Global perspectives for the management of onychomycosis.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophyte molds, and yeasts. This difficult-to-treat chronic infection has a tendency to relapse despite treatment. This paper aims to offer a global perspective on onychomycosis management from expert physicians from around the world. Overall, the majority of experts surveyed used systemic, topical, and combination treatments approved in their countries and monitored patients based on the product insert or government recommendations. Although the basics of treating onychomycosis were similar between countries, slight differences in onychomycosis management between countries were found. These differences were mainly due to different approaches to adjunctive therapy, rating the severity of disease and use of prophylaxis treatment. A global perspective on the treatment of onychomycosis provides a framework of success for the committed clinician with appreciation of how onychomycosis is managed worldwide.

Tatami Mats: A Source of Pitted Keratolysis in a Martial Arts Athlete?

Dear Editor, Pitted keratolysis (PK), also known as keratosis plantaris sulcatum, is a non-inflammatory, bacterial, superficial cutaneous infection, characterized by many discrete superficial crateriform ''pits'' and erosions in the thickly keratinized skin of the weight-bearing regions of the soles of the feet (1). The disease often goes unnoticed by the patient, but when it is noticed it is because of the unbearable malodor and hyperhidrosis of the feet, which are socially unacceptable and cause great anxiety to many of the patients. PK occurs worldwide, with the incidence rates varying based on the environment and occupation. The prevalence of this condition does not differ significantly based on age, sex, or race. People who sweat profusely or wash excessively, who wear occlusive footwear, or are barefoot especially in hot and humid weather are extremely prone to this condition (2). Physicians commonly misdiagnose it as tinea pedis or plantar warts. Treatment is quite simple and straightforward, with an excellent expected outcome if treated properly. We report a case of a 32-year-old male patient with skin changes of approximately one-year duration diagnosed as plantar verrucae, who was referred to our Department for cryotherapy. The patient presented with asymptomatic, malodorous punched-out pits and erosions along with hyperkeratotic skin on the heel and metatarsal region of the plantar aspect of both feet. The arches, toes, and sides of the feet were spared (Figure 1). Except for these skin changes, the patient was healthy and denied any other medical issues. He was an athlete active in martial arts and had a history of sweating of feet and training barefoot on the tatami mat for extended periods of time. The diagnosis of PK was established based on the clinical findings (crateriform pitting and malodor), negative KOH test for hyphae, and a history of prolonged sweating in addition to contact of the skin with tatami mats, which are often a source of infection if hygiene measures are not adequately implemented. Swabs could have been helpful to identify causative organisms, but they were not crucial for the diagnosis and treatment. The patient was prescribed with general measures to prevent excessive sweating (cotton socks, open footwear, and proper hygiene), antiseptic potassium permanganate foot soaks followed by clindamycin 1% and benzoyl peroxide 5% in a gel vehicle twice daily. At the one-month follow-up visit, the skin changes, hyperhidrosis, and malodor were entirely resolved (Figure 2). Pitted keratolysis is common among athletes (3,4). The manifestations of PK are due to a superficial cutaneous infection caused by several bacterial Gram-positive species including Corynebacterium species, Kytococcus sedentarius, Dermatophilus congolensis, Actynomices keratolytica, and Streptomyces that proliferate and produce proteinase and sulfur-compound by-products under appropriate moist conditions (5-7). Proteinases digest the keratin and destroy the stratum corneum, producing the characteristic skin findings, while sulfur compounds (sulfides, thiols, and thioesters) are responsible for the malodor. Athletes and soldiers who wear occlusive footwear for prolonged periods of time or even barefooted people that sweat extensively and spend time on wet surfaces such as laborers, farmers, and marine workers are more prone to this problem (3,4,8-11). Martial arts athletes are at greater risk of skin infections due to the constant physical contact that can lead to transmission of viral, bacterial, and fungal pathogens directly but also indirectly through contact with the mat and the skin flora of an another infected individual. A national survey of the epidemiology of skin infections among US high school athletes conducted by Ashack et al. supported the prevalent theory that contact sports are associated with an increased risk of skin infections. In this study, wrestling had the highest skin infection rate of predominantly bacterial origin (53.8%), followed by tinea (35.7%) and herpetic lesions (6.7%), which is consistent with other literature reporting (12). Being barefoot on the tatami mat in combination with excessive sweating and non-compliance with hygiene measures makes martial arts athletes more susceptible to skin infections, including PK. The diagnosis is clinical, by means of visual examination and recognition of the characteristic odor. Dermoscopy can be useful, revealing abundant pits with well-marked walls that sometimes show the bacterial colonies (13). Cultures, if taken, show Gram-positive bacilli or coccobacilli. Because of the ease of diagnosis on clinical findings, biopsy of pitted keratolysis is rarely performed. Skin scraping is often performed to exclude tinea pedis, which is one of the main differential diagnosis, the others including verrucae, punctate palmoplantar keratoderma, keratolysis exfoliativa, circumscribed palmoplantar hypokeratosis, and basal cell nevus syndrome. If unrecognized and left untreated, skin findings and smelly feet can last for many years. Sometimes, if unrecognized, PK can be mistreated with antifungals, or even with aggressive treatment modalities such as cryotherapy. Appropriate treatment includes keeping feet dry with adequate treatment of hyperhidrosis, preventive measures, and topical antibiotic therapy. Topical forms of salicylic acid, sulfur, antibacterial soaps, neomycin, erythromycin, mupirocin, clindamycin and benzoyl peroxide, clotrimazole, imidazoles, and injectable botulinum toxin are all successful in treatment and prevention of PK (14,15). Topical antibiotics are the first line of medical treatment, among which fusidic acid, erythromycin 1% (solution or gel), mupirocin 2%, or clindamycin are the most recommended (14). As in our case, a fixed combination of two approved topical drugs - clindamycin 1%-benzoyl peroxide 5% gel, had been already demonstrated by Vlahovich et al. as an excellent treatment option with high adherence and no side-effect (16). The combined effect of this combination showed significantly greater effect due to the bactericidal and keratolytic properties of benzoyl peroxide. Additionally, this combination also lowers the risk of resistance of causative microorganisms to clindamycin. Skin infections are an important aspect of sports-related adverse events. Due to the interdisciplinary nature, dermatologists are not the only ones who should be aware of the disease, but also family medicine doctors, sports medicine specialists, and occupational health doctors who should educate patients about the etiology of the skin disorder, adequate prevention, and treatment. Athletes must enforce the disinfecting and sanitary cleaning of the tatami mats and other practice areas. Keeping up with these measures could significantly limit the spread of skin infections that can infect athletes indirectly, leading to significant morbidity, time loss from competition, and social anxiety as well.

Clinical laser treatment of toenail onychomycoses.

Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis.

Complete cure of Fusarium solani sp. complex onychomycosis with Qs NdYAG treatment.

The incidence of non dermatophytic mould (NDM) onychomycosis (OM) has been steadily increasing Fusarium spp is the most common cause of NDM OM in most geographical locations. Fusarium spp and other NDMs are largely resistant to commonly used anti-fungals. The successful use of laser and light based devices has been demonstrated in dermatophytic OM, but there is no previous report of their successful use in any NDM OM. We describe a patient with OM caused by Fusarium solani spp, who was clinically (with a normal appearing nail) and mycologically (with negative microscopy and culture on repeated samples) cured of her infection following treatment with 2 sessions of Qs NdYAG (532nm and 1064nm) given 1 month apart.

Factors influencing cure rates of non-dermatophyte mold and Candida onychomycosis: analysis of outcomes in 81 patients who completed treatment.

OBJECTIVES: Onychomycosis shows a poor response to current topical, oral, or device-related antifungal therapies. The aim of this study was to identify factors influencing the cure rates of non-dermatophyte mold and Candida onychomycosis. METHODS: Eighty-one patients who completed treatments were divided into "cured" and "non-cured" groups. The statistical significance of differences between the two groups was studied. RESULTS: Male gender (P < 0.01), long duration of disease before the initiation of treatment (P < 0.02), three or more infected nails (P < 0.0002), continuous exposure to water and detergents (P < 0.05), frequent exposure to mud and soil (P < 0.01), barefoot walking (P < 0.025), concomitant diabetes and hypertension (P < 0.04), eczema (P < 0.03), and associated paronychia (P < 0.01) had negative effects on cure rates of onychomycosis. Patient age, occupation, site of illness (hand, foot or big toe), type of disease (distal and lateral subungual onychomycosis, proximal subungual onychomycosis or total dystrophic onychomycosis), pathogenic fungi, and treatment modality had no statistically significant impact on cure rate. CONCLUSIONS: To minimize the failure rate of antifungal therapies in the treatment of onychomycosis, patients are advised to start treatment as soon as possible, and to avoid predisposing factors such as exposure to water, detergents, mud and soil, and barefoot walking.

Treatment of onychomycosis using the 1 064 nm Nd:YAG laser: a clinical pilot study.

BACKGROUND: Nd:YAG lasers could be a safe and effective treatment modality for onychomycosis, without the side effects of drugs. Long and short-pulsed Nd:YAG lasers were used in this clinical study in a side-comparison manner without removal of onychomycotic nail material before treatment. PATIENTS AND METHODS: Big toenails of 10 patients were treated twice in a side-comparison manner with the short-pulsed Nd:YAG laser. Fungal cultures were taken and a histological examination was performed before treatment and after 9 months. Two independent investigators rated clearance using the "Onychomycosis Severity Index (OSI)" and standardized photographs at 3-month intervals. RESULTS: OSI-Scores decreased for 3.8 (15 %; p = 0.006), 4.8 (19 %; p = 0.0002) and 2.9 points (12 %; p = 0.04) within 3, 6 and 9 months. The positive culture rate at 9 months was significantly reduced to 35 % (p = 0.0003). Classification of severity of onychomycosis showed no change. The difference between the treatment regimens was not significant. CONCLUSIONS: These results suggest that treatment of onychomycosis with the Nd:YAG laser without removing mycotic nail material can lead to a temporary clinical improvement, a reduction of positive fungal cultures and an improvement of the Onychomycosis Severity Index. The treatment regimen should be optimized to be used as an effective antimycotic monotherapy.

An investigation into the inhibitory effect of ultraviolet radiation on Trichophyton rubrum.

Fungal infection of nails, onychomycosis, is predominantly caused by Trichophyton rubrum. This infection is an important public health concern due to its persistent nature and high recurrence rates. Alternative treatments are urgently required. One such alternative is phototherapy involving the action of photothermal or photochemical processes. The aim of this novel study was to assess which wavelengths within the ultraviolet (UV) spectrum were inhibitory and equally important nail transmissible. Initial irradiations of T. rubrum spore suspensions were carried out using a tunable wavelength lamp system (fluence ≤3.1 J/cm(2)) at wavelengths between 280 and 400 nm (UVC to UVA) to evaluate which wavelengths prevented fungal growth. Light-emitting diodes (LEDs) of defined wavelengths were subsequently chosen with a view to evaluate and potentially implement this technology as a low-cost "in-home" treatment. Our experiments demonstrated that exposure at 280 nm using an LED with a fluence as low as 0.5 J/cm(2) was inhibitory, i.e., no growth following a 2-week incubation (p < 0.05; one-way ANOVA), while exposure to longer wavelengths was not. A key requirement for the use of phototherapy in the treatment of onychomycosis is that it must be nail transmissible. Our results indicate that the treatment with UVC is not feasible given that there is no overlap between the antifungal activity observed at 280 nm and transmission through the nail plate. However, a potential indirect application of this technology could be the decontamination of reservoirs of infection such as the shoes of infected individuals, thus preventing reinfection.

Is Trichophyton simii endemic to the Indian subcontinent?

Trichophyton simii is considered to be prevalent only in the Indian subcontinent where it was isolated from soil, as well as from infections of humans and animals. We have investigated a case of onychomycosis caused by this exotic dermatophyte, not traceable to endemic areas. This case, as in others due to this fungus in man or animals, that have been previously and sporadically reported worldwide, suggests infections caused by T. simii might be underestimated, especially outside its primary geographic areas. Indeed, there are isolates that do not show species-specific morphology, as in our case isolate, and as a result may be misidentified by classical methods. By checking the identity of some strains preserved in the collection BCCM/IHEM, we found several that proved to be T. simii, originating from non-endemic areas (Belgium, France and Ivory Coast). Therefore, the natural distribution of T. simii is probably not as restricted as has previously been proposed.

Novel treatment of onychomycosis using over-the-counter mentholated ointment: a clinical case series.

BACKGROUND: current medication treatments for onychomycosis have less than full cure-rate efficacy and have the potential for adverse side effects. Vicks VapoRub (The Proctor & Gamble Company, Cincinnati, OH) has been advocated in the lay literature as an effective treatment for onychomycosis. This pilot study tested Vicks VapoRub as a safe, cost-effective alternative for treating toenail onychomycosis. METHODS: eighteen participants were recruited to use Vicks VapoRub as treatment for onychomycosis. Participants were followed at intervals of 4, 8, 12, 24, 36, and 48 weeks; digital photographs were obtained during initial and follow-up visits. Primary outcome measures were mycological cure at 48 weeks and clinical cure through subjective assessment of appearance and quantifiable change in the area of affected nail by digital photography analysis. Patient satisfaction was a secondary outcome, measured using a single-item questionnaire scored by a 5-point Likert scale. RESULTS: fifteen of the 18 participants (83%) showed a positive treatment effect; 5 (27.8%) had a mycological and clinical cure at 48 weeks; 10 (55.6%) had partial clearance, and 3 (16.7%) showed no change. All 18 participants rated their satisfaction with the nail appearance at the end of the study as "satisfied" (n = 9) or "very satisfied" (n = 9). CONCLUSIONS: Vicks VapoRub seems to have a positive clinical effect in the treatment onychomycosis.

Diagnosis of Trichophyton rubrum from onychomycotic nail samples using polymerase chain reaction and calcofluor white microscopy.

BACKGROUND: A high rate of false-negative dermatophyte detection is observed when the most common laboratory methods are used. These methods include microscopic observation of potassium hydroxide-digested nail clippings and culture methods using agar-based media supplemented with cycloheximide, chloramphenicol, and gentamicin to isolate dermatophytes. Microscopic detection methods that use calcofluor white staining or periodic acid-Schiff staining may also be substituted for and have previously been reported to be more sensitive than potassium hydroxide-digested nail clippings. METHODS: Trichophyton rubrum infections were detected directly from nails in a double-round polymerase chain reaction assay that uses actin gene-based primers. This method was compared with detection of fungal hyphae by using calcofluor white fluorescence microscopy of nail samples collected from 83 patients with onychomycosis who were undergoing antifungal drug therapy. RESULTS: Twenty-six of 83 samples (31.3%) were found to be positive by calcofluor white fluorescence microscopy, and 21 of 83 samples (25.3%) yielded positive results for T rubrum when actin gene-based primers in a double-round polymerase chain reaction assay were used. When calcofluor white fluorescence microscopy and polymerase chain reaction assay were used, the combined detection was 46.9% compared with 31.3% when calcofluor microscopy and culture of nail samples on Sabouraud's dextrose agar supplemented with cycloheximide, chloramphenicol, and gentamicin were used. CONCLUSIONS: These results suggest that the use of a direct DNA protocol is an alternative method for detecting Trichophyton infections. When this protocol is used, the presence of T rubrum DNA is directly detected. However, the viability of the dermatophyte is not addressed, and further methods need to be developed for the detection of viable T rubrum directly from nail samples.

Hot tub folliculitis or hot hand-foot syndrome caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a ubiquitous gram-negative rod that can cause a well-recognized, acquired skin infection from bacterial colonization of contaminated water called "hot tub folliculitis." We report an outbreak of pseudomonas skin infection associated with the use of a hot tub at a pool party in 33 children. In particular, 2 of the children were admitted to our hospital; both presented with high leukocyte counts, intermittent low grade fevers, and painful, erythematous nodules and papules on their palms and soles. One of the 2 children also presented with small erythematous pustular lesions on the face and trunk, which led to the diagnosis. Cultures from these pustules grew P aeruginosa. Thirty two other children at this pool/hot tub party developed similar lesions of varying severity 6 to 48 hours after the party. These findings were most consistent with the diagnosis of pseudomonas folliculitis/hot hand.

Low-voltage direct current as a fungicidal agent for treating onychomycosis.

Onychomycosis, most commonly caused by two species of dermatophyte fungi--Trichophyton rubrum and Trichophyton mentagrophytes--is primarily treated with regimens of topical and systemic antifungal medications. This study was undertaken to evaluate in vitro the efficacy of low-voltage direct current as an antifungal agent for treating onychomycosis. Agar plate cultures of T rubrum and T mentagrophytes were subjected to low-voltage direct current electrostimulation, and antifungal effects were observed as zones in the agar around the electrodes lacking fungal growth. Zones devoid of fungal growth were observed for T rubrum and T mentagrophytes around anodes and cathodes in a dose-dependent manner in the current range of 500 microA to 3 mA. Low-voltage direct current electrostimulation has great clinical potential for the treatment of onychomycosis and perhaps other superficial maladies of fungal etiology.

Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream.

The prevalence of onychomycosis, a superficial fungal infection that destroys the entire nail unit, is rising, with no satisfactory cure. The objective of this randomized, double-blind, placebo-controlled study was to examine the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia oil incorporated in a cream to manage toenail onychomycosis in a cohort. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6-36 months duration of disease were randomized to two groups (40 and 20), active and placebo. After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants.

Oral terbinafine (Lamisil) in the treatment of fungal infections of the skin and nails.

The efficacy and safety of antifungal drugs depend upon their mode of action, the minimal inhibitory concentration (MIC) and its relationship to the minimal fungicidal concentration (MFC), the spectrum of activity and drug kinetics at the involved site. Terbinafine acts at the fungal cell wall. Its MIC against dermatophytes is the lowest of all currently available systemic antifungal agents. It is the only one with an MIC:MFC ratio of 1:1 so that terbinafine should be effective over very short treatment durations in dermatophyte infections of the scalp, palms and soles, and nail, providing that drug penetration is adequate, as it appears to be. Therapeutic levels persist for a considerable period after the cessation of treatment, also favouring short-duration therapy. Terbinafine is effective against all varieties of dermatophyte. Terbinafine given over 4 weeks or less is effective against Trichophyton of the scalp in children and adults. Its efficacy in zoophilic ectrothrix infection is anecdotal, but it is likely on theoretical grounds. Terbinafine is also effective against pityriasis versicolor and vaginal candidosis, but only topically. As of March 1996, around 3,000,000 patients have been treated worldwide with terbinafine, mostly for 12 weeks for toe-nail onychomycosis. Gastro-intestinal disturbance and minor skin rashes are seen in 5 and 2% of patients, respectively.

Significance of non-dermatophyte moulds and yeasts in onychomycosis.

In a multicentre, randomised, double-blind, 48-week clinical trial, 118 patients with toe-nail onychomycosis were given terbinafine (250 mg daily) or placebo for 12 weeks, followed by 12 weeks of observation. Non-responders were offered 12 further weeks of terbinafine (250 mg daily) from week 28. Each patient had 8-12 consecutive nail specimens collected from the same nail, allowing for an assessment of the fungal nail flora from 1,321 nail specimens. By week 48, the overall mycological cure rate for terbinafine patients was 94%. 64% of patients had an underlying dermatophyte infection with at least 1 non-dermatophyte mould or yeast isolated from at least 1 specimen. These contaminants often overgrow or mask the presence of a dermatophyte. In only 2.5% of all patients was the same non-dermatophyte isolated from 2 or more consecutive specimens, probably representing secondary colonisation which exploits nutrients released by the underlying dermatophyte. The presence of incidental non-dermatophyte contaminants or secondary colonisers did not affect treatment outcome, and in this study treatment of the primary dermatophyte pathogen with terbinafine cleared the nails from infection in all cases. 80% of patients remained mycologically negative after 2 years.