ABSTRACT
Onychomycosis, defined as a fungal nail infection, affects 5.5% of the global population. Our objectives were to analyse prescription trends of onychomycosis medications using the Medicare Part D Prescribers database from 2016 to 2020, stratified by physician specialty. There was a 4% annual increase in the total cost of onychomycosis medications, with a notable decrease of 12.8% in 2020 during the COVID-19 pandemic. Physicians demonstrated a strong consideration for price when selecting treatments, with the least expensive medications (ciclopirox and terbinafine) accounting for nearly 99% of all prescriptions. In contrast, the more costly medications (efinaconazole and tavaborole) were rarely prescribed. In addition, physicians often opted for the less costly generic versions of ciclopirox and itraconazole, prescribing them 99% and 91% of the time, respectively. Notably, physician assistants and nurse practitioners had higher overall increases in prescription rates, at 15%, compared to 1%-6% for other specialties. There are no recent United States onychomycosis guidelines, and our study emphasizes cost considerations when prescribing onychomycosis treatments.
Subject(s)
Medicare Part D , Onychomycosis , Aged , Humans , United States , Onychomycosis/drug therapy , Onychomycosis/epidemiology , Antifungal Agents/therapeutic use , Ciclopirox/therapeutic use , Retrospective Studies , PandemicsABSTRACT
BACKGROUND: Methylene blue (MB) and flavin mononucleotide (FMN)-mediated photodynamic therapy (PDT) have demonstrated local antimicrobial effect, but no direct comparative study has been published so far for the treatment of toenail onychomycosis. OBJECTIVES: To directly compare the short and medium-term efficacy of MB versus FMN as photosensitizers in PDT for toenail onychomycosis by applying them in a 40% w/w urea cream in two different dye concentrations. METHODS: Forty toenails with distal and lateral subungual moderate onychomycosis due to dermatophyte fungi were randomised to receive 10 weekly sessions of PDT mediated by four topical formulations including MB or FMN at two different concentrations: Group I: 0.1% w/w MB; Group II: 2% w/w MB; Group III: 0.1% w/w FMN; and Group IV: 2% w/w FMN. Photographs were used for onychomycosis severity index (OSI) estimation allowing clinical assessment at any point of the study. Microscopic and microbiological evaluations were carried out at baseline, 27- and 35-week follow-ups. Side effects were recorded along with patient satisfaction. RESULTS: At week 27, mycological cure rates were 60%, 30%, 50% and 40% and complete cure rates were 0%, 20%, 10% and 20%, for Groups I, II, III and IV respectively. At week 35, mycological cure rates were 70%, 70%, 70% and 60% and complete cure rates were 30%, 50%, 70% and 30%, for Groups I, II, III and IV respectively. All cream formulations were safe and patients were fairly satisfied. CONCLUSIONS: Results of the present work confirm PDT as a therapeutic alternative for onychomycosis. Although all cream formulations were safe and effective, with a good degree of satisfaction, higher cure rates were obtained with 2% w/w MB cream and 0.1% w/w FMN cream.
Subject(s)
Foot Dermatoses , Onychomycosis , Humans , Antifungal Agents/therapeutic use , Onychomycosis/drug therapy , Nails , Methylene Blue/therapeutic use , Flavin Mononucleotide/therapeutic use , Foot Dermatoses/drug therapy , Urea , Treatment OutcomeABSTRACT
BACKGROUND: Treatment of onychomycosis is still challenging and warrants the development of new treatment strategies. Different trials were conducted to increase the penetration and efficacy of topical antifungals aiming at finding an alternative treatment especially when systemic antifungals are contraindicated. OBJECTIVES: To evaluate the efficacy of trichloroacetic acid (TCA) 100% either alone or combined with topical tioconazole 28% versus itraconazole pulse therapy in the treatment of onychomycosis. PATIENTS/METHODS: Forty-five patients with onychomycosis were divided into three groups: group (A) treated by topical TCA 100% for 12 sessions, group (B) treated by TCA 100% for 12 sessions combined with topical tioconazole 28% for 18 weeks and group (C) treated by itraconazole (400 mg/day for 1 week/month for 4 months). RESULTS: TCA 100% combined with topical tioconazole 28% showed the highest therapeutic response; however, the difference between the groups was statistically insignificant. Mycological cure (negative culture) was reported in 66.7% of group B versus 60% of group A and 40% of group C at the 20 week. CONCLUSIONS: TCA 100% is an effective and safe treatment option for onychomycosis especially when combined with antifungals. This modality is promising in the treatment of onychomycosis especially with the increased resistance to different antifungals.
Subject(s)
Foot Dermatoses , Imidazoles , Onychomycosis , Humans , Itraconazole/therapeutic use , Onychomycosis/drug therapy , Antifungal Agents/therapeutic use , Trichloroacetic Acid/therapeutic use , Treatment Outcome , Foot Dermatoses/drug therapyABSTRACT
BACKGROUND: Onychomycosis is a chronic nail disorder commonly seen by healthcare providers; toenail involvement in particular presents a treatment challenge. OBJECTIVE: To provide an updated estimate on the prevalence of toenail onychomycosis. METHODS: We conducted a literature search using PubMed, Embase and Web of Science. Studies reporting mycology-confirmed diagnoses were included and stratified into (a) populations-based studies, and studies that included (b) clinically un-suspected and (c) clinically suspected patients. RESULTS: A total of 108 studies were included. Based on studies that examined clinically un-suspected patients (i.e., with or without clinical features suggestive of onychomycosis), the pooled prevalence rate of toenail onychomycosis caused by dermatophytes was 4% (95% CI: 3-5) among the general population; special populations with a heightened risk include knee osteoarthritis patients (RR: 14.6 [95% CI: 13.0-16.5]), chronic venous disease patients (RR: 5.6 [95% CI: 3.7-8.1]), renal transplant patients (RR: 4.7 [95% CI: 3.3-6.5]), geriatric patients (RR: 4.7 [95% CI: 4.4-4.9]), HIV-positive patients (RR: 3.7 [95% CI: 2.9-4.7]), lupus erythematosus patients (RR: 3.1 [95% CI: 1.2-6.3]), diabetic patients (RR: 2.8 [95% CI: 2.4-3.3]) and hemodialysis patients (RR: 2.8 [95% CI: 1.9-4.0]). The prevalence of onychomycosis in clinically suspected patients was significantly higher likely due to sampling bias. A high degree of variability was found in a limited number of population-based studies indicating that certain pockets of the population may be more predisposed to onychomycosis. The diagnosis of non-dermatophyte mould onychomycosis requires repeat sampling to rule out contaminants or commensal organisms; a significant difference was found between studies that performed single sampling versus repeat sampling. The advent of PCR diagnosis results in improved detection rates for dermatophytes compared to culture. CONCLUSION: Onychomycosis is an underrecognized healthcare burden. Further population-based studies using standardized PCR methods are warranted.
Subject(s)
Diabetes Mellitus , Kidney Transplantation , Onychomycosis , Humans , Aged , Onychomycosis/epidemiology , Onychomycosis/drug therapy , Prevalence , Nails , Diabetes Mellitus/epidemiologyABSTRACT
Onychomycosis is a highly prevalent and persistent nail disorder primarily caused by dermatophytes. The effectiveness of current topical and systemic antifungals is limited by the extent and severity of the infection, patient demographics and health status, hepatic toxicity, drug interactions and low compliance. Laser therapy is a promising modality for safe and cost-effective removal of mycotic nail. This prospective study assessed the performance of a multi-series long-pulsed Nd:YAG 1064 nm regimen (30-40 J/cm2 , 1 Hz) in the treatment of 213 mycotic nails in 31 patients. Pain and discomfort were scored at each treatment session and mycological and clinical cure rates were determined 3 months after the last treatment session. Patients presented with mostly severe (mean SCIO score: 21.9 ± 8.9), T. rubrum-positive (87.1%) infections. Most (61%) had a family history of onychomycosis and a significant proportion had comorbidities, including hypertension (38.7%), hyperlipidemia (35.5%) and/or diabetes (12.9%). Treatment was well tolerated and there were no reports of nail deformity or burns. By 3 months post-treatment, mycological cure was achieved by 4 (12.9%) and visual improvements were noted for 10 (32.3%) patients, including 3 (9.7%) with moderate to significant improvements. Clinical response correlated with baseline SCIO ≤ 20 (OR: 0.9 [0.13-6.52]), family history of onychomycosis (OR: 0.27 [0.04-1.50]) and comorbidities (OR: 0.44 [0.05-3.74]). In conclusion, Nd:YAG 1064 nm laser is safe and effective for the management of mild-to-moderate onychomycosis in diverse populations. Further studies will be necessary to adjust treatment parameters to patient and nail profiles and to determine the impact of combined laser and topical therapies.
Subject(s)
Lasers, Solid-State , Onychomycosis , Humans , Onychomycosis/drug therapy , Prospective Studies , Treatment Outcome , Nails , Lasers, Solid-State/therapeutic useABSTRACT
BACKGROUND: Onychomycoses are difficult-to-treat fungal infections with high relapse rates. Combining oral and topical antifungal drugs is associated with higher success rates. Additive or synergistic modes of action are expected to enhance treatment success rates. OBJECTIVES: Investigation of the combined effects of antifungal drugs in vitro with different modes of action and application on clinical isolates from mycotic nails. METHODS: Isolates of Trichophyton rubrum, Trichophyton interdigitale and Scopulariopsis brevicaulis were collected from infected toenail specimens of patients with onychomycosis. Susceptibility testing was performed in 96-well polystyrene plates using a standard stepwise microdilution protocol. Additive or synergistic activity at varying concentrations was investigated by the checkerboard method. RESULTS: Combining terbinafine with amorolfine tended to be more effective than terbinafine in conjunction with ciclopirox. In most combinations, additive effects were observed. Synergy was detected in combinations with involving amorolfine in S. brevicaulis. These additive and synergistic interactions indicate that combined therapy with topical amorolfine and oral terbinafine is justified. Sublimation of amorolfine (and terbinafine) may enhance the penetration in and through the nail plate, and support treatment efficacy. CONCLUSIONS: These in vitro results support the notion that combining oral terbinafine and topical amorolfine is beneficial to patients with onychomycosis, particularly if the pathogen is a non-dermatophyte fungus such as S. brevicaulis.
Subject(s)
Morpholines , Onychomycosis , Humans , Terbinafine/pharmacology , Terbinafine/therapeutic use , Onychomycosis/drug therapy , Onychomycosis/microbiology , Ciclopirox/pharmacology , Ciclopirox/therapeutic use , Antifungal Agents/therapeutic use , NaphthalenesABSTRACT
Fusarium species are an emerging cause of onychomycosis, and the number of cases has dramatically increased in recent decades worldwide. This review presents an overview of the onychomycosis cases caused by Fusarium species and diagnosis and treatment that have been reported in the literature. The most common causative agent of onychomycosis is F. solani species complex, which accounts for 11.68% of the cases of Fusarium onychomycosis, followed by the F. oxysporum species complex (164 out of 1669), which is accounted for 9.83% of the total. F. fujikuroi species complex (42 out of 1669) and F. dimerum species complex (7 out of 1669) are responsible for 2.52% and 0.42 cases, respectively. Fusarium nail infections were reported in patients aged range 1-98, accounting for 5.55% (1669 out of 30082) of all cases. Asia has the highest species diversity of Fusarium onychomycosis (31.51%). South America accounts for 21.09%, and the most common causative agent is F. solani (19.32%), followed by F. oxysporum species complex (15.63%). Europe accounts for 4.90% of cases caused by F. oxysporum, followed by F. solani. Africa accounts for 23.87% of the cases due to the F. solani species complex, followed by F. oxysporum and F. fujikuroi. Distal and lateral subungual onychomycosis was the most common clinical symptom accounting for 58.7% (135 out of 230) of the cases. Data analysis relieved that terbinafine and itraconazole are active treatments for Fusarium onychomycosis. For a definitive diagnosis, combining of direct examination, culture and sequencing of the elongation factor of translation 1α are recommended. Accurate identification of the causative agents of onychomycosis due to Fusarium species and antifungal susceptibility testing is essential in patient management.
Subject(s)
Fusariosis , Fusarium , Onychomycosis , Humans , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Onychomycosis/diagnosis , Onychomycosis/drug therapy , Onychomycosis/epidemiology , Antifungal Agents/therapeutic use , Itraconazole/therapeutic use , Fusariosis/diagnosis , Fusariosis/drug therapy , Fusariosis/epidemiologyABSTRACT
BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.
Subject(s)
Antifungal Agents , Arthrodermataceae , Drug Resistance, Fungal , Onychomycosis , Squalene Monooxygenase , Terbinafine , Humans , Onychomycosis/microbiology , Onychomycosis/epidemiology , Onychomycosis/drug therapy , Squalene Monooxygenase/genetics , Female , Middle Aged , Male , Terbinafine/pharmacology , Terbinafine/therapeutic use , Drug Resistance, Fungal/genetics , United States/epidemiology , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Longitudinal Studies , Aged , Arthrodermataceae/genetics , Arthrodermataceae/drug effects , Adult , Mutation , Cohort Studies , Trichophyton/genetics , Trichophyton/drug effects , Young Adult , Prevalence , Point Mutation , Aged, 80 and over , Adolescent , Nails/microbiologyABSTRACT
All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited. Based on the physicochemical properties of human nails and permeability data of topical onychomycosis drugs, the nail plate is considered a good barrier to chemicals. We examine factors impacting penetration of nail care ingredients through the nail plate, including properties of the nails of the ingredients and formulations. The molecular weight, vapor pressure, logP, water solubility, and keratin binding, as well as formulations properties e.g., polymerization of acrylate monomers are considered important factors affecting penetration. To estimate systemic exposure of nail care ingredients through the nail plate, a standardized framework is applied that quantifies the impacts of these properties on penetration with an adjustment factor for each of these influencing properties. All the adjustment factors are then consolidated to derive an integrated adjustment factor which can be used for calculation of the systemic exposure dose for the ingredient. Several case studies are presented to reflect how this framework can be used in the exposure assessment for nail cosmetic products.
Subject(s)
Cosmetics , Onychomycosis , Humans , Nails , Administration, Topical , Onychomycosis/drug therapy , Onychomycosis/metabolism , Drug Compounding , Permeability , Cosmetics/metabolism , Antifungal AgentsABSTRACT
Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the role of NDMs in the pathogenesis of onychomycosis (i.e. causative vs. contaminant). In studies where the ongoing invasive presence of NDMs is confirmed through repeat cultures, the global prevalence of NDMs in onychomycosis patients is estimated at 6.9% with the 3 most common genus being: Aspergillus, Scopulariopsis and Fusarium. NDM onychomycosis can, in many cases, appear clinically indistinguishable from dermatophyte onychomycosis. Clinical features suggestive of NDMs include proximal subungual onychomycosis with paronychia associated with Aspergillus spp., Fusarium spp. and Scopulariopsis brevicaulis, as well as superficial white onychomycosis in a deep and diffused pattern associated with Aspergillus and Fusarium. Longitudinal streaks seen in patients with distal and lateral onychomycosis may serve as an additional indicator. For diagnosis, light microscopic examination should demonstrate fungal filaments consistent with an NDM with at least two independent isolations in the absence of a dermatophyte; the advent of molecular testing combined with histological assessment may serve as an alternative with improved sensitivity and turnover time. In most instances, antifungal susceptibility testing has limited value. Information on effective treatments for NDM onychomycosis is relatively scarce, unlike the situation in the study of dermatophyte onychomycosis. Terbinafine and itraconazole therapy (continuous and pulsed) appear effective to varying extents for treating onychomycosis caused by Aspergillus, Fusarium or Scopulariopsis. There is scant literature on oral treatments for Neoscytalidium.
Subject(s)
Onychomycosis , Paronychia , Humans , Onychomycosis/diagnosis , Onychomycosis/drug therapy , Onychomycosis/epidemiology , Terbinafine/therapeutic use , Itraconazole/therapeutic use , Treatment OutcomeABSTRACT
Good adherence to treatment is necessary for the successful treatment of onychomycosis and requires that an appropriate amount of medication be prescribed. Most prescriptions for efinaconazole 10% solution, a topical azole antifungal, are for 4 mL per month but there are no data on patient factors or disease characteristics that impact how much medication is needed. Data from two phase 3 studies of efinaconazole 10% solution for the treatment of toenail onychomycosis were pooled and analyzed to determine monthly medication usage based on the number of affected toenails, percent involvement of the target toenail, body mass index (BMI), and sex. Participants with two or more affected nails required, on average, >4 mL of efinaconazole per month, with increasing amounts needed based on the number of nails with onychomycosis (mean: 4.39 mL for 2 nails; 6.36 mL for 6 nails). In contrast, usage was not greatly impacted by target toenail involvement, BMI, or sex. Together, these data indicate that the number of affected nails should be the major consideration when determining the monthly efinaconazole quantity to prescribe. J Drugs Dermatol. 2024;23(2):110-112. doi:10.36849/JDD.7676.
Subject(s)
Foot Dermatoses , Onychomycosis , Humans , Onychomycosis/diagnosis , Onychomycosis/drug therapy , Onychomycosis/microbiology , Nails , Administration, Topical , Triazoles/therapeutic use , Antifungal Agents , Foot Dermatoses/diagnosis , Foot Dermatoses/drug therapy , Foot Dermatoses/microbiologyABSTRACT
The purpose of this review is to consolidate and summarize laser-assisted drug delivery (LADD) for nail diseases, particularly onychomycosis and psoriasis. A PubMed search was conducted in June 2023 using search terms (1) "laser assisted drug delivery" AND "nail," (2) "laser" AND "nail," and (3) "nail disorder" AND "laser treatment." References of papers were also reviewed, yielding 15 papers for this review. Fractional ablative CO2 laser (FACL) and Er:YAG laser can be used for LADD of topical medications such as amorolfine, terbinafine, and tioconazole to treat onychomycosis. A fungal culture should be performed to determine the type of dermatophyte, which will help determine which topical will be most effective. Laser settings varied between studies, but overall LADD tended to be more effective than topical treatments alone. Laser-assisted photodynamic therapy (PDT) was also found to be effective in treating onychomycosis. For psoriatic nails, LADD was used to deliver calcipotriol-betamethasone dipropionate foam, tazarotene, triamcinolone, or methotrexate into the nail. Again, LADD was found to be significantly more effective than topical treatment alone. FACL was the only laser noted for use for LADD in both diseases. Laser-assisted drug delivery for nail disease is a newer approach for onychomycosis and nail psoriasis with several benefits and drawbacks. Dermatologists should discuss the option of LADD with their patients who have recalcitrant onychomycosis or nail psoriasis.
Subject(s)
Lasers, Gas , Nail Diseases , Onychomycosis , Psoriasis , Humans , Onychomycosis/drug therapy , Onychomycosis/radiotherapy , Pharmaceutical Preparations , Antifungal Agents/therapeutic use , Nail Diseases/drug therapy , Psoriasis/drug therapy , Psoriasis/radiotherapy , Administration, Topical , Lasers, Gas/therapeutic use , Treatment OutcomeABSTRACT
Dermatophyte biofilms frequently count for inadequate responses and resistance to standard antifungal treatments, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has clinically proven to exert significant antifungal effects or even capable of eradicating dermatophyte biofilms, considerably less is known about the molecular mechanisms underlying aPDT and the potential dysregulation of signaling networks that could antagonize its action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combat against dermatophyte biofilm in recalcitrant onychomycosis and to decipher the potential detoxification processes elicited by aPDT, facilitating the development of more effective photodynamic interventions. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm formed by three distinct dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, the most frequently occurring pathogenic species. In total, 352.13 Gb of clean data were obtained for the transcriptomes of dermatophyte biofilms with or without aPDT treatment, resulting in 2,422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes, and M. gypseum, respectively. The genome-wide orthologous analysis identified 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following aPDT treatment. Integrative orthology analysis demonstrated the upregulation of oxidoreductase activities is a highly conserved detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified a conserved detoxification regulation upon the aPDT application.
Subject(s)
Arthrodermataceae , Biofilms , Gene Expression Profiling , Photochemotherapy , Biofilms/drug effects , Arthrodermataceae/drug effects , Arthrodermataceae/genetics , Microsporum/drug effects , Microsporum/genetics , Humans , Antifungal Agents/pharmacology , Onychomycosis/microbiology , Onychomycosis/drug therapy , TranscriptomeABSTRACT
BACKGROUND: There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. OBJECTIVES: We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs). METHODS: We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, 'regimen' corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks. RESULTS: Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1â year; safety--related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like 'terbinafine 250â mg daily for 12 weeks' and 'itraconazole 200â mg daily for 12 weeks. We found that an agent's dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250â mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250â mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57-4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine. CONCLUSIONS: This is the first NMA study of monotherapeutic antifungals - and their various dosages - for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.
Subject(s)
Arthrodermataceae , Foot Dermatoses , Onychomycosis , Adult , Humans , Antifungal Agents/therapeutic use , Onychomycosis/drug therapy , Terbinafine , Network Meta-Analysis , Nails , Bayes Theorem , Naphthalenes/adverse effects , Treatment Outcome , Foot Dermatoses/drug therapy , ItraconazoleABSTRACT
BACKGROUND: The prognostic factors for cure have been derived from cases of dermatophyte onychomycosis. However, there are limited studies in non-dermatophyte onychomycosis. Neoscytalidium dimidiatum is the common causative agents of non-dermatophyte onychomycosis which has proven to be recalcitrant to treatment. OBJECTIVE: This retrospective cohort study investigated mycological cure and prognostic factors in Neoscytalidium onychomycosis patients. METHODS: Patients aged 18 or older with newly diagnosed Neoscytalidium onychomycosis were enrolled. All patients were treated and followed up for at least 1 year. Mycological cure was analysed with Cox proportional hazard regression. The hazard ratios (HRs) of previously reported potential prognostic factors were included in univariable and multivariable stratified Cox regression analyses. RESULTS: From total 198 patients, mycological cure was achieved in 108 (54.6%) patients with a median of 490 (± SD 62.2) days. The poor prognostic factors for mycological cure were age ≥ 70 years (HR, 0.63; 95% CI, 0.41-0.97; p = .034); nail thickness ≥2 mm (HR, 0.20; 95% CI, 0.11-0.35; p < .001); and peripheral vascular disease (HR, 0.46; 95% CI, 0.28-0.77; p = .003). Combination therapy was associated with achieving a mycological cure (HR, 2.55; 95% CI, 1.49-4.38; p < .001). CONCLUSIONS: Approximately half of the patients with onychomycosis caused by Neoscytalidium dimidiatum achieved a mycological cure, with a median time to cure exceeding 1 year. Combined topical and systemic antifungal treatments yield a higher chance of mycological cure than monotherapies. Advanced age, nail thickness and peripheral vascular disease are obstacle factors to cure.
Subject(s)
Onychomycosis , Peripheral Vascular Diseases , Humans , Onychomycosis/drug therapy , Prognosis , Retrospective Studies , Antifungal Agents/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Onychomycosis was an ignored disease in children, and the prevalence was still unknown worldwide. OBJECTIVES: This study was conducted to investigate the prevalence and treatment regimens of onychomycosis in children younger than 18 years old. METHODS: We systemically reviewed all publications by searching the key terms to reveal the onychomycosis in children from 1990 to 2022. RESULTS: A total of 44 articles including 2,382 children with onychomycosis were enrolled in this study. The male to female ratio was 1.29:1. The youngest child was 35 days old and the average age was 9.8 years old. The duration of disease usually ranged from 7 days to 4 years. Onychomycosis in children was more prevalent in toenails compared to fingernails (77.6% vs. 18.4%), and 4% patients had both. A total of 527 children (22.12%) had concomitant tinea pedis infection, and in 267 patients (11.21%), their family members had onychomycosis or tinea pedis. The most common clinical type of onychomycosis was DLSO (67.74%) and the predominant isolates were T. rubrum (66.13%), followed by C. albicans (9.08%) and T. mentagrophytes complex (5.34%). There were 419 children (74.03%) receiving systematic treatment only, 74 patients (13.07%) receiving topical treatment only, and 73 patients (12.90%) receiving both systematic and topical treatment. Twelve patients (2.12%) had mild drug-related side effects. During the follow-up, 71.25% children were cured, 17.50% symptoms improved and 4.17% failed. CONCLUSIONS: Onychomycosis was underestimated in children and the diagnosis of onychomycosis should be properly considered in children with nail disorders. For mild patients, topical treatment can be a good choice, and oral antifungal drugs could be added to severe individuals under monitoring.
Subject(s)
Onychomycosis , Child , Humans , Male , Female , Adolescent , Onychomycosis/drug therapy , Onychomycosis/epidemiology , Onychomycosis/diagnosis , Tinea Pedis/microbiology , Retrospective Studies , Antifungal Agents , Nails/microbiology , Candida albicansABSTRACT
BACKGROUND: A new water-soluble formulation with ciclopirox has shown a higher penetration than other ciclopirox nail lacquers currently marketed, thus providing a higher concentration of ciclopirox into the nail. OBJECTIVE: To evaluate the efficacy and safety of a new ciclopirox nail hydrolacquer compared with its vehicle and an active comparator (hydroxypropyl chitosan-based 80 mg/g ciclopirox nail lacquer) for the treatment of toenail fungal infection. METHODS: Phase III, multicenter, randomised, double-blind, clinical trial in patients with distal mild to moderate toenail onychomycosis due to dermatophyte fungi. Patients were randomised to apply topically a ciclopirox nail hydrolacquer, its vehicle or a reference product once daily for 48 weeks with a follow-up period of 4 weeks up to week 52. RESULTS: A total of 381 patients were included. No statistically significant differences were observed between patient groups in the proportion of subjects achieving a complete cure. At week 52, a higher percentage of patients in the ciclopirox nail hydrolacquer group achieved a mycological cure (negative for culture and DTS/KOH test, with results: 32.0% ciclopirox nail hydrolacquer, 23.2% vehicle and 27% reference product, respectively), and similar results were found for improvement (mycological cure and reduction of diseased nail ≥20%, with results: 27.2% ciclopirox nail hydrolacquer, 21.6% vehicle and 20.6% reference product, respectively). Regarding mycological results, only ciclopirox nail hydrolacquer demonstrated significant statistical superiority versus vehicle negativizing dermatophyte culture (p = .039) with no recurrences, relapses or re-infections in a four-week follow-up patients with complete cure. The safety profile was comparable to the vehicle and reference product and consistent with the previously reported. CONCLUSIONS: A new water-soluble formulation for a ciclopirox nail lacquer showed similar efficacy to the reference product to eradicate toenail onychomycosis and superiority in the mycological cure defined by negative culture, thus preventing reinfections and recurrences. Efficacy and safety data demonstrate the positive benefit-risk profile of this new topical antifungal preparation. [Correction added on 13 April 2023, after first online publication: The results and conclusions in the Abstract contained incorrect information and were revised in this version.].
Subject(s)
Foot Dermatoses , Onychomycosis , Humans , Adult , Onychomycosis/drug therapy , Onychomycosis/microbiology , Ciclopirox/adverse effects , Nails , Pyridones/adverse effects , Administration, Topical , Antifungal Agents/adverse effects , Foot Dermatoses/drug therapy , Water , Treatment OutcomeABSTRACT
Onychomycosis is caused by dermatophytes, non-dermatophytes and yeasts. It has a global prevalence of 5.5%, requires long treatment periods, and has high relapse rates following therapy. Oral antifungals are generally the most common treatment. While effective, they have limitations such as drug-drug interactions, hepatotoxicity and adverse side effects; thus, they cannot be used in several populations. Topical antifungals do not have the safety limitations but are typically not as effective. The primary challenge of topical treatment is the permeation of drug molecules across the nail plate barrier, which is a highly cross-linked keratin network. The use of drugs and formulations with favourable characteristics such as small size, absence of lipophilicity, hydrophilic nature, hydrating properties and appropriate pH can greatly improve permeation. Here, we review physical, nanoparticle-based, formulation-based, mechanical and chemical drug delivery strategies to improve the permeation of drugs across the nail plate.
Subject(s)
Onychomycosis , Humans , Onychomycosis/drug therapy , Antifungal Agents , Pharmaceutical Preparations , Nails , Drug Delivery Systems , Administration, TopicalABSTRACT
Antifungal resistance has become prevalent worldwide. Understanding the factors involved in spread of resistance allows the formulation of strategies to slow resistance development and likewise identify solutions for the treatment of highly recalcitrant fungal infections. To investigate the recent explosion of resistant strains, a literature review was performed focusing on four main areas: mechanisms of resistance to antifungal agents, diagnosis of superficial fungal infections, management, and stewardship. The use of traditional diagnostic tools such as culture, KOH analysis and minimum inhibitory concentration values on treatment were investigated and compared to the newer techniques such as molecular methods including whole genome sequencing, and polymerase chain reaction. The management of terbinafine-resistant strains is discussed. We have emphasized the need for antifungal stewardship including increasing surveillance for resistant infection.
Subject(s)
Dermatomycoses , Onychomycosis , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Onychomycosis/diagnosis , Onychomycosis/drug therapy , Onychomycosis/microbiology , Terbinafine/therapeutic use , Dermatomycoses/drug therapy , Drug Resistance, FungalABSTRACT
Onychomycosis is a prevalent condition affecting the United States and global population. Treatment options are limited, with only 3 topical anti-fungal medications garnering approval in the US within the last 25 years: ciclopirox, tavaborole, and efinaconazole. The economic impact and quality of life burden due to onychomycosis are high. Here we provide an up-to-date review of all approved topical anti-fungal therapies for toenail onychomycosis. We discuss treatment efficacies, pharmacology, and use in special populations, as well as current evidence for complementary and alternative medicine. J Drugs Dermatol. 2023;22:9(Suppl 1):s5-10.