Feuilhade de Chauvin, M
A positive mycological examination is required before discussion of treatment of onychomycosis. Onychomycosis is most commonly due to dermatophytes in association with tinea pedis and/or tinea manuum. It is a catched infection. Candida onychomycosis is a rare opportunistic infection and onychomycosis due to non-dermatophytic moulds is very rare as a "chance mishap". The treatment of dermatophyte onychomycosis takes each infected part of the nail into account. Topical antifungal agents should be reserved for mild to moderate onychomycosis. Systemic antifungal agents are required to severe onychomycosis. In all cases, removal of infected nail parts is useful to facilitate the penetration of antifungal drugs and eradication of reinfection sites may be done to prevent recurrences and relapses. In primary, Candida onychomycosis treatment with topical antifungal drugs may be effective but in case of treatment failure, a systemic therapy is required. Suppression predisposing factors is useful. The treatment of non-dermatophytic moulds onychomycosis is still a challenge. Except Neoscytalidium spp., which mimic a dermatophytosis, non-dermatophytic moulds may be isolated from dystrophic nails and it is always difficult to specify their role as a primary pathogen or as a colonizer of nails. The available topical and systemic antifungal drugs are not effective against these non-dermatophytic moulds except itraconazole for onychomycosis due to Aspergillus spp. New therapy such as light and laser therapy are in evaluation.
Arenas, Roberto; Bonifaz, Alexandro; Padilla, Ma Carmen; Arce, Martín; Atoche, Carlos; Barba, José; Campos, Pablo; Fernández, Ramón; Mayorga, Jorge; Nazar, Dulce; Ocampo, Jorge
Onychomycosis is a nail infection caused by dermatophytes, Candida and molds. We aimed to obtain an estimated frequency of onychomycosis in out-patients in private practice through a survey in ten representative cities of Mexico. 12,637 ambulatory patients voluntarily agreed to participate in this National Survey, answering 17 questions on onychomycosis, regardless if they had or did not have any clinical suspicion of onychomycosis. 53% of them were seen for the first time and their main complaint was not onychomycosis. The study was performed in the private offices of 300 physicians in different cities. 48% were clinically diagnosed with onychomycosis. Toenails were affected in 88%, fingernails in 5% and both in 7%. Onychomycosis was diagnosed more frequently in the nails of the first toes and of the thumbs. The main complaint was nail thickening and aesthetic changes. Other associated diseases were diabetes (22%) and arterial hypertension (21%). This survey showed the high frequency of onychomycosis. An intentional search with mycological confirmation is needed in out-patients attending general practice with other complaints, to detect undiagnosed cases.
Onychomycosis and tinea pedis are common fungal infections affecting the nails and feet, respectively. Two newly approved topical agents for onychomycosis are efinaconazole and tavaborole, both of which have demonstrated respectable cure rates in clinical studies. For tinea pedis, naftifine 2% and luliconazole 1% are new agents, both administered for relatively short courses, that may foster greater adherence Semin Cutan Med Surg 35(supp6):S110-S113.
Hwang, Sung Min; Ha, Gyoung Yim
Background Although there have been many studies about onychomycosis due to nondermatophytic molds (NDM), few studies about etiologic agents including NDM in onychomycosis have been reported in Korea. Objective: This study investigated onychomycosis due to NDM in the Gyeongju area of Korea. Objective This study investigated onychomycosis due to NDM in the Gyeongju area of Korea. Methods In the 10-year period from 1999~2009, we reviewed 59 patients with onychomycosis due to NDM. The etiologic agents were identified by cultures on Sabouraud's Dextrose agar with and without cycloheximide. In some cases, internal transcribed spacer sequence analysis was done. NDM isolated considered pathogens when the presence of fungal elements was identified by direct microscopy observation and in follow-up cultures yielding the same fungi. Results Onychomycosis due to NDM comprised 2.3% of all onychomycosis. Of the 59 patients with onychomycosis due to NDM, 84.7% were toenail onychomycosis and 15.3% were fingernail onychomycosis. The incidence rate was highest in the fifth decade (27.1%). The ratio of male to female patients was 1:1.6. The frequency of associated diseases, in descending order, was hypertension, diabetes mellitus, and cerebral hematoma. Distal and lateral subungual onychomycosis (86.4%) was the most common clinical type of onychomycosis. Aspergillus spp. was the most frequently isolated etiologic agent of onychomycosis due to NDM (83.0%). Other causative agents were Scopulariopsis brevicaulis (10.2%), Acremonium spp. (3.4%), Fusarium solani (1.7%), and Chaetomium globosum (1.7%). Conclusion Because of the increase in onychomycosis due to NDM, we suggest the need of a careful mycological examination in patients with onychomycosis. PMID:22577268
Järv, H; Naaber, P; Kaur, S; Eisen, M; Silm, H
The aim of our study was to evaluate the clinical features, predisposing factors and pathogens of toenail onychomycosis in Estonia. During study period we interviewed and examined 436 dermatological patients with clinical signs of toenail onychomycosis in all counties of Estonia. In 69% of cases, the clinical diagnosis of onychomycosis was confirmed by the mycological analysis. The most common clinical symptoms of onychomycosis both in mycologically proven and non-proven cases were discolorization of nail plate, hyperkeratosis and brittle nails. The number of infected toenails positively correlated with patients' age. On average, patient had 5.4 infected nails. In 78% of culture-positive cases, a dermatophyte was isolated as the causative agent, in 10% yeasts and in 7% moulds. In 6% of culture-positive cases we reported mixed infections. Trichophyton rubrum was the most common pathogen. The high occurrence of mixed infections, clinical symptoms characteristic to long lasting or chronic infection and high number of infected toenails indicate that Estonian patients have more advanced stage of toenail onychomycosis compared with other western and central European countries.
Petinataud, D; Berger, S; Contet-Audonneau, N; Machouart, M
Onychomycosis is a frequent cause of nail infections due to dermatophytes. Molds and yeast may also be responsible of these pathologies. Antifungal treatments are frequently given without a mycological diagnosis, partly because of the requisite time for obtaining the biological results. The mycological diagnosis requires a direct microscopic examination and a culture in order to accurately identify the fungal genus and species. Nevertheless, this conventional diagnosis is often time consuming due to the delay of fungal cultures and presents disadvantages that make it not sufficient enough to give a precise and confident response to the clinicians. Therefore additional tests have been developed to help distinguish onychomycosis from other nail disorders. Among them, molecular biology techniques offer modern and rapid tools to improve traditional microbiological diagnosis. In this review, we first present the conventional diagnosis methods for onychomycosis and then we describe the main molecular biology tools and the currently available commercial kits that allow a rapid detection of the pathology.
Bertanha, Laura; Chiacchio, Nilton Di
Onychomycosis is the most prevalent onychopathy and it requires a correct early diagnosis. Currently, the diagnostic gold standard is the association of direct mycological test with culture; however, it shows variable sensitivity. The histopathological examination of the distal nail plate, called clipping, has shown to be an adjuvant in diagnosing onychomycosis. This is an easy-to-perform, relatively cheap examination that is little dependent of the examiner, rapidly provides results, has high sensitivity, and for patients it is painless and harmless. PMID:27828655
Xiong, Zilan; Roe, Jeff; Grammer, Tim; Him, Yeon-Ho; Graves, David B.
Onychomycosis or fungal infection of the toenail or fingernail is a common affliction. Approximately 10% of the world's adult population is estimated to suffer from onychomycosis. Current treatment options such as topical creams, oral drugs, or laser treatments are generally limited by a variety of problems. We present results for an alternative onychomycosis treatment scheme using atmospheric pressure cold air plasmas. Using thinned cow hoof as a model nail material, we tested the ability of various plasma sources to act through the model nail to eradicate either bacteria or fungus deposited on the opposite side. Following 20 minute exposure to a surface microdischarge (SMD) device operating in room air, we observed a ~ 2 log reduction of E. coli. A similar result was obtained against T. rubrum after 45 min plasma treatment. NOx species concentration penetrating through the model nail as well as uptake into the nail were measured as a function of nail thickness. We propose that these plasma-generated species, or perhaps their reaction products, are responsible for at least part of the observed anti-microbial effect. We also explore the use of ultraviolet light acting in synergy with plasma-generated chemical species.
Stein Gold, Linda F
No scientifically rigorous, large, prospective studies have been done to document the true prevalence of onychomycosis; the reported rates vary mainly by climate and by population, but the overall prevalence in the United States is estimated to be at least 10%. Advanced age and diabetes are the most commonly reported risk factors for onychomycosis. The differential diagnosis of onychomycosis is lengthy, and visual inspection alone is not sufficient for a definitive diagnosis-direct microscopic examination of a wet-mount preparation with 10% to 20% potassium hydroxide is the first-line diagnostic test.
Chabasse, D; Pihet, M
Onychomycosis represents about 50% of ungueal pathology. Dermatophytes (especially Trichophyton rubrum and Trichophyton interdigitale) are the main species involved in tinea pedis. Yeasts of the Candida (Candida albicans, Candida parapsilosis,...) genus are predominant on hands and very often associated with ungueal disease and perionyxis. Fungi other than the classic dermatophytes and yeasts can be rarely isolated from nail diseases. Among them, species belonging to Scopulariopsis, Aspergillus and Fusarium genus are mainly found, but their involvement in the disease must be proved. Other fungi, presenting a special affinity to keratin (pseudodermatophytes), such as Neoscytalidium dimidiatum (ex Scytalidium dimidiatum) from tropical and subtropical areas and Onychocola canadensis from Northern America and Europe, are considered as real pathogens in nail diseases. A multidisciplinary approach, including clinicians and biologists, is required to confirm the mycosis. This comparative review emphasizes the importance of histological examination, as well as molecular approaches, which are very contributive to the diagnosis of onychomycosis. The role of the laboratory is to identify at the species level the fungus isolated from nail scrapings and to show its involvement in the ungueal lesions.
Solís-Arias, Martha Patricia; García-Romero, Maria Teresa
Onychomycosis is considered an age-related infection with increasing prevalence in the older age groups. It is rare in the pediatric population, except in children with Down syndrome and with immunodeficiencies, who are more likely to have fungal nail infections. The number of reports about onychomycosis in children is relatively small, and the epidemiologic data vary, but a rise in prevalence has been demonstrated. In this article, we review the most up-to-date literature and summarize the epidemiology, etiology, clinical presentation, diagnosis, and treatment of onychomycosis in children, as well as the differences with the disease presenting in adults. Dermatologists must consider onychomycosis in the differential diagnosis of nail alterations in children and always perform a mycological study to confirm the diagnosis.
Elewski, Boni E.
Although not life-threatening, onychomycosis (a fungal infection of the nail, usually caused by a dermatophyte) constitutes an important public health problem because of its high prevalence (about 10% of the U.S. population) and associated morbidity. The disease can have certain negative consequences for patients, such as pain, and can potentially undermine work and social lives. This review discusses the etiology, classification, diagnosis, and treatment of onychomycosis. Four types of onychomycosis are recognized based on the site and pattern of fungal invasion. Dermatophyte fungi are the predominant pathogens, but yeasts (especially Candida albicans) and nondermatophyte molds may also be implicated. Accurate diagnosis requires direct microscopy and fungal culture. The differential diagnosis includes psoriasis, lichen planus, onychogryphosis, and nail trauma. Onychomycosis is more difficult to treat than most dermatophytoses because of the inherent slow growth of the nail. Older antifungal agents (ketoconazole and griseofulvin) are unsuitable for onychomycosis because of their relatively poor efficacy and potential adverse effects. Three recently developed antimycotic agents (fluconazole, itraconazole, and terbinafine) offer high cure rates and good safety profiles. In addition, the short treatment times (<3 months) and intermittent dosing schedules are likely to enhance compliance and reduce the costs of therapy. PMID:9665975
Martínez-Herrera, Erick Obed; Arroyo-Camarena, Stefanie; Tejada-García, Diana Luz; Porras-López, Carlos Francisco; Arenas, Roberto
BACKGROUND: Onychomycosis are caused by dermatophytes and Candida, but rarely by non- dermatophyte molds. These opportunistic agents are filamentous fungi found as soil and plant pathogens. OBJECTIVES: To determine the frequency of opportunistic molds in onychomycosis. METHODS: A retrospective analysis of 4,220 cases with onychomycosis, diagnosed in a 39-month period at the Institute of Dermatology and Skin surgery "Prof. Dr. Fernando A. Cordero C." in Guatemala City, and confirmed with a positive KOH test and culture. RESULTS: 32 cases (0.76%) of onychomycosis caused by opportunistic molds were confirmed. The most affected age group ranged from 41 to 65 years (15 patients, 46.9%) and females were more commonly affected (21 cases, 65.6%) than males. Lateral and distal subungual onychomycosis (OSD-L) was detected in 20 cases (62.5%). The microscopic examination with KOH showed filaments in 19 cases (59.4%), dermatophytoma in 9 cases (28.1%), spores in 2 cases (6.25%), and filaments and spores in 2 cases (6.25%). Etiologic agents: Aspergillus sp., 11 cases (34.4%); Scopulariopsis brevicaulis, 8 cases (25.0%); Cladosporium sp., 3 cases (9.4%); Acremonium sp., 2 cases (6.25%); Paecilomyces sp., 2 cases (6.25%); Tritirachium oryzae, 2 cases (6.25%); Fusarium sp., Phialophora sp., Rhizopus sp. and Alternaria alternate, 1 case (3.1%) each. CONCLUSIONS: We found onychomycosis by opportunistic molds in 0.76% of the cases and DLSO was present in 62.5%. The most frequent isolated etiological agents were: Aspergillus sp. and Scopulariopsis brevicaulis. PMID:26131862
Scher, Richard K; Rich, Phoebe; Pariser, David; Elewski, Boni
The prevalence of onychomycosis in the United States is estimated to be at least 12%; prevalence increases with increasing age and is highest in individuals more than 65 years of age. Trichophyton rubrum, which also causes tinea pedis, is responsible for approximately 90% of cases of toenail onychomycosis. Risk factors include a family history of onychomycosis and previous injury to the nails, as well as advanced age and compromised peripheral circulation. Patients with compromised immune function may have an increased risk for onychomycosis and are susceptible to infection with less common dermatophytes and nondermatophyte organisms.
D’Antonio, Domenico; Romano, Ferdinando; Iacone, Antonio; Violante, Beatrice; Fazii, Paolo; Pontieri, Eugenio; Staniscia, Tommaso; Caracciolo, Claudia; Bianchini, Stefano; Sferra, Roberta; Vetuschi, Antonella; Gaudio, Eugenio; Carruba, Giuseppe
Blastoschizomyces capitatus was cultured from the nail of a healthy patient with onychomycosis. The identity of the isolate was initially established by standard methods and ultrastructural analysis and was verified by molecular probing. Strains ATCC 200929, ATCC 62963, and ATCC 62964 served as reference strains for these analyses. To our knowledge, this is the first case of nail infection secondary to paronychia caused by this organism reported in the English literature. PMID:10449477
Segal, Rina; Shemer, Avner; Hochberg, Malca; Keness, Yoram; Shvarzman, Rima; Mandelblat, Marina; Frenkel, Michael; Segal, Esther
Onychomycosis is a fungal infection treated orally for prolonged periods of treatment, caused primarily by Dermatophytes, Candida species and non-dermatophyte moulds (NDMs). The prevalence of specific aetiology may differ in dependence of environmental, geographic and demographic factors, and may affect management of the infection. The objective of this survey was to analyse epidemiologic parameters of onychomycosis in Israel. Data of a cohort of 27,093 patients were collected from six centres during a 2- and 10-year period. The diagnosis was based on microscopy of KOH/calcofluor mounts of nail scrapings and culture isolation. A positive result indicates isolation of a fungus in culture. Data were analysed for each centre and expressed as range for the whole cohort, using the spss v18 software. Analysis included three epidemiologic parameters: fungal aetiology in toe- and fingernails; association with gender; association with age group. Dermatophytes were the major causative agents and Trichophyton rubrum the most frequent isolate. Candida species were more frequent in women fingernails; frequency increased with age and C. parapsilosis the most frequent species. NDMs were isolated at low rate and Aspergillus terreus was the most frequent isolate. This is a first large cohort of onychomycosis patients from Israel analysed by defined epidemiological parameters.
Gupta, Aditya K; Elewski, Boni E; Rosen, Ted; Caldwell, Bryan; Pariser, David M; Kircik, Leon H; Bhatia, Neal; Tosti, Antonella
Recurrence (relapse or re-infection) in onychomycosis is common, occurring in 10% to 53% of patients. However, data on prevalence is limited as few clinical studies follow patients beyond 12 months. It has been suggested that recurrence after continuous terbinafine treatment may be less common than with intermittent or continuous itraconazole therapy, probably due to the fungicidal activity of terbinafine, although these differences tended not to be significant. Relapse rates also increase with time, peaking at month 36. Although a number of factors have been suggested to play a role in recurrence, only the co-existence of diabetes has been shown to have a significant impact. Data with topical therapy is sparse; a small study showed amorolfine prophylaxis may delay recurrence. High concentrations of efinaconazole have been reported in the nail two weeks' post-treatment suggesting twice monthly prophylaxis with topical treatments may be a realistic option, and may be an important consideration in diabetic patients with onychomycosis. Data suggest that prophylaxis may need to be continued for up to three years for optimal effect. Treating tinea pedis and any immediate family members is also critical. Other preventative strategies include avoiding communal areas where infection can spread (such as swimming pools), and decontaminating footwear.
Bhatta, Anil K; Huang, Xin; Keyal, Uma; Zhao, Jun Jing
It has always been difficult to treat onychomycosis due to decrease ability of topical agents to penetrate the nail and reach the affected nail bed. Oral antifungal have shown good response but due to longer duration course it has potential to cause systemic side effects, leading to patient non-adherence and adverse events. Lasers, therefore, have been suggested for the treatment of onychomycosis due to their minimally invasive nature and the potential for requiring fewer treatment sessions. The aim of writing this article is to review a literature regarding treatment of onychomycosis by laser. This article will discuss about all the available laser treatment options for onychomycosis as well as their currently published, peer-reviewed literature.
Ayanlowo, O; Oladele, R O
Onychomycosis is a fungal infection which affects the nail unit. It was previously thought to be just a cosmetic problem, but presently, it is regarded as a major public health issue because of the impact on the quality of life of the patients.A etiologic factors identified in onychomycosis include increasing age,immunosuppression, occupation and genetics. Management of onychomycosisis both pharmacological and non pharmacological. Pretreatment counseling is important in patients with fungal nail infections and this should include probable length of therapy, possible side effects of treatment and the expenses involved.Patients should be educated on proper nail care and the fact that no treatment isI 00% effective. Presently, combination therapy is advocated for the management of onychomycosis. This is a review of the epidemiology, clinical types,investigations and current considerations in the management of onychomycosis.
de Almeida Jr., Hiram Larangeira; Boabaid, Roberta Oliveira; Timm, Vitor; Silva, Ricardo Marques e; de Castro, Luis Antonio Suita
Superficial white onychomycosis is characterized by opaque, friable, whitish superficial spots on the nail plate. We examined an affected halux nail of a 20-year-old male patient with scanning electron microscopy. The mycological examination isolated Trichophyton mentagrophytes. Abundant hyphae with the formation of arthrospores were found on the nail's surface, forming small fungal colonies. These findings showed the great capacity for dissemination of this form of onychomycosis. PMID:26560225
Chadeganipour, Mostafa; Nilipour, Shahi; Ahmadi, Gholamreza
A mycological study was undertaken in 488 patients suspected of onychomycosis in Isfahan, a large province of Iran, to gain more insight into the prevalence and aetiology of this infection. Direct microscopy of the nail clips was positive in 194 (39.8%) and fingernail onychomycosis was recognised in 141 (72.7%) and toenail onychomycosis in 53 (27.3%) cases. As agents of onychomycosis, yeast were detected in 112 (57.7%), dermatophytes in 27 (13.9%) and non-dermatophyte fungi in 55 (28.4%) patients. Of the samples cultured, Candida albicans was the most prevalent (84%) yeast. Among dermatophytes, Trichophyton mentagrophytes var. interdigitale was found to be the commonest aetiological agent (8.6%) followed by Epidermophyton floccosum and T. rubrum. Among the non-dermatophyte moulds, Aspergillus flavus was the most prevalent species (13%). Moreover, nine samples with positive direct microscopy yielded no growth. Females were affected more frequently with fingernail candidal infections than males, and children under 7 years of age were predominantly involved with candidal paronychia. The majority of fungal nail infections were characterised clinically by distal and proximal subungual onychomycosis. The growing trend towards the frequency of fingernail onychomycosis in housewives was noticeable in the last decade in Iran.
Elewski, Boni E; Tosti, Antonella
Onychomycosis causes approximately one-half of all nail disorders and its prevalence has been steadily increasing. It is difficult to treat, partly due to the subungual location and the inability of both oral and topical antifungals to reach the site of infection. Published cure rates with oral drugs are < 50% and even lower with topical drugs. Pathogenic factors include the diversity of fungal organisms and the difficulty of drugs penetrating the nail plate. Tavaborole is a broad-spectrum oxaborole antifungal agent with low molecular weight, permitting optimal nail plate penetration. In vitro and ex vivo studies have demonstrated the superior nail-penetrating properties of tavaborole compared to existing topical antifungal medications approved for the treatment of onychomycosis. The clinical characteristics and prevalence of onychomycosis, currently available treatments, and the chemistry, safety and pharmacokinetic properties of tavaborole for the treatment of onychomycosis. Tavaborole is a novel, topical antifungal pharmaceutical agent pending FDA approval for the treatment of toenail onychomycosis due to dermatophytes. Efficacy has been demonstrated by a clinical development program including in vitro data and two large Phase III trials that enrolled ∼ 1200 patients. When approved, tavaborole topical solution, 5% may become a safe and effective option for the treatment of onychomycosis.
Bunyaratavej, Sumanas; Prasertworonun, Nuntida; Leeyaphan, Charussri; Chaiwanon, Onjuta; Muanprasat, Chanai; Matthapan, Lalita
Studies of demographic data, predisposing factors and clinical manifestations of non-dermatophyte mold (NDM) infection particularly in Scytalidium spp. have been limited. This study aimed to compare these data between dermatophytes (DMP) and NDM onychomycosis with statistical analysis. This was a retrospective chart review of outpatients with onychomycosis in the Nail Clinic of Department of Dermatology between January 2011 and December 2013. A total of 237 patients who had presented with onychomycosis were included. One hundred and eighty patients (75.9%) were infected with DMP: Trichophyton mentagrophytes, 46.8%; and Trichophyton rubrum, 28.3%. Of patients who had NDM onychomycosis, 17.3% were Scytalidium dimidiatum and 6.8% were Fusarium spp. Comparing the DMP and NDM groups, family history of superficial fungal infection was significantly demonstrated in the DMP group. Approximately 50% of patients in both groups had feet infections. However, no patients with NDM onychomycosis had fungal glabrous skin infection at other sites beyond the feet that was statistically different from cases with DMP onychomycosis. In conclusion, The distinct characteristic of patients with NDM onychomycosis was absence of fungal glabrous skin infection in areas other than the feet. This was statistically different from DMP.
Godoy-Martinez, Patricio; Nunes, Fabiane G; Tomimori-Yamashita, Jane; Urrutia, Milton; Zaror, Luis; Silva, Victor; Fischman, Olga
Onychomycosis is a fungal infection of the nails with broad aetiological scope, and it represents 18-40% of all onychopathies and 39% of all superficial mycotic infections. From July 1996 to December 1999, samples of nails were collected from 588 patients with presumptive diagnosis of onychomycosis at the Dermatology and Mycology Divisions EPM\\UNIFESP, Brazil, and the diagnosis was confirmed in 247 of these cases. The most common pathogens isolated in this study were yeasts in 52% of positive cultures (Candida albicans 18.3%, Candida parapsilosis 13.8%, other species of Candida 15.4% and other yeasts 4.6%), followed by dermatophytes in 40.6% of positive cultures (the most commonly isolated organisms were Trichophyton rubrum in 33.2%, followed by Trichophyton mentagrophytes in 6.3% and others 1.2%). Non-dermatophyte moulds were isolated in 7.4% of positive cultures (Fusarium spp. 4.5%, Nattrassia mangiferae 2.3% and Aspergillus spp. 0.6%). Distal and lateral subungual onychomycosis (DLSO) was the commonest clinical pattern 44.6% followed by free edge onycholysis (FEO) 38.8% and others. In conclusion, this study demonstrated that T. rubrum is the main agent causing onychomycosis in toenails, and species of genus Candida were the main agents isolated in fingernail onychomycosis in our region.
Milobratović, Danica; Janković, Slavenka; Vukičević, Jelica; Marinković, Jelena; Janković, Janko; Railić, Zoran
Onychomycosis is a common, chronic fungal nail infection that can have a significant negative impact on patients' physical and social functioning and emotional well-being. This study was undertaken to assess health-related quality of life (HRQoL) in patients with toenail onychomycosis. The Onychomycosis QoL questionnaire (ONYCHO), as a disease-specific instrument, and the Short Form 36 Health Survey (SF-36) as a generic instrument, were applied in 140 consecutive patients affected by onychomycosis. Women and patients who were experiencing toenail onychomycosis for more than 2 years were reporting worse disease-specific HRQoL. The patients working in blue-collar occupations and patients with greater involvement of individual nails were more affected by onychomycosis regarding symptoms. The results of this study confirm that although onychomycosis is not a life-threatening disease, it can significantly reduce patients' QoL.
Dias, N; Santos, C; Portela, M; Lima, N
Onychomycosis is a common fungal infection of the nail but few data of mycological features in geriatric Portuguese population are yet available. The aim of this study was to perform a mycological examination and characterization of fungal nail pattern of a geriatric population from the north of Portugal clinically suspected of onychomycosis. A total of 108 patients attending the Podology Service in the Centro Hospitalar do Alto Ave (Portugal) from October 2007 to January 2009 were enrolled. All were suspected of having onychomycosis by the abnormal appearance of their nails. From these, 59.3% were diabetic. Distal and lateral subungual onychomycosis was the more common clinical pattern followed by total dystrophic onychomycosis. In 21.3% cases, every nail in both feet had an abnormal appearance. In 86%, the hallux was involved in at least one foot. Fifty samples were culture positive, and fifty-four isolates were reported regardless of the questionable pathogenicity of the infectious agent. In three cases, clinical feature of the nail, direct microscopy, and culture were consistent with Scopulariopsis infection. Fusarium spp. were identified in three cases; however, only one isolate was preceded by the observation of branching septate filaments by direct microscopy. No mixed infections with dermatophytes were reported. Trichophyton rubrum was the dermatophyte most frequently isolated (83.3%) followed by Trichophyton interdigitale. In Portugal, onychomycosis is still viewed by general population as a cosmetic condition. Health risk is enhanced in geriatrics that only perceived the severity of their condition when experiencing further foot complications that include bacterial infection and pain.
Lipner, Shari R; Scher, Richard K
Efinaconazole 10% topical solution is a new triazole recently approved for the treatment of onychomycosis. It inhibits fungal lanosterol 14α-demethylase in the ergosterol biosynthesis pathway, has potent antifungal activity against dermatophytes, as well as activity against Candida spp. and non-dermatophyte molds, and showed promising results in clinical trials. This review summarizes the mechanism of action, in vitro and in vivo data, clinical trials, safety, and quality-of-life data of efinaconazole as it applies to the treatment of onychomycosis. PMID:26082652
Romano, C; Paccagnini, E; Pelliccia, L
A case of distal subungual onychomycosis of the big toe due to Microsporum canis is reported in a 69-year-old male asthma patient who had been treated with systemic corticosteroids for the last 3 years. The nail infection was contracted from a cat who was a healthy carrier. The patient was treated successfully with intermittent itraconazole therapy.
Piraccini, B M; Gianni, C
Onychomycosis is a fungal infection of the nail which is highly prevalent in the general population, particularly among older individuals. Patients seek care because the disease is infectious or simply for an esthetic discomfort. The difficulty in treating onychomycosis results from the deep-seated nature of the infection within the nail unit and the inability of drugs to effectively reach all sites. Present treatment options include both oral and topical drugs, with oral therapies giving better outcomes. New derivatives with a favorable risk-benefit ratio and new formulations of older azoles seem to be promising. The research for new drugs or formulations has the objective of discovering new active antifungals or new technologies to facilitate incorporation or persistence of existing antifungal drugs inside the nail plate. In fact, the same antimycotics that heal skin fungal infections are rendered less efficacious in nail disease. This update has the aim to synthesize and focus the therapies currently in use and new therapeutic approaches on onychomycosis. It also summarizes the newer areas of research in the treatment of onychomycosis as photodynamic and laser therapy.
Gazes, Michael I; Zeichner, Joshua
Onychomycosis is defined as a fungal infection of the nail bed and/or nail plate. The prevalence of onychomycosis has increased dramatically as a worldwide condition in the twentieth century due to occlusive footwear, global wars and natural migration. Risk factors generally leading to onychomycosis development include bodily spread of dermatophyte and non-dermatophyte tinea pedis, peripheral vascular disease, damaged nails via sports and trauma, older age, genetics, immunodeficiency and diabetes. Many publications discuss prevalence, symptoms and treatment of the disease in individual cases, hospitals or specific locations, but few strongly link the cause of onychomycosis to living environments. This is a review of the current literature on the prevalence of onychomycosis and its relationship to surrounding living environments of those infected. A Pubmed search was performed with 'onychomycosis'. Articles were selected based on the relevance to close quarter living environments. All ages can be affected with onychomycosis, ranging from children in boarding schools to elderly in nursing homes. Although not directly linking living environments to transmission and infection in all articles reviewed, onychomycosis was very prevalent in many different close quarter living settings, including within families, boarding schools, military quarters and nursing homes. This review demonstrates that various close quarter living environments are highly associated with increased transmission and infection with onychomycosis.
Fryca, Jaroslaw; Nowakowski, Antoni; Urbanowski, Slawomir
The paper shows the results of the research on the active dynamic thermography used for diagnostics of onychomycosis and progress of the healing process. It seems that the most essential factor affecting the development of mycosis in nails is the microcirculation in the tissue close to the nail. Active dynamic thermography may prove to be a new diagnostic method and a sufficient tool for measurements of this parameter.
Klaassen, K M G; Dulak, M G; van de Kerkhof, P C M; Pasch, M C
We systematically reviewed all available literature concerning the prevalence of onychomycosis in patients with nail psoriasis and the distribution of pathogens causing onychomycosis in this specific group of patients. Databases searched were Pubmed, EMBASE and the Cochrane Controlled Clinical Trial Register. All studies reporting on the prevalence of onychomycosis in nail psoriasis were obtained, and quality assessment was determined by the STrengthening the Reporting of OBservational studies in Epidemiology checklist. Literature search revealed 720 studies, of which 10 studies met the inclusion criteria. The major limitation of the review was the heterogeneity of the included studies, which prevented the possibility to conduct a meta analysis. However, the average prevalence of 18.0% of onychomycosis in psoriatic patients seems to be increased when compared with control groups and literature on healthy population, even though the ultimate evidence remains lacking. As in the literature hypothesized shift in causative agents from dermatophytes to yeasts and/or moulds could not be confirmed. The clinical consequence of the relatively high prevalence of onychomycosis in psoriasis may be a general advice to rule out onychomycosis or concomitant onychomycosis in these patients with (suspected) nail psoriasis. This advice is stressed by the relative simplicity of treating the contribution of onychomycosis in the nail dystrophy but also the fact that nail psoriasis mostly is treated by immunosuppressive drugs, like steroids, methotrexate or biologics which may aggravate mycotic nail infections.
Szepietowski, Jacek C; Reich, Adam
Patients with onychomycosis may experience significant psychosocial problems, similarly to other skin diseases. The objectives of this study were to analyse the level of stigmatisation among subjects with onychomycosis and the effect of anti-mycotic therapy on this feeling. This prospective study was carried out among 1684 patients (1050 women and 634 men, mean age 52.2 ± 15.5 years) with onychomycosis. All subjects were asked to fulfil the stigmatisation questionnaire at the baseline visit and after the completion of the anti-mycotic therapy. Stigmatisation level was assessed with reference to gender, age, education, type and duration of onychomycosis and the number of involved nails. Patients with onychomycosis reported markedly increased feeling of stigmatisation. Fingernail involvement was the major variable negatively influencing the stigmatisation level. Female patients and younger ones appeared to be more stigmatised. No significant relationships were found between stigmatisation level and education, number of involved fingernails or toenails, as well as the duration of onychomycosis. The anti-mycotic therapy resulted in significant reduction of all analysed aspects of stigmatisation to about 40% of the baseline level. Onychomycosis should be considered as an important problem for patients, significantly reducing their physical, mental and social well-being, also leading to marked stigmatisation of patients. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
Pavlović, Milos D; Bulajić, Nina
Nondermatophyte molds are fungi found in soil and decaying plant debris and are generally considered to be uncommon or secondary pathogens of diseased nails. Prevalence rates of onychomycoses caused by nondermatophyte molds range between 1.45 percent and 17.60 percent. The most common nondermatophyte molds associated with nail disease are Scopulariopsis, Scytalidium, Fusarium, Aspergillus and Onychocola canadensis. Syncephalastrum racemosum, a nondermatophyte mold, belongs to the class Zygomycetae. Only one well-documented case of human disease attributed to this organism has been described. We describe a 45-year-old man with culture proven toenail onychomycosis due to Syncephalstrum racemosum.
Bonifaz, Alexandro; Cruz-Aguilar, Pamela; Ponce, Rosa María
A retrospective study of onychomycohosis by molds was carried out during a 14-year period (1992-2005). All cases were clinically and mycologically proven (repetitive KOH and culture) and then each of the molds was identified. A total of 5,221 cases of onychomycosis were evaluated, 78 of which were molds (1.49%). Mean patient age was 44.1 years. 75/78 cases occurred in toenails. Associated factors were detected in 39/78 (50.0%) cases, with the major ones being: peripheral vascular disease, contact with soil, and trauma. The most frequent clinical presentation was distal and lateral subungual onychomycosis (DLSO), in 54/78 cases (69%). The most frequent causative agents were: Scopulariopsis brevicaulis in 34/78 cases and Aspergillus niger in 13/78 cases. Onychomycoses by molds are infrequent; in this study they accounted for 1.49% of cases. The clinical features are virtually similar to those caused by dermatophytes, which makes the clinicomycological tests necessary.
Kim, Dong Min; Ha, Gyoung Yim; Sohng, Seung Hyun
Onychomycosis is usually caused by dermatophytes, but some species of nondermatophytic molds and yeasts are also associated with nail invasion. Aspergillus niger is a nondermatophytic mold which exists as an opportunistic filamentous fungus in all environments. Here, we report a case of onychomycosis caused by A. niger in a 66-year-old female. The patient presented with a black discoloration and a milky white base and onycholysis on the proximal portion of the right thumb nail. Direct microscopic examination of scrapings after potassium hydroxide (KOH) preparation revealed dichotomous septate hyphae. Repeated cultures on Sabouraud's dextrose agar (SDA) without cycloheximide produced the same black velvety colonies. No colony growth occurred on SDA with cycloheximide slants. Biseriate phialides covering the entire vesicle with radiate conidial heads were observed on the slide culture. The DNA sequence of the internal transcribed spacer region of the clinical sample was a 100% match to that of A. niger strain ATCC 16888 (GenBank accession number AY373852). A. niger was confirmed by KOH mount, colony identification, light microscopic morphology, and DNA sequence analysis. The patient was treated orally with 250 mg terbinafine daily and topical amorolfine 5% nail lacquer for 3 months. As a result, the patient was completely cured clinically and mycologically. PMID:23197914
Ledon, Jennifer A; Savas, Jessica; Franca, Katlein; Chacon, Anna; Nouri, Keyvan
More than just a cosmetic concern, onychomycosis is a prevalent and extremely difficult condition to treat. In older and diabetic populations, severe onychomycosis may possibly serve as a nidus for infection, and other more serious complications may ensue. Many treatment modalities for the treatment of onychomycosis have been studied, including topical lacquers and ointments, oral antifungals, surgical and chemical nail avulsion, and lasers. Due to their minimally invasive nature and potential to restore clear nail growth with relatively few sessions, lasers have become a popular option in the treatment of onychomycosis for both physicians and patients. Laser or light systems that have been investigated for this indication include the carbon dioxide, neodymium-doped yttrium aluminum garnet, 870/930-nm combination, and femtosecond infrared 800-nm lasers, in addition to photodynamic and ultraviolet light therapy. This systematic review will discuss each of these modalities as well as their respective currently published, peer-reviewed literature.
Rosa, Priscila D; Heidrich, Daiane; Corrêa, Carolina; Scroferneker, Maria Lúcia; Vettorato, Gerson; Fuentefria, Alexandre M; Goldani, Luciano Z
Fusarium species have emerged as an important human pathogen in skin disease, onychomycosis, keratitis and invasive disease. Onychomycosis caused by Fusarium spp. The infection has been increasingly described in the immunocompetent and immunosuppressed hosts. Considering onychomycosis is a difficult to treat infection, and little is known about the genetic variability and susceptibility pattern of Fusarium spp., further studies are necessary to understand the pathogenesis and better to define the appropriate antifungal treatment for this infection. Accordingly, the objective of this study was to describe the in vitro susceptibility to different antifungal agents and the genetic diversity of 35 Fusarium isolated from patients with onychomycosis. Fusarium spp. were isolated predominantly from female Caucasians, and the most frequent anatomical location was the nail of the hallux. Results revealed that 25 (71.4%) of isolates belonged to the Fusarium solani species complex, followed by 10 (28.5%) isolates from the Fusarium oxysporum species complex. Noteworthy, the authors report the first case of Neocosmospora rubicola isolated from a patient with onychomycosis. Amphotericin B was the most effective antifungal agent against the majority of isolates (60%, MIC ≤4 μg/mL), followed by voriconazole (34.2%, MIC ≤4 μg/mL). In general, Fusarium species presented MIC values >64 μg/mL for fluconazole, itraconazole and terbinafine. Accurate pathogen identification, characterisation and susceptibility testing provide a better understanding of pathogenesis of Fusarium in onychomycosis. © 2017 Blackwell Verlag GmbH.
Souza, L K H; Fernandes, O F L; Passos, X S; Costa, C R; Lemos, J A; Silva, M R R
Onychomycosis defined as fungal infection of the nail represents more than 50% of all onychopathies. Epidemiological studies have shown that this mycosis is worldwide in occurrence, but with geographical variation in distribution. The direct microscopy and culture of the nail samples were performed to identify the causative agent. Out of 2273 patients with nail infection examined between January 2000 and December 2004 in Goiania, state of Goias, Brazil, diagnosis of onychomycosis was confirmed in 1282 cases, with dermatophytes and Candida species being the most common aetiological agents isolated. Dermatophyte onychomycosis was more common in toenails than in fingernails, while onychomycosis caused by yeast had a similar frequency in both toenails and fingernails. Among the species identified, Candida albicans was responsible for 492 cases (38.4%) of onychomycosis, Trichophyton rubrum was found in 327 cases (25.6%) and Trichophyton mentagrophytes in 258 cases (20.1%). Other fungi isolated from nail infections included Aspergillus sp., Trichosporon sp., Geotrichum sp. and Fusarium sp. In our study, yeast of the genus Candida were the dominant cause of onychomycosis in women and dermatophytes were the principal cause of this condition in men.
Flores, Fernanda C; Beck, Ruy C R; da Silva, Cristiane de B
Onychomycosis are fungal infections affecting finger and toenails mainly caused by dermatophyte fungi and some Candida species. Low cure rates and frequent recurrence, development of a fungal resistance front to various antimicrobial agents topical and systemic, and an ineffective topical treatment make onychomycosis difficult to treat. Essential oils are excellent candidates for the topical treatment for onychomycosis because the development of resistance by fungi is rare, and the presence of side effects is low. They are composed of a complex variety of compounds, mainly terpenes, with low molecular weight, which may easily penetrate into the nail plate, finding the fungi elements. The complex mixture confers a broad antifungal spectrum of action, through interaction with biological membranes, interference in radical and enzymatic reaction of fungi cells. Essential oils may become the source of new therapeutic molecules, and the use of an essential oil incorporated into a topical formulation is an interesting, safe, and effective alternative for the treatment for onychomycosis. However, studies are needed to evaluate the efficacy of essential oils in the treatment for onychomycosis in vivo. This mini-review aims to present the potential use of essential oils for the treatment for onychomycosis, focusing on the last decade.
Adekhandi, Shamanth; Pal, Shekhar; Sharma, Neelam; Juyal, Deepak; Sharma, Munesh; Dimri, Deepak
Onychomycosis is a chronic fungal infection of the nails that is largely underdiagnosed in developing countries such as India due to poor health care facilities. In this study, we evaluated the nails of 134 patients with a clinical suspicion of onychomycosis using direct microscopy and fungal culture techniques. The majority of participants (47.8%) were older than 40 years. On both direct microscopy and fungal culture, 71.6% of participants were confirmed with onychomycosis. Among the cases confirmed by laboratory testing, distal lateral subungual onychomycosis was the most common clinical pattern observed, followed by proximal subungual onychomycosis (PSO), candidal onychomycosis (CO), and white superficial onychomycosis (WSO). We concluded that laboratory examination is of great importance in the diagnosis and identification of the underlying pathogen in patients with onychomycosis as well as in the selection of a suitable antifungal agent for treatment.
da Silva, Ana Paula; Fortunato, Thereza Cury; Stringasci, Mirian D.; Kurachi, Cristina; Bagnato, Vanderlei S.; Inada, Natalia M.
Onychomycosis is a common disease of the nail plate, constituting approximately half of all cases of nail infection. Onychomycosis diagnosis is challenging because it is hard to distinguish from other diseases of the nail lamina such as psoriasis, lichen ruber or eczematous nails. The existing methods of diagnostics so far consist of clinical and laboratory analysis, such as: Direct Mycological examination and culture, PCR and histopathology with PAS staining. However, they all share certain disadvantages in terms of sensitivity and specificity, time delay, or cost. This study aimed to evaluate the use of infrared and fluorescence imaging as new non-invasive diagnostic tools in patients with suspected onychomycosis, and compare them with established techniques. For fluorescence analysis, a Clinical Evince (MM Optics®) was used, which consists of an optical assembly with UV LED light source wavelength 400 nm +/- 10 nm and the maximum light intensity: 40 mW/cm2 +/- 20%. For infrared analysis, a Fluke® Camera FKL model Ti400 was used. Patients with onychomycosis and control group were analyzed for comparison. The fluorescence images were processed using MATLAB® routines, and infrared images were analyzed using the SmartView® 3.6 software analysis provided by the company Fluke®. The results demonstrated that both infrared and fluorescence could be complementary to diagnose different types of onychomycosis lesions. The simplicity of operation, quick response and non-invasive assessment of the nail patients in real time, are important factors to be consider for an implementation.
Bombace, Francesca; Iovene, Maria Rosaria; Galdiero, Marilena; Martora, Francesca; Nicoletti, Giovanni Francesco; D'Andrea, Mirella; Della Pepa, Maria Elena; Vitiello, Mariateresa
Non-dermatophytic moulds (NDMs) have been increasingly recognised as causative agents of onychomycosis. The diagnosis of onychomycosis is most often obtained by microscopic observation of nail specimens where fungal elements can be detected and cultured by standard mycological techniques. Direct microscopic examination does not always result positive in NDM onychomycosis; therefore to perform a correct diagnosis, a proper mycological culture is often required. The purpose of our study was to evaluate the role of direct microscopic examination in the NDM onychomycosis diagnosis. The results show that only 57.2% of the specimens from onychomycosis patients could be properly diagnosed showing positivity to both direct microscopic examination and NDMs culture isolation in two or more subsequent inoculations, while 42.8% of analysed specimens with a negative direct microscopic examination, showed NDMs growth after three or more subsequent inoculations. The large proportion of false negatives (more than 42%) could be related to the duration of the infection and/or to the experience and skills of the personnel dedicated to specimen collection. We point out the need for thoroughly evaluating all specimens showing cultural growth in at least three subsequent medium inoculations, whatever the result of the microscopic examination, in order to reduce false-negative rates. This strategy would allow for more accurate diagnosis of this mycosis.
Konate, A; Yavo, W; Kassi, K F; Djohan, V; Angora, K E; Bosson-Vanga, H; Barro-Kiki, P; E I H Menan
The epidemiological profile of onychomycosis is poorly determined in Cote d'Ivoire. This study aimed to determine the fungal aetiologies of these onychomycosis in Abidjan. This cross-sectional study was conducted from February to August 2011 at the Department of Dermatology of the University Hospital of Treichville. All patients who consulted for onycholysis were interviewed. All samples were analyzed by direct examination and Sabouraud-chloramphenicol and Sabouraud-chloramphenicol-actidione culture was performed. Species identification was based on microscopic characteristics of the fungus observed. A total of 53 patients were included. The prevalence of onychomycosis was estimated at 66%. The unilateral lesions were statistically different from bilateral lesions (P=0.010). Women were more affected at the hands than men (P=0.010). Five species of yeasts and two dermatophytes species were identified. Yeasts species were essentially Candida tropicalis (36.4%) and Candida albicans (30.3%). Trichophyton rubrum and Trichophyton soudanense were the only dermatophytes isolated. No contributing factors were statistically related to the occurrence of onychomycosis in our series. The observed onychomycosis in Côte d'Ivoire are mainly caused by yeasts. Although in our series the risk factors have not been identified, hygiene of the nails should provide effective prevention. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Fernández, Mariana S; Rojas, Florencia D; Cattana, María E; Sosa, María de Los Ángeles; Mangiaterra, Magdalena L; Giusiano, Gustavo E
The incidence of onychomycosis due to non-dermatophyte moulds (NDM) is increasing. Aspergillus terreus is relatively undocumented as an agent of this fungal infection. The aim of this work is to show the prevalence of onychomycosis caused by A. terreus and to describe its clinical features. Nail samples were collected for microscopic examination and culturing in selective media. All cases of onychomycosis due to NDM were confirmed by a second sample. Aspergillus terreus isolates were identified through their morphological characteristics and using molecular methods. A total of 2485 samples were obtained. Positive cultures were obtained in 1639 samples. From 124 NDM confirmed cultures, 23 were identified as A. terreus (18.5%). Superficial white onychomycosis was the most frequent clinical pattern. A high percentage was found in fingernails. The prevalence of A. terreus in this study considerably exceeded the percentages reported by other authors. Onychomycosis due to A. terreus presents similar clinical patterns to those caused by dermatophytes, but is difficult to eradicate and is associated with less predictable treatment outcomes. Better knowledge of the aetiology of A. terreus may be important for accomplishing more accurate and effective treatment.
Natarajan, Vidhya; Nath, Amiya Kumar; Thappa, Devinder Mohan; Singh, Rakesh; Verma, Surendra Kumar
Psoriatic nail changes predispose to onychomycosis because it becomes easier for fungi to penetrate an already compromised nail plate. Moreover, some of the psoriatic nail changes closely resemble onychomycosis. To investigate cases of nail psoriasis for any evidence of onychomycosis. Seventy-two patients with psoriasis were included in the study. The patients were selected from the psoriasis clinic and dermatology in-patient ward. Direct microscopic examination with 20% KOH and culture were carried out in all patients showing psoriatic nail changes. Histopathological examination with Periodic Acid-Schiff (PAS) stain was done in cases negative by KOH examination and culture. Nail changes were seen in 66.66% (48/72) of psoriasis patients. The most common fingernail changes observed were pitting, onycholysis and subungual hyperkeratosis, and the most common toenail changes were onycholysis and subungual hyperkeratosis. Nail changes were significantly more common in males. The duration of skin lesions of psoriasis and Psoriasis Area Severity Index scores were significantly higher in patients with nail changes. Out of 48 patients with psoriatic nail change, 23 (47.91%) had investigative evidence of onychomycosis. The fungal isolates on culture were non-dermatophytic molds in nine patients (18.75%) and yeast like fungi also in nine patients (18.75%). Coexistent onychomycosis in psoriatic nails does occur.
Recent progress in the epidemiology, diagnosis and treatment of onychomycosis is summarized. The risk factors of this condition were investigated, and the results of analyses of the systemic state of patients, shape of nails, blood circulation around nails, nail growth rate and causative fungi were reported. In making a diagnosis of onychomycosis, the major effect of the quality of collected nail samples on the results was reconfirmed. In addition to the KOH method and culture method, a molecular biological method was introduced. From the therapeutic perspective, 1) prevention of recurrence, 2) identification of patients with high risk of onychomycosis, and 3) attempting new treatments (development of new drugs, improvement of administration and dosage, and evaluation of combined therapy) were discussed. The effectiveness of concomitant use with nail lacquer is anticipated in combined therapy. New studies on accurate diagnosis, early detection and early stage treatment are now being undertaken.
Zane, L T; Plattner, J; Chanda, S; Coronado, D; Merchant, T; Alley, M R K; Gupta, A K
Tavaborole topical solution, 5% (tavaborole) is a novel, boron-based, antifungal pharmaceutical agent indicated for treatment of toenail onychomycosis due to the dermatophytes Trichophyton rubrum or Trichophyton mentagrophytes. In preclinical studies, tavaborole effectively penetrated through full-thickness, non-diseased cadaver fingernails, including those with up to four layers of nail polish. Limited systemic absorption was observed following topical application of tavaborole. In phase III clinical trials involving patients with distal subungual onychomycosis affecting 20-60% of a target great toenail, significantly more patients treated with tavaborole versus vehicle achieved completely clear nail with negative mycology following daily application for 48 weeks. Treatment-emergent adverse events reported by at least 1% of patients treated with tavaborole and at a greater frequency versus vehicle included ingrown toenail, exfoliation, erythema and dermatitis. Treatment discontinuations were uncommon. Results from preclinical studies and phase III clinical trials establish tavaborole as a safe and efficacious treatment for toenail onychomycosis.
Rosen, Theodore; Friedlander, Sheila Fallon; Kircik, Leon; Zirwas, Matthew J; Stein Gold, Linda; Bhatia, Neal; Gupta, Aditya K
Onychomycosis is an often overlooked and/or undertreated disease. This may be in part due to an under appreciation among both physicians and patients of its impact on quality of life and the potential for significant complications, from tinea corporis and cruris, to bacterial superinfection. Some health care providers are unaware of the effective low-risk treatments currently available. Changing demographic characteristics such as the relative aging of the population; the increasing prevalence of diabetes and peripheral vascular disease, and widespread iatrogenic immunosuppression; and changes in lifestyle practices such as earlier and greater participation in sports, are likely to lead to an increased prevalence of onychomycosis in both adults and children. Two topical onychomycosis treatments, efinaconazole 10% solution, and tavaborole 5% solution were recently approved by the FDA. This article reviews the state of knowledge and describes, briefly, these new treatment options.
Hajar, Tamar; Fernández-Martínez, Ramon; Moreno-Coutiño, Gabriela; Vásquez Del Mercado, Elsa; Arenas, Roberto
Onychomycosis is the most common nail disease and represents around 50% of nail disorders. Accurate diagnosis with adequate evidence is ideal before starting any treatment. Current diagnostic methods offer low specificity and sensitivity. To create a new method for the diagnosis of onychomycosis, and to compare its sensitivity and specificity with the existing methods. One hundred and ninety-two samples with clinical suspicion of onychomycosis were included and underwent modified PAS stain (M-PAS), KOH/chlorazol black (KOH/CB) and culture testing. Sensitivity, specificity, positive and negative predictive values were calculated. In 152 out of 192 samples (79.2%) fungi structures were found in at least one of the three tests performed, and the patients were diagnosed with onychomycosis; 40 samples out of 192 (20.8%) were negative. Using M-PAS, filaments and/or spores were seen in 143 samples from the 152 positive (94%); 39 of them were negative to KOH/CB and positive to M-PAS (25.6%). With KOH/CB, filaments and/or spores were seen in 113 cases from the 152 positive samples (73.8% of the onychomycosis cases). Thirty-five cultures were positive, of which 77% were identified as Trichophyton rubrum; 117 onychomycosis cases were diagnosed despite the negative culture (76.9%). M-PAS showed 92.5% sensitivity and 55.55% specificity, a 67.5% positive predictive value and a 81.6% negative productive value. This procedure, a combination of the existing methods to diagnose onychomycosis, KOH/CB together with a nail clipping biopsy, proved to have high sensitivity, as well as being rapid, easy, inexpensive and readily available in most hospital settings. M-PAS allowed us to diagnose 39 cases (25.6% of the cases of onychomycosis) that were false negative using only KOH/CB and culture. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.
In considering therapy for onychomycosis, the most important factor to take into account is patient selection rather than treatment selection. Patients should be screened and evaluated for the extent of nail involvement, the amount of subungual debris, the degree of dystrophy, their ability and willingness to follow the regimen, and whether comorbidities are present that may affect the efficacy and/or safety of one or more therapies. Onychomycosis is a chronic disease with a high recurrence rate. Commonsense measures to reduce the risk for reinfection include patient education and a clinician-patient team approach to long-term management.
Galletti, Juliana; Tobaldini-Valerio, Flávia K; Silva, Sónia; Kioshima, Érika Seki; Trierveiler-Pereira, Larissa; Bruschi, Marcos; Negri, Melyssa; Estivalet Svidzinski, Terezinha Inez
The present study evaluated the capacity of three species of Fusarium isolated from onychomycosis to form biofilms and the antibiofilm effect of propolis extract on these biofilms. The biofilms and antibiofilm effects were evaluated by quantifying the colony-forming units, mitochondrial metabolic activity assays, total biomass by crystal violet staining and scanning electron microscopy. Propolis extract demonstrated significant antibiofilm efficiency on Fusarium spp. isolates and reduced F. solani, F. oxysporum and F. subglutinans mature biofilms. Propolis extract can be an alternative topical treatment of onychomycosis caused by Fusarium spp.
Rosen, Theodore; Stein Gold, Linda F
In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals.
Shah, S R; Dalal, B D; Modak, M S
Fusarium onychomycosis is not uncommon in tropical countries but is worth reporting. We report a case of nondermatophytic onychomycosis by Fusarium oxysporum in an immunocompetent woman from Buldhana district of Maharashtra (India). Bilateral involvement of great toe nail, chronic duration and acquisition of infection due to peculiar practice of daily pasting floors with mud and dung, is interesting. The case was successfully treated with topical and oral terbinafine with a dose of 250 mg daily for 3 weeks. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Cabete, Joana; Galhardas, Célia; Apetato, Margarida; Lestre, Sara
Nails have a limited number of reactive patterns to disease. Accordingly, toenail changes of different etiologies may mimic onychomycosis. OBJECTIVE To determine the prevalence of toenail onychomycosis among patients with leg ulcer and toenail abnormalities attending a dermatology clinic. METHODS A cross-sectional study was conducted through the analysis of clinical records and results of mycological examination. RESULTS A total of 81 patients were included, with a median age of 76.0 years. Most ulcers were of venous etiology, followed by those of mixed and arterial pathogenesis. The mycological evaluation confirmed the diagnosis of onychomycosis in 27.2% of the patients. The etiologic agent was a dermatophyte in 59.1% of isolates in nail samples, while Trichophyton interdigitale was the most frequent fungal species (40.9%). CONCLUSIONS Most toenail abnormalities in patients with chronic leg ulcer were not onychomycosis. This study highlights the importance of systematic mycological examination in these patients, in order to avoid overtreatment with systemic antifungals, unnecessary costs and side effects.
Sharma, Hemlata; Pathak, Kamla
Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362
Silva, Ana Paula da; Kurachi, Cristina; Bagnato, Vanderlei Salvador; Inada, Natalia Mayumi
Onychomycosis is a fungal nail disease and is one of the major onychopathy worldwide. Topical or oral antifungal therapies are used to treat this disease, but often they are inefficient and oral medications can even cause several side effects. Photodynamic therapy (PDT) is a well established technique and hence, may represent an alternative non invasive technique for the treatment of onychomycosis. In this work, we present a case of onychomycosis that was completely cured by using the porphyrin-photodynamic therapy. A 59-year-old patient, who had two nails with onychomycosis (the right and the left hallux, with more than thirty and ten years, respectively) caused by fungi was treated once a week for a period of six weeks. The nails were first treated and prepared by a specialist. An hour after the photosensitization, the nail was illuminated using a light source based on light emitting diodes (LEDs) in the red wavelength (630 nm, at a total dose of 54 J/cm(2)).
Jinna, Sphoorthi; Finch, Justin
Onychomycosis is a fungal nail plate infection that has been increasing in prevalence. A variety of oral and topical anti-fungal agents are currently available but their use is limited by their adverse effect profile, drug-drug interactions, and limited efficacy. Therefore, there is a great need for newer anti-fungal agents. Tavaborole is one of these newer agents and was approved by the US Food and Drug Administration in July 2014 for the topical treatment of mild to moderate toenail onychomycosis. Tavaborole is a novel, boron-based anti-fungal agent with greater nail plate penetration than its predecessors, due to its smaller molecular weight. It has proven through several Phase II and III trials that it can be a safe and effective topical agent for the treatment of mild to moderate toenail onychomycosis without the need for debridement. In this paper, we review the landscape of topical and systemic treatment of onychomycosis, with particular attention to the pharmacokinetics, safety, and efficacy of topical tavaborole.
Zaikovska, Olga; Pilmane, Mara; Kisis, Janis
Patients of onychomycosis are common in the dermatology practice. Contemporary morphology creates opportunities to study the functional units of the nail when such infections occur from morphopathological point of view. There were 22 nails biopsies from onychomycosis patients taken for the research of morphopathological changes in the thickened nail plate affected by onychomycosis. Samples of cadaverous' nails were used as a control material. The material was stained with haematoxylin and eosin and immunohistochemical methods. Terminal deoxynucleotidyl transferase dUTP nick end labelling reaction and periodic acid-Schiff reaction were also performed. We found patchy hypertrophy in the granulose layer of the epidermis, with focal acanthosis. In the horn layer, we identified nests of parakeratosis of various sizes, with incorporations of homogenous and eosinophil masses. We found high levels of interleukin 6 and interleukin 10 positive cells in the nail bed and in the bloodstream. Interleukin 1, however, was not a part of any of the functional units of any of the nails. Significant amount of fibres containing human beta defensin-2 were found in the bed and plate of the nail. Therefore one can conclude that as regards the nails affected by onychomycosis, the most effective morphopathogenical processes include cytokine and defensin excretion occurrence in the nail bed.
Shemer, Avner; Davidovici, Batya; Grunwald, Marcelo H; Trau, Henri; Amichai, Boaz
Onychomycosis is a common problem. Obtaining accurate laboratory test results before treatment is important in clinical practice. The purpose of this study was to compare results of curettage and drilling techniques of nail sampling in the diagnosis of onychomycosis, and to establish the best technique and location of sampling. We evaluated 60 patients suffering from distal and lateral subungual onychomycosis and lateral subungual onychomycosis using curettage and vertical and horizontal drilling sampling techniques from three different sites of the infected nail. KOH examination and fungal culture were used for detection and identification of fungal infection. At each sample site, the horizontal drilling technique has a better culture sensitivity than curettage. Trichophyton rubrum was by far the most common pathogen detected by both techniques from all sampling sites. The drilling technique was found to be statistically better than curettage at each site of sampling, furthermore vertical drilling from the proximal part of the affected nail was found to be the best procedure for nail sampling. With each technique we found that the culture sensitivity improved as the location of the sample was more proximal. More types of pathogens were detected in samples taken by both methods from proximal parts of the affected nails.
Raghavendra, K.R; Yadav, Devendra; Kumar, Akshay; Sharma, Mukul; Bhuria, Jitendra; Chand, Anita E.
Background: Onychomycosis is a fungal disease of the nail apparatus caused by both dermatophytic and nondermatophytic strains. Treatment involves long duration antifungal therapy. However, long treatment duration without identifying the causative species may lead to resistance. Confirmation of diagnosis and speciation by culture before administering antifungal therapy is ideal. Aims: To study the clinical and epidemiological aspects of onychomycosis in Hadoti region (south-east Rajasthan) and identify various mycological strains and predisposing factors causing onychomycosis. Materials and Methods: A prospective study of clinically diagnosed cases of onychomycosis attending the outpatient Department of Dermatology in our institute conducted from June 2012 to May 2013. The clippings were subjected to potassium hydroxide (KOH) examination and culture in the appropriate medium. Results: A total of 150 cases were enrolled in our study. There were 110 males (73.33%) and 40 females (26.66%) and male to female ratio was 2.75:1. The total dystrophic onychomycosis was the most common presentation seen in the majority of cases (46%) followed by distal lateral subungual onychomycosis in 52 cases (34.6%), mixed onychomycosis in 16 cases (10.66%), superficial white onychomycosis in 11 cases (7.33%), and proximal subungual onychomycosis in 2 cases. None had the endonyx variant. Direct microscopic examination of the nail clipping mounted with 40% KOH demonstrated fungal elements in 83 (55.33%) cases. Rate of isolation of organisms by culture was 64%. Nondermatophytes were isolated in 53 (35.33%), dermatophytes in 28 (18.66%), and yeasts in 15 (10%) of cases. The most commonly isolated species was Aspergillus in 45 (30%) cases. Aspergillus flavus was more commonly isolated compared to Aspergillus niger. Conclusion: The nondermatophyte molds appear to be more common causative agents of onychomycosis compared to usual dermatophyte species in south-east Rajasthan. Our study re
Motamedi, Marjan; Ghasemi, Zeinab; Shidfar, Mohammad Reza; Hosseinpour, Leila; Khodadadi, Hossein; Zomorodian, Kamiar; Mirhendi, Hossein
Background Non-dermatophyte onychomycosis (NDO) is caused by a wide range of mold fungi other than dermatophytes, and has been reported at various rates in different countries worldwide. Studies on the incidence of NDO in the community are essential for understanding its epidemiology and control, as well as for the appropriate treatment of these infections. Objectives In this study, the incidence of NDO in Tehran, Iran, was compared to the incidence of onychomycoses due to dermatophytes and yeasts. Methods From 2014 through 2015, samples from a total of 1,069 patients with suspected fungal nail diseases, who were referred to three medical mycology laboratories in Tehran, were collected and subjected to direct examination (all samples) and culture (788 samples). Differentiation of the causative agents of onychomycosis was based on microscopic observation of characteristic fungal elements in the nail samples and growth of a significant number of identical colonies on the culture plate. Results Based on only direct microscopy, onychomycosis was diagnosed in 424 (39.6%) cases, among which 35.8% were caused by dermatophytes, 32.7% by yeasts, and 29.3% by non-dermatophyte molds (NDMs), while 2.2% were mixed infections. Direct exam was significantly more sensitive than culture for the diagnosis. The most commonly isolated NDMs were Aspergillus spp. (69.3%, n = 52), followed by Fusarium spp. (n = 7). The other isolated species were Paecilomyces spp., Scopulariopsis spp., Acremonium spp., Cladosporium spp., and Chrysosporium spp., with only one case of each. Conclusions An increasing frequency of NDO compared to onychomycosis due to other causative agents has been noticeable over the past few years in Iran. This epidemiological data may be useful in the development of preventive and educational strategies. PMID:27800138
Bet, Diego Leonardo; dos Reis, Ana Lucia; Chiacchio, Nilton Di; Belda Junior, Walter
Mycological examination is still the cornerstone for the diagnosis of onychomycosis for many dermatologists, but sampling technique interferes on its sensitivity and specificity. Nail abrasion may be used to reach the most proximal part of the lesion and can be easily accomplished with an electric abrasor. We suggest nail plate dermoscopy to identify the best location for localized abrasion to obtain adequate samples for mycological examination. PMID:26734877
Zisova, L; Valtchev, V; Sotiriou, E; Gospodinov, D; Mateev, G
1-3% of human population is affected by psoriasis. Nail disorders are reported in 10-80% of patients with psoriasis. Nail deformations vary according to their degree of severity but are mainly represented by pitting, Beau's lines, hyperkeratosis, onycholysis, leuconychia or oil drops. Onychomycosis is a fungal infection of the nails, caused by dermatophytes, yeast and moulds. In this study, 228 patients with psoriasis aged between 18 and 72 were examined (48 - from Plovdiv, Bulgaria; 145 - from Pleven, Bulgaria and 35 - from Thessaloniki, Greece); 145 of them were male and 83 of them were female. The examination of the nail material was performed via direct microscopy with 20% KOH and nail samples plated out on Sabouraud agar methodology. The severity of the nail disorders was determined according to the Nail Psoriasis Severity Index (NAPSI). Positive mycological cultures were obtained from 62% of the patients with psoriasis (52%- Plovdiv, Bulgaria; 70%- Pleven, Bulgaria and 43%- Thessaloniki, Greece). In 67% of the cases, the infection was caused by dermatophytes, in 24% by yeast, in 6% by moulds and in 3% by a combination of causes. All patients with psoriasis were identified with high levels of NAPSI, whereas the ones with isolated Candida had even higher levels. Seventeen percentage of the patients have been treated with methotrexate, 6% have been diagnosed with diabetes and 22% have been reported with onychomycosis and tinea pedis within the family. An increased prevalence of onychomycosis among the patients with psoriasis was found. Dystrophic nails in psoriasis patients are more predisposed to fungal infections. The mycological examination of all psoriasis patients with nail deformations is considered obligatory because of the great number of psoriasis patients diagnosed with onychomycosis.
Ahmadi, Bahram; Hashemi, Seyed Jamal; Zaini, Farideh; Shidfar, Mohammad Reza; Moazeni, Maryam; Mousavi, Bita; Noorbakhsh, Fatemeh; Gheramishoar, Mohsen; Hossein pour, Leila; Rezaie, Sassan
Based on epidemiological studies, Aspergillus candidus has been demonstrated as an emerging fungal agent of toenail onychomycosis. Here we report a case of a toenail infection caused by A. candidus in a healthy 60-year-old woman. Based on macroscopic and microscopic characteristics of the culture as well as nucleotide sequencing of 28S region, the causative agent was identified as A. candidus. PMID:24371736
de Sá, Daniel Coelho; Lamas, Ana Paula Botto; Tosti, Antonella
Onychomycosis is a very common fungal infection of the nail apparatus; however, it is very hard to treat, even when the causative agent is identified, and usually requires prolonged systemic antifungal therapy. Until the 1990s, oral treatment options included only griseofulvin and ketoconazole, and the cure rate was very low. New generations of antimycotics, such as fluconazole, itraconazole and terbinafine have improved treatment success. Literature was identified by performing a PubMed Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) search. Prospective and randomized clinical trials were chosen to be included in this review. Forty-six trials were included. Fluconazole, itraconazole and terbinafine are effective in the treatment of onychomycosis and have a good safety profile. When a dermatophyte is the pathogen, terbinafine produces the best results. For Candida and nondermatophyte infections, the azoles, mainly itraconazole, are the recommended therapy. In the majority of the studies, terbinafine treatment showed a higher cure ratio than the other drugs for dermatophyte onychomycosis.
Manzano-Gayosso, Patricia; Hernández-Hernández, Francisca; Méndez-Tovar, Luis Javier; Palacios-Morales, Yanni; Córdova-Martínez, Erika; Bazán-Mora, Elva; López-Martinez, Rubén
The onychomycosis incidence was determined in 250 type 2 diabetes mellitus (T2DM) patients who were registered at the Internal Medicine Service from a Mexico city General Hospital throughout a year (January-December 2006). Out of the total of studied T2DM patients, 93 (37.2%) showed ungual dystrophy and from these, in 75.3% a fungal etiology was corroborated. Out of 70 patients, 34 were men and 36 women, with an average of 63.5 years. Correlation between T2DM evolution time and onychomycosis was significant (P < 0.01). Distal-lateral subungual and total dystrophic onychomycosis were the most frequent clinical types (55.1% and 33.7%, respectively). Fifty-eight fungal isolates were obtained; 48.6% corresponded to dermatophytes, Trichophyton rubrum being the first species (37.1%). All these strains corresponded to two morphological varieties: "yellow" and typical downy. From the yeast-like isolates, 12 corresponded to Candida spp., firstly C. albicans and C. parapsilosis; three to Cryptococcus spp. (C. albidus, C. uniguttulatus and C. laurentii); two Trichosporon asahii; and only one to Pichia ohmeri. Six non-dermatophytic molds were isolated: two Chrysosporium keratinophylus, two Scopulariopsis brevicaulis, one Aspergillus fumigatus, and one Acremonium sp. The fungal mixture corresponded to T. mentagrophytes with C. guilliermondii; T. mentagrophytes with C. glabrata; T. rubrum with C. glabrata; T. rubrum with P. ohmeri.
Robres, P; Aspiroz, C; Rezusta, A; Gilaberte, Y
Onychomycosis, or fungal infection of the nails, is one of the most prevalent fungal diseases in the general population. Treatment is of limited effectiveness, tedious, and must be administered for long periods. Furthermore, systemic antifungal agents are associated with adverse effects. Photodynamic therapy (PDT) may prove to be a viable alternative in the treatment of superficial skin infections, including onychomycosis. We review articles relating to the usefulness of PDT in onychomycosis in both in vitro and in vivo settings and discuss the potential and limitations of various photosensitizing agents. In vivo, methylene blue and 5-aminolevulinic acid have led to cure rates in 80% and 43% of cases, respectively, at 12 months. Finally, based on data in the literature and our own experience, we propose a protocol of 3 PDT sessions, separated by an interval of 1 or 2 weeks, using methyl aminolevulinate 16% as a photosensitizing agent and red light (λ=630 nm, 37 J.cm(-2)). Each session is preceded by the topical application of urea 40% over several days. Clinical trials are needed to optimize PDT protocols and to identify those patients who will benefit most from this treatment. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.
Mochizuki, Takashi; Kawasaki, Masako; Tanabe, Hiroshi; Ishizaki, Hiroshi
We describe a nail drilling method suitable for the diagnosis of onychomycosis. Thirty-three patients with onychomycosis in which the big toenail had a white band or spike were enrolled in this study. We drilled a hole about 3-mm-wide in the most proximal part of the white band or spike using a ball-shaped metal file and then, through the hole, sampled the underlying nail material softened by fungi after removing the superficial hard nail plate. Fungi in 32 (97.0%) of the nail samples were detected by direct KOH examination. When incubated on Sabouraud's dextrose agar slant with chloramphenicol and cycloheximide, fungal cultures were obtained from 27 (81.8%) of the 33 nail samples. Fourteen of the fungal isolates were identified as T. rubrum, 11 as T. mentagrophytes, and 2 as Acremonium sp. The nail drilling method is suitable for diagnosing onychomycosis with a white band or spike, because it gives a high isolation rate and leaves the patients' nail relatively more intact compared with other methods.
Francuzik, W; Fritz, K; Salavastru, C
The number of medical devices designed specifically to treat onychomycosis has recently increased, although their mechanism of action is not clear. We evaluated available laser therapies for onychomycosis by reviewing the existing literature. Twenty-two reports, published in peer-reviewed journals and as white papers out of 926 initial search results conveyed enough details to be included in this study. In most cases, the methodology of the trials described in the papers we reviewed was not comprehensive and the reporting of outcomes was not unified. We therefore found it hard to compare different clinical trials to one another. The majority of studies (81.82%) reported using an Nd:YAG laser device to treat onychomycosis. A total of 47.37% of the studies which used a 1064 device (and 47.83% of all studies we reviewed) reported that all treated patients responded positively to laser therapy. A total of 60% of studies reported achieving a complete cure (no clinical symptoms, nor negative mycology) in at least 50% of the treated patients. A low number of adverse events and their mild intensity were consistently reported across all studies, which makes this form of therapy particularly attractive to patients with contraindications for receiving systemic antifungal medication. In order to achieve more unified, comparable studies in the future, we suggest that researchers report a minimum set of outcome measurements: the calculation of the infected nail area pre- and posttreatment, as well as the number of patients achieving mycological, clinical and complete cures.
Papini, Manuela; Piraccini, Bianca Maria; Difonzo, Elisa; Brunoro, Andrea
The prevalence of onychomycosis differs according to geographic area and over time and is influenced by several factors. The epidemiology of onychomycosis in Italy is still unclear. To evaluate the prevalence of onychomycosis in a representative sample of the Italian population a group of Dermatologists and General Practitioners carried out an observational survey on the patients coming to their office during a 1-month period. Any patient with skin or systemic disease giving their consent was enrolled. Demographic characteristics, comorbidities, lifestyles, history of previous mycosis, clinical aspects of onychomycosis and mycological evaluation were studied. A total of 8331 patients (56.7% female and 43.3% male) were evaluated. More than half of them were aged ≥46 years. Onychomycosis was diagnosed in 14.2% of patients. Big toe and thumb were the most frequently affected nails. Onychomycosis was moderate-severe in 74.1% of the cases. Mycological tests were positive in 81.3% of the cases. Dermatophytes were found in 76.6% of the cases, yeasts in 17.2% and moulds in 6.3%. Risk factors and/or comorbidities were present in 68.2% of the cases. This survey showed a 14% prevalence of onychomycosis in the evaluated population. The main risk factors were previous onychomycosis, diabetes, hallux valgus and use of occlusive footwear.
Gupta, Aditya K; Versteeg, Sarah G; Shear, Neil H
Onychomycosis accounts for 50% of all nail disease cases and is commonly caused by dermatophytes. Diabetes, human immunodeficiency virus, immunosuppression, obesity, smoking, and advancing age are predisposing factors of this fungal infection. Potassium hydroxide and culture are considered the current standard for diagnosing onychomycosis, revealing both fungal viability and species identification. Other diagnostic tests currently available include periodic acid-Schiff staining, polymerase chain reaction techniques, and fluorescent staining. Across 6 recently published epidemiology studies, the global prevalence of onychomycosis was estimated to be 5.5%, falling within the range of previously reported estimates (2%-8%). Newly approved onychomycosis treatments include efinaconazole, tavaborole, and laser therapy with lasers only approved to temporarily increase the amount of clear nail. Additional onychomycosis treatments being investigated include iontophoresis and photodynamic therapy with small open-label studies reported thus far. Preventative strategies, to help decrease recurrence and reinfection rates, include sanitisation of footwear and prophylactic topical antifungal agents.
Hapcioglu, Bilge; Yegenoglu, Yildiz; Disci, Rian; Erturan, Zayre; Kaymakcalan, Hande
The purpose of this study is to determine the prevalence of tinea pedis and onychomycosis in children of elementary school age and to examine the socio-demographic attributes that may be effective in correlation of both mycoses. 3,390 female and 3,768 male children between ages 6-14 have been examined in seven schools. Skin scrapings and nail samples were taken from 13 students who were suspected to have tinea pedis and from 49 students who were suspected to have onychomycosis. According to direct microscopy (10-15% KOH+calcofluor white) and culturel examination (Sabouraud dextrose agar and dermatophyte test medium) 11 students were diagnosed as tinea pedis and 24 were diagnosed as onychomycosis. Trichophyton rubrum was isolated in 3 students with tinea pedis whose culture was positive and five Candida albicans, five Candida glabrata and one Candida tropicalis cases were isolated from 11 samples with onychomycosis. Tinea pedis prevalence has been found to be 3.3%0. Differences between onychomycosis prevalence based on age have been found to be significant (p < 0.001). In conclusion, it has been determined that the prevalence of tinea pedis and onychomycosis among children is low. Candida spp. was isolated from all of the 14 samples diagnosed as onychomycosis. Our study shows similar results with previous studies done in Turkey and that Trichophyton rubrum continues to be the most isolated agent.
Shemer, Avner; Gupta, Aditya K; Amichai, Boaz; Baum, Sharon; Barzilai, Aviv; Farhi, Renata; Kaplan, Yehonathan; MacLeod, Melissa A
Tinea pedis and onychomycosis often co-occur in individuals. A relationship between swimming pools and tinea pedis exists; however, little research has investigated the relationship between onychomycosis, tinea pedis, and swimming pools. This study sought to examine the prevalence of tinea pedis and onychomycosis among swimming pool employees, a population that may be at risk of tinea infections. Samples were taken from 169 employees at 21 swimming pools in the Netanya area, Israel. KOH microscopy and culture was used to identify fungi. About 46 % of swimming pool employees had concurrent tinea pedis and onychomycosis, 30 % had tinea pedis only, and 6 % had onychomycosis only, compared to 10, 8, and 8 % of controls, respectively. After adjusting for age and gender, swimming pool employees were 20× more likely to have concurrent tinea pedis and onychomycosis, 15× more likely to have tinea pedis only, and 3× more likely to have onychomycosis only compared to controls. The present results are in agreement with previous research and support that swimming pools remain an important source of fungal contamination. More attention to hygienic guidelines and preventative measures may be needed in these settings.
Amichai, B; Nitzan, B; Mosckovitz, R; Shemer, A
Background Onychomycosis is a common disease; topical treatment is usually poorly effective, while systemic treatment is more effective but may be associated with side-effects. Iontophoretic drug delivery may improve drug penetration through the nail and lead to better therapeutic results. Objectives To evaluate the efficacy, safety and tolerability of topical treatments with terbinafine HCl delivered with or without an iontophoretic patch in patients with onychomycosis of the toenails. Methods Patients enrolled into the study were divided randomly into two groups. Group A was treated with terbinafine and an iontophoretic patch (at a constant current density of 100 microA cm(-2)). Group B was treated with terbinafine without iontophoresis. Treatment was overnight wear, every day, 5 days per week, for 4 weeks. Follow-up period was 8 weeks from the end of treatment. Results A significant clinical response was recorded in patients of group A (active group). The percentage of patients having healthy toenail growth of more than 1.5 mm at the end of treatment was 40% compared with 11% in patients treated with terbinafine without current (passive group). The percentage of patients having fungal elements (KOH) in nail specimens decreased significantly at 8 weeks following the completion of treatment: 16% in the active group vs. 53% in the passive group. Patients in the active group reported a tingling sensation that is expected when using an iontophoretic drug delivery treatment. Conclusions The delivery of terbinafine under an electrical current of 100 microA cm(-2) appears to be efficacious and safe and is well tolerated for the treatment of nail onychomycosis.
Altunay, Zeynep Tülay; Ilkit, Macit; Denli, Yaşargül
The data about the prevalence of onychomycosis in patients with psoriasis is contradictory. In this study, we investigated the prevalence of onychomycosis and tinea pedis in patients with psoriasis compared to control group. A total of 60 patients with psoriasis (27 male, 33 female; mean age: 40.8 +/- 17.6 years) and 60 subjects without psoriasis (27 male, 33 female; mean age: 42.8 +/- 17.3 years) who were admitted to dermatology outpatient clinics of our hospital were included to the study. Scrapings from both normal and abnormal toenails as well as toewebs were examined using microscopy and fungal culture. Foot dermatomycosis was diagnosed in 6 (5 onychomycosis and 1 tinea pedis) patients with psoriasis (10%) and in 8 (5 onychomycosis and 3 tinea pedis) control subjects (13.3%) (p > 0.05). The only dermatophyte fungi isolated in both patients with psoriasis and control group were Trichophyton rubrum (75%) and Trichophyton interdigitale (25%). Onychomycosis was more predominant in male psoriatic patients (p = 0.01). Both distero-lateral subungual onychomycosis (DLSO) and total dystrophic onychomycosis were detected in patients with psoriasis, however, DLSO, was the only clinical type in the control group. Pitting is the most typical lesions in nails in patients with psoriasis (p = 0.04). The use of common showers play a role in transmission of foot dermatomycosis (p = 0.04). In this study, psoriasis was not found as a risk factor for onychomycosis. However, onychomycosis is a major problem in psoriatic nails, and mycological methods would be useful in differential diagnosis. Since dermatomycosis is still an important public health problem, it may be controlled by education of the patient about proper foot hygiene and avoiding walking barefooted in shower areas.
Meireles, Tereza Elizabeth Fernandes; Rocha, Marcos Fábio Gadelha; Brilhante, Raimunda Sâmia Nogueira; Cordeiro, Rossana de Aguiar; Sidrim, José Júlio Costa
Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts and moulds, accounting for about 50% of onychopathies. A high frequency of onychomycosis caused by Candida species has been reported during the last few years in northeast Brazil, as well as in other regions of the world. A clinical diagnosis of onychomycosis needs to be confirmed through laboratory exams. We evaluated the importance of serial repetition of direct microscopic exams and fungal culture for the diagnosis of onychomycosis in the city of Fortaleza, Ceará, in northeast Brazil. We first made a retrospective study of 127 patients with onychomycosis, identifying the fungi that had been isolated from fingernails and toenails. We then made a prospective study of 120 patients, who were submitted to three successive mycological examinations. Ungual residues were scraped off and directly examined with a microscope and fungal cultures were made. In the retrospective study, in which only one sample was analyzed, the incidence of onychomycosis was 25.0%. In our prospective study, in which we had data from successive mycological examinations, 37.8% had onychomycosis. The most commonly isolated fungi in both studies were yeasts from the genera Candida, especially C albicans, C. parapsilosis and C. tropicalis. We found a high proportion of onychomycosis caused by Candida species. We also concluded that serial repetition of direct microscopic examination and fungal culture, with intervals of 2-5 days improved the diagnosis of onychomycosis. We suggest that this laboratorial strategy is necessary for accurate diagnosis of this type of mycosis, especially when the standard procedures fail to diagnose fungal infection, despite strong clinical suspicion.
Young, Lindsay S; Arbuckle, Harvey A; Morelli, Joseph G
Onychomycosis (OM) is a common nail disorder in adults but has been rare in children. Recent international studies have demonstrated a rise in the prevalence of OM in children and adolescents, with Trichophyton rubrum being the most common pathogen. This 5-year retrospective chart review of children (aged <18) found that 66 of 141 patients (46.8%) presenting to Children's Hospital Colorado or Denver Health Medical Center Dermatology clinics with nail complaints had OM, with the highest prevalence in those aged 6 to 10 and a slight male predominance. Toenails were more commonly affected, and Trichophyton rubrum was the most common pathogen.
Chanussot, Caroline; Arenas, Roberto
In patients with onychomycosis (OM) 71.5% of them have been reported with plantar fungal infection. The aim of this study was to study the frequency and distribution of plantar and interdigital affection in diabetic patients and in a control group without diabetes, all of them with OM. Diabetic patients with OM were more frequently diagnosed with plantar (61.2%) than interdigital (46.7%) infection. In the control group similar results were obtained; patients with OM in 76.5% had plantar mycotic infection and 67.1% interdigital involvement.
Romano, Clara; Massai, Lucia; Strangi, Rosa; Feci, Luca; Miracco, Clelia; Fimiani, Michele
We report two cases of tinea corporis purpurica of the legs, presumably caused by self-inoculation of the mycete from the toenails, in two elderly women (80 and 78 years). Trichophyton violaceum was isolated from the skin and nails. Histological examination of a biopsy specimen from the leg lesions confirmed the diagnosis. The source of infection was an Ethiopian carer who had tinea capitis in the first case, and was undiagnosed in the second patient. Cases of purpuric variants of tinea corporis are rare and this is the first report of probable self-inoculation of T. violaceum from onychomycosis.
Souza, Linton Wallis Figueiredo; Souza, Simone Vilas Trancoso; Botelho, Ana Cristina de Carvalho
This study shows the effectiveness of photodynamic therapy based on methylene blue dye for the treatment of endonyx toenail onychomycosis. Four patients with endonyx onychomycosis caused by Trichophyton rubrum were treated with 2% methylene blue aqueous solution irradiated with light emission diode at 630 nm and an energy density of 36 J/cm2 for 6 months at 2-week intervals. The preliminary study showed the effectiveness of this therapy in the treatment of endonyx onychomycosis, and also indicated that the disease can be caused by T. rubrum.
Tadepalli, Karuna; Gupta, Pradeep Kumar; Asati, Dinesh P.; Biswas, Debasis
Onychomycosis is a fungal infection of nails seen frequently in immune competent and immune compromised patients due to dermatophytes, Candida spp., Fusarium spp., Scopulariopsis brevicaulis, Penicillium spp., and Aspergillus spp. We report a case of onychomycosis in a young immunocompetent male who presented onycholysis of a solitary nail without inflammation. The etiological agent was diagnosed to be Cunninghamella bertholletiae, a fungus pertaining to the order Mucorales (subdivision Mucoromycotina) and known for some of the invasive lesions among immunocompromised patients. This case demonstrates the association of onychomycosis with Cunninghamella bertholletiae in an immune competent individual, not reported so far. PMID:26640729
Tosti, Antonella; Elewski, Boni E.
Introduction Toenail onychomycosis is a common disease in which treatment options are limited and treatment failures and disease recurrence are frequently encountered. It usually requires many months of treatment, and recurrence may occur in more than half of the patients within 1 year or more after the infection has been eradicated. Data on long-term treatment, follow-up and recurrence are limited. Objective Our objective is to interpret these data and recommend practical approaches that should minimize recurrence based on our clinical experience. Results Several factors have been suggested to play a role in the high incidence of recurrence, but only the extent of nail involvement and co-existing diabetes mellitus have been shown to have a significant impact. Conclusion The use of topical antifungals to prevent recurrences after complete cure was achieved has been suggested by various workers and used successfully in our practice. However, it has never been validated through clinical studies. Topical prophylaxis once weekly or twice monthly would seem appropriate in those patients most at risk. Prompt treatment of tinea pedis is essential, as is ensuring family members are free from disease. Patient education and pharmacologic intervention are equally important, and there are a number of simple strategies patients can employ. Managing onychomycosis is a significant long-term commitment for any patient, and minimizing recurrence is critical to meet their expectations. PMID:27843933
Totri, Christine R; Feldstein, Stephanie; Admani, Shehla; Friedlander, Sheila F; Eichenfield, Lawrence F
Onychomycosis (OM) is thought to be a rare disease in children, although there are few epidemiologic studies. This 3-year retrospective case series of nearly 400 children seen at Rady Children's Hospital-San Diego (RCHSD) describes the characteristics of OM found in this pediatric population. From 2011 to 2013, the Pediatric and Adolescent Dermatology Clinic at RCHSD saw a total of 36,634 unique patients, of whom 433 were unique patients with OM. Thirty-four patients met exclusion criteria, leaving 399 (1.1%) with a diagnosis of OM by a pediatric dermatologist. Nail cultures were obtained in 242 cases (60.7%), 116 (48.0%) of which were positive. Trichophyton rubrum was the most commonly isolated pathogen, responsible for 106 cases (91.3%) of positive cultures in the cohort. Our study provides important regional information regarding epidemiologic data in pediatric onychomycosis, highlighting the diagnostic methods most commonly used and the pathogens most frequently encountered in our practice. © 2016 Wiley Periodicals, Inc.
Menéndez, Silvia; Falcón, Leopoldina; Maqueira, Yordana
The results of the use of ozonised sunflower oil (OLEOZON(®)) in the treatment of onychomycosis, based on its known antimycotic action and good skin tolerance, by means of a controlled randomised phase III assay are presented. A total of 400 outpatients were randomly divided into two groups: experimental, treated with topical OLEOZON(®), two times per day and control, treated also two times per day, with ketoconazole cream 2%, for 3 months. A patient was considered cured when the sick nails regained the normal colour, growth and thickness, with a negative mycological study. In the experimental group, a regression of signs was achieved from the first month of treatment, while in the control group, it was obtained after the third month of treatment. All patients treated with OLEOZON(®) had improvement in their condition (9.5%) or were cured (90.5%). However, in the control group, only 13.5% of patients were cured, 27.5% improved and 59% remained the same, with significant differences between both the groups. After 1 year of follow-up, experimental and control groups presented 2.8% and 44.4% of relapses, respectively. Topical OLEOZON(®) demonstrated effectiveness in the treatment of onychomycosis, superior to that of ketoconazole. No side effects were observed.
Jennings, Maureen B; Weinberg, Jeffrey M; Koestenblatt, Evelyn K; Lesczczynski, Christine
Onychomycosis, by definition, is a mycotic infection of the keratinized tissue of the nail plate. Although it is commonly considered to be caused by one of the dermatotropic fungi, a variety of other organisms have been implicated as etiologic agents in the disease, including some bacteria and yeasts. When it is caused by a fungus, any or all of three types of organisms can be involved: dermatophytes, yeasts, and nondermatophyte organisms. The purpose of this study was to identify the microorganisms found in fungal cultures of clinically suspected onychomycosis in the patient population of the Foot Clinics of New York in New York City, the largest foot clinic in the world. Of the 1,800 medical charts reviewed, 214 had culture results, of which 120 were positive. Trichophyton rubrum was the most prevalent pathogen, found in 67% of positive cultures. The most remarkable risk factor was age, with 80% of affected individuals older than 35 years. False-negatives may account for the high percentage (44%) of negative cultures in this study.
Uludag Altun, Hatice; Turk Aribas, Emel; Gorpelioglu, Canan; Karabicak, Nilgun
Rhodotorula spp. have emerged as opportunistic pathogens, particularly in immunocompromised patients. The current study reports a case of onychomycosis caused by Rhodotorula glutinis in a 74-year-old immunocompetent female. The causative agent was identified as R. glutinis based on the pinkish-orange color; mucoid-appearing yeast colonies on Sabouraud Dextrose Agar at 25°C; morphological evaluation in the Corn Meal-Tween 80 agar; observed oval/round budding yeast at 25°C for 72 hours; no observed pseudohyphae; positive urease activity at 25°C for 4 days; and assimilation features detected by API ID 32C kit and automated Vitek Yeast Biochemical Card 2 system. Antifungal susceptibility test results were as follows: amphotericin B (MIC = 0.5 µg/mL), fluconazole (MIC = 128 µg/mL), itraconazole (MIC = 0.125 µg/mL), voriconazole (MIC = 1 µg/mL), posaconazole (MIC = 0.5 µg/mL), anidulafungin (MIC = 0.5 µg/mL), and caspofungin (MIC = 16 µg/mL). Antifungal therapy was initiated with oral itraconazole at a dose of 400 mg/day; seven-day pulse therapy was planned at intervals of three weeks. Clinical recovery was observed in the clinical evaluation of the patient before the start of the third cure. Although R. glutinis has rarely been reported as the causative agent of onychomycosis, it should be considered. PMID:25328721
Dai, T.; Tegos, G.P.; Rolz-Cruz, G.; Cumbie, W.E.; Hamblin, M.R.
Summary Background Onychomycosis responds to systemic antifungals and sometimes to topical lacquers, but alternative treatments are desirable. Topical application of germicidal ultraviolet (UV) C radiation may be an acceptable and effective therapy for infected nails. Objectives To test the ability of UVC to inactivate dermatophyte suspensions in vitro and to sterilize a novel ex vivo model of nail infection. Methods Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum and Microsporum canis suspensions were irradiated with UVC (254 nm) at a radiant exposure of 120 mJ cm−2 and surviving colony-forming units quantified. T. rubrum infecting porcine hoof slices and human toenail clippings was irradiated with UVC at radiant exposures of 36–864 J cm−2. Results In vitro studies showed that 3–5 logs of cell inactivation in dermatophyte suspensions were produced with 120 mJ cm−2 UVC irradiation. Depending on factors such as the thickness and infectious burden of the ex vivo cultures, the radiant exposure of UVC needed for complete sterilization was usually in the order of tens to hundreds of J cm−2. Resistance of T. rubrum to UVC irradiation did not increase after five cycles of subtotal inactivation in vitro. Conclusions UVC irradiation may be a less invasive treatment option for onychomycosis, when the appropriate consideration is given to safety. PMID:18410410
Kymplová, Jaroslava; Jelínek, Miroslav; Urzová, Jana; Mikšovský, Jan; Dušek, Karel; Bauerová, Lenka
Since it is known that UV-C radiation kills fungus, we wanted to verify the hypothesis that the use of excimer laser could be an alternative method for treating onychomycosis - nail fungus. The aim of the first stage of this work was to determine the transmission, reflection and absorption of nails. In the following stage we focused on irradiation of fungi. Our final task is to assess whether it is possible to determine the parameters of radiation (a total dose,a dose per pulse frequency, a repetition rate, a number of pulses) for which the elimination of fungi would be the most effective but without damaging the nail and soft tissue underneath it. The results so far have showed that UV-C radiation does not pass through a fingernail to such an extent that it could damage the soft tissue beneath it. Fungi are destroyed by the application of only small doses of radiation using the excimer laser. Additional measurements will be required to determine the modulation parameters of the excimer laser radiation for the treatment of onychomycosis.
Souza, Linton Wallis Figueiredo; Souza, Simone Vilas Trancoso; Botelho, Ana Cristina de Carvalho
The study showed the effectiveness of photodynamic therapy based on methylene blue to treat severe distal and lateral subungual toenail onychomycosis. 22 patients were divided into two groups: group A consisting of 11 patients with severe toenail onychomycosis and group B consisting of 11 patients with mild-to-moderate toenail onychomycosis. All patients had onychomycosis caused by Trichophyton rubrum. The patients were treated with sessions of 2% methylene blue aqueous solution irradiated with light emission diode device with 630 nm and 36 J/cm2 biweekly for six months. The clinical response was significantly better in patients with mild-to-moderate (100%) onychomycosis compared with patients with severe onychomycosis (63.6%).
Bhatta, Anil Kumar; Keyal, Uma; Wang, Xiuli; Gellén, Emese
Onychomycosis is one of the most common diseases in the field of dermatology. It refers to the fungal infection of the nail plate or nail bed with high incidence in the general population. The available treatment options for onychomycosis have limited use due to side effects, drug interactions, and contraindications, which necessitates the application of an alternative treatment for onychomycosis. In the recent years, lasers and photodynamic therapy (PDT) have been recognized as alternative treatment options. Most of the previous studies have found them to be safe and effective treatment modalities in this indication; however, the results varied greatly and the in vitro and in vivo outcomes are contradictory. In the present review, studies related to the mechanism of action of lasers and PDT for the treatment of onychomycosis will be discussed, with a focus on to find explanation to the contradictory results.
Gayoso, C W; Lima, E O; Oliveira, V T; Pereira, F O; Souza, E L; Lima, I O; Navarro, D F
The antifungal activity of Eugenia cariophyllata essential oil and eugenol, its major constituent, on fungal strains isolated from onychomycosis was evaluated. The natural products presented prominent antifungal action with MIC of 1% and 4%, respectively.
Shi, Dongmei; Lu, Guixia; Mei, Huan; de Hoog, G Sybren; Zheng, Hailin; Liang, Guanzhao; Shen, Yongnian; Li, Tianhang; Liu, Weida
Onychomycosis is usually caused by dermatophytes, although also other filamentous and yeast-like fungi are associated with nail invasion. Chaetomium is an environmental genus of ascomycetes exhibiting a certain degree of extremotolerance. We report the first case of onychomycosis in a 46-year-old woman in China caused by Chaetomium globosum. The patient showed yellowish black discoloration with periungual inflammation on the left first toenail. We confirmed the causative agent, C. globosum, by KOH mount, culture, micromorphology and DNA sequence analysis.
Gupta, A K; Daigle, D; Foley, K A
Onychomycosis is a fungal infection of the nail and is the most common nail affliction in the general population. Certain patient populations are at greater risk of infection and the prevalence of onychomycosis reported in the literature has yet to be summarized across these at-risk groups. We performed a systematic review of the literature and calculated pooled prevalence estimates of onychomycosis in at-risk patient populations. The prevalence of dermatophyte toenail onychomycosis was as follows: general population 3.22% (3.07, 3.38), children 0.14% (0.11, 0.18), the elderly 10.28% (8.63, 12.18), diabetic patients 8.75% (7.48, 10.21), psoriatic patients 10.22% (8.61, 12.09), HIV positive patients 10.40% (8.02, 13.38), dialysis patients 11.93% (7.11, 19.35) and renal transplant patients 5.17% (1.77, 14.14). Dialysis patients had the highest prevalence of onychomycosis caused by dermatophytes, elderly individuals had the highest prevalence of onychomycosis caused by yeasts (6.07%; 95% CI = 3.58, 10.11) and psoriatic patients had the highest prevalence of onychomycosis caused by non-dermatophyte moulds (2.49%; 95% CI = 1.74, 3.55). An increased prevalence of onychomycosis in certain patient populations may be attributed to impaired immunity, reduced peripheral circulation and alterations to the nail plate which render these patients more susceptible to infection.
Ekhtiari, Masoome; Farahyar, Shirin; Falahati, Mehraban; Razmjou, Elham; Ashrafi-Khozani, Mahtab; Ghasemi, Zeinab; Abbasi-Nejat, Ziba
Yeasts are common etiologic agents of onychomycosis. This study reported a case of onychomycosis due to Cryptococcus friedmannii (Naganishia friedmannii). This yeast was isolated of the right great toenail of 57-year-old man. Microscopic examination of nail scrapings showed budding cells with thin capsule. Sequence analyzes of the internal transcribed spacer regions was closely related to Cryptococcus friedmannii. The results of susceptibility testing showed the Cryptococcus friedmannii to be sensitive to fluconazole, itraconazole and amphotericin B.
We report the first case of onychomycosis caused by Onychocola canadensis in Estonia. We believe that the number of nail infections caused by this fungus is underestimated due to the current diagnostic algorithm of non-dermatophytic onychomycosis. The need to define categories and criteria for 'proven' and 'probable' non-dermatophyte mold infections to promote more extensive studies in the future is also discussed.
Van Duyn Graham, Lauren; Elewski, Boni E
Onychomycosis and tinea capitis are prevalent fungal diseases that are difficult to cure and usually require systemic treatment. Onychomycosis has high recurrence rates and can significantly affect a patient's quality of life. Oral terbinafine has been approved for onychomycosis for 20 years in Europe and 15 years in the United States. Over these past 20 years, numerous studies show that oral terbinafine is a safe and efficacious treatment for onychomycosis. More recently, oral terbinafine also has been approved for tinea capitis. Once difficult to treat, terbinafine has revolutionised treatment of these fungal diseases. It has minimal side effects and its limited drug interactions make it an excellent treatment option for patients with co-morbidities. This review discusses oral terbinafine and new insights into the treatment of onychomycosis and tinea capitis. Recent publications have enhanced our knowledge of the mechanisms of oral terbinafine and its efficacy in treating onychomycosis. Oral terbinafine vs. other antifungal therapeutic options are reviewed. Overall, terbinafine remains a superior treatment for dermatophyte infections because of its safety, fungicidal profile, once daily dosing, and its ability to penetrate the stratum corneum.
Feng, Xiaobo; Ling, Bo; Yang, Xianwei; Liao, Wanqing; Pan, Weihua; Yao, Zhirong
Candida is a common cause of onychomycosis, especially for fingernail onychomycosis. In this study, two simple PCR-based assays combined with the internal transcribed spacers sequencing were performed to reveal the prevalence of Candida species including emerging species in onychomycosis, and triazole antifungal susceptibility profiles for Candida species were also evaluated. Among 210 Candida strains isolated from onychomycosis, Candida parapsilosis was the most common species (54.3%), followed by C. albicans (23.3%) and C. metapsilosis (9.5%). However, C. metapsilosis became the second leading species in toenail onychomycosis and accounted for 19.5% of Candida isolates from toenail samples. C. nivariensis, an emerging species, was firstly recovered from a toenail sample. Other emerging species such as C. orthopsilosis, C. pararugosa and C. fabryi were also identified by molecular tools. C. metapsilosis isolates exhibited significantly higher fluconazole minimum inhibitory concentrations than those exhibited by C. parapsilosis and C. albicans (P < 0.001). This study provides insight into the prevalence, distribution and susceptibility profiles of Candida species including emerging Candida species in onychomycosis.
Del Rosso, James Q.
Topical antifungal management of toenail onychomycosis has been fraught with several therapeutic challenges including difficulty gaining access to the site of infection and the need for prolonged durations of therapy. In addition, there has been a marked lack of information on the impact of toenail polish application on drug penetration after application. This article reviews available data from studies evaluating the effect of nail polish on antifungal drag penetration using ex vivo laboratory models with cadaver fingernail plates with both tavaborole 5% solution and efinaconazole 10% solution. In addition, changes in nail polish appearance and color transfer to applicators are also discussed, with changes noted with topical efinaconazole. Importantly, there are no data on whether or not nail polish application alters the efficacy of these topical agents. PMID:27672416
Rodríguez-Soto, M E; Fernández-Andreu, C M; Moya Duque, S; Rodríguez Díaz, R M; Martínez-Machín, G
Physical examination of nails was carried out in 210 elderly patients and nail scrapings were obtained from onychomycosis suggested lesions in order to determine their causative agents, incidence and clinical characteristics. Diagnostic was confirmed by the isolation of the agents from 74 patients, mainly from toe-nails (incidence 35.2). Tinea pedis occurred in 25% of the cases and Diabetes mellitus was the most prevalent associated disease and the most frequent clinical characteristics were the thickening, the opacity and the presence of longitudinal strias in the surface of the nails. It was compared the results obtained by microscopic examination and by culture. Trichophyton rubrum was the most common dermatophyte isolated; Candida parapsilosis was dominant among Candida species.
Jung, M Y; Shim, J H; Lee, J H; Lee, J H; Yang, J M; Lee, D-Y; Jang, K-T; Lee, N Y; Lee, J-H; Park, J-H; Park, K K
Traditionally, the gold standard for diagnosis of onychomycosis has been the combination of direct microscopy with potassium hydroxide (KOH) staining and fungal culture. However, several studies have suggested that periodic-acid-Schiff (PAS) staining of nail-plate clippings may be a very sensitive method for the diagnosis of onychomycosis. To compare the sensitivities of direct microscopy with KOH, fungal culture and PAS staining of nail-plate clippings, and to define an efficient, high-yield and cost-effective diagnostic strategy for the diagnosis of onychomycosis in the clinical setting. We evaluated a total of 493 patients with clinically suspected onychomycosis. Group A comprised 400 patient samples, evaluated using fungal culture and PAS stain, while group B comprised 93 patient samples evaluated using KOH, fungal culture and PAS. Diagnosis of onychomycosis was defined as clinical morphology plus at least one positive test result. In group A, sensitivities of fungal culture and PAS were 49.5% and 93.1% (P < 0.005), respectively. In group B, the most sensitive single test was PAS (88.2%) followed by KOH (55.9%) and fungal culture (29.4%). The combination of fungal culture and PAS (94.1%) was significantly (P < 0.001) more sensitive than that of KOH and culture (72.1%). PAS staining of nail clippings is much more sensitive than KOH and fungal culture for the diagnosis of onychomycosis. Based on our results, we propose a diagnostic algorithm for onychomycosis that takes into consideration the sensitivity, cost-effectiveness and necessary time for each test. © 2015 British Association of Dermatologists.
Asz-Sigall, Daniel; López-García, Lirio; Vega-Memije, María Elisa; Lacy-Niebla, Rosa María; García-Corona, Cristina; Ramírez-Rentería, Claudia; Granados, Julio; Villa, Antonio; Ameen, Mahreen; Arenas, Roberto
Onychomycosis is multifactorial in origin. Studies have suggested an autosomal dominant pattern of inheritance and human leukocyte antigen DR4 (HLA-DR4) has been shown to protect against onychomycosis in an Ashkenazi Jewish population. This study investigates HLA class II association in a Mexican Mestizo population with Trichophyton rubrum onychomycosis. This was a prospective case-control study. Mexican Mestizos with a clinical diagnosis of onychomycosis and culture positive for T. rubrum were recruited, together with age- and sex-matched controls. First-degree relatives were also investigated for onychomycosis. Case-control samples were HLA typed by polymerase chain reaction sequence-specific primer based analysis. Twenty-one cases and 42 controls were recruited with a mean age of 40 years (range: 18-58 years). HLA-DR6 was found in seven (33%) cases and 19 (45%) controls [P < 0.023, odds ratio (OR) = 0.088, 95% confidence interval (CI): 0.01-0.71]. Six (29%) cases and three (7%) controls had an affected child (P < 0.043, OR = 9.15, 95% CI: 1.07-78.31), and 13 (62%) cases and 12 (29%) controls had an affected first-degree relative (P < 0.02, OR = 4.0, 95% CI: 1.1-14.3). These results suggest that HLA-DR6 confers protection against the development of onychomycosis in a Mexican Mestizo population. Having an affected first-degree relative significantly increases the risk of onychomycosis, suggesting genetic susceptibility. © 2010 The International Society of Dermatology.
Barot, Bhavesh S; Parejiya, Punit B; Patel, Hetal K; Mehta, Dharmik M; Shelat, Pragna K
Onychomycosis is one of the most common nail disorders. It affects 10-30% of the world population and is caused by dermatophytes, non-dermatophytes, molds, and yeasts. Present treatment methods of onychomycosis include oral therapy, topical therapy, and a combination of both; they have mild-to-moderate efficacy, with a relapse and reinfection rate of 20-25%. For oral therapy, newer antifungal compounds (azole class and allylamine class) are being investigated to increase efficacy and minimize side effects. Oral therapy with antifungal agents have severe side effects, with lesser bioavailability and longer duration of treatment. By contrast, topical therapy of onychomycosis is associated with greater patient compliance and fewer systemic side effects and drug interactions. Current topical treatment options of onychomycosis are nail lacquers, ointments, lotions, solutions, and gels, but these formulations have been unsuccessful due to poor penetration and distribution of drugs at the infected site. Therefore, novel therapeutic options are constantly being researched to improve the efficacy of onychomycosis treatment by enhancing the permeation of the drug across the nail to reach the infected site. Various physical and chemical enhancement methods have been studied to increase the permeation of drugs across the nail plate to the nail bed. Device-based therapeutic options have also been investigated to increase the antifungal drug concentration and its effects in the onychomycotic nail. Randomized clinical trials of these novel therapies have demonstrated better efficacy. The present review discusses the anatomy of the human nail, onychomycosis and its types, onycholysis, and conventional and novel therapies. We also review patents granted as well as design challenges facing optimal drug formulation for onychomycosis treatment.
Kaya, Tamer Irfan; Eskandari, Gulcin; Guvenc, Ulas; Gunes, Gulcan; Tursen, Umit; Burak Cimen, M Y; Ikizoglu, Guliz
The essential role played by CD25+CD4+ regulatory T (Treg) cells in the control of immunity against some pathogens such as Helicobacter pylori is now well established. But their role in cutaneous fungal infections is still unknown. Onychomycosis is the chronic fungal infection of the nails, which is very common. The aim of this study was to evaluate possible relationship of CD4+CD25+ Treg cells and onychomycosis. Peripheral blood samples were investigated for CD4+CD25+ Treg cells using flow cytometry analysis in 43 toenail onychomycosis patients and in 30 healthy controls. We have found that onychomycosis patients had a higher expression of CD25+CD4+ Treg cells than controls, with values of 8.45 +/- 4.47% versus 4.64 +/- 1.59%, respectively (P = 0.001). The results of this study suggests that increased numbers of CD4+CD25+ Treg cells may play a role in failure of clearance of dermatophytes from skin by preventing the protective inflammation which is leading to development of onychomycosis. Accordingly, we address the possibility that CD4+CD25+ Treg cells may play a role in immune pathogenesis of other superficial fungal infections.
Gupta, A K; Studholme, C
Efinaconazole 10% nail solution is a novel topical antifungal drug for the treatment of onychomycosis. Two Phase III trials were completed using efinaconazole 10% nail solution, where 17.8% and 15.2% of patients achieved complete cure, and 55.2% and 53.4% achieved mycological cure. Several post hoc analyses were carried out using data from Phase III trials to determine the efficacy of efinaconazole with respect to disease duration, disease progression, and comorbidities of diabetes or tinea pedis with onychomycosis. Efinaconazole produced higher efficacy rates with patients presenting onychomycosis in a small portion of the toenail (≤25%) for a shorter duration of time (<1 year and 1-5 years). When patients presenting with both onychomycosis and tinea pedis underwent concurrent treatment, efficacy of efinaconazole increased from 16.1% to 29.4%, suggesting combination therapy improved results. Most interestingly, there was no difference in efinaconazole efficacy between diabetic and non-diabetic groups, indicating efinaconazole could be a safe and effective form of treatment for diabetics. Overall, efinaconazole 10% nail solution shows potential as an antifungal therapy for the treatment of onychomycosis.
LaSenna, Charlotte E; Tosti, Antonella
Onychomycosis is a difficult diagnosis to manage and treatment is sometimes avoided, as this diagnosis is often wrongly perceived as a cosmetic problem. However, onychomycosis has a negative impact on patients’ quality of life, affecting social interaction, psychological well-being, and physical activities. Onychomycosis is also a risk factor for patients with diabetes, with proven increased rates of cellulitis, gangrene, and foot ulcers. Treatments are only mild to moderately effective, and rates of relapse and reinfection are high. Oral treatments require laboratory monitoring due to risk of hepatotoxicity and may be contraindicated in some patients due to risk of drug–drug interactions. Topical treatments require prolonged application and are not very effective. Efinaconazole 10% solution is a new topical triazole treatment for mild to moderate distal subungual onychomycosis, with good efficacy and without the need for debridement of nails. In onychomycosis of the toenails, efinaconazole 10% solution is documented to have a statistically significant, positive impact on patient satisfaction and quality of life. PMID:26170638
Kiki-Barro, P C M; Konaté, A; Kassi, F K; Angora, E K; Bosson-Vanga, H; Bedia-Tanoh, A V; Djohan, V; Yavo, W; Menan, E I H
The aim of this study is to determine the prevalence and the fungi involved in onychomycosis located on fingers in Abidjan. This study includes the sellers of cooked cassava semolina served with fried tuna fish called "garba". Fines squames specimen was processed with 30% KOH for a direct microscope examination. Serous collection were done in physiological serum. Part of the original sample was cultured on Sabouraud medium with antibiotics (chloramphénicol, actidione). Species distribution and antifungal susceptibility by the technique on agar were noted. A total of 205 male sellers were involved. The Onychomycosis prevalence was 6.3%; (95% CI : 3.6-10.3). Five species of yeasts were identified. Candida spp were the most frequent (84.6%) and Candida albicans represented 30.8% of isolated yeasts. Trichosporon cutaneum were isolated in two case (15.4%). Susceptibility for amphotericin-B was 92.3% contrary to 5-fluorocytosine 30.8%. The subjects aged between 15 to 24 (69.2%), with a higher seniority (84.6%) and illiterate (69.2%) were the most affected. The main risk factors of fungal infections were the presence of previous fingernail onychomycosis (P<0.0001) and the frequent fingernail cutting (P=0.0009). Onychomycosis caused by yeast is infrequent among "garba" sellers in Abidjan. The main fungi involved in fingernail onychomycosis were Candida species. It is nevertheless necessary to implement sensitization for them on contributing factors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Yadav, Pravesh; Singal, Archana; Pandhi, Deepika; Das, Shukla
Introduction: There is a constant need to define the epidemiological and mycological characteristics of onychomycosis (OM) for optimal management strategies. Objectives: To define the epidemiological and mycological characteristics of patients with dermatophyte toenail OM in a tertiary care hospital. Materials and Methods: Hundred consecutive patients of KOH and culture-positive dermatophyte toenail OM were subjected to detailed history, clinical examination and investigations. Results: Maximum number of patients (40%) belonged to 31-45 years age group and there was a male preponderance (M:F = 6.7:1). The mean duration of disease was 54 months. Thirty-three patients had fingernail involvement in addition to the toenail OM and 37% had co-existent cutaneous dermatophyte infection. Discoloration was the most common symptom (98%). Ninety-four (94%) patients had distal lateral subungual onychomycosis (DSLO) while two had superficial onychomycosis (SO) and only one had proximal superficial onychomycosis (PSO). Trichophyton interdigitale was the most common etiological agent (61%) followed by Trichophyton rubrum and Trichophyton verrucosum. Conclusions: Toenail OM is more common in males. DSLO was the most common clinical variant and T. interdigitale the most common etiological fungus responsible for toenail OM in our region. The importance of early diagnosis and treatment is highlighted as long-standing toenail OM predisposes to fingernail onychomycosis and recurrent tinea pedis. PMID:25814703
Prohic, Asja; Kuskunovic-Vlahovljak, Suada; Sadikovic, Tamara Jovovic; Cavaljuga, Semra
Introduction: There are limited numbers of studies which focused on the identification of Malassezia yeasts to a species level in onychomycosis. Therefore, the aim of our study was to determine the prevalence and species composition of Malassezia yeasts in patients with clinically suspected onychomycosis and to examine if the range of species varies with patient gender, age, site of involvement and clinical pattern of onychomycosis. Methods: Specimens were taken from 785 patients presenting signs of onychomycosis and then incubated on Sabouraud dextrose agar and modified Dixon agar. The yeasts isolated were identified according to their macroscopic and microscopic features and physiological characteristics. Results: Malassezia species were diagnosed both by microscopy and culture in fourteen (1.8%) patients. M. globosa was the predominant, if not only, species identified from nail samples. Mixed cultures were observed in five cases: in 4 cases Malassezia was co-isolated with Candida albicans and in one case with dermatophyte. Fingernails were affected more frequently than toenails (85.7%) and distolateral subungual onychomycosis was the most common clinical type (78.6%). Conclusion: No significant differences were found in the distribution of Malassezia species isolated according to demographic parameters. PMID:26005253
Scher, Richard K; Tosti, Antonella; Joseph, Warren S; Vlahovic, Tracey C; Plasencia, Jesse; Markinson, Bryan C; Pariser, David M
Onychomycosis prevalence is expected to rise as the population ages and the prevalence of diabetes, peripheral vascular disease, and other significant risk factors rise. Until recently, treatment options were limited due to safety concerns with oral antifungals and low efficacy with available topical agents. Efinaconzole and tavaborole were approved by the FDA in 2014 for onychomycosis treatment and provide additional effective topical treatment options for patients with mild-to-moderate disease. Dermatologists and podiatrists both regularly treat onychomycosis, yet there are striking differences between specialties in approach to diagnosis and treatment. In order to explore these differences a joint dermatology-podiatry roundtable of onychomycosis experts was convened. Although it has little effect on mycologic cure, debridement may be a valuable adjunct to oral or topical antifungal therapy, especially in patients with greater symptom burden. However, few dermatologists incorporate debridement into their treatment plans and referral to podiatry may be appropriate for some of these patients. Furthermore, podiatrists may be better equipped to manage patients with concurrent diabetes or peripheral vascular disease and elderly patients who are unable to maintain proper foot hygiene. Once cure is achieved, lifestyle and hygiene practices, maintenance/prophylactic onychomycosis treatment, and proactive tinea pedis treatment in patients and family members may help to maintain patients' cured status.
Daniel, Ralph C
Onychomycosis is not just a cosmetic problem. It is a common disorder that may be a reservoir of infection and lead to significant medical problems. In addition, onychomycosis may cause a substantial decrease in quality of life. An understanding of the disorder and updated management is important for all health care professionals. Onychomycosis is the most common nail disorder in adults. It is four to seven times more frequent in toenails, where it often involves several nails. It is a progressive disease, and although not life threatening it is inappropriately considered purely a cosmetic problem, with some physicians still believing there is no need to treat. The fungal infection usually begins in the nail bed, and often extends to the nail plate. Onychomycosis is unsightly and can be uncomfortable; with discoloration of the nail plate and more severe disease resulting in loss of the nail plate altogether. Onychomycosis may become a source of more widespread fungal lesions, spreading to other nails, body sites (groin, skin, scalp), and even to family members.
Gupta, Aditya K; Daigle, Deanne; Paquet, Maryse
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.
Capriotti, Kara; Capriotti, Joseph A
Background Povidone–iodine (PVP-I) 10% aqueous solution is a well-known, nontoxic, commonly used topical antiseptic with no reported incidence of fungal resistance. We have been using a low-dose formulation of 1% PVP-I (w/w) in a solution containing dimethyl sulfoxide (DMSO) in our clinical practice for a variety of indications. Presented here is our clinical experience with this novel formulation in a severe case of onychomycosis that was resistant to any other treatment. Findings A 49-year-old woman who had been suffering from severe onychomycosis for years presented after failing to find any remedy including over the counter (OTC), topical, and systemic oral prescribed therapies. Conclusion The topical povidone–iodine/DMSO system was very effective in this case at alleviating the signs and symptoms of onychomycosis. This novel combination warrants further investigation in randomized, controlled trials to further elucidate its clinical utility. PMID:26491374
Falahati, Mehraban; Ghojoghi, Aynaz; Abastabar, Mahdi; Ghasemi, Zeinab; Farahyar, Shirin; Roudbary, Maryam; Hedayati, Mohammad Taghi; Armaki, Mojtaba Taghizadeh; Hoseinnejad, Akbar
Onychomycosis is a common fungal infection of nails which is mainly caused by dermatophyte species and less often by yeasts and non-dermatophyte molds. We present a case of onychomycosis due to Aspergillus clavatus for the first time worldwide. The patient was an immunocompetent 32-year-old woman who identified with Psoriasis of the nail. The presence of A. clavatus in a nail sample was confirmed using microscopic and culture analysis followed by PCR of the β-tubulin gene. After antifungal susceptibility test, it is revealed that the isolate was resistant to the majority of common antifungal drugs, but finally the patient was treated with itraconazole 200 mg daily. A. clavatus and drug-resistant A. clavatus have not previously been reported from onychomycosis.
Background Onychomycosis is a common nail pathology which has proven to be a treatment challenge to healthcare professionals. Antifungal drugs have been the mainstay of therapy for many years. Recently, laser technologies have been introduced as a treatment for onychomycosis avoiding the disadvantages of systemic and topical drug therapies, offering a rapid treatment for an often persistent nail condition. The purpose of this study was to review published evidence regarding the effectiveness of laser technologies in the treatment of onychomycosis. Methods The primary question for this review was “what evidence is there for the use of lasers in the treatment of onychomycosis”? A systematic literature search of published papers indexed on Pubmed and Web of Science® was undertaken in June 2014 for original, published research. The primary outcome measures for efficacy were mycological cure and clearance of the affected nail (clinical cure). Results This review returned a total of twelve eligible published studies evaluating the use of lasers in the treatment of onychomycosis. Two were randomised controlled trials, four were comparative design studies (with no placebo/control groups) and the remainder were case series. The level of evidence was generally low level reflecting predominantly small sample size and lack of control groups. The results from studies were conflicting and follow up periods for patients in studies were generally short. Many studies excluded patients with severe or dystrophic onychomycosis. Conclusions The evidence pertaining to the effectiveness of laser treatment of onychomycosis is limited and of poor methodological quality. Future studies using a randomised controlled trial designs with larger study populations and clear procedures are required to permit a full evaluation of this emerging technology. PMID:25104974
Gupta, Aditya K; Korotzer, Andrew
Although a completely normal nail would be the ideal outcome when treating onychomycosis, this is not always achievable and long treatment courses or patient expectations can impact patient adherence. We analyzed cure rates from a number of subpopulations derived from the two pivotal phase III studies with efinaconazole topical solution (10%) to provide some insights into clinically meaningful treatment outcomes and support for effective long-term management programs. Efinaconazole affords greater efficacy in milder disease, female patients, and those patients whose disease is relatively recent and confined to the great toenail, following 48 weeks' treatment. With longer treatment courses, similar results may be achieved in other subpopulations. Clinically meaningful results (a 40% improvement in the involvement of the diseased nail) were achieved with efinaconazole within six months in half the patients treated, and in over 90% of patients by study end. A greater proportion of female patients achieved clinically meaningful results at six months, although treatment success did not seem to be influenced by baseline disease severity. The majority of patients treated with efinaconazole could expect to see clinically meaningful results within six months.
J Drugs Dermatol. 2016;15(10):1260-1266.
Szepietowski, Jacek C; Reich, Adam; Garlowska, Emilia; Kulig, Marzena; Baran, Eugeniusz
To evaluate the prevalence and factors influencing the presence of concomitant dermatomycoses in patients with toenail onychomycosis. Prospective study based on a specially designed questionnaire completed by dermatologists. A total of 2761 patients with toenail onychomycosis. The diagnosis of fungal skin infections was confirmed by direct microscopic examination or by culture. In 1181 patients (42.8%) with toenail onychomycosis, concomitant fungal skin infections were noted. Tinea pedis was the most common and was found in 933 patients (33.8%). Other concomitant fungal skin infections were fingernail onychomycosis (7.4%), tinea cruris (4.2%), tinea corporis (2.1%), tinea manuum (1.6%), and tinea capitis (0.5%). The presence of concomitant fungal skin infections depended on number of involved toenails; duration of onychomycosis; sex, age, and education level; area of residence; and type of isolated fungus. The coexistence of toenail onychomycosis with other types of fungal skin infections is a frequent phenomenon. It could be hypothesized that infected toenails may be a site from which the fungal infections could spread to other body areas. Effective therapy for onychomycosis might therefore be essential not only to treat the lesional toenails but also to prevent spreading the infection to other sites of the skin.
Ghannoum, M; Isham, N; Catalano, V
Approval of topical onychomycosis drugs by regulatory agencies may be negatively impacted by an overly stringent definition of complete cure, which includes nail clearing plus mycological cure. In this position paper, we discuss interpretation of mycological outcome and clinical trial length. We reviewed data from seven international onychomycosis trials that enrolled subjects with positive KOH and dermatophyte-positive culture at screening followed by 48 weeks of treatment. Further, we examined 94 KOH-positive/culture-negative week 52 follow-up samples for morphological hyphal damage. From 3054 samples collected at week 52 follow-up visits, 2360 were culture-negative. However, a significant percentage (78.7%) of these subungual samples (n = 1857) remained KOH-positive. From the subset of follow-up samples examined for morphological changes, we identified hyphal breakage or distortion in 56 direct smears (60%), which may indicate nonviability. Reassessment of the definition of onychomycosis cure is critical. For clinical trials of topical agents, length of treatment should be re-examined. Further, in our experience, a high rate of subungual debris samples remained direct smear-positive while converting to negative culture. Evidence of morphological hyphal damage suggests that late-visit microscopic results may be false-positives. Therefore, the absence of clinical signs following an adequate washout period, coupled with a negative culture, with or without negative microscopy, should be considered the definition of onychomycosis cure. © 2013 British Association of Dermatologists.
Sleven, Reindert; Lanckacker, Ellen; Boulet, Gaëlle; Delputte, Peter; Maes, Louis; Cos, Paul
A novel in vitro onychomycosis model was developed to easily predict the topical activity potential of novel antifungal drugs. The model encompasses drug activity and diffusion through bovine hoof slices in a single experimental set-up. Results correspond well with the antifungal susceptibility assay and Franz cell diffusion test.
Guerrer, L.V.; Cunha, K. C.; Nogueira, M. C. L.; Cardoso, C. C.; Soares, M. M. C. N.; Almeida, M. T. G.
The “in vitro” antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporon asahii, Candida tropicalis and Candida guilliermondii. PMID:24031958
Carney, Caitlin; Cantrell, Wendy; Warner, Judy; Elewski, Boni
Laser treatment has emerged as a novel treatment modality for onychomycosis. We sought to determine thermal response and optical effects of a submillisecond neodymium:yttrium-aluminum-garnet (Nd:YAG) 1064-nm laser on common fungal nail pathogens, and the clinical efficacy and safety of the Nd:YAG 1064-nm laser on onychomycotic toenails. A 4-part in vitro and in vivo study was conducted using a Nd:YAG 1064-nm laser. The first portion evaluated 3 different nail pathogens in suspension at 7 heat and time exposures. The second and third parts of the study irradiated pure fungal colonies. The final portion involved an in vivo treatment of toenails over 5 treatment sessions. A fungicidal effect for Trichophyton rubrum was seen at 50°C after 15 minutes, and for Epidermophyton floccosum at 50°C after 10 minutes. Limited growth of Scytalidium was seen at 55°C after 5 minutes. No inhibition was observed after laser treatment of fungal colonies or suspensions. In vivo treatment of toenails showed no improvement in Onychomycosis Severity Index score. The Nd:YAG 1064-nm laser was the only laser tested. Laser treatment of onychomycosis was not related to thermal damage or direct laser effects. In vivo treatment did not result in onychomycosis cure. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Carrillo-Meléndrez, Hilda; Ortega-Hernández, Esteban; Granados, Julio; Arroyo, Sara; Barquera, Rodrigo; Arenas, Roberto
Background Patients with nail psoriasis have an increased risk of onychomycosis. Previous studies suggest it may be due to structural changes of the nails. However, a genetic predisposition seems to be also at play. Objective To determine a genetic susceptibility for onychomycosis in nails with changes of psoriasis. Methods This is a prospective case-control study of patients with suggestive changes of nail psoriasis with onychomycosis (cases) and without onychomycosis (controls) confirmed by mycological tests. HLA typing was performed in all of them by sequence-specific primers. Results Twenty-five patients and 20 controls with a mean age of 50 years (range 37-72 years) were studied. HLA-DRB1*08 was found in 12 cases (48%) and only 3 controls (15%) [p < 0.033, odds ratio (OR) = 3.8, 95% confidence interval (CI): 0.9-19]. HLA-DR1 was found in 9 cases (36%) and only 1 control (5%) (p < 0.023, OR = 8.5, 95% CI: 1-188). Conclusion HLA-DR*08 and HLA-DR*01 probably increase the susceptibility to fungal infection in psoriasis-affected nails, but larger studies are required to confirm this observation. PMID:27843918
Onychomycosis is a common infection of the nail unit that is usually caused by a dermatophyte (tinea unguium) and most frequently affects toenails in adults. In most cases, onychomycosis is associated with limited treatment options that are effective in achieving complete clearance in many cases. In addition, recurrence rates are high in the subset of treated patients who have been effectively cleared, usually with an oral antifungal agent. There has been a conspicuous absence of medical therapies approved in the United States since the introduction of topical ciclopirox (8% nail lacquer), with no new effective agents introduced for more than 10 years. Fortunately, newer agents and formulations have been under formal development. While patients might prefer a topical therapy, efficacy with ciclopirox 8% nail lacquer, the only available agent until the very recent approval of efinaconazole 10% solution, has been disappointing. The poor therapeutic outcomes achieved with ciclopirox 8% nail lacquer were not unexpected as the cure rates achieved in the clinical trials were unimpressive, despite concomitant nail debridement, which was an integral part of the pivotal trials with ciclopirox 8% nail lacquer. Efinaconazole 10% solution and tavaborole 5% solution are new topical antifungals specifically developed for the treatment of dermatophyte onychomycosis. In Phase 3 clinical trials, both newer agents were applied once daily for 48 weeks without concomitant nail debridement. Mycologic cure rates with efinaconazole 10% solution are markedly superior to what was achieved with ciclopirox 8% nail lacquer. To add, they appear to be nearly comparable to those achieved with oral itraconazole in pivotal clinical trials. However, it is important to remember that direct comparisons between different studies are not conclusive, are not generally considered to be scientifically sound, and may not be entirely accurate due to differences in study design and other factors. Well
Gupta, A K; Nakrieko, K-A
The dermatophyte Trichophyton rubrum is responsible for approximately 80% of onychomycosis cases. Genetic strain typing was developed to help elucidate its epidemiology and pathogenicity. To determine T. rubrum DNA strain types in North American patients with onychomycosis and to track the patients before and after their course of treatments. T. rubrum DNA strain types were determined by restriction fragment length polymorphisms in ribosomal DNA and Southern blotting from toenails that were cultured from 50 North American patients with onychomycosis prior to treatment. Some of the patients were subsequently typed from oral terbinafine (n = 6), laser (n = 9) or placebo (n = 8) treatment groups. Three European DNA strains were obtained for comparison. DNA strains from the terbinafine group were tested for in vitro susceptibility to terbinafine. Six DNA strain types (A-F) accounted for 94% of T. rubrum DNA strains and corresponded to European isolates. Three DNA strains (6%) novel to North America were detected. DNA strain type switching occurred in all treatment groups: terbinafine (83%), laser (56%) and placebo (25%). Most of the switches (50%) observed in the terbinafine group coincided with mycological cures followed by relapse. Patients treated with laser therapy or placebo exhibited no intermittent cures. DNA strains from the terbinafine group were all susceptible to terbinafine in vitro. Nine T. rubrum DNA strains were identified in a North American population: three novel and six predominant to a European population. Although DNA strain type switching in onychomycosis is a natural phenomenon, with presence in the placebo group, increases following the course of failed onychomycosis treatment suggest an antifungal-induced response. © 2014 British Association of Dermatologists.
Although there are limited data available on gender as an outcome variable in the treatment of onychomycosis, differences in disease prevalence and impact in males versus females have been observed. This article provides a gender subgroup analysis based on results from recent studies evaluating the efficacy, safety, and tolerability of efinaconazole topical solution 10% in the treatment of onychomycosis. Data were collected from two 52-week, prospective, multicenter, randomized, double-blind studies of patients (age range, 18-70 years) randomized to receive either efinaconazole topical solution 10% or vehicle for treatment of onychomycosis. Results from this analysis indicated that once-daily application of efinaconazole topical solution 10% may provide a useful topical option for treatment of mild to moderate toenail onychomycosis, especially in female patients.
Jeelani, Shazia; Ahmed, Qazi Masood; Lanker, Audil Mohmad; Hassan, Iffat; Jeelani, Nasir; Fazili, Tawheeda
Onychomycosis is fungal infection of one or more of the nail units. However, because fungi cause only about half of all nail dystrophies, the use of appropriate diagnostic techniques is important to ensure correct diagnosis and treatment. Aim of the present study was to compare direct microscopy, culture and HPE-PAS for diagnosis of onychomycosis by evaluating their sensitivity and various other relevant statistical parameters. A prospective, hospital-based, cross-sectional study was conducted on 216 patients with a high degree of clinical suspicion of onychomycosis. Nail specimens were evaluated using three diagnostic methods, i.e. direct microscopy using 20% Potassium hydroxide (KOH) & 40% Di-methyl-suphoxide (DMSO), culture and histopathological examination using PAS stain (HPE-PAS). Of 216 patients direct microscopy was positive in 138 (63.9%), culture in 147 (68%) and HPE-PAS in 164 patients (76%). One hundred and seventy-nine patients fitted into the criteria set for confirmed diagnosis of onychomycosis. Using this as a denominator; direct microscopy, culture and HPE-PAS had sensitivities of 77.1%, 70% and 91.6% respectively. Also, HPE-PAS showed the highest sensitivity of 94.7% in 19 cases with prediagnostic antimycotic treatment compared to direct microscopy (42.1%) or culture (57.9%). HPE-PAS shows high sensitivity for diagnosis of onychomycosis and can be considered as a gold standard in the diagnosis of onychomycosis.
Arrua, Juliana M M; Rodrigues, Luis A S; Pereira, Fillipe O; Lima, Edeltrudes O
Over time, as the etiology of onychomycosis has developed, yeasts from the genus Candida have emerged as important etiological agents. This study aimed to determine the frequency of yeast caused onychomycosis in Joao Pessoa, Paraíba, Brazil from 1999 to 2010. A retrospective study from January 1999 to December 2010 evaluated the results of onychomycosis positive direct mycological exams (DME) - for yeast and realized in the Hemato(r) Clinical Laboratory. Women were the most affected by onychomycosis which occur preferentially in adults, and the toenails are the favorite yeast targets. The prevalent yeasts were Candida tropicalis and C. krusei.
Sleven, Reindert; Lanckacker, Ellen; Delputte, Peter; Maes, Louis; Cos, Paul
Many topical commercial products are currently available for the treatment of onychomycosis. However, limited data are available concerning their antifungal activity. Using an in vitro onychomycosis model, the daily application of seven nail formulations was compared to the antifungal reference drug amorolfine (Loceryl(®) ) and evaluated for inhibitory activity against Trichophyton mentagrophytes using an agar diffusion test. Of all commercial nail formulations, only Excilor(®) and Nailner(®) demonstrated inhibitory activity, which was much lower compared to the daily application of Loceryl(®) . However, Excilor(®) showed similar efficacy compared to the conventional weekly application of Loceryl(®) . These results suggest a role for organic acids in the antifungal effect of Excilor(®) (acetic acid, ethyl lactate) and Nailner(®) (lactic acid, citric acid, ethyl lactate) as all tested formulations without organic acids were inactive.
Topical treatment for toenail onychomycosis has been fraught with a long-standing reputation of poor efficaey, primarily due to physical properties of the nail unit that impede drug penetration. Newer topical agents have been formulated as Solution, which appear to provide better therapeutic response in properly selected patients. It is important to recognize the impact the effects that mitigating and concomitant factors can have on efficaey. These factors include disease severity, gender, presence of tinea pedis, and diabetes. This article reviews results achieved in Phase 3 pivotal studies with topical efinaconazole 10% Solution applied once daily for 48 weeks with a focus on how the aforementioned factors influenced therapeutic outcomes. It is important for clinicians treating patients for onychomycosis to evaluate severity, treat concomitant tinea pedis, address control of diabetes if present by encouraging involvement of the patient’s primary care physician, and consider longer treatment courses when clinically relevant. PMID:27047631
Syed, T A; Qureshi, Z A; Ali, S M; Ahmad, S; Ahmad, S A
The prevalence of onychomycosis, a superficial fungal infection that destroys the entire nail unit, is rising, with no satisfactory cure. The objective of this randomized, double-blind, placebo-controlled study was to examine the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia oil incorporated in a cream to manage toenail onychomycosis in a cohort. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6-36 months duration of disease were randomized to two groups (40 and 20), active and placebo. After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants.
Tanrıverdi, Sakine Tuncay; Özer, Özgen
Terbinafine hydrochloride (TBF-HCl) is an active substance that is using for treatment of onychomycosis. Onychomycosis is a fungal infection which is the most common disease of nail plate. The nail plate is a barrier which prevents effective topical treatment of ungual disorders. In this study, TBF-HCl loaded liposome and ethosome formulations and also gel form of these formulations were prepared. The formulations were characterized and in vitro and ex vivo release studies were performed. Nail characterization studies were also performed to examine the effect of formulations and experimental conditions on nail surface. As a result, all formulations can serve as efficient formulations for ungual application of TBF-HCl. By the way, the results of the accumulation studies suggested that liposome poloxamer gel formulation could be promising system for ungual drug delivery due to the better accumulation and easier application of the formulation. Copyright © 2012 Elsevier B.V. All rights reserved.
Bristow, Ivan; Baran, Robert; Score, Michelle
Onychomycosis continues to be a common and intractable problem in adults, often responding poorly to topical treatment due to limited drug penetration of the nail plate. Improving penetration has been attempted previously by chemical and physical means with some success. The authors present three cases of toenail onychomycosis treated topical terbinafine 1% solution using controlled micro-penetration of the nail using a novel intelligent nail drill system which is able to drill nail plate without penetrating the delicate nail bed beneath. The cases illustrate how the device has been successfully employed to deliver the anti-fungal drug directly and rapidly to the site of infection with minimal side effects or complications, whilst maintaining the nail integrity.
J Drugs Dermatol. 2016;15(8):974-978.
Dhib, I; Fathallah, A; Yaacoub, A; Zemni, R; Gaha, R; Said, M B
Onychomycosis is the most frequently encountered nail disease and may be difficult to diagnose and treat. The objective of this study was to determine the prevalence, the clinical and mycological characteristics of onychomycosis in central Tunisia. It is a retrospective study performed over a 22-year period (1986-2007). It included 7151 patients (4709 women and 2442 men) with suspected fingernails and/or toenails onychomycosis. The patients were referred to the Mycology-Parasitology Laboratory of Farhat Hached hospital in Sousse for mycological examination. Both direct microscopy and culture of the nail material were performed to diagnose and identify the causative fungal species. Onychomycosis was confirmed in 78.6% of investigated patients (5624/7151). The positivity rate was higher in women as compared with men. In both men and women, fingernails were most frequently involved than toenails. No significant relation was found between gender and toenails onychomycosis, whereas fingernails were frequently involved in women. As far as aetiological agents are considered, dermatophytes, yeast and moulds were responsible for 49.9%, 47.4% and 2.7% of onyxis cases respectively. In fingernail infections, yeast were the most frequent fungi (83.6%), Candida albicans being the leading species (51.6%). In contrast, in toenail infections, dermatophytes were more frequent (74.1%). Trichophyton rubrum was by far the dominant species (88.1%). Yeast were observed more frequently in women whereas dermatophytes were more common in men. Moulds were involved in 4.2% of cases. The most frequent species were Aspergillus sp. and Chrysosporium sp. Onychomycosis is a frequent disease in central Tunisia. T. rubrum is the predominant agent in toenails infection and yeast, mainly C. albicans, in fingernails onychomycosis.
Waibel, Jill; Wulkan, Adam Jared; Rudnick, Ashley
Onychomycosis affects five percent of the worldwide population. Onychomycosis is a therapeutic challenge. Current therapies on the market are either ineffective or require patient monitoring. Laser and light technologies are being investigated as a possible treatment option for onychomycosis. The proposed mechanism of action is unknown. All infectious agents may be killed by heat (except prions). One possible theory is the photothermal effect from water absorbing lasers creates bulk heating in the nail plate to kill fungal hyphae. Laser technology may be a promising new treatment option for onychomycosis. This is a prospective trial with real-time temperature feedback to evaluate efficacy and safety of laser therapy for onychomycosis. Twenty-one patients with PAS or culture proven fungal onychomycosis were prospectively treated with laser until target temperature of 46 - 48 degrees Celsius was achieved using real-time infrared temperature feedback. The laser and light therapies used were 1319 nm, 1064 nm and BroadBand Light. Exclusion criteria included mixed infection and no other prior therapeutic interventions. Subjects received four treatment sessions one week apart. Assessments included PAS & cultures at one, three and six months post treatment. Patients also were asked a pain score from 1-10 during treatment. Patients tolerated the procedures well with high satisfaction. Average treatment time was 10 minutes. No adverse events were noted. Patients reported mild-moderate transient discomfort during treatment. Six-month culture results revealed 20/21 negative for fungal organisms. Laser therapy offers a safe and effective new option for onychomycosis. This may be the optimal therapy for a large market that needs alternative or adjunct to current therapies. Laser is quick, painless therapy that does not require any oral medications or blood test for monitoring. Additional larger scientific studies are needed to confirm our pilot study results.
Bhatta, Anil Kumar; Keyal, Uma; Huang, Xin; Zhao, Jing Jun
Inability of topical medications to penetrate via nail plate brings a great challenge to clinicians in treating onychomycosis. Furthermore, oral medications are not appropriate for all patients because of drug interactions, adverse effects, and contraindications. We sought to evaluate the clinical efficacy of fractional carbon-dioxide laser-assisted topical therapy for onychomycosis. In total, 75 patients with 356 onychomycotic nails confirmed by mycologic examination were included in this study. All the affected nails received 3 sessions of laser therapy at 4-week intervals and once-daily application of terbinafine cream for 3 months. In all, 94.66% and 92% of the treated patients were potassium hydroxide and culture negative, respectively, after 3 months of treatment. However, only 84% and 80% were potassium hydroxide and culture negative, respectively, at 6 months of follow-up. Using Scoring Clinical Index for Onychomycosis electronic calculator, 73.33% of the patients scored higher than 6 and 26.66% of the patients scored 6 or less. Those who scored more than 6 were evaluated clinically and 98.18% of them showed response to treatment at 3 months and 78.18% of them at 6 months of follow-up. Lack of control group and short duration of follow-up are limitations. Fractional carbon-dioxide laser therapy combined with topical antifungal was found to be effective in the treatment of onychomycosis. However, randomized clinical studies are needed before it can be widely used in clinics. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Vlahovic, Tracey C; Joseph, Warren S; Scher, Richard K; Tosti, Antonella; Plasencia, Jesse; Pariser, David M; Markinson, Bryan C
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.
Silva, Ana Paula da; Chiandrone, Daniel José; Tinta, Jefferson Wanderson Rossi; Kurachi, Cristina; Inada, Natalia Mayumi; Bagnato, Vanderlei Salvador
Onychomycosis is the most common nail disorder. The treatment for this type of infection is one of the main difficult ones in clinical practice, due to the fact that the nails are nonvascularized structures, which compromise the penetration of drugs delivered systemically and favor slow nail growth. We present two devices based on light-emitting diode arrays as light sources for the treatment of onychomycosis by photodynamic therapy (PDT). PDT is an emerging technique that uses a photosensitizer (PS) activated by light in the presence of oxygen. The PS absorbs energy from light and transfers it to oxygen, producing reactive oxygen species such as hydroxyl radicals, superoxide, and singlet oxygen which inactivate fungi and bacteria. Our proposal is the use of a portable and secure light source device in patients with onychomycosis. Additional advantages are the low cost involved, the possibility of topical treatment rather than systemic and the simplicity of operation. These advantages are important to ensure the implementation of this technology for the treatment of an impacting health problem.
Yang, Yun-Seok; Ahn, Jae-Jun; Shin, Min-Kyung; Lee, Mu-Hyoung
Fusarium species are non-dermatophytic moulds, which are commonly known soil saprophytes and important plant pathogens, and have been frequently reported to be aetiological agents of opportunistic infections in humans. The prevalence of onychomycosis caused by Fusarium species varies in the literature because of geographical differences in mould distribution and diagnostic methods. Onychomycosis caused by Fusarium species is considered rare in Korea, and only four cases have been described to date. Pseudomonas aeruginosa also can infect nails and cause green nail syndrome, and recent research has shown that fungal infection may potentiate the colonisation or growth of P. aeruginosa within a nail. Furthermore, such coinfection with P. aeruginosa can prevent the isolation of the fungus because of bacterial overgrowth in culture. The authors report the cases of two immunocompetent patients with F. solani onychomycosis coinfected with P. aeruginosa. Both presented with a greenish/yellowish discolouration and thickening of a thumbnail, and were treated with systemic ciprofloxacin in combination with itraconazole or terbinafine.
Mulvaney, Patrick M; Telang, Gladys H; Jellinek, Nat
We present a 45 year-old man with an eight-year history of discoloration of the nail plate on his left hallux. He had been treated with two courses of oral terbinafine and topical 8% ciclopirox for presumed onychomycosis. On exam, his left great toenail contained a wide yellow-white longitudinal band involving a majority of the nail plate. No subungual debris, hyperkeratosis, or paronychial inflammation was present in the affected nail. Histopathology of the nail plate revealed numerous fungal elements arranged transversely and longitudinally, solely within the keratin layers of the nail plate; these were highlighted with periodic acid-Schiff (PAS) stain confirming endonyx onychomycosis. Cultures grew Trichophyton rubrum. All types of onychomycosis under the new classification system proposed by Hay et al. have now been associated with T. rubrum. Endonyx related to T. rubrum may be a particularly difficult infection to treat with oral or topical agents owing to the absence of robust local immune response and limited drug penetration to the interior nail plate. Physicians should be aware that this type of infection may require treatment with dual-agent therapy or alternative modalities including chemical or surgical plate avulsion or photodynamic therapy.
Sipponen, Pentti; Sipponen, Arno; Lohi, Jouni; Soini, Marjo; Tapanainen, Riikka; Jokinen, Janne J
In in vitro tests, natural coniferous resin from the Norway spruce (Picea abies) is strongly antifungal. In this observational study, we tested the clinical effectiveness of a lacquer composed of spruce resin for topical treatment of onychomycosis. Thirty-seven patients with clinical diagnosis of onychomycosis were enrolled into the study. All patients used topical resin lacquer treatment daily for 9 months. A mycological culture and potassium hydroxide (KOH) stain were done from nail samples in the beginning and in the end of the study. Treatment was considered effective, if a mycological culture was negative and there was an apparent clinical cure. At study entry, 20 patients (20/37; 54%; 95% CI: 38–70) had a positive mycological culture and/or positive KOH stain for dermatophytes. At study end, the result of 13 patients was negative (13/19; 68%; 95% CI: 48–89). In one case (1/14; 7%; 95% CI: 0–21) the mycological culture was initially negative, but it turned positive during the study period. By 14 compliant patients (14/32; 44%; 95% CI: 27–61), resin lacquer treatment was considered clinically effective: complete healing took place in three cases (9%) and partial healing in 11 cases (85%). The results indicate some evidence of clinical efficacy of the natural coniferous resin used for topical treatment of onychomycosis. PMID:23131104
Sipponen, Pentti; Sipponen, Arno; Lohi, Jouni; Soini, Marjo; Tapanainen, Riikka; Jokinen, Janne J
In in vitro tests, natural coniferous resin from the Norway spruce (Picea abies) is strongly antifungal. In this observational study, we tested the clinical effectiveness of a lacquer composed of spruce resin for topical treatment of onychomycosis. Thirty-seven patients with clinical diagnosis of onychomycosis were enrolled into the study. All patients used topical resin lacquer treatment daily for 9 months. A mycological culture and potassium hydroxide (KOH) stain were done from nail samples in the beginning and in the end of the study. Treatment was considered effective, if a mycological culture was negative and there was an apparent clinical cure. At study entry, 20 patients (20/37; 54%; 95% CI: 38-70) had a positive mycological culture and/or positive KOH stain for dermatophytes. At study end, the result of 13 patients was negative (13/19; 68%; 95% CI: 48-89). In one case (1/14; 7%; 95% CI: 0-21) the mycological culture was initially negative, but it turned positive during the study period. By 14 compliant patients (14/32; 44%; 95% CI: 27-61), resin lacquer treatment was considered clinically effective: complete healing took place in three cases (9%) and partial healing in 11 cases (85%). The results indicate some evidence of clinical efficacy of the natural coniferous resin used for topical treatment of onychomycosis. © 2012 Blackwell Verlag GmbH.
Yue, Xueping; Li, Qing; Wang, Hongwei; Sun, Yilin; Wang, Aiping; Zhang, Qi; Zhang, Cuiping
Onychomycosis is a common dermatological problem and can be identified by direct microscopic examination and fungal culture. However, the positive rate of fungal culture is low. This study investigated the application of scanning electron microscopy in the diagnosis of onychomycosis in 20 patients with negative fungal culture. In this study, a routine glutaraldehyde fixation method was used to prepare specimens for electron microscope examination. Results showed that under the scanning electron microscope, significant structural damage was observed in the nail plate in all patients. Hyphaes were seen in 70% of cases. A mixture of scattered hyphaes, pseudohyphaes, and spores was observed in 30% of cases. A mixture of spores and bacteria was observed in 10% of cases. A mixture of hyphaes and bacteria was observed in 20% of cases. The typical hyphae pierced a thin layer or single layer of corneocytes. Hyphaes could be smooth, sleek, and straight with visible separation, or dry, bent, and folded with a smooth surface. The diameter of hyphaes was 1-2 µm. The scattered spores were the main form of spore growth, and the growth of budding spores can be seen attached to the surface of layered armor. Most of the bacteria were gathered in clumps on the ventral surface, especially in grooves. In conclusion, scanning electron microscopy can be used to preliminarily identify the pathogen involved and the degree of damage in cases where onychomycosis is clinically diagnosed, but fungal culture is negative.
Shimamura, Tsuyoshi; Kubota, Nobuo; Nagasaka, Saori; Suzuki, Taku; Mukai, Hideki; Shibuya, Kazutoshi
We developed a novel model of onychomycosis in which we observed fungi in the deep layer of the nail, and we used the model to evaluate the efficacy of two topical antifungal drugs. To establish an experimental, in vivo model of onychomycosis, we applied Trichophyton mentagrophytes TIMM2789 to the nails of the hind limbs of rabbits that underwent steroid treatment. The nails were taken from the rabbits' feet at 0, 2, and 6 weeks after a 2-week infection. The localization of the fungi was evaluated histopathologically. Some fungi were seen to penetrate to the nail bed, and the infection rate in the sample at 0, 2, and 6 weeks after infection was 57, 87, and 93%, respectively. In addition, fungi proliferated and moved proximally into the nail plate in a manner that depended on the duration of infection. Second, using this model we evaluated antifungal efficacy both by the culture recovery method and histopathological examination. Two topical antifungal drugs, 8% ciclopirox nail lacquer and 5% amorolfine nail lacquer, were applied to the nail for 4 weeks in each group. On histopathological examination, two antifungal treatment groups showed no significant difference against the nontreated control group. However, there were a significantly low fungus-positive rate and intensity of the recovery of fungi on culture between antifungal treatment and nontreated control groups. We therefore suggest that we have established an in vivo model of onychomycosis that is useful for the evaluation of the efficacy of antifungal agents. PMID:21555762
Gupta, Chhavi; Das, Shukla; Ramachandran, V G; Saha, Rumpa; Bhattacharya, S N; Dar, Sajad Ahmad; Atri, Dharmendra
The immunology of onychomycosis is poorly understood. Th1 and Th17 are the principal effector cells responsible for protective immunity against fungi, while it is assumed that Th2 responses are associated with deleterious effects. The study was conducted to appraise the role of interleukin-6 (IL-6), transforming growth factor β (TGF-β) and immunoglobulin E (IgE) in onychomycosis patients and to study skin reactivity to trichophytin antigen in them. Serum samples of 60 cases of chronic onychomycosis and 30 healthy controls were assayed for serum IgE, IL-6 and TGF-β levels using specific immunoassay kits; 0.01 ml of trichophytin antigen, Candida antigen and phosphate-buffered saline using separate syringes were injected intradermal at three independent sites of the forearm in cases and controls. Serum IL-6 levels were significantly lower in cases as compared to controls, while serum TGF-β levels in both cases and controls were comparable. Serum IgE levels in cases were significantly higher when compared with controls. Thirty-eight patients showed immediate hypersensitivity response to trichophytin antigen, while none showed delayed hypersensitivity reaction to trichophytin antigen. Constant fungal antigenic stimuli induce a state of anergy as indicated by low serum IL-6 levels and the absence of delayed hypersensitivity reaction to trichophytin antigen in cases, leading to chronicity of infection. High total IgE may indicate a high probability of prior fungal sensitization.
Otašević, Suzana; Barac, Aleksandra; Pekmezovic, Marina; Tasic, Sinisa; Ignjatović, Aleksandra; Momčilović, Stefan; Stojanović, Predrag; Arsic Arsenijevic, Valentina; Hay, Roderick
Despite the increasing of onychomycosis caused by Candida spp., in referent literature, there is still data insufficiency about this nail infection. The objectives of this retrospective study were to determine epidemiological characteristics of Candida onychomycosis, the antifungal susceptibility of isolated species in vitro, and to compare the results of antifungal susceptibility testing with conducted treatment in period from 2011 to the end of March 2015. Out of 761 patients who were underwent clinical and mycological examinations, 137 had Candida species isolated from nails. The dominant species was Candida albicans (C. albicans) (36.59%) followed by C. parapsilosis (23.78%), C. krusei (9.76%), and C. guilliermondii (6.71%). Antifungal susceptibility in vitro testing showed good susceptibility to antimycotics, except C. krusei, which was resistance to fluconazole (FCZ) and isolates of C. tropicalis and C. glabrata which were dose dependent to itraconazole (ITZ) and fluconazole. Evaluation of medical histories determined that combined therapy, which included pulsed systemic regimen of ITZ with topical application of clotrimazole, had better clinical outcomes regarding the proscribed only topical application of clotrimazole. Multidisciplinary approach of dermatologists and mycologists is required in solving the problem of onychomycosis, which is the dominant nail disease.
Wen, Wei; Meng, Yaoyong; Xiao, Jun; Zhang, Pingli; Zhang, Hao
For the purpose of investigating the secondary structural changes of keratins in onychomycosis patient nail, Raman spectra of nail clippings from onychomycosis patients were obtained and used to describe the molecular structure differences from normal nail specimens. Raman spectroscopy revealed that nail from onychomycosis patients had a significant decrease in the content of the sulfur-containing amino acids in comparison to normal nail. And the spectral analysis also demonstrated that the disulfide bonds had the trend to the energetically less favored gauche-gauche-trans (g-g-t) forms in onychomycosis patient nail samples. These results showed that the increased amounts of less stable disulfide conformers were contributed to or associated with the nail brittleness observed in onychomycosis patients. We also found that the positions of the S-S band (500-550 cm-1) in onychomycosis patients were different, which gave us an indication that the disulfide groups might be related to the histopathological level and morphological characteristics. In the region of amide I, the α-helical (1652 cm-1) and β-sheet (1671 cm-1) content changed, these ratios (peak area of 1652 cm-1 divided by peak area of the 1671 cm-1) were between 0.67 and 0.75, while drastically altered ratios for the two conformers were changed to 0.25-0.63 in onychomycosis patient nail, the α-helix form seriously decreased in comparison to the normal nail. This result suggested unfolding of proteins and a more amorphous structure in the onychomycosis nail. On the other hand, the amide III (unordered) band intensity, assigned to the random coil form in normal nail clippings, at 1250 cm-1 is much higher than that for the amide III (α) content (1272 cm-1), and the peak area ratios of random coil band and α-helix band were about 10.00, while in the onychomycosis nail, these ratios were close to 2.00, the random coil form remarkably decreased. All the results of the present work implied that fungal erosion
Mayer, Eliza; Izhak, Ofer Ben; Bergman, Reuven
The diagnosis of onychomycosis, using direct microscopy and fungal cultures, is often negative despite the presence of disease. Periodic acid-Schiff (PAS) staining of nail clippings, using histopathological processing, may be positive in these cases. It is not always clear, however, whether the fungal elements detected by PAS staining are pathogenic fungi or some are saprophytes. We aimed to study the efficacy of histopathological PAS staining of nail clippings as a second-line diagnostic tool in onychomycosis. The study included 100 consecutive cases in which direct microscopy and fungal cultures from suspected onychomycosis were negative on one occasion or more. The obtained nail clippings were processed for routine histology, stained with hematoxylin and eosin and PAS, and examined microscopically. Of the 100 cases, 38 (38%) showed positive fungal elements. As a result, 9 patients had sought and received oral antifungal therapy and all achieved complete clinical cure. The histological examination also revealed parakeratosis and globules of plasma, which were statistically significantly more common in the fungal infected nail samples. This may indicate an ongoing inflammatory process associated with onychomycosis. Neutrophils and bacteria were not statistically and significantly more common in the fungal infected nails. We conclude that as a second-line diagnostic tool, PAS stain of nail clippings increases markedly the diagnostic yield of onychomycosis and, consequently, the outcome of therapy.
Morales-Cardona, Camilo A; Valbuena-Mesa, Martha C; Alvarado, Zulma; Solorzano-Amador, Andrea
Worldwide prevalence of non-dermatophyte mould onychomycosis has increased in recent years; however, available information on the topic is confusing and oftentimes contradictory, probably due to the small number of reported cases. The aim of this study was to determine and describe the aetiological agents, as well as the epidemiological and clinical characteristics of non-dermatophyte mould onychomycosis in a dermatology referral centre in Bogota, Colombia. A cross-sectional descriptive study was conducted between January 2001 and December 2011 among patients who attend the National Institute of Dermatology with a confirmed diagnosis of onychomycosis by non-dermatophytes moulds. There were 317 confirmed cases of non-dermatophyte mould onychomycosis in 196 women and 121 men whose average age was 43 years. Twenty-seven per cent of them had a history of systemic disease. The habit of walking and showering barefoot was the major infection-related factor. Distal and lateral subungual presentation was the most common pattern of clinical presentation. The most frequent non-dermatophyte mould was Neoscytalidium dimidiatum followed by Fusarium spp. No relationship was observed with predisposing factors previously reported in the literature. Clinical features found in this population are indistinguishable from onychomycosis caused by dermatophytes. High prevalence of N. dimidiatum found here was in contrast to a large number of studies where other types of moulds predominate.
Wanitphakdeedecha, Rungsima; Thanomkitti, Kanchalit; Bunyaratavej, Sumanas; Manuskiatti, Woraphong
Onychomycosis is a common nail disease, especially in older patients. Various treatment options are currently available for onychomycosis; however, their limitations include high failure rates, time-consuming nature, high cost and high risk of drug interactions. Previous studies on the treatment of dermatophyte onychomycosis with a long-pulsed 1064-nm Nd:YAG laser demonstrated excellent outcomes without severe side effects. To evaluate the efficacy and side effects of onychomycosis treatment with a long-pulsed 1064-nm Nd:YAG laser. Sixty-four onychomycotic nails (35 patients) were evaluated. The first treatment cycle involved treatment with a long-pulsed 1064-nm Nd:YAG laser in four sessions at 1-week intervals. A potassium hydroxide examination and fungal culture were performed every week during this treatment course and then at a 1-month follow-up visit. If either test was positive for a pathogenic organism, a second treatment cycle was performed. If the two tests produced negative results, each affected nail was followed up at 3- and 6-month visits after completion of the second treatment protocol. In cases of resistance (positive for a pathogenic organism after completion of the second treatment cycle), the onychomycotic nails were excluded from the study and treated by standard methods. Of all 64 nails evaluated, 59 completed the first cycle of treatment and 24 (40.7%) demonstrated mycological clearance at the 1-month follow up. Thirty-five of the 59 nails (59.3%) were positive for a pathogenic organism and underwent a second treatment cycle. Upon completion of the second treatment cycle, 28 nails remained enrolled in the study, and the mycological test results were negative in nine of these (31.2%). For all nails that completed the first or second treatment cycle, the overall cure rates at the 1-, 3- and 6-month follow-up visits were 63.5, 57.7 and 51.9%, respectively. Side effects were mild and limited to erythema and swelling after the laser procedure. Long
Ruíz-López, Patricia; Moreno-Coutiño, Gabriela; Fernández-Martínez, Ramón; Espinoza-Hernández, Jessica; Rodríguez-Zulueta, Patricia; Reyes-Terán, Gustavo
Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ≤450 cel μl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.
Ranawaka, Ranthilaka R; de Silva, S H Padmal
Onychomycosis shows a poor response to current topical, oral, or device-related antifungal therapies. The aim of this study was to identify factors influencing the cure rates of non-dermatophyte mold and Candida onychomycosis. Eighty-one patients who completed treatments were divided into "cured" and "non-cured" groups. The statistical significance of differences between the two groups was studied. Male gender (P < 0.01), long duration of disease before the initiation of treatment (P < 0.02), three or more infected nails (P < 0.0002), continuous exposure to water and detergents (P < 0.05), frequent exposure to mud and soil (P < 0.01), barefoot walking (P < 0.025), concomitant diabetes and hypertension (P < 0.04), eczema (P < 0.03), and associated paronychia (P < 0.01) had negative effects on cure rates of onychomycosis. Patient age, occupation, site of illness (hand, foot or big toe), type of disease (distal and lateral subungual onychomycosis, proximal subungual onychomycosis or total dystrophic onychomycosis), pathogenic fungi, and treatment modality had no statistically significant impact on cure rate. To minimize the failure rate of antifungal therapies in the treatment of onychomycosis, patients are advised to start treatment as soon as possible, and to avoid predisposing factors such as exposure to water, detergents, mud and soil, and barefoot walking. © 2016 The International Society of Dermatology.
Tanrıverdi, Sakine Tuncay; Hilmioğlu Polat, Süleyha; Yeşim Metin, Dilek; Kandiloğlu, Gülşen; Özer, Özgen
Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.
Helou, J; Maatouk, I; Hajjar, M A; Moutran, R
Until recently, pharmacologic molecules have been the only available treatments for onychomycosis. Laser treatments were introduced for recurrent or resistant cases or in patients in whom oral treatments are contra-indicated. Some devices were approved by the Food and Drug Administration (FDA). Neodymium yttrium aluminium garnet (Nd:YAG) is used for onychomycosis as a short-pulse or a long-pulse system. We aim to evaluate the efficacy of the short-pulse Nd:YAG in treating onychomycosis, its side effects, cure rates, and 12-month recurrence rates. Efficacy was evaluated based on a subjective measure of patient satisfaction on a scale from 1 to 10, and an objective measure based on the results of the mycologic cultures. Medical records of 30 patients were reviewed. Ages ranged from 22 to 85, with a mean of 44. Mycologic cure at 12 months was not achieved in 5 patients (16.67%) who had received laser treatment. None of these patients showed any signs of clinical improvement. Twenty patients (66.67%) were completely cured at 12 months, with corroborating negative mycologic cultures. The remaining five patients (16.67%) had discordance between their clinical cure status and their mycologic cultures. Side effects were reported by 7 patients out of 30 (33%): pain within 48 hours of the treatment session, burning sensation in the treated nail bed area. Our primary end point of negative mycologic cultures at 12 months was seen in 24 out of 30 (80%) of our patients. Similar culture cure rates have not been reported before, not even with systemic treatments with oral antifungals. However, few limitations should warrant us (False-negative results in fungal cultures; time limitation; sample size…). Still, we propose that this alternative should be offered for patients in whom antifungals are contraindicated or for patients previously treated, but not cured by oral antifungals, and in elderly and polymedicated patients. © 2015 Blackwell Verlag GmbH.
Elewski, Bom E.
Objective: To evaluate the benefits of efinaconazole topical solution, 10% on quality of life in onychomycosis patients. Methods: An analysis of 1,655 patients, aged 18 to 70 years, randomized to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled, 48-week studies evaluating safety and efficacy. The primary endpoint was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture); clinical improvement defined as ≤ 10-percent improvement in nail involvement both at Week 52. Quality of life was assessed using a validated OnyCOE-t™ questionnaire. Improvement in quality of life was compared in those patients clinically and not clinically improved. Results: Efinaconazole topical solution, 10%, was significantly more effective than vehicle irrespective of QoL domain. Greatest improvement in mean score was seen in those domains with the lowest baseline scores. All mean scores in the group considered to have clinically improved with efinaconazole exceeded 80.0 at Week 52. Mean treatment satisfaction scores with efinaconazole in those patients who were clinically improved increased from 79.9 (Week 24) to 89.2 (Week 52), compared to a corresponding drop in those patients considered not improved from 65.3 to 58.0. The correlation between change in percent affected nail and change in mean domain scores was significant with efinaconazole for all domains. Limitations: A period of 52 weeks may be too brief to evaluate improvement in quality of life in onychomycosis patients. Some of the questions in the OnyCOE-t questionnaire may be more relevant than others to the study population and the onychomycosis population as a whole. Conclusion: Once-daily efinaconazole topical solution, 10%, provided statistically greater improvement in all aspects of quality of life compared to vehicle. Improvement was most marked in those patients considered
Smijs, Threes; Dame, Zoë; de Haas, Ellen; Aans, Jan-Bonne; Pavel, Stan; Sterenborg, Henricus
Novel multifunctional photosensitizers (MFPSs), 5,10,15-tris(4-N-methylpyridinium)-20-(4-phenylthio)-[21H,23H]-porphine trichloride (PORTH) and 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE), derived from 5,10,15-Tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and designed for treatment of onychomycosis were characterized and their functionality evaluated. MFPSs should function as nail penetration enhancer and as photosensitizer for photodynamic treatment (PDT) of onychomycosis. Spectrophotometry was used to characterize MFPSs with and without 532 nm continuous-wave 5 mW cm(-2) laser light (± argon/mannitol/NaN3 ). Nail penetration enhancement was screened (pH 5, pH 8) using water uptake in nails and fluorescence microscopy. PDT efficacy was tested (pH 5, ± argon/mannitol/NaN3 ) in vitro with Trichophyton mentagrophytus microconida (532 nm, 5 mW cm(-2) ). A light-dependent absorbance decrease and fluorescence increase were found, PORTH being less photostable. Argon and mannitol increased PORTH and PORTHE photostability; NaN3 had no effect. PDT (0.6 J cm(-2) , 2 μm) showed 4.6 log kill for PORTH, 4.4 for Sylsens B and 3.2 for PORTHE (4.1 for 10 μm). Argon increased PORTHE, but decreased PORTH PDT efficacy; NaN3 increased PDT effect of both MFPSs whereas mannitol increased PDT effect of PORTHE only. Similar penetration enhancement effects were observed for PORTH (pH 5 and 8) and PORTHE (pH 8). PORTHE is more photostable, effective under low oxygen conditions and thus realistic candidate for onychomycosis PDT.
McAuley, W J; Jones, S A; Traynor, M J; Guesné, S; Murdan, S; Brown, M B
The treatment of onychomycosis remains problematic even though there are several potent antifungal agents available for patient use. The aim of this investigation was to understand whether the structural modifications that arise when a patient's nail become infected plates influences the permeation of drugs into the nail following topical application. It was hoped that through improving understanding of the nail barrier in the diseased state, the development of more effective topical treatments for onychomycosis could be facilitated. The permeation of three compounds with differing hydrophobicities, caffeine, terbinafine and amorolfine (clogD at pH 7.4 of -0.55, 3.72 and 4.49 respectively), was assessed across both healthy and onychomycosis infected, full thickness, human nail plate sections. Transonychial water loss (TOWL) measurements performed on the healthy and diseased nails supported previous observations that the nail behaves like a porous barrier given the lack of correlation between TOWL values with the thicker, diseased nails. The flux of the more hydrophilic caffeine was twofold greater across diseased in comparison with the healthy nails, whilst the hydrophobic molecules terbinafine and amorolfine showed no statistically significant change in their nail penetration rates. Caffeine flux across the nail was found to correlate with the TOWL measurements, though no correlation existed for the more hydrophobic drugs. These data supported the notion that the nail pores, opened up by the infection, facilitated the passage of hydrophilic molecules, whilst the keratin binding of hydrophobic molecules meant that their transport through the nail plate was unchanged. Therefore, in order to exploit the structural changes induced by nail fungal infection it would be beneficial to develop a small molecular weight, hydrophilic antifungal agent, which exhibits low levels of keratin binding. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Bseiso, Eman A; Nasr, Maha; Sammour, Omaima A; Abd El Gawad, Nabaweya A
The systemic treatment of onychomycosis has been hampered by the reported side effects of antifungals in addition to the limited blood circulation to the affected nails. Topical ungual treatment would circumvent the limitations of systemic onychomycosis treatment. Preparation and characterization of nail penetration enhancer containing nanovesicles (nPEVs) loaded with sertaconazole for topical treatment of onychomycosis. nPEVs were prepared using different nail penetration enhancers (N-acetyl-L-cysteine, thioglycolic acid, thiourea and ethanol) by the thin film hydration method, and characterized for their particle size, zeta potential, entrapment efficiency (EE%), elasticity, viscosity, physical stability and morphology. The selected nPEVs formula and the marketed Dermofix® cream were compared in terms of nail hydration, transungual drug uptake and antifungal activity against Trichophyton rubrum. N-acetyl-l-cysteine was the optimum nail penetration enhancer for incorporation within vesicles. nPEVs showed high EE% of sertaconazole ranging from 77 to 95%, a size ranging from 38-538 nm and a zeta potential ranging from +48 to +72 mV. The selected nPEVs formula displayed spherical morphology and good storage stability. Compared to the conventional marketed cream, the selected nPEVs formula showed 1.4-folds higher hydration and drug uptake enhancement into nail clippings. Furthermore, it showed significantly higher zone of inhibition for Trichophyton rubrum (20.9 ± 0.25 mm) than the marketed cream (11.6 ± 0.44 mm). Nail penetration enhancer containing nanovesicles (nPEVs) present a very promising option, worthy of clinical experimentation on onychomycotic patients.
McAuley, W.J.; Jones, S.A.; Traynor, M.J.; Guesné, S.; Murdan, S.; Brown, M.B.
The treatment of onychomycosis remains problematic even though there are several potent antifungal agents available for patient use. The aim of this investigation was to understand whether the structural modifications that arise when a patient’s nail become infected plates influences the permeation of drugs into the nail following topical application. It was hoped that through improving understanding of the nail barrier in the diseased state, the development of more effective topical treatments for onychomycosis could be facilitated. The permeation of three compounds with differing hydrophobicities, caffeine, terbinafine and amorolfine (clog D at pH 7.4 of −0.55, 3.72 and 4.49 respectively), was assessed across both healthy and onychomycosis infected, full thickness, human nail plate sections. Transonychial water loss (TOWL) measurements performed on the healthy and diseased nails supported previous observations that the nail behaves like a porous barrier given the lack of correlation between TOWL values with the thicker, diseased nails. The flux of the more hydrophilic caffeine was twofold greater across diseased in comparison with the healthy nails, whilst the hydrophobic molecules terbinafine and amorolfine showed no statistically significant change in their nail penetration rates. Caffeine flux across the nail was found to correlate with the TOWL measurements, though no correlation existed for the more hydrophobic drugs. These data supported the notion that the nail pores, opened up by the infection, facilitated the passage of hydrophilic molecules, whilst the keratin binding of hydrophobic molecules meant that their transport through the nail plate was unchanged. Therefore, in order to exploit the structural changes induced by nail fungal infection it would be beneficial to develop a small molecular weight, hydrophilic antifungal agent, which exhibits low levels of keratin binding. PMID:26969264
Ramalingam, R; Kunalan, S; Tang, M M
Onychomycosis is a common nail disease with numerous etiological pathogens. In order to determine and trend the local mycological pattern of culture-positive diseased nail samples sent from the Department of Dermatology, Hospital Kuala Lumpur, a five-year retrospective audit was carried out, which revealed that non-dermatophyte molds were the predominant fungi isolated, followed by yeasts and dermatophytes. This is similar to two previous studies in Malaysia, but varies greatly from other studies around the world which showed a dermatophyte-predominant prevalence. This could be due to the nature of the environment our patients encountered.
Godoy, P; Nunes, E; Silva, V; Tomimori-Yamashita, J; Zaror, L; Fischman, O
Fusarium species are common soil saprophytes and plant pathogens that have been frequently reported as etiologic agents of opportunistic infections in humans. We report eight cases of onychomycosis caused by Fusarium solani (4) and Fusarium oxysporum (4) in São Paulo, Brazil. These species were isolated from toenails in all cases. The infections were initially considered to be caused by dermatophytes. The clinical appearance of the affected toenails was leukonychia or distal subungual hyperkeratosis with yellowish brown coloration. The eight cases reported here suggest that Fusarium spp. should be taken into consideration in the differential diagnosis of tinea unguium.
Veasey, John Verrinder; Nappi, Flávio; Zaitz, Clarisse; Muramatu, Laura Hitomi
This is a retrospective study of 160 patients treated in private practice in São Paulo from March 2003 to March 2015. We analyzed 171 results of direct mycological examinations and fungal cultures from nail scrapings. The agreement between direct mycological examination results and fungal culture was satisfactory, consistent with the literature (kappa 0.603). The main agent identified was Trichophyton rubrum (51%). We observed an isolation rate of non-dermatophyte filamentous fungi superior to the literature (34%). Determining the agent is key to defining the appropriate onychomycosis treatment, and knowing the epidemiology of patients treated in private practice helps the dermatologist who works in this context. PMID:28225975
Pichardo-Geisinger, Rita; Mora, Dana C; Newman, Jill C; Arcury, Thomas A; Feldman, Steven R; Quandt, Sara A
Latino immigrant workers experience elevated rates of skin disease that result from their working and living conditions. Working in manual occupations exposes workers to a variety of challenges, including occlusive shoes, vigorous physical activity, and wet conditions. These challenges predispose workers to fungal infection. The objectives of this article are to examine the comorbidity of tinea pedis and onychomycosis and to identify possible risk factors among Latino immigrant poultry and nonpoultry workers in western North Carolina. Data were obtained from a cross-sectional study conducted between June 2009 and November 2010 in rural western North Carolina among 518 manual Latino immigrant workers to assess their occupational injuries. Participants completed a face-to-face interview and a dermatologic examination. Nearly one-third of the participants (32%) were diagnosed as having onychomycosis and more than one-third (37.8%) were diagnosed as having tinea pedis. There was a greater prevalence of tinea pedis in men than women (71.3% vs 28.7%, respectively). Of the 518 participants, 121 (23.5%) had both conditions. Participants who reported the use of occlusive shoes as "always" or "most of the time" had a higher prevalence of comorbid onychomycosis and tinea pedis than the rest of the group. Comorbidity of tinea pedis and onychomycosis is common among immigrant Latino men and women who perform manual labor. Further studies confirming the presence and type of dermatophyte should be conducted.
Sakamoto, Misao; Sugimoto, Noriaki; Kawabata, Hideki; Yamakawa, Eiko; Kodera, Nobuyuki; Pillai, Radhakrishnan; Tatsumi, Yoshiyuki
Effective transungual delivery of topical antifungal agents in onychomycosis has been hampered by poor nail permeation. To be effective they must have antifungal efficacy, and effectively permeate through the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. The therapeutic efficacy of efinaconazole topical solution, 10% has been established in two phase 3 clinical trials in distal lateral subungual onychomycosis. To investigate the transungual delivery of efinaconazole in onychomycosis patients and its fungicidal activity in the toenail. Concentrations of efinaconazole were determined as part of a multi-center, open label study in forty onychomycosis patients following repeated application of efinaconazole topical solution, 5% and 10% to the toenails over 28 days, with a 2-week follow-up. Fungicidal activity against T. rubrum in the ventral layer of human nails was determined using an in vitro human nail infection model (ChubTur®). Efinaconazole concentrations in the nail were four orders of magnitude higher than MIC values of efinaconazole against dermatophytes. Further, nail drug concentrations were not influenced by the presence of disease or nail thickness, and maintained at high antifungal levels post-treatment. Efinaconazole was effective in reducing fungal viability, suggesting that sufficient amounts of efinaconazole were being delivered into the ventral layer of the nail plate.
Effective transungual delivery of efinaconazole was demonstrated. The high efinaconazole concentrations in patient toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase 3 studies.
Gupta, Aditya K; Paquet, Maryse
Cosmetic improvement in nail appearance is a great concern to patients with onychomycosis. Although oral and topical treatments for onychomycosis can potentially eradicate the infection, unsightly nails may remain despite negative mycology. Laser-based devices have been approved for the temporary clearance of nails with onychomycosis, thus providing a means of improving the aesthetic appearance of the nails. A retrospective chart review of patients treated with a Nd:YAG 1064-nm laser and debridement for onychomycosis, and terbinafine 1% cream for associated tinea pedis, between July 2012 and February 2014 was performed to ascertain the proportion of patients who achieved clinical outcomes. A temporary improvement in the appearance of the target nail was observed in 78% of patients and the affected area of the nail plate was reduced by at least 50% from baseline in 46% of patients. It appears that patients whose great toenails are potentially infected with non-dermatophyte molds may particularly benefit from laser therapy. Higher clinical outcome rates were observed with administration of four or more treatments, but additional observations and/or studies are needed to optimize the regimen of laser therapy to improve the cosmetic appearance of infected nails.
Takahata, Y; Hiruma, M; Shiraki, Y; Tokuhisa, Y; Sugita, T; Muto, M
We assessed the safety and efficacy of pulse therapy with terbinafine tablets in 55 patients with dermatophytic onychomycosis. One pulse consisted of oral terbinafine tablets (500 mg day(-1)) given for 1 week usually followed by a 3-week interval. This regimen was repeated twice. Topical 1% terbinafine cream was applied daily. Efficacy was assessed based on both clinical and mycological examinations 1 year after treatment initiation. We observed a complete cure in 41 patients (74.5%), marked improved in three patients (5.6%), slight improvement in three patients (5.6%) and drop out in six patients (10.7%). Two patients (3.6%) discontinued terbinafine because of gastrointestinal disturbance (one patient) and drug-induced eruption (one patient). No patient had abnormal laboratory findings, including liver function tests. In summary, a regimen of three pulses of terbinafine therapy given daily for 1 week in combination with topical application of terbinafine cream appears to be safe and effective in treating dermatophytic onychomycosis and offers advantages in convenience and cost-effectiveness compared with continuous dosing.
Caneschi, César Augusto; Almeida, Angelina Maria de; Martins, Francislene Juliana; Hyaric, Mireille Le; Oliveira, Manoel Marques Evangelista; Macedo, Gilson Costa; Almeida, Mauro Vieira de; Raposo, Nádia Rezende Barbosa
Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a-4f) and p-hydroxybenzoic acid (9a-9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b-4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312μg/mL). On the other hand, the amide series (9a-9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C-11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.
Zaias, Nardo; Rebell, Gerbert; Escovar, Sandra
Asymmetric gait nail unit syndrome (AGNUS) is the result of asymmetric shoe pressure on the toes and foot caused by ubiquitous uneven flat feet that affect the gait. The pressure produces clinical changes in the toenails, which are identical to all clinical types of dermatophyte and opportunistic onychomycosis, yet they are dermatophytes-free. AGNUS produces additional signs that make it easy to identify. Its coexistence with fungal disease has resulted in reports describing new clinical types of onychomycosis, identifying signs of drug resistance, assessing severity index, and defining complete clinical cure when taking a systemic or topical antifungal, as well as "retronychia." These signs are typically seen in the toenails of patients with AGNUS. AGNUS has a mechanical etiology and can coexist with dermatophytosis, which is a hereditary disease. AGNUS can coexist with any other disease affecting the toenails and results in greater clinical severity than each condition individually. AGNUS is and has been the most common worldwide toenail abnormality in shoe-wearing societies.
Flores, Fernanda C; Rosso, Roberta S; Cruz, Letícia; Beck, Ruy C R; Silva, Cristiane B
Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL(-1)), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid(®) in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.
Tosti, A; Hay, R; Arenas-Guzmán, R
The aims of this workshop were to identify risk factors for onychomycosis and to reach consensus on the management of high-risk groups to allow the development of guidelines to help doctors recognize risk factors that complicate treatment. Previous Trichophyton rubrum infection, older age, abnormal nail morphology, immunodeficiency and genetic factors were identified as risk factors for initial infections. Risk factors for recurrence (relapse and re-infection) are largely the same. The experts agreed that the prevention of onychomycosis and its recurrence should be based on the correct treatment of tinea pedis, screening family members and adequate patient education. In addition, generic management recommendations for each high-risk group were discussed: * Immunosuppressed patients Usual dose and treatment length not appropriate Follow-up required Beware of drug interactions * Diabetics Prophylactic foot care combined with nail treatment Good opportunity for patient education, footwear, foot care, etc. Beware of drug interactions * Psoriatics and patients with abnormal nails Dermatophyte eradication does not restore normal nails * Children High failure rate possibly due to compliance problems.
Gupta, Aditya K; Drummond-Main, Chris; Cooper, Elizabeth A; Brintnell, William; Piraccini, Bianca Maria; Tosti, Antonella
Nondermatophyte mold (NDM) onychomycosis is difficult to diagnose given that NDMs are common contaminants of the nails and of the mycology laboratory. Diagnostic criteria and definition of cure are inconsistent between studies, which may affect the quality of published data. We identified 6 major criteria used in the literature: identification of the NDM in the nail by microscopy (using potassium hydroxide preparation), isolation in culture, repeated isolation in culture, inoculum counting, failure to isolate a dermatophyte in culture, and histology. Most studies used 3 or more of these (range = 1-5). We recommend using at least 3 of the criteria to rule out contamination; these should include potassium hydroxide preparation for direct microscopy and isolation of the organism in culture. We review geographic distribution and clinical presentations associated with different NDMs. The treatment with the greatest quantity of data and highest reported cure rates is terbinafine, for the treatment of Scopulariopsis brevicaulis and Aspergillus species infections. Topicals such as ciclopirox nail lacquer may also be effective (data originating from Scopulariopsis brevicaulis and Acremonium species infections), especially when combined with chemical or surgical avulsion of the nail. We recommend that future studies use (and clearly indicate) at least 3 of the main criteria for diagnosis, and report the clinical type of onychomycosis and the isolated organism. When evaluating different treatments, we suggest that authors clearly define their efficacy outcomes. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Ruiz-Esmenjaud, Julieta; Arenas, Roberto; Rodríguez-Alvarez, Mauricio; Monroy, Elena; Felipe Fernández, Ramón
Tinea pedis and onychomycosis in childhood are unusual, The previous reported prevalence range from 4.2 to 8.2%. In a mestizo population, in the South of Mexico a 3.4% has been found. To determine the frequency of dermatophytosis of feet and toenails in scholars in an Indian Mazahua community. A total of 456 children were studied. The age range from 5 to 15 years of age (average 11.4). Only 71 children with suggestive lesions of dermatophytosis were studied (15.57%). Mycological samples (66/71) and a KOH and Chlorazol black, and cultures on Mycocel agar were performed. 71 children (15.57%) presented suggestive lesions of dermatophytosis of the feet and toenails. A fungal infection was demonstrated in 13 cases (18%), 8 males and 5 females (mean age 12.3 years), but pathogenic fungi were isolated only in 7 (10%). All of them with tinea pedis and three also had toenail involvement (4.2%) and also Trichosporon sp was isolated in two cases and Candida albicans in one. We found a low frequency of tinea pedis and onychomycosis in children from this Mazahua community. The environmental factors such as humidity, and the frequently use of rubber and leather shoes instead of the traditional "huarache" (sandals), make them prone to maceration and can be cofactors in the development of mycotic infections and in the high incidence of pitted keratolysis (29.5%).
Repka, Michael A; Mididoddi, Praveen K; Stodghill, Steven P
The purpose of this investigation was to study the physico-chemical properties of hot-melt extruded films containing ketoconazole and to determine the influence of 'nail etching' on film bioadhesion and drug permeability for the assessment of topical onychomycosis therapies. Hot-melt extrusion (HME) was used to prepare films containing 20% w/w ketoconazole. Ketoconazole 0.125% gel was also prepared using Carbopol 974P NF. Films were processed at a temperature range of 115-120 degrees C utilizing a Killion extruder (KLB-100), and were evaluated for post-extrusion drug content, content uniformity, bioadhesion, thermal behavior and nail drug permeation. The extruded films demonstrated excellent content uniformity and post-processing drug content. Tensile and peel tests were recorded to determine the bioadhesive profiles. In this study, work of adhesion and peak adhesive force determinations using the peel tests provided more sensitive results for evaluating the bioadhesivity of the HME films than the tensile tests. The in vitro permeability profiles have demonstrated, that nail samples treated with an 'etchant' demonstrated a significant increase in drug permeability compared to control. Differential scanning calorimetry (DSC) thermograms indicated that ketoconazole was in solid solution within the HME films. These findings are encouraging for the future design and formulation of novel drug delivery systems for the topical treatment of onychomycosis.
Bhatt, V; Pillai, R
Transungual drug delivery of antifungals is considered highly desirable to treat common nail disorders such as onychomycosis, due to localized effects, and improved adherence resulting from minimal systemic adverse events. However, the development of effective topical therapies has been hampered by poor nail penetration. An effective topical antifungal must permeate through, and under the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. We present here the formulation development program to provide effective transungual and subungual delivery of efinaconazole, the first topical broad spectrum triazole specifically developed for onychomycosis treatment. We discuss the important aspects encompassing the formulation development program for efinaconazole topical solution, 10%, focusing on its solubility in a number of solvents, in vitro penetration through the nail, and in vivo efficacy. Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a unique combination of ingredients added to an alcohol-based formulation to provide low surface tension and good wetting properties. This low surface tension is believed to affect effective transungual delivery of efinaconazole and believed to provide a dual mode of delivery by accessing the nail bed by wicking into the space between the nail and nail plate. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
Chowdhary, Anuradha; Randhawa, H S; Sharma, Sonal; Brandt, Mary E; Kumar, Sunil
The etiologic role of Malassezia furfur in onychomycosis is a contentious diagnostic problem because its keratinolytic ability has never been verified. This case report describes the isolation of M. furfur from the infected nails of a child clinically diagnosed with onychomycosis, and discusses the role of this organism as an etiologic agent/colonizer. The patient presented with subungual hyperkeratosis and onycholysis without associated paronychia. Budding yeast cells compatible with M. furfur were repeatedly demonstrated in KOH wet mounts of damaged nails, histopathology of hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stained sections showed penetration of fungal elements between deeper layers of keratin, and numerous colonies of M. furfur were isolated on three consecutive occasions from nail specimens collected from different areas of hand and toenail lesions. No evidence of nail invasion by dermatophytic or nondermatophytic filamentous fungi were found by direct microscopy or culture. Microscopy and culture were negative following 12 weeks of ketoconazole treatment, which resulted in growth of healthy nail plates with normal beds. We can infer from these observations that M.furfur was an etiologic agent rather than a colonizer in the patient's nails even though direct keratinolytic character of this fungus was not demonstrated.
Ribeiro, Clarissa Santos de Carvalho; Zaitz, Clarisse; Framil, Valéria Maria de Souza; Ottoboni, Thaíssa Santos de Carvalho; Tonoli, Melissa Santos de Carvalho; Ribeiro, Renata Pinto; Ribeiro, Renata Pinheiro
Onychomychosis, a nail fungus infection is the most frequent nail ailment, constituting about half of all nail disorders. It can be caused by dermatophytes, non-dermatophytes, yeasts and Prothoteca spp. Methods include 5407 samples of patients with suspected onychomycosis, studied from January 2002 to December 2006, by direct mycological examination and fungi culture. The diagnosis of onychomycosis was confirmed in samples from 3822 direct mycological and/or culture positive. The diagnosis was established by culture for fungi. Among the 1.428 identified agents, the dermatophytes were responsible for 68.6% (N = 980) of cases, followed by yeasts with 27.6% (N = 394), non-dermatophytes fungi with 2.2% (N = 31), Prothoteca spp with 0.1% (N = 2), and associations with 1.5% (N = 22). Females were more affected, with 66% (N = 2527) of cases, and the most affected age group ranged from 31 to 60 years of age (median 47 years). Fungal microbiota is often changed in the world, both quantitatively and qualitatively, and is affected by several environmental factors. Thus, the periodic review of the composition of this microbiota is important to evaluate the epidemiology and thus proportion a better therapeutic response.
Morgado, Luciano Ferreira; Trávolo, Ana Regina Franchi; Muehlmann, Luís Alexandre; Narcizo, Paulo Souza; Nunes, Rodrigo Barbosa; Pereira, Pedro Alencar Gomes; Py-Daniel, Karen Rapp; Jiang, Cheng-Shi; Gu, Jinsong; Azevedo, Ricardo Bentes; Longo, João Paulo Figueiró
The conventional treatment of onychomycosis, a common fungal infection, consists in the use of local and systemic drugs for 4-6 months. This long protocol is often ineffective due to patient compliance, and usually promotes important collateral effects such as liver and kidney failure. As the alternative, Photodynamic Therapy (PDT) has been used as a noninvasive alternative local treatment for onychomycosis due to the reduction of systemic side effects, fact indicates their use for patients undergoing other systemic treatments. In the present article, we evaluated the effectiveness, as well as the safety of PDT mediated by Aluminium-Phthalocyanine Chloride, entrapped in nanoemulsions, as a drug carrier, to treat onychomycosis in a proof of concept clinical trial. To the date, this is the first published clinical trial that uses PDT mediated by nanomedicines to treat onychomycosis. As main results, we can highlight the safety of the clinical protocol and the antifungal effectiveness similar to the conventional treatments. We observed the (1) clinical cure of 60% of treated lesions; (2) the absence of local and systemic adverse effects; (3) from these clinically healed lesions, 40% were negative for fungal infection in laboratorial exams; and (4) nails that presented negative fungal culture were kept without fungal infection for at least four weeks. The innovation of this approach is the absence of collateral effects, due to the local therapeutically treatment, and the possibility to repeat the treatment without inducing fungal resistance, a fact that indicates this approach as a possible alternative protocol for onychomycosis management. Copyright © 2017 Elsevier B.V. All rights reserved.
Espírito-Santo, Graciela Araújo Do; Leite, Diniz Pereira; Hoffmann-Santos, Hugo Dias; Dias, Luciana Basili
Onychomycosis is an infection of the nail plate by fungal microorganisms. This infection has an important social impact on women and men and poses a major challenge for its treatment. The traditional treatment of onychomycosis involves the use of topical and oral antifungal agents. However, the presence of adverse effects frequently associated with oral antifungals, their high cost, and their potential interactions with other drugs reflect some of the problems associated with conventional therapy. The current report details the evaluation of a 1340nm laser as monotherapy for toenails affected by onychomycosis. A 1340nm, neodymium-yttrium:yttrium-aluminum-perovskite (Nd:YAP) (e) laser (Etherea, Industra technologies, Brazil) was used with the following treatment parameters: a spot size of 6mm, pulse duration of 5ms, fluence of 22 to 25J/cm2, and repetition rate of 1.5 to 2.5Hz. In all, 72 toenails were evaluated in 30 patients who had clinical and laboratory confirmation of onychomycosis. The efficacy of treatment was measured by the degree of patient satisfaction on a scale of 0 to 10 and by mycological cure evidenced by direct mycological exam and culture. Considering three applications of laser therapy and a clinical/laboratory follow-up period of 12 weeks, monotherapy with 1340nm laser was not effective, since 93.3 percent of the assessed patients remained without clinical and mycological cure. Despite reports of variable success rates with the use of different lasers for the treatment of onychomycosis, it is not yet possible to state that this therapeutic alternative is indicated for the treatment of these infections, mainly due to the limited number of patients and/or nail plates evaluated and the controversial results described in the literature. PMID:28979665
Zhang, Jing; Lu, Sha; Huang, Huaiqiu; Li, Xiqing; Cai, Wenying; Ma, Jianchi; Xi, Liyan
Onychomycosis remains difficult to cure by traditional methods. The aim of this study was to evaluate the efficacy of combination therapy with a fractional erbium yttrium aluminum garnet (Er:YAG) laser and 5 % amorolfine lacquer on onychomycosis. Nine patients with bilateral nails affected by distal and lateral subungual onychomycosis were included. The bilateral nails of each patient were divided into two groups. The 20 affected nails on one side of each patient as group 1 were treated with a fractional Er:YAG laser once a week and 5 % amorolfine lacquer twice weekly, while the 20 nails on the symmetrical side of each patient as group 2 were treated with amorolfine lacquer only. The laser treatment was conducted at weeks 1, 2, 3, 4, 8, and 12 in group 1. The clinical improvement, onychomycosis severity index (OSI), maximum linear clear nail growth (MLCNG), and mycological cure rate were evaluated. At week 24, 18 of 20 (90 %) nails in group 1 had achieved obvious clinical responses. The mean OSI score showed a significant decrease (5.24) and the average MLCNG was 3.1 mm in group 1. At week 24, 15 of 20 (75 %) nails achieved a negative mycological examination in group 1, compared with four of 20 (20 %) nails in group 2. The treatments were well-tolerated by most patients. This clinical study suggests that combination therapy of a fractional 2940-nm Er:YAG laser and 5 % amorolfine lacquer is an effective, safe, and convenient treatment method for onychomycosis.
Torres-Rodríguez, Josep M; Sellart-Altisent, Maite
We report a case of proximal fold cellulitis in both big toes, associated with a bilateral proximal onychomycosis and an intertrigo of the fourth space due to Fusarium solani. The infection occurred in an immunocompetent man with diabetes mellitus type II. Apparently, the infection was acquired in a tropical country and once the patient was in Spain the infection progressed causing nail detachment (onychomadesis). Seven months later a relapse that affected the left toenail occurred. The patient was treated topically with chemical toenail avulsion contained 40% urea associated with bifonazole followed by ciclopirox-olamine nail lacquer for 12 months. Complete cure without relapse was observed after 10 years of follow-up. In vitro antifungal susceptibility study demonstrated that two of the recovered isolates were both resistant to itraconazole and voriconazole.
Succi, Isabella B; Bernardes-Engemann, Andréa R; Orofino-Costa, Rosane
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.
Kubota, Natsuki; Takei-Masuda, Naomi; Yamada, Tsuyoshi; Maeda, Mari; Alshahni, Mohamed Mahdi; Abe, Shigeru; Tabata, Yuji; Maebashi, Kazunori
Despite the existing treatment options for onychomycosis, there remains a strong demand for potent topical medications. ME1111 is a novel antifungal agent that is active against dermatophytes, has an excellent ability to penetrate human nails, and is being developed as a topical agent for onychomycosis. In the present study, we investigated its mechanism of action. Trichophyton mentagrophytes mutants with reduced susceptibility to ME1111 were selected in our laboratory, and genome sequences were determined for 3 resistant mutants. The inhibitory effect on a candidate target was evaluated by a spectrophotometric enzyme assay using mitochondrial fractions. Point mutations were introduced into candidate genes by a reverse genetics approach. Whole-genome analysis of the 3 selected mutants revealed point mutations in the structural regions of genes encoding subunits of succinate dehydrogenase (complex II). All of the laboratory-generated resistant mutants tested harbored a mutation in one of the subunits of succinate dehydrogenase (SdhB, SdhC, or SdhD). Most of the mutants showed cross-resistance to carboxin and boscalid, which are succinate dehydrogenase inhibitors. ME1111 strongly inhibited the succinate-2,6-dichlorophenolindophenol reductase reaction in Trichophyton rubrum and T. mentagrophytes (50% inhibitory concentrations [IC50s] of 0.029 and 0.025 μg/ml, respectively) but demonstrated only moderate inhibition of the same reaction in human cell lines. Furthermore, the target protein of ME1111 was confirmed by the introduction of point mutations causing the amino acid substitutions in SdhB, SdhC, and SdhD found in the laboratory-generated resistant mutants, which resulted in reduced susceptibility to ME1111. Thus, ME1111 is a novel inhibitor of the succinate dehydrogenase of Trichophyton species, and its mechanism of action indicates its selective profile. PMID:26596944
Yin, Zhiqiang; Xu, Jiali; Luo, Dan
As the most frequently used systemic antifungal agents for onychomycosis, terbinafine and itraconazole have both proved to have the conditions of recurrence in various degrees during follow-up period after end of therapy; very little is known about their comparative recurrences after long-term follow-up. We conducted a meta-analysis of available trials to compare the long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole. Meta-analysis was performed by the Review Manager version 5.0.25. Risk ratio and 95% confidence intervals were calculated by the fixed effect model. Five trials and total 251 eligible patients were included in this meta-analysis. The combined risk ratio of the meta-analysis comparing terbinafine with itraconazole for mycological recurrence rate was 0.44 (95% CI 0.29-0.66), which suggests that itraconazole therapy is more likely to produce mycological recurrence compared with terbinafine therapy.
Boukachabine, K; Agoumi, A
Cases of onychomycosis diagnosed by mycological examination in the parasitology and mycology laboratory (Children Hospital, Rabat, Marocco) over the 22-year period, between 1982 and 2003, have been reviewed. 17,177 dermatophytes have been isolated in 4,940 patients. Dermatophytes presented 61.46% of onychomycosis, yeasts Candida albicans were responsible in 25.5%, moulds in 1.53% and for 12% fungi identification was not determined (positive direct examination or negative direct examination and culture despite typical clinical aspect). The most frequent dermatophyte was Trichophyton rubrum (83.6%), followed by Trichophyton violaceum var. glabrum (9%) and Trichophyton mentagrophytes var. interdigitale (6.9%). Candida albicans was the prevalent yeast. Moulds were mainly Fusarium spp. (47%), followed Scopulariopsis brevicaulis (16%) and Aspergillus spp. (12%). Dermatophytes and moulds most commonly infected the toenails, yeasts the fingernails.
Sugimoto, Noriaki; Hosaka, Shinya; Katafuchi-Nagashima, Maria; Arakawa, Yoshio; Tatsumi, Yoshiyuki; Jo Siu, William; Pillai, Radhakrishnan
Onychomycosis is a common fungal nail disease that is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. Keratin affinity of topical drugs is an important physicochemical property impacting therapeutic efficacy. To be effective, topical drugs must penetrate the nail bed and retain their antifungal activity within the nail matrix, both of which are adversely affected by keratin binding. We investigated these properties for efinaconazole, a new topical antifungal for onychomycosis, compared with those of the existing topical drugs ciclopirox and amorolfine. The efinaconazole free-drug concentration in keratin suspensions was 14.3%, significantly higher than the concentrations of ciclopirox and amorolfine, which were 0.7% and 1.9%, respectively (P < 0.001). Efinaconazole was released from keratin at a higher proportion than in the reference drugs, with about half of the remaining keratin-bound efinaconazole removed after washing. In single-dose in vitro studies, efinaconazole penetrated full-thickness human nails into the receptor phase and also inhibited the growth of Trichophyton rubrum under the nail. In the presence of keratin, efinaconazole exhibited fungicidal activity against Trichophyton mentagrophytes comparable to that of amorolfine and superior to that of ciclopirox. In a guinea pig onychomycosis model with T. mentagrophytes infection, an efinaconazole solution significantly decreased nail fungal burden compared to that of ciclopirox and amorolfine lacquers (P < 0.01). These results suggest that the high nail permeability of efinaconazole and its potent fungicidal activity in the presence of keratin are related to its low keratin affinity, which may contribute to its efficacy in onychomycosis. PMID:24752277
Sugiura, Keita; Sugimoto, Noriaki; Hosaka, Shinya; Katafuchi-Nagashima, Maria; Arakawa, Yoshio; Tatsumi, Yoshiyuki; Jo Siu, William; Pillai, Radhakrishnan
Onychomycosis is a common fungal nail disease that is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. Keratin affinity of topical drugs is an important physicochemical property impacting therapeutic efficacy. To be effective, topical drugs must penetrate the nail bed and retain their antifungal activity within the nail matrix, both of which are adversely affected by keratin binding. We investigated these properties for efinaconazole, a new topical antifungal for onychomycosis, compared with those of the existing topical drugs ciclopirox and amorolfine. The efinaconazole free-drug concentration in keratin suspensions was 14.3%, significantly higher than the concentrations of ciclopirox and amorolfine, which were 0.7% and 1.9%, respectively (P < 0.001). Efinaconazole was released from keratin at a higher proportion than in the reference drugs, with about half of the remaining keratin-bound efinaconazole removed after washing. In single-dose in vitro studies, efinaconazole penetrated full-thickness human nails into the receptor phase and also inhibited the growth of Trichophyton rubrum under the nail. In the presence of keratin, efinaconazole exhibited fungicidal activity against Trichophyton mentagrophytes comparable to that of amorolfine and superior to that of ciclopirox. In a guinea pig onychomycosis model with T. mentagrophytes infection, an efinaconazole solution significantly decreased nail fungal burden compared to that of ciclopirox and amorolfine lacquers (P < 0.01). These results suggest that the high nail permeability of efinaconazole and its potent fungicidal activity in the presence of keratin are related to its low keratin affinity, which may contribute to its efficacy in onychomycosis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Tsang, Chi-Ching; Hui, Teresa W S; Lee, Kim-Chung; Chen, Jonathan H K; Ngan, Antonio H Y; Tam, Emily W T; Chan, Jasper F W; Wu, Andrea L; Cheung, Mei; Tse, Brian P H; Wu, Alan K L; Lai, Christopher K C; Tsang, Dominic N C; Que, Tak-Lun; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y
Thirteen Aspergillus isolates recovered from nails of 13 patients (fingernails, n=2; toenails, n=11) with onychomycosis were characterized. Twelve strains were identified by multilocus sequencing as Aspergillus spp. (Aspergillus sydowii [n=4], Aspergillus welwitschiae [n=3], Aspergillus terreus [n=2], Aspergillus flavus [n=1], Aspergillus tubingensis [n=1], and Aspergillus unguis [n=1]). Isolates of A. terreus, A. flavus, and A. unguis were also identifiable by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The 13th isolate (HKU49(T)) possessed unique morphological characteristics different from other Aspergillus spp. Molecular characterization also unambiguously showed that HKU49(T) was distinct from other Aspergillus spp. We propose the novel species Aspergillus hongkongensis to describe this previously unknown fungus. Antifungal susceptibility testing showed most Aspergillus isolates had low MICs against itraconazole and voriconazole, but all Aspergillus isolates had high MICs against fluconazole. A diverse spectrum of Aspergillus species is associated with onychomycosis. Itraconazole and voriconazole are probably better drug options for Aspergillus onychomycosis.
de Oliveira, Guilherme Bueno; Antonio, João Roberto; Antonio, Carlos Roberto; Tomé, Fernanda Alves
BACKGROUND Onychomycosis is a fungal infection of the nails caused in most cases by dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Despite numerous available antifungal drugs for therapy of this infection, the cure rate is low, with high rates of relapse after treatment and side effects. OBJECTIVES To present a new option for the treatment of onychomycosis, in search of a more effective and rapid method than conventional ones. METHODS Patients underwent two sessions of CO2 fractional laser 10.600nm associated with photodynamic therapy. Mycological and digital photography were performed before and after the treatment. RESULTS McNemar test with continuity correction and degrees of freedom = 1: for clinical cure rate, 13.06, with p=0.00005; for mycological cure, 17.05, with p=0.00005; 72% felt fully satisfied with the procedure. CONCLUSIONS The use of fractional CO2 laser 10.600nm associated with photodynamic therapy can be effective in the treatment of onychomycosis, decreasing the risk of systemic lesions that may be triggered with prolonged use of oral antifungals. PMID:26375214
García-Romero, M T; Granados, J; Vega-Memije, M E; Arenas, R
Onychomycosis is known to have predisposing factors and a high prevalence within families that cannot be explained by within-family transmission. We determined the frequency of HLA-B and HLA-DR haplotypes in 25 families of Mexican patients with onychomycosis in order to define the role of the class II major histocompatibility complex (MHC) in genetic susceptibility to this infection. Seventy-eight subjects participated in the study, 47 with onychomycosis and 31 healthy individuals. The frequencies of the HLA-B and HLA-DR haplotypes were compared with those found in first-degree relatives without onychomycosis and in a historic control group of healthy individuals. The frequencies in the controls were similar to those of the healthy relatives of the patients. However, on comparison of the patients with historic controls, we detected a higher frequency of the HLA-DR8 haplotype (P=.03; odds ratio, 1.89; 95% confidence interval, 0.98-36). These findings suggest that there are polymorphisms in genes of the MHC that increase susceptibility to onychomycosis, particularly haplotype HLA-DR8.
García-Romero, M T; Granados, J; Vega-Memije, M E; Arenas, R
Onychomycosis is known to have predisposing factors and a high prevalence within families that cannot be explained by within-family transmission. We determined the frequency of HLA-B and HLA-DR haplotypes in 25 families of Mexican patients with onychomycosis in order to define the role of the class II major histocompatibility complex (MHC) in genetic susceptibility to this infection. Seventy-eight subjects participated in the study, 47 with onychomycosis and 31 healthy individuals. The frequencies of the HLA-B and HLA-DR haplotypes were compared with those found in first-degree relatives without onychomycosis and in a historic control group of healthy individuals. The frequencies in the controls were similar to those of the healthy relatives of the patients. However, on comparison of the patients with historic controls, we detected a higher frequency of the HLA-DR8 haplotype (P=.03; odds ratio, 1.89; 95% confidence interval, 0.98-36). These findings suggest that there are polymorphisms in genes of the MHC that increase susceptibility to onychomycosis, particularly haplotype HLA-DR8.
Renner, Regina; Grüsser, Kathrin; Sticherling, Michael
Onychomycosis is one of the most prevalent nail disorders in adults, where conventional topical therapy is often protracted and in most cases ineffective. On the other hand, systemic/oral therapy is not suitable for all patients and might be associated with relevant side effects. Therefore, laser therapy can be used as an alternative to or extension of existing treatment protocols. We used diode laser treatment for onychomycosis to evaluate the efficacy of this treatment as single therapy as well as in combination with an ongoing antimycotic treatment. We used a 1,064-nm diode laser (FOX Laser, ARC Laser GmbH, Germany) in pulse mode with a spot size of 4 mm. The laser's settings were: 8 W, with a pulse duration of 80 ms and a repetition rate of 5.6 Hz; the energy fluence/pulse was 5.1 J/cm(2), and a total energy of 250-500 J for large and/or thickened nails (digit I), 120-200 J for medium nails (digits II-IV) and 60-120 J for small and/or very thin nail plates (digit V) was counted in the laser display. Two to three passes where applied continuously over the entire area of the nail (nail plate, nail folds and eponychium) in a grid pattern. Eighty-two affected toenails were treated at least twice every 8 weeks; all nails treated were clinically diagnosed as onychomycosis. The evaluation of the treated nails was conducted by two dermatologists, initially by semiquantitative visual examination, followed by evaluation with the Onychomycosis Severity Index (OSI). In addition, the patients were asked to state their satisfaction with the treatment and its results in a written questionnaire. All nails showed an improvement ranging between 14 and 56% including the analytical evaluation scale (OSI). Two dermatologists evaluated 34 nails. Both reported significant improvement and/or good clinical improvement, which corresponds to about 41% for both evaluations. The mean OSI of all patients was 18.9/19.9 before treatment which changed to 14.3/14.8 after treatment. This
Oz, Yasemin; Qoraan, Iman; Oz, Ali; Balta, Ilknur
Diabetes patients are particularly susceptible to fungal infections because their vascular and immunological systems are compromised. The present study aimed to determine prevalences of tinea pedis and onychomycosis, factors predisposing to their development, and antifungal susceptibilities of causative fungal species against fluconazole, itraconazole, and terbinafine in patients with type 2 diabetes mellitus (DM). Study groups were defined according to hemoglobin A1C rates of ≥6.5% for the diabetes group and ≤5.7% for control subjects. A total of 600 diabetes subjects and 152 control subjects were evaluated. Rates of onychomycosis and tinea pedis in diabetes patients, and associations with age, gender, blood glucose level, duration of diabetes and serum lipid profile were investigated, as were the distribution and antifungal susceptibility of agents isolated. Patients with onychomycosis and/or tinea pedis numbered 85 in the diabetes group and nine in the control group (P = 0.006). The development of onychomycosis or tinea pedis was significantly related to increasing age and male gender. Although the most common agents were dermatophytes, non-dermatophyte fungal isolates were not uncommon. Terbinafine was the most effective drug against dermatophytes but was invalid for non-dermatophyte isolates by in vitro antifungal susceptibility testing. The development of onychomycosis or tinea pedis was significantly related to type 2 DM, increasing age, and male gender. The most common isolate was Trichophyton rubrum. The isolation and identification of the fungus is important to the effective management of tinea pedis and onychomycosis in diabetes patients because non-dermatophyte fungi can cause these infections. © 2016 The International Society of Dermatology.
Mohri, Shinobu; Watanabe, Shinichi; Toshio, Kusunoki; Shibuya, Kazutoshi; Nishiyama, Yayoi; Abe, Michiko; Uno, Jun; Oguri, Toyoko; Maeasaki, Shigefumi; Ikeda, Reiko; Abe, Shigeru
After the rapid progress in therapeutic pharmaceutics against onychomycosis caused by dermatophytes in the 1990s, an optimal therapeutic strategy for individual patients with the onychomycosis has become possible for clinical dermatologists. In this review, we discuss on clinical problems concerning this disease and propose recommendable treatments for each patient with topical and/or systemic use of antifungal agents. Finally, with consideration of already published therapeutic guidelines, we stress the necessity of "order-made" therapy for each patient with his/her medical status and wishes taking into account.
Vlahovic, Tracey C.; Korotzer, Andrew
Background: The current definition of complete cure is considered too stringent to reflect the true benefit of onychomycosis treatment seen in general practice and may limit the use of newer topical agents in mild-to-moderate disease. In addition, outcomes reported in clinical trials do not consistently report secondary endpoints, making data comparison difficult. Methods: The authors review the clinical data reported on two new topical antifungals, efinaconazole and tavaborole, in light of the latest thinking of more practical approaches to assess improvement and treatment success. Results: Almost 20 percent (19.7%) of patients treated with efinaconazole had absence of clinical signs, and almost a third (31.6%) had ≤10 percent affected toenail and mycologic cure at Week 52. Cure rates for tavaborole (<10% affected toenail and mycologic cure) were 15.3 percent and 17.9 percent at week 52. With both topical treatments, cure rates were higher when only negative culture was considered. Conclusion: These clinical cure rates likely better reflect the efficacy we see in practice. It is probable that efficacy would be further improved with longer treatment courses and/or longer follow-up periods and appropriate prophylactic strategies. This clinical judgment is predicated by any risk of nonadherence or disease recurrence. PMID:28210388
Thatai, Purva; Sapra, Bharti
The present study was aimed to optimize, develop, and evaluate microemulsion and microemulsion-based gel as a vehicle for transungual drug delivery of terbinafine hydrochloride for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the composition of microemulsion having amount of oil (X 1), Smix (mixture of surfactant and cosurfactant; X 2), and water (X 3) as the independent variables. The formulations were assessed for permeation (micrograms per square centimeter per hour; Y 1), particle size (nanometer; Y 2), and solubility of the drug in the formulation (milligrams per milliliter; Y 3). The microemulsion containing 3.05% oil, 24.98% Smix, and 71.96% water was selected as the optimized formulation. The microemulsion-based gel showed better penetration (∼5 folds) as well as more retention (∼9 fold) in the animal hoof as compared to the commercial cream. The techniques used to screen penetration enhancers (hydration enhancement factor, ATR-FTIR, SEM, and DSC) revealed the synergistic effect of combination of urea and n-acetyl cysteine in disruption of the structure of hoof and hence, leading to enhanced penetration of drug.
Arenas, R; Fernández, G; Domínguez, L
An open, comparative, randomized study was conducted using griseofulvin or itraconazole for the treatment of onychomycosis of the foot. Group I (45 patients) received itraconazole and Group II (45 patients) received griseofulvin. Each group was divided into three subgroups that received different topical treatment: antimycotic cream (isoconazole 1%), keratolytic cream (urea 40%), or placebo cream. The itraconazole group showed complete clearance in combination with isoconazole cream in 73.3% (11 of 15 patients), in combination with keratolytic cream in 78.5% (11 of 14 patients), and in combination with placebo cream in 91.6% (11 of 12 patients). The griseofulvin group showed complete clearance in combination with isoconazol cream in 46.1% (7 of 15 patients), in combination with keratolytic cream in 42.8% (6 of 15 patients), and in combination with placebo cream in 26.6% (4 of 15 patients). The itraconazole group showed better results compared with the griseofulvin group when the chi-square statistical method was used.
Zalacain, A; Obrador, C; Martinez, J P; Viñas, M; Vinuesa, T
Due to the increase of choices relative to antifungals, there is a need to improve the standardization of in vitro methods used to determine the antifungal susceptibility of fungal pathogens. Our study evaluated the in vitro susceptibility of filamentous fungi isolated from patients with toenail onychomycosis against itraconazole, ciclopirox, eberconazole, fluconazole and terbinafine. The minimum inhibitory concentration (MIC) of these antifungal agents was determined with 100 isolates, including dermatophytes (70 strains) and non-dermatophyte molds (30 strains). The susceptibility of fungal isolates was measured by using a technique modified for dermatophytes (0.5 × 10(3)-0.5 × 10(4) conidia/ml as inocula) which followed the procedures described by the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST) and the Clinical and Laboratory Standard Institute (CLSI M38-A). MIC ranges were 0.016-8.0 μg/ml for itraconazole, ciclopirox and eberconazole, 0.063-32.0 μg/ml for fluonazole, and 0.004-2.0 μg/ml for terbinafine. In vitro susceptibility tests indicated that eberconazole has a broad antimicrobial profile, including dermatophytes, as well as other filamentous fungi. Terbinafine was active (0.016-0.250 μg/ml) against dermatophytes.
Turner, Rob; Weaver, Sean; Caserta, Francesco; Brown, Marc B
The aim of this study was to use in vitro nail models to investigate the potential of a novel base formulation (Recura) containing either fluconazole or miconazole for the treatment of onychomycosis in comparison to two commercial comparators (Jublia and a Penlac generic). Initially, a modified Franz cell was used, where sections of human nail served as the barrier through which drug penetrated into an agar-filled chamber infected with dermatophytes. A second study was performed using a novel infected nail model where dermatophytes grew into human nail and adenosine triphosphate levels were used as biological marker for antimicrobial activity. The novel enhancing system Recura increased the permeation of both existing drugs through human nail sections mounted in a modified Franz cell. Furthermore, the infected nail model also confirmed that the system also enhanced the permeation through infected nail resulting in a decrease in adenosine triphosphate levels superior (P ≤ 0.05) to Penlac generic and equivalent (P > 0.05) to the commercial comparator Jublia. This study demonstrated that with the use of a novel permeation-enhancing formulation base, Recura enhances delivery of miconazole and fluconazole when applied ungually such that the efficacy was equivalent or superior to commercial comparators. Such a topically applied system has the possibility of overcoming the systemic side effects of antifungals when taken orally.
Chrysosporium pannorum (Link) Hughes is a soil keratinophilic fungus present in organic residues, on human skin surface and in the general environment of human beings. Clear evidence for the pathogenicity of this fungus for human beings was lacking. In 1999, a case of fungal infection in a chow-chow dog and its owner was published, where Chrysosporium pannorum (Link) Hughes was determined as the only possible infection trigger. The State Hygiene Institute in Bratislava repeatedly confirmed the cultivation results. Chrysosporium pannorum (Link) Hughes was detected in the material provided by a ZOO: camel, tiger and antelope hair, whereby the same finding as in the dog mentioned above was described, i.e. extensive alopecic foci of various size. Since 2000 the cultivations have been monitored with due care. Eight positive cultivations of Chrysosporium pannorum (Link) Hughes have been detected until now, two of them in patients with a flair for horticulture. In a male patient, fingernail onychomycosis with affected skin on forearms, hands and fingers was determined. In a female patient only nail plates were affected. Chrysosporium pannorum was confirmed to be the only possible pathogen. Therapy with itraconazole produced excellent results in both patients and no relapses were recorded. Based on our repeated findings it is concluded that the evidence for non-pathogenicity of Chrysosporium pannorum should be revised.
Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori
Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori
Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333
Li, Yan; Xu, Jing; Zhao, Jun-Ying; Zhuo, Feng-Lin
Background: Onychomycosis is a fungal infection of the nail plate and subungual area. In this study, we examined the efficacy of laser treatment using self-controlled study programs involving a long-pulsed Nd:YAG 1064-nm laser combined with oral medication. Methods: Self-controlled strategies were followed in this study. The patients received treatment with oral itraconazole in conjunction with long-pulsed Nd:YAG 1064-nm laser treatment at the nails of the unilateral limb once a week for a total of four times. A total of 84 affected nails were divided into Group A (mild to moderate) and Group B (severe) according to disease severity. Affected nails with the same Scoring Clinical Index for Onychomycosis scores were selected to compare the therapeutic effects of the pure medication treatment group and the combination treatment group with a 24-week follow-up period. Results: In Group A, at the 8th, 16th, and 24th weeks of follow-up, the efficacies in the pure medication treatment group were 81.0%, 81.0%, and 90.5%, respectively, while those in the combination treatment group were 100%, 95.2%, and 90.5%, respectively. The differences between groups were not significant (8th week: χ2 = 4.421, P > 0.05; 16th week: χ2 = 2.043, P > 0.05; 24th week: χ2 = 0.00, P > 0.05). In Group B, at the 8th, 16th, and 24th weeks of follow-up, the efficacies in the pure medication treatment group were 61.9%, 66.7%, and 52.4%, respectively, while those in the combination treatment group were 95.2%, 90.5%, and 100%, respectively. The differences between groups at the 8th and 24th weeks of follow-up were statistically significant (8th week: χ2 = 6.929, P < 0.05; 24th week: χ2 = 13.125, P < 0.05). Conclusions: For patients with mild or moderate onychomycosis, we recommended a pure medication treatment or combination treatment with medication and laser. For those patients with severe onychomycosis, we recommended a combination of medication and laser therapy. PMID:27503017
Potter, Lori P; Mathias, Susan D; Raut, Monika; Kianifard, Farid; Tavakkol, Amir
Background This research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t™, a questionnaire specifically designed to measure patient-reported outcomes (PRO) associated with toenail onychomycosis. Methods 504 patients with toenail onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD® trial completed the OnyCOE-t™ at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t™ is composed of 6 multi-item scales and 1 single-item scale. These include a 7-item Toenail Symptom assessment, which comprises both Symptom Frequency and Symptom Bothersomeness scales; an 8-item Appearance Problems scale; a 7-item Physical Activities Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3-item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific items are included in the OnyCOE-t™. Clinical data, in particular the percent clearing of mycotic involvement in the target toenail, and OnyCOE-t™ responses were used to evaluate the questionnaire's reliability, validity, responsiveness, and the minimally clinical important difference (MCID). Results The OnyCOE-t™ was shown to be reliable and valid. Construct validity and known groups validity were acceptable. Internal consistency reliability of multi-item scales was demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72, 1.31, 1.13, and 1.11, respectively). MCID was evaluated for three different clinical measures, and indicated that approximately an 8.5-point change (on a 0 to 100 scale) was clinically meaningful based on a 25% improvement in target nail clearing. Conclusion The OnyCOE-t™ questionnaire is a unique, toenail-specific PRO questionnaire that can be
Piraccini, Bianca M; Bruni, Francesca; Alessandrini, Aurora; Starace, Michela
The aim of this study was to verify efficacy and tolerability of sequential therapy with 40% urea paste followed by 1% bifonazole urea in mild to moderate distal subungual onychomycosis of the toenails. It was an seven weeks open study. Sequential patients affected by mild to moderate distal subungual onychomycosis of the toenails agreed to apply on the affected nail 40% urea paste in occlusion overnight for the first three weeks, with gentle scraping with a spatula the following day, followed by 1% bifonazole cream once a day for 4 weeks. Efficacy evaluation was based on mycology, clinical photography and investigator and patient assessment. Tolerability assessment included subjective and objective evaluations. The ten patients enrolled (mean age 57.5 years) completed the study. Onychomycosis was caused in nine cases by dermatophytes and by Scopulariopsis brevicaulis in one patient. At the end of the study, mycological examination was negative in all 10 patients. Clinical photographs showed a reduction of the percentage of the nail affected by onychomycosis in 8 cases, cure in 2 and considerable reduction of the nail thickness, already evident after 7 days. All patients reported to be satisfied by the treatment, which was judged easy to perform and well tolerated. Treatment with urea and bifonazole is effective and well tolerated, and easy to do also by elderly patients.
Ghannoum, Mahmoud; Isham, Nancy; Herbert, Jacqueline; Henry, William; Yurdakul, Sam
TDT 067 is a novel carrier-based dosage form (liquid spray) of 15 mg/ml of terbinafine in Transfersome that has been developed to deliver terbinafine to the nail bed to treat onychomycosis. In this study, we report the in vitro activities of TDT 067 against dermatophytes, compared with those of the Transfersome vehicle, naked terbinafine, and commercially available terbinafine (1%) spray. The MICs of TDT 067 and comparators against 25 clinical strains each of Trichophyton rubrum, T. mentagrophytes, and Epidermophyton floccosum were determined according to the CLSI M38-A2 susceptibility method (2008). Minimum fungicidal concentrations (MFCs) were determined by subculturing visibly clear wells from the MIC microtiter plates. TDT 067 demonstrated potent activity against the dermatophyte strains tested, with an MIC range of 0.00003 to 0.015 μg/ml. Overall, TDT 067 MIC(50) values (defined as the lowest concentrations to inhibit 50% of the strains tested) were 8-fold and 60-fold lower than those of naked terbinafine and terbinafine spray, respectively. The Transfersome vehicle showed minimal inhibitory activity. TDT 067 demonstrated lower MFC values for T. rubrum and E. floccosum than naked terbinafine and terbinafine spray. TDT 067 has more potent antifungal activity against dermatophytes that cause nail infection than conventional terbinafine preparations. The Transfersome vehicle appears to potentiate the antifungal activity of terbinafine. Clinical investigation of TDT 067 for the topical treatment of onychomycosis is warranted.
Barot, Bhavesh S; Parejiya, Punit B; Patel, Hetal K; Gohel, Mukesh C; Shelat, Pragna K
The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion-based gel of terbinafine for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the amount of oil (X(1)), Smix (mixture of surfactant and cosurfactant; X(2)) and water (X(3)) in the microemulsion. The formulations were assessed for globule size (in nanometers; Y(1)) and solubility of drug in microemulsion (in milligrams per milliliter; Y(2)). The microemulsion containing 5.75% oil, 53.75% surfactant-cosurfactant mixture and 40.5% water was selected as the optimized batch. The globule size and solubility of the optimized batch were 18.14 nm and 43.71 mg/ml, respectively. Transmission electron microscopy showed that globules were spherical in shape. Drug containing microemulsion was converted into gel employing 0.75% w/w carbopol 934P. The optimized gel showed better penetration and retention in the human cadaver skin as compared to the commercial cream. The cumulative amount of terbinafine permeated after 12 h was 244.65 ± 18.43 μg cm(-2) which was three times more than the selected commercial cream. Terbinafine microemulsion in the gel form showed better activity against Candida albicans and Trichophyton rubrum than the commercial cream. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.
Ghannoum, Mahmoud; Isham, Nancy; Herbert, Jacqueline; Henry, William; Yurdakul, Sam
TDT 067 is a novel carrier-based dosage form (liquid spray) of 15 mg/ml of terbinafine in Transfersome that has been developed to deliver terbinafine to the nail bed to treat onychomycosis. In this study, we report the in vitro activities of TDT 067 against dermatophytes, compared with those of the Transfersome vehicle, naked terbinafine, and commercially available terbinafine (1%) spray. The MICs of TDT 067 and comparators against 25 clinical strains each of Trichophyton rubrum, T. mentagrophytes, and Epidermophyton floccosum were determined according to the CLSI M38–A2 susceptibility method (2008). Minimum fungicidal concentrations (MFCs) were determined by subculturing visibly clear wells from the MIC microtiter plates. TDT 067 demonstrated potent activity against the dermatophyte strains tested, with an MIC range of 0.00003 to 0.015 μg/ml. Overall, TDT 067 MIC50 values (defined as the lowest concentrations to inhibit 50% of the strains tested) were 8-fold and 60-fold lower than those of naked terbinafine and terbinafine spray, respectively. The Transfersome vehicle showed minimal inhibitory activity. TDT 067 demonstrated lower MFC values for T. rubrum and E. floccosum than naked terbinafine and terbinafine spray. TDT 067 has more potent antifungal activity against dermatophytes that cause nail infection than conventional terbinafine preparations. The Transfersome vehicle appears to potentiate the antifungal activity of terbinafine. Clinical investigation of TDT 067 for the topical treatment of onychomycosis is warranted. PMID:21411586
Velasquez-Agudelo, Verónica; Cardona-Arias, Jaiberth Antonio
Onychomycosis is a highly prevalent disease worldwide. There is no standard test for its diagnosis, which remains costly, wasteful, and is sometimes delayed. The diagnostic tests for this disease are few and discordant. The objective was to evaluate the diagnostic validity, performance, and accuracy of culture, nail clipping with Periodic Acid-Schiff -PAS- staining (biopsy), and direct potassium hydroxide (KOH) examination for the study of onychomycosis. A systematic review was conducted via meta-analysis using 5 databases and 21 search strategies. An ex ante protocol was applied with inclusion and exclusion criteria. Quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool, and the sensitivity, specificity, predictive values, likelihood ratios, diagnostic odds ratios, receiver operating characteristic (ROC) curves, and proportion of correctly diagnosed patients were evaluated with the meta-analysis of studies of evaluations of diagnostic and screening tests (Meta-DiSc) and Epidat using a random effects model. The efficiency or accuracy of the three tests is influenced by the methodological quality of the studies. These values are lower for KOH and culture and higher for biopsy in moderate quality studies. The diagnostic tests evaluated in this meta-analysis independently showed acceptable validity, performance, and efficiency, with nail clipping with PAS staining outperforming the other two tests.
Isham, N.; Long, L.
The treatment of onychomycosis has improved considerably over the past several decades following the introduction of the oral antifungals terbinafine and itraconazole. However, these oral agents suffer from certain disadvantages, including drug interactions and potential liver toxicity. Thus, there is a need for new topical agents that are effective against onychomycosis. ME1111 is a novel selective inhibitor of succinate dehydrogenase (complex II) of dermatophyte species, whose small molecular weight enhances its ability to penetrate the nail plate. In this study, we determined the antifungal activity of ME1111 against dermatophyte strains, most of which are known to cause nail infections, as measured by the MIC (n = 400) and the minimum fungicidal concentration (MFC) (n = 300). Additionally, we examined the potential for resistance development in dermatophytes (n = 4) following repeated exposure to ME1111. Our data show that the MIC90 of ME1111 against dermatophyte strains was 0.25 μg/ml, which was equivalent to that of the comparators amorolfine and ciclopirox (0.25 and 0.5 μg/ml, respectively). ME1111 was fungicidal at clinically achievable concentrations against dermatophytes, and its MFC90s against Trichophyton rubrum and Trichophyton mentagrophytes were 8 μg/ml, comparable to those of ciclopirox. Furthermore, ME1111, as well as ciclopirox, did not induce resistance in 4 dermatophytes tested. Our studies show that ME1111 possesses potent antifungal activity and suggest that it has low potential for the development of resistance in dermatophytes. PMID:26055386
Mididoddi, Praveen K; Repka, Michael A
The objectives of this investigation were to study the physico-chemical properties of hot-melt extruded (HME) films for onychomycosis and to determine the stability of the model antifungal drug incorporated within these films. The influence of etching and instrument variables on the bioadhesion of these drug delivery systems for the human nail was also studied. Six 250 g batches (F1-F6) of hydroxypropyl cellulose (HPC) and/or poly(ethylene oxide) films containing ketoconazole (20%) were extruded using a Killion extruder (Model KLB-100). The thermal properties of HME films were investigated using differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) was used to examine the surface morphology of the films and X-ray diffraction (XRD) was used to investigate the crystalline properties of the drugs, physical mixtures as well as the HME films. Stability studies were performed on the films stored at 25 degrees C/60%RH. The bioadhesive properties of these films were investigated on the human nail (ex vivo) using a Texture Analyzer. The nail samples tested were either non-treated (control) or treated with an etching gel. The parameters measured were peak adhesion force (PAF) and area under the curve (AUC). The Hansen solubility parameter was calculated using a combination of Hoy and Hoftyzer/Van Krevelen methods to estimate the likelihood of drug-polymer miscibility. SEM provided direct physical evidence of the physical state of the drug within the films. The theoretical post-extrusion content of ketoconazole remaining in the six film batches ranged from 90.3% (+/-2.2) to 102.4% (+/-9.0) for up to 6 months and from 83.9% (+/-3.6) to 91.6% (+/-3.0) for up to 12 months. Bioadhesion studies of HPC film tested on 'etched' nails recorded significantly higher PAF and AUC than that of the non-treated 'control' nails. Ketoconazole was found to be relatively stable during the extrusion process. Melting points corresponding to the crystalline drugs were not
Zhou, Bing Rong; LU, Yan; Permatasari, Felicia; Huang, He; Li, Jin; Liu, Juan; Zhang, Jia An; Luo, Dan; Xu, Yang
Abstract Background: To evaluate the efficacy of fractional carbon dioxide (CO2) laser combined with luliconazole 1% cream for the treatment of onychomycosis and to compare it with that of fractional CO2 laser alone. Methods: This was a randomized, parallel group, 2-arm, positive-controlled, single-center, superiority trial with a 1:2 allocation ratio. Sixty patients with clinical and mycological diagnosis of onychomycosis were enrolled from the Dermatology Department of the First Affiliated Hospital of Nanjing Medical University in Nanjing, China from March 2015 to May 2015. Patients were randomized following simple randomization procedures (computerized random number generator) into 2 groups; L group only received 12 sessions of laser treatment at 2-week interval for 6 months, while L + D group received 12 sessions of laser treatment at 2-week interval combined with luliconazole 1% cream once daily for 6 months. This was not a blind trial. The main outcome measures were the clinical efficacy rate (CER) assessed from the percentage of fully and >60% normal-appearing nails and the mycological clearance rate (MCR) assessed from the percentage of nails with negative fungal microscopy. There were no changes to trial outcome measures after the trial commenced. Results: A total of 60 patients (N = 233 nails) completed treatments and follow-up, and were randomized and divided into 2 groups: L group (31 patients, N = 108 nails) and L + D group (29 patients, N = 115 nails). The CER and MCR of L + D group were 69.6% and 57.4%, respectively. L + D group showed significantly higher CER (69.6% vs 50.9%; χ2 = 8.1, P = 0.004) and MCR (57.4% vs 38.9%; χ2 = 7.6, P = 0.006) compared with those in L group. Some patients experienced mild pain during laser treatment, but there was no bleeding or oozing during or after treatment. There were no adverse effects reported during the observation period. Conclusion: Fractional CO2 laser treatment
Pal, Paulami; Thakur, R S; Ray, Subhabrata; Mazumder, Bhaskar
The main objective of this study is to develop a safer non-invasive treatment for nail infections since the current treatment regimen has drawbacks like, incidence of systemic side-effects and higher cost. Proposed topical treatment on the other hand can drastically improve the situation, hence highly desirable. This work was undertaken with a hypothesis to develop a transungual microemulsion gel for topical treatment of onychomycosis. Benzyl alcohol and isopropyl myristate were used as oil, Pluronic F68 as surfactant and ethanol as co surfactant, in double-distilled water and loading itraconazole as the model antifungal drug. Pseudo-ternary phase diagram was developed by titrating different ratios of total oil and water with total surfactant, and Km ratio was fixed at 1:1. Microemulsion formulations were prepared based on the phase diagram and incorporated in gels by adding Carbopol 934P. Nail permeation enhancers like urea and salicylic acid were used to increase drug permeation through the nail plate. Parameters like drug loading, clarity, particle size distribution, drug entrapment efficiency (DEE), drug release profile, release kinetics and nail uptake were checked for the evaluation of the formulations. Complete release of drug from the formulation varied from 60 to 120 min. The optimized formulation had DEE of 92.75%, complete drug release in 60 min and highest nail uptake of 0.386%/mm(2) (39 µg of drug) with 5% urea as nail permeation enhancer. The formulation may prove beneficial in safer treatment of onychomycosis.
Mayser, P A; Gries, A; Hamrouni, N
A 12-year-old with a functional circulatory disturbance had toe nail onychomycosis caused by Trichophyton rubrum. There were no other underlying diseases. Oral therapy with terbinafine 125 mg once weekly in addition to ciclopirox nail lacquer was ineffective. Two years later the disease worsened and A. versicolor was found in pure culture. A preparation of 10% terbinafine HCl in a 20% urea ointment (Onychomal®) applied daily for 4 weeks, then once weekly resulted in complete cure after 7 months.
Scherer, William P; Scherer, Michael D
An investigative study was performed to compare the results from two mycology laboratories for the diagnosis of onychomycosis in a geriatric population and to determine the possible pharmacologic treatments based on the two laboratories' results. In this study, 85 cases of suspected onychomycosis involving men and women 65 years and older from a nursing home setting in South Florida were used. Samples were taken from the hallux toenail and sent to two different mycology laboratories for fluorescent potassium hydroxide preparation and microscopic examination of a fungal culture. Of the 85 cases studied, the two mycology laboratories reported similar potassium hydroxide preparation results for 58.8% of the patients and similar fungal culture results for genus and species identification for 37.6% of the patients. When the potassium hydroxide preparation and fungal culture results were combined, the two mycology laboratories reported similar results for only 27.1% of the patients. As a result of the two mycology laboratories' findings, the possible US Food and Drug Administration-approved pharmacologic treatments may differ for 43.5% of the patients studied. The discrepancy between the two independent laboratories leaves physicians to question the reproducibility of fluorescent potassium hydroxide preparation and fungal culture analysis in a geriatric patient population for the diagnosis of onychomycosis.
Tiwari, Nikita; Pandit, Raksha; Gaikwad, Swapnil; Gade, Aniket; Rai, Mahendra
Aim: The authors report the biological synthesis of zinc oxide nanoparticles (ZnO-NPs) from the petals extract of Rosa indica L. (rose). Its efficacy was evaluated against two dermatophytes: namely: Trichophyton mentagrophytes and Microsporum canis which cause onychomycosis. The activity of antibiotics against the tested dermatophytes was enhanced, when evaluated in combination with ZnO-NPs. Methods and results: The synthesised ZnO-NPs were preliminary detected by using ultraviolet UV visible spectroscopy, which showed specific absorbance. The ZnO-NPs were further characterised by nanoparticle tracking analysis (NTA), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction and Zetasizer. Moreover, nanoparticles containing nail paint (nanopaint) was formulated and its antifungal activity was also assessed against T. mentagrophytes and M. canis. ZnO-NPs and formulated nanopaint containing ZnO-NPs, both showed significant antifungal activity. The maximum activity was noted against M. canis and lesser against T. mentagrophytes. Minimum inhibitory concentration of ZnO-NPs was also determined against the dermatophytes causing onychomycosis infection. Conclusion: ZnO-NPs can be utilised as a potential antifungal agent for the treatment of onychomycosis after more experimental trials.
Watanabe, Shinichi; Kishida, Hiroshi; Okubo, Akihiro
Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20-50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.
Emtestam, L; Kaaman, T; Rensfeldt, K
Onychomycosis is difficult to cure as this requires eradication of the primary infection and protection of new areas of growth from reinfection. A new topical treatment (K101) has been developed. The aim of this study was to assess the efficacy, safety and tolerability of K101 treatment of distal subungual onychomycosis. This was a 24-week (plus 2-week washout), multicentre, randomised, double-blind, placebo-controlled study in 493 patients with distal subungual onychomycosis (K101, n = 346; placebo, n = 147), stratified according to degree of nail involvement. More patients with ≤50% nail involvement achieved the primary endpoint (mycological cure after 26 weeks) in the K101 group (27.2%) than placebo (10.4%; P = 0.0012). Proportions for patients with 51-75% involvement were 19.1% for K101 and 7.0% for placebo (not significant). More patients applying K101 than placebo judged that their condition had improved from week 2 (P = 0.0148) to week 24 (P = 0.0004). No safety issues were identified. K101 provides early visible improvements in nail appearance and a clinically meaningful antifungal activity.
Parekh, Manoj; Ramaiah, Girisha; Pashilkar, Prachi; Ramanujam, Ranjani; Johnston, Peter; Ilag, Leodevico L
Most of the current anti-fungal treatments are chemical-based, fungistatic, have low efficacy in the treatment of tinea and toxicity concerns, while onychomycosis remains recalcitrant to most antifungal therapies. The study aimed to establish the fungicidal, efficacy and safety profile of Calmagen® dermaceutical cream and lotion containing AMYCOT® as a topical treatment in patients with severe to very severe presentations of fungal skin (tinea) and nail infections (onychomycosis). A randomized, placebo-controlled, double blind, parallel, single centre study was conducted on 28 subjects with severe to very severe tinea or onychomycosis. All patients were randomized in a ratio of 1:1 for treatment or placebo group. Subjects in the treatment arm received Calmagen® cream or lotion, while subjects in the placebo arm received a similar inert topical preparation. Tinea subjects were treated with cream for four weeks, while onychomycosis subjects were treated with lotion for 12 weeks. Mycological cure, the primary endpoint, was assessed by three parameters: KOH (potassium hydroxide) smear, fungal culture and live spore count. Clinical cure was defined as Investigator Global Assessment (IGA) response of 'cleared' or 'excellent'. All three parameters constituting mycological cure were confirmed in 92.8% (13/14) of subjects in the treatment arm, while all 14 subjects in the placebo arm remained positive for KOH smear. Calmagen® cream and lotion treatment showed a significant improvement in all three parameters: KOH smear, (95% CI (Calmagen): 79.4, 100.0; 95% CI (placebo): 0.0, 0.0; p < 0.0001); fungal culture (95% CI (Calmagen); 100.0, 100.0; 95% CI (Placebo): 17.0, 100.0; p < 0.0019); and live spore count (95% CI (Calmagen): 100.0, 100.0; 95% CI (Placebo): 17.0, 100.0; p < 0.0019). Clinical cure was achieved in all subjects in the treatment arm while none in the placebo arm were clinically cured. No treatment-related adverse effects were observed in either group
Matthieu, L; De Doncker, P; Cauwenbergh, G; Woestenborghs, R; van de Velde, V; Janssen, P A; Dockx, P
Nail-matrix kinetics were studied in 21 patients (19 with onychomycosis, two with tinea corporis) as soon as taking itraconazole (Sporanox) 100 mg daily for up to 7 months. Itraconazole was detected in the distal nail as soon as 1 month after the start of therapy (42 ng/g in fingernails and 16 ng/g in toenails). During the course of treatment, this concentration rose and reached a mean of 160 ng/g in fingernail clippings and 197 ng/g in toenail clippings. Moreover, in fingernails of 12 out of 21 patients and in toenails of six out of 20 patients, itraconazole was detected in the distal nail clippings before full outgrowth of the fastest-growing nail. In most patients, itraconazole was detected in the distal nail clippings earlier than would be expected if the drug were incorporated only via the nail matrix, indicating that in addition to the nail matrix, a second route of penetration into the nail exists, i.e. the nail bed.
Gupta, Aditya K; Simpson, Fiona C
The route of antifungal drug entry into the nail plate and the underlying nail bed plays an important role in determining the efficacy of therapy. Oral antifungal agents reach the nail bed and nail plate by being ingested and achieving antifungal levels in the blood stream that are well in excess of the minimum inhibitory concentration. The reticular circulation at the distal end of the digit enables the drug to reach the nail bed, the proximal matrix and the lateral nail folds. The drug then diffuses into the proximal, ventral and lateral nail plate. The primary route of drug delivery for topical lacquers is transungual, with drug applied to the dorsal aspect of the nail plate and penetrating to the underlying nail bed. The new topical agents approved in the US for the treatment of onychomycosis are solutions with lower viscosity and increased nail penetration characteristics; therefore, these agents penetrate through the transungual route, but also through the space between the nail plate and the nail bed. This subungual route is an important method of drug delivery and is able to in part circumvent the thickness of the nail plate.
Moț, Augustin C; Pârvu, Marcel; Pârvu, Alina E; Roşca-Casian, Oana; Dina, Nicoleta E; Leopold, Nicolae; Silaghi-Dumitrescu, Radu; Mircea, Cristina
Rhodotorula mucilaginosa was isolated from a patient with onychomycosis, and identification was confirmed by morphological and cultural characteristics as well as by DNA molecular analysis. Antifungal agents naftifine (10 mg/mL, active substance in Exoderil) and bifonazole (10 mg/mL, active substance in Canespor) were tested in different concentrations to assess in vitro effects on fungal growth and carotenoid synthesis. The antifungal mechanisms of action of naftifine and bifonazole against R. mucilaginosa isolates were similar and affected the biosynthetic pathway of ergosterol. For the first time, this research demonstrates that naftifine affects the carotenoid biosynthetic pathway, producing depigmentation of R. mucilaginosa in solid and liquid media. Furthermore, depigmentation was a reversible process; naftifine-treated yeast cells that were depigmented resumed carotenoid production upon transfer to fresh media. Raman and UV-vis spectrophotometry in conjunction with chromatographic analysis detected changes in carotenoids in yeast cells, with torulene decreasing and B-carotene increasing after repigmentation. Transmission electron micrographs revealed critical ultrastructural modifications in the depigmented cells after naftifine treatment, i.e., a low-electron-density cell wall without visible mucilage or lamellate structure.
Akkus, Gamze; Evran, Mehtap; Gungor, Dilek; Karakas, Mehmet; Sert, Murat; Tetiker, Tamer
Objective: Impaired cellular immunity and reduced phagocytic function of polymorphonuclear leukocytes facilitate the development of skin fungal and bacterial infections due to uncontrolled hyperglycemia in diabetic patients. In our study, we aimed to assess onychomycosis and/or tinea pedis frequency in diabetic patients, and effects on the development of chronic complications, particularly foot ulcer. Methods: We included 227 diabetic patients in the study. Forty-three patients had diabetic foot ulcer. We screened and recorded demographic characteristics, HbA1c levels of patients, and presence of complications We examined patients dermatologically, and collected samples by scalpel from skin between toes, and from sole, toe nail, and area surrounding nails from suspected to have fungal infection. Results: Native positivity between toes was higher in men compared to women (p<0.05). We obtained significant relation between HbA1c elevation and native positivity between toes (p<0.05). Fungal infection between toes, at sole and toe nail significantly increased in patients with diabetic foot ulcer compared to patients without diabetic foot ulcer (p<0.05). Moreover, native positivity in patients with diabetic foot ulcer correlated with presence of fungal infection examination findings (p<0.05). Conclusion: Fungal infections were more frequently observed in the presence of poor glycemic control and peripheral vascular disease in diabetic patients in compliance with the literature, and the presence of fungal infection may also responsible for the development of foot ulcers. PMID:27648034
Akkus, Gamze; Evran, Mehtap; Gungor, Dilek; Karakas, Mehmet; Sert, Murat; Tetiker, Tamer
Impaired cellular immunity and reduced phagocytic function of polymorphonuclear leukocytes facilitate the development of skin fungal and bacterial infections due to uncontrolled hyperglycemia in diabetic patients. In our study, we aimed to assess onychomycosis and/or tinea pedis frequency in diabetic patients, and effects on the development of chronic complications, particularly foot ulcer. We included 227 diabetic patients in the study. Forty-three patients had diabetic foot ulcer. We screened and recorded demographic characteristics, HbA1c levels of patients, and presence of complications We examined patients dermatologically, and collected samples by scalpel from skin between toes, and from sole, toe nail, and area surrounding nails from suspected to have fungal infection. Native positivity between toes was higher in men compared to women (p<0.05). We obtained significant relation between HbA1c elevation and native positivity between toes (p<0.05). Fungal infection between toes, at sole and toe nail significantly increased in patients with diabetic foot ulcer compared to patients without diabetic foot ulcer (p<0.05). Moreover, native positivity in patients with diabetic foot ulcer correlated with presence of fungal infection examination findings (p<0.05). Fungal infections were more frequently observed in the presence of poor glycemic control and peripheral vascular disease in diabetic patients in compliance with the literature, and the presence of fungal infection may also responsible for the development of foot ulcers.
Vila, Taissa Vieira Machado; Rozental, Sonia; de Sá Guimarães, Claudia Maria Duarte
Onychomycoses represent approximately 50 % of all nail diseases worldwide. In warmer and more humid countries like Brazil, the incidence of onychomycoses caused by non-dermatophyte molds (NDM, including Fusarium spp.) or yeasts (including Candida albicans) has been increasing. Traditional antifungal treatments used for the dermatophyte-borne disease are less effective against onychomycoses caused by NDM. Although some laser and light treatments have demonstrated clinical efficacy against onychomycosis, their US Food and Drug Administration (FDA) approval as "first-line" therapy is pending, partly due to the lack of well-demonstrated fungicidal activity in a reliable in vitro model. Here, we describe a reliable new in vitro model to determine the fungicidal activity of laser and light therapies against onychomycosis caused by Fusarium oxysporum and C. albicans. Biofilms formed in vitro on sterile human nail fragments were treated with 1064 nm neodymium-doped yttrium aluminum garnet laser (Nd:YAG), 420 nm intense pulsed light (IPL) IPL 420, followed by Nd:YAG, or near-infrared light ((NIR) 700-1400 nm). Light and laser antibiofilm effects were evaluated using cell viability assay and scanning electron microscopy (SEM). All treatments were highly effective against C. albicans and F. oxysporum biofilms, resulting in decreases in cell viability of 45-60 % for C. albicans and 92-100 % for F. oxysporum. The model described here yielded fungicidal activities that matched more closely to those observed in the clinic, when compared to published in vitro models for laser and light therapies. Thus, our model might represent an important tool for the initial testing, validation, and "fine-tuning" of laser and light therapies against onychomycosis.
Saini, T. R.
The treatment of onychomycosis is a challenging task because of unique barrier properties of the nail plate which hampers the passage of antifungal drugs in a concentration required to eradicate the deeply seated causative fungi in the nail bed. In present investigation, application of hydroxypropyl-β-cyclodextrin (HP-β-CD) was established as an effective and nail friendly transungual drug permeation enhancer especially for poorly water soluble drugs using terbinafine hydrochloride as a poorly soluble drug. HP-β-CD significantly improves hydration of nail plates and increases solubility of terbinafine hydrochloride in the aqueous environment available therein, which leads to uninterrupted drug permeation through water filled pores of hydrogel-like structure of hydrated nail plates. A nail lacquer formulation was designed with an objective to deliver the drug in an effective concentration across nail plates, using HP-β-CD as a permeation enhancer. The formulations containing HP-β-CD showed higher flux than the control formulation in in vitro drug permeation study. The formulation containing 10% w/v of HP-β-CD showed maximum flux of 4.586 ± 0.08 μg/mL/cm2 as compared to the control flux of 0.868 ± 0.06 μg/mL/cm2. This finding supports application of HP-β-CD as an effective permeation enhancer for transungual delivery of terbinafine hydrochloride and possibly other poorly water soluble drugs where HP-β-CD can act as a solubilizer. PMID:25177500
Lavorato, Fernanda G; Guimarães, Dávson A; Premazzi, Mario G; Piñeiro-Maceira, Juan M; Bernardes-Engemann, Andréa R; Orofino-Costa, Rosane
Improvement of laboratory diagnosis of onychomychosis is important so that adequate treatment can be safely implemented. To evaluate and compare the performance of mycological and histopathological examinations in onychomycoses caused by dermatophyte and non-dermatophyte moulds. Patients with lateral/distal subungual onychomycosis in at least one hallux were enrolled in the protocol and assessed via mycological and histopathological tests. The isolation of filamentous fungi was considered the gold standard. Test performance was evaluated through sensitivity, specificity and positive and negative predictive values. A total of 212 patients were enrolled in the study. Direct microscopy (DM) was positive in 57.5% patients, and cultures in 34.4%. Among these patients, 23.3% were positive for dermatophytes, with Trichophyton rubrum the most frequently isolated, and 86.3% were positive for non-dermatophytes, with Neoscytalidium dimidiatum predominance. Histopathology was positive in 41.0% samples. Direct microscopy showed better sensitivity for non-dermatophyte moulds (P=.000) and nail clipping was more specific for dermatophyte (P=.018). Histopathology of the distal nail plate is a valuable complementary tool for the diagnosis of onychomycosis caused by dermatophytes and direct microscopy is especially useful for non-dermatophyte molds. © 2017 Blackwell Verlag GmbH.
Petinataud, Dimitri; Berger, Sibel; Ferdynus, Cyril; Debourgogne, Anne; Contet-Audonneau, Nelly; Machouart, Marie
Onychomycosis is a common nail disorder mainly due to dermatophytes for which the conventional diagnosis requires direct microscopic observation and culture of a biological sample. Nevertheless, antifungal treatments are commonly prescribed without a mycological examination having been performed, partly because of the slow growth of dermatophytes. Therefore, molecular biology has been applied to this pathology, to support a quick and accurate distinction between onychomycosis and other nail damage. Commercial kits are now available from several companies for improving traditional microbiological diagnosis. In this paper, we present the first evaluation of the real-time PCR kit marketed by Bio Evolution for the diagnosis of dermatophytosis. Secondly, we compare the efficacy of the kit on optimal and non-optimal samples. This study was conducted on 180 nails samples, processed by conventional methods and retrospectively analysed using this kit. According to our results, this molecular kit has shown high specificity and sensitivity in detecting dermatophytes, regardless of sample quality. On the other hand, and as expected, optimal samples allowed the identification of a higher number of dermatophytes by conventional mycological diagnosis, compared to non-optimal samples. Finally, we have suggested several strategies for the practical use of such a kit in a medical laboratory for quick pathogen detection.
The study objective was to evaluate the safety, tolerability, systemic exposure, and pharmacokinetics (PK) of 10% luliconazole solution (luliconazole) when topically applied once daily to all 10 toenails and periungual areas in patients with moderate to severe distal subungual onychomycosis. In this single-center, open-label study, 24 patients applied 20 mg/ml of luliconazole (twice the clinical dose) for 29 days with a 7-day follow-up. Complete PK profiles were determined on days 1, 8, 15, and 29. Safety/tolerability assessments included application site reactions, adverse events, vital signs, clinical laboratory findings, and electrocardiograms. Mean luliconazole plasma concentrations remained around the lower limit of quantitation (0.05 ng/ml) and were comparable on days 8, 15, and 29 (range, 0.063 to 0.090 ng/ml), suggesting steady state occurred by day 8. Every patient had undetectable plasma luliconazole levels for at least 11% of the time points, and 12 of the 24 patients had undetectable levels for at least 70% of the time points. The maximum plasma concentration of luliconazole (Cmax) observed in any patient was 0.314 ng/ml and the maximum area under the concentration-time curve from 0 to 24 h (AUC0–24) was 4.34 ng · h/ml. Five patients (21%) had measureable luliconazole levels in the plasma 7 days after the last dose. The median concentration of luliconazole in the nail at this time point was 34.65 mg/g (from 42 of 48 collected toenail samples). There was one mild incidence of skin erythema on day 5 that resolved on day 8, there were no reports of drug-induced systemic side effects, and there was no evidence of QT prolongation. Luliconazole, when applied once daily to all 10 fungus-infected toenails for 29 days, is generally safe and well tolerated and results in significant accumulation of drug in the nail. Systemic exposure is very low, with no evidence of drug accumulation. PMID:23545529
Del Rosso, James Q
Topical antifungal management of toenail onychomycosis has been fraught with several therapeutic challenges including difficulty gaining access to the site of infection and the need for prolonged durations of therapy. In addition, there has been a marked lack of information on the impact of toenail polish application on drug penetration after application. This article reviews available data from studies evaluating the effect of nail polish on antifungal drag penetration using ex vivo laboratory models with cadaver fingernail plates with both tavaborole 5% solution and efinaconazole 10% solution. In addition, changes in nail polish appearance and color transfer to applicators are also discussed, with changes noted with topical efinaconazole. Importantly, there are no data on whether or not nail polish application alters the efficacy of these topical agents.
Matsuda, Yoshiki; Sugiura, Keita; Hashimoto, Takashi; Ueda, Akane; Konno, Yoshihiro; Tatsumi, Yoshiyuki
Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeated full-thickness human nails more deeply than luliconazole. Amorolfine and terbinafine did not show any detectable permeation. The free-drug concentration of efinaconazole in a 5% human nail keratin suspension was 24.9%, which was significantly higher than those of the other drugs (1.1-3.9%). Additionally, efinaconazole was released from human nail keratin at a greater proportion than the other drugs. The MICs of the five drugs for Trichophyton rubrum were determined at various concentrations of keratin (0-20%) in RPMI 1640 medium. The MICs of ciclopirox were not affected by keratin, whereas those of efinaconazole were slightly increased and those of luliconazole and terbinafine were markedly increased in the presence of 20% keratin. Efficacy coefficients were calculated using the nail permeation flux and MIC in media without or with keratin. Efinaconazole showed the highest efficacy coefficient, which was determined using MIC in media with keratin. The order of efficacy coefficients determined using MIC in keratin-containing media rather than keratin-free media was consistent with that of complete cure rates in previously reported clinical trials. The present study revealed that efficacy coefficients determined using MIC in keratin-containing media are useful for predicting the clinical efficacies of topical drugs. In order to be more effective, topical drugs have to possess higher efficacy coefficients.
Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeated full-thickness human nails more deeply than luliconazole. Amorolfine and terbinafine did not show any detectable permeation. The free-drug concentration of efinaconazole in a 5% human nail keratin suspension was 24.9%, which was significantly higher than those of the other drugs (1.1–3.9%). Additionally, efinaconazole was released from human nail keratin at a greater proportion than the other drugs. The MICs of the five drugs for Trichophyton rubrum were determined at various concentrations of keratin (0–20%) in RPMI 1640 medium. The MICs of ciclopirox were not affected by keratin, whereas those of efinaconazole were slightly increased and those of luliconazole and terbinafine were markedly increased in the presence of 20% keratin. Efficacy coefficients were calculated using the nail permeation flux and MIC in media without or with keratin. Efinaconazole showed the highest efficacy coefficient, which was determined using MIC in media with keratin. The order of efficacy coefficients determined using MIC in keratin-containing media rather than keratin-free media was consistent with that of complete cure rates in previously reported clinical trials. The present study revealed that efficacy coefficients determined using MIC in keratin-containing media are useful for predicting the clinical efficacies of topical drugs. In order to be more effective, topical drugs have to possess higher efficacy coefficients. PMID:27441843
Adigun, Chris G; Vlahovic, Tracey C; McClellan, Michael B; Thakker, Kailas D; Klein, Ryan R; Elstrom, Tuan A; Ward, Daniel B
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.
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.
A vertical diffusion cell system was used to evaluate the ability of efinaconazole 10% and tavaborole 5% to
... oral medication, and debridement (removal of diseased nail matter and debris) of an infected nail. Newer oral ... lines of defense against fungal nails. Clean and dry feet resist disease. Wash your feet with soap ...
Malay, D Scot; Yi, Sang; Borowsky, Pamela; Downey, Michael S; Mlodzienski, Alan J
Pedal onychomycosis is a common malady caused by dermatophytes, saprophytes, and yeasts. Traditional treatment options for this condition include toenail debridement, and pharmacological therapies that range from the application of topical agents to the oral administration of antifungal medications. In this study, 55 patients (289 toenails) were randomly allocated to either nail debridement (27 [49.09%] patients) or debridement plus application of topical antifungal nail lacquer (28 [50.91%] patients). The primary outcome was mycological cure, and secondary outcomes included foot-related quality of life, and a number of clinically important toenail characteristics. After a median follow-up of 10.5 months (range, 3.25-14.25) months), patients in the antifungal nail lacquer group improved statistically significantly more than did those in the debridement alone group, and displayed a 76.74% rate of mycological cure. None of the patients in the debridement-only group experienced mycological cure. Variables that statistically significantly decreased the likelihood of cure included yeast on culture, pedal hyperhidrosis, cigarette smoking, involvement of the lunula, and involvement of >50% of the transverse width of the nail. Variables statistically significantly associated with an increased likelihood of cure included intervention before 6 months' duration, treatment at a large, urban practice, black race, and loss of protective sensation. 1.
Kalokasidis, Kostas; Onder, Meltem; Trakatelli, Myrto-Georgia; Richert, Bertrand; Fritz, Klaus
In this prospective clinical study, the Q-Switched Nd:YAG 1064 nm/532 nm laser (Light Age, Inc., Somerset, NJ, USA) was used on 131 onychomycosis subjects (94 females, 37 males; ages 18 to 68 years). Mycotic cultures were taken and fungus types were detected. The laser protocol included two sessions with a one-month interval. Treatment duration was approximately 15 minutes per session and patients were observed over a 3-month time period. Laser fluencies of 14 J/cm(2) were applied at 9 billionths of a second pulse duration and at 5 Hz frequency. Follow-up was performed at 3 months with mycological cultures. Before and after digital photographs were taken. Adverse effects were recorded and all participants completed "self-evaluation questionnaires" rating their level of satisfaction. All subjects were well satisfied with the treatments, there were no noticeable side effects, and no significant differences were found treating men versus women. At the 3-month follow-up 95.42% of the patients were laboratory mycologically cured of fungal infection. This clinical study demonstrates that fungal nail infections can be effectively and safely treated with Q-Switched Nd:YAG 1064 nm/532 nm laser. It can also be combined with systemic oral antifungals providing more limited treatment time.
A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement.
Baran, R; Sigurgeirsson, B; de Berker, D; Kaufmann, R; Lecha, M; Faergemann, J; Kerrouche, N; Sidou, F
Onychomycosis is common, accounting for up to 50% of all nail disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain and walking difficulties. Some populations, such as individuals with diabetes, are at higher risk for developing secondary complications such as infections. Treatment takes many months and therapeutic choices can increase clinical effectiveness, lower toxicity and minimize healthcare costs. Based on the results of a previous pilot study, the objective of the present study was to show, in a larger population, the enhanced efficacy of a combination of amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis with matrix involvement. In addition, a cost-effectiveness analysis was performed. In this multicentre, randomized, open-label, parallel group study, patients were randomized to receive either a combination of amorolfine hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg once daily for 3 months (AT group) or terbinafine alone once daily for 3 months (T group). The study duration was 18 months including a 6-month treatment-free phase following the 12-month active treatment phase for the AT group and a 15-month treatment-free phase following the 3-month active treatment phase for the T group. The primary efficacy criterion was overall response, dichotomized into success or failure, success being the combination of clinical cure and negative mycology at month 18. This criterion was used as the effectiveness measure in the pharmacoeconomic analysis, conducted from a payer perspective. In total, 249 patients were included into the study: 120 in the AT group and 129 in the T group. A significantly higher success rate was observed for patients in the AT group relative to those in the T group at 18 months (59.2% vs. 45.0%; P = 0.03). Both treatment regimens were safe and well tolerated. Treatment cost per cured patient was lower for the combination than for terbinafine alone in all
Hubka, Vit; Nissen, Christoffer V; Jensen, Rasmus Hare; Arendrup, Maiken C; Cmokova, Adela; Kubatova, Alena; Skorepova, Magdalena; Kolarik, Miroslav
Trichophyton onychocola is a recently described geophilic dermatophyte that has been isolated from a toenail of Czech patient with a history of onychomycosis due to T. rubrum and clinical suspicion of relapse. In this study, we report a similar case from Denmark in an otherwise healthy 56-year-old man. The patient had a history of great toenail infection caused by T. rubrum in 2004 and presented with suspected relapse in 2011 and 2013. Trichophyton onychocola was the only microbial agent isolated at the second visit in 2013 and the identification was confirmed by DNA sequencing. Direct microscopic nail examination was positive for hyphae, however the etiological significance of T. onychocola was not supported by repeated isolation of the fungus. This new species may be an overlooked geophilic species due to the resemblance to some common species, for example, zoophilic T. interdigitale or some species of geophilic dermatophytes. We included differential diagnosis with phenotypically similar species; however, it is recommended that molecular methods are used for correct identification. The MAT locus of Danish strain was of opposite mating type than in the previously isolated Czech strain and the two isolates were successfully mated. The mating experiments with related heterothallic species T. thuringiense and Arthroderma melis were negative. The sexual state showed all typical signs of arthroderma-morph and is described by using optical as well as scanning electron microscopy. The sexual state was induced on a set of agar media, however low cultivation temperature and the presence of keratin source were crucial for the success rather than formulation of medium.
Opportunistic toenail onychomycosis. The fungal colonization of an available nail unit space by non-dermatophytes is produced by the trauma of the closed shoe by an asymmetric gait or other trauma. A plausible theory.
Zaias, N; Escovar, S X; Rebell, G
Opportunistic onychomycosis is defined, when a non-dermatophyte mould is cultured from an abnormal nail unit in the absence of a dermatophyte. The presumption is that the mould has caused the abnormal clinical appearance of the nail unit, yet there are no data available to substantiate this claim. Reports have only identified the mould being recovered from the nail unit niche. A review of the published dermatologic literature describing toenail opportunistic onychomycosis by non-dermatophyte fungi has shown toenails with onycholysis, nail bed (NB) keratosis and nail plate surface abnormalities. The appearance of these clinical changes is indistinguishable from the diagnosis of the Asymmetric Gait Nail Unit Signs (AGNUS). AGNUS is produced by the friction of the closed shoe in patients with an asymmetric gait, resulting primarily from the ubiquitous uneven flat feet. Most commonly, species of Acremonium (Cephalosporium), Aspergillus, Fusarium, Scopulariopsis and rarely species of many different fungi genera are capable of surviving and reproducing in a keratinous environment and change the clinical appearance of the involved nail unit. AGNUS toenails predispose to the colonization by the non-dermatophyte opportunistic fungi but not by dermatophyte fungi.
Application of cosmetic nail varnish does not affect the antifungal efficacy of amorolfine 5% nail lacquer in the treatment of distal subungual toenail onychomycosis: results of a randomised active-controlled study and in vitro assays.
Sigurgeirsson, B; Ghannoum, M A; Osman-Ponchet, H; Kerrouche, N; Sidou, F
As onychomycosis is unsightly, this study clinically evaluated whether the antifungal efficacy of amorolfine 5% nail lacquer (NL) was affected by a masking, natural-coloured, cosmetic nail varnish applied 24 h later; in vitro investigations were also performed. Subjects with mild-to-moderate distal subungual toenail onychomycosis were randomised to receive amorolfine 5% NL once weekly with or without cosmetic nail varnish applied 24 h later. After 12-week treatment, antifungal activity of affected toenail clippings was assessed by measurement of zones of inhibition (ZOIs) on Trichophyton mentagrophytes seeded agar plates. Mean diameters were 53.5 mm for the amorolfine 5% NL-alone group (n = 23) and 53.6 mm for amorolfine 5% NL plus cosmetic nail varnish group (n = 25). Also, mycological cultures of subungual debris at week 12 were negative for all subjects in both groups. Most subjects (88%) reported that cosmetic nail varnish masked their infected toenails. Additionally, cadaver human nails coated in vitro with or without cosmetic nail varnish 10 min or 24 h post amorolfine NL application all gave ZOIs on Trichophyton rubrum agar plates representing potent antifungal activity. In conclusion, cosmetic nail varnish applied post amorolfine had no effect on the subungual antifungal activity of amorolfine 5% NL or its penetration through toenails. © 2016 The Authors Mycoses published by Blackwell Verlag GmbH.
Efficacy, safety and tolerability of an optimized avulsion technique with onyster® (40% urea ointment with plastic dressing) ointment compared to bifonazole-urea ointment for removal of the clinically infected nail in toenail onychomycosis: a randomized evaluator-blinded controlled study.
Lahfa, M; Bulai-Livideanu, C; Baran, R; Ortonne, J P; Richert, B; Tosti, A; Piraccini, B M; Szepietowski, J C; Sibaud, V; Coubetergues, H; Voisard, J J; Paul, C
Toenail onychomycosis is highly prevalent, with 14-28% of people aged 60 or over suffering from the disease. Use of a topical antifungal alone in toenail onychomycosis is associated with low cure rates. This may be due to limited penetration of the topical antifungal through the diseased nail. The objective of the present study was to compare two treatment modalities to obtain diseased nail chemical avulsion in toenail onychomycosis. In this European, multicenter, randomized, parallel-group, open-label, active-controlled study, male or female adult patients with distal-lateral or lateral subungual dermatophyte onychomycosis on at least 12.5% of the great toenail were randomized either to a 40% urea ointment with plastic dressing group (n = 53) or to a bifonazole-urea ointment group (n = 52). The ointments were applied daily for a maximum of 3 weeks according to the summary of product characteristics. After assessment of infected nail debridement, topical antifungal treatment with bifonazole cream was applied daily in both groups for 8 weeks. 102 patients were evaluated, i.e. 51 in the 40% urea ointment with plastic dressing group and 51 in the bifonazole-urea group. The primary end point was complete removal of the nail plate at day 21 (D21). Secondary end points were: complete cure and mycological cure evaluated at D105. Ease of use and local tolerability were also assessed. Complete removal of the clinically infected target nail plate area, assessed by blinded evaluators, was significantly higher in the 40% urea ointment with plastic dressing group (61.2%) than in the control group (39.2%), showing the superiority of 40% urea ointment with plastic dressing (p = 0.028). The same results were observed in the per-protocol population (63.0 vs. 36.6%; p = 0.014). Complete removal of the infected area assessed by the investigator at D21 showed a significantly higher success rate in patients treated with 40% urea ointment with plastic dressing (86.3%) as compared to
Méndez-Tovar, Luis Javier; Arévalo-López, Alfredo; Domínguez-Aguilar, Sofía; Manzano-Gayosso, Patricia; Hernández-Hernández, Francisca; López Martínez, Rubén; Silva González, Israel
Introducción: los cambios ungueales en los pacientes con psoriasis pueden ser muy parecidos a la onicomicosis y, por lo tanto, las infecciones fúngicas pueden ser subdiagnosticadas. Se investigó la frecuencia de onicomicosis en manos y pies de 150 pacientes con psoriasis de un servicio de dermatología. Métodos: se obtuvieron los datos clínicos de la psoriasis. Se cultivaron escamas de las uñas en agar dextrosa Sabouraud con y sin antibióticos y se hizo un examen directo con KOH. Resultados: de los 150 pacientes, 67 (45 %) presentaron uñas sanas; 42 (28 %) tuvieron onicomicosis, y 41 (27 %) onicopatía sin infección. Las alteraciones ungueales en las manos estuvieron más asociadas con onicopatía psoriásica (82.5 %); los cambios de las uñas de los pies se asociaron más frecuentemente a infección fúngica (26.4 frente a 9.45 % en psoriasis). De 20 cultivos positivos, se aislaron 22 agentes: 11 Candida spp. (50 %). Como factor de riesgo para desarrollar onicomicosis, el tiempo de evolución de la psoriasis mostró una diferencia significativa (p = 0.03). Conclusión: en los pacientes con psoriasis, las alteraciones ungueales de manos se deben principalmente a psoriasis, mientras que los cambios ungueales en los pies se asocian a onicomicosis. Esta fue causada principalmente por Candida sp. El único factor de riesgo asociado para onicomicosis fue la larga evolución de la psoriasis.
Onalan, Orhan; Adar, Adem; Keles, Hakan; Ertugrul, Goksen; Ozkan, Nurhayat; Aktas, Habibullah; Karakaya, Ekrem
Hintergrund: Wir haben die Beziehung der Onychomykose an den Fuβnägeln mit der subklinischen Arteriosklerose bei Patienten mit Diabetes untersucht. Patienten und Methoden: Aufeinanderfolgende Diabetiker, die wir ambulant gesehen haben, wurden registriert. Die Intima-Media Dicke der Arteria carotis (CIMT) wurde bewertet. Die Fuβnagelonychomykose wurde mikroskopisch diagnostiziert. Ergebnisse: Wir haben 127 Patienten untersucht. Bei 48 (37,8 %) fanden wir eine Fuβnagelonychomykose. Von den 127 Patienten hatten 60 (47,2 %) eine subklinische Arteriosklerose (CIMT > 1 mm). Das männliche Geschlecht (43,3 % vs. 22,4 %, p = 0,012) und die Onychomykose (53,3 % vs. 23,9 %, p = 0,001) waren bei Paitenten mit subklinischer Arteriosklerose signifikant häufiger. Unter den biochemischen Parametern war das LDL Cholesterin (122+38 mg/dl vs. 108+36 mg/dl, p = 0,039) und das glykolisierte Hämoglobin (median 8.4 %, IQR: 2.1 % vs. median 7.5 %, IQR: 1.6 %, p = 0,002) bei Patienten mit subklinischer Arteriosklerose signifikant höher. Die Gruppen waren im Hinblick auf alle anderen demografischen, klinischen, und laborchemischen Parametern ähnlich. Nach Adjustierung für alle potentiellen Einflussgrössen war die Existenz der Onychomykose in der multivariaten Regressionsanalyse eigenständig mit der subklinischen Arteriosklerose (OR 2.77, 95 % CI 1.16 bis 6.30) vergesellschaftet. Schlussfolgerungen: Onychomychose kann ein Marker der Arteriosklerose bei Diabetikern sein.
Vineetha, Mary; Palakkal, Seena; Sobhanakumari, K; Celine, MI; Letha, V
A 57 year healthy farmer with congenital nail pterygium presented with a verrucous growth on nail bed since 8 months. He was not diabetic and HIV rapid card test negative. Our clinical diagnosis was chromoblastomycosis but culture showed growth of curvularia species on two occasions and histopathology showed hyphal and yeast forms of the pigmented fungus. After excision biopsy patient was started on oral itraconazole. This case is reported due to rarity of verrucous cutaneous lesions caused by curvularia in immunocompetent individuals. PMID:27904208
Mahtab, Asiya; Anwar, Mohammed; Mallick, Neha; Naz, Zrien; Jain, Gaurav K; Ahmad, Farhan J
Ketoconazole (KCZ) nanoemulgel containing permeation enhancer was formulated as a vehicle for transungual drug delivery, and its efficacy to inhibit the growth of onychomycotic dermatophytes was investigated in vitro. Different components of oil-in-water nanoemulsions were moderately agitated by classical titration method and passed through a high-pressure homogenizer to formulate various nanoemulsions, which were further identified by constructing pseudo-ternary phase diagrams. Stress-stability testing was carried out for the nanoemulsions, and those that passed these tests were characterized for mean droplet size, zeta potential, morphology, pH, refractive index, viscosity and transmittance. Mean droplet size and zeta potential of the optimized nanoemulsion (NE3) were found to be 77.52 ± 0.92 nm (polydispersity index (PDI) = 0.128 ± 0.035) and -5.44 ± 0.67 mV, respectively. Optimized nanoemulsion was converted into nanoemulgel (NEG1) with 1% (w/w) of gelling agent (Carbopol® Ultrez 21) and 1%-2% (v/v) thioglycolic acid as permeation enhancer, and evaluated for pH, viscosity, spreadability, extrudability, tensile strength and bio-adhesion measurement. In vitro cumulative drug released at the end of 24 h from NE3, NEG1 and drug suspension were found to be 98.87 ± 1.29, 84.42 ± 2.78% and 54.86 ± 2.19%, respectively. Ex vivo transungual permeation values for KCZ through goat hooves from NE3, NEG1 and drug suspension were found to be 62.49 ± 2.98, 77.54 ± 2.88% and 38.54 ± 2.54%, respectively, in 24 h. The antifungal effect of NEG1 on Trichophyton rubrum and Candida albicans showed a significant (p < 0.05) zone of inhibition as compared to drug solution. Skin irritation and histopathology studies on rat skin showed the safe topical use and enhanced permeation of formulated nanoemulgel.
Vineetha, Mary; Palakkal, Seena; Sobhanakumari, K; Celine, M I; Letha, V
A 57 year healthy farmer with congenital nail pterygium presented with a verrucous growth on nail bed since 8 months. He was not diabetic and HIV rapid card test negative. Our clinical diagnosis was chromoblastomycosis but culture showed growth of curvularia species on two occasions and histopathology showed hyphal and yeast forms of the pigmented fungus. After excision biopsy patient was started on oral itraconazole. This case is reported due to rarity of verrucous cutaneous lesions caused by curvularia in immunocompetent individuals.
Elmer, Kathleen B; Elston, Dirk M; Libow, Lester F
Trichosporon beigelii is a fungal organism that causes white piedra and has occasionally been implicated as a nail pathogen. We describe a patient with both hair and nail changes associated with T. beigelii.
Baraldi, A; Jones, S A; Guesné, S; Traynor, M J; McAuley, W J; Brown, M B; Murdan, S
Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations. The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail's density was determined via pycnometry and the nail's ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake. Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm(3); diseased 1.29 ± 0.00 g/cm(3)). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle. Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.
Nair, Anroop B; Kim, Hyun D; Chakraborty, Bireswar; Singh, Jagpal; Zaman, Muhammad; Gupta, Aditya; Friden, Phillip M; Murthy, S Narasimha
The application of iontophoresis was demonstrated in the nail drug delivery of terbinafine (TH) recently. This study explored a systematic assessment of this approach to enhance the drug delivery using a novel topical formulation, and the subsequent release of TH from the drug loaded nails. For the first time, a nail on-agar plate model was used to study the release of drug from the iontophoresis (0.5 mA/cm(2)) loaded nails. In addition, the activity of the drug released from the drug loaded nail plate was studied against Trichophyton rubrum. An increase in applied current density and current duration enhanced the transport of TH into and through the nail plate. In vitro release of drug from the iontophoretic loaded nails into agar plates exhibited 2-phase release pattern. The amount of drug released in both of the in vitro models was comparable, and the nails loaded using iontophoresis continued to release levels of TH > 2 orders of magnitude above the minimum inhibitory concentration over at least 52 days. Results indicate that iontophoresis enhances the delivery of terbinafine into and through the nail plate and suggest that the use of this treatment approach could result in a safe and more efficacious outcome with less frequent treatments. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association
Mirhendi, H; Nishiyama, Y; Rezaei-Matehkolaei, A; Satoh, K; Makimura, K
Superficial mycotic infections have been only poorly described in koalas and there are no reliable mycologically confirmed data regarding clinical isolation of dermatophytes in this animal. We report an 11-year-old female koala, kept in a zoo in Tokyo, Japan, and presenting with hyperkeratotic lesions and scaly plaques on forepaw claws and pads reminiscent of fungal infection. Direct microscopy of the scrapings was indicative of a dermatophyte infection. By culture and subsequent repeated subculturing of clinical specimens on Sabouraud dextrose agar, Mycobiotic agar, and potato dextrose agar, two distinct strains with different colony morphotypes (designed as types I and II) were identified. Macroscopic and microscopic characteristics of the strains were suggestive of three different species, i.e. Microsporum canis, M. gypseum, and M. fulvum. However, partial sequencing of internal transcribed spacer (ITS) region of rDNA, translation elongation factor-1α (Tef-1α), and beta-tubulin (BT2) genes confirmed the identity of both isolates as M. gypseum. The animal was treated with a continuous terbinafine regimen (250 mg/kg) once daily for 12 weeks. To the best of our knowledge, the present report is the first confirmed case of dermatophytosis in a koala. The genetics underlying a variety of phenotypic traits in most classical dermatophyte species are unknown, and further studies are needed to understand this phenomenon.
Allergy and autoimmune processes were found in patients with onychomycosis caused by Tr. rubrum and with mycoses caused by Tr. gypseum and Tr...with experimental mycoses caused by Tr. gypseum and onychomycosis caused by Tr. rubrum.
Jesús-Silva, Miriam América; Fernández-Martínez, Ramón; Roldán-Marín, Rodrigo; Arenas, Roberto
Background: Onychomycosis is the most common nail disease, representing 50% of cases affecting the nail apparatus. The diagnosis is made by clinical examination along with the KOH exam of the nail and culture of the sample. However, not all dermatologists have access to a mycology lab. Objective: To determine the correlation between KOH examination and dermoscopic patterns in patients with clinical diagnosis of onychomycosis. Patients/Methods: A descriptive, open, observational, prospective, cross-sectional study of 178 patients with clinical suspicion of onychomycosis was conducted. All patients underwent clinical examination, dermoscopy with a DermLite PHOTO dermatoscope (3Gen, San Juan Capistrano, CA, USA), KOH assessment and culture analysis. The most frequent dermoscopic patterns were identified and their correlation with the clinical subtype of onychomycosis was analyzed. Results: The study included 178 patients with clinical suspicion of onychomycosis. Of these, 155 (87.1%) had positive direct KOH examination for onychomycosis. Eighty-seven patients (56.13%) presented with clinical onychomycosis pattern of total dystrophic onychomycosis (TDO), 67 (43.23%) with distal lateral subungual onychomycosis (DLSO), 1 (0.65%) with trachyonychia). Dermoscopic patterns of onychomycosis showed the following frequencies: the spiked pattern was present in 22 patients (14.19%), longitudinal striae pattern in 51 patients (32.9%) and linear edge pattern in 21 patients (13.55%). We identified a pattern described as “distal irregular termination” in 41 patients with TDO and 26 with DLSO. Conclusions: This is the fist study conducted in a Mexican population that uses dermoscopy as a diagnostic tool along with the KOH examination for the diagnosis of onychomycosis. Dermoscopy may be used as an important diagnostic tool when evaluating nail disease. However, it should not be used as the only diagnostic criteria for onychomycosis. PMID:26114050
Vender, Reid; Vender, Ronald
Occasionally, psoriatic nail changes are seen in psoriatic patients. The prevalence of psoriasis of the nails has been reported to range from 15% to 79%. Even with effective systemic treatment for psoriasis, the nails may not improve, and these nails are considered nonresponsive psoriatic nails. Psoriatic nails are rarely investigated, and it is assumed that the nail changes are simply attributed to psoriasis because of their clinical similarity. Even patients with nails unresponsive to systemic treatment, or psoriasis treated topically or with phototherapy, onychomycosis is often forgotten, and patients may be left with both onychomycosis and psoriasis or onychomycosis alone. A retrospective chart review of 361 patients was carried out. The investigators report the prevalence of psoriasis and onychomycosis as less than 1%. A new term, "psoronychomycosis," is suggested to denote the rare combination of psoriasis and onychomycosis.
Suga, Yasushi; Kimura, Utako; Hiruma, Masataro
Onychomycosis is a common disease seen in dermatology practice. Most patients with onychomycosis opt for treatment due to the social stigma attached to the unsightly appearance, as well as the pain that can at times make walking difficult. However, in many cases, onychomycosis is resistant to oral antifungal medication, which is the first-line therapy for this disease. In recent years, we have attempted a new treatment method using a long-pulsed 1,064nm Nd :YAG laser (Cutera Inc., Brisbane, CA, USA) in refractory cases with onychomycosis. Using 1) a laser beam with a spot size of 5.0 mm and 2) sequential irradiation at low fluence, we 3) applied the laser to the infected lesions in a motion similar to showering, while maintaining a distance of several centimeters from the skin (Laser Genesis(TM)). Treatment efficacy was assessed using nail turbidity scores on a five-point scale. Improvement in onychomycosis was noted in more than 68.8% of all cases, thus demonstrating the high efficacy of this method. No major adverse reactions were observed during the treatment period. Since its mechanism of action clearly differs from that of antifungal agents, it can be considered a useful treatment option for cases with onychomycosis resistant to antifungal therapy. Future studies should examine "combined therapy" with oral / topical antifungal agents and this laser treatment, which may provide a significant improvement in the level of satisfaction among patients with onychomycosis.
González-Avila, Marisela; Gómez-Gómez, Juan Vicente; Texis, Alejandra Paula Espinosa; Imbert-Palafox, José Luis; Becerril-Flores, Marco Antonio; Blasco, José Luis
Kodamaea ohmeri and Prototheca wickerhamii are rare pathogens for humans, and even more rare as cause of onychomycosis. This work reports the second case of onychomycosis by K. ohmeri and the fourth of onycoprotothecosis; it was made in public health institutions in the Hidalgo State, Mexico, studying 261 diabetic patients during 2005 and 2006. Kodamaea ohmeri was isolated from toenails of a 51-year-old female patient, and P. wickerhamii from three female patients of 48, 49, and 61 years old, respectively, all of them with type 2 diabetes mellitus (DM 2). Identifications were done by standard microbiological methods and a commercial system. Only one patient infected with P. wickerhamii showed mixed infection with dermatophytes. Out of the total studied DM 2 patients, 1.15% presented onycoprotothecosis and 0.38% onychomycosis by K. ohmeri, high percentages if it is considered that few cases have been reported of K. ohmeri and P. wickerhamii as onychomycosis causal agents.
Ortega-Springall, María Fernanda; Arroyo-Escalante, Sara; Arenas, Roberto
Yeasts cause only 5-10% of onychomycosis; the most common yeast is Candida albicans, and rarely Trichosporon spp. is found. Recently, it has become an important cause of fungemia with a high mortality rate in immunocompromised patients. Superficial infections caused by Trichosporon spp., including piedra and onychomycosis, occur in immunocompetent patients. Herein, we report a case of a fungal nail infection characterized by onycholysis and chromonychia caused by Trichosporon inkin. PMID:27171745
Szepietowski, Jacek C; Salomon, Joanna
Onychomycosis is the most common disease of the nails and constitutes about a half of all nail abnormalities. Some factors like increasing age, male sex, repeated nail damage, genetic predispositions and underlying conditions, such as diabetes, immunodeficiency or peripheral arterial disease may predispose to develop onychomycosis. It is also suggested that abnormalities in nail morphology are the predisposing factors to onychomycosis. Psoriasis is one of the most common reasons of disturbed nail morphology and the spectrum of nail changes in psoriasis is very wide. Thus, there were suggestions that dystrophic nails in psoriatic patients lose their natural preventing barrier and therefore are more predisposed to fungal infection. This paper summarizes the knowledge about prevalence of onychomycosis among psoriatic patients and contains a literature review concerning this problem. Most authors report that the prevalence of onychomycosis in psoriatic patients is not higher than that in control population. However, especially yeasts and maybe moulds, probably as concomitant pathogens, are more often isolated from psoriatic patients than from non-psoriatic population. In reasonable cases, the mycological examination is required, especially when the clinical picture of the nails suggests the presence of fungal infection. In these cases, antifungal treatment may be beneficial for psoriatic patients.
Pföhler, Claudia; Hollemeyer, Klaus; Heinzle, Elmar; Altmeyer, Wolfgang; Graeber, Stefan; Müller, Cornelia S L; Stark, Alexandra; Jager, Sven Uwe; Tilgen, Wolfgang
The incidence and prevalence of onychomycosis are rising worldwide. Common diagnostic techniques often lack sensitivity or specificity. Differentiation between non-infectious nail disorders is frequently not possible. The aim of this study was to establish a better diagnostic routine procedure based on modern mass spectrometric peptide analysis techniques. One hundred and fifty-five nail samples from 145 patients with clinically suspected onychomycosis (n = 96, 62%) and without onychomycosis [e.g. nail psoriasis or nail dystrophy resulting from eczema (n = 59, 38%)] were investigated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) peptide mass fingerprinting in comparison with standard techniques. We demonstrated that MALDI-TOF MS represents a precise, robust and fast tool in diagnostic investigation of nail disorders, which is superior to common standard methods.
Gold, Linda Stein; Korotzer, Andrew
Onychomycosis is a common nail disorder with significant medical impacts and aesthetic consequences. Patients seek treatment for several reasons, including the unsightliness of the nail(s). Even with successful management, it takes months for the diseased nail to appear cosmetically normal. Patients commonly apply nail polish to mask the appearance of the dystrophic nail, though it is contraindicated with the currently available topical lacquers for onychomycosis. The authors’ nonclinical study using a cadaver nail model showed that penetration of efinaconazole topical solution, 10%, a new antifungal being developed for the treatment of mild-to-moderate toenail onychomycosis, was not influenced by application of nail polish. Polishes showed an increase in surface tackiness with repeated efinaconazole topical solution, 10% application. The medical and aesthetic significance of the authors’ findings have yet to be assessed clinically. PMID:25276275
Kircik, Leon H
Onychomycosis is a very common nail disorder seen in dermatological practice. It is difficult to treat successfully for a multitude of reasons, and although topical antifungal therapy might be considered ideal for mild to moderate onychomycosis, efficacy has been limited by poor nail penetration of active ingredient through the nail plate into the nail bed and nail matrix to the site of infection. The intrinsic properties of an antifungal and its vehicle formulation are both considered important contributors to effective treatment. Here we review the formulation approach to efinaconazole topical solution, 10% an effective and well-tolerated treatment for onychomycosis. We demonstrate that the low surface tension formulation affords better penetration of efinaconazole through the nail plate, and also to the site of infection by spreading into the space between the nail and nail bed.
Stefanato, Catherine M; Verdolini, Roberto
Nondermatophytic toenail infection with Scopulariopsis brevicaulis is rare, but may occur often in association with dermatophytes. We report a case of an 84-year-old man who presented with onychomycosis of the big toenail. Histopathologic examination of the avulsed nail showed evidence of S. brevicaulis coinfection with a dermatophyte, despite negative mycology results for the latter. Our case underscores the importance of histopathologic examination of nail specimens as an additional invaluable tool in the diagnosis of onychomycosis, as it may unmask false-negative mycology findings.
de Magalhães, Alba Regina; Nishikawa, Marília Martins; de Mondino, Silvia Suzana Bona; de Macedo, Heloisa Werneck; da Rocha, Elisabeth Martins da Silva; Baptista, Andrea Regina de Souza
BACKGROUND Although dermatophytes are considered the major cause of onychomycosis, many reports have incriminated non-dermatophyte moulds and yeasts in the disease’s etiology. Successive Trichosporon isolation from onychomycosis has led to the genus being suspected as a nail primary pathogen. OBJECTIVE To determine the prevalence of Trichosporon isolation in onychomycosis patients who attended a mycology diagnostic service in Rio de Janeiro, Brazil, between January 2003 and December 2006. The study also includes a worldwide review on Trichosporon isolation prevalence in ungueal disease, emphasizing T. ovoides. METHODS This retrospective study was conducted with the support of staff from the Mycology Laboratory at the Dermatological Service of Rio de Janeiro’s Santa Casa da Misericórdia (MLDS). RESULTS Mycological analysis provided positive results equaling 47/5036 (0.93%) for Trichosporon spp.; obtained mainly as a single agent (72.35%), and from mixed cultures (27.65%; X2= 6.397; p= 0.018). The great majority belongs to the T. ovoides species (91.5%; n=43), obtained as a single isolate (74.41%; n= 32/43; X2 = 7.023; p= 0.014). CONCLUSIONS Although T. ovoides is classically associated as an etiologic agent of white piedra, this study highlights its potential as a human nail disease pathogen. Our study opens doors for future epidemiologic and virulence factors aimed at determining whether T. ovoides is an important causative agent of onychomycosis in Brazil. PMID:27192516
Ismail, M T; Al-Kafri, A
It is important to follow annually the probable changes in distribution pattern of dermatophytosis and its etiological agents in different communities. In this study, we determined the prevalence of dermatophytosis and its causative agents in Damascus, Syria, between 2008 and 2016. A total of 4080 outpatients who visited the dermatological clinics in Damascus, were evaluated. The specimens were collected from clinically suspected tinea. The patients were referred to our laboratory for direct examination by 30 %KOH. Some of the specimens were cultured on Sabouraud Dextrose Agar for fungal identification. Out of the 4080 cases, 1138 cases were positive in direct examination(%27.89) , including Tinea pedis (%46.98), followed by tinea capitis(%39.79) , tinea corporis (%25.38), toenail onychomycosi (%20.33), tinea manuum (%16.06), and fingernail onychomycosis .(%15.22) Tinea pedis and toenail onychomycosis were more common in summer %41.19) and %25.78 respectively .(Trichophytic rubrum was the most prevalent fungal pathogen, especially in toenail onychomycosis. Dermatophytosis is highly prevalent in Syria. This study provides valuable data for differential diagnosis of dermatophytosis.
Neff, Luke; Lee, Samuel A.; Sutton, Deanna A.; Wiederhold, Nathan P.; Lindner, Jonathan; Fan, Hongxin
Neoscytalidium dimidiatum is a mold known to cause onychomycosis and dermatomycosis; however, it is an extremely rare cause of systemic infection. We report a case of pulmonary infection with Neoscytalidium dimidiatum in an immunocompromised patient and discuss in vitro susceptibility data from this case and previous literature. PMID:25948605
Zalacain, Antonio; Merlos, Alejandra; Planell, Elena; Cantadori, Erica G; Vinuesa, Teresa; Viñas, Miguel
Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis.
Galletti, J; Negri, M; Grassi, F L; Kioshima-Cotica, É S; Svidzinski, T I E
Onychomycosis caused by Fusarium spp. is emerging, but some factors associated with its development remain unclear, such as whether this genus is keratinolytic. The main aim of the present study was to evaluate the ability of Fusarium to use the human nail as a single source of nutrients. We also performed an epidemiological study and antifungal susceptibility testing of Fusarium spp. that were isolated from patients with onychomycosis. The epidemiological study showed that Fusarium species accounted for 12.4 % of onychomycosis cases, and it was the most common among nondermatophyte molds. The most frequent species identified were F. oxysporum (36.5 %), F. solani (31.8 %), and F. subglutinans (8.3 %). Fluconazole was not active against Fusarium spp., and the response to terbinafine varied according to species. Fusarium was able to grow in vitro without the addition of nutrients and invade healthy nails. Thus, we found that Fusarium uses keratin as a single source of nutrients, and the model proposed herein may be useful for future studies on the pathogenesis of onychomycosis.
Restrepo, A; Arango, M; Velez, H; Uribe, L
Botryodiplodia theobromae not known to produce onychomycosis was repeatedly recovered from a healthy woman with evident lesions in a toe nail. Mycelial fragments were observed in the scales and the fungus was isolated in cycloheximide-free culture media. The report indicates that many fungi, hitherto considered non-pathogens, may still be able to colonize a vaiety of human tissues.
Zhan, Ping; de Hoog, Sybren
ABSTRACT One strain of Trichophyton rubrum CMCC(F)T1i (=CBS 139224) isolated from onychomycosis and one strain of Trichophyton violaceum CMCC(F)T3l (=CBS 141829) isolated from tinea capitis in China were whole-genome sequenced by Illumina/Solexa, while the former was also sequenced by Pacific Biosciences sequencing in parallel. PMID:28963202
Zhan, Ping; de Hoog, Sybren; Liu, Weida
One strain of Trichophyton rubrum CMCC(F)T1i (=CBS 139224) isolated from onychomycosis and one strain of Trichophyton violaceum CMCC(F)T3l (=CBS 141829) isolated from tinea capitis in China were whole-genome sequenced by Illumina/Solexa, while the former was also sequenced by Pacific Biosciences sequencing in parallel. Copyright © 2017 Zhan et al.
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Ismail, MT; Al-Kafri, A
Background and Purpose: It is important to follow annually the probable changes in distribution pattern of dermatophytosis and its etiological agents in different communities. In this study, we determined the prevalence of dermatophytosis and its causative agents in Damascus, Syria, between 2008 and 2016. Materials and Methods: A total of 4080 outpatients who visited the dermatological clinics in Damascus, were evaluated. The specimens were collected from clinically suspected tinea. The patients were referred to our laboratory for direct examination by 30 %KOH. Some of the specimens were cultured on Sabouraud Dextrose Agar for fungal identification. Results: Out of the 4080 cases, 1138 cases were positive in direct examination(%27.89) , including Tinea pedis (%46.98), followed by tinea capitis(%39.79) , tinea corporis (%25.38), toenail onychomycosi (%20.33), tinea manuum (%16.06), and fingernail onychomycosis .(%15.22) Tinea pedis and toenail onychomycosis were more common in summer %41.19) and %25.78 respectively .(Trichophytic rubrum was the most prevalent fungal pathogen, especially in toenail onychomycosis. Conclusion: Dermatophytosis is highly prevalent in Syria. This study provides valuable data for differential diagnosis of dermatophytosis. PMID:28681027
Ely, John W; Rosenfeld, Sandra; Seabury Stone, Mary
Tinea infections are caused by dermatophytes and are classified by the involved site. The most common infections in prepubertal children are tinea corporis and tinea capitis, whereas adolescents and adults are more likely to develop tinea cruris, tinea pedis, and tinea unguium (onychomycosis). The clinical diagnosis can be unreliable because tinea infections have many mimics, which can manifest identical lesions. For example, tinea corporis can be confused with eczema, tinea capitis can be confused with alopecia areata, and onychomycosis can be confused with dystrophic toenails from repeated low-level trauma. Physicians should confirm suspected onychomycosis and tinea capitis with a potassium hydroxide preparation or culture. Tinea corporis, tinea cruris, and tinea pedis generally respond to inexpensive topical agents such as terbinafine cream or butenafine cream, but oral antifungal agents may be indicated for extensive disease, failed topical treatment, immunocompromised patients, or severe moccasin-type tinea pedis. Oral terbinafine is first-line therapy for tinea capitis and onychomycosis because of its tolerability, high cure rate, and low cost. However, kerion should be treated with griseofulvin unless Trichophyton has been documented as the pathogen. Failure to treat kerion promptly can lead to scarring and permanent hair loss.
Nenoff, P; Paasch, U; Handrick, W
Infections of the finger and the toe nails are most frequently caused by fungi, primarily dermatophytes. Causative agents of tinea unguium are mostly anthropophilic dermatophytes. Both in Germany, and worldwide, Trichophyton rubrum represents the main important causative agent of onychomycoses. Yeasts are isolated from fungal nail infections, both paronychia and onychomycosis far more often than generally expected. This can represent either saprophytic colonization as well as acute or chronic infection of the nail organ. The main yeasts causing nail infections are Candida parapsilosis, and Candida guilliermondii; Candida albicans is only in third place. Onychomycosis due to molds, or so called non-dermatophyte molds (NDM), are being increasingly detected. Molds as cause of an onychomycosis are considered as emerging pathogens. Fusarium species are the most common cause of NDM onychomycosis; however, rare molds like Onychocola canadensis may be found. Bacterial infections of the nails are caused by gram negative bacteria, usually Pseudomonas aeruginosa (recognizable because of green or black coloration of the nails) but also Klebsiella spp. and gram positive bacteria like Staphylococcus aureus. Treatment of onychomycosis includes application of topical antifungal agents (amorolfine, ciclopirox). If more than 50 % of the nail plate is affected or if more than three out of ten nails are affected by the fungal infection, oral treatment using terbinafine (in case of dermatophyte infection), fluconazole (for yeast infections), or alternatively itraconazole are recommended. Bacterial infections are treated topically with antiseptic agents (octenidine), and in some cases with topical antibiotics (nadifloxacin, gentamicin). Pseudomonas infections of the nail organ are treated by ciprofloxacin; other bacteria are treated according to the results of culture and sensitivity testing.
Ataides, F S; Chaul, M H; El Essal, F E; Costa, C R; Souza, L K H; Fernandes, O F L; Silva, M R R
Onychomycosis is the nail infection caused by a wide spectrum of fungi species, including yeasts, dermatophytes and filamentous fungi non-dermatophytes (FFND). This fungal infection represents an important medical problem because it involves the patient's life quality. The aim was to isolate and identify the fungal agents of onychomycosis, and to determine the in vitro susceptibility to antifungal agents. During the period of March 2008 to March 2009, 114 patients clinically suspected of having onychomycosis were examined. Demographic data, mainly age and gender were obtained from each patient. The nail samples collected (136) were submitted to direct examination with potassium hydroxide 20% and grown on Sabouraud dextrose agar. The in vitro antifungal susceptibility testing was performed according to the method of broth microdilution, recommended by the Clinical Laboratory Standards Institute (CLSI). Onychomycosis was observed in 95 (83.3%) patients, including 16 men (16.8%) and 79 women (83.2%), with mean age of 48.1 years. Candida parapsilosis, Trichophyton rubrum and Fusarium spp were the fungi most frequently isolated. The most of the isolated yeasts showed susceptibility to antifungal agents studied. Among filamentous fungi, high MIC values to itraconazole were found for T. rubrum and T. mentagrophytes, while Fusarium spp showed decreased susceptibility to itraconazole and voriconazole. C. parapsilosis was the most common fungal species isolated from patients with onychomycosis. The different response obtained by in vitro susceptibility testing to drugs shows the importance of these methods to assist clinicians in choosing the best therapeutic option. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.
Stewart, Campbell L; Rubin, Adam I
Nail unit dermatopathology is a growing field filled with many challenges. Many advances in this field have been made in the last 5 years. This review article provides an update on new information and studies published in that period of time. We divided these works into different sections, including clinical and pathologic challenges in diagnosis and treatment of nail disorders, nail unit biopsy and processing techniques, normal nail unit histology, nail plate structural and growth pathology, metabolic disease, inflammatory conditions, onychomycosis, benign growths, malignant growths, and dyschromias. Specific highlights include advances in the marking and orientation of nail unit biopsies for improved histologic interpretation, improved nail plate softening techniques, new methods for histologic evaluation of onychomycosis, descriptions of newly described benign growths unique to the nail unit, and the morphologic and immunohistochemical distinction between benign and malignant pigmented lesions of the nail unit.
Gupta, A K; Brintnell, W
Ozone gas possesses antimicrobial potential against many microorganisms, however limited data exist on its effect on the keratinophilic dermatophyte fungi Trichophyton rubrum and Trichophyton mentagrophytes; two organisms commonly isolated as the etiological agent in onychomycosis and tinea pedis patients. We utilized a commercial ozone gas generation device for testing the fungicidal effects of ozone on ATCC strains of Trichophyton rubrum and Trichophyton mentagrophytes. We demonstrated that ozone gas is effective in killing > 99% of viable fungi present in various experimental systems. This work represents a proof of principle regarding ozone gas and its fungicidal effect on dermatophyte fungi. From these findings, further ozone gas studies will be conducted to develop a novel adjunct therapy for use in parallel with current antifungal medications and/or devices to better treat onychomycosis and tinea pedis patients in the short and long term.
Neubert, R H H; Gensbügel, C; Jäckel, A; Wartewig, S
This article reports the characterization of the physicochemical properties of two important antifungal topical drugs, amorolfine and ciclopirox. Furthermore, the release of the drugs from commercial lacquer formulations for treatment of onychomycosis was studied using the online FTIR-ATR technique. Based on the physicochemical background of these two drugs and their release from commercial lacquer formulations for treatment of onychomycosis, the suitability of these drugs for optimized local antifungal therapy to human nails is discussed. Amorolfine appears to be more suitable for drug delivery to human nails because it penetrates into the nails via the hydrophilic pathway. Furthermore amorolfine penetrates very well into fungal cells, due to the pH value of the nail, as well as the pKa value of this antimycotic agent and the lipophilic properties of its base form.
Purim, Kátia Sheylla Malta; de Freitas, Camila Fernanda Novak Pinheiro; Leite, Neiva
Athletes present risk of cutaneous mycosis. A study was carried out with 23 soccer players using clinical and mycological examination (direct microscopic examination and culture) and nail clipping. Eighteen (78.26%) did not present mycosis; two (8.70%) presented tinea pedis, and three (13.04%) presented onychomycosis associated to tinea pedis, mainly for Trichophyton mentagrophytes. Infected tinea pedis has produced cellulitis in one of the athletes. It is necessary to create an educative program of skin care during sports practice.
Lysková, P; Hubka, V; Navrátilová, P; Kolařík, M; Skořepová, M
Reported are two cases of suspected onychomycosis with participation of Cryptendoxyla hypophloia. The species C. hypophloia have not been isolated from human and animal clinical material yet. It is a rarely reported cleistothecial ascomycete that has been found to be naturally present on cellulose-rich materials. Its strains tested in a laboratory demonstrated very good susceptibility to terbinafine. The identification of isolates was verified based on rDNA sequencing and by comparison with C. hypophloia ex-type strain.
Szepietowski, Jacek C; Matusiak, Lukasz
Kerion-like lesions are usually caused by zoophilic dermatophytes. Here, we present a rare case report - an inflammatory tinea barbae due to an anthropophilic fungus (Trichophyton rubrum), which is the main pathogen of onychomycosis and tinea pedis. Probably the infection, in the presented case, spread from diseased fingernails. We do postulate that physicians should consider autoinoculation as a not so rare way of fungal infection transmission.
van Diepeningen, Anne D; de Hoog, G Sybren
Fusarium species are emerging human pathogens, next to being plant pathogens. Problems with Fusarium are in their diagnostics and in their difficult treatment, but also in what are actual Fusarium species or rather Fusarium-like species. In this issue Guevara-Suarez et al. (Mycopathologia. doi: 10.1007/s11046-016-9983-9 , 2016) characterized 89 isolates of Fusarium from Colombia showing especially lineages within the Fusarium solani and oxysporum species complexes to be responsible for onychomycosis.
Bonifaz, A; Araiza, J; Koffman-Alfaro, Susana; Paredes-Solis, Vanessa; Cuevas-Covarrubias, S; Rivera, M R
We report on 9 confirmed cases of tinea imbricata (Tokelau, infection due to Trichophyton concentricum) out of 16 family members. They had a common mother with three different fathers. The genetic analysis of the family suggests an autosomal dominant pattern of susceptibility. Most cases (8/9) were presented as concentric and lamellar forms. One patient also had onychomycosis due to T. concentricum. Only two out of nine cases had a positive response to trichophytin.
Oppel, Tilmann; Korting, Hans Christian
Onychodystrophy represents various pathologic processes of the nails such as infectious and noninfectious disorders including onychomycosis, psoriasis and allergic and irritant dermatitis. Nail changes may also be a clue to other dermatological or systemic diseases. But often it is difficult to establish the diagnosis as most nail changes are unspecific. The purpose of this article is to give an overview of the anatomy of the nail organ and possible causes of onychodystrophy. Therapeutic modalities are reviewed as well as modes of analysis.
Kaur, Ravinder; Maheshwari, Megha
Fusarium species are common soil-inhabiting organisms and plant pathogens. Human infections are usually precipitated by local or systemic predisposing factors, and disseminated infection is associated with impaired immune responses. Skin infections caused by Fusarium spp. include keratitis, onychomycosis, mycetoma, painful discrete erythematous nodules. Hyperkeratotic skin lesions caused by Fusarium spp. are, however, rarely reported. We report a case of hyperkeratotic verrucous warty skin lesion in the foot of a 50-year-old immunocompetent male, farmer by occupation. PMID:23716829
Hafeez, Farhaan; Hui, Xiaoying; Chiang, Audris; Hornby, Sidney; Maibach, Howard
Onychomycosis, a common fungal infection of the nail, can have a substantial impact on quality of life. The success of topical therapy for onychomycosis depends on effective penetration, which can be enhanced using an appropriate delivery method. This study evaluated the effectiveness of a novel topical lacquer on enhancing [(14)C]-ketoconazole penetration by comparing nail absorption, nail distribution, and nail penetration of [(14)C]-ketoconazole dissolved in the novel lacquer versus a commercial ketoconazole cream. Using the in vitro finite dose model, the formulations were applied daily to human nail plates for 7 days. Drug absorption was measured by monitoring rate of appearance in each nail layer and the supporting bed. After the multiple day treatment, cumulative concentrations of ketoconazole formulated in novel lacquer in the deep nail layer and the nail bed were significantly greater than cumulative concentrations of commercial ketoconazole (p<0.05), as well as several orders of magnitude greater than the minimal inhibitory concentration (MIC) deemed necessary to inhibit the growth of causative dermatophytic and yeast species. These results suggest that this novel ketoconazole lacquer has the potential to be an effective topical treatment for onychomycosis.
Zaias, Nardo; Rebell, Gerbert; Casal, German; Appel, Jason
The aim of this investigation was to resolve a diagnostic problem and report toenail unit changes attributable to shoe friction that resemble onychomycosis, but that are fungus-negative, and identify common skeletal causes in patients with an asymmetric walking gait. X-ray and clinical feet inspections were performed to evaluate skeletal components that change normal foot biodynamics. Forty-nine patients, all dermatophyte-negative, were reviewed. All patients were those seen in our private practice who demonstrated skeletal and toenail unit abnormalities such as onycholysis, nail bed keratosis resembling distal subungual onychomycosis, nail plate surface abnormalities, distal toe skin keratosis, a diagnostic nail plate shape, as well as several skeletal abnormalities. The clinical abnormalities of the asymmetric gait syndrome include onycholysis, nail bed keratosis, nail plate surface abnormalities, and a diagnostic nail plate shape. By the patient's history, the skeletal findings that were present worsened with age and, in many patients, they were familial. Onychomycosis does not lead to an asymmetric gait nail problem, asymmetric gait toenail does not favor dermatophyte infection, and not all nail dystrophies are the result of an asymmetric walking gait.
Monod, Michel; Bontems, Olympia; Zaugg, Christophe; Léchenne, Barbara; Fratti, Marina; Panizzon, Renato
Fusarium spp. and other non-dermatophyte fungi are repeatedly isolated from abnormal nails. To investigate whether these fungi are the aetiological agents of infection or simply transient contaminants, a PCR/sequencing/RFLP assay was developed for direct and routine identification of the infecting fungi in onychomycosis. Fungal DNA was readily extracted using a commercial kit after dissolving nail fragments in a Na2S solution. Amplification of part of the 28S rDNA by PCR was performed with universal primers and the fungal species were identified by sequencing. The PCR/sequencing results were comparable with microbiological identification from the same nail sample. In addition to dermatophytes, Fusarium spp. and other less frequently isolated non-dermatophyte fungi were identified as single fungal agents in onychomycosis. Moreover, mixed infections were clearly demonstrated in 10% of cases by RFLP analysis of PCR products. Identification of infectious agents could be obtained in 2 days, whilst results from fungal cultures take 1-3 weeks. Rapid and reliable molecular identification of the infectious fungus expedites the choice of appropriate antifungal therapy, thereby improving the cure rate of onychomycosis.
Nestor, Mark; Andriessen, Anneke; Berman, Brian; Katz, Bruce E; Gilbert, Dore; Goldberg, David J; Gold, Michael H; Kirsner, Robert S; Lorenc, Paul Z
Non-thermal laser therapy in dermatology, is a growing field in medical technology by which therapeutic effects are achieved by exposing tissues to specific wavelengths of light. The purpose of this review was to gain a better understanding of the science behind non-thermal laser and the evidence supporting its use in dermatology. A group of dermatologists and surgeons recently convened to review the evidence supporting the use of non-thermal laser for body sculpting, improving the appearance of cellulite, and treating onychomycosis. The use of non-thermal laser for body sculpting is supported by three randomized, double-blind, sham-controlled studies (N = 161), one prospective open-label study (N = 54), and two retrospective studies (N = 775). Non-thermal laser application for improving the appearance of cellulite is supported by one randomized, double-blind, sham-controlled study (N = 38). The use of non-thermal laser for the treatment of onychomycosis is supported by an analysis of three non-randomized, open-label studies demonstrating clinical improvement of nails (N = 292). Non-thermal laser is steadily moving into mainstream medical practice, such as dermatology. Although present studies have demonstrated the safety and efficacy of non-thermal laser for body sculpting, cellulite reduction and onychomycosis treatment, studies demonstrating the efficacy of non-thermal laser as a stand-alone procedure are still inadequate.
Elewski, Boni E; Pollak, Richard A; Pillai, Radhakrishnan; Olin, Jason T
To evaluate the ability of efinaconazole vehicle to reach the site of toenail onychomycosis by spreading through the subungual space between the nail plate and nail bed. Lacquer-based vehicles are primarily limited to application on the nail plate and dependent on nail plate permeation. 11 patients (mean age 48.5 years) were entered with clinically determined onychomycosis. Presence of fungal infection was confirmed by KOH testing in eight patients. Two separate applications of vehicle (with fluorescein incorporated for better visualization) were applied at the hyponychium, avoiding application to the exterior nail plate surface. Affected nails were later clipped to allow examination of the nail bed and further examination of the underside of the nail. Spread of formulation was assessed under visible and UV light conditions by photographing target toenails after vehicle application, and after nail clipping. Assessments under both visible and UV light indicated that the vehicle had spread into the subungual space, with deposition of flourescein wherever vehicle had reached, including in the nail bed. Nail clippings also indicated deposition to the underside of the nail plate. The relative contributions of spreading into the subungual space, or permeation through the nail plate to the efficacy of efinaconazole topical solution, 10% in treating onychomycosis were not assessed. This study suggests that the vehicle developed for efinaconazole topical solution, 10%, when applied at the hyponychium, spreads into the subungual space between the nail plate and nail bed, reaching the site of infection.
Hafeez, Farhaan; Hui, Xiaoying; Selner, Marc; Rosenthal, Bert; Maibach, Howard
Onychomycosis is a common fungal infection of the nail plate and bed that affects up to 14% of the population and can have a substantial impact on the quality of life of those affected. This study compared the onychopharmacokinetics, nail absorption, nail distribution, and nail penetration of [(14)C]-ciclopirox dissolved in novel lipid diffusion enhancers with that of a commercial ciclopirox nail lacquer using the in vitro finite dose model. The penetration rate of ciclopirox was determined by applying doses of topical formulation twice daily to human nail plates for 11 d. Drug absorption was then measured by monitoring its rate of appearance in each nail layer and in the cotton pad/nail supporting bed. After a multiple day treatment, cumulative concentrations of ciclopirox formulated with lipid enhancers in the deep nail layer and the nail bed were significantly greater than cumulative concentrations of the commercial ciclopirox lacquer (p < 0.001) as well as several orders of magnitude greater than the minimal inhibitory concentration (MIC) deemed necessary to inhibit the growth of the causative dermatophyte species. When formulated with lipid enhancers, the amount of ciclopirox in the ventral/intermediate layer and supporting bed dramatically exceed the inhibitory concentration of ciclopirox for the most common onychomycosis organisms. These results suggest that topical ciclopirox with lipid enhancers has the potential to be an effective topical treatment for onychomycosis, and the lipidic pathway of the nail can be utilized as a means of effective transungual delivery.
Thapa, Raj Kumar; Choi, Ju Yeon; Go, Toe Gyung; Kang, Min Hyung; Han, Sang Duk; Jun, Joon-Ho; Son, Mi Won; Yong, Chul Soon; Kim, Jong Oh
Onychomycosis is a prevailing disease caused by fungal infection of nails that mostly affects athletes and the elderly. Ciclopirox is approved by the US Food and Drug Administration for the topical treatment of onychomycosis. However, the desired penetration of ciclopirox into the nail bed has not been achieved via topical application for efficient treatment. Therefore, the main aim of this study was to enhance ciclopirox permeation and retention in nail by the development of a new nail lacquer formulation. We screened the effects of different solvents, alkalizing agents, and permeation enhancers on the permeation of bovine hooves by ciclopirox and its retention in human nail clippings. The results suggest that isopropyl alcohol, potassium hydroxide, and urea as the solvent, alkalizing agent, and permeation enhancer, respectively, improved the permeation of the ciclopirox nail lacquer formulation the most with high flux rates. Comparison of the final formulation and marketed product revealed enhanced retention of ciclopirox from our developed formulation in human nail clippings. Therefore, our newly developed nail lacquer may be a potentially effective formulation for the treatment of onychomycosis in humans.
Elewski, Boni; Tavakkol, Amir
Clinicians now have five oral antifungal therapeutic agents to choose from when assessing the risk–benefits associated with a particular treatment for onychomycosis (OM): griseofulvin, itraconazole, terbinafine, ketoconazole, and fluconazole. Only the first three are approved by the FDA for this indication. Griseofulvin is fungistatic and inhibits nucleic acid synthesis, arresting cell division at metaphase, and impairing fungal wall synthesis. Due to its low cure rates and high relapse, it is rarely used for treatment of onychomycosis. Itraconazole is a broad spectrum drug and is effective against dermatophytes, candida, and some nondermatophytic molds. Itraconazole works by inhibiting ergosterol synthesis via cytochrome P-450 (CYP450)-dependent demethylation step. This azole antifungal agent is metabolized in the liver by cytochrome P-450 3A4 (CYP3A4), and therefore has the potential to interact with drugs metabolized through this pathway. Terbinafine, an allylamine, is fungicidal and remains at therapeutic levels in keratinized tissues, but with a short plasma half-life of 36 hours. Terbinafine has the advantage in that it does not inhibit CYP3A4 isoenzyme during its metabolism where some 50% of all commonly prescribed drugs are metabolized. The only potentially significant drug interaction with terbinafine is with the cytochrome P-450 2D6 (CYP2D6) isoenzyme. The lack of widely reported or published clinically relevant drug interactions, and extensive experience from a large prospective, surveillance study conducted in “real world” setting with no patient exclusions, suggest that this is not a major issue. The high cure rates of terbinafine against dermatophytes, as shown in many studies since its launch in the 1990s, together with lack of clinically significant drug interactions and well established safety record, indicate the use of continuous oral terbinafine as the top choice for the treatment of onychomycosis in most patients. PMID:18360572
Salari, Samira; Ayatollahi Mousavi, Seyyed Amin; Hadizadeh, Sanaz; Izadi, Alireza
Superficial and cutaneous fungal infections (SCFIs) are an important public health problem and are common in tropical and subtropical countries. Pityriasis versicolor, dermatophytosis, erythrasma, onychomycosis, and otomycosis are the major diseases associated with SCFIs. The aim of this study was to evaluate the prevalence and causative agents of dermatomycoses over a period of 10 years in Kerman province, southeast of Iran. A number of 1782 subjects, including 1096 females and 686 males, with cutaneous disorders in their skin, nail, and hair suspected to have SCFIs participated in this study. The collected specimens were examined using direct microscopy examination, staining, culture on specific media and PCR-RFLP technique. In total, 617 (34.62%) subjects had SCFIs, of whom 290 (47%) were female and 327 (53%) were male. Identified SCFIs included yeast infections, dermatophytosis, saprophyte onychomycosis, erythrasma, and otomycosis due to non-dermatophytic molds (NDMs). The highest prevalence of dermatomycoses was found among the 41-50-year and 31-40-year age groups. Tinea unguium was the most common clinical pattern of dermatomycoses, and T. mentagrophytes was the predominant agent. Also, Aspergillus spp. were the most common NDMs agents of onychomycosis and otomycosis. This study summarized the epidemiological trends and etiologic agents of SCFIs in a 10-year period in Kerman, southeast of Iran. Consideration of the current epidemiologic trends in the prevalence and knowledge of the exact causative agents of SCFIs may play an important key role towards further investigations, diagnosis, and modification of current treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.
Machado Vila, Taissa Vieira; Sousa Quintanilha, Natália; Rozental, Sonia
Onychomycosis is a fungal nail infection that represents ∼50 % of all nail disease cases worldwide. Clinical treatment with standard antifungals frequently requires long-term systemic therapy to avoid chronic disease. Onychomycosis caused by non-dermatophyte moulds, such as Fusarium spp., and yeasts, such as Candida spp., is particularly difficult to treat, possibly due to the formation of drug-resistant fungal biofilms on affected areas. Here, we show that the alkylphospholipid miltefosine, used clinically against leishmaniasis and cutaneous breast metastases, has potent activity against biofilms of Fusarium oxysporum and Candida albicans formed on human nail fragments in vitro. Miltefosine activity was compared with that of commercially available antifungals in the treatment of biofilms at two distinct developmental phases: formation and maturation (pre-formed biofilms). Drug activity towards biofilms formed on nail fragments and on microplate surfaces (microdilution assays) was evaluated using XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assays, and drug effects on fingernail biofilms were analysed by scanning electron microscopy (SEM). For F. oxysporum, miltefosine at 8 μg ml- 1 inhibited biofilm formation by 93%, whilst 256 μg ml- 1 reduced the metabolic activity of pre-formed nail biofilms by 93%. Treatment with miltefosine at 1000 μg ml- 1 inhibited biofilm formation by 89% and reduced the metabolic activity of pre-formed C. albicans biofilms by 99%. SEM analyses of biofilms formed on fingernail fragments showed a clear reduction in biofilm biomass after miltefosine treatment, in agreement with XTT results. Our results show that miltefosine has potential as a therapeutic agent against onychomycosis and should be considered for in vivo efficacy studies, especially in topical formulations for refractory disease treatment.
Fich, Felix; Abarzúa-Araya, Alvaro; Pérez, Mario; Nauhm, Yalile; León, Eugenia
Background: Onychomycosis of the fingernails and toenails is generally caused by dermatophytes and yeasts. Toenail mycoses involve mainly dermatophytes but when Candida is also involved, the strain most commonly isolated worldwide is C. albicans. Aims: To determine Candida strains prevailing in onychomycosis. Materials and Methods: A retrospective, observational and descriptive study of fungal cultures retrieved from the registry of the microbiology laboratory of the Pontificia Universidad Católica was performed. Specimens obtained from patients attending the healthcare network between December 2007 and December 2010 was analyzed. Statistical Analysis: A descriptive statistical analysis was performed. Results: Candida was retrieved from 467 of 8443 specimens (52% fingernails and 48% toenails). Cultures were negative in 5320 specimens (63.6%). Among Candida-positive cultures, parapsilosis was the most commonly isolated strain with 202 cases (43.3%). While isolates of Candida guillermondii were 113 (24.2%), those of Candida albicans were 110 (23.6%), those of spp. were 20 (4.3%) and there were 22 cases of other isolates (4.71%). Among the 467 patients with positive cultures for Candida, 136 (29,1%) were men and 331 (70,9%) were women. All patients were older than 18 years old. Clinical files were available for only 169 of the 467 patients with positive cultures for Candida. For those, age, gender, underlying illnesses and use of immunossupresive agents during the trial was reviewed. Conclusions: The present study shows that both C. parapsilosis as well as C. guillermondii appear as emerging pathogens that would be in fact taking the place of C. albicans as the most commonly isolated pathogen in patients with Candida onychomycosis. The relative percentage of C parapsilosis increases every year. Identification of Candida strains as etiological agents of nail candidiasis becomes relevant to the management both nail as well as systemic candidiasis, in view of the
Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I
Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.
Decker, Ashley; Scher, Richard K.; Avarbock, Andrew
Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years. PMID:27171597
Stephen, Sasha; Tosti, Antonella; Rubin, Adam I
"Nail clipping is a simple technique for diagnosis of several nail unit dermatoses. This article summarizes the practical approach, utility, and histologic findings of a nail clipping in evaluation of onychomycosis, nail unit psoriasis, onychomatricoma, subungual hematoma, melanonychia, and nail cosmetics, and the forensic applications of this easily obtained specimen. It reviews important considerations in optimizing specimen collection, processing methods, and efficacy of special stains in several clinical contexts. Readers will develop a greater understanding and ease of application of this indispensable procedure in assessing nail unit dermatoses."
Weisenborn, Jascha L F; Kirschner, Roland; Cáceres, Orlando; Piepenbring, Meike
In a survey of mycotic human skin and nail lesions in Chiriquí, Western Panama, Talaromyces indigoticus was isolated in one case. This ascomycete is characterised by formation of gymnothecia containing oval, spinose and yellow ascospores, which become blue in mounting fluids, and by short monoverticillate or biverticillate penicilli. It is here reported the first time for Panama and the American continent. Because the strain was isolated from an onychomycosis together with a dermatophyte and other fungal strains, the pathological impact of Talaromyces indigoticus is not evident.
Møller, Maiken; Bygum, Anette
Cutaneous lupus erythematosus can be induced or precipitated by a variety of drugs. Among the cutaneous variants of lupus, subacute cutaneous lupus erythematosus is the one most often associated with drug intake. The time lag between drug intake and skin eruption makes the clinical association less obvious, and the condition is often overlooked. We report on a 50-year-old woman with previously diagnosed systemic lupus erythematosus who had a severe cutaneous flare-up seven weeks after starting treatment with terbinafine for suspected onychomycosis.
Saedi, Nazanin; Green, Jeremy B; Dover, Jeffrey S; Arndt, Kenneth A
Quality-switched (QS) lasers and their applications have evolved greatly since the ruby laser's effect on tattoo ink was first reported in the 1960s. The 1983 description of selective photothermolysis explained the efficacy of QS lasers for the treatment of cutaneous pigmented lesions and tattoos and cemented their status as the gold standard for these targets. Within the past decade, the uses for QS lasers have expanded dramatically, including nonablative rejuvenation and the treatment of onychomycosis. Additional applications and refined techniques and technologies promise to maintain the stature of QS lasers as an integral part of the laser surgeon's arsenal.
Adams, B B; Lucky, A W
We present a case report of a 14-year-old white male who developed hyperkeratotic plaques on the distal aspects of 2 toes. He was referred by his primary care physician for the treatment of onychomycosis. With questioning, the patient stated that he played center for his high school basketball team. After physical examination, he was diagnosed with callosities caused by his basketball activities. Proper nail hygiene and wearing of larger footwear resulted in improvement of his callosities. Sports-related cutaneous injuries should be included in the differential diagnosis of nail and toe abnormalities.
The dermatophytic infections are superficial mycoses common in Mexico, they have an estimated frequency of 5% in dermatological outpatients. In this review we present a global view of these mycoses as well as their etiological agents in tinea capitis, tinea pedis, tinea corporis, tinea cruris and onychomycosis and also uncommon infections such as tinea imbricata and epidermophytosis of the diaper area. We also analyze these infections in diabetic patients, healthy carriers and dermatophytic infections in pets and laboratory animals. The most important publications about dermatophytosis in Mexico in the dermatological, epidemiological or mycological area are reviewed, specially those published in the last ten years.
Khebizi, S; Mansouri, R
We report an observation of extensive and atypical dermatophytosis to Trichophyton rubrum coexisting with fingernails and tinea manuum candidiasis in a 13-year-old girl presenting inflammatory cutaneous lesions, involvement of scalp, as well as total dystrophic onychomycosis of feet associated with a perionyxis of hands. The results of the mycological examination of specimen showed fungal elements of septate hyphae and pilar parasitism. The fungal culture allowed the diagnosis of certainty of the dermatophytosis to T. rubrum. The therapeutic success of this infection was obtained thanks to the administration of antifungals by oral route. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Squeo, R F; Beer, R; Silvers, D; Weitzman, I; Grossman, M
A 55-year-old renal transplant recipient with onychomycosis and chronic tinea pedis presented with tender nodules on his left medial heel. He then developed papules and nodules on his right foot and calf. A skin biopsy demonstrated periodic acid-Schiff (PAS) positive, thick walled round cells, 2 to 6 microm in diameter, in the dermis. Skin biopsy culture grew Trichophyton rubrum. T. rubrum has been described as an invasive pathogen in immunocompromised hosts. The clinical presentation, histopathology, and early fungal culture growth suggested Blastomyces dermititidis in the differential diagnosis before the final identification of T. rubrum.
Hopp, Shelby; Quest, Tyler L; Wanat, Karolyn A
The article highlights different educational and practice gaps in infectious diseases as they pertain to dermatology. These gaps include the use of antibiotics in relation to atopic dermatitis and acne vulgaris, treatment of skin and soft tissue infection, and diagnosis and treatment of onychomycosis. In addition, practice gaps related to use of imiquimod for molluscum contagiosum, risk of infections related to immunosuppressive medications and rates of vaccination, and the use of bedside diagnostics for diagnosing common infections were discussed. Copyright © 2016 Elsevier Inc. All rights reserved.
Dermatophytic infections of the skin, hairs and nails are very common and are very variable in aspect. In skin, inflammatory symptoms are often absent, but in other cases they may be very pronounced, in particular when caused by zoophilic dermatophytes. In onychomycosis, it is very difficult to make the differential diagnosis with other causes of onychodystrophy on purely clinical grounds; indeed, even in case of fungal infection, the causative agent can be suspected on clinical grounds only in a minority of cases. The clinical presentation of skin infections, infections of the scalp and beard, and the nails are presented more in detail.
Oppel, Tilmann; Korting, Hans Christian
Onychodystrophy represents various pathologic processes of the nails such as infectious and noninfectious disorders including onychomycosis, psoriasis and allergic and irritant dermatitis. Nail changes may also be a clue to other dermatological or systemic diseases. But often it is difficult to establish the diagnosis as most nail changes are unspecific. The purpose of this article is to give an overview of the anatomy of the nail organ and possible causes of onychodystrophy. Therapeutic modalities are reviewed as well as modes of analysis. PMID:19675700
Gregorí Valdes, Barbara S; Serro, Ana Paula; Gordo, Paulo M; Silva, Alexandra; Gonçalves, Lídia; Salgado, Ana; Marto, Joana; Baltazar, Diogo; Dos Santos, Rui Galhano; Bordado, João Moura; Ribeiro, Helena Margarida
Onychomycosis is a fungal nail infection. The development of new topical antifungal agents for the treatment of onychomycosis has focused on formulation enhancements that optimize the pharmacological characteristics required for its effective treatment. Polyurethanes (PUs) have never been used in therapeutic nail lacquers. The aim of this work has been the development of new PU-based nail lacquers with antifungal activity containing 1.0% (wt/wt) of terbinafine hydrochloride. The biocompatibility, wettability, and the prediction of the free volume in the polymeric matrix were assessed using a human keratinocytes cell line, contact angle, and Positron Annihilation Lifetime Spectroscopy determinations, respectively. The morphology of the films obtained was confirmed by scanning electron microscopy, while the nail lacquers' bioadhesion to nails was determined by mechanical tests. Viscosity, in vitro release profiles, and antifungal activity were also assessed. This study demonstrated that PU-terbinafine-based nail lacquers have good keratinocyte compatibility, good wettability properties, and adequate free volume. They formed a homogenous film after application, with suitable adhesion to the nail plate. Furthermore, the antifungal test results demonstrated that the terbinafine released from the nail lacquer Formulation A PU 19 showed activity against dermatophytes, namely Trichophyton rubrum. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Gandham, N R; Vyawahare, C R; Chaudhaury, N; Shinde, R A
Onychomycosis is a fairly common condition seen in a dermatology clinic. Dermatophytes Trichophyton and Epidermophyton are the known filamentous fungi implicated. The yeast-like fungi such as Candida less commonly cause Onychomycosis. The genus Prototheca may on preliminary observation resemble yeast-like fungi but a detailed microscopy will reveal the absence of budding and presence of endospores. Onychoprotothecosis is an uncommon presentation of human protothecosis. Of the two Prototheca species (Prototheca zopfii and Prototheca wickerhamii) known to cause the disease, P. wickerhamii has been reported more commonly. We report a culture proven case of this condition caused by P. zopfii. The patient, a 55-year-old housewife presented with discolouration and breaking off of the right thumb and forefinger nails since a period of six months. Samples of nail scrapping sent to the Microbiology Laboratory were culture-positive for Prototheca. Speciation by the automated Vitek-2 system (bioMerieux) identified the isolate as P. zopfii, which was further confirmed at PGI, Chandigarh.
Archer-Dubon, Carla; Orozco-Topete, Rocío; Leyva-Santiago, Jaime; Arenas, Roberto; Carbajosa, Josefina; Ysunza, Alberto
Superficial mycotic infections of the feet are usually caused by Tricophyton rubrum, predominantly affecting adults and resulting from the use of occlusive footwear. We carried out a mycologic study of superficial foot infections in a rural school in Mexico where most people wear a leather, nonocclusive sandal. Forty students had clinical signs of 50 fungal infections of the foot: 39 athlete's foot and 11 onychomycosis. Thirty-one boys and 9 girls were studied. Hyphae were seen in 11 cases of athlete's foot and 5 of onychomycosis. Twenty-one cultures were positive (42%). The most frequently isolated fungi were the opportunistic Trichosporon cutaneum in 42.8%, Candida sp. (23.8%), Trichophyton mentagrophytes (23.8%), and Candida glabrata (9.5%). Superficial mycotic infections of the feet and nails were most frequent in children and adolescents who usually wear nonocclusive shoes. The most frequent pathogens were Candida sp. and T. mentagrophytes. It is interesting to note the prevalence of T. cutaneum that has recently been implicated in mycoses of the feet and nails. We did not isolate T. rubrum in any patient.
Bassiri-Jahromi, Shahindokht; Khaksari, Ali Asghar
Cutaneous fungal infections are common in Tehran, Iran, and causative organisms include dermatophytes, yeasts and non-dermatophyte molds. The prevalence of superficial mycosis infections has risen to such a level that skin mycoses now affect more than 20-25% of the world's population, making them the most frequent form of infection. Our aim was to determine the prevalence of superficial cutaneous fungal infections especially dermatophytosis in our Medical Mycology Laboratory in the Pasteur Institute of Iran, Tehran. A total of 17,573 specimens were collected from clinically suspected tinea corporis, tinea cruris, tinea capitis, tinea faciei, tinea pedis, tinea manuum and finger and toe onychomycosis from 2000 to 2005. Patients were referred to our laboratory for direct examination, fungal culture and identification. The incidence of each species was thus calculated. Dermatophytes remain the most commonly isolated fungal organisms, except from clinically suspected finger onychomycosis, in which case Candida species comprise >7% of the isolates. Epidermophyton floccosum remains the most prevalent fungal pathogen and increased incidence of this species was observed in tinea cruris. Trichophyton tonsurans continues to increase in incidence. This study identifies the epidemiologic trends and the predominant organisms causing dermatophytosis in Tehran, Iran. These data can be used to ascertain the past and present trends in incidence, predict the adequacy of our current pharmacologic repertoire and provide insight into future developments. Consideration of the current epidemiologic trends in the incidence of cutaneous fungal pathogens is of key importance to investigational effort, diagnosis and treatment.
Sato, Tomotaka; Takayanagi, Atsushi; Nagao, Keisuke; Tomatsu, Nobuhiro; Fukui, Toshifumi; Kawaguchi, Masahiro; Kudoh, Jun; Amagai, Masayuki; Yamamoto, Nobuko; Shimizu, Nobuyoshi
Fungal diseases in immunocompromised hosts pose significant threats to their prognoses. An accurate diagnosis and identification of the fungal pathogens causing the infection are critical to determine the proper therapeutic interventions, but these are often not achieved, due to difficulties with isolation and morphological identification. In an effort to ultimately carry out the simultaneous detection of all human pathogenic microbes, we developed a simple system to identify 26 clinically important fungi by using a combination of PCR amplification and DNA microarray assay (designated PCR-DM), in which PCR-amplified DNA from the internal transcribed spacer region of the rRNA gene was hybridized to a DNA microarray fabricated with species-specific probes sets using the Bubble Jet technology. PCR-DM reliably identified all 26 reference strains; hence, we applied it to cases of onychomycosis, taking advantage of the accessibility of tissue from skin. PCR-DM detected fungal DNA and identified pathogens in 92% of 106 microscopy-confirmed onychomycosis specimens. In contrast, culture was successful for only 36 specimens (34%), 3 of which had results inconsistent with the results of PCR-DM, but sequence analysis of the isolates proved that the PCR-DM result was correct. Thus, PCR-DM provides a powerful method to identify pathogenic fungi with high sensitivity and speed directly from tissue specimens, and this concept could be applied to other fungal or nonfungal infectious human diseases in less accessible anatomical sites.
Tanase, Alina; Colita, Anca; Ianosi, Gabriel; Neagoe, Daniela; Branisteanu, Daciana Elena; Calina, Daniela; Docea, Anca Oana; Tsatsakis, Aristidis; Ianosi, Simona Laura
Fusarium infection is a severe fungal infection caused by fungi of the genus Fusarium. It most commonly occurs in immunocompromised patients with malignant hematological comorbidities or secondary to hematopoietic stem cell transplant. The classical route of contamination is through inhalation but infection may also occur through contiguity with a skin lesion. This report describes the case of a 24-year-old woman who developed graft-vs.-host disease (GVHD) at 220 days after receiving an allogeneic stem cell transplant from a sibling donor for Hodgkin disease. On day 330 after transplant the patient presented with fever and several painful subcutaneous, tender, red nodules with ulcerative and necrotic features on the pelvic region and right leg, extensive glass infiltrative lesions in the lungs and pansinusitis; however, the patient did not have onychomycosis. Following skin biopsy, culture of cutaneous lesions, computed tomography (CT) scanning of the lungs and CT scanning and magnetic resonance imaging of facial sinuses the patient was diagnosed with disseminated Fusarium species infection. Despite intensive treatment with voriconazole, the patient succumbed with respiratory insufficiency on day 400 after transplant. This case is noteworthy because the patient did not have any additional risk associated with the allogeneic transplant; there was no transplant mismatch, no severe neutropenia and no prior clinical signs of onychomycosis. The association of skin lesions with GVHD lesions increased the initial immunosuppression and delayed diagnosis. PMID:27698695
Diongue, K; Diallo, M A; Badiane, A S; Seck, M C; Ndiaye, M; Ndoye, N W; Ndiaye, Y D; Dieye, B; Déme, A; Ndiaye, I M; Ndir, O; Ndiaye, D
In recent years, the incidence of superficial fungal infections involving nondermatophytic and noncandidal fungi increased considerably. The objective of this work was to analyze the epidemiological, clinical and mycological fungal infections due to nondermatophytic and noncandidal fungi diagnosed in the laboratory of parasitology-mycology of Le Dantec hospital in Dakar. With a retrospective study of the various cases of nondermatophytic and noncandidal fungi isolated in the laboratory of parasitology-mycology during the period of November 2013 to December 2014, we collected 22 cases of infections in 11 men and 11 women; age ranging from 17 to 75 years with a mean of 45.3 years (sex ratio=1): eight cases of intertrigo, seven cases of onychomycosis, four cases of palmoplantar keratoderma (KPP), a case of onychomycosis associated with interdigital intertrigo, a case of infectious myositis and one case of African histoplasmosis. We have isolated and identified a total of 22 nondermatophytic and noncandidal fungi: ten Fusarium, five Trichosporon, two Chrysosporium, two Geotrichum, one Rhodotorula, one Neoscytalidium dimidiatum and one Histoplasma capsulatum var. duboisii. So we are seeing the emergence of nondermatophytic and noncandidal increasingly isolated from superficial and local lesions. These fungi, generally contaminants or commensal, cause a problem regarding their direct involvement in pathological processes in which they are isolated. So we should respect the recommendations proposed for their involvement in pathological processes and, by a collaboration between clinician and biologist, demonstrate their real involvement through effective, targeted treatment.
García-Humbría, Leila; Richard-Yegres, Nicole; Pérez-Blanco, Maigualida; Yegres, Francisco; Mendoza, Mireya; Acosta, Arnaldo; Hernández, Rosaura; Zárraga, Eluz
Superficial mycoses are considered to affect more frequently patients with type 2 diabetes mellitus (DM-2), specially onychomycosis and Tinea pedis. The purpose of this study was to compare the dermatophytoses, candidiasis and Pitiriasis versicolor frequency between 40 patients with DM-2 and 40 healthy persons of either sex, 40 years old or more. Clinical, metabolic, mycologic and inmunologic studies against Candida albicans, were carried out. Both diabetics 75% (30/40) and controls 65% (26/40) presented a high frequency of superficial mycoses (no significant difference p = 0.329). Pitiriasis versicolor was not detected in diabetic patients. They presented Tinea unguium, concomitant with Tinea pedis, with a higher frequency. The predominant dermatophyte was Trichophyton rubrum 18/23 (78%) in diabetics and 8/16 (50%) in non diabetics. Candida was isolated as commensal from oral mucous: 23/40 (58%) in diabetics and 21/40 (52%) in non diabetics (serotipo A was the more frequent), and from onychomycosis: 11/40 (28%) in diabetics and 12/40 (30%) in non diabetics. The immunological response was the same in both groups: celular 100%, humoral 20%. No statistical correlation among superficial mycoses, blood glucose level, glycosylated hemoglobin values or the time suffering the disease was observed. The high susceptibility to dermatophytes and Candida sp. infection showed to be associated with age and no with the diabetic type 2 condition in those patients.
Hernández-Salazar, Amparo; Carbajal-Pruneda, Patricia; Fernández Martínez, Ramón; Arenas, Roberto
Dermatophytosis is the most common mycosis in the world up to 80% caused by Trichophyton rubrum. The aim of the present study was to describe the clinical characteristics of the dermatophytosis caused by T. rubrum in a dermatological outpatient clinic during a ten years period, from 1996 to 2005. We collected the data from patients with a dermatophytosis from which we have isolated T. rubrum. A total of 776 patients with dermatophytosis caused by T. rubrum were found. A slight predominance of female patients (56.2%) was observed. The most commonly affected age group was those in the third to the fifth decade of life, and house working women (33.5%) were predominant. Onychomycosis was found in 63% of the cases, tinea pedis in 22.7%, tinea corporis in 5.2% and tinea cruris in 2.8%. In onychomycosis, the first toe nail was the most commonly affected (58.9%) and the dystrophic type was seen in 50.7% of them.
Tawfik, Abeer Attia; Noaman, Islam; El-Elsayyad, Hasan; El-Mashad, Noha; Soliman, Mona
Onychomycosis is a widespread public health problem, in which T. rubrum and T. mentagrophytes is the commenest causative organisms. Current medical therapy has many drawbacks and side effects. Methylene blue (m.b) photodynamic therapy (pdt) proved efficacy but with lengthy sessions. Optimizing methylene blue photodynamic therapy by combination of methylene blue photosensitizer and gold nanoparticles (aunps) in a composite as gold nanoparticles are efficient delivery systems and efficient enhancers of photosensitizers for antifungal photodynamic therapy. Eighty newzealand rabbit (Oryctolagus cuniculus) were used and categorized in eight equal groups as follows; healthy and infection control, composite photodynamic therapy and five comparative groups. Photodynamic therapy was initiated at day three to five post inoculation, for four sessions forty eight hours apart. Each group divided and light exposure at two fluencies; 80J and 100J. All groups were investigated macroscopically and microscopically (histopathology and scanning electron microscope) also flowcytometry assessment for cell death and X-ray analysis for gold nanoparticles accumulation in brain and liver tissues were determined. Recovery from infection approaching 96% in gold nanoparticles+light group, around 40% in methylene blue photodynamic therapy and 34% in composite photodynamic therapy. The observed findings confirmed by apparent decrease of apoptosis, however small amounts of gold nanoparticles detected in brain and liver. Light stimulated gold nanoparticles is a promising tool in treatment of onychomycosis. Copyright © 2016 Elsevier B.V. All rights reserved.
Bohni, Nadine; Hofstetter, Valérie; Gindro, Katia; Buyck, Bart; Schumpp, Olivier; Bertrand, Samuel; Monod, Michel; Wolfender, Jean-Luc
The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species in co-culture revealed de novo induction of fusaric acid based on HRMS. Structure confirmation of this toxin, using sensitive microflow NMR, required only three 9-cm Petri dishes of fungal culture. A targeted metabolomics study based on UHPLC-HRMS confirmed that the production of fusaric acid was strain-dependent. Furthermore, the detected toxin levels suggested that onychomycosis-associated fungal strains of the F. oxysporum and F. fujikuroi species complexes are much more frequently producing fusaric acid, and in higher amount, than strains of the F. solani species complex. Fusarium strains producing no significant amounts of this compound in pure culture, were shown to de novo produce that compound when grown in co-culture. The role of fusaric acid in fungal virulence and defense is discussed.
Verrier, Julie; Monod, Michel
Identification of fungi in dermatological samples using PCR is reliable and provides significantly improved results in comparison with cultures. It is possible to identify the infectious agent when negative results are obtained from cultures. In addition, identification of the infectious agent can be obtained in 1 day. Conventional and real-time PCR methods used for direct fungus identification in collected samples vary by DNA extraction methods, targeted DNA and primers, and the way of analysing the PCR products. The choice of a unique method in a laboratory is complicated because the results expected from skin and hair sample analysis are different from those expected in cases of onychomycosis. In skin and hair samples, one dermatophyte among about a dozen possible species has to be identified. In onychomycosis, the infectious agents are mainly Trichophyton rubrum and, to a lesser extent, Trichophyton interdigitale, but also moulds insensitive to oral treatments used for dermatophytes, which renders fungal identification mandatory. The benefits obtained with the use of PCR methods for routine analysis of dermatological samples have to be put in balance with the relative importance of getting a result in a short time, the price of molecular biology reagents and equipment, and especially the time spent conducting laboratory manipulations.
Hui, Xiaoying; Baker, Stephen J; Wester, Ronald C; Barbadillo, Sherry; Cashmore, Anne K; Sanders, Virginia; Hold, Karin M; Akama, Tsutomu; Zhang, Yong-Kang; Plattner, Jacob J; Maibach, Howard I
Onychomycosis is a challenging fungal infection to treat topically, likely due to the unique properties of the nail plate. This seemingly impenetrable barrier has high resistance to the passage of antifungal drugs in sufficient concentrations to kill the causative fungi deep in the nail bed. Recently, a new class of antifungal agent was described, termed oxaboroles, which have broad-spectrum activity. These oxaboroles were designed with properties believed to be required to allow for easier transit through the nail plate. Herein, we report (i) the nail penetration results of four oxaboroles that led to the selection of AN2690, (ii) the results of the nail penetration of AN2690 from four vehicles, and (iii) the nail penetration of AN2690 in its chosen vehicle compared to a commercial control, ciclopirox. AN2690 has superior penetration compared to ciclopirox, and achieves levels within and under the nail plate that suggest it has the potential to be an effective topical treatment for onychomycosis. (c) 2007 Wiley-Liss, Inc.
Amichai, Boaz; Mosckovitz, Rachel; Trau, Henri; Sholto, Orit; Ben-Yaakov, Shirly; Royz, Michael; Barak, David; Nitzan, Boaz; Shemer, Avner
Onychomycosis is a common disease. Topical treatment is usually not effective due to limitation of trans-nail delivery of antifungal drugs. Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. To evaluate the influence of several parameters including; the effect of low electrical current, incubation time and the presence of electrolyte (NaCl or KCl) on the penetration of terbinafine through the nail plate into the nail bed, using various formulations and concentrations of terbinafine HCl. Iontophoresis was applied across porcine and human nail in vitro to assess its efficiency in enhancing delivery of terbinafine HCl. In this study, we have demonstrated that an optimal electrolyte concentration (1% NaCl or KCl) is required for an effective delivery. There is a significant increase in drug delivery into the nail and into the receiving compartment in the presence of 3% DMSO. This study demonstrates the efficacy of iontophoresis in enhancing the trans-nail delivery of terbinafine. Clinical studies are needed to evaluate the feasibility, efficacy and safety of iontophoresis of terbinafine in onychomycosis in human.
Delgado-Charro, Maria Begoña
Topical drug delivery to treat nail diseases such as onychomycosis and psoriasis is receiving increasing attention. Topical nail delivery is challenged by the complicated structure of the nail and the low permeability of most drugs across the nail plate. Considerable effort has been directed at developing methods to promote drug permeation across the nail plate. Iontophoresis efficiently enhances molecular transport across the skin and the eye and is now being tested for its potential in ungual delivery. This review covers the basic mechanisms of transport (electro-osmosis and -migration) and their relative contribution to nail iontophoresis as well as the key factors governing nail permselectivity and ionic transport numbers. Methodological issues concerning research in this area are summarized. The data available in vivo on nail iontophoresis of terbinafine specifically are reviewed in separate sections. Our understanding of nail iontophoresis has improved considerably since 2007; most decisively, the feasibility of nail iontophoresis in vivo has been clearly demonstrated. Future work is required to establish the adequate implementation of the technique so that its clinical efficacy to treat onychomycosis and nail psoriasis can be unequivocally determined.
The absorption of drugs into the nail unit, following topical application to the nail plate, is highly desirable to treat nail disorders, such as onychomycosis (fungal infections of the nail). Nail permeability is however quite low and limits topical therapy to early/mild disease states. In this paper, the recent research into ungual drug delivery is reviewed. The nail unit and the two most common diseases affecting the nail--onychomycosis and nail psoriasis--are briefly described to set the scene and to give an overview of the nature and scope of the problem. The factors, which affect drug uptake and permeation through the nail plate such as solute molecular size, hydrophilicity/hydrophobicity, charge, and the nature of the vehicle, are then discussed, followed by ways of enhancing drug transport into and through the nail plate. Finally, drug-containing nail lacquers which, like cosmetic varnish, are brushed onto the nail plates to form a film, and from which drug is released and penetrates into the nail, are reviewed.
Abadi, Danielle; Zderic, Vesna
A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative.
Ngan, Antonio H. Y.; Tsang, Chris C. C.; Ling, Ian W. H.; Chan, Jasper F. W.; Leung, Shui-Yee; Yuen, Kwok-Yung
We characterized 12 Exophiala strains isolated from patients over a 15-year period to the species level using phenotypic tests and internal transcribed spacer (ITS) and Rpb1 sequencing and described the clinical spectrum of the 12 patients. Eight patients had nail or skin infections, two had invasive infections, and two had colonization of the gastrointestinal tract. ITS and Rpb1 sequencing showed that 11 of the 12 strains were known Exophiala species (E. oligosperma [n = 3], E. jeanselmei [n = 2], E. lecanii-corni [n = 2], E. bergeri [n = 1], E. cancerae [n = 1], E. dermatitidis [n = 1], and E. xenobiotica [n = 1]), which included the first reported cases of onychomycosis caused by E. bergeri and E. oligosperma. The 12th strain (HKU32T), isolated from the nail clipping of the right big toe of a 68-year-old female patient with onychomycosis, possessed unique morphological characteristics distinct from other Exophiala species. It grew very slowly and had a velvety colony texture after 28 days, short conidiophores of the same olivaceous color as the supporting hyphae, numerous spores, and no chlamydospore-like cells. ITS, Rpb1, β-tubulin, and β-actin gene sequencing unambiguously showed that HKU32T was clustered with but formed branches distinct from other Exophiala species in phylogenetic trees. We propose the new species Exophiala hongkongensis to describe this novel fungus. PMID:23152554
Koksal, Fatma; Er, Emine; Samasti, Mustafa
The aim of the present study was to determine the percentage of agents, which can give rise to superficial fungal infections in Istanbul, Turkey. Between 2000 and 2007, the clinical samples collected from 8,200 patients attending the outpatient Dermatology Clinic at Mihrimahsultan Medical Center were examined by direct microscopy and culture. Pathogen fungi were detected in 5,722 of the patients. Of the isolates were 4,218 (74%) dermatophytes, 1,196 (21%) Candida sp., 170 (3%) Malassezia furfur, and 138 (2%) Trichosporon sp. Among the dermatophytes, Trichophyton sp. was the most common isolate followed by Epidermophyton floccosum (243) and Microsporum sp. Among the Candida species, C. albicans (549) was also frequently found. Onychomycosis was the most prevalent type of infection, followed by tinea pedis, tinea cruris, tinea corporis, and tinea capitis. In conclusion, our study showed that the most common isolated agents from superficial infections were T. rubrum being Candida sp. the second most prevalent.
Kumar, Kartik; Gill, Anna; Shafei, Rachelle; Wright, Janine L
Terbinafine is a commonly prescribed antifungal agent used in the treatment of trichophytic onychomycosis and chronic cutaneous mycosis that are resistant to other treatments. This case report highlights a rarely documented but important adverse hepatic reaction that was caused by the use of oral terbinafine. A woman in her thirties presented with a 3-week history of jaundice, malaise, itching, nausea, decreased appetite, weight loss, dark orange urine and intermittent non-radiating epigastric pain. She had recently finished a 3-week course of oral terbinafine for a fungal nail infection. Liver biopsy findings were consistent with chronic active hepatitis secondary to a drug reaction. A few days after initial presentation, the patient developed erythema nodosum. Delayed development of erythema nodosum secondary to terbinafine could not be excluded.
Ma, Y; Chen, X; Guan, S
Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine.
Ferwerda, Bart; Ferwerda, Gerben; Plantinga, Theo S.; Willment, Janet A.; van Spriel, Annemiek B.; Venselaar, Hanka; Elbers, Clara C.; Johnson, Melissa D.; Cambi, Alessandra; Huysamen, Cristal; Jacobs, Liesbeth; Jansen, Trees; Verheijen, Karlijn; Masthoff, Laury; Morré, Servaas A.; Vriend, Gert; Williams, David L.; Perfect, John R.; Joosten, Leo A.B.; Wijmenga, Cisca; van der Meer, Jos W.M.; Adema, Gosse J.; Kullberg, Bart Jan; Brown, Gordon D.; Netea, Mihai G.
SUMMARY Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the β-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate β-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with β-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense. PMID:19864674
Rocha, N; Velho, G; Horta, M; Martins, A; Massa, A
Familial amyloidotic polyneuropathy is an autosomal dominant amyloidosis, characterized by the systemic deposition of amyloid with a particular involvement of the peripheral nerves. The disease generally manifests as a severe sensory, motor and autonomic neuropathy. Cardiomyopathy, nephropathy, vitreous opacities and carpal tunnel syndrome may occur in a variable association with the neuropathy. Trophic dermatological lesions are frequent in the more advanced stages of the disease. We examined the skin of 142 patients. The cutaneous manifestations more frequently observed were: xerosis (81.6%), seborrheic dermatitis (21.8%), traumatic and burn lesions (19.7%), acne (18.3%), neurotrophic ulcers (14%) and onychomycosis (10.5%). Among the hepatic transplanted patients (31%), seborrheic dermatitis and acne were the most frequent diagnoses.
Padilha, Carolina Barbosa de Sousa; Balassiano, Laila Klotz de Almeida; Pinto, Julyana Calegari; de Souza, Flávia Crespo Schueler; Kac, Bernard Kawa; Treu, Curt Mafra
Although subungual squamous cell carcinoma is rare, it is the most common primary malignant neoplasms in this location. The higher incidence occurs in the fingernails, but involvement of the toenails is also possible. Subungual squamous cell carcinoma often looks like other more common benign lesions, such as fungal infection, onychomycosis, or viral wart. These factors, together with a general lack of awareness of this disease among physicians, often result in delayed diagnosis. Therefore, it is underdiagnosed, with few reports in the literature. The authors present a case of a man with a diagnosis of subungual squamous cell carcinoma in the hallux, without bone involvement, which was submitted to the appropriate surgical treatment. PMID:28099608
Latka, Chitra; Dey, Sanchita Sanchaya; Mahajan, Siddharth; Prabu, Ramachandira; Jangir, Pramod Kumar; Gupta, Chhavi; Das, Shukla; Ramachandran, Vishnampettai Ganapathysubramanian; Bhattacharya, Sambit Nath; Pandey, Rajesh; Sharma, Rakesh; Ramachandran, Srinivasan; Taneja, Bhupesh
Trichophyton rubrum is one of the major causative agents of dermatophytosis in humans worldwide. We report the draft genome sequence of T. rubrum var. raubitschekii from Delhi, India, isolated from a patient presenting symptoms of onychomycosis. The total estimated genome size of the clinical isolate is 25.2 MB containing 8265 predicted protein-coding sequences, 91 tRNA and 15 rRNA genes. Sequence analysis of the secreted subtilases, one of the major virulence factors in dermatophytes, clusters them into three subfamilies with distinct sequence features. The genome sequence is a step in understanding diversity of dermatophytes worldwide and will aid in identification of virulence factors and dissecting mechanisms of pathogenesis among them.
Jagielski, Tomasz; Kosim, Kinga; Skóra, Magdalena; Macura, Anna Barbara; Bielecki, Jacek
The genus Scopulariopsis contains over 30 species of mitosporic moulds, which although usually saprophytic may also act as opportunistic pathogens in humans. They have mainly been associated with onychomycosis, and only sporadically reported as a cause of deep tissue infections or systemic disease. Identification of Scopulariopsis species still largely relies on phenotype-based methods. There is a need for a molecular diagnostic approach, that would allow to reliably discriminate between different Scopulariopsis species. The aim of this study was to apply sequence analysis of partial 28S rRNA gene for species identification of Scopulariopsis clinical isolates. Although the method employed did reveal some genetic polymorphism among Scopulariopsis isolates tested, it was not enough for species delineation. For this to be achieved, other genetic loci, within and beyond the rDNA operon, need to be investigated.
Alvarez, María Inés; Caicedo, Luz Dary
The presence of medically important fungi was studied in hallux nails scrapings obtained from 504 students (204 males, 300 females) of three universities in Cali. Specimens were examined by direct microscopic examination and fungal culture. Medically important fungi were found in 49 (9.7%) students, 24 (4.8%) had onychomycosis while the rest did not have nail lesions. Trichophyton rubrum was the most commonly isolated fungi in students with lesions, where as T. mentagrophytes predominated in healthy nails. Most of the students with fungi were males. The prevalence of fungi was higher in individuals between 26 and 35 years. No association was observed between fungi and practicing sports or undergoing pedicures. These results suggest that dermatophytes can be found in healthy hallux nails, which can be reservoirs of pathogenic fungi.
Krönauer, C; Gfesser, M; Ring, J; Abeck, D
The objective of this study was to determine the transonychial water loss (TOWL) in both healthy and affected nails in different diseases and to compare it with the transepidermal water loss (TEWL). TOWL was measured by a new evaporimetric method: Plasticine was used to fix the protection cover of the evaporimeter probe to the nails. The TOWL behaved contrary to the TEWL. Affected nails in patients with atopic eczema (p <0.01), psoriasis (p<0.05) and onychomycosis (p<0.001) showed a significantly lower TOWL than did nails of healthy test subjects. The decrease in TOWL in diseased nails in comparison to healthy nails could be due to the formation of a stratum granulosum in atopic, psoriatic or fungus-affected nails, as this layer is normally absent in healthy nails.
Tiessen, Renger G; Lagerwey, Hendrik Jan G; Jager, Gea J; Sprenger, Herman G
A 58-year-old man, who spoke very little Dutch, had various symptoms and used several drugs including simvastatin. He was prescribed itraconazole for onychomycosis. Simvastatin was concurrently replaced with pravastatin to prevent drug interactions. However, the interaction still occurred when the pravastatin ran out, and the patient resumed taking simvastatin on his own initiative. Myalgia and muscle weakness developed after one week. The general practitioner found a strongly elevated creatine kinase level in the blood. The patient required hospitalisation for severe rhabdomyolysis. He was treated with an infusion of an ample quantity of physiological saline solution and made a full recovery. Due to the elevated risk of toxic interactions, doctors should beware of communication problems in complex patients and avoid new prescriptions not strictly required.
Halacli, Sevil Oskay; Ayvaz, Deniz Cagdas; Sun-Tan, Cagman; Erman, Baran; Uz, Elif; Yilmaz, Didem Yucel; Ozgul, Koksal; Tezcan, İlhan; Sanal, Ozden
Combined immunodeficiencies (CIDs) are heterogeneous group of disorders characterized by abrogated/impaired T cell development and/or functions that resulted from diverse genetic defects. In addition to the susceptibility to infections with various microorganisms, the patients may have lymphoproliferation, autoimmunity, inflammation, allergy and malignancy. Recently, three groups have independently reported patients having mutations in STK4 gene that cause a novel autosomal recessive (AR) CID. We describe here two siblings with a novel STK4 mutation identified during the evaluation of a group of patients with features highly overlapping with those of DOCK-8 deficiency, a form of AR hyperimmunoglobulin E syndrome. The patients' clinical features include autoimmune cytopenias, viral skin (molluscum contagiosum and perioral herpetic infection) and bacterial infections, mild onychomycosis, mild atopic and seborrheic dermatitis, lymphopenia (particularly CD4 lymphopenia), and intermittent mild neutropenia. Determination of the underlying defect and reporting the patients are required for the description of the phenotypic spectrum of each immunodeficiency.
Kong, Q T; Du, X; Yang, R; Huang, S Y; Sang, H; Liu, W D
A 31-year-old immunocompetent male who presented with a 4-year history of extensive erythematous and scaly plaques involving the abdomen, gluteal and inguen regions with concomitant tinea pedis and onychomycosis is described. Diagnosis was based on positive mycological examination and positive histopathologic examination. Species identification was performed by growth on Sabouraud dextrose agar and by sequencing of the internal transcribed spacer regions of the rDNA region. The pathogen identified was Trichophyton rubrum. The same fungal species was cultured from his abdominal, gluteal, foot and toenail. A combination therapy with systemic terbinafine and topically applied terbinafine cream was successful. A 1-year follow-up did not show any recurrence of infection.
A survey of dermatophytes and dermatophytoses was carried out among patients of the Department of Dermatology, Medical University of Gdańsk, in the years 1984-95. Over the 12-year period, 1195 cases of ringworm were seen: 55% in men and 45% in women. Listing the dermatophytes isolated and their frequencies as a percentage of the total are as follows: Trichophyton mentagrophytes 42.1%, Microsporum canis 26.0%, Trichophyton rubrum 14.7%, Epidermophyton floccosum 11.0%, Trichophyton tonsurans 4.6%, Trichophyton verrucosum 1.3%, Trichophyton violaceum 0.3%. The most common clinical variant of dermatophytosis in the Gdańsk area was tinea cutis glabrae (32.9%), followed by tinea pedis (24%), onychomycosis (16.5%), tinea capitis (11.9%)), tinea inguinalis (10.3%) and tinea manuum (4.4%). Dermatophytoses were significantly more frequent among adults (> 15 years) (71.3%).
Coutellier, A.; Théate, I.
Onychomatricoma is a rare and benign tumour of the nail matrix but originates rarely from the ventral portion of the proximal nail fold. This tumour is characterised by fingerlike projections that invade the nail plate. This lesion, of unknown aetiology, is typically asymptomatic with slow progression. Localisation on the finger is the most frequently described. We report the case of a 68-year-old woman who has an onychomatricoma in an unusual location, the fifth toe of the left foot. Due to its clinical appearance, the tumour can be confused with and treated as onychomycosis. However, if it is resistant to an oral antifungal well behaved treatment, one must consider onychomatricoma diagnosis. PMID:27478656
Schumpp, O; Bruderhofer, N; Monod, M; Wolfender, J-L; Gindro, K
Ultraviolet-C irradiation as a method to induce the production of plant compounds with antifungal properties was investigated in the leaves of 18 plant species. A susceptibility assay to determine the antifungal susceptibility of filamentous fungi was developed based on an agar dilution series in microtiter plates. UV irradiation strongly induced antifungal properties in five species against a clinical Fusarium solani strain that was responsible for an onychomycosis case that was resistant to classic pharmacological treatment. The antifungal properties of three additional plant species were either unaffected or reduced by UV-C irradiation. This study demonstrates that UV-C irradiation is an effective means of modulating the antifungal activity of very diverse plants from a screening perspective.
Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François
Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations.
Singh, Harminder; Singh, Prabhakar; Tiwari, Pavan; Dey, Vivek; Dulhani, Navin; Singh, Amita
Cutaneous disorders during HIV infection are numerous and skin is often the first and only organ affected during most of the course of HIV disease. Some Cutaneous disorders reflect the progression of HIV disease; though the relation is still controversial. The objective of this study, conducted at a tertiary care centre in Bastar, Jagdalpur, is to estimate the status of cutaneous manifestation in HIV-infected patients and its relationship with CD4 cell counts. We enrolled 137 HIV positive subjects. Demographic information such as age, gender, weight, height, socioeconomic status, and educational status were recorded. Laboratory parameter (CD4 counts) and treatment regimen were noted. Patients were examined for skin disorders by a dermatologist. Data were analyzed using chi-square test for categorical variables. Majority of the patients were from rural area (65.69%) and belonged to a low socioeconomic and educational status. 30.65% of the patients were housewives, 23.35% drivers, and 16.78% labourers. Predominant mode of transmission was heterosexual contact (94.16%). Most common HIV-related dermatological manifestations were seborrheic dermatitis (74.16%), xerosis (52.5%), generalized skin hyperpigmentation 56 (46.67%), onychomycosis 53 (44.16%), pruritic papular eruption 27 (22.5%), oral candidiasis 21 (17.5%), photo dermatitis 21 (17.5%), and scabies 4 (3.33%). Significant correlation with low CD4+ cell counts was found for oral candidiasis (P < 0.0001) and Kaposi's sarcoma (P = 0.03), while other disorders such as seborrheic dermatitis (P = 0.22), xerosis (P = 0.25), and onychomycosis (P = 0.08) were not statistically significant. This study showed high prevalence of dermatological manifestations in HIV-infected subjects, and they occur more frequently with progression of HIV and decline in immune functions. Therefore, early diagnosis and management of skin disorders can improve the quality of life of HIV-infected subjects.
Lemus-Espinoza, Druvic; Teresa Maniscalchi, María; Villarroel, Oskarina; Bónoli, Stefano B; Wahab, Fadi; García, Oswaldo
Superficial fungal diseases that affect the skin and its appendages are frequently seen in basic triage and in dermatology services. These diseases are distributed in Venezuela with an incidence of 92.9%. The aim of this study was to determine the genera and species that cause dermatomycoses in residents of Anzoátegui state, Venezuela, during the period 2002-2012. A total of 4257 patients with a presumptive diagnosis of superficial mycoses were studied, with ages from 7 months to 79 years. The overall prevalence was 30.9%. The most frequent were dermatophytosis (44.7%). M. canis produced 148 cases of tinea capitis. Three dermatophytic agents represented 95% of all cases, with a significant predominance of T. mentagrophytes with 50%. Candidosis occurred in 28.4%. C. albicans, and the C. parapsilosis complex, were responsible for 80% of the cases. The other species identified were C. tropicalis (n = 41, 11.0%), C. glabrata (n = 10, 2.7%), C. guilliermondii (n = 6, 1.6%), C. krusei (n = 4, 1.1%). Pityriasis versicolor occurred in 22.4% of the cases studied, and less frequently were present onychomycosis produced by a non dermatophytic mold: Fusarium oxysporum (n = 34, 65.4%), Aspergillus terreus (n=16, 30.8%) and Scytalidium dimidiatum (n=2; 3.8%). Rare cases of Trichosporon onychomycosis (0.5%) and one case of black tinea were also found. Health education in the population is recommended to promote measures to prevent transmission of these fungi and prevent the spread of this silent public health problem.
Hoekstra, W. J.; Moore, W. R.; Schotzinger, R. J.; Long, L.
Current therapies used to treat dermatophytoses such as onychomycosis are effective but display room for improvement in efficacy, safety, and convenience of dosing. We report here that the investigational agent VT-1161 displays potent in vitro antifungal activity against dermatophytes, with MIC values in the range of ≤0.016 to 0.5 μg/ml. In pharmacokinetic studies supporting testing in a guinea pig model of dermatophytosis, VT-1161 plasma concentrations following single oral doses were dose proportional and persisted at or above the MIC values for at least 48 h, indicating potential in vivo efficacy with once-daily and possibly once-weekly dosing. Subsequently, in a guinea pig dermatophytosis model utilizing Trichophyton mentagrophytes and at oral doses of 5, 10, or 25 mg/kg of body weight once daily or 70 mg/kg once weekly, VT-1161 was statistically superior to untreated controls in fungal burden reduction (P < 0.001) and improvement in clinical scores (P < 0.001). The efficacy profile of VT-1161 was equivalent to those for doses and regimens of itraconazole and terbinafine except that VT-1161 was superior to itraconazole when each drug was dosed once weekly (P < 0.05). VT-1161 was distributed into skin and hair, with plasma and tissue concentrations in all treatment and regimen groups ranging from 0.8 to 40 μg/ml (or μg/g), at or above the MIC against the isolate used in the model (0.5 μg/ml). These data strongly support the clinical development of VT-1161 for the oral treatment of onychomycosis using either once-daily or once-weekly dosing regimens. PMID:25605358
Néji, S; Trabelsi, H; Cheikhrouhou, F; Sellami, H; Guidara, R; Trigui, A; Feki, J; Boudaya, S; Turki, H; Makni, F; Ayadi, A
The genus Fusarium, initially known for its important agro-economic impact, is more and more often implicated in human pathology. In fact, multiples allergic, toxic and infectious manifestations are more reported in immunocompetent and immunocompromised hosts. The objective of our study was to analyse the epidemiological, mycological and clinical features of fusariosis reported in our CHU. Eighty-seven cases of Fusarium infections were collected: 34 cases of onychomycosis (39%), 26 cases of intertrigos (30%), 25 cases of keratomycosis (29%), one case of atypical invasive fusariosis due to Fusarium oxysporum species complex (FOSC) and one case of localized gingivolabial fusariosis due to Fusarium solani species complex (FSSC) in a patient with leukemia in phase of deep bone marrow aplasia, whose outcome was favorable after exiting of aplasia period and a treatment by amphotericine B. The case of pseudotumoral cutaneous fusariosis to F. oxysporum complicated with osteolysis and septic arthritis occurred in a pregnant woman without any immune deficit. The evolution was fatal in spite of prescription of multiple systemic antifungals. Concerning keratomycosis, Fusarium was the first agent responsible for these infections (43%). The corneal traumatism was found in 37.5% of cases and FSSC was the most isolated (72%). For superficial dermatomycosis, Fusarium was the third agent of onychomycosis in molds (25%). The most isolated species were FSSC (68%) and FOSC (20%). The intertrigo frequency was 0.07% and they were mostly caused by FSSC (84%) and FOSC (16%). Fusarium is an important cause of mold infections in our region. So, the species identification is useful because some species are resistant to the most common systemic antifungal agents. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Garvey, E P; Hoekstra, W J; Moore, W R; Schotzinger, R J; Long, L; Ghannoum, M A
Current therapies used to treat dermatophytoses such as onychomycosis are effective but display room for improvement in efficacy, safety, and convenience of dosing. We report here that the investigational agent VT-1161 displays potent in vitro antifungal activity against dermatophytes, with MIC values in the range of ≤0.016 to 0.5 μg/ml. In pharmacokinetic studies supporting testing in a guinea pig model of dermatophytosis, VT-1161 plasma concentrations following single oral doses were dose proportional and persisted at or above the MIC values for at least 48 h, indicating potential in vivo efficacy with once-daily and possibly once-weekly dosing. Subsequently, in a guinea pig dermatophytosis model utilizing Trichophyton mentagrophytes and at oral doses of 5, 10, or 25 mg/kg of body weight once daily or 70 mg/kg once weekly, VT-1161 was statistically superior to untreated controls in fungal burden reduction (P < 0.001) and improvement in clinical scores (P < 0.001). The efficacy profile of VT-1161 was equivalent to those for doses and regimens of itraconazole and terbinafine except that VT-1161 was superior to itraconazole when each drug was dosed once weekly (P < 0.05). VT-1161 was distributed into skin and hair, with plasma and tissue concentrations in all treatment and regimen groups ranging from 0.8 to 40 μg/ml (or μg/g), at or above the MIC against the isolate used in the model (0.5 μg/ml). These data strongly support the clinical development of VT-1161 for the oral treatment of onychomycosis using either once-daily or once-weekly dosing regimens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Khanna, Deepshikha; Bharti, Subhash
Luliconazole is an imidazole antifungal agent with a unique structure, as the imidazole moiety is incorporated into the ketene dithioacetate structure. Luliconazole is the R-enantiomer, and has more potent antifungal activity than lanoconazole, which is a racemic mixture. In this review, we summarize the in vitro data, animal studies, and clinical trial data relating to the use of topical luliconazole. Preclinical studies have demonstrated excellent activity against dermatophytes. Further, in vitro/in vivo studies have also shown favorable activity against Candida albicans, Malassezia spp., and Aspergillus fumigatus. Luliconazole, although belonging to the azole group, has strong fungicidal activity against Trichophyton spp., similar to that of terbinafine. The strong clinical antifungal activity of luliconazole is possibly attributable to a combination of strong in vitro antifungal activity and favorable pharmacokinetic properties in the skin. Clinical trials have demonstrated its superiority over placebo in dermatophytosis, and its antifungal activity to be at par or even better than that of terbinafine. Application of luliconazole 1% cream once daily is effective even in short-term use (one week for tinea corporis/cruris and 2 weeks for tinea pedis). A Phase I/IIa study has shown excellent local tolerability and a lack of systemic side effects with use of topical luliconazole solution for onychomycosis. Further studies to evaluate its efficacy in onychomycosis are underway. Luliconazole 1% cream was approved in Japan in 2005 for the treatment of tinea infections. It has recently been approved by US Food and Drug Administration for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis. Topical luliconazole has a favorable safety profile, with only mild application site reactions reported occasionally. PMID:25285056
Gursu, Meltem; Uzun, Sami; Topcuoğlu, Derya; Koc, Leyli Kadriye; Yucel, Lamiye; Sumnu, Abdullah; Cebeci, Egemen; Ozkan, Oktay; Behlul, Ahmet; Koc, Leyla; Ozturk, Savas; Kazancioglu, Rumeyza
AIM: To examine all skin changes in peritoneal dialysis (PD) patients followed up in our unit. METHODS: Patients on PD program for at least three months without any known chronic skin disease were included in the study. Patients with already diagnosed skin disease, those who have systemic diseases that may cause skin lesions, patients with malignancies and those who did not give informed consent were excluded from the study. All patients were examined by the same predetermined dermatologist with all findings recorded. The demographic, clinical and laboratory data including measures of dialysis adequacy of patients were recorded also. Statistical Package for Social Sciences (SPSS) for Windows 16.0 standard version was used for statistical analysis. RESULTS: Among the patients followed up in our PD unit, those without exclusion criteria who gave informed consent, 38 patients were included in the study with male/female ratio and mean age of 26/12 and 50.3 ± 13.7 years, respectively. The duration of CKD was 7.86 ± 4.16 years and the mean PD duration was 47.1 ± 29.6 mo. Primary kidney disease was diabetic nephropathy in 11, nephrosclerosis in six, uropathologies in four, chronic glomerulonephritis in three, chronic pyelonephritis in three, autosomal dominant polycystic kidney disease in three patients while cause was unknown in eight patients. All patients except for one patient had at least one skin lesion. Loss of lunula, onychomycosis and tinea pedis are the most frequent skin disorders recorded in the study group. Diabetic patients had tinea pedis more frequently (P = 0.045). No relationship of skin findings was detected with primary renal diseases, comorbidities and medications that the patients were using. CONCLUSION: Skin abnormalities are common in in PD patients. The most frequent skin pathologies are onychomycosis and tinea pedis which must not be overlooked. PMID:27458566
Vlahovic, Tracey C; Coronado, Dina; Chanda, Sanjay; Merchant, Tejal; Zane, Lee T
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. 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. 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. 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
Nenoff, P; Winter, I; Winter, A; Krüger, C; Herrmann, J; Gräser, Y; Rangno, N; Maier, T; Simon, J C
In 1969, Kolipp and Hoffmann isolated Trichophyton (T.) thuringiense spec. nov. Koch when they performed their thesis dealing with the distribution and epidemiology of dermatophytes and keratinophilic fungi in mice and other small mammals. At that time, T. thuringiense was detected as saprophytic fungus of the skin of different mice species (e.g. Mus musculus) both in rural and urban settings in the area of Thuringia in Germany. There were no further reports on this dermatophyte species until now, neither in animals, nor in man. Currently, we were able to isolate this geophilic fungus for the first time from a human being. A 58 year old patient baker by trade and living in a rural setting (village) suffered from nail changes like hyperkeratosis and thickening of the nail plate of his big toe. From his nail samples grew a dermatophyte with peripheral radiating and flat colonies which were a bit cottony in the centre. On Sabouraud's 4 % dextrose agar the thallus of the fungus was white to purple stained, the reverse side showed a dark red to brown color. In a typical manner, macroconidia were cylindrical to clavate, microconidia obovoidal to short-clavate with broad base. The species identification of T. thuringiense was done and confirmed by sequence analysis of the internal transcribed spacer (ITS) region of the ribosomal DNA. Antifungal treatment has been refused from the patient. In conclusion, this is the second description of the geophilic dermatophyte T. thuringiense, which could be isolated for the first time from a human being, in particular from nail sample of the big toe under the suspicion of onychomycosis. However, it is still uncertain if this fungus should be considered either as secondary colonization of the nail plate, or as causative agent of tinea unguium or onychomycosis.
Monti, D; Saccomani, L; Chetoni, P; Burgalassi, S; Senesi, S; Ghelardi, E; Mailland, F
Two nail lacquers, containing ciclopirox (CPX) or amorolfine (MRF), based on water-insoluble polymers are currently considered mainstays of topical treatment of onychomycosis. The present study aimed at evaluating the antimycotic activity of a new water-soluble nail lacquer containing CPX (CPX/sol), easily removable by washing with water and applicable to periungual skin. To compare transungual permeation of CPX with that of MRF in the same hydroxypropyl chitosan-based nail lacquer (MRF/sol) and with a nonwater-soluble reference (Loceryl); Galderma International, La Défense, France), and to evaluate the antimycotic activity of CPX/sol and Loceryl against the most common fungal strains that cause onychomycosis. Methods In vitro drug permeation experiments with CPX/sol, MRF/sol and Loceryl were carried out through bovine hoof slices. Experimental permeates from CPX/sol and Loceryl underwent in vitro susceptibility testing against clinical isolates of dermatophytes, moulds and yeast. Results MRF transungual flux from MRF/sol lacquer was significantly higher when compared with Loceryl. CPX was able to permeate hoof membranes more easily compared with MRF. CPX and MRF concentrations in the subungual fluids collected after application of CPX/sol or Loceryl were sufficient to inhibit fungal growth, with the exception of Candida parapsilosis. Smaller amounts of fluid containing CPX were required for complete inhibition of fungal growth. Efficacy index values were significantly higher for CPX/sol. Conclusions Application of the CPX/sol nail lacquer allows rapid nail penetration of CPX, providing CPX levels sufficient to inhibit fungal growth for a prolonged period of time (30 h) after application of lacquer dose. CPX/sol nail lacquer appeared superior to the market reference Loceryl in terms of both vehicle (hydroxypropyl chitosan) and active ingredient (CPX) as witnessed by its higher efficacy on all nail pathogens.
Vejnovic, Ivana; Huonder, Cornelia; Betz, Gabriele
Existing treatments of onychomycosis are not satisfactory. Oral therapies have many side effects and topical formulations are not able to penetrate into the human nail plate and deliver therapeutical concentrations of active agent in situ. The purpose of the present study was to determine the amount of terbinafine, which permeates through the human nail plate, from liquid formulations containing enhancers, namely hydrophobins A-C in the concentration of 0.1% (w/v). The used reference solution contained 10% (w/v) of terbinafine in 60% (v/v) ethanol/water without enhancer. Permeability studies have been performed on cadaver nails using Franz diffusion cells modified to mount nail plates and filled with 60% (v/v) ethanol/water in the acceptor chamber. Terbinafine was quantitatively determined by HPLC. The amount of terbinafine remaining in the nail was extracted by 96% ethanol from pulverized nail material after permeation experiment and presented as percentage of the dry nail weight before the milling test. Permeability coefficient (PC) of terbinafine from reference solution was determined to be 1.52E-10 cm/s. Addition of hydrophobins improved PC in the range of 3E-10 to 2E-9 cm/s. Remaining terbinafine reservoir in the nail from reference solution was 0.83% (n=2). An increase of remaining terbinafine reservoir in the nail was observed in two out of three tested formulations containing hydrophobins compared to the reference. In all cases, known minimum inhibitory concentration of terbinafine for dermatophytes (0.003 microg/ml) has been exceeded in the acceptor chamber of the diffusion cells. All tested proteins (hydrophobins) facilitated terbinafine permeation after 10 days of permeation experiment, however one of them achieved an outstanding enhancement factor of 13.05 compared to the reference. Therefore, hydrophobins can be included in the list of potential enhancers for treatment of onychomycosis. Copyright 2010 Elsevier B.V. All rights reserved.
Elsherif, Noha Ibrahim; Shamma, Rehab Nabil; Abdelbary, Ghada
Treating a nail infection like onychomycosis is challenging as the human nail plate acts as a formidable barrier against all drug permeation. Available oral and topical treatments have several setbacks. Terbinafine hydrochloride (TBH), belonging to the allylamine class, is mainly used for treatment of onychomycosis. This study aims to formulate TBH in a nanobased spanlastic vesicular carrier that enables and enhances the drug delivery through the nail. The nanovesicles were formulated by ethanol injection method, using either Span® 60 or Span® 65, together with Tween 80 or sodium deoxycholate as an edge activator. A full factorial design was implemented to study the effect of different formulation and process variables on the prepared TBH-loaded spanlastic nanovesicles. TBH entrapment efficiency percentages, particle size diameter, percentage drug released after 2 h and 8 h were selected as dependent variables. Optimization was performed using Design-Expert® software to obtain an optimized formulation with high entrapment efficiency (62.35 ± 8.91%), average particle size of 438.45 ± 70.5 nm, and 29.57 ± 0.93 and 59.53 ± 1.73% TBH released after 2 and 8 h, respectively. The optimized formula was evaluated using differential scanning calorimetry and X-ray diffraction and was also morphologically examined using transmission electron microscopy. An ex vivo study was conducted to determine the permeation and retainment of the optimized formulation in a human cadaver nail plate, and confocal laser scanning microscope was used to show the extent of formulation permeation. In conclusion, the results confirmed that spanlastics exhibit promising results for the trans-ungual delivery of TBH.
Ghannoum, M; Isham, N; Henry, W; Kroon, H-A; Yurdakul, S
TDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes. Trichophyton rubrum hyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure of T. rubrum hyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmed in vivo in subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Our in vivo data confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects.
Isham, N.; Henry, W.; Kroon, H.-A.; Yurdakul, S.
TDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes. Trichophyton rubrum hyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure of T. rubrum hyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmed in vivo in subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Our in vivo data confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects. PMID:22354309
Bandh, Suhaib A; Kamili, Azra N; Ganai, Bashir A; Lone, Bashir A
Natural habitats of opportunistic fungal pathogens are outside of the host; therefore, it is critically important to understand their ecology and routes of transmission. In this study, we investigated the presence of human pathogenic opportunistic fungi in lake water and incidence of fungal infections in associated population in Kashmir, India. Six hundred forty water samples were taken on seasonal basis from a wide network of sampling stations of the lake for an extended period of two years for screening their occurrence. The samples were inoculated onto rose bengal agar, malt extract agar, potato dextrose agar and other specified culture media supplemented with Chloramphenicol and Streptomycin followed by incubation at 37 °C. All the samples were positive for fungi, which were later identified by sequencing the rDNA internal transcribed spacer region aided by classical morphological culture techniques and physiological profiling. The whole process led to the isolation of sixteen species of opportunistic fungal pathogens belonging to genus Aspergillus, Candida, Penicillium, Cryptococcus, Fusarium, Rhizopus and Mucor in decreasing order of prevalence. Furthermore, 20% population (n = 384) of Dal inhabitants was examined for possible fungal infections and it was observed that only 8.07% individuals were positive for fungal infections with 4.68% skin infection cases, 2.34% onychomycosis cases and 1.04% candidiasis cases. Scrapings from onychomycosis and candidiasis patients showed the presence of Aversicolor and Calbicans respectively, resembling exactly the strains isolated from the lake water. However, the skin infection was because of a dermatophyte not isolated for the lake water. Higher prevalence of infection (6.77%) was seen in people using lake water followed by a positive prevalence of 1.30% using tap water. The results of present study suggest that the lake inhabitants are at a greater risk of getting life threatening fungal diseases which may lead to
Singh, Harminder; Singh, Prabhakar; Tiwari, Pavan; Dey, Vivek; Dulhani, Navin; Singh, Amita
Background: Cutaneous disorders during HIV infection are numerous and skin is often the first and only organ affected during most of the course of HIV disease. Some Cutaneous disorders reflect the progression of HIV disease; though the relation is still controversial. Aims: The objective of this study, conducted at a tertiary care centre in Bastar, Jagdalpur, is to estimate the status of cutaneous manifestation in HIV-infected patients and its relationship with CD4 cell counts. Methods: We enrolled 137 HIV positive subjects. Demographic information such as age, gender, weight, height, socioeconomic status, and educational status were recorded. Laboratory parameter (CD4 counts) and treatment regimen were noted. Patients were examined for skin disorders by a dermatologist. Data were analyzed using chi-square test for categorical variables. Results: Majority of the patients were from rural area (65.69%) and belonged to a low socioeconomic and educational status. 30.65% of the patients were housewives, 23.35% drivers, and 16.78% labourers. Predominant mode of transmission was heterosexual contact (94.16%). Most common HIV-related dermatological manifestations were seborrheic dermatitis (74.16%), xerosis (52.5%), generalized skin hyperpigmentation 56 (46.67%), onychomycosis 53 (44.16%), pruritic papular eruption 27 (22.5%), oral candidiasis 21 (17.5%), photo dermatitis 21 (17.5%), and scabies 4 (3.33%). Significant correlation with low CD4+ cell counts was found for oral candidiasis (P < 0.0001) and Kaposi's sarcoma (P = 0.03), while other disorders such as seborrheic dermatitis (P = 0.22), xerosis (P = 0.25), and onychomycosis (P = 0.08) were not statistically significant. Conclusion: This study showed high prevalence of dermatological manifestations in HIV-infected subjects, and they occur more frequently with progression of HIV and decline in immune functions. Therefore, early diagnosis and management of skin disorders can improve the quality of life of HIV
Lee, Jae In; Lee, Young Bok; Oh, Shin Tack; Cho, Baik Kee
Background Pincer nail is a nail deformity characterized by transverse overcurvature of the nail plate. Pincer nail can affect a patient's quality of life due to its chronic, recurrent course; however, there have been no clinical studies on the pincer nail condition in Korean patients. Objective The purpose of this study was to characterize the clinical findings and treatment of pincer nail. In addition, possible etiological factors were considered, and treatment efficacy was evaluated. Methods The medical records and clinical photographs of 35 patients (12 males, 23 females) who were diagnosed with pincer nail between August 1, 2005 and July 31, 2009 were studied. Results Patient age ranged from 10 to 77 (52.09±17.26) years, and there was a predominance of female (23 out of 35 patients, F:M=2:1). The mean duration of the disorder was 7.45 years (range 0.25~40); 85% had pincer nail for at least 1 year. In addition, 40% had a history of previous treatment and recurrence. There were 82.8% patients with the common type of pincer nails. The most commonly involved nails were both great toenails. Among 35 patients, nail grinding was started in 30 patients, and 25 patients showed clinical improvement with nail grinding. The width index increased and the height index decreased after treatment. The mean follow up period was 8.42 months (range 1~27), and 7 patients showed recurrence after 8.8 months (range 2~20). Among 35 patients, 5 patients were treated with nail extraction with matricectomy, and the symptoms resolved immediately. The mean follow up period was 7.6 months (range 0~19), and recurrence was not observed. Onychomycosis was also present in 37.1% of patients, and itraconazole pulse therapy for 3 months was added. Conclusion The results of this study demonstrate the clinical features of pincer nail in Korean patients. The findings show that the common type of pincer nail was most common, and nail grinding as a conservative treatment greatly improved pincer nails
Deo, Maneka S; Vandal, Alain C; Jarrett, Paul
Objectives To estimate the prevalence of dermatological disease in aged care facilities, and the relationship between cognitive or physical disability and significant disease. Setting 2 large aged care facilities in Auckland, New Zealand, each providing low and high level care. Participants All 161 residents of the facilities were invited to participate. The only exclusion criterion was inability to obtain consent from the individual or designated guardian. 88 participants were recruited—66 females (75%), 22 males (25%) with average age 87.1 years (SD 5.5 years). Primary and secondary outcome measures Primary—presence of significant skin disease (defined as that which in the opinion of the investigators needed treatment or was identified as a patient concern) diagnosed clinically on full dermatological examination by a dermatologist or dermatology trainee. Secondary—functional and cognitive status (Rehabilitation Complexity Scale and Abbreviated Mental Test Score). Results 81.8% were found to have at least one significant condition. The most common disorders were onychomycosis 42 (47.7%), basal cell carcinoma 13 (14.8%), asteototic eczema 11 (12.5%) and squamous cell carcinoma in situ 9 (10.2%). Other findings were invasive squamous cell carcinoma 7 (8%), bullous pemphigoid 2 (2.3%), melanoma 2 (2.3%), lichen sclerosus 2 (2.3%) and carcinoma of the breast 1 (1.1%). Inflammatory disease was more common in those with little physical disability compared with those with serious physical disability (OR 3.69; 95% CI 1.1 to 12.6, p=0.04). No significant association was found between skin disease and cognitive impairment. Conclusions A high rate of dermatological disease was found. Findings ranged from frequent but not life-threatening conditions (eg, onychomycosis), to those associated with a significant morbidity (eg, eczema, lichen sclerosus and bullous pemphigoid), to potentially life-threatening (eg, squamous cell carcinoma, melanoma and breast cancer
Vasudevan, Biju; Sagar, Amitabh; Bahal, Ashish; Mohanty, Ap
Cutaneous manifestations are early and easily identifiable markers of human immunodeficiency virus (HIV) infection. They can help in predicting severity and progress of the disease and can be correlated well with CD4 counts. This study was undertaken to study the cutaneous manifestations of HIV infection and to correlate them with CD4 counts. It also aimed to study the changing spectrum of these manifestations and describe cutaneous manifestations seen in advanced disease. A total of 234 HIV-positive patients not on anti-retroviral therapy, who attended the outpatient department or were admitted as inpatients at Military Hospital, Shillong during the period between May 2008 and October 2009 were included. Cutaneous, mucosal, and genitourinary manifestations in these patients were studied in detail and were correlated with CD4 counts. Infections were the most common group of mucocutaneous manifestations, while onychomycosis was the commonly observed individual manifestation. A different set of cutaneous markers for advanced HIV disease was observed and new parameters for therapy were also arrived at. Specific morphological variants of cutaneous markers may provide a better clue to early diagnosis of HIV and can help in diagnosing advanced stages of the disease. Fresh cutaneous markers are required for indicating cut-off levels of CD4 count at 350/μL for starting therapy.
Kalińska-Bienias, Agnieszka; Kowalewski, Cezary; Woźniak, Katarzyna
So far in the literature there have been reported only 5 patients with a recognized and well-documented history of systemic lupus erythematosus (SLE) who developed SCLE after terbinafine introduction. Here we report two women suffering from SLE who developed SCLE after initiation of oral terbinafine for onychomycosis. Skin lesions in both of them were extensive, located on the trunk, and upper and lower extremities. No exacerbation of SLE symptoms was observed at that time. Despite severe skin lesions, patients revealed good response to topical corticosteroids within a few weeks. The systemic review of the literature and our experience on terbinafine-induced SCLE developing in patients with SLE allowed to create a description for this special subset: a) terbinafine-induced SCLE usually develop in 1-8 weeks after terbinafine introduction, b) skin lesions are usually severe, disseminated including lower extremities, c) patients present Ro/SS-A La/SS-B antibodies, but anti-histone antibodies are rarely observed, d) exacerbation of SLE symptoms is rather not observed, e) eruptions clear within 2-8 weeks, f) withdrawal of terbinafine and topical corticosteroids should be considered as a first-line therapy in these cases, g) terbinafine should be carefully used in patients suffering from SLE.
Täuber, Anja; Müller-Goymann, Christel C
Onychomycosis is a fungal infection mostly induced by dermatophytes such as Trichophyton rubrum. Due to slow nail growth, the treatment takes 3-9 months depending on the nail size and infected area. Hence, high efficacy of the active ingredient without systemic side effects is of major interest. To test the efficacy of an antifungal formulation, an appropriate in vitro model reflecting the in vivo situation as close as possible is required. In this study, a variety of antifungal formulations, i.e., commercial ones (Ciclopoli and Lamisil cream), those used in compounding pharmacies (Pentravan) as well as poloxamer 407-based systems, have been evaluated in an infected nail plate model. The active pharmaceutical ingredients (APIs) were ciclopirox olamine and terbinafine hydrochloride. The poloxamer 407-based formulations consisted of poloxamer 407, double distilled water, propylene glycol, isopropyl alcohol, medium chain triglycerides and either 1% ciclopirox olamine or 1% terbinafine hydrochloride as API, respectively. Former studies have shown high permeation rates of terbinafine hydrochloride from similar poloxamer 407-based formulations with dimethyl isosorbide instead of propylene glycol. The present contribution shows superior inhibition of T. rubrum growth from poloxamer 407-based formulations in comparison to the commercial Lamisil cream. Moreover, poloxamer 407-based formulations were equally effective as the nail lacquer Ciclopoli even though the poloxamer formulations contained only 1% of the drug instead of 8% in the marketed lacquer. Poloxamer 407-based systems containing ciclopirox olamine proved to be about as effective as similar terbinafine hydrochloride systems.
Bebawi, Emmanuel; Jouni, Suhail S; Tessier, Andrée-Anne; Frenette, Anne Julie; Brindamour, Dave; Doré, Maxime
To report a sinus bradycardia induced by metoprolol and terbinafine drug-drug interaction and its management. A 63 year-old Caucasian man on metoprolol 200 mg/day for stable coronary artery disease was prescribed a 90-day course of oral terbinafine 250 mg/day for onychomycosis. On the 49th day of terbinafine therapy, he was brought to the emergency room for a decrease of his global health status, confusion and falls. The electrocardiogram revealed a 37 beats/min sinus bradycardia. A score of 7 on the Naranjo adverse drug reaction probability scale indicates a probable relationship between the patient's sinus bradycardia and the drug interaction between metoprolol and terbinafine. The heart rate ameliorated first with a decrease in the dose of metoprolol. It was subsequently changed to bisoprolol and the heart rate remained normal. By inhibiting the cytochrome P450 2D6, terbinafine had decreased metoprolol's clearance, leading in metoprolol accumulation which has resulted in clinically significant sinus bradycardia.
Terbinafine, a synthetic antifungal of allylamine class, has fungicidal activity against dermatophytes, moulds and certain dimorphic fungi and fungistatic activity against Candida albicans. Following oral administration the terbinafine is absorbed rapidly (>70%) and reaches within 2 hours the peak plasma concentration. The drug is highly lipophilic and keratophilic and is highly bound to plasma protein (>90%) with a bioavailability of 70% to 80%. The drug is rapidly delivered and it is present in the stratum corneum, sebum, nails and hair for months after stopping the medication. The drug has been proven to be the choice treatment in the therapy of onychomycosis as it is very effective, well tolerated and has a relatively low potential for drug interactions. The pharmacologic and pharmacokinetic properties of terbinafine give strong support to the possibility that the pulse therapy may be equally effective in onychomycoses, possibly reducing medication costs and drug exposure. Several therapeutic patterns have been proposed: weekly intermittent terbinafine (500 mg/d for 1 week each month for 4 months), or single-dose terbinafine (1000 mg per month for 4 months). Use of topical terbinafine 1% may be practical where the tinea involvement is not extensive or chronic. Recently, the terbinafine is available in a novel topical solution (film-forming solution--FFS) effective in the treatment of tinea pedis (athlete's foot).
Ghannoum, Mahmoud A.; Elewski, Boni
Increasing incidence of resistance to conventional antifungal therapy has demanded that novel therapies be introduced. Recent in vitro studies have shown that combinations involving azoles and allylamines may be effective in inhibiting fluconazole-resistant fungi. In this report, we describe the case of a 39-year-old woman who presented with white patches on her buccal mucosa, tongue, and palate with a bright erythematous erosive base. A fungal culture revealed Candida albicans. The patient failed to respond to the initially prescribed fluconazole therapy. Failure of therapy can be attributed to a developed resistance to fluconazole from the patient’s intermittent use of this antifungal agent at varying dosages for the preceding 2 years due to a diagnosis of onychomycosis. In vitro testing of the culture from the patient showed elevated MICs of fluconazole, itraconzole, and terbinafine (MICs were 32, 0.5, and 64 μg/ml, respectively). Our goal was to combine therapies of fluconazole and terbinafine in an attempt to clear the fungal infection. Impressively, this combination resulted in the clearing of the clinical symptoms and the patient has successfully been asymptomatic for more than 12 months posttreatment. PMID:10548586
Purim, Kátia Sheylla Malta; Bordignon, Gisele Pesquero Fernandes; Queiroz-Telles, Flávio de
This study was conducted to evaluate the occurrence of mycoses affecting the feet of soccer players and to compare this results with those in non-athlete individuals of the same age and sex. Initial evaluation consisted of a dermatological examination of the foot in 22 Chinese athletes, 83 Brazilian athletes and 24 Brazilian non-athletes. Scales of plantar skin, interdigital and subungual areas of the foot were collected for mycological examination (direct and culture). Nail clippings were obtained for histopathologic analysis. Tinea pedis was diagnosed more frequently among the non-athlete individuals. None of the Chinese athletes had tinea pedis alone. However, in this group onychomycosis was frequently higher when compared to the other groups. The fungal microbiota comprised Trichophyton rubrum (40%), Trichophyton mentagrophytes (36.4%) and Candida spp (20%). Candida spp was isolated only from Brazilian athletes. Results obtained with KOH wet mounts agreed with the results obtained in culture and with histopathologic examinations (50.5% vs 40.9%). The frequency of tinea pedis among soccer players was lower than the other groups in this study, possibly due to health education and professional feet care.
Palmeri, A; Pichini, S; Pacifici, R; Zuccaro, P; Lopez, A
In recent years, drug analysis in keratinised matrices, such as hair and nails, has received considerable attention because of several advantages over drug testing methodologies employing body fluids, such as urine or serum. For example, keratinic matrices, such as finger- and toenails, can accumulate drugs during long term exposure. Drugs are incorporated into nails by a double mechanism: (i) deposition into the root of the growing nail via the blood flow in the nail matrix; and (ii) incorporation via the nail bed during growth from the lunula to the beginning of the free margin. Together, these account for a wide retrospective window of drug detection. Nails can provide a good forensic matrix for the detection of drugs of abuse. Indeed, the international literature has reported the use of nail analysis in postmortem detection of drugs of abuse, drug testing in the workplace and drug screening to detect prenatal exposure, even though further studies are needed for correct interpretation of the data obtained. Another application of drug analysis in nails consists of the possibility of detecting the presence of an antimycotic at the site of action during antifungal therapy for patients with onychomycosis. When available, this evidence has permitted drug treatment of a shorter duration and reduced toxicity. However, so far the potential of drug monitoring in nails still lacks harmonisation and validation of analytical methodologies and a better comprehension of the possible correlation between drug concentrations in the matrix and period of exposure.
Ruben, Beth S
Probably the most common reason to perform biopsy of the nail unit is for the evaluation of irregular pigmentation, especially longitudinal melanonychia or pigmented bands. When narrow and solitary, these are usually the product of melanocytic activation/hypermelanosis, lentigines, or melanocytic nevi. Multiple pigmented bands are generally a benign finding, the result of melanocytic activation, as seen in racial pigmentation in darker-skinned patients, for example. In the context of an irregular, broad, heterogeneous or "streaky" band, the chief concern is the exclusion of subungual melanoma. Before assessing the histologic features of any such entities, it is important to understand the normal nail anatomy and melanocytic density of nail unit epithelium, as well as the type of specimen submitted, and whether it is adequate to undertake a proper histologic evaluation. The criteria for diagnosis and prognosis of melanoma of the nail unit are still evolving, and a variety of factors must be weighed in the balance to make a correct diagnosis. The importance of the clinical context cannot be overemphasized. There are also nonmelanocytic conditions to be considered that may produce worrisome nail discoloration, such as subungual hemorrhage, squamous cell carcinoma, and pigmented onychomycosis.
Hossin, B; Rizi, K; Murdan, S
We hypothesised that Hansen Solubility Parameters (HSPs) can be used to predict drug-nail affinities. Our aims were to: (i) determine the HSPs (δD, δP, δH) of the nail plate, the hoof membrane (a model for the nail plate), and of the drugs terbinafine HCl, amorolfine HCl, ciclopirox olamine and efinaconazole, by measuring their swelling/solubility in organic liquids, (ii) predict nail-drug interactions by comparing drug and nail HSPs, and (iii) evaluate the accuracy of these predictions using literature reports of experimentally-determined affinities of these drugs for keratin, the main constituent of the nail plate and hoof. Many solvents caused no change in the mass of nail plates, a few solvents deswelled the nail, while others swelled the nail to varying extents. Fingernail and toenail HSPs were almost the same, while hoof HSPs were similar, except for a slightly lower δP. High nail-terbinafine HCl, nail-amorolfine HCl and nail-ciclopirox olamine affinities, and low nail-efinaconazole affinities were then predicted, and found to accurately match experimental reports of these drugs' affinities to keratin. We therefore propose that drug and nail Hansen Solubility Parameters may be used to predict drug-nail interactions, and that these results can assist in the design of drugs for the treatment of nail diseases, such as onychomycosis and psoriasis. To our knowledge, this is the first report of the application of HSPs in ungual research.
Ben Abdeljelil, Jihene; Saghrouni, Fatma; Khammari, Imene; Gheith, Soukeina; Fathallah, Akila; Ben Said, Moncef; Boukadida, Jalel
Nosocomial invasive candidiasis (IC) has emerged as a major problem in neonatal intensive care units (NICUs). We investigated herein the temporal clustering of six cases of neonatal IC due to Candida albicans in an NICU. Eighteen isolates obtained from the six neonates and two isolates from two health care workers (HCWs) working at the same unit and suffering from fingers' onychomycosis were genotyped by electrophoretic karyotyping (EK) and restriction endonuclease analysis of genomic DNA by using Sfi I (PFGE-Sfi I). PFGE-Sfi I was more effective in discriminating between temporally related isolates. It showed that (i) both HCWs had specific strains excluding them as a source of infections in neonates. (ii) Isolates collected from three neonates were identical providing evidence of their clonal origin and the occurrence of a horizontal transmission of C. albicans in the unit. (iii) The three remaining neonates had specific strains confirming that the IC cases were coincidental. (iv) Microevolution occurred in one catheter-related candidemia case. Our results illustrate the relevance of the molecular approach to investigate suspected outbreaks in hospital surveys and the effectiveness of PFGE-Sfi I for typing of epidemiologically related C. albicans isolates. PMID:22547975
Baswan, Sudhir M; Li, S Kevin; LaCount, Terri D; Kasting, Gerald B
The electrical properties of human nail plate are poorly characterized yet are a key determinate of the potential to treat nail diseases, such as onychomycosis, using iontophoresis. To address this deficiency, molar conductivities of 17 electrolytes comprising 12 ionic species were determined in hydrated human nail plate in vitro. Cation transport numbers across the nail for 11 of these electrolytes were determined by the electromotive force method. Effective ionic mobilities and diffusivities at infinite dilution for all ionic species were determined by regression analysis. The ratios of diffusivities in nail to those in solution were found to correlate inversely with the hydrodynamic radii of the ions according to a power law relationship having an exponent of -1.75 ± 0.27, a substantially steeper size dependence than observed for similar experiments in skin. Effective diffusivities of cations in nail were 3-fold higher than those of comparably sized anions. These results reflect the strong size and charge selectivity of the nail plate for ionic conduction and diffusion. The analysis implies that efficient transungual iontophoretic delivery of ionized drugs having radii upward of 5 Å (molecular weight, ca. ≥ 340 Da) will require chemical or mechanical alteration of the nail plate.
Paz-Cristobal, Manuel Pablo; Gilaberte, Yolanda; Alejandre, Carmen; Pardo, Julián; Revillo, M José; Rezusta, Antonio
Hypericin is a natural photosensitizer used in photodynamic therapy (PDT), which has shown in vitro antifungal effect against Candida spp. The aim of this study was to evaluate the in vitro fungicidal effect of hypericin-PDT on dermatophytes. Trichophyton rubrum and Trichophyton mentagrophytes strains were incubated with different concentrations of hypericin for different times and exposed to light-emitting diode lamp (602 ± 10 nm, 10.3 mW cm(-2), and fluence 37 J cm(-2)). Using the optimal incubation time, 60 min, a 3-log fungicidal effect was achieved with hypericin concentration ranges of 10-20 μM for T. rubrum and 20-50 μM for T. mentagrophytes (p = 0.95). Confocal fluorescence microscopy showed the localization of hypericin inside the dermatophytes diffusely distributed in the cytoplasm of conidia and hyphae and outside the nucleus. In conclusion, hypericin-PDT has a fungicidal effect in vitro on dermatophytes. Hypericin seems to be a promising photosensitizer to treat localized dermatophytic infections such as tinea pedis and onychomycosis.
Pires, Carla Andréa Avelar; Cruz, Natasha Ferreira Santos da; Lobato, Amanda Monteiro; Sousa, Priscila Oliveira de; Carneiro, Francisca Regina Oliveira; Mendes, Alena Margareth Darwich
The cutaneous mycoses, mainly caused by dermatophyte fungi, are among the most common fungal infections worldwide. It is estimated that 10% to 15% of the population will be infected by a dermatophyte at some point in their lives, thus making this a group of diseases with great public health importance. To analyze the clinical, epidemiological, and therapeutic profile of dermatophytosis in patients enrolled at the Dermatology service of Universidade do Estado do Pará, Brazil, from July 2010 to September 2012. A total of 145 medical records of patients diagnosed with dermatophytosis were surveyed. Data were collected and subsequently recorded according to a protocol developed by the researchers. This protocol consisted of information regarding epidemiological and clinical aspects of the disease and the therapy employed. The main clinical form of dermatophyte infection was onychomycosis, followed by tinea corporis, tinea pedis, and tinea capitis. Furthermore, the female population and the age group of 51 to 60 years were the most affected. Regarding therapy, there was a preference for treatments that combine topical and systemic drugs, and the most widely used drugs were fluconazole (systemic) and ciclopirox olamine (topical). This study showed the importance of recurrent analysis of the epidemiological profile of dermatophytosis to enable correct therapeutic and preventive management of these conditions, which have significant clinical consequences, with chronic, difficult-totreat lesions that can decrease patient quality of life and cause disfigurement.
Paugam, A; L'ollivier, C; Viguié, C; Anaya, L; Mary, C; de Ponfilly, G; Ranque, S
A PCR detecting dermatophytes within a short turnaround time would significantly enhance the management of patients with suspected dermatophytosis. This study aimed at comparing the results of a real-time PCR assay with those of the conventional diagnostic (direct microscopy and culture) performed by a dermatologist working in a medical mycology laboratory for the detection of dermatophytes in nail and skin samples. A total of 112 specimens (54 nail and 58 skin) were collected from 52 patients with one to four suspected dermatophytosis lesions. The PCR diagnostic indices were calculated for either sample- or patient-based dermatophytosis diagnosis. The sample-based diagnostic efficacy yielded 79% sensitivity and 73% specificity. The patient-based diagnostic efficacy was higher with 100% sensitivity and 82% specificity. Interestingly, PCR yielded significantly (p < 0.004) lesser false negative results and performed overall better (diagnostic odds ratio = 24.0 vs. 5.5) in nail than in skin samples. In conclusion, this real-time PCR assay performance was consistent with those of the conventional methods in the hands of a skilled expert and particularly efficacious in diagnosing dermatophyte onychomycosis. This PCR is suited to high throughput batch processing; if used instead of direct microscopy, it could reduce hands-on time in the routine clinical laboratory workflow. © 2013 Elsevier B.V. All rights reserved.
Dermatophytoses in animals are fungal diseases of the skin caused by dermatophyte fungi of the genus Microsporum or Trichophyton. Because the infection is generally follicular, the most common clinical sign is one or many circular areas of alopecia with variable erythema, scaling and crusting, and the primary differential diagnoses are follicular infections, such as bacterial folliculitis and demodicosis. Although dermatophyte folliculitis or ringworm is the most commonly observed lesion of dermatophytoses in animals, other presentations may be observed according to the host species and the dermatophyte involved: dermatophyte folliculitis or ringworm, scaling and crusting in dermatophytosis due to Microsporum persicolor, nodule in case of kerion or mycetoma, matted hairs, seborrheic dermatosis or miliary dermatitis in cats, generalized exfoliative dermatoses in dogs, cats and horses, superficial non-follicular pustules, papules and macules in the Devon Rex cat, pruritic dermatophytoses in dogs, cats and horses, and onychomycosis in dogs, cats and horses. Since manifestations of dermatophytosis are highly variable, particularly in the cat, dermatophytosis should be considered in case of any annular, papular, nodular or pustular dermatoses, alopecic or not, sometimes pruritic, and nodular dermatoses as well.
Seebacher, Claus; Bouchara, Jean-Philippe; Mignon, Bernard
The spectrum of dermatophytes isolated from skin lesions had changed in last 70 years. Before the Second World War in Germany, Microsporum audouinii and Epidermophyton floccosum ranked the first, whereas Trichophyton rubrum is the most common dermatophyte since the fifties of last century, accounting for 80-90% of the strains, followed by T. mentagrophytes. This evolution is typical for Central and North Europe and it needs to be connected with the increase in the incidence of tinea pedis. In contrast, in Southern Europe and in Arabic countries, zoophilic dermatophytes, such as Microsporum canis or Trichophyton verrucosum, are the most frequently isolated. In Europe, especially in Mediterranean countries, the incidence of M. canis infection has strongly increased during the recent years and this dermatophyte is now the most prevalent in tinea capitis in children. An analysis of the frequency and distribution of tinea pedis in different occupations and leisure-time activities as well as the routes of infection are reported. The spreading of this disease in most developed countries of the world represents a considerable economic problem, since it was accompanied by a parallel increase in the frequency of onychomycosis which implies, as tinea pedis, large financial charges. In poor developing countries, mycoses appear endemically, primarily with children, and their treatment often fails because of the lack of efficient antifungals. The particular epidemiological situations of dermatophytoses and the pathogenic spectrum of dermatophytes are examined at the example of numerous countries.
Birhanu, Teshome; Molenberghs, Geert; Sotto, Cristina; Kenward, Michael G
Generalized estimating equations (GEE), proposed by Liang and Zeger (1986), provide a popular method to analyze correlated non-Gaussian data. When data are incomplete, the GEE method suffers from its frequentist nature and inferences under this method are valid only under the strong assumption that the missing data are missing completely at random. When response data are missing at random, two modifications of GEE can be considered, based on inverse-probability weighting or on multiple imputation. The weighted GEE (WGEE) method involves weighting observations by the inverse of their probability of being observed. Imputation methods involve filling in missing observations with values predicted by an assumed imputation model, multiple times. The so-called doubly robust (DR) methods involve both a model for the weights and a predictive model for the missing observations given the observed ones. To yield consistent estimates, WGEE needs correct specification of the dropout model while imputation-based methodology needs a correctly specified imputation model. DR methods need correct specification of either the weight or the predictive model, but not necessarily both. Focusing on incomplete binary repeated measures, we study the relative performance of the singly robust and doubly robust versions of GEE in a variety of correctly and incorrectly specified models using simulation studies. Data from a clinical trial in onychomycosis further illustrate the method.
Kim, Miri; Kang, Jin Hee; Cho, Baik Kee; Song, Chan Hee; Ock, Sun Myeong
Background There have been a few reported cases of congenital great toenail dystrophy (GTND), described as a congenital malalignment of the great toenails. However, acquired GTDN is rare, and has not been documented extensively. This study aimed to describe the clinical features of 21 patients with acquired GTND. Methods Twenty-one patients with acquired GTND who visited Yeouido St. Mary's Hospital between June 2005 and August 2012 were retrospectively reviewed. Results The mean patient age was 43.1 years (range, 17 to 88 years), and the cohort predominantly comprised women (18/21). In our experience, all acquired GTND patients presented with yellow or yellow-brownish chromonychia, onychotrophy, and onycholysis. Conservative treatment with tape methods and grinding, as well as nail extraction, was provided and yielded little improvement in any case. Conclusion This study provides initial data on the nail changes affecting the great toenail, such as yellowish chromonychia, onychomadesis, and onycholysis. These data may help physicians to distinguish various nail disorders, including onychomycosis, congenital malalignment of the great toenails, and yellow nail syndrome. PMID:25802692
Geria, Aanand N; Scheinfeld, Noah S
Pramiconazole from Barrier Therapeutics Inc is a new addition to the family of triazole antifungal agents that act by inhibiting fungal cell membrane ergosterol synthesis, thereby leading to increased cell permeability and destruction. Barrier Therapeutics was developing an oral formulation of pramiconazole for the potential treatment of seborrheic dermatitis (erythematosquamous skin disease), onychomycosis and dermatomycosis (including tinea versicolor, tinea pedis and tinea cruris/corporis). In preclinical studies, pramiconazole exhibited similar or superior antifungal activity to ketoconazole and itraconazole, and selectively inhibited ergosterol synthesis with a broad spectrum activity. Pramiconazole was absorbed rapidly and had a long half-life, allowing for once-daily dosing. In phase I and II clinical trials, pramiconazole reduced the growth of Candida albicans, Malassezia globosa, Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum, and was generally well tolerated. At the time of publication, Barrier Therapeutics had suspended the development of pramiconazole as part of a series of cost-cutting initiatives; the company had also been acquired by Stiefel Laboratories Inc. No formal announcement had been made regarding the further development of pramiconazole. The results of studies performed to date suggest that pramiconazole may be useful in the treatment of dermatomycoses when oral treatment is mandated. Promising preclinical and early phase II clinical data warrant the further development of the drug in larger clinical trials.
El-Khalawany, Mohamed A; Mahmoud, Ali M
Context: Hepatitis-C virus (HCV) infection and diabetes mellitus (DM) have a significant association with skin disorders. Aims: The aim of this study was to assess the impact of HCV infection on the pattern of cutaneous infections among diabetic patients. Methods and Material: A prospective study included diabetic patients who attended Al-Hussein University hospital, Cairo during the period from 2008 to 2010. Patients were examined for skin infections, and investigated for HCV infection. Statistical Analysis Used: SPSS (version 11.5). Results: The study included 163 patients (102 males and 61 females) with a mean age of 46.2 ± 4.83 years. Ninety five patients (58.3%) were HCV+ve (group A) while 68 patients (41.8%) were HCV-ve (group B). Skin infections in group A included fungal (48.4%), viral (26.3%), bacterial (22.1%) and parasitic (3.2%) while in group B, the spectrum included bacterial (41.2%), fungal (39.7%), viral (11.7%) and parasitic (7.4%). Onychomycosis was the commonest infection in group A (25.2%) compared with folliculitis in group B (19.1%). Cutaneous infections in HCV+ patients were more characterized by increased severity, aggressive course, resistance to treatment and rapid relapse. Conclusions: HCV infection has a significant impact in increasing and changing the spectrum of skin infections in diabetic patients. Severe and resistant infections in diabetics could be an important sign of HCV infection. PMID:24891654
Woodfolk, Judith A.
Tinea pedis (athlete's foot) and onychomycosis (infection of the toenails) caused by the dermatophyte fungus Trichophyton are highly prevalent in adults. Several Trichophyton allergens have been identified based on elicitation of immunoglobulin E antibody-mediated immediate-hypersensitivity (IH) responses. Evidence of an etiologic role for Trichophyton in asthma in some subjects with IH and chronic dermatophytosis is provided by bronchial reactivity to Trichophyton. Improvement of asthma after systemic antifungal treatment corroborates this link. A unique feature of Trichophyton allergens is the ability of the same antigen to elicit delayed-type hypersensitivity (DTH) in individuals who lack IH reactivity. Delayed responses appear to confer protection, while IH responses do not, based on the association with acute versus chronic skin infection. The amino acid sequence identity of Trichophyton allergens with diverse enzyme families supports a dual role for these proteins in fungal pathogenesis and allergic disease. Characterizing the immunologic properties of Trichophyton allergens and defining immune mechanisms which drive dichotomous responses are pivotal to understanding the dermatophyte-allergy relationship. Recent studies have identified DTH-associated major T-cell epitopes which could facilitate the development of peptide vaccines. Characterization of additional molecular targets by using new techniques may aid not only in the eradication of infection but also in the resolution of allergic symptoms. PMID:15653817
Paasch, Uwe; Nenoff, Pietro; Seitz, Anna-Theresa; Wagner, Justinus A; Kendler, Michael; Simon, Jan C; Grunewald, Sonja
Onychomycosis is a worldwide problem with no tendency for self-healing, and existing systemic treatments achieve disease-free nails in only 35 to 76% of cases. Recently, treatment of nail fungus with a near-infrared laser has been introduced. It is assumed that fungal eradication is mediated by local heat. To investigate if laser treatment has the potential to eradicate fungal hyphae and arthrospores, laser heat application and propagation needs to be studied in detail. This study aimed to measure nail temperatures using real-time videothermography during laser irradiation. Treatment was performed using 808- and 980-nm linear scanning diode lasers developed for hair removal, enabling contact-free homogeneous irradiation of a human nail plate in one pass. Average and peak temperatures increased pass by pass, while the laser beam moved along the nail plates. The achieved mean peak temperatures (808 nm: 74.1 to 112.4°C, 980 nm: 45.8 to 53.5°C), as well as the elevation of average temperatures (808 nm: 29.5 to 38.2°C, 980 nm: 27.1 to 32.6°C) were associated with pain that was equivalent to that of hair removal procedures and was not significantly different for various wavelengths. The linear scanning laser devices provide the benefits of contact-free homogeneous heating of the human nail while ensuring adequate temperature rises.
Hubka, Vit; Cmokova, Adela; Skorepova, Magdalena; Mikula, Peter; Kolarik, Miroslav
A previously undescribed Trichophyton species was isolated from the nail of a 33-year-old man with a history of probable distal lateral subungual onychomycosis (without confirmation by mycological examination). The infection occurred for the first time five years earlier (in 2006) and affected the right great toenail, with complete clinical remission after treatment with ciclopirox olamine. This undescribed species was isolated during probable relapse in 2011, but its etiological significance was not confirmed, that is, direct microscopy was negative and additional clinical samples were not collected. The species is probably geophilic based on phylogenetic analysis (internal transcribed spacer [ITS] rDNA) and is most closely related to the anamorphic T. thuringiense, homothallic Arthroderma ciferrii (anamorph T. georgiae), and heterothallic A. melis. The new species is characterized by yellowish colonies, red reverse on several media, positive urease test, negative hair-perforation test, absence of growth at 34°C, absence of macroconidia, formation of one-celled clavate microconidia, and spiral hyphae. The species grows well on sterilized human hairs placed on agar medium without any additional nutrients and forms gymnothecium-like structures covered by peridial hyphae. The combination of unique micro- and macromorphological features and physiological and sequence data from four unlinked loci (ITS, benA, RPB2, and act1 gene) justified the proposal of a new species T. onychocola sp. nov.
Verrier, Julie; Pronina, Marina; Peter, Corinne; Bontems, Olympia; Fratti, Marina; Salamin, Karine; Schürch, Stéphanie; Gindro, Katia; Wolfender, Jean-Luc; Harshman, Keith; Monod, Michel
A fast and reliable assay for the identification of dermatophyte fungi and nondermatophyte fungi (NDF) in onychomycosis is essential, since NDF are especially difficult to cure using standard treatment. Diagnosis is usually based on both direct microscopic examination of nail scrapings and macroscopic and microscopic identification of the infectious fungus in culture assays. In the last decade, PCR assays have been developed for the direct detection of fungi in nail samples. In this study, we describe a PCR-terminal restriction fragment length polymorphism (TRFLP) assay to directly and routinely identify the infecting fungi in nails. Fungal DNA was easily extracted using a commercial kit after dissolving nail fragments in an Na(2)S solution. Trichophyton spp., as well as 12 NDF, could be unambiguously identified by the specific restriction fragment size of 5'-end-labeled amplified 28S DNA. This assay enables the distinction of different fungal infectious agents and their identification in mixed infections. Infectious agents could be identified in 74% (162/219) of cases in which the culture results were negative. The PCR-TRFLP assay described here is simple and reliable. Furthermore, it has the possibility to be automated and thus routinely applied to the rapid diagnosis of a large number of clinical specimens in dermatology laboratories.
Coronado, Dina; Merchant, Tejal; Chanda, Sanjay; Zane, Lee T
An effective topical antifungal medication must penetrate through the nail plate at sufficient concentrations to eradicate the fungal infection. Tavaborole topical solution, 5% is a novel boron-based pharmaceutical approved for the treatment of toenail onychomycosis due to Trichophyton rubrum or T mentagrophytes. Four in vitro studies assessed the antifungal activity and nail penetration of tavaborole. In Study 1, tavaborole demonstrated minimum inhibitory concentration (MIC) values ranging from 0.25-2 μg/mL against all fungi tested; addition of 5% keratin powder did not affect the MIC against T rubrum. The minimum fungicidal concentration (MFC) values for tavaborole against T rubrum and T mentagrophytes were 8 and 16 μg/mL, respectively. In Study 2, tavaborole effectively penetrated through the nail plate; mean concentrations in the ventral/intermediate nail layer were significantly higher than ciclopirox at day 15. In Study 3, mean cumulative tavaborole penetration through ex vivo human nails was significantly higher than ciclopirox at day 15. In Study 4, tavaborole demonstrated superior nail penetration and fungicidal activity, as measured by zones of inhibition. These studies demonstrated the superior penetration of tavaborole through the nail plate vs ciclopirox. Tavaborole demonstrated robust antifungal activity, with low MIC and MFC values, even in the presence of keratin.
Nowrozi, Hossein; Nazeri, Golrokh; Adimi, Parvaneh; Bashashati, Mohsen; Emami, Masood
Onychomycosis is a difficult condition to treat and cure rates are disappointing. Moreover fungicidal action of antifungal agents in NCCLS assays and their rapid accumulation in nails in vivo are not compatible with the duration of treatment. This study aimed to find the effectiveness of 4 different antifungal agents in an in vitro model with some similarities to in vivo conditions. Strains of Trichophyton rubrum I-III, Trichophyton mentagrophytes (usual form), Trichophyton mentagrophytes 73, Epidermophyton Flucosom, Microsporum Canis, and Trichophyton Schoenleini which were isolated from the nails of patients, were hired. Inocula suspensions were prepared from 7 to 14 day-old cultures of dermatophytes. Antifungal agents including fluconazole, ketoconazole, terbinafine, and griseofulvin were obtained as standard powders. For each antifungal agent, initial MIC was calculated by registering the optical density for 10 two-fold serially diluted forms which was incubated with diluted fungal suspensions with RPMI 1640. Human nail powder inoculated with different strains and incubated in RPMI 1640 and different concentrations of antifungal drugs for 4 weeks. Final MIC at different steps of 1, 2, 3 and 4 weeks were investigated. The final MIC that resulted from the incubation of dermatophytes with nail powder was much more than the initial which was concluded from conventional MIC assay. Terbinafine had the lowest rate of initial and final MICs. The model described here may present more similar conditions to clinical fungal infections; therefore the results such as MIC may be more helpful for hiring the most effective antifungal agent.
van Diepeningen, Anne D; Feng, Peiying; Ahmed, Sarah; Sudhadham, Montarop; Bunyaratavej, Sumanas; de Hoog, G Sybren
Fusarium species are emerging causative agents of superficial, cutaneous and systemic human infections. In a study of the prevalence and genetic diversity of 464 fungal isolates from a dermatological ward in Thailand, 44 strains (9.5%) proved to belong to the genus Fusarium. Species identification was based on sequencing a portion of translation elongation factor 1-alpha (tef1-α), rDNA internal transcribed spacer and RNA-dependent polymerase subunit II (rpb2). Our results revealed that 37 isolates (84%) belonged to the Fusarium solani species complex (FSSC), one strain matched with Fusarium oxysporum (FOSC) complex 33, while six others belonged to the Fusarium incarnatum-equiseti species complex. Within the FSSC two predominant clusters represented Fusarium falciforme and recently described F. keratoplasticum. No gender differences in susceptibility to Fusarium were noted, but infections on the right side of the body prevailed. Eighty-nine per cent of the Fusarium isolates were involved in onychomycosis, while the remaining ones caused paronychia or severe tinea pedis. Comparing literature data, superficial infections by FSSC appear to be prevalent in Asia and Latin America, whereas FOSC is more common in Europe. The available data suggest that Fusarium is a common opportunistic human pathogens in tropical areas and has significant genetic variation worldwide.
Nicola, Aste; Laura, Atzori; Natalia, Aste; Monica, Pau
Tinea faciei is an uncommon dermatophytosis affecting the glabrous skin of the face. Between 1988 and 2007 at the Dermatology Department of Cagliari University, 107 cases of tinea faciei have been diagnosed, involving 72 females and 35 males, aged 2-72 years. Incidence peaks were observed between 6 and 15 years (48.59%) and between 36 and 45 years (17.76%). Males below and females above 15 years of age were the most affected. In 61 patients (57.1%), typical forms of tinea faciei were observed, whereas in 46 (42.9%), atypical forms were observed, mainly mimicking discoid lupus erythematosus (nine cases), and polymorphous light eruption (eight cases). Typical cases were present in younger patients, aged between 2 and 15 years, while atypical forms were distributed in any of the decades, but mostly between 36 and 72 years. Of the 46 cases of atypical presentation, 33 were females. The isolated dermatophytes were Microsporum canis (63 cases), Trichophyton rubrum (24 cases) and T. mentagrophytes var. mentagrophytes (20 cases). Seven males and two females aged 4-10 years were also affected by tinea capitis and eight patients (three males and five females) of various ages by tinea corporis. Eleven patients (two males and nine females) aged >35 years were affected by onychomycosis. All patients recovered after local and/or systemic antifungal therapy, without relapse or side effects.
Magiatis, Prokopios; Hantschke, Markus; Bassukas, Ioannis D.; Velegraki, Aristea
Summary: In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis. PMID:22232373
Haedersdal, Merete; Erlendsson, Andrés M; Paasch, Uwe; Anderson, R Rox
Ablative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice. We systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy. We searched PubMed and Embase databases; 34 articles met the inclusion criteria. Studies were categorized into experimental preclinical studies and clinical trials, the latter graded according to level of evidence. All preclinical trials (n = 16) documented enhanced topical drug uptake into skin after ablative fractional laser treatment. Clinical evidence encompassed 18 studies, of which 9 were randomized controlled trials and 2 were controlled trials, examining neoplastic lesions, photodamaged skin, scars, onychomycosis, and topical anesthetics. The highest level of evidence was reached for actinic keratoses treated with methylaminolevulinate for photodynamic therapy (level IB, 5 randomized controlled trials), substantiating superior and long-lasting efficacy versus conventional photodynamic therapy. No adverse events were reported, but ablative fractional laser-assisted drug delivery implies risks of systemic drug absorption, especially when performed over large skin areas. Fractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Nelson, P E; Dignani, M C; Anaissie, E J
There are several taxonomic systems available for identifying Fusarium species. The philosophy used in each taxonomic system is discussed as well as problems encountered in working with Fusarium species in culture. Fusarium species are toxigenic, and the mycotoxins produced by these organisms are often associated with animal and human diseases. The implications for the association of the carcinogens, fumonisins, produced by Fusarium moniliforme and other Fusarium species with human diseases are discussed. Foreign-body-associated fusarial infection such as keratitis in contact lens wearers, onychomycosis, skin infections, and disseminated multiorgan infections are discussed. Disseminated fusarial hyalohyphomycosis has emerged as a significant, usually fatal infection in the immunocompromised host. Successful outcome is determined by the degree of immunosuppression, the extent of the infection, and the presence of a removable focus such as an indwelling central venous catheter. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy, probably with one of the newer antifungal agents. Perhaps the use of such agents or the use of colony-stimulating factors may improve the outcome of this devastating infection. However, until new approaches for treatment develop, effective preventive measures are urgently needed. Images PMID:7834602
Beirão, F; Araujo, R
The epidemiology of fungal diseases changed, and molds have been increasingly associated with high mortality in severe immunocompromised patients. Invasive mold diseases may originate from the airborne conidia through inhalation or inoculation in skin fissures associated with indwelling catheters, wounds, burns, or onychomycosis. The diagnosis and treatment of fungal diseases is problematic and raises considerable challenges. Diagnosis of invasive mold diseases includes several methodologies, of which the most commonly used are the cultural methods, antigen testing, nucleic acid detection, and radiological imaging. Galactomannan and (1 → 3)-β-D-glucan detection significantly improved mold diagnosis in the last decade. Several molecular strategies have been proposed over the years but no consensus was achieved for standardized protocols or cut-off values. Recently, the first commercially available molecular assay for detection of Aspergillus was tested and the results were highly reproducible. In addition, blood cultures may also be helpful for invasive aspergillosis by following a novel procedure for the recovery of Aspergillus spp. from blood cultures. The association of distinct diagnostic methods, particularly molecular tests, galactomannan, and/or (1 → 3)-β-D-glucan detection, may provide earlier and more sensitive diagnosis of mold diseases and be indicative for early antifungal treatment. Accurate routine use of diagnostic tests can be cost-effective for laboratories and be of great value to patients.
Miklić, Paola; Skerlev, Mihael; Budimcić, Dragomir; Lipozencić, Jasna
Fungal infections involving the skin, hair and nails represent one of the most common mucocutaneous infections. Significant changes in the epidemiology, etiology and clinical pattern of mycotic infections have been observed during the last years. The aim of this retrospective study was to determine the incidence and the etiologic factors of superficial fungal infections in Zagreb area, Croatia, over a 10-year period (1999-2008). A total of 75828 samples obtained from 67 983 patients were analyzed. Dermatomycosis was verified by culture in 17410 (23%) samples obtained from 16086 patients. Female patients were more commonly affected than male (59% vs. 41%). Dermatophytes were responsible for 63% of all superficial fungal infections, followed by yeasts (36%) and molds (1%). Trichophyton (T.) mentagrophytes (both var. interdigitalis and var. granulosa) was the most frequent dermatophyte isolated in 58% of all samples, followed by Microsporum (M). canis (29%) and T. rubrum (10%). The most common clinical forms of dermatomycosis were onychomycosis (41%), tinea corporis (17%) and tinea pedis (12%). Candida spp. was mainly isolated from fingernail debris.
Belinchón Romero, I; Ramos Rincón, J M; Reyes Rabell, F
Leprosy, a disease caused by Mycobacterium leprae, primarily affects the skin and nerves, but the nails are also involved in as many as 3 out of 4 patients .The factors that trigger nail changes in leprosy are numerous and include repeated trauma, neuropathy, vascular impairment, infections, lepra reactions, and the drugs used to manage the disease. The changes most often reported include subungual hematomas, onycholysis, onychauxis, onychogryphosis, pterygium unguis, and onychoheterotopia, most of which can be attributed to nerve damage and trauma. Furthermore, the acro-osteolysis that occurs in the advanced stages of the disease may present with brachyonychia, racquet nails, or even anonychia. Infections of the nail bed leading to paronychia and onychomycosis should also be taken into account in leprosy. Other typical changes include longitudinal striae, pitting, macrolunula, Terry nails, leukonychia, hapalonychia, and Beau lines. In this review, we describe the principal nail changes associated with leprosy. These changes, which are highly varied and diverse in origin, are in fact a reflection of the significant morbidity caused by M. leprae infection. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.
Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa
Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the correlations between nail abnormalities and various clinical parameters. This study included 100 vitiligo patients and 100 healthy subjects. Full medical histories were collected from the subjects, who underwent thorough general and nail examinations. All nail changes were noted. In the event of clinical suspicion of a fungal infection, additional mycological investigations were performed. Nail abnormalities were more prevalent in the patients (78%) than in the controls (55%) (p=0.001). Longitudinal ridging was the most common finding (42%), followed by (in descending order): leukonychia, an absent lunula, onycholysis, nail bed pallor, onychomycosis, splinter hemorrhage and nail plate thinning. The frequency of longitudinal ridging was significantly higher in patients than in controls (p<0.001). Nail abnormalities were more prevalent in vitiligo patients than in controls. Systematic examination of the nails in such patients is useful because nail abnormalities are frequent. However, the causes of such abnormalities require further study. Longitudinal ridging and leukonychia were the most common abnormalities observed in this study.
Ben Abdeljelil, Jihene; Saghrouni, Fatma; Cabaret, Odile; Boukadida, Jalel; Bretagne, Stéphane; Ben Saïd, Moncef
The nosocomial transmission of Candida albicans in neonatal intensive care units (NICUs) is an increasing concern and understanding the route of this transmission is critical for adequate infection control measures. The aim of our study was to assess the likeliness of nosocomial acquisition of C. albicans in the NICU of Farhat Hached hospital in Sousse (Tunisia). We genotyped 82 isolates from 40 neonates and 7 isolates from 5 health care workers (HCWs) with onychomycosis, by using CDC3 microsatellite length polymorphism (MLP) and the high-resolution melting (HRM) analysis. Combined MLP and HRM CD3 analysis led to the delineation of 12 genotypes. Five temporal clustering caused by five genotypes occurred during the study period. Three of these genotypes were isolated in both neonates and HCWs. The first clustering included 28 isolates obtained between January 2003 and May 2004 from 16 neonates and 2 HCWs. The second clustering included three isolates collected in 2004 from three neonates and two HCWs. The third clustering included 11 isolates obtained from 6 neonates and 1 HCW in 2006. The two remaining clustering could not be associated with any HCW's contamination. These results argue for the nosocomial transmission of C. albicans in our NICU. The combined MLP and HRM analysis is a rapid first approach for tracking cross-contamination.
Ben Abdeljelil, J; Ben Saida, N; Saghrouni, F; Fathallah, A; Boukadida, J; Sboui, H; Ben Said, M
Candida albicans has become an important cause of nosocomial infections in neonatal intensive care units (NICUs). The aim of the present study was to compare C. albicans strains isolated from neonates (NN) suffering from systemic candidosis and from nurses in order to determine the relatedness between NN and health workers' strains. Thirty-one C. albicans strains were isolated from 18 NN admitted to the NICU of the neonatology service of Farhat Hached Hospital of Sousse, Tunisia and suffering from systemic candidosis, together with five strains recovered from nurses suffering from C. albicans onychomycosis. Two additional strains were tested, one from an adult patient who developed a systemic candidosis and the second from an adult with inguinal intertrigo. All strains were karyotyped by pulsed-field gel electrophoresis (PFGE) with a CHEF-DR II system. Analysis of PFGE patterns yielded by the 38 strains tested led to the identification of three pulsotypes that were designated I, II and III, and consisted of six chromosomal bands with a size ranging from 700 to >2500 kbp. The most widespread was the pulsotype I, which was shared by 17 NN and the five nurses' strains. The identity between NN and nurses' strains is very suggestive of a nosocomial acquisition from health-workers.
Ben Abdeljelil, Jihene; Saghrouni, Fatma; Khammari, Imene; Gheith, Soukeina; Fathallah, Akila; Ben Said, Moncef; Boukadida, Jalel
Nosocomial invasive candidiasis (IC) has emerged as a major problem in neonatal intensive care units (NICUs). We investigated herein the temporal clustering of six cases of neonatal IC due to Candida albicans in an NICU. Eighteen isolates obtained from the six neonates and two isolates from two health care workers (HCWs) working at the same unit and suffering from fingers' onychomycosis were genotyped by electrophoretic karyotyping (EK) and restriction endonuclease analysis of genomic DNA by using Sfi I (PFGE-Sfi I). PFGE-Sfi I was more effective in discriminating between temporally related isolates. It showed that (i) both HCWs had specific strains excluding them as a source of infections in neonates. (ii) Isolates collected from three neonates were identical providing evidence of their clonal origin and the occurrence of a horizontal transmission of C. albicans in the unit. (iii) The three remaining neonates had specific strains confirming that the IC cases were coincidental. (iv) Microevolution occurred in one catheter-related candidemia case. Our results illustrate the relevance of the molecular approach to investigate suspected outbreaks in hospital surveys and the effectiveness of PFGE-Sfi I for typing of epidemiologically related C. albicans isolates.
Polishchuk, N A
The course of time itself in alive organisms is treated from positions of the special theory of the relativity created by A. Einstein in 1905 and added by the Nobel winners H.A.Lorentsem, M. Plankom, M. fon Laue. These achievements of fundamental physics have been put in a basis of special medical technology "Resonant chronophytotherapy" (SMT RCPT) which is applied in practice of treatment of chronic diseases for 27 years. Grass tinctures in various dosages are used in SMT RCPT, which patients take once a day during precisely designated time. Parameters "dosage-time" daily vary. SMT RCPT have been conducted in treatment of epilepsy bronchial asthma, rheumatism, sclerodermia, hypertension, chronic glomerulonephritis, vegeto-vascular dystonia, female sterility, circular alopecia, vitiligo, eczema, psoriasis, onychomycosis. SMT RCPT does have adverse events, has no contra-indications to its use, directed, first of all, on elimination of nonspecific signs of a disease, reduces dependence and complications of the use of chemical synthetic preparations. SMT RCPT can be combined with any kind of specific treatment. Internet-variant of SMT RCPT has been developed. Chronomedicine is priority tendency in industrialized countries of the world--the USA, the Great Britain, Germany, France, Russia, China, Japan and appears on lead positions among alternative methods of treatment, both traditional, and non-traditional.
Long, L.; Hager, C.
The treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, the in vivo efficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with a P value of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding. PMID:26833160
Iglesias, A; Tamayo, L; Sosa-de-Martínez, C; Durán-McKinster, C; Orozco-Covarrubias, L; Ruiz-Maldonado, R
The purpose of this investigation was to explore the frequency and nature of ungual alterations in patients of a pediatric dermatology department at a third-level pediatric hospital. The first 20 patients with nail alterations seen each year during a 5-year period from 1992 through 1996 were included, totaling 100 patients. The rate of nail alterations was 11% (1/9) in pediatric dermatology patients. There were 5 infants, 19 preschoolers (2- to 5-year-olds), 38 school children (6- to 11-year-olds), and 38 adolescents (12- to 17-year-olds). The most frequent diagnoses were onychomycosis (23), nail alterations in a genodermatosis (23), nail alterations associated with dermatoses (16), onychocryptosis (11), and paronychia (10). Toenails were involved in 54 patients, fingernails in 25, and both in 21 patients. Twenty nails were involved in 21 patients. A high prevalence of nail alterations was found in pediatric dermatology patients, some of which were nonspecific, while others provided important diagnostic clues.
Long, L; Hager, C; Ghannoum, M
The treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, thein vivoefficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused byTrichophyton mentagrophytesusing a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with aPvalue of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Méndez-Tovar, Luis Javier; Lemini-López, Alicia; Hernández-Hernández, Francisca; Manzano-Gayosso, Patricia; Blancas-Espinosa, Roberto; López-Martínez, Rubén
In order to know mycosis frequency in the North of the State of Puebla, Mexico, in habitants from the communities of Ayotoxco, Mazatepec and Zacatipan were studied. Previous medical study biological samples were submitted to direct examination, smear and culture. Histoplasmin and sporotrichin skin test were applied to 57 individual from Zacatipan. From 110 patients 146 mycological studies were performed. Eighty six cases (59%) of mycosis were detected: 43 finger or toenails onychomycosis, 25 tinea pedis, seven tinea capitis, four cases of tinea manum and, finally, five cases of seborrhoeic dermatitis and two of pitiriasis versicolor. We isolated: 18 streins of dermatophytes, mainly Trichophyton rubrum and T. mentagrophytes (11 and 5 strains respectively); 12 cultures of non-dermatophytes filamentous fungi; six cases of mycelia sterile; six yeast strains, most of them Candida spp but none C. albicans. From 57 patients to whom skin tests were applied, five of them (8.8%) were positive to both antigens; ten positive (17.6%) only to histoplasmin and eight (14%) to sporotrichin. This study showed that rural population from Puebla present a high frequency of superficial mycosis (61% of mycological studies). Considering the percentage of positive skin test we suppose that there are many not diagnosed sporotrichosis and histoplasmosis cases.
Ginter-Hanselmayer, G; Nenoff, P; Kurrat, W; Propst, E; Durrant-Finn, U; Uhrlaß, S; Weger, W
Pubogenital tinea or tinea genitalis represents a rare type of dermatophytosis which, however, is increasingly being diagnosed. The mons pubis is affected, but also the outer regions to the penis shaft and the labia together with the groins. Pubogenital tinea is a more superficial erythrosquamous type, but strong inflammatory dermatomycoses of the genital area as tinea genitalis profunda ranging to kerion celsi are observed. A total of 30 patients (14-63 years of age, 11 men and 19 women) with pubogenital tinea are described. Most patients originated from Graz, Austria, while 2 patients were from Germany (Saxony and Isle of Sylt). Causative agents were mainly zoophilic dermatophytes: Microsporum (M.) canis (11), Trichophyton (T.) interdigitale (9), T. anamorph of Arthroderma benhamiae (2), and T. verrucosum (1). Anthropophilic fungi were T. rubrum (6) and T. tonsurans (1). Anamnestic questions should include contact with pets, physical activities, and travel. Genital shaving and concurrent tinea pedis and onychomycosis are disposing factors. Treatment consisted of oral antifungals except in the three women who were pregnant. Preferably, itraconazole or terbinafine was used, while in a single case, fluconazole was administered. Griseofulvin was not used, because this classic systemic antifungal agent is not allowed any more in Austria. In one patient, oral antifungal therapy was changed from itraconazole to terbinafine due to inefficacy.
In vitro model of infected stratum corneum for the efficacy evaluation of poloxamer 407-based formulations of ciclopirox olamine against Trichophyton rubrum as well as differential scanning calorimetry and stability studies.
Täuber, Anja; Müller-Goymann, Christel C
Superficial fungal skin infections are a common disease and concern 20-25% of the world's population with the dermatophyte Trichophyton rubrum being the main trigger. Due to autoinoculation, fungal skin infections of the feet (tinea pedis) often occur simultaneously with fungal nail infections (onychomycosis). Therefore, the overall objective was the development and characterisation of poloxamer 407-based formulations with the antimycotic active ingredient ciclopirox olamine (CPX) for simultaneous antifungal therapy. The formulations consisted of poloxamer 407, water, isopropyl alcohol, propylene glycol and medium chain triglycerides in given ratios. The in vitro antifungal efficacy against T. rubrum was tested in a novel in vitro model of infected stratum corneum in comparison to a marketed semi-solid formulation containing 1% (w/w) ciclopirox olamine and a marketed nail lacquer containing 8% ciclopirox. Several liquid poloxamer 407-based formulations with only 1% CPX completely inhibited fungal growth after 6 days of incubation, whereas the marketed semi-solid formulation did not inhibit fungal growth. Differential scanning calorimetry studies revealing the interaction between the formulations and the SC showed that increasing isopropyl alcohol/propylene glycol concentrations as well as increasing CPX concentrations caused increasing endothermic transition shifts. Moreover, stability studies at 30 °C exhibited only a slight decrease of the CPX amount after 12 months of storage. Each formulation contained >90% of the initial CPX concentration after termination of the stability studies. Copyright © 2015 Elsevier B.V. All rights reserved.
Zapata, Luis Fernando; Paulo, José David; Restrepo, Carlos A; Velásquez, Luis Fernando; Montoya, Andrés E Toro; Zapata, Melissa A
Purpose To report an interesting case of infectious endotheliitis of presumed mycotic origin. Methods A case report of a 56-year-old male farmer who sought medical attention after a month-long evolution of irritative symptoms in his right eye, accompanied by visual acuity (VA) impairment. The patient received topical and oral broad-spectrum antibiotic treatment with no improvement before being referred to a cornea specialist, where he was found to have VA of 20/150 and was noted on biomicroscopy to have endothelial feathery coalescent lesions. The patient was admitted to the hospital for an aqueous humor sample and intravenous voriconazole. Results The microbiological studies did not isolate any micro-organisms. However, clinical evidence of improvement was confirmed after 5 days of antimycotic intravenous therapy. Complete clinical resolution was achieved at 1 month after treatment completion with oral voriconazole, as evidenced by VA of 20/20 and disappearance of endothelial lesions. Conclusion Endothelial involvement by fungi is a rare condition. In this case, no microbes were isolated, but the characteristic morphology of the lesions, the history of onychomycosis, and the spectacular response to voriconazole turn this case into a valid presumptive diagnosis. PMID:23901253
Paasch, Uwe; Nenoff, Pietro; Seitz, Anna-Theresa; Wagner, Justinus A.; Kendler, Michael; Simon, Jan C.; Grunewald, Sonja
Onychomycosis is a worldwide problem with no tendency for self-healing, and existing systemic treatments achieve disease-free nails in only 35 to 76% of cases. Recently, treatment of nail fungus with a near-infrared laser has been introduced. It is assumed that fungal eradication is mediated by local heat. To investigate if laser treatment has the potential to eradicate fungal hyphae and arthrospores, laser heat application and propagation needs to be studied in detail. This study aimed to measure nail temperatures using real-time videothermography during laser irradiation. Treatment was performed using 808- and 980-nm linear scanning diode lasers developed for hair removal, enabling contact-free homogeneous irradiation of a human nail plate in one pass. Average and peak temperatures increased pass by pass, while the laser beam moved along the nail plates. The achieved mean peak temperatures (808 nm: 74.1 to 112.4°C, 980 nm: 45.8 to 53.5°C), as well as the elevation of average temperatures (808 nm: 29.5 to 38.2°C, 980 nm: 27.1 to 32.6°C) were associated with pain that was equivalent to that of hair removal procedures and was not significantly different for various wavelengths. The linear scanning laser devices provide the benefits of contact-free homogeneous heating of the human nail while ensuring adequate temperature rises.
Khorchani, H; Haouet, H; Amri, M; Zanned, I; Babba, H; Azaiz, R
Despite of socio-economical improvement in our population and the efficacy of available antifungal treatment, superficial mycoses remain a common condition in dermatologic practice. To determine the epidemio-clinical pattern of superficial mycoses in our region, a retrospective study of 3578 cases have been carried out in the Department of Dermatology of the University Hospital of Monastir during a 4 year-period. The mean age of patients was 33 years (range: 6 months-91 years). The male to female sex-ratio was 0.82. Rural origin, history of previous mycoses, diabetes, topic or systemic corticosteroids and the presence of animals in surroundings were the most predisposing factors. The most frequent clinical patterns were: tinea corcoris and pedis (40.3%), Tinea versicolor (21.6%), Tinea capitis (9.7%) dermatophytosis of hairless skin (9.6%) and onychomycosis (8.6%). Dermatophyte was the most frequent (55.5%). The occurrence of superficial mycose especially if it affects diffuse area of the body, or if it is relapsing and resistant to treatment, requires looking for predisposing factors.
Pires, Carla Andréa Avelar; da Cruz, Natasha Ferreira Santos; Lobato, Amanda Monteiro; de Sousa, Priscila Oliveira; Carneiro, Francisca Regina Oliveira; Mendes, Alena Margareth Darwich
BACKGROUND The cutaneous mycoses, mainly caused by dermatophyte fungi, are among the most common fungal infections worldwide. It is estimated that 10% to 15% of the population will be infected by a dermatophyte at some point in their lives, thus making this a group of diseases with great public health importance. OBJECTIVE To analyze the clinical, epidemiological, and therapeutic profile of dermatophytosis in patients enrolled at the Dermatology service of Universidade do Estado do Pará, Brazil, from July 2010 to September 2012. METHOD A total of 145 medical records of patients diagnosed with dermatophytosis were surveyed. Data were collected and subsequently recorded according to a protocol developed by the researchers. This protocol consisted of information regarding epidemiological and clinical aspects of the disease and the therapy employed. RESULTS The main clinical form of dermatophyte infection was onychomycosis, followed by tinea corporis, tinea pedis, and tinea capitis. Furthermore, the female population and the age group of 51 to 60 years were the most affected. Regarding therapy, there was a preference for treatments that combine topical and systemic drugs, and the most widely used drugs were fluconazole (systemic) and ciclopirox olamine (topical). CONCLUSION This study showed the importance of recurrent analysis of the epidemiological profile of dermatophytosis to enable correct therapeutic and preventive management of these conditions, which have significant clinical consequences, with chronic, difficult-totreat lesions that can decrease patient quality of life and cause disfigurement. PMID:24770502
Flores, F C; de Lima, J A; Ribeiro, R F; Alves, S H; Rolim, C M B; Beck, R C R; da Silva, Cristiane Bona
The aim of this study was to evaluate, for the first time, the antifungal efficacy of nanocapsules and nanoemulsions containing Melaleuca alternifolia essential oil (tea tree oil) in an onychomycosis model. The antifungal activity of nanostructured formulations was evaluated against Trichophyton rubrum in two different in vitro models of dermatophyte nail infection. First, nail powder was infected with T. rubrum in a 96-well plate and then treated with the formulations. After 7 and 14 days, cell viability was verified. The plate counts for the samples were 2.37, 1.45 and 1.0 log CFU mL(-1) (emulsion, nanoemulsion containing tea tree oil and nanocapsules containing tea tree oil, respectively). A second model employed nails fragments which were infected with the microorganism and treated with the formulations. The diameter of fungal colony was measured. The areas obtained were 2.88 ± 2.08 mm(2), 14.59 ± 2.01 mm(2), 40.98 ± 2.76 mm(2) and 38.72 ± 1.22 mm(2) for the nanocapsules containing tea tree oil, nanoemulsion containing tea tree oil, emulsion and untreated nail, respectively. Nail infection models demonstrated the ability of the formulations to reduce T. rubrum growth, with the inclusion of oil in nanocapsules being most efficient.
Lange, M; Nowicki, R; Barańska-Rybak, W; Bykowska, B
During a 3-year period (1999-2001) a total of 94 cases of dermatophytosis were seen in patients from 0 to 18 years of age attending the Department of Dermatology, Venerology and Allergology of Gdańsk Medical University. Mycoses were diagnosed on the basis of clinical picture and direct microscopy and were confirmed by positive cultures. The most frequent pathogens were Microsporum canis (62%) and Trichophyton rubrum (12%). The most often forms of dermatophytosis in children were tinea cutis glabrae (42%) and tinea capitis (30%). Microsporum canis predominated in both locations. Glabrous skin lesions were the most frequent in children aged 8-15 years; the peak of scalp lesions was observed mainly in children aged 4-7 years. Tinea pedis occurred more frequently than suspected. Tinea pedis was observed mainly in adolescents (above the age of 12 years)--the majority of cases were caused by T. rubrum and T. mentagrophytes var. granulosum. Onychomycosis was highly uncommon, caused mainly by T. rubrum. Dermatomycoses in general were most frequent in October and November.
Hazen, K C
The most common yeast species that act as agents of human disease are Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Cryptococcus neoformans. The incidence of infections by other yeasts has increased during the past decade. The most evident emerging pathogens are Malassezia furfur, Trichosporon beigelii, Rhodotorula species, Hansenula anomala, Candida lusitaniae, and Candida krusei. Organisms once considered environmental contaminants or only industrially important, such as Candida utilis and Candida lipolytica, have now been implicated as agents of fungemia, onychomycosis, and systemic disease. The unusual yeasts primarily infect immunocompromised patients, newborns, and the elderly. The role of central venous catheter removal and antifungal therapy in patient management is controversial. The antibiograms of the unusual yeasts range from resistant to the most recent azoles and amphotericin B to highly susceptible to all antifungal agents. Current routine methods for yeast identification may be insufficient to identify the unusual yeasts within 2 days after isolation. The recognition of unusual yeasts as agents of sometimes life-threatening infection and their unpredictable antifungal susceptibilities increase the burden on the clinical mycology laboratory to pursue complete species identification and MIC determinations. Given the current and evolving medical practices for management of seriously ill patients, further evaluations of the clinically important data about these yeasts are needed. PMID:8665465
Del Rosso, James Q.; Plattner, Jacob J.
The development of new drug classes and novel molecules that are brought to the marketplace has been a formidable challenge, especially for dermatologic drugs. The relative absence of new classes of antimicrobial agents is also readily apparent. Several barriers account for slow drug development, including regulatory changes, added study requirements, commercial pressures to bring drugs to market quickly by developing new generations of established compounds, and the greater potential for failure and higher financial risk when researching new drug classes. In addition, the return on investment is usually much lower with dermatologic drugs as compared to the potential revenue from “blockbuster” drugs for cardiovascular or gastrointestinal disease, hypercholesterolemia, and mood disorders. Nevertheless, some researchers are investigating new therapeutic platforms, one of which is boron-containing compounds. Boron-containing compounds offer a wide variety of potential applications in dermatology due to their unique physical and chemical properties, with several in formal phases of development. Tavaborole, a benzoxaborole compound, has been submitted to the United States Food and Drug Administration for approval for treatment of onychomycosis. This article provides a thorough overview of the history of boron-based compounds in medicine, their scientific rationale, physiochemical and pharmacologic properties, and modes of actions including therapeutic targets. A section dedicated to boron-based compounds in development for treatment of various skin disorders is also included. PMID:24578778
Banga, Gurvinder; Patel, Kalpana
Background: With the increasing use of nail paints, nail art, acetone, repeated manicures, cosmetic nail procedures and detergents, the nail plate undergoes regular damage resulting in rough, lusterless and pigmented nails. Besides that onychomycosis, nail lichen planus, nail pitting and ridging due to various diseases also cause cosmetically disfiguring nails. Objective: The study is directed toward use of 70% glycolic acid for controlled keratolysis of the nail-plate, resulting that could result in shinier, smoother and brighter nails. Materials and Methods: A prospective single-center open-label uncontrolled study of 31 patients, 22 with dry, rough, discolored nails and 9 with hyperkeratotic nails were included in the study group. After examination and ruling out any infection, petroleum jelly was applied on the cuticle margins of the nails for protection and 70% glycolic acid was applied over the nail plate for 45 minutes. In dry rough discolored nails, only a single sitting was done while in hyper-keratotic nail conditions multiple weekly sittings were done. Results: In 22 patients with dry rough nails, 80% showed good improvement, 10% showed average improvement, whereas 10% were non-responsive. Nine patients with thickened nail plate showed good improvement in 60% average improvement in 25% improvement and 15% were non-responsive, after multiple sessions. Conclusion: Controlled keratolysis of the nail plate with application of 70% glycolic acid can be a promising treatment for modality for thick, uneven, rough and pigmented nail-plate conditions with cosmetically pleasing results. PMID:25722596
Murthy, S Narasimha; Vaka, Siva Ram Kiran; Sammeta, Srinivasa Murthy; Nair, Anroop B
Topical monotherapy of nail diseases such as onychomycosis and nail psoriasis has been less successful due to poor permeability of the human nail plate to topically administered drugs. Chemical enhancers are utilized to improve the drug delivery across the nail plate. Choosing the most effective chemical enhancers for the given drug and formulation is highly critical in determining the efficacy of topical therapy of nail diseases. Screening the large pool of enhancers using currently followed diffusion cell experiments would be tedious and expensive. The main objective of this study is to develop TranScreen-N, a high throughput method of screening trans-ungual drug permeation enhancers. It is a rapid microwell plate based method which involves two different treatment procedures; the simultaneous exposure treatment and the sequential exposure treatment. In the present study, several chemicals were evaluated by TranScreen-N and by diffusion studies in the Franz diffusion cell (FDC). Good agreement of in vitro drug delivery data with TranScreen-N data provided validity to the screening technique. In TranScreen-N technique, the enhancers can be grouped according to whether they need to be applied before or simultaneously with drugs (or by either procedures) to enhance the drug delivery across the nail plate. TranScreen-N technique can significantly reduce the cost and duration required to screen trans-ungual drug delivery enhancers. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association
Naumann, Sandy; Meyer, Jean-Philippe; Kiesow, Andreas; Mrestani, Yahya; Wohlrab, Johannes; Neubert, Reinhard H H
The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established. Copyright © 2014 Elsevier B.V. All rights reserved.
Gunt, Hemali B; Kasting, Gerald B
The impact of hydration on the permeation of the antifungal drug, ketoconazole, through excised human nails in vitro was evaluated in diffusion cell studies. Nails treated with [(3)H]ketoconazole solvent-deposited onto the dorsal surface were maintained in incubators at 32 degrees C and exposed sequentially to relative humidities (dorsal side) of 15, 40, 80 and 100% over a period of 40 days. The ventral side was bathed in a pH 7.4 phosphate buffer. Ascending and descending humidity regimens were tested. Increasing the ambient RH from 15 to 100% enhanced permeation of radiolabel associated with [(3)H]ketoconazole by a factor of three. Diffusivities estimated from these data and the associated nail water contents (estimated in a separate study) can be described by a free volume theory. Therefore, formulations or treatments, which increase nail hydration, have potential to improve topical therapy for onychomycosis, if a favorable balance between drug delivery and growth conditions for the dermatophytes can be achieved.
The first ever symposium dedicated solely to drug delivery to the nail following topical application was held on the 2nd April 2007, in London, UK, organised by Dr Clive Roper (Charles River Laboratories, Scotland) and Dr Sudaxshina Murdan (School of Pharmacy, University of London, UK), under the auspices of Skin Forum. The 1-day meeting was attended by approximately 35 delegates from industry, academia and hospitals, and provided a much-needed forum for the presentation and discussion of research and problems in this emerging field. Topical drug delivery is especially suitable for onychomycosis (fungal infections of the nail plate and/or nail bed) and nail psoriasis, which affect 2 - 13 and 1 - 3% of the general population, respectively, and make up the bulk of nail disorders. Topical therapy would avoid the adverse events and drug interactions of systemic antifungal agents and the pain of injection when antipsoriatic agents are injected into affected nail folds. However, successful topical therapy is extremely challenging due to the very low permeability of the nail plate. Five speakers spoke about various aspects of topical drug delivery to the nail, including review of the nail plate structure, function, diseases, their existing therapies (systemic and topical), limitations and global sales. The need for effective topical drug delivery to the nail to overcome the problems associated with present treatment, and the fact that there are few topical formulations available for the treatment of nail fungal infections and psoriasis, and the even fewer effective formulations, was highlighted.
Palliyil, Biji; Lebo, David B; Patel, Pankil R
Onychomycosis is associated with the cutaneous fungal infection of the nail and the nail folds (skin surrounding the nail). It is therefore important to target drug delivery into the nail folds along with nail plate and the nail bed. Systematic and strategic selection of the penetration enhancers specific for the skin and the nail is discussed. Twelve penetration enhancers were screened for their ability to improve solubility, in vitro nail penetration, in vitro skin permeation, and in vitro skin penetration of the antifungal drug ciclopirox olamine. In contrast to transdermal drug delivery, the main selection criteria for skin penetration enhancer in topical drug delivery were increased drug accumulation in the epidermis and minimal permeation across the skin. Thiourea improved the solubility and nail penetration of ciclopirox olamine. It also showed enhancement in the transungual diffusion of the drug. Propylene glycol showed a 12-fold increase in solubility and 3-fold increase in epidermal accumulation of ciclopirox olamine, while minimizing the transdermal movement of the drug. Thiourea was the selected nail permeation enhancer and propylene glycol was the selected skin penetration enhancer of ciclopirox olamine. A combination of the selected enhancers was also explored for its effect on drug delivery to the nail and nail folds. The enhancer combination reduced the penetration of ciclopirox in the skin and also the permeation through the nail. The proposed preformulation strategy helps to select appropriate enhancers for optimum topical delivery and paves way towards an efficient topical formulation for passive transungual drug delivery.
Monti, Daniela; Tampucci, Silvia; Chetoni, Patrizia; Burgalassi, Susi; Mailland, Federico
One of the pre-requisite for a successful topical antifungal drug indicated for onychomycosis is its bioavailability into the nail unit for achieving fungal eradication and clinical benefit. The aim of this study was to compare in vitro permeation/penetration through and into human nails of amorolfine (MRF) from a 5% anhydrous commercial formulation (Loceryl®) and ciclopirox (CPX) from the 8% aqueous formulation in hydroxypropyl chitosan (HPCH) technology (Onytec®). The ability of the active ingredient to reach efficacious concentrations to inhibit nail pathogens was also evaluated. The amounts of drug permeated and retained in human healthy nails were determined using a suitably modified diffusion apparatus. HPLC analysis of the samples was performed. The HPCH-based CPX formulation demonstrated an efficient penetration into and permeation through the nail plates. Conversely, Loceryl® produced an amount of MRF permeated through and penetrated into the human toenails significantly lower than CPX. The evaluation of the efficacy index showed a higher potential efficacy of Onytec® with respect to Loceryl® on nail pathogens. The present work not only reinforced the previous results on different experimental substrates, but pointed out the superiority of HPCH-based Onytec® formulation containing CPX with respect to Loceryl® commercial product with MRF, both in terms of higher permeation through and penetration into the human nail, and for the efficacy towards the most common ungual pathogens.
The topical therapy of nail diseases, especially of onychomycosis, and to a smaller extent, of nail psoriasis, is desirable to avoid the side effects associated with their systemic therapy, to increase patient compliance and reduce the cost of treatment. Systemic therapy is however the mainstay of treatment due to the poor permeability of the nail plate to topically applied drugs. For effective topical therapy, ungual drug permeation must be enhanced. This can be achieved by disrupting the nail plate using physical techniques or chemical agents. Alternatively, drug permeation into the intact nail plate may be encouraged, for example, by iontophoresis or by formulating the drug within a vehicle which enables high drug partition out of the vehicle and into the nail plate. The physical techniques (manual and electrical nail abrasion, acid etching, ablation by lasers, microporation, application of low-frequency ultrasound and electric currents) and chemicals (thiols, sulphites, hydrogen peroxide, urea, water, enzymes) that have shown ungual enhancer activity are discussed in this review. Optimal drug formulation, while crucial to ungual drug delivery, is only briefly reviewed due to the limited literature.
Saner, Manish V; Kulkarni, Abhijeet D; Pardeshi, Chandrakantsing V
Topical therapy is at the forefront in treating nail ailments (especially onychomycosis and nail psoriasis) due to its local effects, which circumvents systemic adverse events, improves patient compliance and reduces treatment cost. However, the success of topical therapy has been hindered due to poor penetration of topical therapeutics across densely keratinized nail plate barrier. For effective topical therapy across nail plate, ungual drug permeation must be enhanced. Present review is designed to provide an insight into prime aspects of transungual drug delivery viz. nail structure and physiology, various onychopathies, techniques of nail permeation enhancement and in vitro models for trans-nail drug permeation studies. Updated list of drug molecules studied across the nail plate and key commercial products have been furnished with sufficient depth. Patents pertinent to, and current clinical status of transungual drug delivery have also been comprehensively reviewed. This is the first systematic critique encompassing the detailed aspects of transungual drug delivery. In our opinion, transungual drug delivery is a promising avenue for researchers to develop novel formulations, augmenting pharmaceutical industries to commercialize the products for nail disorders.
Shivakumar, H N; Juluri, Abhishek; Desai, B G; Murthy, S Narasimha
Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate.
Baswan, Sudhir M.; Li, S. Kevin; LaCount, Terri D.; Kasting, Gerald B.
The electrical properties of human nail plate are poorly characterized, yet are a key determinate of the potential to treat nail diseases such as onychomycosis using iontophoresis. In order to address this deficiency, molar conductivities of 17 electrolytes comprising 12 ionic species were determined in hydrated human nail plate in vitro. Cation transport numbers across the nail for 11 of these electrolytes were determined by the electromotive force method. Effective ionic mobilities and diffusivities at infinite dilution for all ionic species were determined by regression analysis. The ratios of diffusivities in nail to those in solution were found to correlate inversely with the hydrodynamic radii of the ions according to a power law relationship having an exponent of −1.75 ± 0.27, a substantially steeper size dependence than observed for similar experiments in skin. Effective diffusivities of cations in nail were three-fold higher than those of comparably sized anions. These results reflect the strong size and charge selectivity of the nail plate for ionic conduction and diffusion. The analysis implies that efficient transungual iontophoretic delivery of ionized drugs having radii upwards of 5 Å (approximately MW ≥ 340 Da) will require chemical or mechanical alteration of the nail plate. PMID:26886342
Nair, Anroop B; Vaka, Siva Ram K; Sammeta, Srinivasa M; Kim, Hyun D; Friden, Phillip M; Chakraborty, Bireswar; Murthy, S Narasimha
Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. The aim of the present study was to attain rapid trans-ungual delivery of an antifungal agent, terbinafine, via the topical route using iontophoresis. Initial studies revealed that application of current (0.5 mA/cm(2)) could significantly enhance the trans-ungual delivery of terbinafine. An increase in the applied current or duration of current application enhanced the trans-ungual delivery of terbinafine. Permeation of terbinafine through the nail and drug load in the nail correlated well with the applied electrical dose. Release of drug from nails loaded using iontophoresis followed a two-phase release profile. Light microscopy studies substantiated the capability of iontophoresis to drive a charged molecule across the nail plate. The results of these studies indicate that iontophoresis could be developed as a potential technique for onychomycosis therapy.
Lusiana; Reichl, Stephan; Müller-Goymann, Christel C
A novel model of infected nail plate for testing the efficacy of topical antifungal formulations has been developed. This model utilized keratin film made of human hair keratin as a nail plate model. Subsequent to infection by Trichophyton rubrum, the common causative agent of onychomycosis, keratin films as infected nail plate models were treated with selected topical formulations, that is cream, gel, and nail lacquer. Bovine hoof was compared to keratin film. In contrast to the common antifungal susceptibility test, the antifungal drugs tested were applied as ready-to-use formulations because the vehicle may modify and control the drug action both in vitro and in vivo. Extrapolating the potency of an antifungal drug from an in vitro susceptibility test only would not be representative of the in vivo situation since these drugs are applied as ready-to-use formulations, for example as a nail lacquer. Although terbinafine has been acknowledged to be the most effective antifungal agent against T. rubrum, its antifungal efficacy was improved by its incorporation into an optimal formulation. Different gels proved superior to cream. Therefore, this study is able to discriminate between efficacies of different topical antifungal formulations based on their activities against T. rubrum. Copyright © 2013 Elsevier B.V. All rights reserved.
Chouhan, P; Saini, T R
Drug delivery by topical route for the treatment of onychomycosis, a nail fungal infection, is challenging due to the unique barrier properties of the nail plate which imparts high resistance to the passage of antifungal drugs. Permeation enhancers are used in transungual formulations to improve the drug flux across the nail plate. Selection of the effective permeation enhancer among the available large pool of permeation enhancers is a difficult task. Screening the large number of permeation enhancers using conventional Franz diffusion cells is laborious and expensive. The objective of present study was to evolve a simple, accurate and rapid method for screening of transungual drug permeation enhancers based on the principle of hydration of nail plate. The permeation enhancer which affects the structural or physicochemical properties of nail plate would also affect their hydration capacity. Two screening procedures namely primary and secondary screenings were evolved wherein hydration and uptake of ciclopirox olamine by nail plates were measured. Hydration enhancement factor, HEF(24) and drug uptake enhancement factor, UEF(24) were determined for screening of 23 typical permeation enhancers. The Pearson's correlation coefficient between HEF(24) and UEF(24) was determined. A good agreement between the HEF(24) and UEF(24) data proved the validity of the proposed nail plate hydration model as a screening technique for permeation enhancers. Copyright © 2012 Elsevier B.V. All rights reserved.
Shimamura, Tsuyoshi; Miyamae, Akiko; Arai, Masakazu; Minemura, Aya; Nozawa, Akira; Kubota, Nobuo
To clarify the character of luliconazole nail solution we have developed, we investigated luliconazole distribution and antifungal activity in nail plate. An in vitro permeation study which measured luliconazole concentration of sliced nail in the transverse direction after treatment of luliconazole nail solution was conducted to investigate for concentration dependency and the influences of nail thickness and treatment duration. When 0.2, 1, 3, 5, and 7.5% luliconazole nail solutions were used, luliconazole was detected in the all the layers of nail and there was a concentration gradient from the dorsal side to deep nail layers. The luliconazole concentration was almost same after 14-day treatment with 5% luliconazole nail solution when using nails of different thicknesses. And we confirmed that concentration of luliconazole into the nail was increased depending on the treatment duration. In zone of inhibition test after 14-day treatment, 5% luliconazole nail solution showed statistically high formation rate of zones of inhibition compared to 8% ciclopirox nail lacquer. Above all, these data suggested that 5% luliconazole nail solution has the potential to show high therapeutic effect for onychomycosis.
Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa
Background Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. Objective We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the correlations between nail abnormalities and various clinical parameters. Methods This study included 100 vitiligo patients and 100 healthy subjects. Full medical histories were collected from the subjects, who underwent thorough general and nail examinations. All nail changes were noted. In the event of clinical suspicion of a fungal infection, additional mycological investigations were performed. Results Nail abnormalities were more prevalent in the patients (78%) than in the controls (55%) (p=0.001). Longitudinal ridging was the most common finding (42%), followed by (in descending order): leukonychia, an absent lunula, onycholysis, nail bed pallor, onychomycosis, splinter hemorrhage and nail plate thinning. The frequency of longitudinal ridging was significantly higher in patients than in controls (p<0.001). Conclusions Nail abnormalities were more prevalent in vitiligo patients than in controls. Systematic examination of the nails in such patients is useful because nail abnormalities are frequent. However, the causes of such abnormalities require further study. Longitudinal ridging and leukonychia were the most common abnormalities observed in this study. PMID:27579738
Gaitanis, Georgios; Magiatis, Prokopios; Hantschke, Markus; Bassukas, Ioannis D; Velegraki, Aristea
In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis.
Kushwaha, Avadhesh Singh; Sharma, P; Shivakumar, H N; Rappleye, C; Zukiwski, A; Proniuk, S; Murthy, S Narasimha
AR-12 is a novel small molecule with broad spectrum antifungal activity. Recently, AR-12 was found to be highly active against Trichophyton rubrum, one of the predominantly responsible organisms that cause onychomycosis. The primary objective of this project was to investigate the ability of AR-12 to penetrate into and across the human nail plate followed by improving its trans-ungual permeation using different penetration enhancers. TranScreen-N™, a high throughput screening method was utilized to explore the potential nail penetration enhancers to facilitate the drug delivery through the nail. This screen demonstrated that dexpanthenol and PEG 400 were the most efficient enhancers. The in vitro permeation studies were performed across the human cadaver nail plates for 7 days with three AR-12 (5% w/v) formulations containing 10% w/v dexpanthenol (Formulation A), 10% w/v PEG 400 (Formulation B), and a combination of 10% w/v dexpanthenol + 10% w/v PEG 400 (Formulation C). The in vitro studies concluded that dexpanthenol and PEG 400 were able to deliver a significant amount of AR-12 into and across the nail plate that was found to be more than MIC 50 level of the drug.
Rodrigues, Anderson Messias; Cruz Choappa, Rodrigo; Fernandes, Geisa Ferreira; de Hoog, G Sybren; de Camargo, Zoilo Pires
A combination of phylogeny, evolution, morphologies and ecologies has enabled major advances in understanding the taxonomy of Sporothrix species, including members exhibiting distinct lifestyles such as saprobes, human/animal pathogens, and insect symbionts. Phylogenetic analyses of ITS1/2 + 5.8s sequences split Sporothrix genus in two well-defined groups with dissimilar ecologies. Species embedded in the Sporothrix schenckii complex are frequently agents of human and animal sporotrichosis, and some of these are responsible for large sapronoses and zoonoses around the warmer temperate regions of the world. At the other extreme, basal saprophytic species evolved in association with decaying wood and soil, and are rarely found to cause human disease. We propose to create a new taxa, Sporothrix chilensis sp. nov., to accommodate strains collected from a clinical case of onychomycosis as well as from environmental origins in Chile. Multigene analyses based on ITS1/2 + 5.8s region, beta-tubulin, calmodulin and translation elongation factor 1α revealed that S. chilensis is a member of the Sporothrix pallida complex, and the nearest taxon is Sporothrix mexicana, a rare soil-borne species, non-pathogenic to humans. The ITS region serves as a primary barcode marker, while each one of the protein-coding loci easily recognized species boundaries providing sufficient information for species identification. A disseminated model of murine sporotrichosis revealed a mild-pathogenic potential, with lung invasion. Although S. chilensis is not a primary pathogen, accidental infection may have an impact in the immunosuppressed population. With the introduction of distinct species with similar routes of transmission but different virulence, identification of Sporothrix agents at the species level is mandatory.
Nowrozi, Hossein; Nazeri, Golrokh; Adimi, Parvaneh; Bashashati, Mohsen; Emami, Masood
Background: Onychomycosis is a difficult condition to treat and cure rates are disappointing. Moreover fungicidal action of antifungal agents in NCCLS assays and their rapid accumulation in nails in vivo are not compatible with the duration of treatment. Aims: This study aimed to find the effectiveness of 4 different antifungal agents in an in vitro model with some similarities to in vivo conditions. Materials and Methods: Strains of Trichophyton rubrum I-III, Trichophyton mentagrophytes (usual form), Trichophyton mentagrophytes 73, Epidermophyton Flucosom, Microsporum Canis, and Trichophyton Schoenleini which were isolated from the nails of patients, were hired. Inocula suspensions were prepared from 7 to 14 day-old cultures of dermatophytes. Antifungal agents including fluconazole, ketoconazole, terbinafine, and griseofulvin were obtained as standard powders. For each antifungal agent, initial MIC was calculated by registering the optical density for 10 two-fold serially diluted forms which was incubated with diluted fungal suspensions with RPMI 1640. Human nail powder inoculated with different strains and incubated in RPMI 1640 and different concentrations of antifungal drugs for 4 weeks. Final MIC at different steps of 1, 2, 3 and 4 weeks were investigated. Results: The final MIC that resulted from the incubation of dermatophytes with nail powder was much more than the initial which was concluded from conventional MIC assay. Terbinafine had the lowest rate of initial and final MICs. Conclusion: The model described here may present more similar conditions to clinical fungal infections; therefore the results such as MIC may be more helpful for hiring the most effective antifungal agent. PMID:19882010
Ali-Shtayeh, M S; Yaish, S; Jamous, R M; Arda, H; Husein, E I
To determine the epidemiology of dermatophytosis in Palestinian patients, detect changes in the etiological agents during the last three decades, and to correlate between concomitant tinea pedis infections, and other cutaneous lesions. 220 suspected dermatophytosis patients were involved in this study. In an additional 38 cases, where consultation was prompted by tinea pedis, the presence of other lesions of concomitant dermatophytosis was studied, to further investigate the diagnosis. Clinical specimens were collected and identification of dermatophyte species was based on gross and microscopic morphology. Epidemiology of tinea capitis has gone the most radical changes in Palestine in the last three decades, with the zoophilic dermatophyte Microsporum canis replacing Trichophyton violaceum, becoming the predominant causative agent. During this study, 21.6% (38/176) patients with tinea pedis and concomitant lesions caused by the same dermatophytes at sites distant from the primary lesions in the foot were prospectively identified. About 63.2% of patients with tinea pedis have a concomitant toenail onychomycosis infection. The epidemiology of dermatophytosis, especially tinea capitis, has gone the most radical changes in Palestine in the last three decades, with M. canis replacing T. violaceum, and becoming the predominant causative agent of all cases of infections. The coexistence of tinea pedis with other types of fungal skin infections is a frequent phenomenon; we believe that the infected foot may be a site of primary infection. Thus, the effective therapy for tinea pedis is essential to prevent spreading the infection to other sites of the skin. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Chaturvedi, V.; Diekema, D.; Ostrosky-Zeichner, L.; Rennie, R.; Walsh, T.; Wengenack, N.; Fothergill, A.; Wiederhold, N.
ME1111 is a novel small molecule antifungal agent under development for the topical treatment of onychomycosis. Standardization of the susceptibility testing method for this candidate antifungal is needed. Toward this end, 8 independent laboratories determined the interlaboratory reproducibility of ME1111 susceptibility testing. In addition, we subsequently identified 2 strains as quality control (QC) isolates for the method. In the reproducibility study, 5 blinded clinical strains each of Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum were tested, while the QC study tested 6 blinded T. rubrum or T. mentagrophytes ATCC strains. Testing was performed in frozen microtiter panels according to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 methodology. In the reproducibility study, 9 of 15 clinical strains showed interlaboratory agreement of >90% at the 80% inhibition endpoint, with a range of agreement of 76.2% to 100%. In the QC study, 4 of the 6 ATCC strains showed interlaboratory agreement of >90%. ME1111 demonstrated excellent interlaboratory agreement when tested against dermatophytes. Based on this data, the CLSI Subcommittee on Antifungal Susceptibility Tests approved the susceptibility testing of ME1111 against dermatophytes according to M38-A2 methodology, which stipulates RPMI 1640 as the test medium, an inoculum size of 1 to 3 × 103 CFU/ml, and an incubation time and temperature of 96 h at 35°C. The MIC endpoint should be 80% inhibition compared with the growth control. T. rubrum ATCC MYA-4438 and T. mentagrophytes ATCC 28185 were selected as QC isolates, with an acceptable range of 0.12 to 1 μg/ml for the two strains. PMID:26719434
Haenssle, Holger A; Blum, Andreas; Hofmann-Wellenhof, Rainer; Kreusch, Juergen; Stolz, Wilhelm; Argenziano, Giuseppe; Zalaudek, Iris; Brehmer, Franziska
Pigmented and non-pigmented nail alterations are a frequent challenge for dermatologists. A profound knowledge of clinical and dermatoscopic features of nail disorders is crucial because a range of differential diagnoses and even potentially life-threatening diseases are possible underlying causes. Nail matrix melanocytes of unaffected individuals are in a dormant state, and, therefore, fingernails and toenails physiologically are non-pigmented. The formation of continuous, longitudinal pigmented streaks (longitudinal melanonychia) may either be caused by a benign activation of matrix melanocytes (e.g., as a result of trauma, inflammation, or adverse drug reactions) or by a true melanocytic proliferation (e.g., in a nevus or melanoma). In general, non-continuous nail alterations, affecting only limited parts of the nail apparatus, are most frequently of non-melanocytic origin. Important and common differential diagnoses in these cases are subungual hemorrhage or onychomycosis. In addition, foreign bodies, bacterial infections, traumatic injuries, or artificial discolorations of the nail unit may less frequently cause non-continuous nail alterations. Many systemic diseases that may also show involvement of the nails (e.g., psoriasis, atopic dermatitis, lichen planus, alopecia areata) tend to induce alterations in numerous if not all nails of the hands and feet. A similar extensive and generalized alteration of nails has been reported after treatment with a number of systemic drugs, especially antibiotics and cytostatics. Benign or malignant neoplasms that may also affect the nail unit include glomus tumor, Bowen's disease, squamous cell carcinoma, and rare collision tumors. This review aims to assist clinicians in correctly evaluating and diagnosing nail disorders with the help of dermatoscopy.
Macura, Anna B.
Introduction In the genus Scopulariopsis, Scopulariopsis brevicaulis is the most common aetiological agent of infections in humans. It usually affects nails and is one of the commonest moulds associated with onychomycoses. Other forms of infections (skin, subcutaneous, deep tissues, and disseminated infections) have also been described. Aim To examine the prevalence of S. brevicaulis in clinical materials obtained from patients suspected of keratinized tissues mycoses. Material and methods The analysis of the prevalence of S. brevicaulis in clinical specimens was based on mycological test's results carried out for patients who were referred with a suspicion of superficial mycoses to the Department of Mycology, Chair of Microbiology, Jagiellonian University Medical College from 1992 till 2012. Results In the years 1992–2012 16,815 clinical samples (nail scrapings, nail swabs, skin scrapings, skin swabs, hair) were collected. Pathogenic fungi were detected in 7193 samples and S. brevicaulis was present in 255 (3.5%). The prevalence of S. brevicaulis in males and females was comparable. The species was most often isolated from toenails (80%), both from males and females. In the analysed period we observed a decrease in the prevalence of S. brevicaulis. In most cases (60%) S. brevicaulis occurred alone in 40% of S. brevicaulis positive cultures, other fungi were also isolated. The fungi most frequently isolated with S. brevicaulis were Trichophyton rubrum, T. mentagrophytes, Penicillium sp., Candida sp., and Aspergillus sp. Conclusions Scopulariopsis brevicaulis is not a common cause of superficial fungal infections of keratinized tissues, but is a typical mould associated with toenail onychomycosis. A proper identification of this species in onychomycoses is essential for the implementation of effective antifungal therapy. PMID:26161060
Scytalidium dimidiatum is the leading cause of fungal foot diseases in Thailand, in contrast to similar studies in which dermatophytes have been identified as the predominant pathogens. By contrast, the prevalence of Candida albicans in our study was only 2.6 approximately 3.0%. Scytalidium fungal foot infection is clinically indistinguishable from that caused by dermatophytes and should be included as a possible cause of treatment failure in tinea pedis and onychomycosis. Without proper culture identification, clinically diagnosed patients would be treated with a standard antifungal regimen leading to minimal response and be interpreted as drug resistant cases resulting in switching of drugs and more aggressive management procedures. Tinea capitis is another health problem in young children. However, for Microsporum canis and some ectothrix organisms, the effectiveness of treatment may be less than endothrix infection. Griseofulvin is still the mainstay antifungal although itraconazole and terbinafine are as effective. Pulse regimen may be another option with advantages of increased compliance and convenience. Two pulses of terbinafine may be sufficient for treating most cases of Microsporum infection, although additional treatment may be needed if clinical improvement is not evident at week 8 after initiating therapy. Chromoblastomycosis is another subcutaneous infection that requires long treatment duration with costly antifungal drugs. The most common pathogen in Thailand is Fonsecaea pedrosoi. Preliminary study of pulse itraconazole 400 mg/d 1 week monthly for 9-12 consecutive months showed promising results. The prevalence of Penicillium marneffei infection is alarming in HIV infected patients living in endemic areas. Diagnosis relies on direct examination of the specimens and confirmation by culture. Treatment regimens include systemic amphotericin B or itraconazole followed by long-term prophylaxis. Treatment outcome depends on the immune status of the
Guevara-Suarez, Marcela; Cano-Lira, José Francisco; de García, María Caridad Cepero; Sopo, Leticia; De Bedout, Catalina; Cano, Luz Elena; García, Ana María; Motta, Adriana; Amézquita, Adolfo; Cárdenas, Martha; Espinel-Ingroff, Ana; Guarro, Josep; Restrepo, Silvia; Celis, Adriana
Fusariosis have been increasing in Colombia in recent years, but its epidemiology is poorly known. We have morphologically and molecularly characterized 89 isolates of Fusarium obtained between 2010 and 2012 in the cities of Bogotá and Medellín. Using a multi-locus sequence analysis of rDNA internal transcribed spacer, a fragment of the translation elongation factor 1-alpha (Tef-1α) and of the RNA-dependent polymerase subunit II (Rpb2) genes, we identified the phylogenetic species and circulating haplotypes. Since most of the isolates studied were from onychomycoses (nearly 90 %), we carried out an epidemiological study to determine the risk factors associated with such infections. Five phylogenetic species of the Fusarium solani species complex (FSSC), i.e., F. falciforme, F. keratoplasticum, F. lichenicola, F. petroliphilum, and FSSC 6 as well as two of the Fusarium oxysporum species complex (FOSC), i.e., FOSC 3 and FOSC 4, were identified. The most prevalent species were FOSC 3 (38.2%) followed by F. keratoplasticum (33.7%). In addition, our isolates were distributed into 23 haplotypes (14 into FOSC and nine into FSSC). Two of the FSSC phylogenetic species and two haplotypes of FSSC were not described before. Our results demonstrate that recipients of pedicure treatments have a lower probability of acquiring onychomycosis than those not receiving such treatments. The antifungal susceptibility of all the isolates to five clinically available agents showed that amphotericin B was the most active drug, while the azoles exhibited lower in vitro activity.
Ranganathan, S; Balajee, S A; Raja, S M
Two hundred and eleven dogs (including strictly house and stray dogs) and 170 cattle in and around the city of Madras, India were screened for the presence of dermatophytosis. 106 strains of dermatophytes (89 strains from dogs and 17 strains from bovines) were isolated. 57/106 strains were Trichophyton mentagrophytes var. mentagrophytes and 42/106 strains were of the Microsporum gypseum complex. 5 strains of T. rubrum and 2 strains of T. simii were also obtained in culture. A predominance of M. gypseum complex isolates was recorded in stray dogs and cattle and T. mentagrophytes var. mentagrophytes and T. rubrum in strictly house dogs. The family history of the owners of the most of the dogs had clear records of dermatophytosis. Further, the owners of the 11 dogs that yielded T. mentagrophytes var. mentagrophytes had either tinea corporis or tinea pedis. The etiological agent of all the 11 human cases was T. mentagrophytes var. interdigitale. Similarly the owners of 4 of the 5 dogs that yielded T. rubrum were known T. rubrum patients. All these patients responded to oral griseofulvin or ketaconozole, but the recurrence of lesions was noted with the cessation of treatment. None of the patients had onychomycosis and the family history of all the patients revealed no reports of T. rubrum infections. The pet dogs were presumed to be the source of re-infection. Reversed transmission of dermatophytes from humans to animals may be the reason for the selective predominance of these organisms in strictly house dogs. They also may act as sources of reinfection. Most of the animals had small, occult, scattered lesions. These lesions may either go unnoticed or are ignored by the owners of the animals. The taxonomic status of T. mentagrophytes and T. mentagrophytes var. interdigitale was aligned to their teleomorph Arthroderma vanbreuseghemii. Our study suggests that the periodic screening and medication of all live-stock are essential for the prevention and management of the
Ranganathan, S; Arun Mozhi Balajee, S; Mahendra Raja, S
Two hundred and eleven dogs (including strictly house and stray dogs) and 170 cattle in and around the city of Madras, India were screened for the presence of dermatophytosis. 106 strains of dermatophytes (89 strains from dogs and 17 strains from bovines) were isolated. 57/106 strains were Trichophyton mentagrophytes var. mentagrophytes and 42/106 strains were of the Microsporum gypseum complex. 5 strains of T. rubrum and 2 strains of T. simii were also obtained in culture. A predominance of M. gypseum complex isolates was recorded in stray dogs and cattle and T. mentagrophytes var. mentagrophytes and T. rubrum in strictly house dogs. The family history of the owners of the most of the dogs had clear records of dermatophytosis. Further, the owners of the 11 dogs that yielded T. mentagrophytes var. mentagrophytes had either tinea corporis or tinea pedis. The etiological agent of all the 11 human cases was T. mentagrophytes var. interdigitale. Similarly the owners of 4 of the 5 dogs that yielded T. rubrum were known T. rubrum patients. All these patients responded to oral griseofulvin or ketaconozole, but the recurrence of lesions was noted with the cessation of treatment. None of the patients had onychomycosis and the family history of all the patients revealed no reports of T. rubrum infections. The pet dogs were presumed to be the source of re-infection. Reversed transmission of dermatophytes from humans to animals may be the reason for the selective predominance of these organisms in strictly house dogs. They also may act as sources of reinfection. Most of the animals had small, occult, scattered lesions. These lesions may either go unnoticed or are ignored by the owners of the animals. The taxonomic status of T. mentagrophytes var. mentagrophytes and T. mentagrophytes var. interdigitale was aligned to their teleomorph Arthroderma vanbreuseghemii. Our study suggests that the periodic screening and medication of all live-stock are essential for the prevention and
Chabasse, D; Pihet, M
Onychomycoses represent about 30% of superficial mycosis that are encountered in Dermatology consults. Fungi such as dermatophytes, which are mainly found on the feet nails, cause nearly 50% of these onychopathies. Yeasts are predominantly present on hands, whereas non-dermatophytic moulds are very seldom involved in both foot and hand nails infections. According to literature, these moulds are responsible for 2 to 17% of onychomycoses. Nevertheless, we have to differentiate between onychomycoses due to pseudodermatophytes such as Neoscytalidium (ex-Scytalidium) and Onychocola canadensis, which present a high affinity for keratin, and onychomycoses due to filamentous fungi such as Aspergillus, Fusarium, Scopulariopsis, Acremonium... These saprophytic moulds are indeed most of the time considered as colonizers rather than real pathogens agents. Mycology and histopathology laboratories play an important role. They allow to identify the species that is involved in nail infection, but also to confirm parasitism by the fungus in the infected nails. Indeed, before attributing any pathogenic role to non-dermatophytic moulds, it is essential to precisely evaluate their pathogenicity through samples and accurate mycological and/or histological analysis. The treatment of onychomycoses due to non-dermatophytic moulds is difficult, as there is today no consensus. The choice of an antifungal agent will first depend on the species that is involved in the infection, but also on the severity of nail lesions and on the patient himself. In most cases, the onychomycosis will be cured with chemical or mechanical removing of the infected tissues, followed by a local antifungal treatment. In some cases, a systemic therapy will be discussed.
Atalay, Mustafa Altay; Koc, Ayşe Nedret
Scedosporium apiospermum is a saprophytic fungus which is isolated worldwide in soil, fertilizers, polluted water, rotten vegetables, and other natural environments. It is the cause of mycetoma, a subcutaneous infection, characterized by granule formation. It may also cause severe local or diffuse infections in immunosuppressive patients. S.apiospermum-induced arthritis, endocarditis, keratitis, scleritis, endophthalmitis, meningitis, osteomyelitis, otomycosis, onychomycosis, chronic prostatitis, peritonitis, esophagitis, renal infection, and hepatosplenic abscess have been previously reported in the literature. Possible risk factors of fungal keratitis, one of the major causes of fungal ocular infection, include ocular injury, long-term therapy with topical or systemic steroids, immunosuppressive agents, and underlying diseases such as pre-existing corneal surface abnormality and diabetes mellitus, and wearing contact lenses. We paid great attention to the case report presented by Kalkan Akçay E et al. titled "Fungal keratitis caused by Scedosporium apiospermum: first report from Turkey", which was published in the October 2013 issue of Bulletin of Microbiology [Mikrobiyol Bul 2013; 47(4): 727-33]. Although it is deemed as the first case report of S.apiospermum-related fungal keratitis in Turkey, there were several previous case reports of ocular infections associated with this type of fungus in Turkey, including those of Yucel A titled "An eye mycosis caused by Scedosporium apiospermum (Monosporium apiospermum)" published in 1989, Kiratli et al. titled "Scedosporium apiospermum chorioretinitis" in 2001, Saracli et al. titled "Scedosporium apiospermum keratitis treated with itraconazole" in 2003 and Erdem et al. titled "Clinical follow up of a keratomycosis case with total corneal melting" in 2005. In conclusion, it should be highlighted that the report of Kalkan Akcay et al. is not the first case report of Scedosporium apiospermum-related fungal keratitis in
Griseofulvin is a metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fongistatic, the exact mechanism in witch it inhibits the growth of dermatophytes is doubtful. Several ways are invoked: inhibition of fungal cell mitosis and nuclear acid synthesis, probable interference with the function of microtubules. Griseofulvin is poorly absorbed from the gastrointestinal tract. Absorption is enhanced by administration with fatty meal. Peak plasma occurs four hours after oral administration. Griseofulvin is detected in the outer layer of the stratum corneum soon after it is ingested, it is diffused from the extracellular fluid and sweat. There is no information regarding the mechanism by witch the drug is delivered to nails and hair. Deposition in the newly formed cells could be the major factor. Griseofulvin has also anti-inflammatory properties and some direct vasodilatory effects when it is used in high doses. It is metabolised by the liver microsomial enzyme system and excreted in the urine. The half-life is 9 to 21 hours. Griseofulvine has been used in the therapy of dermatophyte onychomycosis, treatment periods from 6 to 18 months were necessary with disappointing results and numerous relapses. Newer oral antifungal agents are now preferred especially in toenail infections. For many authors griseofulvin is still the treatment of choice of tinea capitis. Doses are 15-20 mg/kg/d for 6 to 8 weeks in children with the microsized form. Clinical response rates have been reported between 80 and 90 p. 100 in controlled studies. Griseofulvin is well-tolerated particulary in children. More frequent side effects are minor: headaches, gastrointestinal reactions and cutaneous eruptions. The major drug interactions has been noted with phenobarbital, anticoagulants and oral contraceptives.
The aim of this paper was to explore how aging influences the nail unit, its disorders and its response to treatment, and to identify some of the age-related gaps in the ungual drug delivery literature. Aging causes obvious changes to the nail, some of which are inherently due to old age, while others are due to diseases/conditions which become more prevalent as we age. Alterations in the nail plate's colour, contour, thickness, fragility, surface features, cell size, chemical composition and growth rate are some of the changes, with toenails and fingernails showing different effects. With respect to disease, the incidence of onychomycosis - the most common nail disorder - is considerably higher in older people. Similarly, brittle nails become more common as we age. In contrast, the literature about aging and the incidence of nail psoriasis is inconclusive, although, it is clear that as one gets older, the negative impact of nail psoriasis on one's quality of life decreases. Pharmaceutical treatment of the diseases comprises local and systemic therapies, sometimes in combination. Systemic therapies have the inherent disadvantages of adverse systemic effects, drug interactions and the need for monitoring, disadvantages which are especially problematic for older people who are more likely to suffer from co-morbidities and be on other medications. Topical therapy avoids such disadvantages. However, the success rates of commercially available preparations are low, and older people may need help with their application. It is also proposed that regular inspection and grooming of nails should become part of routine care of older people, as these would provide opportunities to identify and treat any problems at an earlier stage. Copyright © 2016 Elsevier B.V. All rights reserved.
Werner, Betina; Antunes, Andre
Nail clipping analysis for diagnosing causes of onychodystrophy other than onychomycosis is investigated to a very small extent. In order to achieve acceptance as a diagnostic method for any kind of nail abnormalities, normal microscopic parameters have to be established first. In most reported cases, nail plates were fixed in formalin with processing of the specimens with routine automated histotechnique. Fifteen pairs of normal nails were studied. One nail fragment was placed in a container with formalin, and the other was kept dry in a proper receptacle. Fixed specimens were submitted to standard automated tissue processing (formalin group) and dry specimens were directly embedded in paraffin (dry group). Several microscopic parameters were analyzed. Nail plate thickness ranged from 0.25 to 0.50 mm (mean 0.36 mm) and subungual region from 0 to 0.31 mm (mean 0.11 mm). Forty-one percent of cases presented onychokaryosis, and hypereosinophilic nuclear shadows were detected in 63%, statistically more frequent in the dry group (p=0.002). Parakeratosis was present in 86% of nails varying from 1 to 13 layers (mean 5.6). None of the nails presented fungi, neutrophils, and blood or serum collections. Bacteria were seen in 60% of specimens. Both groups yielded adequate microscopic preparations for analysis with no statistical difference in the dryness or hardness of specimens or difficulty in cutting the paraffin blocks (p=1). These microscopic findings of a normal population can be used as parameters for evaluating any cause of onychodystrophy. The dry method is faster and cheaper and yields adequate slide preparations for microscopic analysis of nail clippings.
Ghannoum, Mahmoud A; Long, Lisa; Cirino, Amber J; Miller, Anthony R; Najafi, Ron; Wang, Lu; Sharma, Kuldeepak; Anderson, Mark; Memarzadeh, Bahram
Dermatophytes, belonging to genera including Trichophyton, Epidermophyton, and Microsporum, are the causative agents of superficial fungal infections, prevalences of which are estimated to be as high as 25% in the worldwide population. This study evaluated the activity of topical formulations of NVC-422 (sodium 2-[dichloroamino]-2-methylpropane-1-sulfonate), the lead compound in a new class of antimicrobials that consist of broad-spectrum, fast-acting, nonantibiotic antimicrobial molecules based on the endogenously produced N-chlorotaurines. The antifungal efficacy of NVC-422 was investigated using a guinea pig model of infection with Trichophyton mentagrophytes. Infected guinea pigs were randomly assigned to four treatment and two control groups. The efficacy of the treatments was assessed clinically and mycologically at 72 hours after the final topical dose. The test compound 2% NVC-422 in 1% Noveon Gel demonstrated the highest level of clinical efficacy. Outcomes of treatment with all other test compounds differed significantly from outcomes in the untreated control group (P = 0.003, P = 0.029, P = 0.012, and P < 0.0001, respectively). Fungal elements were detectable in skin sections from untreated guinea pigs but not in skin sections obtained from any of the treatment groups. Evaluation of the efficacy of NVC-422 in the treatment of dermatophytosis using an experimental guinea pig model showed that this compound possesses potent antifungal efficacy as measured by mycological and clinical endpoints. The highest degree of clinical and mycological efficacy was demonstrated by 2% NVC-422 in 1% Noveon Gel. These data show that NVC-422 has potent antifungal activity in vivo. Clinical evaluation of NVC-422 in the treatment of superficial infections caused by dermatophytes, including onychomycosis, is warranted. © 2013 The International Society of Dermatology.
Haenssle, Holger A.; Blum, Andreas; Hofmann-Wellenhof, Rainer; Kreusch, Juergen; Stolz, Wilhelm; Argenziano, Giuseppe; Zalaudek, Iris; Brehmer, Franziska
Pigmented and non-pigmented nail alterations are a frequent challenge for dermatologists. A profound knowledge of clinical and dermatoscopic features of nail disorders is crucial because a range of differential diagnoses and even potentially life-threatening diseases are possible underlying causes. Nail matrix melanocytes of unaffected individuals are in a dormant state, and, therefore, fingernails and toenails physiologically are non-pigmented. The formation of continuous, longitudinal pigmented streaks (longitudinal melanonychia) may either be caused by a benign activation of matrix melanocytes (e.g., as a result of trauma, inflammation, or adverse drug reactions) or by a true melanocytic proliferation (e.g., in a nevus or melanoma). In general, non-continuous nail alterations, affecting only limited parts of the nail apparatus, are most frequently of non-melanocytic origin. Important and common differential diagnoses in these cases are subungual hemorrhage or onychomycosis. In addition, foreign bodies, bacterial infections, traumatic injuries, or artificial discolorations of the nail unit may less frequently cause non-continuous nail alterations. Many systemic diseases that may also show involvement of the nails (e.g., psoriasis, atopic dermatitis, lichen planus, alopecia areata) tend to induce alterations in numerous if not all nails of the hands and feet. A similar extensive and generalized alteration of nails has been reported after treatment with a number of systemic drugs, especially antibiotics and cytostatics. Benign or malignant neoplasms that may also affect the nail unit include glomus tumor, Bowen’s disease, squamous cell carcinoma, and rare collision tumors. This review aims to assist clinicians in correctly evaluating and diagnosing nail disorders with the help of dermatoscopy. PMID:25396079
Perea, Sofia; Ramos, Maria Jose; Garau, Margarita; Gonzalez, Alba; Noriega, Antonio R.; del Palacio, Amalia
This study prospectively evaluated the prevalence and risk factors of tinea unguium and tinea pedis in the general adult population in Madrid, Spain. One thousand subjects were clinically examined, and samples of nails and scales from the interdigital spaces of the feet were taken from those patients presenting with signs or symptoms of onychomycosis and/or tinea pedis, respectively. In addition, a sample from the fourth interdigital space of both feet was collected from all individuals with a piece of sterilized wool carpet. Tinea unguium was defined as a positive direct examination with potassium hydroxide and culture of the etiological agent from subjects with clinically abnormal nails. Patients with positive dermatophyte cultures of foot specimens were considered to have tinea pedis. The prevalence of tinea unguium was 2.8% (4.0% for men and 1.7% for women), and the prevalence of tinea pedis was 2.9% (4.2% for men and 1.7% for women). The etiological agents of tinea unguium were identified as Trichopyton rubrum (82.1%), followed by Trichopyton mentagrophytes var. interdigitale (14.3%) and Trichopyton tonsurans (3.5%). Trichophyton rubrum (44.8%) and Trichophyton mentagrophytes (44.8%), followed by Epidermophyton floccosum (7%) and T. tonsurans (3.4%), were the organisms isolated from patients with tinea pedis. The percentage of subjects who suffered simultaneously from both diseases was 1.1% (1.7% for men and 0.6% for women). In a multivariate logistic regression analysis, age (relative risk [RR], 1.03) and gender (RR, 2.50) were independent risk factors for tinea unguium, while only gender (RR, 2.65) was predictive for the occurrence of tinea pedis. In both analyses, the presence of one of the two conditions was associated with a higher risk for the appearance of the other disease (RR, >25). PMID:10970362
Pichardo-Geisinger, Rita; Muñoz-Ali, Diana; Arcury, Thomas A; Blocker, Jill N; Grzywacz, Joseph G; Mora, Dana C; Chen, Haiying; Schulz, Mark R; Feldman, Steve R; Quandt, Sara A
Immigrant Latino workers represent an expanding workforce in rural areas of the USA, where their employment is concentrated in occupations such as poultry processing that entail chemical, infectious, and mechanical skin exposures. Occupation-related skin illnesses in this vulnerable population are not well characterized. This study was designed to describe the prevalences of skin diseases among immigrant Latino poultry processors and other manual workers in North Carolina. Community-based sampling was used to recruit 742 immigrant Latino workers, 518 of whom underwent a physical examination supervised by a board-certified dermatologist. The presence or absence of skin disease on the face, neck, arms, hands, and feet was recorded. Workers ranged in age from 18 years to 68 years. Slightly over half of the sample were male (52.6%). Poultry workers represented 55.8% of the study sample. Infectious skin diseases were the most common diagnosis, present in 52.3% of workers. Inflammatory skin diseases were present in 28.2% and pigmentary disorders in 21.8% of workers. The most common skin conditions were tinea pedis (37.6%), onychomycosis (31.9%), scars (13.7%), acne (11.8%), and melasma (9.3%). Age, sex, first language, and work as a poultry processor accounted in part for the prevalence of these diseases. Several skin diseases are highly prevalent in immigrant Latino workers and may relate to work environment. These may impair the quality of life of these workers and predispose them to further illness. © 2013 The International Society of Dermatology.
Täuber, Anja; Müller-Goymann, Christel C
Fungal infections of skin and/or nails are common diseases resulting in major challenges in topical treatment. Therefore, the objective of the present study was to develop a dermal formulation targeting both tinea pedis and onychomycosis. The antifungal agent ciclopirox olamine (CPX) was incorporated into a variety of poloxamer 407-based formulations and analysed regarding its in vitro permeation and penetration behaviour across keratin films (KF) and bovine hoof plates as artificial nail models as well as human stratum corneum (SC). The novel compositions consisted of poloxamer 407 (P407), double distilled water, propylene glycol, isopropyl alcohol and medium chain triglycerides in given ratios. All the formulations exhibited semi-solid to liquid consistencies and were isotropic under a polarising microscope. Upon CPX incorporation, the formulations became softer and the yield stresses decreased. Increasing temperature led to higher complex viscosities. Permeation coefficients (P) from P407-based formulations across KF and bovine hoof plates and normalised retained CPX amounts in KF and bovine hoof plates were higher in comparison to the nail lacquer Ciclopoli(®) as a marketed reference. Data of KF and bovine hoof plates were comparable, therefore KF are suggested as artificial nail model for in vitro permeation studies besides the well-accepted nail model of bovine hoof plates. With regard to SC permeation, several liquid formulations indicated higher P in comparison to the references Ciclopoli(®) and the antimycotic skin formulation Selergo(®) 1% cream, while the normalised retained API amounts in SC were higher in comparison with Selergo(®) 1% cream or in the same range as Ciclopoli(®). Copyright © 2015 Elsevier B.V. All rights reserved.
Nascimento, Maria do Desterro Soares Brandão; Leitão, Valéria Maria Sousa; Neto Silva, Marcos Antonio Custódio da; Maciel, Leonardo Bezerra; Filho Muniz, Walbert Edson; Viana, Graça Maria de Castro; Bezerra, Geusa Felipa de Barros
There are more than 300,000 extractors using the babaçu coconut as a source of income in the States of Maranhão, Pará, Tocantins and Piauí, and this activity is associated with fungal infections. The objective of this study was to examine the occurrence of emergent fungi in the conjunctiva, nails and surface and subcutaneous injuries of female coconut breakers in Esperantinópolis, Maranhão. Additionally, soil samples and palm structures were collected. The obtained samples were cultured in Petri dishes containing potato-dextrose-agar and chloramphenicol. The etiological agent was confirmed by a direct mycological exam and growth in culture. In total, 150 domiciles were visited, and samples were collected from 80 patients. From the ground, the most frequently isolated fungus was Aspergillus niger (53. 8%). the most frequently detected fungus in babaçu coconut was Aspergillus niger (66.7%). Conjunctival fungal growth occurred in 76.3% of the women. The ocular fungal microbiota consisted of filamentous fungi (80.6%), and yeasts were present in 19.4% of cases. Onychomycosis was diagnosed in 44% (11/25) of the women. The identification of the genera Neosartorya, Rhizopus and Curvularia in onychomycoses shows that emergent filamentous fungi can be isolated. Aspergillus sp., Penicillium sp. and Scedosporium sp. were the predominant genera found in the babaçu coconut. From ocular conjunctiva, Candida spp. were the most prevalent species isolated, and Fusarium sp. was present only in one woman. The nearly permanent exposure of coconut breakers to the external environment and to the soil is most likely the reason for the existence of a mycotic flora and fungal infections, varying according to the individual's practices and occupation.
Monti, D; Saccomani, L; Chetoni, P; Burgalassi, S; Tampucci, S; Mailland, F
Topical therapy has recently been proposed for treating onychomycosis and other nail disturbances. However, the clinical outcome may be limited by the difficulty of active ingredients effectively penetrating the nail plate. Bovine hoof membranes have been widely used to predict in vitro efficacy of drug products in nail diseases. Many studies have compared bovine hooves with human healthy nails, considering the difference between healthy and unhealthy nails to be negligible. To validate bovine hoof slices as a model for human unhealthy nails by investigating the transungual permeation/retention of ciclopirox (CPX) through bovine hoof slices and excised infected human toenails after application of a new film-forming formulation (P-3051). To investigate the ability of CPX to achieve fungicidal concentrations in and through infected toenails. A new experimental technique based on a permeation unit allowed analysis by high-performance liquid chromatography of the amounts of CPX permeating through and retained in the membranes. The efficacy index was evaluated as follows: amount of permeated CPX/Trichophyton rubrum minimum inhibiting concentration. Extrapolated CPX flux through bovine hoof slices was about 14-fold higher than through infected human toenails, the difference being mainly due to the fourfold higher thickness of the toenails. In toenails, the CPX efficacy index for T. rubrum was positive (>1·0) soon after P-3051 application. This study confirms the validity of bovine hoof slices as a model for infected human nails, and suggests a substantial equivalence between the two models. Following P-3051 application, CPX reaches fungicidal concentrations in and through human infected toenails. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.
Shah, Viral H; Jobanputra, Amee
The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.
Kushwaha, Avadhesh; Shivakumar, H N; Murthy, S Narasimha
In present studies, a hyponychium pathway (from ventral side of the nail plate) was investigated as a potential route of drug delivery into the nail apparatus using iontophoresis as an active physical method. In vitro transport studies were performed across the human nail plate using sodium fluorescein as a marker substrate for 24 h. After transport studies, the amount of sodium fluorescein extracted from an active diffusion area of the nail plate in case of iontophoresis was found to be ∼54-folds more to that of passive. The amount of sodium fluorescein retained in the peripheral area of the nail plate after application of iontophoresis was found to be ∼30-folds more relative to passive. Ex vivo transport studies were performed on excised human cadaver toe using terbinafine hydrochloride as a model drug for three days (8 h/day). The amount of terbinafine retained in the nail plate after application of iontophoresis (3.43 ± 1.34 µg/mg) was ∼20-folds more when compared with passive (0.17 ± 0.10 µg/mg). The amount of drug extracted from the nail bed and nail matrix was 1.73 ± 0.12 µg/mg and 0.55 ± 0.22 µg/mg, respectively. On the other hand, there was no detectable amount of terbinafine found in the nail bed and nail matrix in case of control (passive delivery). These studies show that the iontophoretic drug delivery through hyponychium region to other parts of the nail apparatus could be a potential way of onychomycosis treatment.
Vlahovic, Tracey; MPharm, Tejal Merchant; Chanda, Sanjay; Zane, Lee T; Coronado, Dina
Onychomycosis is a common infection of the toenails that causes nail thickening and discoloration. The physical appearance of the infected nail can diminish self-image and negatively impact quality of life. Patients may use nail polish to mask the appearance of infected nails. To evaluate the in vitro nail penetration properties of tavaborole topical solution, 5%, through nail polish using ex vivo, non-diseased human fingernails. In study 1, tavaborole penetration was evaluated over 20 days of dosing using the Franz finite dose technique and modified Franz diffusion cells. Nails received either 1 coat of over-the-counter (OTC) typical polish or were left unpolished (controls). In study 2, tavaborole penetration was measured over 14 days of dosing using the finite dose technique and vertical diffusion cells. Nails were polished with either 4 coats or 1 coat of salon typical polish or with 2 coats or 1 coat of OTC typical polish, or they were left unpolished. In study 1, the mean ± standard deviation (SD) cumulative tavaborole penetration at day 21 was numerically higher, though not statistically significant, through polished nails (3,526 ± 1,433 μg/cm(2))vs unpolished nails (2,661 ± 1,319 μg/cm(2)).In study 2, the mean cumulative tavaborole penetration was also numerically higher (statistical significance not assessed) through all nails that received polish vs unpolished nails. At day 15, mean ± SD cumulative tavaborole nail penetration was 1,179 ± 554 μg/cm(2) through 4 coats of salon typical polish, 1,227 ± 974 μg/cm(2) through 1 coat of salon typical polish, 1,493 ± 1,322 μg/cm(2) through 2 coats of OTC typical polish, 1,428 ± 841 μg/cm(2) through 1 coat of OTC typical polish, and 566 ± 318 μg/cm(2) through unpolished nails. Results from these in vitro studies demonstrated that tavaborole penetrated through human nails with up to 4 layers of nail polish.
Diongue, K; Diallo, M A; Ndiaye, M; Badiane, A S; Seck, M C; Diop, A; Ndiaye, Y D; Ndiaye, D
Superficial fungal infections, particularly of the skin, scalp and nails are very common and have been reported worldwide. The most common causative agents of these mycoses are dermatophytes, yeasts and molds. However, these agents vary with time and depend on many factors including the geography. The objective of this study was to identify the causative agents of superficial mycoses diagnosed at the Le Dantec University Hospital in Dakar (Senegal). The study concerned 1851 outpatients received in the parasitological and mycological laboratory of Le Dantec hospital during the period from January 2011 to December 2015. Every patient benefited from direct examination and mycological culture. Among the 1851 patients, 633 were confirmed with superficial mycoses and the prevalence was 34.2 %. The age of patients ranged from two months to 81 years with a mean age of 31 years. Superficial mycoses were found more in women (70.3 %) than men (29.7 %) and a little more than thirty-nine percent (39.3 %) were adults. The causative agents identified were: dermatophytes (58 %), yeast (36.7 %) and non-dermatophytic filamentous fungi (NDFF, 5.3 %). The most isolated species were: Candida albicans (26.9 %), Trichophyton soudanense (24.9 %) and T. rubrum (13.7 %). These fungi were responsible for different clinical aspects, isolated and other associated. Among the isolated clinical aspects, those affecting hair (tinea capitis) were by far the largest with 44.8 %, followed by tinea unguium (34.5 %). Associations were especially type of tinea capitis and tinea manuum (2.4 %) and toenails onychomycosis associated with interdigital tinea pedis (2.7 %). Tinea capitis agents were exclusively dermatophytes and the predominant agent was T. soudanense with 47,8 %. Tinea unguium agents were yeast (79 %), dermatophytes (18 %) or NDFF (3 %) and the most found species was C. albicans (63.9 %). Dermatophytes, yeasts and molds were respectively found more in children and
Berk, Elife; Kuştimur, Semra; Kalkancı, Ayşe; Oztaş, O Murat
Trichophyton rubrum is the most frequently encountered dermatophyte species causing onichomycosis. The routine diagnosis of dermatophytes depends on the direct microscopic examination (DME) and culture methods, however due to the phenotypic identification problems related to those agents, the molecular methods come into question. The aim of this study was to evaluate the diagnostic performance of real-time polymerase chain reaction (RT-PCR) for the identification of T.rubrum by comparing to DME and culture methods, from nail samples of patients with the complaints of onychomycosis. A total of 90 patients of whom 58 were male who were admitted to the dermatology outpatients clinics of our hospital with the complaints of color/shape changes in the nails and thickening of the nail, were included in the study, together with the 20 healthy volunteer subjects as controls. The nail scraping samples obtained from the patients and controls were examined with direct microscopy using 15% potassium hydroxide, dimethyl sulphoxide and chlorazole black mixture and cultivated onto Sabouraud dextrose agar with and without cycloheximide. For DNA isolation, after the disruption of nail samples with a steel tool, phenol-chloroform-isoamyl alcohol purification method were used. The amplification and demonstration of the T.rubrum DNA have been performed by using specific primers and probes following TaqMan protocol of RT-PCR (LightCycler-Roche, USA) method. Seventy-two of the patients yielded positive and 18 yielded negative results with DME. Growth of molds was detected in the cultures of 20 (27.8%) of the 72 DME positive patients and all of the isolates were identified as T.rubrum. No fungal growth was seen in the samples of 18 patients who were DME negative. In DME positive group, 67 (93%) patients were found to be positive in RT-PCR, while 8 (44.4%) patients were RT-PCR positive in DME negative group. All of the culture positive samples (n= 20) were also found positive in RT
Tlougan, Brook E; Mancini, Anthony J; Mandell, Jenny A; Cohen, David E; Sanchez, Miguel R
Participation in ice-skating sports, particularly figure skating, ice hockey and speed skating, has increased in recent years. Competitive athletes in these sports experience a range of dermatological injuries related to mechanical factors: exposure to cold temperatures, infectious agents and inflammation. Part I of this two part review discussed the mechanical dermatoses affecting ice-skating athletes that result from friction, pressure, and chronic irritation related to athletic equipment and contact with surfaces. Here, in Part II, we review the cold-induced, infectious and inflammatory skin conditions observed in ice-skating athletes. Cold-induced dermatoses experienced by ice-skating athletes result from specific physiological effects of cold exposure on the skin. These conditions include physiological livedo reticularis, chilblains (pernio), Raynaud phenomenon, cold panniculitis, frostnip and frostbite. Frostbite, that is the literal freezing of tissue, occurs with specific symptoms that progress in a stepwise fashion, starting with frostnip. Treatment involves gradual forms of rewarming and the use of friction massages and pain medications as needed. Calcium channel blockers, including nifedipine, are the mainstay of pharmacological therapy for the major nonfreezing cold-induced dermatoses including chilblains and Raynaud phenomenon. Raynaud phenomenon, a vasculopathy involving recurrent vasospasm of the fingers and toes in response to cold, is especially common in figure skaters. Protective clothing and insulation, avoidance of smoking and vasoconstrictive medications, maintaining a dry environment around the skin, cold avoidance when possible as well as certain physical manoeuvres that promote vasodilation are useful preventative measures. Infectious conditions most often seen in ice-skating athletes include tinea pedis, onychomycosis, pitted keratolysis, warts and folliculitis. Awareness, prompt treatment and the use of preventative measures are
Ingordo, Vito; Naldi, Luigi; Fracchiolla, Stefania; Colecchia, Bruno
Limited studies on the prevalence and risk factors for superficial mycoses are available. The aim of this paper was to evaluate the prevalence and risk factors for superficial mycoses (dermatophytes and Candida spp.) in a sample of young Italian people resident at a military school. A total of 1,024 young cadets from the Italian Navy Petty Officers School in Taranto, including 975 (95.21%) males and 49 (4.79%) females, mean age 22.5 +/- 3.0 years (range 18-30), were consecutively examined by the same observer. A complete dermatological examination was performed on all the subjects, and skin scrapings for microscopy and fungal culture were obtained from suspected lesions. All the subjects completed a questionnaire providing information on sports practice, swimming-pool attendance, marching, wearing shower sandals, frequent use of 'gummed' shoes, history of severe traumas to the nails, presence of hyperhidrosis and history of superficial mycoses. The affected subjects were also asked if they were aware of their condition. Data were analysed by the Statistical Analysis System, version 8.0. The Fisher exact test and odds ratios were calculated. A total of 33 subjects (3.2%) were found to suffer from a mycologically confirmed fungal infection (3% by dermatophytes and 0.2% by Candida albicans): tinea pedis/Candida intertrigo of the feet was suspected in 126 (12.1%) subjects and confirmed in 30 (2.9%), including 28 cases of tinea pedis and 2 cases of Candida intertrigo; tinea cruris/Candida intertrigo of the groin was suspected in 28 (2.7%) subjects, but confirmed in only 1 case (0.1%); onychomycosis was suspected in 64 (6.1%) subjects and confirmed in 2 cases (0.2%). The organism most frequently responsible in tinea pedis was Trichophyton mentagrophytes var. interdigitale (82.1%). The same species (50%) and T. mentagrophytes var. mentagrophytes (50%) were associated with tinea unguium, Epidermophyton floccosum was the only species detected in tinea cruris. Non
Crous, P W; Wingfield, M J; Richardson, D M; Le Roux, J J; Strasberg, D; Edwards, J; Roets, F; Hubka, V; Taylor, P W J; Heykoop, M; Martín, M P; Moreno, G; Sutton, D A; Wiederhold, N P; Barnes, C W; Carlavilla, J R; Gené, J; Giraldo, A; Guarnaccia, V; Guarro, J; Hernández-Restrepo, M; Kolařík, M; Manjón, J L; Pascoe, I G; Popov, E S; Sandoval-Denis, M; Woudenberg, J H C; Acharya, K; Alexandrova, A V; Alvarado, P; Barbosa, R N; Baseia, I G; Blanchette, R A; Boekhout, T; Burgess, T I; Cano-Lira, J F; Čmoková, A; Dimitrov, R A; Dyakov, M Yu; Dueñas, M; Dutta, A K; Esteve-Raventós, F; Fedosova, A G; Fournier, J; Gamboa, P; Gouliamova, D E; Grebenc, T; Groenewald, M; Hanse, B; Hardy, G E St J; Held, B W; Jurjević, Ž; Kaewgrajang, T; Latha, K P D; Lombard, L; Luangsa-Ard, J J; Lysková, P; Mallátová, N; Manimohan, P; Miller, A N; Mirabolfathy, M; Morozova, O V; Obodai, M; Oliveira, N T; Ordóñez, M E; Otto, E C; Paloi, S; Peterson, S W; Phosri, C; Roux, J; Salazar, W A; Sánchez, A; Sarria, G A; Shin, H-D; Silva, B D B; Silva, G A; Smith, M Th; Souza-Motta, C M; Stchigel, A M; Stoilova-Disheva, M M; Sulzbacher, M A; Telleria, M T; Toapanta, C; Traba, J M; Valenzuela-Lopez, N; Watling, R; Groenewald, J Z
), Ochroconis dracaenae (on Dracaena reflexa), Rasamsonia columbiensis (air of a hotel conference room), Paecilomyces tabacinus (on Nicotiana tabacum), Toxicocladosporium hominis (from human broncoalveolar lavage fluid), Nothophoma macrospora (from respiratory secretion of a patient with pneumonia), and Penidiellopsis radicularis (incl. Penidiellopsis gen. nov.) from a human nail. Novel taxa described from Malaysia include Prosopidicola albizziae (on Albizzia falcataria), Proxipyricularia asari (on Asarum sp.), Diaporthe passifloricola (on Passiflora foetida), Paramycoleptodiscus albizziae (incl. Paramycoleptodiscus gen. nov.) on Albizzia falcataria, and Malaysiasca phaii (incl. Malaysiasca gen. nov.) on Phaius reflexipetalus. Two species are newly described from human patients in the Czech Republic, namely Microascus longicollis (from toenails of patient with suspected onychomycosis), and Chrysosporium echinulatum (from sole skin of patient). Furthermore, Alternaria quercicola is described on leaves of Quercus brantii (Iran), Stemphylium beticola on leaves of Beta vulgaris (The Netherlands), Scleroderma capeverdeanum on soil (Cape Verde Islands), Scleroderma dunensis on soil, and Blastobotrys meliponae from bee honey (Brazil), Ganoderma mbrekobenum on angiosperms (Ghana), Geoglossum raitviirii and Entoloma kruticianum on soil (Russia), Priceomyces vitoshaensis on Pterostichus melas (Carabidae) (Bulgaria) is the only one for which the family is listed, Ganoderma ecuadoriense on decaying wood (Ecuador), Thyrostroma cornicola on Cornus officinalis (Korea), Cercophora vinosa on decorticated branch of Salix sp. (France), Coprinus pinetorum, Coprinus littoralis and Xerocomellus poederi on soil (Spain). Two new genera from Colombia include Helminthosporiella and Uwemyces on leaves of Elaeis oleifera. Two species are described from India, namely Russula intervenosa (ectomycorrhizal with Shorea robusta), and Crinipellis odorata (on bark of Mytragyna parviflora). Novelties from Thailand