RESUMO

Chromoblastomycosis is a chronic, often debilitating, suppurative, granulomatus mycosis of the skin and subcutaneous tissues beginning after inoculation trauma. It occurs world-wide, but is more frequently observed in tropical countries such as Brazil. The disease is usually insidious, and the lesions increase slowly but progressively, not responding to the usual treatments and quite often reappearing. The host defense mechanism in chromoblastomycosis has not been extensively investigated. Some studies have focused on fungus-host interaction, showing a predominantly cellular immune response, with the activation of macrophages involved in fungus phagocytosis. Although phagocytosis did occur, death of fungal cells was rarely observed. The ability of Fonsecaea pedrosoi to produce secreted or cell wall-associated melanin-like components, protects against destruction by host immune cells in vitro. Until now, the T cell immune response in chromoblastomycosis is undefined. In the present work, it was shown that, in patients with the severe form of the disease, predominant production of IL-10 cytokine, low levels of IFN-gamma and inefficient T cell proliferation were induced. In contrast, in patients with a mild form of the disease, predominant production of IFN-gamma cytokine, low levels of IL-10 and efficient T cell proliferation were observed.

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A cromoblastomicose e uma infeccao subcutanea causada por fungos demacios. Essa micose ja foi diagnosticada em todo mundo, e frequente em paises de clima tropical, sendo o Brasil o primeiro pais em incidencia dessa doenca. Algumas especies de fungos demacios estao envolvidas na cromoblastomicose, no Brasil a mais comum e a Fonsecaea pedrosoi. Varios esquemas terapeuticos para o tratamento da cromoblastomicose ja foram utilizados, e ate o momento nao existe uma terapia padrao. A resistencia aos antifungicos tem sido diagnosticada grandemente, tano in vivo, como in vitro. Por causa dessa resistencia, os testes de susceptibilidade aos antifungicos precisam rapidamente ser adaptados a rotina laboratorial para uma melhor indicacao de antifungicos para os pacientes. O NCCLS desenvolveu o documento M38-A, antifungigrama acurado e preciso, mas trabalhosos, inviavel para a rotina, contudo a industria lancou a antifungigrama ETEST, bastante eficiente, pratico e rapido. E este sera nosso objeto de estudo, uma vez que o ETEST ainda nao foi testado frente aos fungos demacios. Os metodos moleculares serao aplicados de modo a estudar as variabilidades geneticas, caracter filogenetico e taxonomico, e tentaremos correlacionar as diferencas geneticas com o antifungigrama. Objetivando concluir que os metodos moleculares podem tornar-se uma ferramenta para ajudar, tanto na terapeutica como na correta identificacao do agente.

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The in vitro susceptibility of chromoblastomycosis and phaeohyphomycosis agents to antifungal drugs was appraised using the reference macrodilution method proposed by the National Committee for Clinical Laboratory Standards (NCCLS) for yeasts modified for filamentos fungi. The antifungal drugs amphotericin B, 5-fluorocytosine, intraconazole and fluconazole were tested agsints one environmental and 18 clinical isolates. This work amented the macrodilution methods proposed by NCCLS and suggests that a conidial suspension free of hyphae leads to a more reliable assay and provides for better reproducibility. The macrodilution method was performed with 10 (elevado ao 4) conidia ml-1. The MIC values ranged from 1.0 to 16.0 ug ml-1 for amphotericin B and 3.12 to 25.0 ug ml-1 for 5-fluorocytosine. A MIC range of 0.06 to 1.95 ug ml-1 was determined for itraconazole while 2.0 to 64.0 ug ml-1 was detected for fluconazole

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Amplicons of SSU and ITSI + 2rDNA of 13 strains of Fonsecaea pedrosoi and three strains of F. compacta were digested with seven restriction enzymes. In addition, the ITS1 region of strains was sequenced. With both methods significant variation was found which, however, did not coincide with established species limits based on morphology

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Congenitally athymic (nu/.nu) mice were inoculated sc with 105 conidia of Fonsecae pedrosoi and treated orally from the ls to the 16th week of infection with either a new triazole, SCH39304, or itraconazole at doses of 20 or 60 mg/kg/day. The volumes of the lesions were measured with calipers at 4 week intervals and compared statistically by the Wilcoxon test. At the end of the experiment, mice were killed and samples of thelesions were examinated histopathologically and by electron microscopy. Treatment with itraconazole or SCH39304 significantly reduced lesion sizes as compared with controls. There were no differences between the 2 drugs at the dosages used. Histopathologically, lesions of mice treated with either drug had less inflammation with fewer fungi and more diffuse fibrosis than controls. Electron microscopy showed damage to the fungal cell walls in mice treated with itraconazole or SCH39304, characterized by gaps, fragmentation, and delamination. These studies confirm clinical observations that itraconazole is effective in chromoblatomycosis and suggest that SCH39304 should be considered for clinical evaluation

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Congenitally athymic (nu/nu) mice, mice defective in NK cell and macrophage function (bg/bg) and normal BALB/c mice were inoculated sc with 10 5-6 conidia of Fonsecae pedrosoi (FP). In immunologically intact and immunodeficient mice, a local infection developed approximately 2 weeks post-inoculation and enlarged over 1-2 weeks. In bg/bg and normal nu/+ mice, lesions resolved within 5-6 weeks. However, nu/nu mice continued to have enlarging cs lesions during >4-6 months od observation. These eventually metastasized. Lesions contained, few hyphal elements and massive numbers of sclerotic bodies. Five weeks after inoculation. 10 4-6 conidia froming units/gm of tissue were recovered from lesions. Delayed type hypersensitivity and serum antibody to FP antigens were demonstrated. Adoptive transfer of lymphocytes from nu/+ mice was followed in months bu the resolution of the lesions

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Foram realizados testes de susceptibilidade "in vitro" com varias amostras de agentes, isoladas de pacientes com cromomicose frente a 5-fluorocitosina e butil-simpatol (Vasculat), nas concentracoes de 0,1, 1,0, 5,0, 10,0 mcg/ml. Em alguns casos, em que se verificou resistencia a 5-fluorocitosina, a concentracao desta chegou a 100,0 mcg/ml

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Relatam os AA. a observação de paciente do sexo masculino, de 27 anos, preto, portador de lepra tuberculóide reacional, com lesões localizadas na face, de aspecto nitidamente verrucoso. Nos antecedentes mórbidos há referência à tuberculose pulmonar ainda em tratamento e na vigência da qual ocorrem as lesões da lepra T.R. Fazem o diagnóstico diferencial com a tuberculose verrucosa que pode ser afastada cl¡nicamente e pela histopatologia que foi compatível com o diagnóstico de lepra tuberculóide reacional com lesões verrucosas. Na revisão de literatura encontraram apenas 6 trabalhos referentes à lesão verrucosa no mal de Hansen, sendo o presnte, o primeiro referido com o tipo tuberculóide reacional.

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Os AA. apresentam 2 casos de cromomicose associada à lepra, num dos quais conseguiram isolar o fungo causador da moléstia que foi identificado como Phialophora pedrosoi. Comentando a literatura mundial sôbre o assunto e ausência de diagnósticos desta associação nos principais Institutos de Pesquisa sôbre Lepra, do pa¡s, salientam a necessidade de pesquisas mais sérias para apurar as causas da raridade desta associação.

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