Onychomycosis: Treatment and prevention of recurrence

doi:10.1016/j.jaad.2018.05.1260

Journal of the American Academy of Dermatology

Volume 80, Issue 4, April 2019, Pages 853-867

https://doi.org/10.1016/j.jaad.2018.05.1260 Get rights and content

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophytes, and yeast, and is the most common nail disorder seen in clinical practice. It is an important problem because it may cause local pain, paresthesias, difficulties performing activities of daily living, and impair social interactions. The epidemiology, risk factors, and clinical presentation and diagnosis of onychomycosis were discussed in the first article in this continuing medical education series. In this article, we review the prognosis and response to onychomycosis treatment, medications for onychomycosis that have been approved by the US Food and Drug Administration, and off-label therapies and devices. Methods to prevent onychomycosis recurrences and emerging therapies are also described.

Section snippets

Overview of treatment

The goals of onychomycosis therapy are to both eliminate the infecting fungal organism and restore the nail to its normal state as it grows. Patients should be counseled that this process can take some time because fingernails grow about 2 to 3 mm per month and toenails grow 1 to 2 mm per month. The US Food and Drug Administration (FDA) requires treatment efficacy endpoints that are based on clinical examination and negative cultures/stains for drug approvals.¹ Endpoints used in clinical trials

Prevention of recurrence

After treatment of onychomycosis, recurrences (ie, relapse [same infection after incomplete cure] or reinfection [same infection after complete cure]) occur at a rate of 20% to 25%.4, 163, 164 In a retrospective chart review on patients with complete cure treated with oral terbinafine for toenail onychomycosis who then used a topical antifungal for prophylaxis (n = 320), the recurrence rate was significantly lower in patients receiving prophylaxis.²⁵ The ideal duration of prophylaxis is

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Dissolving microneedle to improve transdermal delivery of terbinafine for treatment of onychomycosis
2024, Journal of Drug Delivery Science and Technology
The topical formulation of antifungal agents has demonstrated prominent success in treating fungal infection. However, traditional topical cream or solution limited ability to penetrate the nail plate and target the infected area contributes to the inefficacy of antifungals in the treatment of onychomycosis. In this work, the problem of topical administration reaching only the skin's surface was addressed by dissolving microneedles (MN) to pierce the skin and deliver drugs directly to the site of infection. Terbinafine (TH) was encapsulated into polydopamine (PDA) nanoparticles (TH@PDA) to increase the antifungal efficacy of TH. The results of checkerboard microdilution assays showed that the antifungal efficacy of TH@PDA was increased up to 2–8 times in comparison to free TH. In animal experiment, TH@PDA was incorporated into MN to target the infected site and increase the therapeutic effect. Our results demonstrated TH@PDA MN significantly decreased the fungal burden in the nails and relieved inflammation at the site of infection when compared to TH MN, TH cream, and oral TH. These results suggested that the TH@PDA MN exhibited enhanced antifungal effects and can serve as a potentially promising approach for onychomycosis treatment.
Nail psoriasis and nail lichen planus: Updates on diagnosis and management
2024, Journal of the American Academy of Dermatology
Inflammatory diseases of the nail, including nail psoriasis and nail lichen planus, are associated with significant disease burden and have a negative impact on quality of life. Diagnosis is often delayed, especially when patients present without cutaneous findings. Therefore, recognizing clinical signs and symptoms of inflammatory nail diseases, and initiating timely and appropriate treatment, is of utmost importance.
We review recent studies on diagnostic techniques, discuss severity grading and scoring systems, and describe consensus treatment recommendations for nail psoriasis and nail lichen planus.
An updated literature review was performed using the PubMed database on studies assessing diagnostic techniques or treatment modalities for nail psoriasis and nail lichen planus.
Recent studies on diagnostic techniques for inflammatory nail disease have focused on use of dermoscopy, capillaroscopy, and ultrasound modalities. Treatment of these conditions is dichotomized into involvement of few (≤3) or many (>3) nails. Recent psoriatic therapeutics studied for nail outcomes include brodalumab, tildrakizumab, risankizumab, deucravacitinib, and bimekizumab, while emerging treatments for nail lichen planus include JAK inhibitors and intralesional platelet rich plasma injections.
We emphasize the need for increased awareness and expanded management strategies for inflammatory nail diseases to improve patient outcomes.
Boron-containing carbonic anhydrases inhibitors
2024, Bioorganic Chemistry
Over the last decades, the medicinal chemistry of boron-based compounds has been extensively explored, designing valuable small molecule drugs to tackle diseases and conditions, such as cancer, infections, inflammatory and neurological disorders. Notably, boron has proven to also be a valuable element for the development of inhibitors of the metalloenzymes carbonic anhydrases (CAs), a class of drug targets with significant potential in medicinal chemistry. Incorporating boron into carbonic anhydrase inhibitors (CAIs) can modulate the ligand ability to recognize the target and/or influence selectivity towards different CA isoforms, using the tail approach and boron-based tails. The electron-deficient nature of boron and its associated properties have also led to the discovery of novel zinc-binding CAIs, such as boronic acids and the benzoxaboroles, capable of inhibiting the CAs upon a Lewis acid-base mechanism of action. The present manuscript reviews the state-of-the-art of boron-based CAIs. As research in the applications of boron compounds in medicinal chemistry continues, it is anticipated that new boron-based CAIs will soon expand the current array of such compounds. However, further research is imperative to fully unlock the potential of boron-based CAIs and to advance them towards clinical applications.
Onychomycosis
2024, Hand Surgery and Rehabilitation
Onychomycosis is a fungal infection of the nail, and the most common nail infection worldwide, causing discoloration and thickening of the nail plate. It is predominantly caused by dermatophytes. Clinical presentation is polymorphous. Diagnosis must be confirmed by mycological examination before initiating any therapy. Management is an ongoing challenge, often requiring several months’ treatment, with a high risk of recurrence. Treatment must be adapted to clinical presentation and severity and to the patient’s history and wishes. Debridement of all infected keratin is the first step, reducing fungal load. Systemic treatments are more effective than topical treatments, and combining the two increases the cure rate. Terbinafine is the drug of choice for dermatophyte onychomycosis, due to low drug interaction and good cost-effectiveness. Itraconazole and fluconazole are broad‐spectrum antifungals that are effective against dermatophytes, yeasts, and some non‐dermatophytic molds. Recurrence rates for onychomycosis are high. Prophylactic application of topicals and avoiding walking barefoot in public places may help prevent recurence.
Formulation development and characterization of an antifungal nail patch based on Pistacia atlantica gum for transungual treatment of onychomycosis
2023, Journal of Drug Delivery Science and Technology
Recently, there has been considerable interest in using patches as drug carriers for the treatment of numerous diseases. Due to the severe side effects associated with systemic or surgical treatment for onychomycosis, as well as the drug's limited penetration into the nail plate, new methods of local drug administration are required for the treatment of this infection. The primary objective of this study was therefore to develop a novel and, of course, effective formulation of Terbinafine hydrochloride nail patches for the treatment of onychomycosis. In this work, Pistacia atlantica gum was employed for the first time as a natural adhesive agent instead of synthetic polymers. The patches were produced by solvent evaporation and were characterized both physically and biologically. Using Design-Expert software, the response surface method (RSM) was employed to determine the most appropriate formulation. The elongation at break of the optimized patch was 530.38 $\pm$ 25.22% and the modulus was 0.15 $\pm$ 0.02 MPa. Adhesion properties such as tack and peel were 0.32 $\pm$ 0.03 N/mm² and 5.34 $\pm$ 0.52 N/25 mm, respectively. The patch had an aesthetically pleasing appearance and uniform thickness. In addition, the disk diffusion test revealed that the patches had a good antifungal effect, with a considerable growth inhibition zone. It was observed that the patch containing 1% of the active agent would be the most effective. It was most effective against species of Trichophyton verrucosum, with inhibition zone diameters of 88 $\pm$ 1.4 mm, and least effective against species of Trichophyton mentagrophytes, with inhibition zone diameters of 62 $\pm$ 9.4 mm. The cumulative drug amount per unit area after 72 h was approximately 335.43 $\pm$ 4.10 μg/cm². The obtained results indicate that the developed formulation has a potential drug delivery system for the treatment of tinea unguium (onychomycosis).
Comparative evaluation of the efficacy of itraconazole with terbinafine cream versus itraconazole with sertaconazole cream in dermatophytosis: A within person pilot study
2023, Medical Journal Armed Forces India
Current trend of rising drug-resistant dermatophyte infection is alarming and fretted by dermatologists. Dilemma prevails regarding use of the same or different class of antifungal agents topically and systemically. The aim was to study the efficacy of oral itraconazole 200 mg with 1% terbinafine cream versus oral itraconazole 200 mg with 2% sertaconazole cream in dermatophytosis.
This within-person open-label pilot study enrolled 50 patients with dermatophytosis. Two lesions of comparable size within each patient were randomly allotted to group A and B and treated with 2% sertaconazole and 1% terbinafine cream, respectively. Both groups received itraconazole 200 mg once daily for 4 weeks. The remaining lesions received 1% terbinafine cream. Response and adverse effects were assessed at 2 and 4 weeks. Reduction in erythema, scaling, pruritus and clinical, and mycological cure constituted efficacy outcomes.
The mean duration of lesions was 2.82 ± 1.35 months. Complete clinical cure was observed in 50% and 48%, whereas mycological cure was attained in 56% and 52% patients in groups A and B, respectively, after 4 weeks, which was statistically insignificant. Reduction in erythema, scaling, and pruritus after 4 weeks when compared between the two groups, was also statistically insignificant.
Same class of oral and topical antifungal agents has comparable efficacy with different classes of oral and topical antifungal agents in dermatophyte infection.

View all citing articles on Scopus

: Date of release: April 2019

: Expiration date: April 2022

: Funding sources: None.

: Dr Scher has received honoraria from MOE Medical Devices, Epihealth, Medicxi, and Valeant. Dr Lipner has received grants for clinical trials from MOE Medical Devices.

: Reprints not available from the authors.

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Continuing medical educationOnychomycosis: Treatment and prevention of recurrence

Section snippets

Overview of treatment

Prevention of recurrence

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Allergy Clin Immunol Pract

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Dermatol Clin

Clin Dermatol

J Am Acad Dermatol

Lancet

J Am Acad Dermatol

J Am Acad Dermatol

Cell Rep

J Am Acad Dermatol

Medical devices and clinical trial design for the treatment or improvement in the appearance of fungally-infected nails—draft guidance for industry and FDA staff

How do we measure efficacy of therapy in onychomycosis: patient, physician, and regulatory perspectives

J Dermatolog Treat

Long-standing onychodystrophy in a young woman

JAMA

Clinical study of onychomycosis: factors contributing to the prognosis and response rate according to each factor and summation of factors

Korean J Med Mycol

Onychomycosis and other superficial fungal infections of the foot in the elderly: a pan-European survey

Dermatology

Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment

Mycoses

Disseminated Fusarium infection originating from paronychia in a neutropenic patient: a case report and review of the literature

Cutis

A case of fusariosis in an immunocompromised patient successfully treated with liposomal amphotericin B

Acta Biomed

Invasive aspergillosis due to subungual onychomycosis during treatment for non-Hodgkin lymphoma

Br J Dermatol

Malassezia furfur onychomycosis in an immunosuppressed liver transplant recipient

Indian J Dermatol Venereol Leprol

Majocchi’s granuloma after kidney transplantation

Exp Clin Transpl

Prevalence of superficial dermatomycoses in 73 renal transplant recipients

Dermatology

Recurrent proximal white subungual onychomycosis associated with a defect of the polymorphonuclear chemotaxis

Eur J Dermatol

Onychomycosis and keratomycosis caused by Alternaria sp. A bipolar opportunistic infection in a wood-pulp worker on chronic steroid therapy

Am J Dermatopathol

Relapsing severe Trichophyton rubrum infections in an immunocompromised host: evidence of onychomycosis as a source of reinfection based on lectin typing

Mycoses

Review of antifungal therapy and the severity index for assessing onychomycosis: part I

J Dermatolog Treat

Factors that may affect the response of onychomycosis to oral antifungal therapy

Australas J Dermatol

Prognostic factors for cure following treatment of onychomycosis

J Eur Acad Dermatol Venereol

Topical amorolfine for 15 months combined with 12 weeks of oral terbinafine, a cost-effective treatment for onychomycosis

Br J Dermatol

Topical antifungal treatment prevents recurrence of toenail onychomycosis following cure

Dermatol Ther

Lateral edge nail involvement indicates poor prognosis for treating onychomycosis with the new systemic antifungals

Acta Derm Venereol

Onychomycosis: predisposed populations and some predictors of suboptimal response to oral antifungal agents

Eur J Dermatol

A bipartite interaction between Pseudomonas aeruginosa and fungi in onychomycosis

Arch Dermatol

Fusarium solani onychomycosis of the thumbnail coinfected with Pseudomonas aeruginosa: report of two cases

Mycoses

Toenail abnormalities and onychomycosis in chronic venous insufficiency of the legs: should we treat?

J Eur Acad Dermatol Venereol

Prognostic factors in onychomycosis treatment

J Infect Dis Ther

Cure rate, duration required for complete cure and recurrence rate of onychomycosis according to clinical factors in Korean patients

Mycoses

Evaluation of nail lines: color and shape hold clues

Cleve Clin J Med

Subungual dermatophytoma complicating dermatophyte onychomycosis

Br J Dermatol

Dermatophytoma: recalcitrance to treatment because of existence of fungal biofilm

Continuing medical education
Onychomycosis: Treatment and prevention of recurrence