power supply is switched on, Ar gas discharge takes place in between the electrodes and inside the quartz tube, and it comes out of the tube orifice as Ar plasma and starts ionizing the environmental gases to generate reactive oxygen/nitrogen species (ROS/RNS), atomic oxygen, and hydroxyl ions (OH−) which is now known as “atmospheric plasma.” Researchers have mentioned nonthermal plasma as cold plasma. Borges et al. reported the effects of plasma jet on Trichophyton rubrum conidia germination and mycelia growth by in vitro assays.[1] Others reported that the cold atmospheric plasma (CAP) treatment did not induce normal cell death but led to proliferation arrest with an increase in p53/p21 and DNA damage.[2] The clinical impact of microplasma jets on rabbit eyes infected by Candida albicans has been reported by Park et al.[3] The first clinical experiences of Ar plasma coagulation with endoscopic application (with anesthesia) have been reported.[4] Kim et al. treated atopic dermatitis by cold plasma.[5] The possible mechanism of plasma jet in our study is that fungus-rich affected areas are electrically polarized which are selectively targeted by plasma, destroying fungal cell walls and sparing normal human cells simultaneously. Possible three principal factors with fungicidal activity may be summarized as electric field and discharge, ROS/RNS generation, and localized heat transfer. A recent study by Hoppanová and Kryštofová mentioned about potential role of plasma in fungal cell destruction.[6] Three patients aged above 18 years were recruited after obtaining informed consent. The institutional ethics committee’s permission was taken. The plasma device used in this study is driven at 70 ± 5 kHz coupled with 3.8 kV (peak to peak) [Figure 1a and e]. The average current across the human body in one half cycle is 20 mA and the corresponding effective power is about 38W. We maintained the Ar gas flow at 7.5 SLPM to maintain a constant plasma generation. Peak pulse power is 38W, and it is effective (or sustain) for 3 µs (half cycle) on the skin during the plasma treatment [Figure 1d]. Figure 1c shows an optical emission spectrum of the plasma device in this study.Figure 1: (a) Plasma jet setup ([i] Quartz tube, [ii] Positive electrode at center, [iii] Negative electrode at periphery, [iv] Ground electrode (aluminum foil) at the orifice, [v] Whole system is covered by Delrin material, and [vi] Plasma plume); (b) Different sections of plasma plume; (c) Optical emission spectral lines of reactive nitrogen and reactive oxygen species with argon lines; (d) Current (blue) versus voltage (black) characteristics of the plasma; and (e) cold atmospheric plasma treatment devicePatients are clinically diagnosed and scored on erythema, scaling, and pruritus by two dermatologists, using a 5-grade scale (0: absence; 1–2: mild; 3–5: moderate; 6–7: severe; and 8–10: very severe), and the mean score was taken. The intensity of pruritus was classified and scored by the Visual Analog Scale in a similar way (0: no itching, 1–2: mild, 3–5: moderate, 6–7: severe, and 8–10: very severe or bad). Blood pressure (BP) was measured before, during, and after the plasma treatment that are referred as BP1, BP2, and BP3, respectively. Cases were photographed, and samples for microbiological analysis were collected before initiating therapy. The infected area was first primed by the tip of the plasma plume for 5 s/cm2 area to generate an electrostatic charge at the skin surface making it convenient for treatment. Anesthesia was not needed. The same area was then treated for a further 10 s by the lower middle and middle part [Figure 1b] of the plasma plume. The plasma treatment was to 10 s/cm2 affected area. Depending on induration, higher indurated areas needed longer plasma treatment. Therapy was scheduled weekly at weeks 1, 2, 3, and 4 (week 0 = before plasma treatment). The treated patient was asked to return after 7 days. No topical application was advised, but the patient could take oral paracetamol if needed for pain. Patients were scored on the 7th day, tested for fungal elements with potassium hydroxide (KOH) mount, and retreated with plasma plume. Fungal culture was repeated on the 14th day, and patients were rescored for erythema, induration, and itching on every visit on days 0, 7, 14, and 21 [Figures 2-4]. Side effects were noted on each visit after plasma jet treatment. No antifungal drugs in any form were given to the patients at any point of time. Patients were followed up to 3 years. Details of the demography and treatment parameters of three patients at scheduled intervals are depicted in Tables 1 and 2.Figure 2: Clinical outcomes of the first case (a) Untreated fungal patch over buttock, (b) Just after plasma treatment, (c) 7 days after 1st dose of plasma treatment, (d) 2nd dose of plasma treatment, (e) After 14 days of 1st dose of plasma treatment, the red-marked area shows small erosion, (f) After 21 days, (g) After 1 year, and (h) After 3 years of plasma treatment, (i) to (l) The graphical representation of erythema, induration, itching (visual analogue scale) and blood pressure versus time respectivelyFigure 3: Clinical outcomes of the second case (a) Untreated fungal patch over the ankle, (b) Just after plasma treatment, (c) 7 days after 1st dose of plasma treatment and the red-marked area show small erosion, (d) After 14 days, on the same day, 3rd dose of plasma treatment is given on the periphery of the patch, (e) After 21 days, (f) After 28 days, (g) After 1 year, and (h) After 3 years of plasma treatment, (i) to (l) The graphical representation of erythema, induration, itching (visual analogue scale) and blood pressure versus time respectivelyFigure 4: Clinical outcomes of the third case (a) Untreated fungal patch over the waist, (b) Just after plasma treatment, (c) 7 days after 1st dose of plasma treatment and the red-marked area show small erosion, (d) After 14 days, on the same day 3rd dose of plasma treatment is given on the periphery of the patch, (e) After 21 days, (f) After 1 year, and (g) After 3 years of plasma treatment, (h) to (k) The graphical representation of erythema, induration, itching (visual analogue scale) and blood pressure versus time respectivelyTable 1: Demographic profile of three patientsTable 2: Different treatment parameters of three patients at scheduled intervalsAfter the first sitting of successful plasma jet therapy, all skin-scrapping samples sent on subsequent visits tested negative for fungus. The therapy was well-tolerated in all patients, and they could return to work directly after treatment or the following day. Mild erythema and local exfoliation resulting in initial 2–3 days were the insignificant side effects noticed. Plasma jet therapy promises to be a novel tool to counter “difficult-to-treat” dermatophyte infection in a relatively safe and effective manner. Studies with larger sample sizes are needed to prove its potential. Financial support and sponsorship This work was supported by Board of Research in Nuclear Science (BRNS) (grant number: 39/13/2015-BRNS) fund, Dept. of atomic energy, Govt. of India. Conflicts of interest There are no conflicts of interest.