Onychomycosis: burden of disease and the role of topical antifungal treatment.

Onychomycosis is not just a cosmetic problem. It is a common disorder that may be a reservoir of infection and lead to significant medical problems. In addition, onychomycosis may cause a substantial decrease in quality of life. An understanding of the disorder and updated management is important for all health care professionals. Onychomycosis is the most common nail disorder in adults. It is four to seven times more frequent in toenails, where it often involves several nails. It is a progressive disease, and although not life threatening it is inappropriately considered purely a cosmetic problem, with some physicians still believing there is no need to treat. The fungal infection usually begins in the nail bed, and often extends to the nail plate. Onychomycosis is unsightly and can be uncomfortable; with discoloration of the nail plate and more severe disease resulting in loss of the nail plate altogether. Onychomycosis may become a source of more widespread fungal lesions, spreading to other nails, body sites (groin, skin, scalp), and even to family members.

Toenail onychomycosis: current and future treatment options.

Onychomycosis is a common disease affecting as much as 8% of the general population. Treatment of onychomycosis is challenging, complicated by low cure rates and relatively high relapse rates. This paper reviews the efficacy of current oral, topical, and surgical treatment options. Currently, the treatment of choice for toenail onychomycosis is oral terbinafine because of its high efficacy, low relapse rates, and cost-effectiveness. Oral itraconazole or fluconazole could be considered for infections caused by Candida. Topical therapies may be a useful adjunct to these systemic therapies, but are less effective when used alone. More research is needed to determine the best measures for preventing reinfection.

Toenail assessment tool for quantitation of visibly infected mycotic nail plate in onychomycosis.

Typically, the amount of mycotic nail involvement in onychomycosis (fungal infection of the nail) before and after drug therapy is determined visually. Because there is an inherent element of subjectivity, it is difficult to accurately measure and compare results across clinical trials or to assess how much improvement has been achieved in response to therapy. We developed a simple tool for measuring mycotic nail involvement. This novel tool consists of a large grid containing 5 toenail templates of varying nail morphologies that are derived from the actual shape of the toenail of the great toe in several males and females, and one standardized computer-generated nail shape. The toenail templates are presented in 7 different sizes to match different nail sizes. Each toenail template is further divided into 8 segments, each comprising approximately 12.5% of the total nail surface. Measurement of the percentage of mycotic nail involvement is accomplished by the following procedure: (1) placing tracing film over the target toenail; (2) tracing the outline of the entire toenail, followed by tracing the affected portion of the toenail on the same film; (3) placing the tracing film over a nail template on the grid that best fits the shape of the toenail; and (4) counting the number of grid segments that correspond to 50% or more involvement. To assess feasibility, the tool was used in a large randomized trial involving over 30 sites and 500 subjects with onychomycosis. This tool is a more accurate and less biased alternative to visual assessment for measuring nail involvement or progression of nail clearing.

Utility of histopathologic analysis in the evaluation of onychomycosis.

Onychomycosis is a common problem seen in clinical practice. Given the differential diagnosis of dystrophic nails, it is helpful to obtain a definitive diagnosis of dermatophyte infection before initiation of antifungal therapy. Potassium hydroxide preparation and fungal culture, which are typically used in the diagnosis of these infections, often yield false-negative results. Recent studies have suggested that nail plate biopsy with periodic acid-Schiff stain may be a very sensitive technique for the diagnosis of onychomycosis. In this article, we review the literature on the utility of histopathologic analysis in the evaluation of onychomycosis. Many of these studies indicate that biopsy with periodic acid-Schiff is the most sensitive method for diagnosing onychomycosis. We propose that histopathologic examination is indicated if the results of other methods are negative and clinical suspicion is high; therefore, it is a useful complementary technique in the diagnosis of onychomycosis.

Influence of human nail etching for the assessment of topical onychomycosis therapies.

The purpose of this investigation was to study the physico-chemical properties of hot-melt extruded films containing ketoconazole and to determine the influence of 'nail etching' on film bioadhesion and drug permeability for the assessment of topical onychomycosis therapies. Hot-melt extrusion (HME) was used to prepare films containing 20% w/w ketoconazole. Ketoconazole 0.125% gel was also prepared using Carbopol 974P NF. Films were processed at a temperature range of 115-120 degrees C utilizing a Killion extruder (KLB-100), and were evaluated for post-extrusion drug content, content uniformity, bioadhesion, thermal behavior and nail drug permeation. The extruded films demonstrated excellent content uniformity and post-processing drug content. Tensile and peel tests were recorded to determine the bioadhesive profiles. In this study, work of adhesion and peak adhesive force determinations using the peel tests provided more sensitive results for evaluating the bioadhesivity of the HME films than the tensile tests. The in vitro permeability profiles have demonstrated, that nail samples treated with an 'etchant' demonstrated a significant increase in drug permeability compared to control. Differential scanning calorimetry (DSC) thermograms indicated that ketoconazole was in solid solution within the HME films. These findings are encouraging for the future design and formulation of novel drug delivery systems for the topical treatment of onychomycosis.