Jennifer E. Ryder

Non-dermatophyte onychomycosis

Non-dermatophyte organisms are becoming increasingly prevalent in onychomycosis. This apparent emergence might be an artifact of improved diagnostic techniques and increased awareness that these fungi are potential etiologic agents. It is important to bear in mind that all isolated organisms should be evaluated as potential pathogens when diagnosing fungal infections, especially given the increasing use of immunosuppressive drugs and the increasing numbers of chronically immunocompromised individuals. While many patients with non-dermatophyte mold onychomycosis will respond to oral or topical antifungal therapy, poor or incomplete response might still be expected in some patients.

Optimal Management of Fungal Infections of the Skin, Hair, and Nails

Superficial fungal infections are chronic and recurring conditions. Tinea capitis is a scalp infection, primarily affecting prepubescent children. Ringworm infections, such as tinea corporis and tinea cruris, involve the glabrous skin. Tinea nigra is a rare mycotic infection that may be related to travel abroad. Piedra, black or white, is limited to the hair shaft without involvement of the adjacent skin. Pityriasis (tinea) versicolor and seborrheic dermatitis are dermatoses associated with yeasts of the genus Malassezia that affect the lipid-rich areas of the body. The taxonomy of the Malassezia yeasts has been revised to include nine species, eight of which have been recovered from humans. Tinea pedis, an infection of the feet and toes, is one of the most common forms of dermatophytosis. Onychomycosis is a fungal infection affecting the nail bed and nail plate; it may be chronic and can be difficult to treat. In instances where the superficial fungal infection is severe or chronic, an oral antifungal agent should be considered. Terbinafine, itraconazole, and fluconazole are oral antifungals that are effective in the treatment of superficial mycoses.

The use of topical therapies to treat onychomycosis

The management of onychomycosis using topical agents has improved with the introduction of ciclopirox and amorolfine nail lacquers; other topical agents may be less effective. The combination of a nail lacquer with an oral antifungal agent may further improve efficacy rates in certain clinical presentations (eg, among those individuals with severe onychomycosis). Topical agents have a favorable adverse events profile. Further studies are required on the treatment of onychomycosis with nail lacquers.

Photodynamic Therapy and Topical Aminolevulinic Acid

Photodynamic therapy is a non-invasive technique used in the treatment of skin diseases which has various advantages, one being the ability to localize treatment to the area being treated, which is common among most photosensitizers. Aminolevulinic acid is a prodrug that is metabolized intracellularly to form the photosensitizing molecule protoporphyrin IX (PpIX). When PpIX is activated by light, cytotoxic reactive oxygen species and free radicals are generated. This phototoxic effect may cause malignant and non-malignant hyperproliferative tissue to be destroyed, to decrease in size, and to eventually disappear. The application of topical aminolevulinic acid 20% followed by the use of a blue light photodynamic therapy illuminator is indicated in the US for the treatment of non-hyperkeratotic actinic keratoses of the face or scalp. There are data suggesting that aminolevulinic acid/photodynamic therapy may also be beneficial in acne vulgaris, verrucae, psoriasis, mycosis fungoides, and human papillomavirus. This treatment modality has also proven effective in the management of skin cancer such as, Bowen disease and basal cell carcinoma. Further experience in the use of photodynamic therapy will help define its utility in the management of actinic keratosis and other dermatoses.

The use of oral antifungal agents to treat onychomycosis

Onychomycosis has been treated for years with oral antifungal agents, and more recently in the United States with a topical nail lacquer. Griseofulvin was the first significant oral agent available to manage onychomycosis. The introduction of the azoles (ketoconazole, itraconazole, and fluconazole) and the allylamine, terbinafine, led to improved cure rates and a broad spectrum of activity. Pharmacokinetic studies have shown that the newer oral agents penetrate the nail within approximately one to two weeks after the start of therapy and remain for several months after the end of treatment. This article reviews the oral antifungal agents used to treat onychomycosis.

How to improve cure rates for the management of onychomycosis

To improve the treatment of onychomycosis clinicians need to identify correctly the causative organism, choose a therapy that is effective against the pathogen, and take into consideration the pharmacokinetics (eg, bioavailability, drug interactions) of the oral agent. In addition, variations of the standard regimens may need to be considered (ie, booster or supplemental therapy). To reduce the recurrence of onychomycosis, once mycologic cure has been achieved, clinicians should educate their patients about proper foot care. Familiarity with the symptoms and signs of tinea pedis and onychomycosis may enable patients to seek appropriate care when the disease is at an early stage.

Comparison of efficacy criteria across onychomycosis trials: need for standardization

Background The last 10 years have seen a substantial increase in the number of studies reporting the efficacy of the various antifungal agents used to treat onychomycosis.

Naftifine: a review.

Background: Naftifine is a topical allylamine that is effective and safe in the management of superficial dermatomycoses. Naftifine is fungicidal in vitro against a broad spectrum of dermatophyte fungi and provides good activity against Candida and Aspergillus species. It is also effective against gram-negative and gram-positive bacteria. Objective: To provide a review of the pharmacologic properties and clinical efficacy of topical naftifine preparations. Methods: A review of the medical literature was performed using PubMed (1965–2006) using the search term “naftifine.” All available English-language articles discussing the pharmacology and clinical use of naftifine were reviewed for the article. Results: Naftifine causes interruption of fungal ergosterol synthesis and accumulation of squalene in fungal organisms. Naftifine also has demonstrated anti-inflammatory properties such as a reduction in superoxide production and a reduction in polymorphonuclear leukocyte chemotaxis/endothelial adhesion. Naftifine has shown good efficacy and safety for a variety of conditions and is a useful treatment that provides both antifungal action and relief of inflammatory signs and symptoms. Few adverse events have been noted with naftifine use, the most frequent being mild and transient burning, stinging, or itching in the application area. Conclusion: Naftifine remains a reliable multifunctional agent for a variety of superficial infections.

Onychomycosis: Quality of Studies

Objective: The quality of original clinical trial publications pertaining to the use of oral antifungal agents to treat onychomycosis was evaluated using predetermined criteria. Methods: The list of studies included in this analysis was determined by conducting a search in Medline. For each clinical trial, two independent reviewers each determined a composite score by evaluating a list of criteria that were felt to represent a good study, for example, randomization and blinding, prior sample size calculated, and treatment regimen clearly explained. A citation count was performed to determine whether higher-quality papers were cited more often than lower-quality papers. Results: Forty-five studies were included in this quality analysis of study design. Of these, 27 were considered to be “high quality” (score greater than or equal to 11 out of 20). A significant correlation coefficient of 0.997 was found between the two reviewers (P < 0.00001). Higher-quality papers were cited significantly more often than lower-quality papers (P = 0.03). Conclusion: The scale that we use to evaluate the quality of onychomycosis studies has high interrater reliability. According to this scale, many published studies (18 out of 45) pertaining to treatments for onychomycosis do not meet the criteria required to be considered “high quality.” SommaireObjectif: Évaluation de la qualité des publications initiales relatives aux essais cliniques sur l’usage d’agents antifongiques oraux, au moyen de critères prédéterminés. Méthodes: La liste des études considérées dans cette analyse a été tirée de la base de données Medline. Deux examinateurs indépendants ont déterminé chacun le score composite de chaque essai clinique en tenant compte d’une liste de critères qui définiraient une bonne étude. Par exemple, la randomisation, l’insu, le calcul de la taille de l’échantillon et l’explication claire du schema thérapeutique. Un compte des références a été fait au préalable pour voir si les travaux de haute qualité étaient cités plus que les travaux de moindre qualité. Résultats: L’analyse de la qualité de la méthodologie a porté sur 45 études. Parmi ces études, 27 ont été considérées de « haute qualité » (score supérieur ou égal à 11 sur 20). Un coefficient de corrélation élevé de 0,997 a été trouvé entre les deux examinateurs (P < 0,00001). Les travaux de haute qualité ont été cités plus fréquemment que les travaux de moindre qualité (P = 0,03). Conclusion: L’échelle que nous avons adoptée dans l’évaluation de la qualité des études sur l’onychomycose présente un coefficient d’objectivité élevé. Selon cette échelle, un grand nombre d’études publiées (18 sur 45) sur le traitement des onychomycoses ne répondent pas aux critères requis pour étre considérées de « haute qualite ».