Histoplasma panniculitis in a patient with systemic lupus erythematosus

Abstract: Histoplasmosis usually presents primarily as lung infection. Occasionally, mainly in immunocompromised hosts, it can spread and cause systemic manifestations. Skin lesions have been reported in 10 to 15 percent of cases of disseminated histoplasmosis, and panniculitis has been described as an unusual form of presentation in affected patients. We present the case of a patient with systemic lupus erythematosus who presented cellulitis due to disseminated histoplasmosis.

Atypical presentation of histoplasmosis in an immunocompromised patient

We present a case of disseminated cutaneous histoplasmosis in a male patient, rural worker, HIV positive for 20 years, with a history of irregular use of antiretroviral therapy, T cell counts below 50 cells/mm3 and with good response to treatment with Itraconazole. We highlight importance of skin lesions in clarifying early diagnosis, since this co-infection often leads patients to death.

Cutaneous histoplasmosis as a complication after anti-TNF use - Case report

Anti-TNF agents are effective in the treatment of psoriasis. However, they render individuals more susceptible to infections. We report an atypical case of histoplasmosis in an immunosuppressed patient due to anti- TNF therapy. A patient who used anti-TNF for the treatment of psoriasis had had a lesion on the right eyebrow since discontinuation of the medication. The diagnostic hypothesis was basal cell carcinoma, but the histopathological examination was compatible with histoplasmosis.

Primary cutaneous histoplasmosis developed in the penis of an immunocompetent patient

A 70-year-old male presenting a 3-month history of genital painless erythematous nodules in the balanopreputial sulcus was referred to our service. Histopathological exam presented a chronic dermatitis with epithelioid granulomas and Grocott staining revealed numerous fungal structures with a suggestive morphology of Histoplasma sp. Cultures evidenced Histoplasma capsulatum var. capsulatum. Treatment with oral itraconazole led to complete remission of lesions.

Histoplasmosis in immunocompetent individuals living in an endemic area in the Brazilian Southeast

Introduction The distribution of infection by Histoplasma capsulatum in Brazil is heterogeneous, and the number of cases affecting immunocompetent individuals is relatively small. This study reports the epidemiological and clinical data regarding histoplasmosis in non-immunosuppressed individuals. Methods The study included only the immunocompetent patients with histoplasmosis who were diagnosed between 1970 and 2012 at a university hospital located in Ribeirão Preto, State of São Paulo, Brazil. Clinical and epidemiological data were collected retrospectively from the patient records. Results Of the 123 patients analyzed, 95 had an active disease that manifested in the different clinical forms of histoplasmosis. Men were the predominant gender, and most patients resided in the Northeast of the State of São Paulo and in the nearby municipalities of the State of Minas Gerais. The risk factors for acquiring histoplasmosis and prolonged contact in a rural environment were recorded in 43.9% and 82.9% of cases, respectively. Smoking, alcoholism, and comorbidity rates were high among the patients with the chronic pulmonary and subacute/chronic disseminated forms of histoplasmosis. Many patients achieved clinical cure spontaneously, but 58.9% required antifungals; the disease lethality rate was 5.3%. Conclusions Immunocompetent individuals manifested the diverse clinical forms of histoplasmosis over a period of 4 decades, revealing an additional endemic area of this fungal disease in the Brazilian Southeast. .

Carbohydrate-rich high-molecular-mass antigens are strongly recognized during experimental Histoplasma capsulatum infection / Antígenos de alta massa molecular ricos em carboidratos são fortemente reconhecidos durante infecção experimental por Histoplasma capsulatum

INTRODUCTION: During histoplasmosis, Histoplasma capsulatum soluble antigens (CFAg) can be naturally released by yeast cells. Because CFAg can be specifically targeted during infection, in the present study we investigated CFAg release in experimental murine histoplasmosis, and evaluated the host humoral immune response against high-molecular-mass antigens (hMMAg. >150 kDa), the more immunogenic CFAg fraction. METHODS: Mice were infected with 2.2x10(4) H. capsulatum IMT/HC128 yeast cells. The soluble CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg circulating immune complexes (CIC) levels were determined by enzymelinked immunosorbent assay, at days 0, 7, 14, and 28 post-infection. RESULTS: We observed a progressive increase in circulating levels of CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg CIC after H. capsulatum infection. The hMMAg showed a high percentage of carbohydrates and at least two main immunogenic components. CONCLUSIONS: We verified for the first time that hMMAg from H. capsulatum IMT/HC128 strain induce humoral immune response and lead to CIC formation during experimental histoplasmosis.

INTRODUÇÃO: Durante a histoplasmose, os antígenos solúveis de Histoplasma capsulatum (CFAg) podem ser liberados naturalmente pelas células leveduriformes. Considerando que os CFAg constituem um alvo específico durante a infecção, no presente estudo nós investigamos a liberação de CFAg durante a histoplasmose murina experimental, e avaliamos a resposta imune humoral do hospedeiro contra antígenos de alta MM (hMMAg; >150 kDa), altamente imunogênicos. MÉTODOS: Camundongos foram infectados com 2.2x10(4) leveduras de H. capsulatum, cepa IMT/HC128. Os níveis de CFAg solúveis, IgG anti-CFAg, IgG anti-hMMAg, e também de imunocomplexos circulantes (CIC) IgG-hMMAgs foram determinados por ELISA nos dias 0, 7, 14 e 28 após a infecção. RESULTADOS: Após a infecção por H. capsulatum, observamos um aumento progessivo de CFAg circulantes, IgG anti-CFAg, IgG anti-hMMAg, e também de CIC IgG-hMMAgs. Os hMMAg apresentaram alta porcentagem de carboidratos e, pelo menos, dois componentes imunogênicos. CONCLUSÕES: Mostramos pela primeira vez que os hMMAg de H. capsulatum cepa IMT/HC128 induzem resposta imune humoral e levam à formação de CIC durante a histoplasmose experimental.

Una actualización acerca de histoplasmosis / Histoplasmosis updating

La histoplasmosis infección causada por el hongo Histoplasma capsulatum ha sido reportada en todos los continentes y se considera endémica en el continente americano, incluida Cuba. El hongo se desarrolla en el suelo con excretas de aves y murciélagos, donde es capaz de producir abundantes microconidios, que al ser inhalados por el hombre son capaces de causar la infección. El cuadro clínico puede variar, desde infecciones asintomáticas hasta cuadros diseminados graves que involucran a uno o varios órganos y sistemas y que afectan sobre todo a pacientes con sida, neoplasias hematológicas, con trasplantes u otras inmunodeficiencias. Los principales grupos de riesgo incluyen además, aquellos individuos que por razones ocupacionales se expongan los aerosoles contaminados con el hongo. El diagnóstico de laboratorio se basa en la observación de este en fluidos y tejidos orgánicos, en el cultivo de esos materiales y en la detección de anticuerpos y antígenos específicos. Los métodos moleculares, en especial mediante la reacción en cadena de la polimerasa, aunque no han sido suficientemente evaluados, pudieran representar un importante avance en el diagnóstico temprano de esta micosis. Para el tratamiento de las formas agudas moderadas, localizadas y respiratoria crónica se recomienda el itraconazol, mientras que para las formas graves y diseminadas la droga de elección es la anfotericina B, con preferencia en alguna de sus formulaciones lipídicas. La histoplasmosis representa hoy una de las micosis sistémicas más importante en las Américas, con una amplia distribución en todas las regiones de Cuba.

Histoplasmosis, an infection caused by the fungus Histoplasma capsulatum, has been reported all over the world and is considered endemic in the American continent, including Cuba. This fungus grows on the soils contaminated with bird and bat excreta, where it produces a great number of microconidia that could cause the infection when they are inhaled. The clinical spectrum varies from asymptomatic infections to serious disseminated diseases involving one or many organ systems and affects mainly AIDS patients, patients with hematological neoplasias, transplant recipients or other immunosuppressed patients. The main risk groups include those individuals whose working activities make them be exposed to aerosols contaminated with H. capsulatum. Lab diagnosis is based on the microscopic observation, isolation and identification of the fungus in fluid or tissue samples of patients, and on specific antigen and antibodies detection. The molecular methods based on polymerase chain reaction have not been sufficiently defined, and they could be an important advance in the early diagnosis of this mycosis. Itraconazole is recommended for treatment of moderate, localized and chronic infection whereas amphotericin B is the drug of choice for disseminated and serious manifestations, particularly in its lipidic formulations. At present, histoplasmosis is considered one of the most important systemic mycoses in the Americas, and it is widely spread over all regions of Cuba.

Síndrome de restauração imune associada à histoplasmose / Histoplasmosis-associated immune reconstitution inflammatory syndrome

Paciente masculino, 27 anos, portador de HIV, com quadro de histoplasmose cutânea disseminada. Terapia antirretroviral oral e anfotericina B por via EV (dose total acumulada 0,5g) foram introduzidas, verificando-se rápida cicatrização das lesões após duas semanas. A anfotericina B foi substituída por itraconazol (200mg/dia). O paciente interrompeu voluntariamente os tratamentos. A terapia antirretroviral foi reintroduzida, havendo aumento da contagem de células T CD4-positivas (No restante do texto, a autora usa o símbolo "+" (T CD4+) ao invés da palavra "positiva". O que fazer neste caso? Seguimos o padrão do restante do texto ou acatamos essa opção da autora no resumo?!). Neste momento, diagnosticou-se histoplasmose ganglionar. O aumento da contagem de células T CD4-positivas (de novo aqui), associado à redução da carga viral a níveis inferiores ao limite de detecção após a reintrodução da terapia antirretroviral, sugere que essa piora clínica paradoxal seja uma síndrome de restauração imune.

A 27-year-old HIV-positive male patient with disseminated cutaneous histoplasmosis was treated with both HAART and amphotericin B (total accumulated dose of 0.5g). Amphotericin B was later replaced with itraconazole (200mg/day). Two months after therapy had been started and the cutaneous lesions had healed, the patient interrupted both treatments voluntarily and his health deteriorated. HAART was then re-introduced and CD4+ cell count increased sharply at the same time as lymph node histoplasmosis was diagnosed. This paradoxical response? the relapse of histoplasmosis and concomitant increase in CD4+ cell count and undetectable viral load after resumption of HAART ? suggests that this was a case of immune reconstitution inflammatory syndrome (IRIS).

The interaction between Histoplasma capsulatum cell wall carbohydrates and host components: relevance in the immunomodulatory role of histoplasmosis

Histoplasma capsulatum is an intracellular fungal pathogen that causes respiratory and systemic disease by proliferating within phagocytic cells. The binding of H. capsulatum to phagocytes may be mediated by the pathogen's cell wall carbohydrates, glucans, which consist of glucose homo and hetero-polymers and whose glycosydic linkage types differ between the yeast and mycelial phases. The ±-1,3-glucan is considered relevant for H. capsulatum virulence, whereas the ²-1,3-glucan is antigenic and participates in the modulation of the host immune response. H. capsulatum cell wall components with lectin-like activity seem to interact with the host cell surface, while host membrane lectin-like receptors can recognize a particular fungal carbohydrate ligand. This review emphasizes the relevance of the main H. capsulatum and host carbohydrate-driven interactions that allow for binding and internalization of the fungal cell into phagocytes and its subsequent avoidance of intracellular elimination.

Mucocutaneous nasal histoplasmosis in an immunocompetent young adult.

A case of mucocutaneous nasal histoplasmosis in an immunocompetent host is described below. A 30-year-old male had a broadened nose with swelling and repeated blockage of nasal passages for the past six months. Diagnosis was made on the basis of histological demonstration of characteristic yeast cells of Histoplasma capsulatum var. capsulatum occurring within histiocytes and extracellularly in stained smears of fine needle aspirates and biopsy from the lesions in ala of the nose and perioral region. The patient showed appreciable regression of lesions after three weeks of itraconazole therapy but was not available for re-assessment.

Histoplasmoma como lesão isolada do sistema nervoso central em paciente imunocompetente / Histoplasmoma as isolated central nervous system lesion in an immunocompetent patient

O acometimento cerebral pela histoplasmose é raro, ocorrendo mais comumente sob a forma de doença disseminada. Raramente, a doença pode ocorrer sob a forma de histoplasmomas, que simulam tumores do sistema nervoso central. Mais raro ainda é a ocorrência de histoplasmomas em pacientes imunocompetentes como única manifestação desta infecção. Neste relato é apresentado um paciente masculino de 13 anos com cefaléia, vômitos, redução da acuidade visual e auditiva à esquerda e hemiparesia à direita. A ressonância magnética mostrou lesão expansiva com impregnação anelar de contraste, localizada na região talâmica, hipotalâmica e quiasmática à esquerda. Foi realizada biópsia estereotáxica e a avaliação histológica do material definiu o diagnóstico de histoplamose. Iniciou-se tratamento com fluconazol, com melhora clínica importante após 6 meses do início do tratamento.

Immune responses in histoplasmosis, a prototype of respiratory mycoses.

The cellular and molecular mechanisms of host defenses to histoplasmosis, a prototype of respiratory fungal infections are described. Although, cell-mediated acquired immunity is considered as a hallmark of protective immunity to histoplasmosis, the recent findings provide mounting evidence on the importance of natural cellular immunity in host resistance to fungal infections. The natural immunity to Histoplasma capsulatum infection is primarily mediated by natural killer cells, endothelial cells and platelets but mechanisms of intercellular communication and their interactions with the pathogen are not clearly defined.

Atypical disseminated cutaneous histoplasmosis in an immunocompetent child, caused by an aberrant variant of Histoplasma capsulatum var. capsulatum

O presente trabalho registra caso de histoplasmose em paciente de 5 anos, HIV negativo, natural e procedente da cidade da Sao Paulo, com lesoes cutaneas nao diagnosticadas clinicamente. Exame histopatologico negativo para infeccao fungica. Cultivos em duas ocasioes, positivos para Histoplasma capsulatum var. capsulatum (amostras 361 e 387). Sorologia negativa para anticorpos anti-Histoplasma capsulatum e Paracoccidioides brasiliensis pelas provas de Imunodifusao dupla e ...

Tipificación de aislados clínicos de Histoplasma capsulatum por métodos fenotípicos y genotípicos / Typing of Histoplasma capsulatum clinical isolates by phenotype and genotype methods

Objetivo: El presente trabajo plantea el estudio fenotípico y genotípico de cinco aislados de Histoplasma capsulatum obtenidos de pacientes mexicanos con hostoplasmosis asociada a síndrome de inmunodeficiencia adquirida (SIDA), con procedencia geográfica bien establecida. Material y métodos: Se utilizaron para relacionar estos aislados clínicos, electrofóresis en geles de poliacrilamida dodecil sulfato de sodio (SDS-PAGE) y electroinmunotransferencia (EIT) para la fenotipificacion, y el polimorfismo del DNA amplificado al azar por la reacción en cadena de la polimerasa (RAPD-PCR) para la genotificación. Las relaciones enter los patrones electoforéticos y polimórficos de todos los aislado se procesaron en el programa SPSS/PC+ versión 2.3. Resultados y discusión: Por SDS-PAGE se observó que todos los aislados se relacionaron en un 86 por ciento. Por EIT se evidenció que todos los aislados revelaron tres bandas de 43, 28 y 18 kDa con suero inmune específico. Por RAPD-PCR, cuatro aislados se relacionaro en 94 por ciento y el último (EH-319) presentó 77 por ciento de relación con los anteriores. Conclusión: El análisis por RAPD.PCR permitió discriminar ligeras diferencias entre los aislados de pacientes mexicanos con histoplasmosis asociada a SIDA, en comparación con los métodos de caracterizacion fenotípica (SDS-PAGE y EIT)

Inmunogénetica de la histoplasmosis / Immunogenetic of histoplasmosis

Introducción: La histoplasmosis es una micosis causada por Histoplama capsulatum: La enfermedad tiene una alta prevalencia en países del continente americano donde los climas tropical y subtropical favorecen el crecimiento del hongo. En la susceptibilidad a la infección se ha descrito la participación de factores inmunológicos, ocupacionales y genéticos. En cuanto a los factores genéticos, los genes del Sistema Principal de Histocompatibilidad (SPH) se han asociado con la susceptibilidad a la histoplasmosis y otras enfermedades. En el humano estos genes se localizan en el cromosoma seis, son muy polimórficos, y sus productos son antígenos HLA, impotantes en la regulación de la respuesta inmunológica contra agentes extraños. Factores genéticos asociados a la histoplasmosis: Estudios realizados en la población mexicana han mostrado que los alelos HLA-B17 y HLA-B22, son frecuentes en pacientes con histoplasmosis pulmonar; el último contenido en el haplotipo extendido [HLA-A2, B22, Cw5]. Por la frecuencia en estos pacientes lo alelos referidos podrían servir como marcadores para la enfermedad. Por lo anterior, se sugiere un efecto predisponentes para la infección y el desarrollo de histoplasmosis en individuos que presentan estos alelos

Producción de antígenos fúngicos autóctonos en el inmunodiagnóstico de micosis en México / Production of fungal antigens from local strains for the immunodiagnosis of mycoses in Mexico

La elaboración de antígenos fúngicos con buena reactividad y especificidad son indispensables para las pruebas inmunológicas que son útiles en el diagnóstico y pronóstico de las enfermedades micóticas. Las diferencias antigénicas de cepas provenientes de diversas regiones plantean la conveniencia de conocer las características morfológicas, antigénicas y moleculares. Este documento presenta datos de antígenos crudos y purificados de Histoplasma capsulatum, Coccidioidis immitis y paracoccidioides brasiliensis que son los de mayor patología en México. Los antígenos crudos de histoplasmina, coccidioidina y paracoccidioidina, constituidos principalmente por moléculas glicoproteínicas, muestran buena reactividad en pruebas de precipitación e intradérmicas. Los purificados (CCPD: complejo polisacárido-proteína desproteinizado) exhiben mayor grado de especificidad que los crudos en pruebas de alta sensibilidad como ELISA y fijación de complemento. Los antígenos crudos son de bajo costo, fácil manejo y rápida detección y son ideales para estudios epidemiológicos; los purificados son ideales para precisar mejor un diagnóstico de micosis

Estudio de 102 casos de histoplasmosis no asociada al SIDA diagnosticados en el Hospital Muñiz durante 1975-1994 / Study of 102 cases of histoplasmosis not associated to AIDS, diagnosed in Muñiz Hospital of Buenos Aires, during 1975-1994

Se estudiaron algunos aspectos epidemiológicos y diagnósticos de 102 casos (89 varones y 13 mujeres) de histoplasmosis (HP) no asociada al SIDA diagnosticados en el Hospital Muñiz (HM) entre 1975 y 1994. La mediana de la edad (ME) de la población estudiada fue de 55 años (rango 9-79); 55 años (9-78) en los varones y 59 años (22-79) en las mujeres. Las causas predisponentes más frecuentes, solas o asociadas a otros factores de riesgo, fueron el tabaquismo (60 por ciento) y el alcoholismo (58 por ciento). Las biopsias de lesiones mucosas bucales, nasales y laríngeas permitieron el diagnóstico inicial en el 54 por ciento de los casos. La realización de tareas características de los centros urbanos fueron referidas por el 77 por ciento de los pacientes y las tareas rurales dentro del área endémica de la micosis por sólo el 23 por ciento de aquellos en quienes este dato fue recabado. El 72 por ciento de los pacientes había nacido dentro del área considerada como endémica de la histoplasmosis en la Argentina: 21 por ciento en la ciudad de Buenos Aires (Bs. As.), 11 por ciento en localidades del Gran Buenos Aires, 19 por ciento en ciudades de la provincia de Buenos Aires y 21,5 por ciento en otras provincias de la Argentina. El 16 por ciento de los pacientes era extranjero. Cerca del 90 por ciento de los pacientes tenía su domicilio, en el momento del diagnóstico, en el territorio de la Provincia de Buenos Aires; el 40 por ciento en la ciudad de Buenos Aires, el 25 por ciento en localidades del Gran Buenos Aires y el 23 por ciento en las ciudades de la provincia de Buenos Aires

Histoplamosis in the Muniz Hospital of Buenos Aires

Foram estudadas, retrospectivamente, algumas caracteristicas epidemiologicas e imunologicas e a metodologia de diagnostico de 44 casos de histoplasmose (HP); 36 (27 homens e 9 mulheres) associados com AIDS (HP+AIDS) e 8 (7 homens e 1 mulher) com outros fatores predisponentes (HP, sem AIDS), diagnosticados no Hospital Muniz (MH) durante 1994. A idade media (MA) de pacientes com HP+AIDS foi 28 anos; 25,5 (22-40) nas mulheres e 28,5 (20-42) nos homens e 50 anos (22-58) nos pacientes HP, sem AIDS. A raspagem das lesoes mucocutaneas e as culturas de sangue estabeleceram o diagnostico inicial em 53 por cento e 36 por cento dos pacientes HP+AIDS, respectivamente e as biopsias de lesoes mucocutaneas em 75 por cento dos casos HP, sem AIDS...

Histoplasmose disseminada em pacientes com sindrome de imunodeficiencia adquirida (SIDA): estudo de 25 casos / Disseminated histoplasmosis in patients with acquired immunodefficiency syndrome (AIDS): study of 25 cases

Sao apresentados 25 casos de histoplasmose disseminada em pacientes com SIDA. O envolvimento mucocutaneo estabeleceu o diagnostico de histoplasmose disseminada em 68 por cento dos casos. Destacamos a importancia da histoplasmose como infeccao oportunistica em paciente HIV positivo.