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Treatment of chromoblastomycosis
Volume 25 Number 5, Part I November 1991
Treatment of chromoblastomycosis TotheEditor: Wereadwithgreatinterest thecasereport by Tuffanelli and Milburn (J AM ACAD DERMATOL 1990;23:728-32). Indeed, the diagnosis ofchromoblastomycosis poses noparticulardifficulties because directmicroscopic examination of the squames clearly shows the "fumagoide cells" (sclerotic bodies). Weprefer to callthe illness chromomycosis because the species of fungi involved are never present in tissue as yeasts.' In contrast, the treatment of chromomycosis is difficult. Newantifungal agents, including itraconazole, offer hope, especially for thosecases caused by Fonsecaea pedrosoi, thepathogen most resistant totreatment. We reo cently studied three cases of chromomycosis in French Guiana.i all of which had proved resistant to a yearlong course ofitraconazole as the sole therapy (thedaily dose varying between 100 and 400 mg). Previously, all three patients hadalso shown littleresponse to other drugs such as thiabendazole, miconazole, and 5-fluorocytosine (5FC). The combination of 5-FC with itraconazole achieved clinical and mycologic remission in thesethreepatients, which occurred within 20 days and 2 and 7 months. It seems that the combination of S-FCand itraconazole is preferable to their use in isolation from oneanother because it reduces themajordifficulties ofthetreatment: (1) Side effects are less common through the use of lower doses. (2) Because of reduced duration of treatment, resistance to 5-FCoccurs less often. (3) Recurrences seem tobeless numerous because thetwodrugs appear to synergistically enhance eachother's action, thereby renderingsterilization of the lesions more likely. The combination of 5-FC and ketoconazole has never, toourknowledge, completely curedchromomycosis.f 4 In vitro thiscombination hasan additive and nota synergistic action.' The activity of ketoconazole is reduced in poorly controlled diabetes mellitus," However, this particular reduction in potency has never been shown with itraconazole, apart from the New Yorkcase. Thesynergistic action ofthe 5-FC-itraconazole combination in vitro' prompts us to believe that this regimen (150 mg/kg/day of 5-FC, 200 mg/day ofitraconazole) is currently the best available treatmentfor chromomycosis. We have also tried to distinguish the criteria for cessation of treatmentfrom thoseof healing because the two events are notsynchronous in thiscondition. (1) The treatment should be stopped after a period twice that required for clinical healing and after direct examination has yielded normal results. (2) Cure will be confirmed only aftera follow-up period of 5 years, analogous to the principle used in oncology, to detect late relapses. The trendtowards combinations ofantifungal agents, withthe
Correspondence 869 use of precise protocols, will certainly enhance our knowledge of chromomycosis and hopefully give risetoa radically curative therapy.
Roger Pradinaud, MD, and Thomas Eo/zinger, MD Department ofDermatology, Hbpital Jean Martial, 97300 Cayenne, French Guiana REFERENCES 1. McGinnis MR. Chromoblastomycosis and phaeohyphornycosis: new concepts, diagnosis, and mycology. J AM ACAD DERMATOL 1983;8:1-16. 2. Bolzinger T,Pradinaud R,Sainte MarieD, et al. Traitement de quatre cas dechromomycose Ii Fonsecaea pedrosoi par l'association 5-fluorocytosine-itraconazole. Nouv Dermatol 1991;10:462-6. 3. Atukorala DN, Pothupitiya OM. Treatment ofchromomycosis with a combination of ketoconazole and 5-fluorocytosine, Ceylon Med J 1985;30:193-5. 4. Silber JG, Gombert ME, Green KM, et al. Treatment of chromomycosis with ketoconazole and 5-fluorocytosine. J AM ACAD DERMATOL 1983;8:236-8. 5. Polak A. Combination therapy with antifungal drugs. Mycoses 1988;31 :45-53. 6. Symoens J, Moons M, Dom J, et al.An evaluation oftwo years ofclinical experiencewith ketoconazole. Rev Infect Dis 1980;2:674-87.
Reply To theEditor: Wefound the comments of Drs.Pradinaud and Bolzinger informative and useful. McGinnis 1 presents the arguments as to why the term chromoblastomycosis ispreferable. Although there isvaluein knowing whether single drug therapy is effective, in fact we would have preferred to treat our patient with 5-fluorocytosine in addition to itraconazole, rather than itraconazole alone, given the past experience with the combination of ketoconazole and 5-fluorocytosine in our institution.? The itraconazole used to treat our patient was obtained from Janssen Pharmaceutica under a compassionate protocol. Food and Drug Administration restrictions didnotallow the useof anyadditional medications. Hopefully itraconazole will be approved for use in the United States soon. Criteria forcessation of treatmentandcure need to be verified experimentally. Fiveyears maybe an excessively longtimetoconfirm a cure.We lookforward to the testing of these and other criteria. PeterB. Milburn, MD, and Lucia Tuffanelli, MD State University ofNew York Health Science Center Box 46 Brooklyn, NY 11203
Treatment of chromoblastomycosis TotheEditor: Wereadwithgreatinterest thecasereport by Tuffanelli and Milburn (J AM ACAD DERMATOL 1990;23:728-32). Indeed, the diagnosis ofchromoblastomycosis poses noparticulardifficulties because directmicroscopic examination of the squames clearly shows the "fumagoide cells" (sclerotic bodies). Weprefer to callthe illness chromomycosis because the species of fungi involved are never present in tissue as yeasts.' In contrast, the treatment of chromomycosis is difficult. Newantifungal agents, including itraconazole, offer hope, especially for thosecases caused by Fonsecaea pedrosoi, thepathogen most resistant totreatment. We reo cently studied three cases of chromomycosis in French Guiana.i all of which had proved resistant to a yearlong course ofitraconazole as the sole therapy (thedaily dose varying between 100 and 400 mg). Previously, all three patients hadalso shown littleresponse to other drugs such as thiabendazole, miconazole, and 5-fluorocytosine (5FC). The combination of 5-FC with itraconazole achieved clinical and mycologic remission in thesethreepatients, which occurred within 20 days and 2 and 7 months. It seems that the combination of S-FCand itraconazole is preferable to their use in isolation from oneanother because it reduces themajordifficulties ofthetreatment: (1) Side effects are less common through the use of lower doses. (2) Because of reduced duration of treatment, resistance to 5-FCoccurs less often. (3) Recurrences seem tobeless numerous because thetwodrugs appear to synergistically enhance eachother's action, thereby renderingsterilization of the lesions more likely. The combination of 5-FC and ketoconazole has never, toourknowledge, completely curedchromomycosis.f 4 In vitro thiscombination hasan additive and nota synergistic action.' The activity of ketoconazole is reduced in poorly controlled diabetes mellitus," However, this particular reduction in potency has never been shown with itraconazole, apart from the New Yorkcase. Thesynergistic action ofthe 5-FC-itraconazole combination in vitro' prompts us to believe that this regimen (150 mg/kg/day of 5-FC, 200 mg/day ofitraconazole) is currently the best available treatmentfor chromomycosis. We have also tried to distinguish the criteria for cessation of treatmentfrom thoseof healing because the two events are notsynchronous in thiscondition. (1) The treatment should be stopped after a period twice that required for clinical healing and after direct examination has yielded normal results. (2) Cure will be confirmed only aftera follow-up period of 5 years, analogous to the principle used in oncology, to detect late relapses. The trendtowards combinations ofantifungal agents, withthe
Correspondence 869 use of precise protocols, will certainly enhance our knowledge of chromomycosis and hopefully give risetoa radically curative therapy.
Roger Pradinaud, MD, and Thomas Eo/zinger, MD Department ofDermatology, Hbpital Jean Martial, 97300 Cayenne, French Guiana REFERENCES 1. McGinnis MR. Chromoblastomycosis and phaeohyphornycosis: new concepts, diagnosis, and mycology. J AM ACAD DERMATOL 1983;8:1-16. 2. Bolzinger T,Pradinaud R,Sainte MarieD, et al. Traitement de quatre cas dechromomycose Ii Fonsecaea pedrosoi par l'association 5-fluorocytosine-itraconazole. Nouv Dermatol 1991;10:462-6. 3. Atukorala DN, Pothupitiya OM. Treatment ofchromomycosis with a combination of ketoconazole and 5-fluorocytosine, Ceylon Med J 1985;30:193-5. 4. Silber JG, Gombert ME, Green KM, et al. Treatment of chromomycosis with ketoconazole and 5-fluorocytosine. J AM ACAD DERMATOL 1983;8:236-8. 5. Polak A. Combination therapy with antifungal drugs. Mycoses 1988;31 :45-53. 6. Symoens J, Moons M, Dom J, et al.An evaluation oftwo years ofclinical experiencewith ketoconazole. Rev Infect Dis 1980;2:674-87.
Reply To theEditor: Wefound the comments of Drs.Pradinaud and Bolzinger informative and useful. McGinnis 1 presents the arguments as to why the term chromoblastomycosis ispreferable. Although there isvaluein knowing whether single drug therapy is effective, in fact we would have preferred to treat our patient with 5-fluorocytosine in addition to itraconazole, rather than itraconazole alone, given the past experience with the combination of ketoconazole and 5-fluorocytosine in our institution.? The itraconazole used to treat our patient was obtained from Janssen Pharmaceutica under a compassionate protocol. Food and Drug Administration restrictions didnotallow the useof anyadditional medications. Hopefully itraconazole will be approved for use in the United States soon. Criteria forcessation of treatmentandcure need to be verified experimentally. Fiveyears maybe an excessively longtimetoconfirm a cure.We lookforward to the testing of these and other criteria. PeterB. Milburn, MD, and Lucia Tuffanelli, MD State University ofNew York Health Science Center Box 46 Brooklyn, NY 11203