Treatment strategies for onychomycosis with the use of devices
Laser devices, iontophoresis, ultrasound and photodynamic therapy are non-invasive therapeutic device-based treatments, which eliminate the need for long-term patient compliance. Iontophoresis, ultrasound and photodynamic therapy, are combined with local pharmacological agents promoting that way the evasion of side effected related with the traditional fundamental antifungal treatments.
When dermatophyte fungi, non-dermatophyte moulds and yeasts, in other words, fungal pathogens, firstly invade and then colonize the matrix, the bed and the nail plate and create an established infection.
The prevalence of onychomycosis is estimated at 2–8% of the global population. A number of medical conditions can also confer an increased risk of co-morbid onychomycosis infection including diabetes, peripheral vasculopathy, HIV, immunosuppressant, obesity, smoking, and increased age.
Many people have experienced persisting infections that resile for months or years and thus, they are discouraged if not motivated to either start or complete the treatment based on the perception that onychomycosis cannot be treated. Onychomycosis has conventionally been treated by topical and oral antifungals which frequently have moderate to low efficacy. More specifically, re-infection and relapse rate is approximately between to 16-25%, even when there are initial results in a mycological treatment. Antifungal drugs when they are able to penetrate the nail bed and plate result in a successful treatment whereas incomplete scattering to the lesion constitutes a problem for both topical and oral agents.
Antifungal drugs may be related with side effects that may result in the discontinuation of the therapy and the treatment and may be perplexed with the existence of another simultaneous condition.
Additionally, the prolonged duration of the treatment may act as a discouraging factor to the patient’s compliance with the therapeutic scheme, which eventually acts as a significant barrier to an effective treatment. Thus, the aforementioned factors may contribute to the minimal delivery of the traditional onychomycosis treatment.
Device-based therapies on the other hand due to their ability to mitigate several negative elements that act in favor of the failure of the treatment, they can be considered as auspicious solutions to the effective treatment of onychomycosis.
Laser treatment for onychomycosis lies in the principle of selective photothermolysis and intends to utilize the differences in thermal conductivity and laser absorption between the surrounding tissue and the fungal infection.
The conversion of the energy into mechanical energy or heat comes as a result of the absorption of light energy by the fungi which are heat sensitive above 55°C. Thus, laser energy absorption may lead in sustained photothermal heating of the mycelium (10+ minutes) and is likely to produce fungicidal effects.
Solid State Lasers
They use a solid crystal rod. As the pulse length decreases, the maximum pulse energy decreases, creating different pulse formats which may require longer treatment lengths to produce a fungicidal effect or require longer treatment lengths to produce a fungicidal effect. In North America, all the approved LASERs for the treatment of onychomycosis are Nd:YAG LASERs. Ti:Sapphire, titanium sapphire, Nd:YAG, neodymium-doped yttrium aluminium garnet are some of the common LASERs that are included in the solid state LASERs.
Long Pulse Laser Systems
Long pulse Nd:YAG lasers have received the mandatory designation, CE, for marketed products in Europe, whereas in they have not been approved yet in North America. Their pulse duration is in millisecond and as they produce a high degree of non-specific heating it may be necessary to operate in the presence of dedicated cooling system.
Short Pulse Laser Systems
The first two lasers that FDA approved for the onychomycosis treatment are both flash lamp pumped short pulse Nd:YAG 1064 nm Lasers.
Q-switched Laser Systems
Q-switched lasers compared to all Nd:YAG lasers have duration pulse in nanonsecond and they produce the highest peak power per pulse. More specifically, one Q-switched Nd:YAG 1064 nm laser, FDA approved, resulted to be very effective in the cleansing of dystrophic toenails diagnosed with onychomycosis. Statistics indicated that there was significant apparent clearing in 95% of the subjects with an average clearance of affected areas of 56 ± 7% at 98% level of confidence.
Near Infrared Diode Lasers
Diode Lasers, operate at near infrared wavelengths and use semi-conductors instead of solid crystals for the optical gain medium. Four treatment sessions are necessary with a six-week period between them.
Photdynamic Therapy (PDT) was initially optimized for actinic keratosis, but can also be applied for the treatment of onychomycosis as photosensitizers can be absorbed by fungi. PDT uses visible spectrum light to activate a topically applied photosensitizing agent, which generates reactive oxygen species that initiate apoptosis.
The effects of various photosensitizing agents have been studied in vitro and in vivo. These include methyl aminolevulinate (MAL), 5-aminolevulinic acid (ALA), 20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and 5,10,15-tris (4-methylpyridiuium).
Heme Biosynthesis Intermediates – ALA and MAL
As heme precursors, ALA and MAL accumulate protoporphyrin IX (PpIX), a photodynamically active molecule. PpIX, when the right spectrum of light is present, produces reactive oxygen species which starts apoptosis. These two medications are available for the treatment of actinic keratosis. Further on, studies demonstrated that the protocols should firstly include the pre-treatment of the nail plate with urea ointment to soften it and then the application of the photosensitizer should follow.
A low-level electrical current is used to increase the transmission of the medication to semi-permeable obstacles. Iontophoresis, contrary to the conventional local treatments that are unable to penetrate the plate of the nail, is more effective in penetrating the medication into the nail plate, pass it through to make sure that the drug inserts the nail matrix and bed.
This technique is now being ameliorated for terbinafine due to the fact that in dermatophytes in vitro, terbinafine demonstrates the best antifungal effect.
There are two iontophoresis devices. Iontophoresis through an uptake from a passive source increases the accumulated amount of terbinafine in the nail plate. That way, a reservoir of terbinafine is created, the nail plate, which releases it (terbinafine) gradually into the matrix and nail bed for the following 60-70 days.
Ultrasound Drug Delivery System
The ultrasound-mediated nail drug delivery system constitutes the latest achievement in device-based therapeutic schemes for the treatment of onychomycosis.
Clinical trials demonstrated that device-based treatments including photodynamic therapy, LASERs, ultrasound-based & iontophoresis are promising as well as advantageous as they don’t require long-term patience adherence.
Being highly localized these schemes are able to eliminate side effects due to the antifungal medications. Furthermore, they can act as another possible choice of treatment for people who are susceptible to onychomycosis due to comorbidity, as these device-based treatments are not able to interact with the medication involved in such conditions.
Aditya K. Gupta, MD, PhD, MBA, FAAD, FRCPC
Fiona Simpson, HBSc