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- Author or Editor: Aditya K. Gupta x
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Onychomycosis is a chronic fungal infection of the nail that is recalcitrant to treatment. It is unclear why normally effective antifungal therapy results in low cure rates. Evidence suggests that there may be a plethora of reasons that include the limited immune presence in the nail, reduced circulation, presence of commensal microbes, and fungal influence on immune signaling. Therefore, treatment should be designed to address these possibilities and work synergistically with both the innate and adaptive immune responses.
Background: Onychomycosis is a chronic fungal nail infection caused predominantly by dermatophytes, and less commonly by nondermatophyte molds and Candida species. Onychomycosis treatment includes oral and topical antifungals, the efficacy of which is evaluated through randomized, double-blind, controlled trials for US Food and Drug Administration approval. The primary efficacy measure is complete cure (complete mycologic and clinical cure). The secondary measures are clinical cure (usually ≤10% involvement of target nail) and mycologic cure (negative microscopy and culture). Some lasers are US Food and Drug Administration approved for the mild temporary increase in clear nail; however, some practitioners attempt to use lasers to treat and cure onychomycosis.
Methods: A systematic review of the literature was performed in July of 2020 to evaluate the efficacy rates demonstrated by randomized controlled trials of laser monotherapy for dermatophyte onychomycosis of the great toenail.
Results: Randomized controlled trials assessing the efficacy of laser monotherapy for dermatophyte toenail onychomycosis are limited. Many studies measured cure rates by means of nails instead of patients, and performed only microscopy or culture, not both. Only one included study reported mycologic cure rate in patients as negative light microscopy and culture (0%). The combined clinical cure rates in short- and long-pulsed laser studies were 13.0%–16.7% and 25.9%, respectively. There was no study that reported the complete cure rate; however, one did report treatment success (mycologic cure [negative microscopy and culture] and ≤10% clinical involvement) in nails as 16.7%.
Conclusions: The effectiveness of lasers as a therapeutic intervention for dermatophyte toenail onychomycosis is limited based on complete, mycologic, and clinical cure rates. However, it may be possible to use different treatment parameters or lasers with a different wavelength to increase the efficacy. Lasers could be a potential management option for older patients and onychomycosis patients with coexisting conditions such as diabetes, liver, and/or kidney diseases for whom systemic antifungal agents are contraindicated or have failed.
Fungal Lung
The Risk of Fungal Exposure to Nail Care Professionals
Foot and nail care specialists spend a great portion of their day using nail drills to reduce nail thickness and smooth foot calluses. This process generates a large amount of dust, some of which is small enough to breathe in and deposit into the deepest regions of the respiratory tract, potentially causing health problems. Foot and nail dust often contains fungi, from both fungus-infected and healthy-appearing nails. Although the majority of healthy individuals can tolerate inhaled fungi, the immune systems of older, immunocompromised, and allergy-prone individuals often react using the inflammatory T helper cell type 2 pathway, leading to mucus overproduction, bronchoconstriction, and, in severe cases, lung tissue damage. To protect vulnerable podiatry professionals, wearing a surgical mask, using a water spray suppression system on nail drills, installing air filtration systems, and considering drilling technique can help reduce exposure to nail dust.
Foot and nail care specialists spend a great portion of their day using nail drills to reduce nail thickness and smooth foot callouses. This process generates a large amount of dust, some of which is small enough to breathe in and deposit into the deepest regions of the respiratory tract, potentially causing health problems. Foot and nail dust often contain fungi, from both fungally-infected and healthy-looking nails. While the majority of healthy individuals can tolerate inhaled fungi, the immune systems of older, immunocompromised, and allergy-prone individuals often react using the inflammatory TH2 pathway, leading to mucus overproduction, bronchoconstriction, and, in severe cases, lung tissue damage. To protect vulnerable podiatry professionals, wearing a surgical mask, using a water spray suppression system on nail drills, installing air filtration systems, and considering drilling technique can help reduce the exposure to nail dust.
Abstract
Drug based treatment of superficial fungal infections, such as onychomycosis, is not the only defense. Sanitization of footwear such as shoes, socks/stockings, and other textiles is integral to the prevention of recurrence, and reduction of spread for superficial fungal mycoses. The goal of this review was to examine the available methods of sanitization for footwear and textiles against superficial fungal infections. A systematic literature search of various sanitization devices and methods that could be applied to footwear and textiles using PubMed, Scopus, and MEDLINE was performed. Fifty-four studies were found relevant to the different methodologies, devices, and techniques of sanitization as it pertains to superficial fungal infections of the feet. These included topics of basic sanitization, antifungal and antimicrobial materials, sanitization chemicals and powder, laundering, ultraviolet, ozone, non-thermal plasma, microwave radiation, essential oils, and natural plant extracts. In management of onychomycosis it is necessary to think beyond treatment of the nail, as infections enter through the skin. Those prone to onychomycosis should examine their environment, including surfaces, shoes, and socks, and ensure that proper sanitization is implemented.
Background: Onychomycosis is a chronic fungal nail infection caused predominantly by dermatophytes, and less commonly by non-dermatophyte molds (NDMs) and Candida species. Onychomycosis treatment includes oral and topical antifungals, the efficacy of which is evaluated through randomized, double-blinded, controlled trials (RCTs) for USA FDA approval. The primary efficacy measure is complete cure (complete mycological and clinical cure). The secondary measures are clinical cure (usually {less than or equal to}10 % involvement of target nail) and mycological cure (negative microscopy and culture). Some lasers are FDA-approved for the mild temporary increase in clear nail; however, some practitioners attempt to use lasers to treat and cure onychomycosis. Methods: A systematic review of the literature was performed in July 2020 to evaluate the efficacy rates demonstrated by RCTs of laser monotherapy for dermatophyte onychomycosis of the great toenail. Results: RCTs assessing the efficacy of laser monotherapy for dermatophyte toenail onychomycosis are limited. Many studies measured cure rates via nails instead of patients, and performed only microscopy or culture, not both. Only one included study reported mycological cure rate in patients as negative light microscopy and culture (0%). The combined clinical cure rates in short- and long-pulsed laser studies were (13.0-16.7% and 25.9%, respectively). There was no study that reported the complete cure rate, however, one did report treatment success (mycological cure (negative microscopy and culture) and {less than or equal to}10% clinical involvement) in nails as 16.7%. Conclusions: The effectiveness of lasers as a therapeutic intervention for dermatophyte toenail onychomycosis is limited based on complete, mycological, and clinical cure rates. However, it may be possible to use different treatment parameters or lasers with a different wavelength to increase the efficacy. Lasers could be a potential management option for older patients and onychomycosis patients with coexisting conditions such as diabetes, liver and/or kidney diseases for whom systemic antifungal agents are contraindicated or have failed.
Fungal Diversity and Onychomycosis
An Analysis of 8,816 Toenail Samples Using Quantitative PCR and Next-Generation Sequencing
Background:
Onychomycosis is a fungal infection of the nail that is often recalcitrant to treatment and prone to relapse. Traditional potassium hydroxide and culture diagnosis is costly and time-consuming. Therefore, molecular methods were investigated to demonstrate effectiveness in diagnosis and to quantify the microbial flora present that may be contributing to disease.
Methods:
A total of 8,816 clinically suspicious toenail samples were collected by podiatric physicians across the United States from patients aged 0 to 103 years and compared with a control population (N = 20). Next-generation sequencing and quantitative polymerase chain reaction were used to identify and quantify dermatophytes, nondermatophyte molds, and bacteria.
Results:
Approximately 50% of suspicious toenails contained both fungi and bacteria, with the dermatophyte Trichophyton rubrum contributing the highest relative abundance and presence in 40% of these samples. Of the remaining 50% of samples, 34% had bacterial species present and 16% had neither. Fungi only were present in less than 1% of samples. Nondermatophyte molds contributed to 11.0% of occurrences in fungus-positive samples. All of the control samples were negative for fungi, with commensal bacterial species composing most of the flora population.
Conclusions:
Molecular methods were successful in efficiently quantifying microbial and mycologic presence in the nail. Contributions from dermatophytes were lower than expected, whereas the opposite was true for nondermatophyte molds. The clinical significance of these results is currently unknown.
Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed. The efficacy of tavaborole is associated with its novel mechanism of action, whereby it inhibits the fungal leucyl-tRNA synthetase (LeuRS) enzyme. Because LeuRS is an essential component in fungal protein synthesis, inhibition of LeuRS ultimately leads to fungal cell death. Tavaborole is the first boron-based antifungal medication approved for the treatment of mild-to-moderate onychomycosis and presents patients with a new topical option. Previously, ciclopirox and efinaconazole were the only approved topical treatments for onychomycosis. This article details the properties that are at the core of the clinical benefits associated with tavaborole.
