Fungal Nail Disease Research Articles

Evaluation of Efficacy and Safety of Topical Nanoliposomal Amphotericin B 0.4% Gel as a Potential Treatment for Onychomycosis: An Interventional Pilot Clinical Study

Onychomycosis is a frequent fungal nail disease that is hard to treat and, in most cases, needs long‐term therapy with oral agents. Traditionally, oral agents are favored over topical agents, but it should not be overlooked that they come with broad adverse effects and concomitant drug interactions, which can be unsuitable for many individuals. Therefore, alternative approaches need to be addressed by the medical team for numerous cases. On the other hand, local administration of antimicrobials can come as advantageous because of having a more selective site of activity, avoiding off‐target systemic adverse effects, and rapid administration at the site of infection. In this study, we are evaluating a new topical delivery method of amphotericin B. To investigate the efficacy and safety of topical nanoliposomal amphotericin B 0.4% as a possible therapeutic option, this pilot, single‐group, before‐after clinical study was conducted on 15 onychomycosis patients. The evaluation was processed during 36 weeks of follow‐up and on three endpoints of week 12, week 24, and week 36, for both clinical and mycological responses. Three patients were excluded; of the remaining 12, 50% showed a complete cure, 16.66% had an effective clinical response, 16.66% had a partial clinical response, and 16.66% showed no response at week 12. Mycological cure was calculated as 50% at week 12. At week 24, our measurements were calculated as 91.66% for complete cure, 8.33% for no response, and 91.66% for mycological cure. One patient reported nail plate detachment at week 2 but continued the topical application; follow‐up between weeks 2 and 24 showed a complete cure and regrowth of healthy nails. No other adverse effects were detected. Overall, our study suggests that topical nanoliposomal amphotericin B 0.4% is an effective treatment, which is accessible, affordable, and user‐friendly, has minimum adverse effects, and could be regarded as an alternative treatment for those ineligible for systemic therapy. This trial is registered with IRCT20150101020514N18.

Therapy of Skin, Hair and Nail Fungal Infections.

Treatment of superficial fungal infections has come a long way. This has, in part, been through the development and evaluation of new drugs. However, utilising new strategies, such as identifying variation between different species in responsiveness, e.g., in tinea capitis, as well as seeking better ways of ensuring adequate concentrations of drug in the skin or nail, and combining different treatment methods, have played equally important roles in ensuring steady improvements in the results of treatment. Yet there are still areas where we look for improvement, such as better remission and cure rates in fungal nail disease, and the development of effective community treatment programmes to address endemic scalp ringworm.

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.

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.

The low keratin affinity of efinaconazole contributes to its nail penetration and fungicidal activity in topical onychomycosis treatment.

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.

Fungal nail disease (Onychomycosis); Challenges and solutions

Onychomycosis (fungal nail infection) is caused by three groups of fungal pathogens namely dermatophyte molds (DM), non-DM (NDM) and yeasts. It is primarily a cosmetic problem but may induce impact on quality of life. Clinically it is characterized by fi ve morphologically distinctive types; distal lateral subungual onychomycosis (DLSO), superfi cial white onychomycosis (SWO), proximal subungual onychomycosis (PSO), and endothrix onychomycosis. It is diffi cult to detect the fungal agent responsible for a particular type of onychomycosis by clinical features alone. Mycological methods like direct demonstration of fungal agents by potassium hydroxide mount or nail plate histopathology with Periodic acid Schiff (PAS) staining are sensitive methods for the detection of pathogens. Fungal culture alone is commonly used as a standard for the detection of etiological agent. Molecular biological techniques are currently used only in research laboratories or epidemiological purposes. Therapy is generally not satisfactory. Both topical and systemic agents are used in the therapy. Topical Ciclopirix and Amorolfi ne are found to be effective but only in early and limited disease. Terbinafi ne and Itraconazole seems to be the best drugs for the systemic therapy. Clinical cure rates are generally lower than the mycological cure rates.

Fast elimination of onychomycosis by hematoporphyrin derivative-photodynamic therapy

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)).

Fungal Nail Disease

A 68-year-old man reports changes in his left big toenail. It has been discolored distally for the past 2 years. It has become thickened and difficult to cut and is painful when the man is walking in certain shoes. He is otherwise well. On physical examination, the nail appears thickened, has crumbling yellow material beneath, and is more discolored distally than proximally. The nearby skin is normal, although the interdigital space of the little toe is macerated. How should his case be managed?

Dermatomykosen mit epidemiologischem Potenzial: Tinea capitis und Onychomykose

Superficial fungal infections caused by dermatophytes (dermatophytoses) are the most common skin infections with about 10-15% of the population throughout the world being affected. Up to now the occurrence of fungal infections of the skin has been connected, like ectoparasitic infections with poor hygiene and poor living conditions. During the last decades, however, there has been a dramatic change with a significant increase in mycotic scalp infections as well as fungal nail disease mainly in highly developed countries like the US and those on the European continent.

Observer agreement in recording the clinical signs of nail disease and the accuracy of a clinical diagnosis of fungal and non-fungal nail disease.

Onychomycosis is increasing in incidence. To date, no studies have examined the detection of abnormalities of the nail apparatus, nor the accuracy of a clinical diagnosis of onychomycosis and non-fungal nail disease. To assess the agreement between and within different groups of observers in detecting signs of nail disease, and to obtain information regarding clinical diagnostic skills. An observational study was performed. Nine observers, including dermatologists, mycologists, general practitioners and a dermatology clinical assistant, completed a questionnaire containing 21 clinical signs of nail disease during examination of nine patients, five with onychomycosis and four with non-fungal nail disease. Observers were additionally requested to suggest the most likely underlying diagnosis for the nail dystrophy. Mean pair observer agreement values were calculated for each of the clinical signs, between all observers and within groups of observers. The chance-corrected agreement index, kappa, was determined. From the clinical diagnoses given, the positive predictive value of a diagnosis of fungal and non-fungal nail disease was calculated. There was substantial between-observer agreement on only three clinical signs: abnormal nails on both hands, abnormal toenails and abnormal fingernails. More specific signs of nail disease such as onycholysis elicited weaker agreement. All observers showed accuracy in making a clinical diagnosis of fungal nail disease, with a mean positive predictive value of 0.91, compared with 0.77 for non-fungal nail disease. Our results showed that agreement between observers, in recording signs of nail disease, was generally poor. The clinical diagnosis of onychomycosis was highly likely to be correct, suggesting that other criteria are being employed by individuals in reaching the diagnosis.

Onychomycosis: recognition, diagnosis, and management.

About 20% of the US population between the ages of 40 and 60 years have fungal nail disease, or onychomycosis. The incidence of this infection is increasing worldwide. Most cases of onychomycosis in the United States are caused by dermatophytes, but nondermatophyte fungi (molds or yeasts) may also be causative agents. To confirm the diagnosis of onychomycosis, a potassium hydroxide examination should be performed. A culture is necessary to determine the fungal pathogen and to aid in selecting appropriate therapy. Worldwide, fluconazole (not yet approved in the United States for onychomycosis), itraconazole, and oral terbinafine have superseded griseofulvin and ketoconazole as the agents of choice in treating onychomycosis. These newer systemic compounds have higher cure rates and cause fewer side effects than traditional agents. Intermittent dosing with itraconazole (3 or 4 one-week pulses of 200 or 400 mg daily) is the latest advance in the treatment of onychomycosis. This regimen has been found to be at least as safe and effective as short-term continuous therapy, yet more flexible, convenient, and economical.

Fungal nail disease: a guide to good practice (report of a Working Group of the British Society for Medical Mycology).

#### Summary points The term onychomycosis refers to fungal infection of the nails whether this is a primary event or a secondary infection of a previously diseased or traumatised nail. Infection may be due to dermatophyte (ringworm, tinea unguium), yeast, or other non-dermatophyte (mould) species, and the clinical appearance may indicate the nature of the infecting organism. In paronychia chronic infection of the nail fold is most often caused by Candida species, but bacterial infection with Gram negative species such as Pseudomonas may coexist. Acute paronychia (whitlow) due to staphylococcal infection may also occur, and the presence of these bacterial infections will influence management. Invasion of the nail plate by Candida species may occur in the presence of paronychia, immune deficiency states (including chronic mucocutaneous candidiasis), Raynaud's disease, or endocrine disorders. This paper reviews the clinical features of onychomycosis and the differential diagnosis of nail dystrophy, gives the reasons for appropriate mycological investigation, and discusses guidelines for appropriate treatment on the basis of laboratory findings and particular clinical situations. Treating onychomycoses is difficult but is important because they do not resolve spontaneously. About 30% of all superficial fungal infections affect the nail.1 2 A recent population survey of dermatophyte onychomycosis has suggested a prevalence of 2.8% for men and 2.6% for women in the United Kingdom.3 …

Oral therapeutic agents in fungal nail disease

Oral griseofulvin has been the first-line drug in the therapy of dermatophyte onychomycosis for many years. Even when used long-term, it is effective in only about 30% of patients. Ketoconazole is not much more effective than griseofulvin in toenail infections, and there are significant problems with hepatotoxicity. Recently the triazoles, itraconazole and fluconazole, and the allylamine, terbinafine, were introduced and are believed to be potentially suitable for the oral treatment of fungal nail infection. Terbinafine is particularly effective in the treatment of dermatophyte onychomycosis, with a much shorter treatment period than griseofulvin. Cure rates of well over 80% have been noted in fingernail and toenail infection during treatment periods of 6 and 12 weeks, respectively. Itraconazole, 200 mg/day, has been noted in some studies to be similarly effective in the same treatment period. Few studies of fluconazole in nail infection have been carried out. These new agents appear to be safe, and results thus far suggest that they will soon overtake griseofulvin as the drug of choice in the oral therapy of nail infection.

Epidemiology of fungal skin and nail disease: roundtable discussion held at Dermatology 2000, Vienna, 17 May 1993.

Epidemiology of fungal skin and nail disease: roundtable discussion held at Dermatology 2000, Vienna, 17 May 1993.