Fungal Nail Infections Research Articles

Case Report of a Woman with Recurrent Thrush and Pneumonia

I present to you a case report of a challenging patient with a history of recurrent fungal infections of nails and feet, recurrent thrush and recurrent bacterial pneumonia requiring treatment with intravenous antibiotics to treat. Case report includes her clinical history and work up.

Sporicidal effect of amorolfine and other antimycotics used in the therapy of fungal nail infections.

Although topical antifungal therapies for treating onychomycosis are available, the cure rate is unsatisfactorily low with a simultaneously high risk of recurrence. One reason might be the formation of dormant fungal cells by the pathogen, known as spores, which can survive in the affected nail keratin, thereby evading the effect of antifungal drugs. In this in vitro study, the ability of amorolfine and four other antimycotics (ciclopirox, bifonazole, terbinafine and fluconazole) to kill microconidia of the dermatophyte Trichophyton rubrum, chlamydospores of the dermatophyte Epidermophyton floccosum and blastospores of the yeast Candida albicans was extensively studied as these fungi occur predominantly in onychomycosis. The effectiveness of all five antimycotics depended on the drug concentration and the incubation time: a concentration of 10-1000 times the minimum inhibitory concentration against growing hyphae cells is needed to exert a sporicidal action. Amorolfine and ciclopirox showed the same sporicidal efficacy and kinetics for all three varieties of spores. Both were more effective than fluconazole and bifonazole against microconidia and chlamydospores as well as slightly more potent against chlamydospores and blastospores than terbinafine after 4 days of incubation and at concentrations of ≥10 μg ml(-1). Finally, sporicidal activity on the tested strains was demonstrated for all five different antimycotics used for onychomycosis treatment.

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

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.

Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation

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.

Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies

Onychomycosis, a fungal nail infection, can impact quality of life. We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail onychomycosis. In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52. Secondary end points included completely or almost clear nail, negative mycology, completely or almost clear nail plus negative mycology, and safety. Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and 1.5%) significantly favored tavaborole versus vehicle (P ≤ .001). Completely or almost clear nail rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for tavaborole versus vehicle (P < .001). Application-site reactions with tavaborole included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%). Duration of follow-up is a limitation. Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis.

Onychomycosis and Children – A Multicenter Study

Summary Onychomycosis is a chronic disease caused by dermatophytes, yeasts and molds, which leads to destruction of the nail plate of the fingernails and toenails. The incidence of onychomycosis in children is considerably smaller compared with that in adults. Onychomycosis in children under 6 years of age is particularly unusual. The trauma and the hyperhidrosis after puberty are the major predisposing factor for fungal nail infection in childhood. Some systemic diseases and congenital syndromes have a crucial role for the development of onychomycosis in children. Wearing infected socks and shoes of other family members, family history for fungal infection of the nails, reduced hygiene and onychophagia are other important predisposing factors. Dermatophytic species Trichophyton rubrum, Trichophyton mentagrophytes and Epidermophyton flocosum are the most frequent causative agents of onychomycosis in adults and much less common yeast of the genus Candida. A retrospective study for a period of 11 years was performed (2003-2013) investigating 292 children aged 0 to 18 years with proven onychomycosis (123 - from Plovdiv, Bulgaria, 94 - from Pleven, Bulgaria, and 75 - from Thessaloniki, Greece). Candida albicans was the main etiologic agent in onychomycosis in children under 18 years of age, according to the performed retrospective study. The diagnose was made by direct microscopic examination and fungal culture on Sabouraud agar media.

In vitro permeation and penetration of ciclopirox olamine from poloxamer 407-based formulations – comparison of isolated human stratum corneum, bovine hoof plates and keratin films

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®.

Epidemiology of superficial mycoses in Northern Greece: a 4-year study.

Superficial mycoses are defined as the fungal infections of skin, hair or nails that are caused by dermatophytes, yeasts and non-dermatophytic moulds. Dermatophytes are the most frequently isolated fungi from specimens of patients with superficial mycoses. Studying the possible alteration of the epidemiology of superficial mycoses in Northern Greece during the last two to three decades. Data concerning the superficial mycoses from patients coming mainly from the region of Macedonia, Northern Greece, between January 2010 and January 2014 were recorded and analysed. They included specimens from 438 patients (146 M/292 F), within an age range of 2-85 years old. 503 samples were collected from skin (81, 16.1%), hair (18, 3.6%) and nails (fingernails 84, 16.7%, toenails 320, 63.6%) lesions. Of a total of 222 positive cultures, 50 were considered as yielding clinically non-significant isolates (saprophytes). Among the rest (172), dermatophytes were the most prevalent isolates (102, 59.3%), followed by yeasts (51, 29.7%) and non-dermatophytic moulds (19, 11%). Trichophyton rubrum (55, 53.9%), Trichophyton mentagrophytes (18, 17.6%) and Microsporum canis (23, 22.5%) were the most common isolates among dermatophytes (total = 102). Candida parapsilosis (26, 51%), and Candida albicans (10, 19.6%) among yeasts (total = 51) whereas Fusarium (6, 31.6%) and Acremonium species (3, 15.8%) among the non-dermatophytic moulds (total=19). Compared to previous studies from Northern Greece, the epidemiology of superficial mycoses in the specific geographic region seems not to have been altered the last two to three decades.

Understanding and diagnosing nail infections

Practice NursingVol. 26, No. 3 DermatologyUnderstanding and diagnosing nail infectionsJean WatkinsJean WatkinsSearch for more papers by this authorJean WatkinsPublished Online:10 Mar 2015https://doi.org/10.12968/pnur.2015.26.3.134AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Bzhalava D, Guan P, Franceschi S, Dillner J, Clifford G (2013) Systematic review of the prevalence of mucosal and cutaneous human papillomavirus types. Virology 445(1-2): 224–31. doi: https://doi.org/10.1016/j.virol.2013.07.015 Crossref, Google ScholarFood Standards Agency (2009) Food handlers: fitness to work. www.food.gov.uk/sites/default/files/multimedia/pdfs/publication/fitnesstoworkguide09v3.pdf (accessed 12 February 2015) Google ScholarJoint Formulary Committee (2014) British National Formulary 67. BMJ Group and Pharmaceutical Press, London Google ScholarMerck Manuals (2013) Chronic paronychia. www.merckmanuals.com/professional/dermatologic_disorders/nail_disorders/chronic_paronychia.html?qt=Chronic%20Paronychia&alt=sh (accessed 12 February 2015) Google ScholarNational Institute for Health and Care Excellence Clinical Knowledge Summaries (2013) Fungal nail infection. http://cks.nice.org.uk/fungal-nail-infection (accessed 12 February 2015) Google ScholarNational Institute for Health and Care Excellence Clinical Knowledge Summaries (2011) Paronychia – acute. http://cks.nice.org.uk/paronychia-acute (accessed 12 February 2015) Google ScholarPark D, Singh D (2012) The management of ingrowing toenails. BMJ 344: e2089. doi: https://doi.org/10.1136/bmj.e2089 Crossref, Google ScholarRigopoulos D, Larios G, Gregioriou S, Alevizos A (2008) Acute and chronic paronychia. Am Fam Physician 77(3): 339–46 Google ScholarWarts Information Center (2012) Periungual warts. www.warts.org/periungual-warts.html (accessed 12 February 2015) Google Scholar FiguresReferencesRelatedDetails 2 March 2015Volume 26Issue 3ISSN (print): 0964-9271ISSN (online): 2052-2940 Metrics History Published online 10 March 2015 Published in print 2 March 2015 Information© MA Healthcare LimitedKeywordsnailsfingerstoesnail infectionPDF download

Onychomycosis caused by Curvularia lunata in an immunocompetent host-A case report

Introduction:Onychomycosis is a fungal infection of nail caused by dermatophytes, yeasts or non-dermatophyte moulds. Curvularia species is a dematiaceous fungi .We are reporting a case of Onychomycosis caused by Curvularia, for its rarity. Case report:A 45 year old female, agriculturist by occupation presented with black discolourationofleft thumbnailsince 6 months.KOH preparation of nail clipping showed dark pigmented septate hyphae with 3 to 4 celled conidia with transverse septa. Growth on sabouraud’s dextrose agar yielded Curvularialunata. Same fungi was isolated on repeat culture. The patient was put on pulse therapy with Itraconazole. Key words:Onychomycosis, Curvularialunata, Itraconazole.

Onychomycosis due to Cunninghamella bertholletiae in an Immunocompetent Male from Central India.

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.

Profile of Dermatophyte and Non Dermatophyte Fungi in Patients Suspected of Dermatophytosis

Fungal infections of hair, nail and skin are common worldwide and continue to increase. The present study was undertaken to determine the prevalence of dermatophytosis, isolation rates and the profile of fungi associated with dermatophytosis. Samples were collected from 305 patients and a portion of each sample was examined microscopically and the remaining portion was cultured on to plates of Sabouraud’s Dextrose Agar containing chloramphinical with and without cychloheximide. Fungal cultures were identified by studying macroscopic and microscopic characteristics of their colonies. Of 305 clinical samples, fungi were detected in 265 (86.9%) samples by KOH and 224 (73.4%) clinical samples were culture positive. Dermatophytes were the most common isolates accounting 130 (58.0%) of the total isolates and this was followed by non- dermatophyte molds and yeasts that accounted 49 (21.9 %.) and 45 (20.0%) respectively. T. violaceum was the dominant species accounting for 49 (37.7%) dermatophyte isolates. Candida albicans was the dominant species accounting 30 (66.7%) of the total yeast isolates. The genus Aspergillus was the most common non-dermatophyte molds consisting of 13 (26.5%) species. Tinea unguium was the predominant clinical manifestation accounting 51.1% of the cases of which 119 (76.3%) were from females and 37 (23.7%) from males. T. violaceum was the most common pathogen in tinea unguium and tinea capitis, whereas T. mentagrophytes was the most common pathogen in tinea pedis and tinea manum. Seventy five percent of yeasts and 77.6% non dermatophyte molds were isolated from nails. Along with dermatophytes, non-dermatophyte fungi are also emerging as important causes of dermatophytosis. Both direct microscopy and culture are important tools for diagnosis of the fungal infections.

Onychomycosis: A study of self-recognition by patients and quality of life.

Onychomycosis accounts for approximately half of all nail disorders and is usually asymptomatic. To evaluate patients' recognition of fungal nail disease, concomitant fungal skin diseases, complications, and quality of life. Patients from the fungal nail clinic were enrolled between May 2011 and April 2012. Patients' awareness of diseased nails was evaluated and the Dermatology Life Quality Index (DLQI) questionnaire was used to evaluate the impact of dermatologic disease on quality of life. A total of 110 patients with onychomycosis were enrolled in the study, of which 64 (58.2%) were female and the mean age was 60.8 years. The number of patients who were able to recognize the presence of onychomycosis was 71 (64.5%), while 32 (29.1%) and 7 (6.4%) were diagnosed by a dermatologist and other physicians, respectively. Multivariate analysis showed that patient recognition of the disease was significantly associated with female sex and young age. The mean DLQI score was 3.6. Patient recall bias including the duration of fungal nail infection, long-term past history and previous treatment was a limitation of this study that affected DLQI scores. About half of onychomycosis patients, especially elderly males, could not recognize the disease by themselves. It is important for physicians to educate patients with risk factors for onychomycosis to recognize this condition early to prevent concomitant infection and complications, and to improve patients' well-being.

Insights to the ethiopathogenesis of human nail diseases

The finger nails or ungues are hard covering which form the horny zone of the epidermis. They overlie the dorsal aspect of the distal phalanges. Nail diseases are distinct from diseases of the skin. Although nails are a skin appendage, they have their own signs and symptoms which may relate to other medical conditions. The nail disease has clinical signs which reflect patho biologic changes of the nail plate and nail matrix. There are a number of conditions that can affect our nails, with different causes and treatments. Common causes of fingernail problems include injury, infection and skin diseases such as eczema and psoriasis. Topical therapy is highly desirable because of its non-invasiveness, ability to target drugs to the site of action, minimizing systemic adverse effects and improving patient compliance. Continuous exposal of nail to warm, moist environments usually develops nail infection. Nail plate is main route for penetration of drug. Varity of conventional formulation like gel, cream and also oral antifungal are available for treatment of nail infection. The major problem associated with conventional nail treatment for nail disorders is to deliver the active therapeutically. However possible means to enhance nail penetration must be explored in greater depth before effective local treatments for fungal nail infections are developed.

Is eucalyptus oil an effective antifungal treatment for onychomycosis with and without nail matrix infection?

Background Onychomycosis is a fungal infection causing progressive destruction of the nail elements, with age increasing frequency of infection and potential for complications. The condition accounts for almost half of all nail issues yet continues to be largely under-reported and untreated. This study will investigate the antifungal efficacy of eucalyptus oil in vivo, for fungal nail infections with and without nail matrix infection.

Ability of hydroxypropyl chitosan nail lacquer to protect against dermatophyte nail infection.

The development of a topical agent that would strengthen the nail, improve the natural barrier, and provide better drug penetration to the nail bed is needed. In this study, we examined the effects of a hydroxypropyl chitosan (HPCH)-based nail solution using a bovine hoof model. Following application of the nail solution, changes in the hardness of the hoof samples were measured using the Vickers method. Tensile and flexural strengths were tested by stretching or punching the samples, respectively. The ultrastructure was examined using scanning electron microscopy (SEM), and samples stained with periodic acid-Schiff (PAS) stain were used to determine the fungal penetration depth. The comparators included 40% urea and 70% isopropyl alcohol solutions. The HPCH nail solution increased hoof sample hardness in comparison to the untreated control sample (mean, 22.3 versus 19.4 Vickers pyramid number [HV]). Similarly, the HPCH solution increased the tensile strength (mean, 33.07 versus 28.42 MPa) and flexural strength (mean, 183.79 versus 181.20 MPa) compared to the untreated control. In contrast, the comparators had adverse effects on hardness and strength. SEM showed that the HPCH solution reduced the area of sample crumbling following abrasion compared to the untreated control (7,418 versus 17,843 pixels), and the PAS-stained images showed that the HPCH solution reduced penetration of the dermatophyte hyphae (e.g., penetration by Trichophyton mentagrophytes was <25 μm at day 9 versus 275 μm in the untreated control). Unlike chemicals normally used in cosmetic treatments, repeated application of the HPCH nail solution may help prevent the establishment of new or recurring fungal nail infection.

To what extent do in vitro tests correctly predict the in vivo residence of nail lacquers on the nail plate?

Pharmaceutical nail lacquers are used to topically treat nail fungal infections. The film's residence on the nail is an important factor, and in the laboratory, rapid in vitro adhesion and water resistance tests are often used to indicate their likely in vivo residence. However, the predictivity of such in vitro tests is unknown. The aim of this work was thus to determine whether, and to what extent, such in vitro tests can correctly predict the in vivo fate of nail lacquers. The in vivo residence of four commercially available nail lacquers (three pharmaceutical and one cosmetic) was determined in 16 volunteers. In vitro, the films' resistance to water, and their adhesion to a model nail plate was measured, and in vitro-in vivo correlations were explored. It was found that the in vitro films' resistance to water correctly predicted the in vivo residence of lacquers, while the adhesion tests did not.

Nonclinical safety assessment of Efinaconazole Solution (10%) for onychomycosis treatment

Efinaconazole is a triazole developed as a 10% solution for topical treatment of onychomycosis, a common fungal nail infection. Efinaconazole solution and topical formulation vehicle administered dermally to mice (13weeks), rats (6months) and minipigs (9months) produced transient erythema, minimal to modest hyperkeratosis, and mild microscopic skin inflammation. The liver was the target organ of systemic toxicity; reversible, minimal to moderate vacuolated changes were noted in the rat dermal study at 15 and 50mg/kg/day. No systemic toxicity was observed in mice and minipigs, at approximate high dermal doses of 930 and 170mg/kg/day, respectively. Daily subcutaneous injection of propylene glycol vehicle or efinaconazole to rats for 6months produced severe local inflammation and systemic spread, evidenced by peritoneal adhesions, spinal cord necrosis and urinary tract disease. Mortalities occurred in all groups but were increased at the high dose (30 or 40mg/kg/day), suggesting that vehicle effects were exacerbated by efinaconazole. Efinaconazole was not carcinogenic in a 2-year mouse dermal study and was not genotoxic. Exposure-based safety margins at the NOAEL were 70–698 relative to onychomycosis patients. In conclusion, efinaconazole demonstrated low/moderate toxicity, consistent with other azole antifungals, and high safety margins for topical onychomycosis therapy.

Psychosocial perception of adults with onychomycosis: a blinded, controlled comparison of 1,017 adult Hong Kong residents with or without onychomycosis.

BackgroundA survey was conducted amongst 1,017 Hong Kong residents ages 18 and over to determine their knowledge of fungal nail infections (onychomycosis) and the psychosocial impact of the disease on the relationships, social lives and careers of sufferers.MethodsThe Fungal Nail Perception Survey was conducted by email and online between May 29th and June 10th, 2013. Participants were shown three photographs of people with and without onychomycosis of the toenails. Respondents were asked ten questions (repeated for each picture) to ascertain their perceptions of the people in the pictures. Questions were related to perceptions around the ability of sufferers and non-sufferers to form relationships with others, social activities of sufferers and non-sufferers, perceptions of the effect of the disease on the potential for career success, and awareness of fungal nail disease and health. The sub-population who themselves suffered from onychomycosis were asked about self-perception as well as their perception of others with onychomycosis.ResultsCompared with non-sufferers, survey respondents perceived those with onychomycosis as less likely to be able to form good relationships. They also indicated that they would be more likely to exclude sufferers than non-sufferers from social activities and that they would be more likely to feel uncomfortable when sitting or standing beside an infected person than beside an uninfected person. Respondents perceived people with onychomycosis to be less able to perform well in their chosen career than with someone without onychomycosis. Interestingly, those respondents who themselves were infected felt socially excluded, upset and embarrassed by their infection.ConclusionsOnychomycosis may lead to stigmatization and social exclusion. Misconceptions of onychomycosis are high and education about the disease needs to be improved. Early recognition and treatment of the disease is essential to avoid complications and improve treatment outcomes, which would lead to reduced psychosocial impact on those with fungal nail infections.

Fungal nail infections (onychomycosis): a never-ending story?

Fungal nail infections (onychomycosis): a never-ending story?