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Topical Treatments for Onychomycosis
A Historical Perspective
Topical treatment of onychomycosis, in contrast to systemic oral therapy, allows the patient to apply medication directly to the affected area, thereby decreasing the potential for adverse events and drug interactions. Historically, several topical antifungal agents have been used in the treatment of onychomycosis; however, the evidence for their effectiveness is based on very limited data or anecdotal reports. Recently, the development of new, effective topical agents has renewed interest in this form of therapy. As clinical experience with newer topical agents expands, they may be found to be an effective option for the treatment of onychomycosis. (J Am Podiatr Med Assoc 93(2): 136-141, 2003)
Onychomycosis is a very common disease, especially in podiatric medical practice. It can be associated with significant patient distress, major disability and pain, and is challenging to treat successfully. This is a case study of a 41-year-old man with distal lateral subungual onychomycosis of 5 years' duration. Forty percent of the great toenail was affected and a total of six toenails were involved. Baseline fungal cultures were positive for Trichophyton rubrum. This patient was treated with efinaconazole 10% solution, a new topical antifungal, once daily for 48 weeks. Mycological cure was noted at the first assessment period (12 weeks), and compete cure was seen at follow-up. This case study alerts physicians to a promising new topical treatment for onychomycosis under development, and to the importance of mycological cure as an early indicator of treatment success.
BACKGROUND:Diabetic foot ulceration is a severe complication of diabetes characterized by chronic inflammation and impaired wound healing. This study aims to evaluate the effect of a medical device gel based on Adelmidrol + Trans traumatic acid in the healing process of diabetic foot ulcers. METHODS: Thirty-seven diabetic patients with foot ulcers of mild/moderate grade were treated with the gel applied daily for 4 weeks on the affected area. The following parameters were evaluated at baseline and weekly: a) wound area, measured drawing a map of the ulcer then calculated with Photoshop6 tools, b) clinical appearance of the ulcer, assessed recording the presence/absence of dry/wet necrosis, infection, fibrin, neoepithelium, exudate, redness, granulation tissue. RESULTS: Topical treatment led to progressive healing of diabetic foot ulcers with a significant reduction of the wound area and an improvement in the clinical appearance of the ulcers. No adverse events treatment-related were observed. CONCLUSIONS: The results of this open-label study show the potential benefits of Adelmidrol + Trans traumatic acid topical administration to promote re-epithelialization of diabetic foot ulcers. Further studies need to confirm the observed results.
Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed. The efficacy of tavaborole is associated with its novel mechanism of action, whereby it inhibits the fungal leucyl-tRNA synthetase (LeuRS) enzyme. Because LeuRS is an essential component in fungal protein synthesis, inhibition of LeuRS ultimately leads to fungal cell death. Tavaborole is the first boron-based antifungal medication approved for the treatment of mild-to-moderate onychomycosis and presents patients with a new topical option. Previously, ciclopirox and efinaconazole were the only approved topical treatments for onychomycosis. This article details the properties that are at the core of the clinical benefits associated with tavaborole.
Diagnosis and Management of Onychomycosis
Perspectives from a Joint Podiatric Medicine–Dermatology Roundtable
Onychomycosis is a fungal infection, and, as such, one of the goals of treatment should be eradication of the infective agent. Despite this, in contrast to dermatologists, many podiatric physicians do not include antifungals in their onychomycosis treatment plans. Before initiating treatment, confirmation of mycologic status via laboratory testing (eg, microscopy with potassium hydroxide preparation, histopathology with periodic acid–Schiff staining, fungal culture, and polymerase chain reaction) is important; however, more podiatric physicians rely solely on clinical signs than do dermatologists. These dissimilarities may be due, in part, to differences between specialties in training, reimbursement patterns, or practice orientation, and to explore these differences further, a joint podiatric medicine–dermatology roundtable was convened. In addition, treatment options have been limited owing to safety concerns with available oral antifungals and relatively low efficacy with previously available topical treatments. Recently approved topical treatments—efinaconzole and tavaborole—offer additional options for patients with mild-to-moderate disease. Debridement alone has no effect on mycologic status, and it is recommended that it be used in combination with an oral or topical antifungal. There is little to no clinical evidence to support the use of lasers or over-the-counter treatments for onychomycosis. After a patient has achieved cure (absence of clinical signs or absence of fungus with minimal clinical signs), lifestyle and hygiene measures, prophylactic/maintenance treatment, and proactive treatment for tinea pedis, including in family members, may help maintain this status.
Therapies for Onychomycosis
A Systematic Review and Network Meta-analysis of Mycological Cure
New therapies for onychomycosis continue to be developed, yet treatments are seldom directly compared in randomized controlled trials. The objective of this study was to compare the rates of mycological cure for oral and topical onychomycosis treatments using network meta-analysis. A systematic review of the literature on onychomycosis treatments published before March 25, 2013, was performed, and data were analyzed using network meta-analysis. Terbinafine, 250 mg, therapy was significantly superior to all treatments except itraconazole, 400 mg, pulse therapy; itraconazole, 200 mg, therapy was significantly superior to fluconazole and the topical treatments; and fluconazole, efinaconazole, ciclopirox, terbinafine nail solution, and amorolfine treatments were significantly superior to only placebo. These results support the superiority of 12-week continuous terbinafine, 250 mg, therapy and itraconazole, 400 mg, pulse therapy (1 week per month for 3 months) while suggesting the equivalence of topical therapies. These results reflect findings from the literature and treatment efficacy observed in clinical practice.
Background
Efinaconazole 10% solution is a new triazole antifungal agent developed for the topical treatment of onychomycosis. This article reviews the pooled results of the two pivotal clinical trials of this drug that have been performed in the United States, Canada, and Japan.
Methods
The two studies of 1,655 patients were both double-blind, vehicle-controlled, parallel-group, randomized, multicenter studies designed to determine the efficacy and safety of efinaconazole 10% solution in the treatment of mild-to-moderate onychomycosis of the toenails caused by dermatophytes. Treatment was provided once daily for 48 weeks, and the primary end point was at week 52.
Results
The combined results show a 56% mycologic cure rate compared with 17% for vehicle at week 52. Clinical treatment success was achieved in 43% of patients treated with efinaconazole 10% solution at follow-up (week 52). Clinical treatment success was achieved in 47% of patients. As expected for a topical agent, the use of efinaconazole 10% solution was found to be safe, with mild, transient irritation at the site of application reported as the most common adverse event.
Conclusions
The efficacy and safety profile of efinaconazole 10% solution suggests that it may represent an important advance in the topical treatment of onychomycosis. Further studies will help us better understand the role of this agent for the treatment of this widespread podiatric medical condition.
Placebo cure rates vary among randomized clinical trials for onychomycosis, but the factors influencing these cure rates have not been systematically investigated. The PubMed database and reference sections of relevant publications were searched for randomized controlled trials of dermatophyte toenail onychomycosis that included a placebo control and that assessed cure rates. From 21 studies, the pooled mean ± SD placebo cure rates regarding mycological, clinical, and complete cure were 8.7% ± 3.7%, 3.4% ± 2.2%, and 1.2% ± 1.4%, respectively. There was no statistically significant difference between oral and topical treatments. None of the cure rates significantly correlated with any of the participant or study design characteristics analyzed. Placebo cure rates in randomized controlled trials of toenail onychomycosis are relatively low and are independent of the study characteristics.
Background: Diabetic foot ulceration is a severe complication of diabetes characterized by chronic inflammation and impaired wound healing. This study aimed to evaluate the effect of a medical device gel based on adelmidrol + trans-traumatic acid in the healing process of diabetic foot ulcers.
Methods: Thirty-seven diabetic patients with foot ulcers of mild/moderate grade were treated with the gel daily for 4 weeks on the affected area. The following parameters were evaluated at baseline and weekly: 1) wound area, measured by drawing a map of the ulcer and then calculated with photo editing software tools, and 2) clinical appearance of the ulcer, assessed by recording the presence/absence of dry/wet necrosis, infection, fibrin, neoepithelium, exudate, redness, and granulation tissue.
Results: Topical treatment led to progressive healing of diabetic foot ulcers with a significant reduction of the wound area and an improvement in the clinical appearance of the ulcers. No treatment-related adverse events were observed.
Conclusions: The results of this open-label study show the potential benefits of adelmidrol + trans-traumatic acid topical administration to promote reepithelialization of diabetic foot ulcers. Further studies are needed to confirm the observed results.
Background:
We sought to develop new recombinant human epidermal growth factor (rhEGF)–containing hydrogels and to investigate their biological activity and therapeutic effects on wound healing in diabetic rats.
Methods:
Levels of rhEGF released from hydrogels were measured by enzyme-linked immunosorbent assay. The cellular proliferating activity of released rhEGF was evaluated by MTT assay. Fifty-six wounded diabetic rats were randomly divided into four groups with different topical treatment daily. The therapeutic effects were evaluated by wound area measurement, histologic analysis, immunohistochemical assessment of proliferating cell nuclear antigen and B-cell lymphoma/leukemia-2, and Western blotting of EGF receptor.
Results:
The rhEGF released from the hydrogel matrix kept its bioactivity on stimulating proliferation of the BALB/c3T3 cell line. Wound closure rates on postoperative day 14 were 75.8% in the negative control group, 82.83% in the group treated with hydrogel matrix, 85.87% in the group treated with rhEGF-containing hydrogel, and 81.18% in the group treated with rhEGF solution. Compared with hydrogel matrix, rhEGF-containing hydrogel had an additional effect on induction of EGF receptor expression (P < .05). Compared with negative controls, protein expression of B-cell lymphoma/leukemia-2 was higher in the rhEGF-containing groups (P < .05). Proliferating cell nuclear antigen was induced at its highest level on day 7 in the rhEGF-containing hydrogel–treated group (P < .05).
Conclusions:
These data from in vitro release and diabetic animal models highlight the efficacy of hydrogels as a controlled releasing system for topical application of EGFs. The rhEGF-containing hydrogel we developed holds the merits of prolonged and sustained releasing of bioactive rhEGF and therapeutic potential in enhancing diabetic wound healing. (J Am Podiatr Med Assoc 102(2): 89–98, 2012)
