Concept: Nail disease
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.
Although surgical treatment of nail conditions can be traced back centuries to the writings of Paul Aegineta (625-690 AC), little is known about the physical laws governing nail growth. Such a poor understanding together with the increasing number of nail salons in the high street should raise legitimate concerns regarding the different procedures applied to nails. An understanding of the physics of nail growth is therefore essential to engage with human medicine and to understand the aetiology of nail conditions. In this context, a theory of nail plate adhesion, including a physical description of nail growth can be used to determine the transverse and longitudinal curvatures of the nail plate that are so important in the physical diagnosis of some nail conditions. As a result physics sheds light on: (a) why/how nails/hooves adhere strongly, yet grow smoothly; (b) why hoof/claw/nail growth rates are similar across species; © potential nail damage incurred by poor trimming; (d) the connection between three previously unrelated nail conditions, i.e. spoon-shaped, pincer and ingrown nails and; last but not least, (e) why ingrown nails occur preferentially in the big toes.
Abstract This is a randomized, double-blind study enrolling 70 patients with onychomycosis of the finger and toenails. Clinical and mycological efficacies as well as measures of safety were assessed monthly for a maximum of 6 months of treatment. The treatment regimens were: fluconazole 1% and fluconazole 1% with urea 40%. These results indicated topical treatment of onychomycosis with a combination of fluconazole 1% and urea 40% was more effective (82.8%) than fluconazole 1% (62.8%) nail lacquer alone in treatment of dermatophytic onychomycosis. Fluconazole was well tolerated and side effects were negligible. At the end of therapy and the end of the 6-month follow-up, fluconazole 1% and urea 40% demonstrated statistically significant superiority in clinical and mycological responses compared with fluconazole 1% alone.
Standard teaching dictates that systemic therapy is required for treatment of onychomycosis. It is unknown whether topical antifungal therapy is effective for pediatric nail infections. This prospective, randomized, double-blind, vehicle-controlled study was conducted in the Pediatric Dermatology Research Unit at Rady Children’s Hospital to determine whether topical antifungal therapy is efficacious for pediatric onychomycosis. Forty patients ages 2 to 16 years with nonmatrix onychomycosis were randomized 1:3 to ciclopirox lacquer or vehicle lacquer. Ciclopirox lacquer or vehicle was applied daily for 32 weeks, with weekly removal of the lacquer and mechanical trimming. Those with poor response were crossed over to active drug at week 12. Thirty-seven patients completed the 32-week study, and follow-up data were collected 1 year after completion of the study from 24 patients. Mycologic cure, effective treatment, and complete cure were assessed, as well as adverse events and effect on quality of life. Mycologic cure was 70% in the treated group and 20% in the vehicle arm (p = 0.03) at week 12. At end of the study (week 32), 77% of treated patients achieved mycologic cure and 71% effective treatment, compared with 22% of the control group. Ninety-two percent of those who were cured and followed for 1 year remained clear. Topical antifungal lacquer (ciclopirox) can be an effective option for children with nonmatrix onychomycosis. Pediatric onychomycosis does not always require systemic therapy and responds better to topical therapy than does adult disease.
Nail psoriasis is common, occurring in up to half of patients with psoriasis and in 90% of patients with psoriatic arthritis. Left untreated, it may progress to debilitating nail disease, which leads to significant functional impairment. The most common clinical signs of nail psoriasis are nail plate pitting and onycholysis. Other classical signs include oil drop discoloration, subungual hyperkeratosis, and splinter hemorrhages. The modified Nail Psoriasis Severity Index (mNAPSI) can be used to grade the severity of nail psoriasis, while the Nail Psoriasis Quality of Life Scale (NPQ10) is a questionnaire that evaluates the impact of nail psoriasis on the patient’s functional status and quality of life. Treatment of nail psoriasis should be individualized according to the patient’s preferences, severity of nail changes, and presence of skin and/or joint involvement. Both topical and intralesional therapies are safe and effective treatment modalities for nail disease, but are limited by poor adherence and pain, respectively. Systemic therapy such as oral retinoids may be considered for widespread nail disease causing significant morbidity. Among biologic agents, tumor necrosis factor-α inhibitors and T-cell-targeted therapies such as ustekinumab may be useful for refractory severe nail psoriasis.
Onychomycosis constitutes up to 50% of all nail disorders. Toenails are generally affected, mostly due to dermatophytes. Terbinafine is the most potent antifungal agent in vitro against dermatophytes. There are few randomised controlled trials using a non-continuous dose of terbinafine. The aim of this open-label pilot study was to reduce the total drug amount, the collateral effects and, specially, the costs; albeit maintaining the same efficacy of the standard regimens. Compare the outcomes of two different intermittent regimens with the same total amount of the medication (42 tablets in 6 months). Forty-one patients were divided into the following groups: terbinafine 250 mg day(-1) , for 7 days, monthly or terbinafine 500 mg day(-1) , once daily, for 7 days, every 2 months, both plus nail abrasion during 6 months. The efficacy was evaluated at months 6, 12 and 18 using the disease free nail criteria. Total cure = group I: eight patients (44.4%) and group II: eight patients (44.4%). Partial cure = group I: five patients (27.8%) and group II: four patients (22.2%). Treatment failure = group I: five patients (27.8%) and group II: three patients (16.7%). Recurrence = group I: zero patients (0.0%) and group II: three patients (16.7%). Two intermittent dosing regimens of terbinafine plus nail abrasion proved to be an alternative statistically effective, safe and with reduced drug costs for dermatophytes toenail onychomycosis.
Poly-ureaurethane has been previously described for the management of dry, brittle, and in general, dystrophic nails. The polymer yields a waterproof, breathable barrier to protect the nail plate and prevent further damage to the nail, while regulating transonychial water loss (TOWL). Because nail dystrophy and dessication are contributing factors to onychomycosis, a barrier that protects the nail but also allows a topical antifungal to permeate its shield is potentially an advantageous combination. Oral antifungals such as terbinafine, itraconazole, and fluconazole, as well as the newer topical antifungals efinaconazole and tavaborole (although formulated to penetrate the nail unit and work with the porosity and inherent electrical charge of the nail plate), do not take into account nail damage that has been created from years of harboring a dermatophyte infection. Up to 50% of cases presumed to be onychomycosis are in fact onychodystrophy without fungal infection, and laboratory testing for fungus should be obtained prior to initiating antifungal treatment. Whether a nail has onychomycosis, or onychodystrophy due to other causes, barrier function and structural integrity are compromised in diseased nails, and should be addressed. A poly-ureaurethane barrier that protects against wetting/drying, fungal reservoirs, and microtrauma, followed by the addition of oral or topical antifungals after laboratory fungal confirmation may optimize outcomes in the treatment of onychomycosis.
OBJECTIVE: The purpose of this work was to determine through in vitro release testing (IVRT) whether poly-ureaurethane 16% allows for penetration of efinaconazole 10% or tavaborole 5%. Results could spur subsequent clinical studies which would have implications for the addition of an antifungal based on fungal confirmation, after addresssing the underlying nail dystrophy primarily.
METHODS: A vertical diffusion cell system was used to evaluate the ability of efinaconazole 10% and tavaborole 5% to penetrate across poly-ureaurethane 16%. The diffusion cells had a 1.0 cm2 surface area and approximately 8 mL receptor volume. Poly-ureaurethane 16% was applied to a 0.45 μm nylon membrane and allowed to dry before use. Efinaconazole 10% or tavaborole 5% was then applied to the poly-ureaurethane 16% coated membrane, and samples were pulled from the receptor chamber at various times. Reverse phase chromatography was then used to assess the penetration of each active ingredient across the membrane.
RESULTS: The flux and permeability of efinaconazole or tavaborole across poly-ureaurethane 16% were determined from efinaconazole 10% or tavaborole 5%, respectively. The flux and permeability of efinaconazole were determined to be 503.9 +/- 31.9 μg/cm2/hr and 14.0 +/- 0.9 nm/sec. The flux and permeability of tavaborole were determined to be 755.5 +/- 290.4 μg/cm2/hr and 42.0 +/- 16.1 nm/sec.
CONCLUSION: In addition to the treatment of onychoschizia, onychorrhexis, and other signs of severe dessication of the nail plate, a barrier that regulates TOWL should be considered in the management onychomycosis to address barrier dysfunction and to promote stabilization of the damaged nail. Previously published flux values across the nail are reported to be 1.4 μg/cm2/day for efinaconazole and 204 μg/cm2/day for tavaborole. These values are substantially lower than the herein determined flux for both molecules across poly-ureaurethane 16%. A comparison of the data suggests that poly-ureaurethane 16%, if used prior to efinaconazole or tavaborole, would not limit the ability of either active ingredient to access the nail, and therefore, would be unlikely to reduce their antifungal effect. Onychodystrophy is inherent in, and often precedes onychomycosis, and consideration should be given for initiation of treatment in the same sequence: stabilizing and protecting the nail plate barrier primarily, and subsequently adding oral or topical antifungals after laboratory confirmation. Future clinical studies will be needed to determine combination efficacy for in vivo use.
J Drugs Dermatol. 2016;15(9):1116-1120.
Patients with onychomycosis may mask infected nails with polish. Tavaborole topical solution, 5% is a boron-based, small-molecule pharmaceutical approved for the treatment of toenail onychomycosis caused by Trichophyton rubrum and Trichophyton mentagrophytes; efinaconazole topical solution, 10% is approved for the same indication. Nail polish appearance after application of tavaborole (dropper) or efinaconazole (brush); respective applicator appearance; presence of color transfer from respective applicators; and color transfer to remaining solutions after dosing of polished nails were evaluated.
METHODS: Twelve ex vivo human cadaver fingernails were cleaned, polished with two coats of L'Oréal® Nail Color, Devil Wears Red #420, and mounted on floral foam. Nails were treated with tavaborole or efinaconazole solutions once daily for 7 days. Dropper and brush applicators were applied to white watercolor paper immediately after dosing to evaluate color transfer from polished nails. On day 7, remaining solutions were transferred to clear glass vials to evaluate color transfer from applicators to solutions. Nails, applicators, and papers were photographed daily following application; remaining solutions were photographed after 7 days of dosing.
RESULTS: Tavaborole-treated polished nails showed no polish discoloration, and tavaborole applicators did not change in appearance during treatment. No color transfer from polished nails was evident to applicator, paper, or remaining solution. Efinaconazole-treated polished nails showed substantial polish changes after the first day of treatment, with polish appearance and discoloration progressively worsening over 7 days of treatment. Color transfer from nails was evident to applicator, paper, and remaining solution.
CONCLUSIONS: Daily dropper application of tavaborole to ex vivo polished nails did not alter polish appearance. Brush application of efinaconazole produced visible changes in polish appearance and color transfer to applicators, paper, and remaining solution. Tavaborole topical solution, 5% may not alter nail polish appearance; the impact of nail polish on tavaborole clinical efficacy has not been evaluated.
J Drugs Dermatol. 2016;15(1):89-94.
Onychomycosis, a fungal nail infection, can impact quality of life.
Various methods are used to treat ingrown or pincer-like toenails. We developed a novel taping method to prevent topical interruption of the circulation and resulting skin conditions and evaluated it over 14.5 years. We instructed 541 patients or their guardians in the use of the technique. Ingrown toenail symptoms and abnormal nail growth were resolved and no additional therapy was required in 276 patients. The novel taping method was significantly more effective than treatments our patients had received previously. Patient-controlled taping is the first-line treatment for every ingrown or curved toenail seen in our clinic.