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Could Microwave Energy Be a Future Treatment for Onychomycosis?
In recent years, the use of microwave technology has become a valuable tool in podiatry practice. The novel modality of treating benign lesions of the skin with sub-ablative doses of microwave energy has already shown great success in the treatment of even the most recalcitrant verrucae and common warts, both of which are result of infections by the human papillomavirus (HPV).1-3
Following the success of treating and clearing HPV-infected cells, the question arose whether other podiatric infections could also be effectively treated using microwave energy. As a result, research has begun to explore the application of this device to treat the most common infection of the nail—onychomycosis. It is important to note that this potential application is, at present, an off-label usage of this system.
What Effect Could Microwave Energy Have On Dermatophytes?
Dermatophytes make up over 90% of toe nail infections.4 Approximately 90% of chronic or recurring dermatophyte infections are caused by the fungus T. rubrum.5 Microwave technology as a sterilization tool for infected insoles dates back to 2014, where it was shown that short 30-second microwave irradiation of various fungi using a standard 2.45GHz microwave oven resulted in inhibition and lack of subsequent growth of T. rubrum. Interestingly, under those conditions, the maximum temperature reached within the insoles during microwave irradiation was only 35°C.6
To test whether fungal growth could also be inhibited by microwaves at 8GHz, preliminary in vitro tests were carried out at the University of Plymouth (United Kingdom). Agar plates were inoculated with T. rubrum, grown to form colonies, and then treated through the bottom of the dish with various doses of microwave energy delivered.7
A microwave-induced temperature rose to 48-50°C within the agar/fungal colonies resulting in areas of fungal clearance restricted to only the treatment site, and inhibition of growth thereafter (Figure 1). Over time, areas of clearance exhibited new fungal growth from the outer borders towards the center, indicating that it is necessary to treat and kill all areas of fungal growth in order to avoid re-infection from untreated areas and disease progression.
Translating In Vitro Data to the Toenail Using Computer Modeling
With success in lab agar, the research team at the Swift microwave device manufacturer (Emblation, UK) investigated further how to translate this to the toenails of patients.7
Using in silico computer modeling of the microwave heating effect at 8GHz on the toenail, it was quickly found that, perhaps unsurprisingly, the keratinous layer of the nail is highly permissible to microwaves and a significant amount of the energy was delivered into the nail bed, whereas the fungal infection resides at the interface of the nail and the nail bed (Figure 2). Hydration of the microwaved nail was found to focus and enhance the heating in the target area of infection. This is an advantage not only over poorly penetrating topical creams, but also over laser energy-based systems where the thickness of nails can affect the depth of penetration reflection in a range of wavelengths.8–10 Furthermore the effectiveness of laser devices is yet to be seen in any large-scale studies.11
Based on the modeling data, a treatment regime of 7-9W microwave energy was proposed, which is applied for 3 seconds and repeated on the same spot 5 times. After those 5 applications of 7-9W for 3s, the tip is moved to the next location, ensuring that there is an Olympic ring-like overlap between treatment areas (Figure 3). Pretreatment was achieved in the practice/clinic by applying wet gauze (saline or tap water) to the debrided nail for 5 minutes prior to treatment. Hydration of the nail is thought to be needed in order to absorb some of the microwave energy as it passes through the nail thereby attenuating the heating effect within the nail bed and not overtreating the healthy tissue. The entire area of fungal involvement under the nail needed to be treated. In severe cases with extensive fungal coverage, re-hydration was required due to the effect of the microwave heating the water within the nail itself.
Currently, I am aware of a number of podiatrists in the UK and US trialing this protocol to gather early feasibility data on the safety and efficacy of this potential treatment modality for onychomycosis.
Is Microwave Therapy For Onychomycosis Clinically Effective?
The earliest published report (in 2022) described a case of successful clearance of a fungal nail spike within the hallux nail. The diagnosis was confirmed using a PreventID® dermatophyte test strip (Preventis GmbH, Germany) where the patient underwent a total of 6 treatments of microwave therapy over the course of 20 months, at which point the nail was visually cleared of fungal infection.7
Since then, I have participated in several conversations with podiatrists anecdotally sharing early outcomes with variable, yet promising results (Figure 4).
What’s In It For the Patients?
As already mentioned above, the treatment of fungal nail is a long process dependent on the speed of new nail growth. However, because treatments with microwave energy are solely carried out within the practice, there are few concerns around patient adherence to the treatment regime, unless one plans combination therapy with additional topical solutions. Indeed, in my experience, the use of topicals or even oral medications in combination with microwaves is not contraindicated and may improve outcomes further.
As a monotherapy, it appears that microwaves are a very well tolerated treatment modality, with patient-reported pain levels being mild-to-moderate, and generally only short lasting. If nails are over-treated, signs of subungual hematoma, prolonged pain, or increased temperature sensitivity can be experienced. In my experience, however, these side effects are rare when the correct dosage protocol is used and all the other benefits of microwave therapy—such as no smoke or plume, no need for dressings or specific aftercare other than the standard advice of changing socks and footwear—are still applicable for this condition.
The Road Ahead
The goal of any fungal nail treatment is total clearance of the fungal infection from the entire nail unit. Due to the inherently slow growth rate of the toenail plate, linear growth and shedding of fungal debris is a long process that can take 12 to 18 months and the overall efficacy of any treatment depends on the fungus-free growth of the new nail. There are several ways in which "cure" can be determined. A mycological cure is the absence of fungus determined by potassium hydroxide microscopy and fungal culture; clinical cure is the appearance of a healthy-looking nail, and complete cure is a combination of both positive mycological and clinical cures.12,13
Currently, existing therapies—oral, topical, energy-based—are seldom efficacious. While topical and device-based monotherapies do not reach mycological cure beyond 55% and clinical cure beyond 20%,14 the latest reports for oral antifungal therapy determined up to 92% mycological cure with 59% complete cure for a daily dose of 250mg terbinafine for 24 weeks.14 While oral antifungal drugs offer the greatest cure rates, avoiding serious side effects such as drug-induced liver injury needs close monitoring. Moreover, the emergence of new resistant dermatophyte strains may threaten their future effectiveness.15 One must acknowledge the increasing threat of terbinafine resistance, which is currently present in around 4% of the US patients with fungal nail infections.14
US Food and Drug Administration (FDA) approval for any fungal nail treatment is generally only sought and given for clinical cure, sometimes even only temporary clinical cure. I feel that microwave therapy, with its possible advantage in nail penetration and novel mechanism of action on dermatophytes, could potentially achieve good efficacy for both clinical and mycological cure with continued research. As mentioned previously, microwave therapy for onychomycosis is not yet FDA cleared, and any current use is off-label, but I am hopeful for its potential future in this area.
To date, pilot work is being undertaken as an open, single-site, pilot study at a dermatology clinic in Canada (NCT05674747) to provide data on the precise effects of microwave on T. rubrum viability in samples.16 Importantly, prior to study enrolment, each subject provides a mycology sample to assess both presence and viability of T. rubrum, tested by potassium hydroxide testing, microscopy, polymerase chain reaction (PCR), and fungal culture, respectively. These mycology tests will be repeated at 6, 9, and 12 months into the study.
The frustration of treating fungal nail infection is well known to podiatrists and consequently any new modality for effectively treating this common condition is welcome. I hope, with this commentary, to be able to open dialogue and academic examination of its potential.
Dr. Bristow is an Associate Professor (Adjunct) at LaTrobe University in Melbourne, Australia, and in Private Practice in Lymington, United Kingdom.
Dr. Bristow discloses that he is a consultant for Emblation, Limited, UK.
References
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16. Mediprobe Research. Pilot study to determine the safety and efficacy of regimen frequencies using the Swift Microwave Device for mild to moderate toenail onychomycosis caused by dermatophytes. Available at https://classic.clinicaltrials.gov/ct2/show/NCT05674747
