Onychomycosis: management and treatment. Proceedings of a clinical roundtable.
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Antifungal Agents↗
Biomedical subjects
Aditya K Gupta
Publications and source records attributed to Aditya K Gupta.
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."
Administration, Oral↗
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.
Aspergillus↗
New antifungal agents.
Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the ability of scientists to detect drug resistance in fungal species. Cross-resistance of fungal species to antifungal drugs must be considered as a potential problem to future antifungal treatment, and so determination of susceptibility of fungal species to antifungal agents is an important component of information in development of new antifungal agents. Heterogeneity in susceptibility of species to azole antifungals has been noted. This heterogeneity suggests that there are differences in activity of azoles, and different mechanisms of resistance to the azoles, which may explain the present lack of cross-resistance between some azoles despite apparent structural similarities. The mechanisms of azole action and resistance themselves are not well understood, and further studies into azole susceptibility patterns are required.
Administration, Oral↗
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.
Administration, Cutaneous↗
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.
Administration, Cutaneous↗
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.
Administration, Oral↗
Seborrheic dermatitis.
Seborrheic dermatitis is present in 1% to 3% of immunocompetent adults, and is more prevalent in men than in women. Seborrheic dermatitis may be seen in conjunction with other skin diseases, such as rosacea, blepharitis or ocular rosacea, and acne vulgaris. Malassezia yeasts have been associated with seborrheic dermatitis. Abnormal or inflammatory immune system reactions to these yeasts may be related to development of seborrheic dermatitis. Treatment modalities for seborrheic dermatitis include keratolytic agents, corticosteroids, and more recently, antifungal agents. Antifungal agents do not carry a risk of skin atrophy or telangiectasia with prolonged use, and it is more prudent to consider antifungals than corticosteroid preparations. The wide range of antifungal formulations available (creams, shampoos, or oral) provides safe, effective, and flexible treatment options for seborrheic dermatitis.
Administration, Cutaneous↗
The efficacy and safety of terbinafine in children.
In summary, terbinafine is a broad-spectrum allylamine, which has been used to treat superficial fungal infections including onychomycosis, and some systemic mycoses in adults. With a fungicidal activity, low minimum inhibitory concentration value, and high selectivity for fungal squalene epoxidase, terbinafine has demonstrated good efficacy in superficial fungal infections. Its lipophilic nature provides excellent, widespread absorption into hair, skin, and nails where it can eradicate fungal infection. Terbinafine has been shown to be effective and safe in several studies of the treatment of tinea capitis and onychomycosis in children. When treating Trichophyton tinea capitis the length of therapy may be 2 or 4 weeks. Microsporum tinea capitis may require somewhat higher or longer doses of terbinafine for adequate efficacy. These regimens still tend to be shorter than treatment with griseofulvin, and terbinafine may provide a higher compliance and a more cost-effective means of managing tinea capitis. It is possible that even higher cure rates and a shorter duration of therapy may be achieved following further optimization of treatment regimens that use a higher daily dosage of terbinafine than is currently recommended. The evidence is strongly in favor of using terbinafine to treat superficial fungal infections in children.
Administration, Oral↗
Efficacy and safety of itraconazole use in children.
Current dosing regimens for itraconazole are effective, safe, and versatile for use in superficial fungal infections in children, particularly tinea capitis. Good efficacy rates have been noted in both Trichophyton and Microsporum tinea capitis infections. Itraconazole has a high affinity for keratin, and accumulates to high levels at the site of superficial fungal infections. A pulse regimen may be chosen over continuous dosing, because the accumulation persists after dosing of itraconazole has been stopped. An oral solution of itraconazole is available, and may be more convenient for children who cannot swallow capsules. The oral solution also produces good rates of efficacy, but may be associated with a somewhat higher potential for gastrointestinal adverse events than the capsules. The range of adverse events noted with itraconazole capsules or oral solution use in children is similar to the range in adults. Events are generally mild and transient. Attention must be taken to note any medications that the child is using, because itraconazole is associated with a range of potential drug interactions. This safety of use, in combination with itraconazole's wide antifungal spectrum and pharmacokinetic properties, which allow for shorter dosing regimens, may make itraconazole a suitable alternative to griseofulvin for pediatric superficial fungal infections.
Administration, Oral↗
Tinea corporis, tinea cruris, tinea nigra, and piedra.
Tinea infections are among the most common dermatologic conditions throughout the world. To avoid a misdiagnosis, identification of dermatophyte infections requires both a fungal culture on Sabouraud's agar media, and a light microscopic mycologic examination from skin scrapings. Topical antifungals may be sufficient for treatment of tinea corporis and cruris and tinea nigra, and the shaving of hair infected by piedra may also be beneficial. Systemic therapy, however, may be required when the infected areas are large, macerated with a secondary infection, or in immunocompromised individuals. Preventative measures of tinea infections include practicing good personal hygiene; keeping the skin dry and cool at all times; and avoiding sharing towels, clothing, or hair accessories with infected individuals.
Administration, Cutaneous↗
Treatments of tinea pedis.
The severity of tinea pedis infection determines the course of treatment required. Mild infections may be resolved using a topical agent. More severe presentations (eg, dermatophytosis complex) may require treatment that eliminates the bacterial and fungal infection. Some topical monotherapies may exhibit both antifungal and antibacterial activity. In other instances, it may be necessary to combine an antifungal agent with an antibacterial agent. If inflammation is present, an agent with known anti-inflammatory action may need to be used. The chronic presentation of tinea pedis (dry type) sometimes does not respond well to topical therapy. In such instances, systemic antifungal therapy is required to ensure that adequate concentrations of the therapeutic agent are present at the site of infection.
Administration, Cutaneous↗
The use of fluconazole to treat superficial fungal infections in children.
Fluconazole has excellent absorption and good persistence in tissues that suggests it may be useful in superficial fungal infections. The predominant use in pediatric superficial fungal infection has been for tinea capitis, and successful treatment has been shown with both daily and weekly fluconazole regimens. The data regarding fluconazole use in superficial fungal infections in children are somewhat limited; however, it seems that there is good potential for the safe use of fluconazole to treat tinea capitis in children. Further studies need to be conducted, particularly in cases of tinea capitis (both T. tonsurans and M. canis), to determine the optimal treatment regimens using fluconazole.
Administration, Oral↗
Oral antifungal drug interactions: a mechanistic approach to understanding their cause.
Oral antifungal drugs are generally regarded as effective and safe when used according to their manufacturer's recommendation. However, when an oral antifungal agent is administered with certain interacting agents or classes of drugs, rare severe iatrogenic adverse experiences including death may occur. This article alerts and demystifies some of the clinically significant oral antifungal drug interactions by exploring their underlying pharmacological basis.
Administration, Oral↗
Pityriasis versicolor.
Pityriasis versicolor is a mild or chronic condition characterized by scaly hypopigmented or hyperpigmented lesions usually affecting the trunk. The lesions vary depending on tropical or temperate climates. The disease seems to occur mainly at adolescence when the sebaceous glands are more active. Malassezia yeasts have been implicated in the pathogenesis of this disease. The mycelial form of the fungus has been suggested to be the cause of lesions. Antifungal preparations have been used to treat the initial presentation effectively, although in a proportion of patients the disease tends to reoccur. They are available in a wide range of formulations and have been shown to be safe.
Administration, Cutaneous↗
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. AIM: To examine the definitions of efficacy parameters reported in clinical studies on the treatment of onychomycosis and discuss the importance of standardized reporting. METHODS: We searched MEDLINE (1966-2001) for studies in which oral treatments, griseofulvin, ketoconazole, terbinafine (continuous and pulse), itraconazole (continuous and pulse), and fluconazole, were used to treat dermatophyte onychomycosis. RESULTS: Mycologic cure was predominantly defined as negative microscopy and culture. Unlike mycologic cure, clinical parameters (e.g. clinical response, clinical cure) were variably defined. Subjective terms, such as "cure" or "markedly improved," were used; although these terms appear to be explicit, what is considered to be "cured" or "markedly improved" by one evaluator may not be by another. Also, infected nails were clinically evaluated to determine the response to treatment. Studies measured the distance between the proximal nail fold and a notch in the nail plate, at the junction between the diseased and normal-appearing nail, or in some cases estimated the diseased nail plate involvement. CONCLUSIONS: This review of the literature on systemic agents used to treat onychomycosis shows that standard and explicit definitions are required for the accurate comparison of the effectiveness of the various therapies.
Antifungal Agents↗
The diagnosis of nondermatophyte mold onychomycosis.
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Humans↗
Critical review of the manner in which the efficacy of therapies for rosacea are evaluated.
BACKGROUND: Rosacea is a relatively common disorder that may affect individuals of all races, particularly those of northern European decent. Its onset generally occurs in individuals between the ages of 20 and 50 years. Rosacea may be classified into four subtypes and one variant. Although individuals with rosacea may not pass through all of the stages, the primary features of the disorder include frequent flushing and blushing, nontransient erythema, the presence of papules and pustules, and telangiectasia. Many agents have been used to treat rosacea stigmata, especially because none of these is uniformly effective. AIM: To identify the parameters that are used to evaluate the response to therapy when different agents are used to treat rosacea. For a given parameter, to determine whether the different trials are consistent in the manner in which this variable is measured. METHODS: The reports on the efficacy and safety of the different drug therapies used to treat rosacea were identified. We searched MEDLINE (1966 to June 2002) for studies where rosacea was treated. The parameters used to evaluate the efficacy of therapy were determined. For each parameter, the ways in which it has been measured were identified. RESULTS: Efficacy of treatment is generally judged by evaluating the effect of the intervention on papules and pustules, erythema, and telangiectasia. Manual lesional counts of papules and pustules are usually performed. There is, however, substantial variation in the methodology chosen for comparison of erythema and telangiectasias. Color scales are popular for erythema and telangiectasia, while grading scales are most commonly used for physician and patient evaluations. CONCLUSIONS: For each of the parameters that are commonly used to measure the efficacy of treatments for rosacea, the different approaches by which it has been measured in the various trials have been highlighted; these dissimilarities can make it problematic to compare between clinical trials. A greater degree of uniformity in the manner in which the various parameters are evaluated would enable a more objective comparison between the studies.
Humans↗