No evidence of resistance to itraconazole in a prospective real-world trial of dermatomycosis in India.

BACKGROUND: The prevalence of superficial fungal infections in India is believed to have increased substantially in the past decade. We evaluated the treatment outcomes and risk factors associated with clinical response to a treatment course of itraconazole for the management of dermatomycosis in India. METHODS: In this real-world, prospective pilot study (August 2019 to March 2020), adult participants (18-60 years), diagnosed with T. cruris or T. corporis, received itraconazole 200 mg/day (any formulation) orally for 7 days, and were followed for an additional 7 days. RESULTS: The study was terminated early due to the COVID-19 pandemic. Of 40 enrolled participants (mean [SD] age, 35.5 [12.73] years; {62.5%}] male; 37 received itraconazole and 20 (50%) completed the study. The median (range) Clinical Evaluation Tool Signs and Symptoms total score at baseline was 5.5 (2-10). Clinical response of "healed" or "markedly improved" based on the Investigator Global Evaluation Tool at day 7 (primary objective) was 42.9% (12/28; 95% CI: 24.53%, 61.19%). Itraconazole minimum inhibitory concentration for identified microorganisms, T. mentagrophytes species complex (91.7%) and T. rubrum (8.3%), was within the susceptibility range (0.015-0.25 mcg/mL). At day 14, 8/13 (61.5%) participants achieved a mycological response, 2/13 participants (15.4%) had a mycological failure and 90% showed a clinical response. CONCLUSION: COVID-19 pandemic affected patient recruitment and follow-up, so the findings call for a careful interpretation. Nevertheless, this real-world study reconfirmed the clinical efficacy and microbial susceptibility to itraconazole for the fungi causing dermatophytosis in India. TRIAL REGISTRATION: Trial registration number: Clinicaltrials.gov NCT03923010.

Itraconazole pulse therapy for the treatment of Candida onychomycosis.

In this open label, multicentre trial, 44 patients with clinical and mycological evidence of Candida onychomycosis were treated with itraconazole pulse therapy. Onychomycosis of the toes alone and concomitant disease involving the fingers and toes was treated with three pulses, and onychomycosis of the fingers alone with two pulses. Final evaluation for patients with finger and toe onychomycosis was at 6-9 months and 9-12 months, respectively. There were 29 patients with toe onychomycosis (C. albicans, 27; C. glabrata, one; Candida species, one), 12 patients with finger onychomycosis (C. albicans, two; C. glabrata, one) and three patients had combined toe and finger onychomycosis (C. albicans, two; C. guillermondii, one). In the patients with toe onychomycosis mycological cure was observed in 29 of 32 patients (90.6%). There was complete cure [mycological cure (negative culture and KOH at endpoint evaluation) with clinical cure] or marked improvement (mycological cure with 75% or greater decrease in area of involvement of target nail compared with pretherapy) in 24 of 32 patients (75.0%). All 12 patients with finger onychomycosis alone due to Candida species achieved a mycological cure (100%). In this group of patients complete cure or marked improvement was observed in 11 of 12 patients (91.7%). Itraconazole pulse therapy was well tolerated and no serious adverse events were reported in the patients treated with this triazole. In conclusion, itraconazole pulse therapy is an effective and safe treatment for both finger and toe onychomycosis associated with Candida.

Effect of ketoconazole 1% and 2% shampoos on severe dandruff and seborrhoeic dermatitis: clinical, squamometric and mycological assessments.

Ketoconazole (KET) is active to control dandruff and seborrhoeic dermatitis. Objective assessments comparing the 1% and 2% shampoo formulations are scant. This open, randomized parallel-group trial was carried out to differentiate the effectiveness of KET 1% and 2% in severe dandruff and seborrhoeic dermatitis. A total of 66 patients with severe dandruff or seborrhoeic dermatitis were randomized to each of the two groups. A 2-week run-in phase was followed by a 4-week treatment phase, in turn followed by a 4-week follow-up. The efficacy of treatments was evaluated by combining squamometry X, Malassezia spp. counts and clinical assessments. After 2 and 4 weeks of treatment, KET 2% was significantly superior over KET 1% (p < 0.001) for decreasing both in flakiness and Malassezia density from baseline. The same trend was observed in the mean change from baseline in the overall dandruff severity score. Only 6 mild adverse events were reported. During follow-up KET 2% showed a trend to fewer relapses than KET 1%. KET 2% had superior efficacy compared to KET 1% in the treatment of severe dandruff and scalp seborrhoeic dermatitis. Biometrological evaluations were correlated with the clinical improvements and therefore useful to incorporate in future dandruff studies.

The use of itraconazole to treat cutaneous fungal infections in children.

BACKGROUND: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. OBJECTIVE: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. METHODS: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). RESULTS: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. CONCLUSIONS: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.

Itraconazole and terbinafine in perspective: from petri dish to patient.

OBJECTIVE: To compare the antifungal activity of itraconazole and terbinafine in vitro and to relate them to their experimental in vivo activity and to their efficacy in patients with superficial fungal infections (tinea pedis and onychomycosis). RESULTS: Fungal infections such as onychomycosis and tinea pedis are often treated with oral antifungals. With the introduction of newer agents such as terbinafine and itraconazole, efficacy and safety have been improved. In vitro evaluation showed somewhat better results against dermatophytes for terbinafine than for itraconazole, but in vivo results were at least equivalent. Moreover, itraconazole is a broad-spectrum agent with higher cure rates for infections other than dermatophytosis (e.g. for Candida infections) than terbinafine, according to ex vivo studies. A review of all published clinical trials, comparing the efficacy and safety of terbinafine and itraconazole in a meta-analysis revealed similar and high cure rates (>70%) for both antifungal agents and similar adverse event profiles. Both treatments were safe and well tolerated. CONCLUSIONS: Antifungal research has responded to the challenges of treating superficial infections by developing effective, well-tolerated, fast-acting antifungal therapies. The reduction in treatment duration has also led to improved patient's compliance. The most noticeable difference between itraconazole and terbinafine is the 1-week pulse concept of itraconazole in contrast to the continuous treatment concept of terbinafine.

Itraconazole and terbinafine in perspective. From petri dish to patient.

This paper compares the antifungal activity and efficacy of itraconazole and terbinafine in vitro with their experimental activity and efficacy in vivo in patients with superficial fungal infections (tinea pedis and onychomycosis). Onychomycosis and tinea pedis are often treated with oral antifungals. With the introduction of newer agents, such as terbinafine and itraconazole, efficacy and safety have been improved. In vitro evaluation showed somewhat better results for terbinafine over itraconazole against dermatophytes, but in vivo results were at least equivalent. Moreover, according to ex vivo studies, itraconazole is a broad-spectrum agent with higher cure rates than terbinafine for fungal infections other than dermatophytosis (e.g., Candida infections). A meta-analysis of data from all published clinical trials comparing the efficacy and safety of terbinafine and itraconazole revealed similar high cure rates (> 70%) for both antifungal agents and similar adverse-event profiles. Both treatments were safe and well tolerated. Antifungal research has responded to the challenges of treating superficial infections by developing effective, well-tolerated, fast-acting antifungal therapies. The reduction in treatment duration also has led to improved patient compliance. The most notable difference between itraconazole and terbinafine is the 1-week pulse regimen available with itraconazole as opposed to the continuous treatment course available for terbinafine.

Safety of itraconazole pulse therapy for onychomycosis. An update.

After experience with more than 34 million patients over 10 years, the safety of itraconazole and its potential drug-drug interactions are well known. In clinical trials, the average incidence of adverse events with a 1-week pulse regimen was 18% in pooled safety data (n = 2,867); only 2.2% of patients dropped out. In direct comparative trials, the incidence of mild and reversible adverse effects was comparable for itraconazole and terbinafine (31% and 28%, respectively) during treatment. The rate of permanent withdrawal because of adverse events was 3.6% for itraconazole and 7.5% for terbinafine (P < .05). Itraconazole was significantly better tolerated as evaluated by the investigator and patients. The analysis of the elderly subpopulation showed that patients 65 and older tolerated itraconazole pulse well, with only 20% experiencing mild and reversible side effects (total group). In direct comparative trials, itraconazole also produced fewer adverse effects than terbinafine (13% vs 32%, respectively). As newer oral antifungal agents gain widespread use, clinicians need to be aware of their potential drug-drug interactions and their possibly serious adverse events. However, pooled data from the 1-week itraconazole pulse regimen indicated a favorable safety profile, and a dose increase to 400 mg had no impact on safety.

Safety of itraconazole in diabetic patients.

BACKGROUND: Onychomycosis and dermatomycoses can result in serious complications in patients with underlying chronic diseases such as diabetes. To avoid these complications, these dermatological disorders need to be treated efficiently, for example with the triazole antifungal itraconazole. Itraconazole can inhibit the metabolism of drugs by CYP 3A4 and therefore might affect the efficacy of antidiabetic agents. OBJECTIVE: To investigate this, we assessed the safety of itraconazole in diabetic patients with onychomycosis or dermatomycoses. METHODS: We reviewed pharmacokinetic and safety data from clinical trials and postmarketing surveillance over the past 10 years. RESULTS: Postmarketing surveillance (a review of all adverse-event reports in patients receiving itraconazole concomitantly with insulin or an oral antidiabetic agent) revealed 15 reports suggestive of hyperglycemia and 9 reports suggestive of hypoglycemia; in most patients, no change in antidiabetic effect was reported. From clinical trials including a total of 189 diabetic patients treated with itraconazole for various infections (mainly systemic infections and vaginal candidiasis), only one itraconazole-related adverse event was recorded; this was a case of aggravated diabetes in a renal transplant recipient who was also receiving cyclosporine. Adverse effects due to drug-drug interactions are not expected in diabetic patients receiving oral antidiabetic agents that are not metabolized through the CYP 3A4 system (e.g. tolbutamide, gliclazide, glibenclamide, glipizide and metformin). CONCLUSION: Itraconazole can be used safely and efficiently for the treatment of dermatological disorders in diabetic patients.

Itraconazole pulse therapy is effective in the treatment of Majocchi's granuloma: a clinical and pharmacokinetic evaluation and implications for possible effectiveness in tinea capitis.

Majocchi's granuloma is a folliculitic and perifolliculitic dermatophyte infection of the dermis, a site that is not generally colonized by fungi in immunocompetent individuals. Topical agents are usually ineffective therapeutically because of the deep location of the infection. The objective of this study was to determine the effectiveness of oral itraconazole. We also examined the pharmacokinetics of the drug in scalp hair during pulse therapy. This information would then be useful in determining the efficacy of itraconazole administered by means of intermittent pulse dosing in the treatment of tinea capitis. Seven patients (age range 25-75 years) were treated up to three times with itraconazole pulse therapy, 200 mg twice daily for 1 week, with 2 weeks off between pulses. Samples of scalp hair and plasma were also obtained to determine the pharmacokinetics of the drug at these two sites. All seven patients responded to therapy, clinical and mycological cure being achieved after one pulse (one patient), two pulses (three patients), or three pulses (three patients, each with toenail onychomycosis); none relapsed over a 6-18-month follow-up period. In all six patients who received two or more pulses of itraconazole, almost complete cure was observed before the second pulse, with full resolution within 2 weeks of its completion. Itraconazole was also detected in the hair after 1 week, and at concentrations 2.6-fold and 3.4-fold higher, respectively, after the second and third pulses. After the discontinuation of therapy, itraconazole was then detectable in the hair for 9 months, at least in a female patient who did not have her hair cut. Two pulses of oral itraconazole therapy thus appear to be effective in the treatment of Majocchi's granuloma, and it is possible that one pulse may be sufficient in some patients. These data suggest that itraconazole pulse therapy should be effective in the treatment of tinea capitis.

Treatment of tinea capitis with itraconazole capsule pulse therapy.

BACKGROUND: The number of newly diagnosed cases of tinea capitis in children appears to be on the rise, particularly in urban centers. OBJECTIVE: The purpose of this study was to assess the effectiveness, safety, and compliance of itraconazole pulse therapy for tinea capitis. METHODS: Fifty subjects (48 children [less than 18 years of age] and 2 adults) with tinea capitis were treated with pulse itraconazole in a multicenter evaluation. Each pulse lasted 1 week, with 2 weeks between the first two pulses and 3 weeks between the second and third pulses. The decision to administer a second or third pulse was determined by the response of the subject at the time that the next pulse was due. During the 1-week pulse of active therapy, itraconazole (5 mg/kg/day) was dosed as follows: more than 40 kg, 200 mg per day (two capsules per day); 20 to 40 kg, 100 mg per day (one capsule per day); and 10 to 19 kg, 50 mg per day (one half of a capsule per day). The duration of the study was 12 weeks with mycologic evaluation at this time. Subjects who were classified as treatment failures at 12 weeks after the start of therapy were given the option of receiving an additional 1-week pulse of active therapy, with 3 weeks between successive pulses. RESULTS: The causative organisms were Trichophyton tonsurans (41 subjects), T violaceum (7), T. soudanense (1), and T rubrum (1). Thirteen subjects were lost to follow-up, with 37 subjects (35 children and 2 adults) available for evaluation 12 weeks after the start of therapy. At this time, cure (clinical and mycologic) was observed in 30 (81%) of 37 subjects. When the tinea capitis was mild, cure was obtained after one pulse in two subjects and after two pulses in five subjects. With tinea capitis of moderate extent, complete cure was obtained after one pulse in one subject, two pulses in eight subjects, and after three pulses in seven subjects. When tinea capitis was severe, two and three pulses produced complete cure in one and six subjects, respectively. Of the seven subjects whose conditions failed to respond (three subjects with moderate disease and four subjects with severe disease), five subjects chose to receive extra itraconazole. Clinical and mycologic cure was observed after four pulses in four subjects and after five pulses in one subject. There were no associated clinical adverse effects with itraconazole therapy. CONCLUSION: With tinea capitis, itraconazole pulse therapy is effective and safe and is associated with high compliance. The pulse regimen enables the duration of treatment to be individualized, according to the extent of disease and its rate of resolution.

An intermittent itraconazole 1-week dosing regimen for the treatment of toenail onychomycosis in dermatological practice.

The efficacy and safety of an intermittent itraconazole dosing regimen was investigated in 354 patients with toenail onychomycosis, from 98 dermatology centres. Patients received itraconazole 400 mg daily for 1 week per month for 3 months. If the nail of the big toe was completely involved, a fourth treatment cycle was administered. Because of the short-term nature of the dosing regimen, renal and liver function tests were not compulsory. Cure rates were influenced by proximal nail involvement, particularly in the big toenails. At the end of month 10, clinical cure (complete clearance or clearance with a few small residual lesions) was achieved in 64% of patients with proximal nail involvement in the big toenails, in 77% of patients with proximal nail involvement in other toenails and in 87% of patients without proximal nail involvement; mycological cure was achieved in 77% of 197 patients examined. Fifty-nine patients (17%) reported adverse events: mainly headache, fatigue or minor gastrointestinal problems; only nine patients (3%) stopped treatment because of adverse events. Response rates were similar to those achieved with 3 months of continuous therapy with itraconazole or terbinafine but intermittent therapy is probably safer and is considerably cheaper than continuous itraconazole treatment.

Itraconazole pulse therapy for tinea capitis: a novel treatment schedule.

Itraconazole 5 mg/kg/day given as pulse therapy, each of 1 week duration, for 1 to 3 pulses appears to be an effective and safe method of treating tinea capitis. The number of pulses of therapy may depend upon several factors, including the severity of disease and area of involvement. Controlled studies are needed to determine the number of pulses of itraconazole required to treat tinea capitis.

Ketoconazole shampoo: effect of long-term use in androgenic alopecia.

BACKGROUND: The pathogenesis of androgenic alopecia is not fully understood. A microbial-driven inflammatory reaction abutting on the hair follicles might participate in the hair status anomaly. OBJECTIVE: The aim of our study was to determine if ketoconazole (KCZ) which is active against the scalp microflora and shows some intrinsic anti-inflammatory activity might improve alopecia. METHOD: The effect of 2% KCZ shampoo was compared to that of an unmedicated shampoo used in combination with or without 2% minoxidil therapy. RESULTS: Hair density and size and proportion of anagen follicles were improved almost similarly by both KCZ and minoxidil regimens. The sebum casual level appeared to be decreased by KCZ. CONCLUSION: Comparative data suggest that there may be a significant action of KCZ upon the course of androgenic alopecia and that Malassezia spp. may play a role in the inflammatory reaction. The clinical significance of the results awaits further controlled study in a larger group of subjects.

Itraconazole in the treatment of onychomycosis: a double-blind comparison with miconazole.

BACKGROUND: In recent years, itraconazole pulse therapy for onychomycosis has been developed [three 1-week pulses with itraconazole 400 (2 x 200) mg daily every month]. This has proved an effective and safe regimen which requires only 50% of the medication used for continuous dosing schedules. Parallel to the development of the new dosage schedule, additional studies were conducted to further document the safety and efficacy of itraconazole 200 mg once daily for 3 months to treat onychomycosis. OBJECTIVE: To compare the safety of itraconazole 200 mg once daily for 3 months, with or without itraconazole 200 mg once weekly for a further 3 months, with that of miconazole cream twice daily for 6 months, in the treatment of onychomycosis. Treatment efficacy was compared as a secondary objective. METHODS: In this multicenter, double-blind study, patients were randomized to receive itraconazole 200 mg once daily for 3 months followed by either itraconazole 200 mg once weekly for 3 months (ITR-ITR group, n = 599) or oral placebo once weekly for 3 months (ITR-PLAC group, n = 613), or to receive miconazole cream twice daily for 6 months (MIC-MIC group, n = 396). The primary variable was elevation of alanine amino-transferase (ALT) concentration above 50 U/I. RESULTS: Overall incidence of elevation of ALT concentration above 50 U/I, adverse events and rate of withdrawal because of adverse events were low and similar in the three treatment groups. Efficacy was significantly greater in the ITR groups than the MIC-MIC group. CONCLUSION: Itraconazole and miconazole were well tolerated and had no significant effect on liver function, but itraconazole was significantly more effective.

Itraconazole for the treatment of onychomycosis.

BACKGROUND: The broad spectrum of activity of itraconazole in vitro manifests itself clinically with the drug being effective for the treatment of onychomycosis caused by dermatophytes, Candida and some non-dermatophyte molds. The pharmacokinetics of itraconazole in the nail results in drug remaining at therapeutic levels for 6-9 months after completion of therapy. METHODS: An overview of studies where continuous or pulse itraconazole therapy has been used in the treatment of fingernail and toenail onychomycosis. RESULTS: Following continuous therapy at 200 mg/day for 3 months for toenail onychomycosis (n = 1741), the rates of clinical cure, clinical response and mycologic cure were: (meta-average +/- 95% standard error (SE)), 52 +/- 9%, 86 +/- 2%, and 74 +/- 3%, respectively, at follow-up 12 months following start of therapy. In fingernail onychomycosis (n = 211), the duration of therapy was 6 weeks and the corresponding efficacy rates at follow-up, 9 months after start of therapy, were meta-average (+/- S.E.) 82 +/- 5%, 90 +/- 2%, and 86 +/- 3%, respectively. In toenail onychomycosis treated with 3 pulses of therapy (n = 1389), the clinical response, clinical cure and mycologic cure were observed in meta-average (+/- S.E.) 58 +/- 10%, 82 +/- 3%, and 77 +/- 5% patients, respectively, at follow-up 12 months after the start of therapy. In fingernail onychomycosis treated with 2 pulses of therapy (n = 210), at follow-up 9 months after the start of therapy, the corresponding efficacy rates were meta-average (+/- S.E.) 78 +/- 10%, 89 +/- 6%, and 87 +/- 8%, respectively. CONCLUSIONS: Both the continuous and pulse therapy regimens are safe with few adverse effects. Compared to continuous therapy, the pulse regimen has an improved adverse-effects profile, is more cost-effective, and is preferred by many patients.

Reduction in the growth of non-dermatophyte moulds by itraconazole: evaluation by corneofungimetry assay.

The activity of itraconazole against fungi of dermatological importance was studied using corneofungimetry performed on four test organisms: Aspergillus flavus, Fusarium oxysporum, Scopulariopsis brevicaulis and Scytalidium dimidiatum. The human stratum corneum used in the bioassay was harvested from healthy volunteers and from patients undergoing treatment with itraconazole 200 mg daily for at least 2 weeks. A fungal mycelium grew on all untreated stratum corneum samples within 1 week. The pattern and extent of growth varied greatly among the test organisms. An inhibitory effect was observed on the itraconazole-treated samples. However, the level of inhibition was higher than that expected by calculating itraconazole minimum inhibitory concentrations in a reference susceptibility test. It is concluded that some non-dermatophyte moulds of medical importance can grow by forming hyphae on human stratum corneum. However, the process is partly inhibited by some unknown mechanisms originating from the stratum corneum itself. It is further inhibited by the oral administration of itraconazole. This global effect might be the result of the complementation inhibition due to the drug and/or some unknown components of the stratum corneum.

Prolonged effects of antidandruff shampoos - time to recurrence of Malassezia ovalis colonization of skin.

Most active antidandruff shampoos exhibit a strong activity against the yeast Malassezia ovalis. The present study was undertaken to compare the prolonged antifungal effect of three proprietary shampoos containing either 2% ketoconazole, 1.5% zinc pyrithione or 2.5% selenium sulphide. Superficial squames were harvested from the scalp in the days following a 6-week antifungal shampoo treatment. Counts of yeasts highlighted by a fluorochrome were made using computerized image analysis. Data show the increased duration of yeast reduction for the ketoconazole shampoo over the two other formulations. The lingering effect of ketoconazole is explained by the combination of its antifungal and pharmacokinetic properties.

Onychomycosis in children: prevalence and treatment strategies.

BACKGROUND: Onychomycosis is observed less frequently in children than adults. Until recently management of onychomycosis in children included topical formulations, oral griseofulvin, and in some cases deferral of treatment. OBJECTIVE: We attempted to determine the prevalence of onychomycosis in North American children 18 years old or younger attending our dermatology offices (three Canadian, two U.S.) and to report the group's experience using fluconazole, itraconazole, and terbinafine for onychomycosis. METHODS: We undertook a prospective, multicenter survey in which all children, regardless of presenting complaint, were examined for onychomycosis by a dermatologist. In instances of clinical suspicion appropriate nail samples were obtained for light microscopy and culture. RESULTS: A total of 2500 children under age 18 were examined in the five-center survey (1117 males and 1383 females, mean +/- S.E. age: 11.2 +/- 0.1 years). There was one child with fingernail and ten with mycologically confirmed toenail dermatophyte onychomycosis. The overall prevalence of onychomycosis was 0.44%. Considering those children whose primary or referring diagnosis was not onychomycosis or tinea pedis, the prevalence of onychomycosis was 0.16%. Outside the survey we have seen six other children with dermatophyte onychomycosis; these 17 cases form the basis for the remainder of the report. Of the 17 children, eight (47%) had concomitant tinea pedis infection, and in 11 (65%) a sibling, parent, or grandparent had onychomycosis or tinea pedis. Management included topical terbinafine (two patients: one cured, one failed therapy), topical ketoconazole (one patient: clinical improvement), oral fluconazole (two patients: one cured, one had Down's syndrome and was noncompliant), oral itraconazole (four patients: three cured with subsequent recurrence at follow-up in one patient, one lost to follow-up), oral terbinafine (five patients: four cured with subsequent recurrence at follow-up in one patient, one failed therapy). One child received no therapy following discussion with the parents, one was lost to follow-up and one was found to have asymptomatic hepatic dysfunction with hepatitis C at pretherapy bloodwork. CONCLUSION: The prevalence of onychomycosis in our sample of North American children 18 years old or younger was 0.44% (n = 2500). In the subset of children whose primary or referring diagnosis was not onychomycosis, the prevalence of onychomycosis was 0.16%. Children with onychomycosis should be carefully examined for concomitant tinea pedis, and their parents and siblings checked for onychomycosis and tinea pedis. The newer oral antifungal agents fluconazole, itraconazole, and terbinafine may be effective and well-tolerated in the treatment of onychomycosis in this age group. These drugs should be carefully evaluated in a larger cohort of children with onychomycosis.