Therapy of nail mycoses

Onchomycosis is the most common nail disease, accounting for approximately 30% of all cutaneous fungal infections. The treatment approach needs to take into account the location and extent of onychomycosis, sensitivity of drug to fungal organism, adverse-effects profile, dosage schedule, duration of therapy, concomitant medical conditions, and concurrent medications. To confirm the diagnosis, it is important to correctly select the appropriate site for specimen collection used for both direct microscopy and fungal culture. Topical antifungal agents may be considered for the treatment of early onychomycosis, in the absence of nail matrix involvement. The newer generation of oral antifungal agents for the treatment of onychomycosis are terbinafine, itraconazole and fluconazole. These drugs used alone, or in combination with topical antifungals, are providing the basis for effective treatment of onychomycosis in a large proportion of patients.     

Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey

The number of individuals diagnosed with diabetes mellitus is increasing. The diabetic may present with complications involving all systems of the body. While onychomycosis is often observed in diabetics, there have been no large studies on the prevalence of the condition in this patient group. We examined the prevalence of onychomycosis in diabetics attending diabetes and dermatology clinics in London, Ontario, Canada and Boston, MA, U.S.A. Diabetic subjects seen in dermatology offices were for unrelated dermatoses; those referred specifically for the management of onychomycosis were excluded from the sample. A total of 550 diabetic subjects was evaluated (283 males and 267 females), age 56.1 +/- 0.7 years (mean +/- SEM). Patients with type I diabetes constituted 34% of the sample. The racial origin was: 531 Caucasians, 17 Asians, one African-American and one American-Indian. Abnormal-appearing nails and mycological evidence of onychomycosis (mostly due to dermatophytes) were present in 253 (46%) and 144 (26%), respectively, of 550 subjects. The development of onychomycosis was significantly correlated with age (P < 0.0001) and male gender (P < 0.0001). Males were 2.99 times more likely to have onychomycosis compared with females (95% confidence interval, CI 1.94-4 61). After controlling for age and sex, the risk odds ratio for diabetic subjects to have toenail onychomycosis was 2.77 times compared with normal individuals (95% CI 2.15-3.57). After controlling for age and sex, a stepwise logistic regression demonstrated that significant predictors for onychomycosis included a family history of onychomycosis (P = 0.0001), concurrent intake of immunosuppressive therapy (P = 0.035) and peripheral vascular disease (P = 0.023). Toenail onychomycosis was present in 26% of the sample and is projected to affect approximately one-third of subjects with diabetes. Predisposing factors include increasing age, male gender, family history of onychomycosis, concurrent intake of immunosuppressive agents and peripheral vascular disease.     

Platelet antibodies in patients with migraine

The newer antifungal agents are increasingly being used for the treatment of onychomycosis. Tinea unguium is uncommon in children. In young children who are unable or unwilling to swallow capsules, the alternative to itraconazole capsules may be the oral solution. The pharmacokinetics of the itraconazole capsule when it is broken open and the contents sprinkled onto food has not been reported. Two sisters, ages 8 and 11 years, presented with fingernail dystrophy that was confirmed to be onychomycosis due to Trichophyton rubrum and T. soudanense, respectively. The patients were reluctant to swallow capsules and were treated with itraconazole pulse therapy using the oral solution, 3 mg/kg/day. The treatment regimen consisted of two pulses, each 1 week long, with a 3-week period between pulses. Both patients were clinically and mycologically cured with no adverse effects. Itraconazole oral solution (3 mg/kg/day) given as pulse therapy may be a consideration in the treatment of onychomycosis in some children.     

Treatment of onychomycosis and tinea pedis with intermittent itraconazole therapy

A 40-year-old woman had a 10-year history of dermatophyte-related toenail onychomycosis (tinea unguium) and dry-type tinea pedis, which had failed to respond to previous therapy with topical antifungal agents or oral griseofulvin. The patient was successfully treated with four cycles of intermittent itraconazole therapy (that is, 400 mg/d for 1 week per month for 4 months). At the end of this time, the tinea pedis had resolved and the onychomycosis improved significantly after four cycles were completed. Twelve months after the onset of therapy, both conditions had resolved completely according to both clinical and mycologic criteria. Itraconazole was well tolerated, with no side effects reported. These observations suggest that itraconazole intermittent dosing is a highly effective therapy for the treatment of onychomycosis caused by dermatophyte organisms, because it provides a high cure rate after only a short course of therapy.     

Oral treatment options for onychomycosis

The author discusses the new oral antifungal agents for the treatment of onychomycosis. The history, mechanisms of action, efficacies, dosing, safety profiles, and costs of itraconazole, terbinafine, and fluconazole are reviewed. The author emphasizes that use of these effective antifungals represents an important paradigm shift for podiatric physicians away from the palliative therapy of nail debridement to a potentially curative treatment.     

Chronic daily headache in children and adolescents: a 2-year prospective study

The newer generation of antifungal agents such as itraconazole and terbinafine are more effective than the older therapies, griseofulvin and ketoconazole, in the treatment of dermatophyte pedal onychomycosis. Itraconazole can be administered as continuous dosing, 200 mg per day for 3 months, or in the form of pulse therapy, 200 mg twice a day for 1 week per month for 3 consecutive months. Terbinafine is given as continuous dosing, 250 mg per day for 3 months.     

Pathologic and diagnostic considerations in onychomycosis

Understanding the physiology and function of the nail unit and its potential avenues of invasion, and properly identifying invading organisms are two key aspects of using the newer therapies available for the treatment of onychomycosis. This article discusses the most common pathologies of onychomycosis, as classified by the sites of entry of the invading fungi. Susceptibility factors leading to infection are also discussed. Obtaining proper tissue samples, using appropriate tests and culture media, and accurately interpreting test results are all paramount to correct identification of the invading organism and, in turn, to effective prescribing. When fungal-growth results do not support the clinical symptoms, or if a more specific identification of the organism is required, additional diagnostic tests are available and are outlined here.     

Onychomycosis associated with Onychocola canadensis: ten case reports and a review of the literature

BACKGROUND: Onychocola canadensis is a nondermatophyte mold associated with onychomycosis particularly in temperate climates (eg, Canada, New Zealand, and France). The slow growth rate of O canadensis and lack of resemblance to any other known nail-infecting fungus may have delayed its discovery. We are aware of 23 mycologically confirmed cases of O canadensis in the literature. OBJECTIVE: We describe 10 previously unreported Canadian patients, specimens from whom grew O canadensis. We also review the literature on infections associated with this organism. METHODS: Cases of O canadensis onychomycosis were diagnosed on the basis of (1) the finding of compatible filaments on direct microscopy of nail and (2) consistent culture from repeated specimens. All patients from whom O canadensis was isolated were followed up, but those in whom outgrowth was not consistent were not accepted as having "authentic" infections. RESULTS: In 10 patients O canadensis was found to be associated with distal lateral subungual onychomycosis (6 patients), white superficial onychomycosis (1 patient), and as an insignificant contaminant in the nails of 3 patients. Less commonly the organism may cause tinea manuum or tinea pedis interdigitalis. O canadensis appears to be more frequent in the elderly, especially females. It is not unusual for a patient with onychomycosis caused by O canadensis to be a gardener or farmer, suggesting that the infectious inoculum may originate from the soil. The optimal therapy for onychomycosis caused by this organism remains unclear. CONCLUSION: O canadensis may be the etiologic agent of distal and lateral subungual or white superficial onychomycosis; however, it may sometimes be present in an abnormal-appearing nail as an insignificant finding, not acting as a pathogen.     

Fibromuscular dysplasia of the internal carotid artery as a cause of transient cerebral ischemia episodes

A person's susceptibility to onychomycosis and the course of the disease once the nails are infected are functions of the interaction of the fungal agent, the host, and environmental factors. The disease is reported to have an overall prevalence of 2% to 13%, but the prevalence is much higher in certain populations, such as older people and those with immunosuppressive conditions. Although onychomycosis may be merely a nuisance and an embarrassment for healthy individuals, some morbidity is seen with all population groups, but especially high-risk patients: diabetics, patients infected with human immunodeficiency virus (HIV), patients with acquired immunodeficiency syndrome (AIDS), and patients with other types of immunosuppression (eg, transplant recipients and patients on long-term corticosteroid therapy). Whether the increased prevalence of onychomycosis in the elderly (up to 30% by age 60) is related to changes in immune function is not known.     

Current trends in onychomycosis therapy: a literature review

Problems with the use of griseofulvin and ketoconazole in the treatment of onychomycosis have led to studies of three new oral antifungal drugs to treat this disease: fluconazole, itraconazole, and terbinafine. These drugs have been superior in relation to a high rate of cure, shorter duration of treatment, minimal adverse effects, and prolonged duration of remission. Although both fluconazole and itraconazole are structurally related to ketoconazole, their triazole ring is more site-specific than the imidazole ring of ketoconazole, which makes these newer drugs less likely to cause liver toxicity. Terbinafine belongs to a new class of compounds called the allylamines, which are fungicidal rather than fungistatic. Terbinafine has become the first line of therapy in Europe and Canada for onychomycosis, and it has recently been approved in the United States in oral form. Itraconazole and fluconazole are available in the United States, but fluconazole is not yet approved for treatment of onychomycosis.     

Oral treatment schedules for onychomycosis: a study of patient preference

BACKGROUND: An improved understanding of patients' attitudes to medication may help promote compliance with oral medications for onychomycosis. This study was performed to assess patients' preference between continuous and intermittent oral treatment schedules for onychomycosis and to determine the reasons underlying the selections made. METHODS: Patients were eligible for inclusion if they had current onychomycosis and were willing to take oral medication for this condition. In a 30-min, face-to-face interview, each patient answered questions about four possible treatment schedules for onychomycosis; regimen 1--continuous (daily regular intake) for 12 weeks; regimen 2--intermittent 1 week/month for 3 months (last week of therapy is week 9); regimen 3--intermittent once weekly for 21 weeks; regimen 4--intermittent 1 week/month for 4 months (last week of therapy is week 13). RESULTS: A total of 102 patients from Germany and Spain participated in the study. When asked to choose between regimens 1, 2, and 3, 46% of patients favored the 9-week intermittent schedule, 42% selected the 12-week continuous schedule, and 12% preferred the 21-week intermittent schedule. The preference for the 9-week intermittent schedule was more notable among younger patients (< 45 years), possibly because they are less used to taking regular medication, and among Spanish patients, an effect that could not be attributed to age because the average age of patients was similar in the participating countries (Germany 47.2 years; Spain 48.0 years). When the patients who preferred regimen 2 were asked to choose between regimens 1, 3, and 4 (both intermittent schedules longer than the continuous schedule), most (57%) favored the shortest treatment schedule (regimen 2). CONCLUSIONS: Overall, patients favored an intermittent schedule lasting 9 weeks. Treatment duration is the critical factor in determining patients' preference for treatment schedules for onychomycosis.     

Nail changes in patients infected with human immunodeficiency virus. A prospective controlled study

OBJECTIVES: To study the frequency of nail changes in a population of human immunodeficiency virus (HIV)-infected patients and to evaluate the specificity of these findings by comparison with HIV-negative control subjects. DESIGN: Prospective controlled study. Nail changes were recorded by a standardized clinical examination (curvature, nail plate, color, onychomycosis). In case of clinical diagnosis of onychomycosis, mycological culture was performed. SETTING: Primary care university hospital. PATIENTS: A total of 155 HIV-1-positive patients and 103 healthy HIV-negative control subjects of comparable age and sex ratio. INTERVENTION: None. MAIN OUTCOME MEASURE: Clinical examination findings. RESULTS: Nail symptoms were present in 67.7% of HIV-positive patients vs 34.0% of controls (P < .001). The following symptoms were significantly more frequent in the HIV group: clubbing (5.8%) (P < .05), transverse lines (7.1%) (P < .01), onychoschizia (7.1%) (P < .05), leukonychia (14.3%) (P < .001), and longitudinal melanonychia (14.8%) (P < .01). The main finding was onychomycosis in 30.3% of patients vs 12.6% of controls (P < .001). Trichophyton rubrum was present in 48% of onychomycoses and unusual Candida species were also recorded. Multiple fungi were frequently cultured in a single patient. The mean CD4+ cell count was lower in patients with onychomycosis and the frequency of onychomycosis increased in advanced stages of HIV disease. Acquired total leukonychia of the 20 nails was present in 4% of patients. CONCLUSION: Nail symptoms are much more frequent in patients with HIV than in healthy controls, and some of them could be linked to the level of immunosuppression.     

Onychomycosis. Baseline results of an observational study

The investigators present an analysis of baseline quality-of-life and patient-management approaches from an observational study of 150 patients being treated by podiatric physicians and dermatologists for onychomycosis. The majority (73%) made the initial office visit specifically because of their onychomycosis. Both men and women indicated that they had substantial physical discomfort as well as concerns related to appearance. Women reported significantly more problems than did men as a result of their onychomycosis. Physicians reported that 54% of patients suffered from toenail discomfort, 36% had pain while walking, 40% reported that their condition limited wearing of shoes, and 67% were embarrassed by the condition. The results of this study suggest that the treatment approach of podiatric physicians is more likely to address the palliative concerns of patients with onychomycosis, while the approach of dermatologists is more likely to attempt a definitive cure.     

Measurement of urine relative density using refractometer and reagent strips

BACKGROUND: Onychomycosis appears to be a variable entity: it presents in different forms in different parts of the world. It is probable that every country has its own particularities of presentation and it is also probable that different regions of the same country, with either different or equivalent environmental conditions, present with different levels of incidence. Large-scale epidemiological studies performed worldwide have demonstrated different epidemiological results. OBJECTIVE: This study was undertaken to determine the epidemiology of onychomycosis in the population of southern Greece. METHODS: Direct microscopic examination and culture were performed on samples from patients with clinical suspected onychomycosis. RESULTS: The most frequently isolated fungus was Candida (52.44%), followed by dermatophytes (41.04%) and saprophytic molds (6.51%). Finger nails were infected more than toe nails in both sexes. The most frequently isolated fungus in finger nails was Candida (76%), followed by dermatophytes (23%), and molds (1%); toe nails were most often infected by dermatophytes (71%), Candida (13%) and molds (16%). Among the infected women patients, the most frequently isolated fungus was Candida (64%), followed by dermatophytes (30.58%); 5.33% were infected by saprophytic molds. Of the 101 men infected, dermatophytes were most frequently isolated (62.37%), followed by Candida (28.71%) and saprophytic molds (8.91%). CONCLUSIONS: Comparison of the results of epidemiological studies of onychomycosis worldwide show great differences, not only between different countries and different climate zones, but also between studies performed in the same country. In our opinion such epidemiological studies should be performed in every country in order to determine the major fungal species responsible; such information is extremely useful in the treatment of nail onychomycosis.     

A retrospective cost-effectiveness analysis of the treatment of onychomycosis in general practice

Analysis of the computer records of 100 general practices from the CompuFile Doctors Independent Network revealed 1492 patients receiving treatment for onychomycosis in the first 6 months of 1994 with terbinafine, tioconazole, amorolfine or griseofulvin. These records indicated the average treatment time for each agent, number of general practitioner consultations and incidence of hospital referrals and minor surgery. Applying standard costs to this resource consumption gave the direct costs for each of these four agents. Published clinical and mycological cure rates allowed a cost per success to be calculated. These were as follows: terbinafine (n = 511) pound258, amorolfine (n = 315) pound312, griseofulvin (n = 196) pound356 and tioconazole (n = 470) pound520. Sensitivity analysis showed that terbinafine remained the most cost-effective option despite variations in resource costs. The cost impact on a typical practice for switching from a less to a more cost-effective treatment is discussed.     

Small-dose itraconazole pulse therapy in the treatment of onychomycosis

The aim was to evaluate efficacy and tolerance of a short-schedule treatment regimen using a small dose of itraconazole in pulse intermittently. The open study evaluated the pulse therapy consisting of monthly 1-week cycles of oral itraconazole 200 mg daily for 2-3 consecutive months in 42 patients with onychomycosis. After active therapy, patients were evaluated for a maximum period of 1 year. Twelve of 42 patients were considered as being clinically cured, 17 were markedly improved, 11 were improved and two were failures. A mycological examination at the final visit was performed on all patients. Thirty-five were negative and seven were positive. This short treatment was well tolerated, with no adverse reactions, and may offer a new option for treatment of onychomycosis.     

Contrast-enhanced three-dimensional magnetic resonance angiography of the splanchnic vasculature before and after caloric stimulation. Original investigation

BACKGROUND: Onychomycosis, a fungal nail infection, has become one of the most important dermatophytoses. Unfortunately, a predictably successful diagnostic approach to onychomycosis does not yet exist. OBJECTIVE: The purpose of this study was to develop a deoxyribonucleic acid (DNA)-based diagnostic method to improve the sensitivity and specificity of the detection and differentiation of the pathogenic fungi of onychomycosis. METHODS: We attempted to detect fungi in the nail using polymerase chain reaction (PCR) primer systems that were designed in conserved sequences of the small ribosomal subunit 18S-rRNA genes shared by most fungi, and differentiated between species by restriction enzyme analysis of the amplified product. RESULTS: Fragments of the gene coding for 18S-rRNA were amplified successfully from medically important fungi species, but not from normal nails. Restriction fragment length polymorphism patterns using HaeIII endonuclease were sufficiently different to allow the recognition of individual species. CONCLUSIONS: The PCR-restriction enzyme analysis method appears to be a more sensitive detection and identification technique for onychomycosis than conventional methods, and has considerable diagnostic value.     

Common dermatophyte infections. A simple diagnostic test and current management

Tinea pedis, onychomycosis, tinea cruris, and tinea capitis are among the most common dermatophyte infections and are seen in all socioeconomic groups. Successful treatment of these conditions depends first on accurate diagnosis, which is often quickly accomplished with a KOH examination. Culture may be needed in some cases, but results may not be available for 2 weeks or more. Immunocompromised patients are particularly susceptible to dermatophyte infection, and any deviations in presentation or failure to respond to treatment should prompt investigation for an underlying problem.     

Tooth bleaching using peroxide-containing agents: current status of safety issues

During the last 10 years, at-home tooth bleaching using peroxide-containing agents has quickly become well accepted. It is one of the most popular cosmetic dental procedures for whitening teeth. Although there are few disputes regarding their efficacy, concerns and debates have continued regarding the safety of peroxide-containing tooth bleaching agents. Potential carcinogenicity and genotoxicity of the peroxides used in bleaching agents are the two most persistent and controversial issues. This article reviews and discusses available information on carcinogenicity and genotoxicity of hydrogen peroxide and the potential risks associated with the use of peroxide-containing bleaching agents. Clinical studies reported after the 1996 international symposium on responses of oral tissues to peroxide-containing bleaching agents are also reviewed. Overall evidence supports the conclusion that the proper use of peroxide-containing at-home tooth bleaching agents is safe. However, potential adverse effects may occur in inappropriate applications, abuses, or the use of inappropriate products. At-home tooth bleaching should be monitored by dental professionals to maximize the benefits while minimizing potential risks.     

Skin and nail infections due to Fusarium oxysporum in Tuscany, Italy

Nine cases of skin and nail infection due to Fusarium oxysporum, diagnosed in Tuscany in the period 1985-97, are described. Two manifested as interdigital intertrigo of the feet and seven as onychomycosis. All were diagnosed on the basis of repeated mycological examination, direct microscope observation and culture, as well as histological examination of biopsy specimens in two cases of intertrigo. Fragments of the fungal colonies were examined by scanning electron microscopy (SEM) for more detailed observation of fungal morphology. All patients had normal immune status and a history of the infection extending several years. Four of the patients with onychomycosis were treated with oral itraconazole, and clinical and mycological recovery was achieved in three cases. Two others were treated with cyclopyrox nail lacquer, successfully in one case. One patient with intertrigo was treated with oral itraconazole and one with oral terbinafine; both were also treated and with topical drugs, however clinical recovery was not confirmed by the mycological results.