Published on 16/03/2015 by admin
Filed under Dermatology
Last modified 16/03/2015
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Antonella Tosti and Bianca Maria Piraccini
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Onychomycosis accounts for about half of all nail abnormalities and a third of all fungal infections of the skin. It affects about 10% of the general population, with figures that vary in different areas of the world. About 85% of cases of onychomycosis are due to dermatophytes, the most common being Trichophyton rubrum, followed by Trichophyton interdigitale. The prevalence of onychomycosis increases with age, and the toenails are most frequently affected. Tinea pedis is associated with onychomycosis in most patients. Predisposing factors for onychomycosis include old age, diabetes, HIV infection, peripheral vascular impairment and peripheral neuropathies, podiatric abnormalities, sports activities, and traumatic nail disorders.
Szepietowski JC, Reich A, Garlowska E, Kulig M, Baran E; Onychomycosis Epidemiology Study Group. Arch Dermatol 2006; 142: 1279–84.
This study evaluated the presence of skin dermatophyte infections in 2761 patients with dermatophyte onychomycosis. Tinea pedis was found in 933 patients (33.8%). Other concomitant infections were tinea cruris, tinea corporis, and tinea manuum.
Different clinical patterns of nail infection result from the way in which fungi colonize the nail. In distal subungual onychomycosis (DSO), the most common type, fungi reach the nail from the hyponychium and colonize the nail bed, producing onycholysis and subungual hyperkeratosis. In proximal subungual onychomycosis (PSO), fungi penetrate the nail matrix via the proximal nail fold and colonize the deep portion of proximal nail plate, resulting in a subungual white patch located in the lunula area. In white superficial onychomycosis (WSO), fungi are localized on the nail plate surface and produce whitish opaque, friable areas on the nail plate. The type of nail invasion depends on both the causative fungus and host susceptibility.
The goals for antifungal therapy are mycological cure and a normal-looking nail. Clinical cure, which requires several months owing to slow nail growth, can be impossible to achieve when onychomycosis is associated with traumatic nail dystrophies. Immediately after treatment with systemic agents, which usually lasts 3 months, it is common to observe a still abnormal nail: signs of a good response are no proximal progression and a proximal area of normal-appearing nail.
Treatment of onychomycosis depends on the clinical type of the onychomycosis, the number of affected nails, and the severity of involvement. A systemic treatment with either terbinafine, itraconazole or fluconazole is always required in PSO and in DSO involving the lunula region. WSO and DSO limited to the distal nail can be treated with a topical agent such as amorolfine or ciclopirox. Combined systemic and topical treatment increases the cure rate.
In recent years, the number of patients with AIDS-related or iatrogenic immunosuppresion has substantially increased, leading to the appearance of new patterns of nail invasion by fungi. There is now evidence that some clinical varieties of superficial onychomycosis (i.e., in transverse lines) may be due to fungal invasion of the nail plate under the ventral nail fold: this substantially changes treatment options, since topical therapy does not cure these cases. New types of PSO have also been described. These include non-dermatophyte PSO, usually due to Fusarium or Aspergillus species, which is typically associated with acute periungual inflammation.
Terbinafine is an allylamine with fungicidal properties. Interactions of terbinafine with other drugs are extremely rare. Adverse effects may involve gastrointestinal function and the skin. Patients with known lupus erythematosus or photosensitivity are predisposed to drug-induced or drug-exacerbated disease. Liver toxicity can occasionally occur. Terbinafine is administered at a dose of 250 mg daily; treatment duration is 6 weeks for fingernails and 12 weeks for toenails. Clinical trials have repeatedly demonstrated a higher efficacy of terbinafine compared to other antifungal treatments. A meta-analysis of 18 studies on terbinafine for onychomycosis showed a mycological cure rate of 76%.
Terbinafine persists in the nail for at least 30 weeks after the completion of treatment, and is effective also when administered as pulse regimen at a dose of 250 mg for 1 week per month every 2 or 3 months.
Itraconazole is a synthetic triazole with fungistatic activity and a broad spectrum of action. It can be administered as a daily 200 mg dose or as pulse therapy at a dose of 400 mg daily for 1 week a month. Treatment duration is 6 weeks for fingernails and 12 weeks for toenails. The drug should be administered with a high-fat meal and/or an acidic beverage to improve its absorption. Agents that increase gastric alkalinity reduce absorption. With itraconazole the basis of some drug interactions is the inhibition/induction of the cytochrome P450-linked enzyme 3A4 (CYP 3A4). Adverse effects may involve gastrointestinal symptoms. The use of itraconazole may be associated with congestive heart failure. A meta-analysis of six studies on pulse itraconazole for onychomycosis showed a mycological cure rate of 63%.
Fluconazole is a bis-triazole broad-spectrum fungistatic drug with high oral bioavailability. It is administered as pulse treatment, with regimens ranging from 150 to 450 mg once a week for 6 (fingernails) to 9 (toenails) months. Fluconazole inhibits cytochrome P450-linked enzymes (CYP 3A4 and CYP 2C9), intensifying the action of many other drugs. Adverse effects may involve gastrointestinal symptoms. A meta-analysis of three studies on fluconazole for onychomycosis showed a mycological cure rate of 48%.
Posaconazole is a new azole that has been evaluated in onychomycosis and its use is likely to be limited to second-line treatment in terbinafine-refractory infections, those with non-dermatophyte mould infections or those sensitive to or intolerant of terbinafine. It showed a mycological cure rate of 48%.
Two transungual delivery systems are currently marketed: amorolfine 5% nail lacquer (not approved in the USA) and ciclopiroxolamine 8% nail lacquer. Amorolfine is applied once a week, whereas ciclopiroxolamine is applied daily. Long-term (6–12 months) monotherapy has been used in the treatment of white superficial onychomycosis and distal subungual onychomycosis limited to the distal nail of a few digits. The clinical efficacy of monotherapy with nail lacquers is low. Nail lacquers combined with oral treatment may increase cure rates. Numerous new topical formulations are currently being evaluated. Several studies are also testing the efficacy of new systemic antifungals with few good results so far.
Surgical or chemical debulking of the thickened nail plate increases cure rate. Photodynamic therapy after application of a solution of ALA methyl ester in aqueous cream on the nails has recently been reported to be effective in T. rubrum onychomycosis. Several laser devices have been marketed to treat onychomycosis, including Nd:YAG lasers and diode lasers. Evidence-based data on efficacy of these different lasers are still poor.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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