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Successful treatment of Aspergillusfiavus brown-black colonies identified as Aspergillusfiavus, sensitive with oral to itraconazole. Whitfield's ointment (benzoic and salicylic acids), I twice daily for several months , was ineffective, and Richard K. Scher, MD, and Jay M. Barnett, MD therefore oral itraconazole, 100 rug/day, was begun. During the 5 months of oral intraconazole treatment, no ad­ New York. New York verse effects were recognized. Improvement in nail dystrophy Systemic therapy with griseofulvin and ketoconazole was noted within I month, with the regrowth of approx.imately has been used in onychomycosis resistant to topical 1.5 rnm of nail plate. At 4 months almost all the nail plate was agents, but because of a cure rate that remains subopti­ normal (Fig. 2), and repeated KOH preparations and cultures, mal, especially in nondermatophyte and toenail infec­ which had been positive during most of the treatment, were tions, the search for more effective therapy has continued. negative. Casereport. A 47-year-old woman had had a dystrophy ofthe Discusslen, Recently a class of agents called azoles, left fourth fingernail for at least 1 year. Ex.amination revealed administered systemically and topically, have been used distal onycholysis,and marked subungual hyperkeratosis of the in the treatment of a variety of deep and superficial fun­ distal third of the digit (Fig. I). Radiographs were unremark­ gal infections. Use of the azoles should be considered in able . Initial cultures grew only Candida organisms. Topical and patients with fungal organisms sensitive to the particular oral ketoconazole treatment (200 mg once daily for 5 months) azole, who meet any of the following criteria: (1) griseo­ and laser destruction of the nail plate were unsuccessful. fulvin resistance, (2) griseofulvin nonresponsiveness, (3) On reevaluation, a KOH preparation suggested the presence griseofulvin intolerance, or (4) griseofulvindrug interac­ of species. Cultures on Sabouraud and fungal syn­ tion. Ketoconazole, an imidazole, is one of the second­ thetic amino acid media, which do not inhibit saprophytes, grew generationazoles.As with other imidazoles,ketoconazole is active against all the main superficial fungal path­ From the Departmentof Dermatology, Collegeof Physicians and Sur­ ogens,? geons,Columbia University-The Presbyterian Hospital. However, its activity against Aspergillus species Costof colorreproductions supportedbyJanssenResearchFoundation. is poor. Reprint requests: RichardK.Scher, MD, DepartmentofDermatology, Itraconazole inhibits fungal sterol synthesis principally Columbia University MedicalCenter,630 W. 168thSt., New York, through interferencewith cytochrome P-450 enzymes.' It NY 10032. is highly lipophilic" and has shown activity against a 16/4/19819

Fig. 1. Left fourth digit shows distal onycholysis, marked subungual hyperkeratosis, and partial nail plate destruction before treatment with itraconazole. Fig. 2. Regrowth of nearly entire nail plate after 4 months of treatment. Culture was neg­ ative. 749 Journal of the American Academy of 750 Briefcommunications Dermatology number of fungal species,including Aspergillusfumiga­ thetreatment ofdermatophytoses: acomparison oftwo daily tus. With a half-life of 15hours, itraconazole has 24-hour dosages. Rev Infect Dis 1987;9:SI04-8. 9. Denning OW,Tucker RM, Hanson LH, etal.Treatment of minimum inhibitory concentrations similar to those of invasive aspergillosis with itraconazole. Am J Moo 1980· and higher than ketoconazole after oral 86:791-800. ' administration.> Variations in blood levels have been re­ ported and have been attributed to induction of an enzyme active against the drug in certain geneticallypre­ disposed persons.' When taken orally, serum levels are -like pyoderma caused by not affected by food.' Excretion is mostly fecal (>85%), Pseudomonas aeruginosa: Report of a case with a small urinary component. It does not appear to in­ responsive to ciprofloxacin teract with anticoagulants, rifampin, or cyclosporine in animal studies," Karen J. Trygg, MD, and Kathi C. Madison, MD Several studies have been undertaken to assess the Iowa City. Iowa usefulness of itraconazole in superficial mycoses. In a study of more than 1000 patients with mycoses, some in­ The initial descriptionof blastomycosis-like pyoderma volving the skin, it was determined that 100 mg of itra­ has been attributed to De Azua and Sada y Pons,J who conazole administered daily for 14 days was effective for in 1903 reportedthe case ofa patient with vegetatingskin or ; 100 mgjday for 30 dayswas lesions that resembled blastomycosis or tuberculosiscutis effectivefor tinea pedisor tinea manus. Further, in a ran­ and had microscopic features of an epithelioma. Similar domized double-blind study that compared 100 mg/day cases have been reported since then; all clinicallyresem­ of itraconazole with 500 mg/day of griseofulvin (un­ bled blastomycosis, , or a halogen erup­ 2 7 knownformulation), itraconazole was foundto beat least tion. - Numerous organisms, including Staphylococcus as effectiveas griseofulvin,"When used in the treatment aureus, ~-hemolytic streptococci, Pseudomonas aerugi­ of chronic and recurrent dermatophytoses, a regimen of nasa, Proteus species, and Escherichia coli, have been 100 mg/day was found to be superior to 50 mg/day dos­ cultured from these lesions; S. aureus is the most ing in time until response, although there was no signif­ common.r" In 1957 these vegetative lesions were given icant difference in response rate," the name "-like pyoderma" by Brown and Itraconazole appears to be welltolerated. In a study of Kligman.' In 1979 Su et aJ.S proposed criteria for the di­ 185 patients given 50 or 100 mg/day, only five reported agnosis of blastomycosis-like pyoderma based on an adverse reactions. These reactions were mildand included analysisof sevencases.These include the clinicalpresen­ headache, vomiting, gastrointestinal complaints, pyrosis, tation of large verrucous plaques with multiple pustules and tachycardia. No liver enzyme or electrolyte abnor­ and elevated borders, the presence of pseudoepithelio­ malitieswere noted,"Otherstudies have confirmeda mild matous hyperplasiawith abscesses, the growth of at least side effect profile.v7,9 one pathogenicbacterial species from culture of a tissue biopsyspecimenwithnegativecultures for deep fungi and mycobacteria, negative fungal serologic findings, and a REFERENCES normal serum bromide level. The initial lesionof blasto­ I. Rosenthal SA, Stritzler R, Villafane 1. Onychomycosis mycosis-like pyoderma usually develops at a site of caused by . Arch Dermatol 1968; trauma, and either local or systemic host compromise is 97:685-7. believed to beimportant in the production of this chronic, 2. HayRJ. Thecurrentstatusof antimycotics inthe treatment vegetating tissue reaction to a superficialbacterial infec­ of local mycoses. Acta Derm Venereal Suppl (Stockh) t 986; 121:103-8. tion. 3. Ganer A, Arathoon E, Stevens DA. Initial experience in Numeroustreatments forblastomycosis-like pyoderma therapy for progressive mycoses with itraconazole, the first have been attempted, including systemic antibiotics, clinically studied triazole, Rev Infect Dis 1987;9:877-86. curettage, topical antibiotics, and carbon dioxide laser 4. Van Cutsem J, Van Gerven F, Janssen PA. Activity oforally, debridement. Although various antibiotics have been topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models. used, including penicillin and minocycline, there have Rev Infect Dis 1987;9:S15-32. been no reported trials with ciprofloxacin. We present a 5. Dupont B,Drouhet E. Earlyexperience with itraconazole in patient with blastomycosis-like pyoderma culture-posi­ vitro and in patients: pharmacokinetic studies and clinical tive for P. aeruginosa who responded to ciprofloxacin. results. Rev Infect Dis 1987;9:S71-6. 6. Janssen Research Foundation. Itraconazole: basic medical From the Department ofDermatology, University ofIowa College of information brochure. 5th ed. Piscataway, NJ: Janssen Re­ Medicine. search Foundation, 1987:55-6. 7. Cauwenbergh G, De Doncker P, Stoops K, et aJ. Itracona­ Correspondence: Kathi C.Madison, MD, Department ofDermatology, zolc inthetreatmentofhuman mycoses: review ofthreeyears 2BT, University ofIowa Hospital, Iowa City, IA 52242. of clinical experience. Rev Infect Dis 1987;9:5146-52. Reprints not available. 8. Degreef H, MarienK, DeVeylder H, et al.Itraconazole in 16/4/19565