Nardo Zaias

A method for the determination of drug effectiveness in onychomycosis: Trials with ketoconazole and griseofulvin ultramicrosize

A new method for assessing drug effectiveness in onychomycosis is presented. It is based on the clinical experience when three systemic antifungal drugs (griseofulvin, thiabendazole, and ketoconazole) are used against onychomycosis. These drugs act clinically as a barrier to the invasion of the fungus toward the proximal areas of the nail plate. A monthly quantity of normal nail plate should be produced by a given subject after the administration of an effective dose of the antifungal being tested. This quantity is best measured at monthly intervals, and this in fact reflects the normal monthly nail plate growth for the individual. Although there is a slight variation among individuals, most normal healthy subjects grow 1.5 to 2 mm of nail plate per month from their large toenails and 3 to 4 mm of nail plate per month from their fingernails. Utilizing this quantitative system, ketoconazole and griseofulvin ultramicrosize were compared in the treatment of distal subungual onychomycosis by Trichophyton rubrum. In a double-blind study, sixteen patients were treated. It appears that both griseofulvin and ketoconazole can eradicate the episode of onychomycosis. One-year use of a topical antifungal cream after clinical cure of onychomycosis prevented reinfection in the 12-month follow-up period. The use of ketoconazole in long-term therapy may result in serious side effects and should be considered carefully prior to treatment.

Efficacy of a 1-week, twice-daily regimen of terbinafine 1 % cream in the treatment of interdigital tinea pedis: Results of placebo-controlled, double-blind, multicenter trials

BACKGROUND Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence. OBJECTIVE Terbinafine, a topical fungicidal agent, was evaluated in double-blind, placebo-controlled trials (159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes. METHODS Mycologic characteristics (with potassium hydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy. RESULTS Both terbinafine and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafine had converted from positive to negative mycology compared with 23% of the patients treated with vehicle. CONCLUSION The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non-compliance.

Pitted and ringed keratolysis: A review and update

The varied clinical manifestations of pitted keratolysis in the soles and of ringed keratolysis in the palms are presented. The etiologic agent, a species of Corynebacterium, has been proved to produce similar lesions in experimental patients. The histopathology in the stratum corneum and its treatment are also summarized.

The successful treatment of pityriasis versicolor by systemic ketoconazole

A double-blind study comparing the antifungal efficacy of systemic ketoconazole in twenty volunteers who had pityriasis versicolor (mycologically proved) was done. Ketoconazole cured 90% of all volunteers taking the drug at the end of the 4-week follow-up, even though they were all treated for only 2 weeks. Of placebo-treated volunteers, 20% were cured of their disease. No adverse reactions were noted.

Multicentre double-blind clinical trials of ciclopirox olamine cream 1% in the treatment of tinea corporis and tinea cruris

In separate multicentre, randomized, double-blind clinical trials, 1% ciclopirox olamine cream was compared with its cream vehicle and with 1% clotrimazole cream as treatment for tinea corporis and tinea cruris. Patients who demonstrated clinical and mycological findings consistent with the diagnoses of tinea corporis or tinea cruris were included in the study. Clinical and mycological evaluations were made pretreatment, at the end of each of the four, weeks of treatment, and weekly for the two weeks immediately following cessation of treatment. In both studies, use of ciclopirox olamine cream resulted in demonstrable improvements after the first week of therapy and in complete clinical and mycological clearing in two thirds of the patients at the end of the treatment period. These results were maintained through the two-week drug-free observation period that followed the end of treatment. Statistically, the results with ciclopirox olamine cream were significantly better than those with the vehicle and were equivalent to those with clotrimazole cream. All treatments were well tolerated.

Treatment of chronic moccasin-type tinea pedis with terbinafine: A double-blind, placebo-controlled trial

Terbinafine is an orally and topically active fungicidal drug of the allylamine series. Its oral efficacy at 125 mg taken twice daily was evaluated in a randomized, double-blind, placebo-controlled study in moccasin-type tinea pedis. The study was conducted simultaneously in two centers and consisted of 41 evaluable cases (23 terbinafine, 18 placebo). Mycologic cure and near to complete clearing of signs and symptoms were obtained in 59% of the terbinafine-treated patients after 6 weeks of treatment and in 65% at 2 weeks after treatment. Corresponding efficacy for placebo-treated patients was zero at both evaluations. Side effects in both groups were minimal. We conclude that terbinafine is well tolerated and highly effective in moccasin-type tinea pedis.

Chronic dermatophytosis caused by Trichophyton rubrum

We believe that patients are genetically predisposed to Trichophyton rubrum infections in a dominant autosomal pattern and that persons with distal subungual onychomycosis caused by T. rubrum invariably have preexisting T. rubrum tinea pedis of the soles. This relationship has many potentially important clinical implications with respect to diagnosis, treatment, and the prevention of reinfection.

Management of onychomycosis with oral terbinafine

The safety and efficacy of oral terbinafine in the treatment of finger onychomycosis caused by Trichophyton rubrum were evaluated in an open study including 11 patients. Treatment consisted of 125 mg of terbinafine given twice daily for 6 months or until the infection cleared. At the end of the treatment period, all patients were clinically and mycologically normal, with the drug acting as a fungal barrier to prevent further distal fungal invasion into the nailplate. Mild gastric discomfort in one patient was the only side effect reported during this study. No laboratory abnormalities were detected.

Efficacy of terbinafine 1% cream in the treatment of moccasin-type tinea pedis: Results of placebo-controlled multicenter trials

I. Dicken CH, Carrington SG, Winkelmann RK. Generalized granulomaannulare. Arch DermatolI969;99:556-63. 2. Mobacken H, Gisslen H, Johannisson G. Granuloma annulare:cortisone-glucose tolerancetest in a non-diabetic group. Acta Derm Venereal (Stockh) 1970;50:440-4. 3. Williamson DM, Dykes JRW. Carbohydrate metabolism in granuloma annulare. J InvestDermatol 1972;58:400-4. 4. BlohmeG, MobackenH, WaldenstromJ. Early insulinresponseto glucoseinjectedintravenously in patientswith 10calizedgranulomaannulare. ActaDerm Venereal(Stockh) 1974;54:259-63. 5. Haim S, Friedman-BirnbaumR, Shafir A, et al. Generalized granulomaannulare: relationshipto diabetes mellitus as revealed in 8 cases. Br J DermatoI1970;83:302-5. 6. Hammond R, DyessK, Castro A. Insulin productionand glucosetolerancein patients with granuloma annulare. Br J DermatoI1972;87:540-7. 7. Andersen BL, VerdichJ. Granuloma annulare and diabetes mellitus. Clin Exp Dermatol 1979;4:31-7. 8. Muhlemann MF, Williams DDR. Localized granuloma Briefcommunications 663

Comparison of once- and twice-daily naftifine cream regimens with twice-daily clotrimazole in the treatment of tinea pedis

1. Steere AC, Malawista SE, Bartcnhagen NR, et al. The clinical spectrum and treatment of Lyme disease. Yale J Bioi Med 1984;57:453-61. 2. Berger BW. Erythema chronicum migrans of Lyme disease. Arch DermatoI1984;120:1017-21. 3. Kramer N, Rickert RR, Brodkin RH, et al. Septal panniculitis as a manifestation of Lyme disease. Am J Med 1986; 81:149-52. 4. Eichenfield AR, Goldsmith DP, Benach JL, et al. Childhood Lyme arthritis: experience in endemic area. J Pediatr 1986;109:753-8. 5. Russell H, Sampson JS, Schmid GP, et al. Enzyme-linked immunosorbent assay and indirect immunofluorescence assay for Lyme disease. ] Infect Dis 1984;149:465-70. 6. Duffy J, Mertz LE, Wobig GH, et al. Diagnosing Lyme disease: the contribution of serologic testing. Mayo Clin Proc 1988;63: 1116-21. 7. Gammon WR. Urticarial vasculitis. Dermatol Clin 1985; 3:97-105. 8. Monroe EW, Schulz CI, Maize JC, et al. Vasculitis in chronic urticaria: an immunopathologic study. J Invest DcrmatoI1981;76:103-7. 9. Midgard R, Hofstad R. Unusual manifestations of nervous system Borrelia burgdorferi infection. Arch Neurol J987; 44:781-3. 10. Camponovo F, Meier C. Neuropathy of vasculitic origin in a case of Garin-Boujadoux-Bannwarth syndrome with positive Borrelia antibody response. J Ncurol 1986;233: 69-72.