Phoebe Rich

Nail psoriasis severity index: a useful tool for evaluation of nail psoriasis

The Nail Psoriasis Severity Index (NAPSI) is a numeric, reproducible, objective, simple tool for evaluation of nail psoriasis. This scale is used to evaluate the severity of nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit. The NAPSI will be useful during clinical trials for evaluating response to treatment of psoriatic nails. The scale is reproducible, and because there are few data points, statistical analysis is simplified.

Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies

BACKGROUND Onychomycosis is a common nail infection, often resulting in nail plate damage and deformity. Topical lacquer treatments have negligible efficacy. Oral treatments, although more efficacious, are limited by drug interactions and potential hepatotoxicity. OBJECTIVE We investigated the safety and efficacy of efinaconazole 10% solution (efinaconazole), the first triazole antifungal developed for distal lateral subungual onychomycosis. METHODS Two identical, multicenter, randomized, double-blind, vehicle-controlled studies were conducted in patients with toenail distal lateral subungual onychomycosis (20%-50% clinical involvement [study 1: N = 870, study 2: N = 785]). Patients were randomized (3:1) to efinaconazole or vehicle, once daily for 48 weeks, with 4-week posttreatment follow-up. Debridement was not performed. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. RESULTS Mycologic cure rates were significantly greater with efinaconazole (study 1: 55.2%, study 2: 53.4%) compared with vehicle (P < .001). The primary end point, complete cure, was also significantly greater for efinaconazole (study 1: 17.8% vs 3.3%, study 2: 15.2% vs 5.5%, P < .001). Treatment success (percent affected target toenail [0%-≤10%]) for efinaconazole ranged from 21.3% to 44.8% in study 1 and from 17.9% to 40.2% in study 2, compared with 5.6% to 16.8% and 7.0% to 15.4%, respectively, with vehicle. Adverse events associated with efinaconazole were local site reactions (2%) and clinically similar to vehicle. LIMITATIONS A period of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis. CONCLUSIONS Once daily topical efinaconazole appears to be a viable alternative to oral treatment options for onychomycosis.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

A New Classification System for Grading the Severity of Onychomycosis: Onychomycosis Severity Index

OBJECTIVE To establish and validate a new system to define the severity of onychomycosis. The Onychomycosis Severity Index (OSI) score is obtained by multiplying the score for the area of involvement (range, 0-5) by the score for the proximity of disease to the matrix (range, 1-5). Ten points are added for the presence of a longitudinal streak or a patch (dermatophytoma) or for greater than 2 mm of subungual hyperkeratosis. Mild onychomycosis corresponds to a score of 1 through 5; moderate, 6 through 15; and severe, 16 through 35. DESIGN Consensus conference. SETTING Teleconference. PARTICIPANTS The consensus group included 5 dermatologists, 1 dermatology resident with an interest in nail disorders, and a statistician. The meetings were held by closed teleconference. MAIN OUTCOME MEASURES Index reliability. RESULTS The reliability of the OSI system was assessed in 2 steps. The first assessment included 37 dermatologists who scored 8 photographs of onychomycosis after being taught how to use the OSI. The scoring system showed very high reliability (Cronbach α = 0.99 and intraclass correlation coefficient [ICC] = 0.95). The second assessment entailed evaluation of 49 nails by 3 dermatologists, including an expert in the OSI. This assessment was conducted at the University of Alabama at Birmingham and at the Oregon Dermatology and Research Center, Portland. The scoring system showed very high reliabilities at both sites (Cronbach α = 0.99 and ICC = 0.96 at the University of Alabama at Birmingham, and Cronbach α = 0.98 and ICC = 0.93 at the Oregon Dermatology and Research Center). CONCLUSION The OSI is a new, simple, objective, reproducible numeric system to grade the severity of onychomycosis.

Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies

Background  Data suggest that photodynamic therapy using topical methyl aminolevulinate (MAL PDT) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma (BCC). In the studies described here, we investigated the histologic response, tolerability, and cosmetic outcome with MAL PDT for primary nodular BCC (≤ 5 mm in depth).

Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies

BACKGROUND Onychomycosis, a fungal nail infection, can impact quality of life. OBJECTIVE We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail onychomycosis. METHODS In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52. Secondary end points included completely or almost clear nail, negative mycology, completely or almost clear nail plus negative mycology, and safety. RESULTS Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and 1.5%) significantly favored tavaborole versus vehicle (P ≤ .001). Completely or almost clear nail rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for tavaborole versus vehicle (P < .001). Application-site reactions with tavaborole included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%). LIMITATIONS Duration of follow-up is a limitation. CONCLUSION Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis.

Nail biopsy: indications and methods.

Nail biopsy is a safe and useful technique for diagnosis and management of many nail conditions. A basic understanding of nail anatomy and biology is a prerequisite for a successful nail biopsy. The patient must be adequately prepared and there needs to be excellent anesthesia and hemostasis. The type of nail biopsy depends largely on the location of the pathology in the nail unit. The techniques of nail biopsy by location in the nail unit and by lesion type are discussed.

Ketoconazole in griseofulvin-resistant dermatophytosis

The efficacy of ketoconazole was evaluated in twenty patients with chronic dermatophyte infections who had failed to clear with griseofulvin therapy. Trichophyton rubrum was the causative organism in nineteen of the patients, and Trichophyton mentagrophytes in one patient. Three of twelve organisms tested showed in vitro resistance to griseofulvin. Duration of infection ranged from 2 to 28 years. Patients received 200 to 400 mg of ketoconazole daily for periods up to 8 months. In addition, patients were followed for 5 months post-therapy to monitor recurrences. Clearing was seen clinically as early as 2 weeks, and by 18 weeks all patients showed marked improvement or clinical clearing, though only six achieved complete mycologic cure. Improvement followed a predictable sequence of sites, with lesions of the trunk healing first, followed by hands, feet, and finally, nails. After 8 months, though all patients showed proximal nail clearing, onychomycosis persisted in thirteen of twenty affected sites. By 5 months post-therapy, four of six patients who had achieved clearing of skin and nails showed recurrences. No significant side effects were observed during therapy, though rare, apparently idiosyncratic cases of hepatotoxicity have been reported. Ketoconazole is an affective therapeutic agent for griseofulvin-resistant dermatophytosis. Apparent cures may subsequently recur after discontinuation of therapy.

Consensus on melanonychia nail plate dermoscopy

This statement, focused on melanonychia and nail plate dermoscopy, is intended to guide medical professionals working with melanonychia and to assist choosing appropriate management for melanonychia patients. The International Study Group on Melanonychia was founded in 2007 and currently has 30 members, including nail experts and dermatopathologists with special expertise in nails. The need for common definitions of nail plate dermoscopy was addressed during the Second Meeting of this Group held in February 2008. Prior to this meeting and to date (2010) there have been no evidence-based guidelines on the use of dermoscopy in the management of nail pigmentation.

Onychomycosis in a special patient population: focus on the diabetic.

Foot problems are a major cause of morbidity, mortality and disability in diabetic patients. Diabetes mellitus is a relatively common disorder that affects over 16 million people in the United States.1 The World Health Organization predicts that the world population of diabetics will double to over 200 million people by the year 2010.2 Diabetes affects patients of all ages and in all socioeconomic segments of the population. There are over 625 000 newly diagnosed diabetics in the US each year.3 There is a high cost associated with diabetes. The health care costs due to morbidity and complications of diabetes mellitus are higher for diabetics than the general population. In addition, there are indirect costs to society from diabetic complications resulting in loss of productivity. Diabetics utilize health care resources at a rate three times higher than the average American. When evaluated in terms of outpatient contacts with health care providers, diabetics have 15.5 encounters per person compared to 5.5 contacts per year for the general population.4 Diabetes is the most common reason for nontraumatic lower extremity amputations in the US. There were 50 000 lower extremity amputations in diabetics in one year. Foot ulcers preceded amputations 85% of the time in diabetics.5 This places an enormous burden on the resources for health care. In addition, there is up to 68% mortality in diabetics within 5 years of lower extremity amputation.6