Fungal Infections

Fungal Infections

A New Medium for the Presumptive Identification of Dermatophytes

Objective.—Dermatophyte test medium (DTM) was developed for simple, quick identification of dermatophytes. However, like other commercially marketed media, DTM has problems with false positive results. These arise because DTM does not completely suppress the growth of nondermatophytes, some of which appear similar to dermatophytes. Dermatophyte identification medium (DIM) is described as a new approach to overcoming such problems with presumptive identification of dermatophytes.

Fungal InfectionsFindings.—Studies have been performed in more than 572 primary, reference, and culture collection isolates, including 42 different genera and 71 different species of molds, dermatophytes, and nondermatophytes. When an unknown isolate was encountered, it could be presumptively identified as a dermatophyte by transferring the colony to DIM. The medium changed color within 24-48 hours to signal a positive result. The only false positive results were those associated with bacterial contamination of the mold isolates. Isolates of Trichophyton verrucosum sometimes caused false negative results.

Conclusions.—Dermatophyte identification medium appears to be a quick, simple, and accurate method for presumptive clinical identification of dermatophytes. It overcomes the problem of false positive results with DTM. It is highly specific and sensitive for the identification of dermatophytes, probably through the use of high concentrations of antifungal antibiotics and high incubation temperatures.

The growth of some nondermatophytic fungi, both saprophytes and pathogens, is not inhibited by the antifungal antibiotic in DTM. Additionally, some nondermatophytic fungi cause a color change in the medium as intense and as rapid as that caused by dermatophytes. Thus, the development of a new medium to eliminate false positive results is welcome.

Comparison of Single Dose 400 mg Versus 10-Day 200 mg Daily Dose Ketoconazole in the Treatment of Tinea Versicolor

Introduction.—Tinea versicolor was historically treated with topical medications, but time-consuming and messy application caused problems with compliance and prompted a search for an oral therapy. Ketoconazole is the first effective oral antifungal drug to be used in the treatment of tinea versicolor. Dosage regimens were evaluated in the tropical conditions of the Philippines, where the humidity ranges from 74% to 77%, and temperatures range from 69°F to 73°F.

Methods.—A total of 120 patients with a moderate degree of infection (25% to 50% body surface area) received either regimen A (two 200-mg tablets as a single dose) or regimen B (one 200-mg tablet for 10 days). Patients were evaluated at 10 days and at 1 month after completion of each treatment regimen using KOH and Wood’s light examinations. If both examinations were negative, patients were considered to have a mycologic cure. Treatment failure occurred if one or both examinations remained positive. Liver enzyme determination was considered unnecessary.

Results.—The mean patient age was 25 years. The 60 patients who received regimen A had a mycologic cure rate of 2% at 10 days after therapy completion and 42% at 1 month. These rates for the 60 patients who received regimen B were 3% and 51%, respectively. Two patients receiving regimen B did not follow-up at 1 month and were considered treatment failures. No patients in either group experienced any untoward side effects.

Conclusion.—Because there were no significant differences in mycologic cure rate at 1 month after completion of ketoconazole therapy, a single dose may be considered as effective as the 10-day regimen for treating tinea versicolor. The highest mycologic cure rate was 51 % at 1 month after treatment completion. Factors affecting the cure rate may have been the exogenous heat and humidity, or unknown hereditary considerations.

 Although there was no statistically significant difference between the 2 groups at the time of the 1 month follow-up, neither regimen was especially effective, with cure rates in the 50% range. Other therapy schedules should be investigated, as should some of the newer oral antifungal drugs.

Nosocomial Transmission of Trichophyton tonsurans Tinea Corporis in a Rehabilitation Hospital

Purpose.—Despite some predisposing characteristics, few studies have described the nosocomial transmission of Trichophtyon tonsurans. An outbreak of tinea corporis caused by T. tonsurans in a hospital setting was reported.

Outbreak.—The outbreak started with a 6-year-old boy admitted to a rehabilitation hospital after prolonged hospitalization for anoxic encephalopathy and variable-thickness burns covering 20% of total body surface area. The patient was exposed to other children during weekly therapeutic home visits. At 9 weeks, during a diaper change, the patient was found to have a red, slightly vesicular, 5-cm lesion on his left buttock. Tinea corporis was diagnosed and treated with topical clotrimazole. The lesion began to clear within 3 days, but another lesion soon appeared, followed by 3 new lesions on the right buttock. With clotrimazole treatment, all lesions had almost completely resolved within 3 weeks. The patient was discharged after 12 weeks and remained free of recurrences at 5 months’ follow-up.

About 3 weeks later, red, slightly vesicular lesions developed on the left hand or forearm of 3 health care workers, and on the chin of another worker. A diagnosis of tinea corporis was made in all cases. The workers were interviewed regarding their previous history of skin lesions, other sources of tinea, and contact with the index patient. Scrapings of lesions from 3 workers were examined microscopically. In 2 cases, culture studies were performed.

Findings.—All microscopic and culture studies were positive for T. tonsurans. In the subsequent 3 months, no additional cases were identified. All 4 workers had been in contact with the index patient, with no other history of exposure to tinea. All lesions responded to topical clotrimazole. A total of 30 health care workers having contact with the index patient were evaluated, 17 of whom had moderate-to-major contact. The rate of infection was 33% with major contact, 17% with moderate contact, and 0% with minimal contact. The infected workers were 2 nurses, an occupational therapist, and a speech therapist. The estimated incubation period of T. tonsurans was 5-7 weeks.

Discussion.—This is the first report of nosocomial T. tonsurans tinea corporis in a rehabilitation hospital setting. The attack rate is high, even with early diagnosis and treatment. Health care workers treating patients with T. tonsurans infection should be sure to cover all skin that could come into contact with the patient. This precaution should be observed even for areas that look clinically normal.

 Although the authors’ interpretation of the data is probably correct, a more convincing case could have been established by isolation of the organism from the index case and more precise biochemical characterization of the isolates from all affected individuals. This would have established that they were indeed infected by the same strain of the organism from the same patient. Nevertheless, the message is clear: dermatophyte infections are contagious, and appropriate precautions must be respected in the presence of active disease.

Tinea Capitis in Adults: Misdiagnosis or Reappearance?

Objective.—Scalp ringworm is thought to be rare in adults and is therefore often misdiagnosed. Recent cases of tinea capitis in adults are discussed.

Methods.—Mycologic examinations were performed in 8 patients (6 women), age 21-72 years, with scalp scaling.

Results.—Five patients had immunosuppressive disease, including 2 who had non-Hodgkin’s lymphoma in remission without treatment; 1 who had thrombocythemia for 7 years; 1 who had cutaneous and articular psoriasis treated with acitretin, systemic corticosteroids, and hydroxychloroquine for 6 years; and 1 who had an HIV infection. All patients had scaling, 5 had alopecia, and 2 had pustular lesions. One patient had typical black-dot tinea capitis. Three patients had tinea corporis on the arms or face. Four patients had an endothrix type of hair invasion, and 4 patients had an ectothrix type.

Conclusion.—Past studies have stated that only 3% to 5% of adults older than 20 years have tinea capitis. It is usually associated with diffuse scaling and sometimes with alopecia. Continuation of childhood tinea capitis is rare. The condition is generally treated with griseofulvin for 45 days to several months. Tinea capitis should be suspected when patients, particularly women, complain of scaling, possibly accompanied by alopecia. Abnormal hairs should be examined microscopically and cultured. Adults may be asymptomatic carriers and should be sought when infected children are found.

 The 11 % incidence of tinea capitis in adults in this study is more than twice that cited in previous reports. The frequent atypical clinical presentation requires a high degree of clinical suspicion. An asymptomatic adult carrier state must be searched for in parents and close relatives of affected siblings.

Treatment of Tinea Capitis With Itraconazole

Introduction.—Griseofulvin is the standard treatment for tinea capitis, a common fungal infection of children. However, some patients fail to respond to or cannot tolerate griseofulvin. The use of itraconazole for such patients is reported.

Methods.—Of approximately 800 patients treated for tinea capitis, 120 had an unsuccessful trial of treatment with griseofulvin. They were either unresponsive, or they could not tolerate it. These patients, most between 5 and 12 years old, were treated with oral itraconazole. Culture was positive for Trichophyton tonsurans in all patients but 1. The dosage was 3-5 mg/kg/day, depending on body weight. Treatment continued for 30 days. The patients also used ketoconazole 2% shampoo 2 or 3 times per week, left on for 5 minutes. Other members of the family were instructed to use ketoconazole 2% shampoo as well. The follow-up schedule called for evaluations at baseline, after 2 weeks of treatment, on completion of therapy (30 days), and at 4 weeks after treatment.

Results.—At the end of treatment, all patients were in clinically improved condition. Inflammation had resolved, and hair had regrown to some extent. All patients had become culture negative. Clinical improvement continued after the end of treatment, and all patients were considered cured at the last follow-up examination. One patient with Microsporum canis infection, who followed treatment for only 21 days, had a recurrence within 6 months after the end of therapy. This patient was successfully treated with another course of itraconazole.

 Although shampoos should be included as part of the treatment regimen for tinea capitis, the added benefit of using ketoconazole shampoo (vs. a much cheaper alternative) is doubtful.

Medication Schedule
Body weight Dosage
22-40 lbs (10-18 kg) 100 mg every other day
40-60 lbs (18-27 kg) 100 mg daily
60-90 lbs (27-41 kg) 100 mg daily or alternating 100 mg and 200 mg daily
90-110 lbs (41-50 kg) Alternating 100 mg and 200 mg daily
>110 lbs 200 mg daily

(Courtesy of Elewski BE: Treatment of tinea capitis with itraconazole. Int J Dermatol 36:539-541,
1997. Used with permission of Blackwell Science Ltd.)

Fluconazole for the Treatment of Tinea Capitis in Children

Introduction.—Fluconazole has yielded favorable results when used to treat various systemic mycoses, candidiasis, and other dermatophyte infections. The efficacy of fluconazole was assessed in 41 children with noninflammatory tinea capitis.

Methods.—The age range of 27 patients with completed data was 2-15 years. Patients were randomized to receive 20 days of treatment with either 1.5, 3, or 6 mg/kg/day of fluconazole. Patients underwent clinical and mycologic examinations at baseline and at 20 days, 6 weeks, and 4 months after treatment was completed.

Results.—Of 8 patients, 2 (25%) treated with 1.5 mg/kg/day responded to therapy by the 20th day of treatment. In patients treated with 3.0 and 6.0 mg/kg/day, these numbers were 6 of 10 (60%) and 8 of 9 (89%), respectively. All patients in all 3 groups who were clinically and mycologically cured by the 20th day remained so at 6-week and 4-month evaluations. Clinical improvements were observed on an average of 12, 16, and 17 days in patients treated with 6, 3, and 1.5 mg/kg/day fluconazole, respectively. Treatment was well tolerated, and no patients were removed from the trial because of intolerance. All laboratory values remained normal throughout follow-up.

Conclusion.—Fluconazole is a bis-triazole antifungal agent that has broad-spectrum activity against a variety of dematophytes and candidal infections. Fluconazole is safe and effective in the treatment of tinea capitis caused by Trichophyton tonsurans in children.

 The purpose of this study was to determine the efficacy and safety of fluconazole in children with noninflammatory tinea capitis. The highest dose of fluconazole, 6 mg/kg/day, was necessary to effect an acceptable cure rate (89%) after 20 days of therapy. Griseofulvin remains the standard therapy for tinea capitis infection in children, with itraconazole being an effective and apparently safe alternative. Because only 9 children were treated with fluconazole at the dose of 6 mg/kg/day for the limited duration of the study, the safety of this regimen in children has not been proven.

Randomized Single-blind Study of Efficacy and Tolerability of Terbinafine in the Treatment of Tinea Capitis

Introduction.—The usual oral fungistatic drug treatment of tinea capitis requires at least 6-12 weeks of therapy. Shorter drug courses are desirable. Preliminary data suggest that terbinafine might be useful in the treatment of tinea capitis. The efficacy and tolerability of terbinafine in the treatment of tinea capitis was assessed in a randomized, single-blind trial.

Methods. —Eighty-nine children from an orphanage in Thailand were randomized to group I, II, or III for treatment with terbinafine for 1, 2, or 4 weeks, respectively. Both Trichophyton tonsurans and Microsporum ferrugineum were identified in inflammatory and noninflammatory lesions of the scalp. Clinical and mycologic examinations and photographs were taken at baseline, completion of therapy, and week 12.

Results.—Seven patients were lost to follow-up, leaving 82 patients with completed data. Three adults working at the orphanage and 79 children over age 7 years were evaluated. Patients in groups I and II had no significant clinical or mycologic improvement at completion of therapy. Eighteen (66.7%) patients in group III had negative mycologic cultures at 4 weeks. The overall cure rate for groups I, II, and III at week 12 were 44.4%, 57.1%, and 77.8%. Three patients infected with M. ferrugineum did not respond.

Conclusion.—Terbinafine was efficacious in the treatment of inflammatory and noninflammatory tinea capitis. The cure rate for T. tonsurans infections was excellent, but rates for M. ferrugineum and mixed infections were lower.

 This study of 82 patients, mostly children, with tinea capitis showed that a 4-week course of terbinafine can produce an acceptable cure rate (77.8%). The groups receiving a briefer duration of treatment, 1 or 2 weeks, showed only a 44.4% and 57.1% cure rate, respectively. Because the study was performed at an orphanage in Thailand, both Trichophyton tonsurans and Microsporum ferrugineum were the causative organisms. Terbinafine was found to be much less efficacious for the M. ferrugineum infections.

Lack of Efficacy of 6-Week Treatment With Oral Terbinafine for Tinea Capitis Due to Microsporum canis in Children

Objective.—Some areas of Europe have seen a sharp rise in Microsporum canis infection in recent years. Most affected patients are children, many of whom have scalp infection. Most lesions are dry and noninflammatory. The results of oral terbinafine treatment in children with dry, noninflammatory M. canis tinea capitis were reported.

Methods.—The patients were 13 boys and 9 girls, aged 2-9 years. In each case, the diagnosis was confirmed by Wood’s light examination, direct microscopy of hair specimens treated with 10% potassium hydroxide, and culture. All patients received terbinafine once daily for 6 weeks. Dosage was 62.5 mg/day for children weighing less than 20 kg; 125

The Number and Percentage of Cured Patients With Negative Mycologic Studies (Wood, KOH, Culture) at the End of 6 Weeks of Treatment and After Follow-up Periods of 4 and 8 Weeks
KOH Wood Culture KOH, Wood, Culture
6 weeks 1   (4.50) 1  (4.5%) 7   (31.8%) 0  (0%)
10 weeks 10 (45%) 9  (40.9%) 11 (50%) 9  (40.9%)
14 weeks 9   (40.9%) 8  (36%) 8   (36%) 7  (31.8%)

Abbreviation: KOH, potassium hydroxide.
(Reprinted by permission of Blackwell Science, Inc., from Dragos V, Lunder M: Lack of efficacy of 6-week treatment with oral terbinafine for tinea capitis due to Microsporum canis in children. Pediair Dermatol 14[1]:46—48, 1997.)

mg/day for those weighing 20-40 kg; and 250 mg/day for those weighing more than 40 kg. The mycologic response was assessed at the end of treatment and after follow-up periods of 4 and 8 weeks.

Results.—After 6 weeks of treatment, none of the patients had mycologic cure by all 3 assessments; however, 7 had become culture negative. By 4 weeks’ follow-up, 9 patients had complete mycologic cure and 11 were culture negative. By 8 weeks’ follow-up, 7 patients had complete mycologic cure and 8 were culture negative. There were no systemic adverse effects.

Conclusions.—For children with M. canis tinea capitis, 6 weeks of oral terbinafine is inadequate therapy. The appropriate duration of treatment for such patients remains to be determined.

 These results should be compared with those reported above by Kullavanijaya etal. (Abstract 5-7). In that study, the organisms isolated included Trichophyton tonsurans and Microsporum ferrugineum. Patients infected with T. tonsurans responded very well, whereas the cure rates for M. ferrugineum and mixed infections were lower. All treatment failures were infected with M. ferrugineum. In the current study, many of the 22 patients infected with M. canis responded only partially. Dosage levels and treatment durations were similar in both studies and were consistent with previous recommendations. These data emphasize the importance of performing a fungal culture to identify the infecting organism at the time the clinical diagnosis is made. It is possible that higher doses given for a more prolonged period may be necessary to cure Microsporum scalp infections.

Oral Terbinafine in the Treatment of Toenail Onychomycosis: North American Multicenter Trial

Objective.—Onychomycosis affects 2.7% to 13% of the population. The condition is difficult to treat. The results of the first United States/ Canadian multicenter, double-blind, placebo-controlled, safety and efficacy 12- or 24-week study of oral terbinafine (250 mg/day) in patients with toenail onychomycosis and of the relapse rate in effectively treated patients at 72 and 96 weeks are presented.

Methods.—Either oral terbinafine (n = 142, 250 mg/day) for 12 weeks then placebo for 12 weeks, oral terbinafine (n = 145, 250 mg/day) for 24 weeks, or placebo (n = 71) for 24 weeks was administered to 358 patients, age 18-70, with subungual onychomycosis, primarily Trichophyton rubrum. This phase was followed by 24 weeks of no treatment. A cohort of patients with negative mycologic findings and at least 5 mm of new unaffected nail growth was followed for an additional 48 weeks.

Results.—During the 48-week blinded phase, terbinafine-treated patients continued to respond progressively even after cessation of 12 or 24 weeks of therapy. At week 48, 70% and 87% of 12- and 24-week-treated patients, respectively, were microscopy and culture negative compared with 9% in the placebo group. Terbinafine treatment significantly decreased the area and number of nails affected by onychomycosis during and after therapy, whereas nail involvement worsened for placebo patients. By week 48, 167 terbinafine-treated patients had negative mycologic findings, and only about 11% showed signs of relapse at 18-21 months after therapy. The 9 severe adverse events possibly or probably terbinafine-related involved the skin or gastrointestinal tract. Terbinafine was discontinued in 5 patients as a result of adverse events. Most other drug-related adverse events were mild to moderate in severity and transient.

Conclusion.—Oral terbinafine is a safe and effective treatment for toenail onychomycosis and achieves a high cure rate in a short time.

 Although the treatment response was similar in the two groups, the relapse rate was somewhat higher in patients treated for 12 weeks (the current FDA recommendation) versus 24 weeks.

Treatment of Candida Nail Infection With Terbinafine

Introduction.—Candida species cause up to one third of toenail infections and at least half of fingernail infections, and C. albicans is reported to account for 50% to 83% of the Candida species causing nail infections. Terbinafine, the first orally active antifungal drug of the allylamines class, was evaluated for its safety and efficacy in treating Candida nail infections.

Methods.—Twenty adult patients took part in an open-label study. In phase A, they received oral terbinafine (250 m g/day) for 16 weeks; a placebo was given for an additional 8 weeks in phase B. Patients then remained off treatment for 24 weeks. Target nails were selected for mycologic testing and clinical evaluation. Mycologic assessments were carried out every 4 weeks for the first 24 weeks, then every 12 weeks in the remaining 24 weeks. Clinical response was graded on a scale from 1 (complete cure) to 4 (failure, defined as clinical improvement of less than 50%).

Results.—Patients were 13 women and 7 men with a mean age of 49.9 years. At the end of the study, 12 target nails were cured, 2 had a mycologic cure, and 5 showed moderate improvement; only 1 nail was classified as a treatment failure. The candidal species most often identified was Candida parapsilosis; only 3 patients were infected with C. albicans. Overall, mycologic cure was obtained in 18 patients after a mean time of 25.8 weeks. The most rapid response was in infections caused by C. parapsilosis. Fingernail infections responded better to terbinafine than toenail infections. Only 1 patient had a relapse (at approximately 48 weeks) during 8 months of follow-up.

Conclusions.—Oral terbinafine (250 mg/day) taken for 16 weeks was effective in the treatment of Candida nail infections. Although an earlier and better response was obtained in cases involving C. parapsilosis compared with C. albicans, end results were almost identical after 48 weeks. Because 2 patients exhibited a reversible elevation of liver enzymes, monitoring for liver enzyme values should be performed during the first month of treatment.

 These results are in accord with a previous study in which clinical and mycologic cures were achieved in 52% of toenails and in 65% of fingernails. The cure rates according to pathogen were 63% for C. parapsilosis and 52% for C. albicans.

A Multicenter, Placebo-controlled, Double-blind Study of Intermittent Therapy With Itraconazole for the Treatment of Onychomycosis of the Fingernail

Introduction.—In skin and nail infections caused by yeasts, dermatophytes, and molds, itraconazole, a broad-spectrum triazole antimycotic agent, has been shown to be effective. Sustained concentrations of drug in the nail are produced by intermittent dosing, or pulse therapy. The effects of this type of pulse therapy were found to be comparable with continuous itraconazole therapy. In patients with onychomycosis of the fingernails, the efficacy and safety of itraconazole given at 200 mg twice daily during the first week of each month for 2 months was devaluated.

Methods.—Itraconazole or placebo was randomly assigned to 73 patients with clinically and mycologically diagnosed fingernail onychomycosis. Evaluation occurred at baseline, week 5, week 12, and week 24. In 46 patients (22 receiving itraconazole and 24 receiving placebo), efficacy of the treatment was evaluated, with clinical success being defined as a global evaluation of cleared or markedly improved nails.

Results.—Itraconazole treatment produced greater clinical success (77% vs. 0%), greater mycologic success (73% vs. 13%), and overall success (68% vs. 0%) than placebo. During the follow-up, clinical or mycologic relapse did not occur in any itraconazole-treated patient. Adverse events occurred in 9 placebo-treated patients (26%) and 10 itracona¬zole-treated patients (28%). For safety reasons, 3 patients discontinued treatment.

Conclusion.—Significantly greater clinical, mycologic, and overall success was produced with pulse therapy with itraconazole than with placebo. For fingernail onychomycosis, short-term itraconazole pulse therapy is well tolerated and effective.

 This study, conducted by some of the foremost nail experts in the country, was a multicenter, double-blind, placebo-controlled trial undertaken to determine the efficacy of pulse therapy with itraconazole in the treatment of fingernail onychomycosis. Early investigations using pulse therapy with itraconazole for the treatment of toenail onychomycosis suggested that 3 or 4 monthly pulses (with treatment given for 1 week per month) were necessary for optimal effect. In this study, researchers demonstrate that 2 monthly pulses of itraconazole, 200 mg twice daily for 1 week, provide both clinical and mycologic success, compared with placebo, when treating infected fingernails.

Unfortunately, the follow-up period was relatively short, concluding only 24 weeks into the study. It may be important to follow these patients for a longer period to assess the true incidence of relapse. Nonetheless, these studies suggest that fewer treatment pulses may be necessary for fingernail onychomycosis than for toenail onychomycosis, resulting in cost savings, increased patient compliance, and, possibly, fewer side effects.

Itraconazole Therapy Is Effective for Pedal Onychomycosis Caused by Some Nondermatophyte Molds and in Mixed Infection With Dermatophytes and Molds: A Multicenter Study With 36 Patients

Introduction.—Dermatophytes, yeasts, and molds are the causative agents of onychomycosis, with onychomycosis caused by molds occurring with varying frequency, depending on the geographic location. No consistently effective therapy has been found for onychomycosis caused by molds. Itraconazole may be effective in treating onychomycosis caused by nondermatophyte molds and Candida. Patients with pedal onychomycosis caused by a mold alone or as a mixed infection of a mold and a dermatophyte were treated with itraconazole.

Methods.—There were 36 patients, and of these, 17 had a single mold infection and 19 had a mixed infection, with 8 having Aspergillus spp., 4 having Fusarium spp., 12 having Scopulariopsis brevicaulis, and 1 having Alternaria spp. Patients were excluded if they had onychomycosis caused by a dermatophyte alone or Candida species. Twenty-seven patients were treated with continuous dosing at 100 or 200 mg/day for 6-20 weeks, and 9 were treated with a 1-week pulse dosing at 200 mg twice daily for 1 week per month for 2-4 pulses.

Results.—In 8 of 9 patients who received continuous therapy (89%), and in 10 of 12 patients who received the 1-week pulse therapy (83%), clinical and mycologic cure was achieved. For the total patient group, in 15 of 17 patients (88%) with onychomycosis caused by a single mold, clinical and mycologic cure was achieved. In 16 of 19 patients (84%) with mixed infection, a clinical cure was achieved, and in 13 of 19 patients (68%) with mixed infection, a mycologic cure was achieved.

Conclusion.—For the treatment of toenail onychomycosis caused by some nondermatophyte molds alone or in combination with dermatophytes, itraconazole appears to be effective and safe. Continuous and pulse regimens are both effective and safe, with pulse therapy having the advantage of the patients being exposed to less systemic drug.

 Treatment of onychomycosis caused either by nondermatophyte molds or by mixed infections with dermatophytes and molds has remained a clinical challenge. This was a noncontrolled trial comparing different treatment regimens, both continuous dosing and pulse dosing, of itraconazole in the treatment of 36 patients with nondermatophyte or mixed infection onychomycosis. At 1 year, the authors claim clinical and mycologic cure rates ranging from 68% to 88%. How this compares with placebo or with other available treatments, including terbinafine, remains to be seen. This study does provide noncontrolled evidence that suggests itraconazole may be beneficial in the treatment of nondermatophyte mold onychomycosis, however, and suggests that further investigation may be warranted.

Childhood White Superficial Onychomycosis Caused by Trichophyton rubrum: Report of Seven Cases and Review of the Literature

Introduction.—White superficial onychomycosis (WSO) is common in adolescents and adults but rare in children. The usual causative organism is Trichophyton mentagrophytes. WSO caused by T. rubrum has never been reported in prepubertal children. The experience with 7 prepubertal children with WSO is reported.

Methods.—The medical records of 7 children with an age range of 2-9 years were reviewed. Only patients with a positive potassium hydroxide (KOH) preparation and positive fungal culture were selected.

Results.—All patients had a chalky-white, firm, platelike layer adherent to the surface of the nail plate that could be easily scraped off with a scalpel blade. Infections in all 7 children were caused by T. rubrum. Six patients also had tinea pedis, and 5 had a family history of same. Topical antifungal therapy with naftifine once daily was partly effective in some patients.

Discussion/Conclusion.—WSO occurs when fungi attack the dorsal surface of the nail plate. It may be that WSO is rare in children because their faster nail growth is inhospitable to fungal infections. The 4 clinical types of onychomycosis and their most common causative organisms are (1) distal and lateral subungual onychomycosis (T. rubrum), (2) proximal subungual onychomycosis (PSO) (T. rubrum), (3) WSO (T mentagrophytes), mainly in patients who are immunocompromised), and (4) total dystrophic onychomycosis (Candida). It may be that most WSO infections are now being caused by T. rubrum. The causative organism of WSO should be reevaluated in adults.

 This important article reports seven cases of WSO which occurred in healthy prepubertal children. All seven cases were caused by T. rubrum. This contrasts with WSO in adults, which is most often caused by T. mentagrophytes. WSO caused by T. tonsurans and C. albicans has been reported to affect fingernails in very young children. Onychomycosis is generally considered to be rare in prepubertal children, but this article suggests that it may be increasing for a number of reasons, including trauma, hyperhidrosis, poor personal hygiene, sports activities, family history of tinea pedis, immunosuppression, and increased use of nonporous athletic shoes, which soften and macerate the nail plate. In this study, the toenails were almost exclusively affected, and the onychomycosis usually was associated with tinea pedis. Only one case resolved with topical antifungal therapy alone; systemic therapy is generally necessary to clear the infection.

Itraconazole Pulse Therapy for Onychomycosis and Dermatomycoses: An Overview

Background.—New antifungal agents have had a significant impact on the treatment of onychomycosis and dermatomycoses. Itraconazole is a broad-spectrum antifungal agent used to treat onychomycosis and dermatomycoses using continuous therapy and, more recently, pulse dosing. Studies of itraconazole pulse therapy for dermatomycoses were reviewed and the data summarized.

Statistics.—Efficacy rates for tinea pedis, tinea corporis/cruris, tinea versicolor, and onychomycosis were determined from studies performed throughout the world. The study results were combined and modified for single group analysis. The result was a sample-size weighted average and standard error for each variable, with a 95% confidence interval of 1.96 X standard error.

Results.—For tinea pedis/manuum, a clinical response rate of 90% and mycologic cure rate of 76% were reported with itraconazole 200 mg twice a day for 1 week in a study of 220 participants. For tinea corporis/cruris, a clinical response rate of 90% and mycologic cure rate of 77% were reported with itraconazole 200 mg once a day for 1 week in a study of 354 participants. For toenail onychomycosis, a clinical cure rate of 58%, a clinical response rate of 82%, and a mycologic cure rate of 77% were reported at 12 months with 3 pulses of itraconazole in a study of 1,389 participants. For fingernail onychomycosis, a clinical cure rate of 78%, a clinical response rate of 89%, and a mycologic cure rate of 87% were reported at 9 months with 2 pulses of itraconazole in the same study of 1,389 participants.

Discussion.—Itraconazole pulse therapy is safe and effective for treatment of tinea pedis/manuum, tinea corporis/cruris, tinea versicolor, and onychomycosis. Further details of the studies reviewed and a list of adverse effects associated with itraconazole pulse therapy for onychomycosis are included.

 The use of the new antifungal agents to treat dermatomycoses other than onychomycosis continues to evolve. Large-scale studies are needed to determine the optimum dose and duration of therapy for itraconazole, fluconazole and terbinafine, as well as to determine their relative effectiveness and benefit-risk ratios. The azole-type antifungal agents are also commonly used in the treatment of life-threatening systemic mycoses. Will their widespread use to treat less serious skin infections lead to the development of resistant organisms?

Short-term Itraconazole Versus Terbinafine in the Treatment of Superficial Dermatomycosis of the Glabrous Skin (Tinea Corporis or Cruris)

Background.—Oral griseofulvin or ketoconazole is an effective treatment for dermatomycoses. However, these agents must be given for a relatively prolonged period, and they carry a high incidence of GI complaints and headache. Thus, they are used mainly for recalcitrant infections. Itraconazole and terbinafine, in 7-day courses, were compared for the treatment of tinea corporis and/or tinea cruris.

Methods.—The randomized, double-blind trial included 230 patients with tinea corporis or tinea cruris. They were randomized in a 2:1 ratio to receive itraconazole, 200 mg/day, or terbinafine, 250 mg/day. Each medication was taken orally with the evening meal for 7 days. The patients were monitored for 6 weeks after the start of treatment. A total of 206 patients were evaluable for efficacy. A negative microscopy or culture result was defined as a myologic cure.

Results.—On intention-to-treat analysis, the myologic cure rate was 61% with itraconazole and 53% with terbinafine at the end of double-blind treatment and 80% and 68%, respectively, at the end of follow-up.

In the evaluable patients, the myologic cure rate was 61% with itraconazole and 51% with terbinafine at the end of treatment and 81% and 68%, respectively, at the end of follow-up. Final clinical response rates were 85% with itraconazole and 75% with terbinafine. Both treatments greatly improved the target symptoms, although symptoms remained more severe in the terbinafine group than they did in the itraconazole group. Scaling, redness, and itching were all less in the itraconazole group than they were in the terbinafine group.

Conclusions.—Seven-day treatment with itraconazole and terbinafine are both mycologically and clinically effective treatments for tinea corporis and tinea cruris. Both drugs are safe, although itraconazole is significantly more effective than terbinafine. The authors recommend oral itraconazole, 200 mg/day for 7 days, for the treatment of tinea corporis or tinea cruris.

 This article does not by any means prove that itraconazole is a better drug than terbinafine. It simply suggests that for the treatment of tinea corporis or tinea cruris, a 7-day course of itraconazole 200 mg daily is more effective than terbinafine 250 mg daily. Altering the dosage of either drug or changing the duration of treatment might produce different results. Possible drug interactions must always be considered before prescribing itraconazole.

Surgical Treatment of Mycotic Toenails

Introduction.—Mycotic infection of the toenails causes thickening, discoloration, and pain. Although onychomycosis can respond to pharmaceutical therapy, some patients may require surgery. Several options for the surgical treatment of painful and dystrophic mycotic toenails were presented.

Surgical Treatments.—Total nail avulsion removes the cause of pain and allows the toenail to regrow, but antifungal therapy may be required as well to prevent recurrence. Adjunctive oral or topical therapy addresses the nail matrix and nail bed, areas likely to play a role in recurrence. Partial nail avulsion is appropriate in cases of onychocryptosis of a nail which is moderately affected by the mycotic infection. Matrixectomy, which eliminates the germinal matrix of the nail and prevents regrowth, may still be the treatment of choice in many cases of severely deformed and painful toenails. Techniques for matrixectomy include chemical, electrical, laser, and excisional procedures. The most popular method of nail matrix destruction is chemical, and the most commonly used agent is 89% phenol.

Partial excisional matrixectomies, including the Winograd and Frost procedures, have the advantage of direct visualization of the matrix tissue, but healing time may be increased. The most common total surgical excisional matrixectomy is the Zadik procedure, which uses an H-shaped excisional approach with skin flaps. Advantages include excellent exposure of the entire nail matrix, the ability to close the defect without resecting bone, and the ability to visualize and resect subungual exostoses through the incision. In a modification of the Zadik procedure, total nail avulsion is combined with relaxation incisions.

Conclusion.—The introduction of potent but safe oral antifungal agents has allowed pharmaceutical treatment of onychomycosis. In many cases of severely thickened or painful mycotic nails, however, surgical intervention is required. A number of options are available for such patients, or for patients unable to receive systemic antifungal therapy.

 Surgical intervention for onychomycosis may be indicated when the affected nail is severely dystrophic or very painful. In such cases, surgical treatment may be combined with oral antifungal therapy. The surgical approach is especially useful for patients in whom systemic antifungal therapy is contraindicated.