Histoplasmosis: epidemiología, diagnóstico y terapéutica / Histoplasmosis: epidemiology, diagnosis and therapy

La histoplasmosis es una enfermedad granulomatosa, producida por hongos dimorfos del género Histoplasma. Se observa en casi todos los países del mundo. En América Latina, en Venezuela, Colombia, Brasil, Argentina, Ecuador, Perú, Paraguay y Uruguay, entre otros. Datos epidemiológicos recienteshanmostrado un aumento de histoplasmosis en Venezuela y otros países.Los clínicos no están conscientes de su importancia en nuestro medio. Objetivo: Dar a conocer la situación actual de esta enfermedad en el Area Metropolitana de Caracas y en otras áreas endémicas, con la intención de crear la inquietud de investigar su incidencia y otras características relevantes en el resto del país. Métodos: Se analizaron las características de todos los pacientes con diagnóstico de certeza de histoplasmosis registrados y realizados por la Sección de Micología Médica ­Dr. Dante Borelli‖ del Instituto de Medicina Tropical de la UCV, referidos de los diferentes hospitales del Distrito Capital y otros estados del país, con énfasis en los datos epidemiológicos, manifestaciones clínicas, diagnóstico, tratamiento y evolución entre 1994 y 2012. Resultados: se encontraron 553 pacientes. La mayoría estaban entre los 20 y 49 años, relacionado con un alto número de pacientes con VIH/SIDA. Hubo más casos en hombres que en mujeres en todos los grupos etarios, menos en los pacientes mayores de 60 años, posiblemente debido a la disminución de los estrógenos, que son protectores en la mujer. Casi todos los pacientes con VIH/SIDA mostraron la forma diseminada, solo uno presentó una forma pulmonar. De los pacientes VIH negativos, 54,62% presentaron infección diseminada y 44,47%, formas pulmonares. 93 de los de enfermedad diseminada tenían estados de inmunocompromiso. El examen directo fue el método más fácil y eficaz para diagnosticar la histoplasmosis. La anfotericina B (AMB) fue el tratamiento para la histoplasmosis en pacientes con o sin SIDA, que requirieron hospitalización, seguido por itraconazol (ITC). Esta droga se utilizó en pacientes que no se encontraban severamente enfermos o con afectación del sistema nervioso central. Conclusiones: histoplasmosis se encuentra en aumento en nuestro país. Se observa con más frecuencia en pacientes con SIDA, inmunosuprimidos y pacientes que han recibido un inóculo abundante. El examen directo con coloraciones especiales es el método de mayor rendimiento para el diagnóstico. Este debe ser realizado por personal con experiencia.Es conveniente utilizar diferentes técnicas para aumentar la probabilidad de obtener un diagnóstico correcto. AMB e ITC son los tratamientos de elección. Los médicos deben estar alertas de los signos y síntomas, correlacionándolos con los antecedentes epidemiológicos, para evitar el retraso del diagnóstico y mejorar la evolución de los pacientes.

Histoplasmosis is a granulomatous disease, caused by dimorphic fungi from the genus Histoplasma. It is described worldwide.In Latin America, Venezuela, Colombia, Brasil, Argentina, Ecuador, Perú, Paraguay and Uruguay among others are affected. Recent epidemiological data have shown an increase of histoplasmosis in Venezuela and other countries. Clinicians are nor aware of the importance of this mycosis. Objective: analyze the current situation of this disease in the Caracas Metropolitan Area and other endemic areas, with intention to create awareness of its incidence and other relevant characteristics in our country. Methods: characteristics of the patients with diagnosis of histoplasmosis, performed and registered at the Sección de Micología Médica ­Dr. Dante Borelli‖, Instituto de Medicina Tropical, UCV, referred from different hospitals at Distrito Capital and other states of the country, with emphasis on epidemiological data, clinical manifestations, diagnosis, treatment and outcome, between 1994 and 2012 are analized. Results: 553 patients were found. Most of them were between 20 and 49 years old, possibly due to a high number of HIV/AIDS patients. There were more male than female patients in all age groups, except in 60 years and older, possibly due to the lack of estrogenic hormones, which protect women from infection. All HIV/AIDS patients but one, presented with a disseminated form of the disease, and one, a pulmonary form. Of the HIV negative patients, 54,62% showed disseminated infection and 44,47%, pulmonary presentation. 93 of the disseminated infection patients had immunocompromising conditions. Direct examination was the easiest and most efficacious diagnostic method. Amphotericin B (AMB) was the drug of choice for the treatment of hospitalized patients, followed by Itraconazole (ITC). This was the preferred treatment for mild to moderate disease or non CNS infection. Conclusions: Histoplasmosis is rising in our country. It is more frequent in HIV/AIDS patients and immune suppression. It is also seen in patients who have inhaled a large inoculum. Direct examination with special stains is the diagnostic method with better results. It must be performed by experienced personnel in fungal diagnosis. The use of different techniques is recommended to improve early and correct diagnosis. AMB and ITC are drugs of choice for the treatment of histoplasmosis. Clinicians should be aware of suggestive symptoms and signs, correlating them with epidemiological data, to avoid diagnostic delay and improve the outcome of the patients.

Pulmonary histoplasmoma: a disguised malady

Histoplasmosis is a mycosis caused by the dimorphic fungus, Histoplasma capsulatum, which is transmitted via dust and aerosols. Lung involvement is the most common, with a varied clinical presentation. Although it is not the only source of infection, H. capsulatum is frequently found in bat guano, which is the reason why it is highly prevalent among caving practitioners. The solitary histoplasmoma of the lung is an unusual and chronic manifestation of this entity, which mimics, or at least is frequently misconstrued, as a malignancy. Almost invariably, the diagnosis of this type of histoplasmosis presentation is achieved after lung biopsy. The authors present the case of a young woman who sought medical care because of chest pain. The diagnostic work-up revealed the presence of a pulmonary nodule. She was submitted to a thoracotomy and wedge pulmonary resection. The histologic analysis rendered the diagnosis of histoplasmoma. Thisreport aims to call attention to this diagnosis as the differential diagnosis of a pulmonary nodule.

Histoplasmosis diseminada como manifestación inicial del linfoma linfocítico de células pequeñas / Disseminated histoplasmosis as a first clinical manifestation in a patient with small lymphocytic lymphoma: A case report

RESUMEN El linfoma linfocítico de células pequeñas es una neoplasia de células B maduras con un amplio espectro de presentaciones clínicas. Las infecciones por gérmenes oportunistas no asociadas con el tratamiento, incluso en estadios avanzados de la enfermedad, tienen baja incidencia. Se han reportado muy pocos casos de pacientes con linfoma linfocítico de células pequeñas asociado a histoplasmosis diseminada que no habían recibido quimioterapia en el momento del diagnóstico. Se presenta el caso de una paciente de 82 años que fue hospitalizada por presentar tos seca intermitente, astenia y adinamia de un mes de evolución. Se le practicaron múltiples estudios para detectar infecciones o compromiso inmunológico o reumático, y se diagnosticó un síndrome adenopático extenso con compromiso cervical, torácico y retroperitoneal. En la citometría de flujo y en la biopsia de ganglio linfático cervical, se reportaron los fenotipos CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg y CD10neg, con restricción de la cadena ligera kappa, lo cual confirmó un linfoma linfocítico de células pequeñas. En la histopatología del ganglio, se observaron granulomas epitelioides sin necrosis, pero las coloraciones especiales no mostraron la presencia de microorganismos, en tanto que el cultivo del ganglio fue positivo para Histoplasma capsulatum. Se inició el tratamiento antifúngico con anfotericina B e itraconazol, y la paciente tuvo una adecuada evolución. Dado que no se cumplían los criterios para el tratamiento oncológico, se continuó con su observación mediante controles periódicos. Las infecciones oportunistas pueden ser la manifestación clínica inicial en pacientes con síndromes linfoproliferativos de bajo grado. Este caso demuestra que pueden desarrollarse, incluso, en ausencia de quimioterapia.

ABSTRACT The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis. A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed. A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma. Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a "watch and wait" basis. Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Predictive factors for disseminated histoplasmosis in AIDS patients with fever admitted to a reference hospital in Brazil

Abstract INTRODUCTION: In many settings, the lack of sensitive biomarkers of disseminated histoplasmosis (DH) leads to a clinical reliance on older diagnostic methods and delayed treatment initiation. The early recognition of DH is critical for survival, especially in patients with human immunodeficiency virus (HIV). This study aimed to identify clinical and laboratory findings associated with the definitive diagnosis of DH in low-income HIV patients in endemic areas. METHODS: Febrile AIDS patients with suspected DH who were admitted to a reference hospital in northeastern Brazil from January 2006 to January 2007 were evaluated for clinical and laboratory findings associated with DH diagnosis. RESULTS: One hundred seventeen patients with fever were included, and 48 (41%) cases of DH were determined by Histoplasma capsulatum identification. A higher fever (≥38.5ºC), maculopapular/papular rash, splenomegaly, hepatomegaly, wheezing, hemoglobin ≤9.5g/dL, platelets ≤80,000/µL, CD4 count ≤75/µL, aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN), lactate dehydrogenase (LDH) ≥5times the ULN; and international normalized ratio (INR) >2 times the ULN were significantly associated with DH. A multivariable analysis identified hepatomegaly [adjusted (a) prevalence ratio (PR)= 1.96; 95% confidence interval (CI): 1.21-3.16), CD4 count ≤75/µL (aPR = 2.02; 95% CI: 1.06-3.83), LDH ≥5 times the ULN (aPR = 2.23; 95% CI: 1.44-3.48), and maculopapular/papular rash (aPR = 1.70; 95% CI: 1.02-2.83) were independent risk factors for DH. CONCLUSIONS: These easily assessed parameters can facilitate clinical decision-making for febrile AIDS patients with suspected DH in low socioeconomic and Histoplasma-endemic regions.

Histoplasmosis diseminada e infección por VIH: serie de casos en un hospital peruano / Disseminated histoplasmosis and HIV infection: case series in a Peruvian hospital

Resumen Introducción: La histoplasmosis es una infección fúngica endémica en Perú, y la co-infección con VIH conlleva dificultades diagnósticas y alta mortalidad asociada. Objetivo: Describir las características clínicas, epidemiológicas y desenlace clínico en pacientes con infección por VIH con diagnóstico de histoplasmosis diseminada (HD) en el Hospital Nacional Guillermo Almenara Irigoyen, Lima-Perú. Material y Métodos: Estudio retrospectivo, descriptivo; se obtuvo información del registro informático de pacientes con infección por VIH con diagnóstico de HD, durante el período 1996-2014. Se describieron características clínicas, epidemiológicas, tratamiento y desenlace. Resultados: Se encontraron 27 pacientes, 25 (92,6%) fueron varones, con edad media de 36,7 años (± 9,4 años) y 22 (81,5%) tuvieron antecedente epidemiológico. Dieciséis (59,3%) tuvieron HD como enfermedad indicadora de SIDA. El recuento medio de LT CD4+ fue de 65 céls/mm3 (RIQ 15-92). Sólo siete (25,9%) recibían al momento del diagnóstico terapia anti-retroviral combinada. La presentación clínica más frecuente fue con fiebre (66,7%), diarrea crónica (40,7%) y linfoadenopatías (33,3%); el diagnóstico fue realizado principalmente mediante histopatología. Seis (22,2%) fallecieron en la etapa aguda de la enfermedad. Siete (25,9%) fueron tratados inicialmente de forma empírica como tuberculosis. Conclusiones: Se describen las características clínicas de un grupo de pacientes que tuvieron HD como co-infección de VIH, siendo esto aún una realidad cuasi endémica en los pacientes que sufren esta patología.

Background: Histoplasmosis is an endemic fungal infection in Peru and HIV coinfection leads to difficult diagnoses and high associated mortality. Aim: To describe clinical, epidemiological and clinical outcomes in patients with HIV infection with diagnosis of disseminated histoplasmosis (DH) at Guillermo Almenara Irigoyen National Hospital, Lima, Peru. Methods: Retrospective, descriptive study; information was obtained from the computer registry of patients with HIV infection diagnosed with DH, during the period 1996-2014. Clinical, epidemiological, treatment and outcome characteristics were described. Results: We found 27 patients, 25 (92.6%) were male, with a mean age of 36.7 years (± 9.4 years) and 22 (81.5%) had an epidemiological history contact. Sixteen patients (59.3%) had DH as an AIDS defining disease. The median CD4 count was 65 cells/mm3 (IQR 15-92). Only 7 (25.9%) received combination antiretroviral therapy at diagnosis. The most common clinical presentation was fever (66.7%), chronic diarrhea (40.7%) and lymphadenopathy (33.3%). The diagnosis was made mainly by histopathology. Six (22.2%) patiens died in the acute stage of the disease. Seven (25.9%) were initially treated empirically as tuberculosis. Conclusion: We describe the clinical characteristics of a group of patients who had DH as HIV coinfection and this is still a quasi endemic reality in patients suffering from this pathology.

Tuberculosis y micosis sistémicas en indígenas del Municipio Cedeño Estado Bolívar Venezuela / Tuberculosis and systemic mycoses in indigenous Cedeño Municipality Bolivar State Venezuela

Determinar la prevalencia de tuberculosis y micosis sistémicas endémicas, Paracoccidioidomicosis e Histoplasmosis, en poblaciones indígenas. Se realizó un estudio transversal en pacientes sintomáticos respiratorios de 3 comunidades indígenas del municipio Cedeño del estado Bolívar, Venezuela. Se obtuvieron muestras de esputo y secreción ganglionar para la búsqueda de bacilos ácido-resistentes, el complejo Paracoccidioides sppe Histoplasma capsulatum; se realizó cultivo en medio Lowëstein Jensen y medios selectivos para hongos, además estudio molecular para micobacterias. Se estudiaron muestras de suero para la demostración de anticuerpos específicos contra el Complejo Paracoccidioides sppe H. capsulatum. Se evaluaron 60 pacientes sintomáticos respiratorios. Se demostraron bacilos ácido-resistentes por baciloscopia en 26 casos (43,3%) y 29 cultivos positivos para Mycobacterium tuberculosis (48,3%) resultando un total de 33 pacientes con diagnóstico de tuberculosis; hubo correlación significativa entre los hallazgos en el Ziehl-Nielsen y el crecimiento de M. tuberculosis en cultivo (p=0,013). Se demostró la presencia del Complejo Paracoccidioides spp en 2 casos (3,3%), con coexistencia de bacilos ácido-resistentes. No se evidenció la presencia de H. capsulatum. La tuberculosis constituye la principal causa de infección respiratoria crónica en estas comunidades indígenas y obliga a que se revisen de forma urgente los programas regionales para la atención de estas poblaciones vulnerables, así como a realizar estudios en otras poblaciones.

To determine prevalence of tuberculosis and endemic systemic mycoses, Paracoccidiodomycosis (PCM) and Hystoplasmosis in native populations. A transversal study in individuals with respiratory symptoms from 3 native populations from Cedeño County from Bolivar state, Venezuela, was realized. Sputum and spontaneous lymphatic node secretion samples were obtained to look for acid-resistant bacilli, Paracoccidioides spp complex and Histoplasma capsulatum. Culture in Lowëstein-Jensen and selective media to fungi, andmolecular study formycobacteria were realized. Serum samples were studied to demonstrate specific antibodies against Paracoccidioides spp complex and H. capsulatum. Sixty individuals had respiratory symptoms. Acid-resistant bacilli were demonstrated in 26 cases by bacilloscopy (43.3%) and 29 positive cultures for Mycobacterium tuberculosis (48.3%), resulting 33 patients with diagnosis of tuberculosis; there was significative correlation between features in bacilloscopy and growing of M. Tuberculosis in Lowëstein-Jensen media (p=0.013). Presence of the characteristic yeastlike forms of Paracoccidioides spp complex was found in 2 cases (3.3%) with coexistence of acidresistant bacilli in both. There was no evidence of H. capsulatum. Tuberculosis constitutes the principal origin of chronic respiratory infection in these native populations and it should conduce to revise urgently the regional programs attending to these vulnerable populations.

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.

HIV-associated tuberculous lymphadenitis: the importance of polymerase chain reaction (PCR) as a complementary tool for the diagnosis of tuberculosis - a study of 104 patients / Linfadenite tuberculosa associada ao HIV: a importância da reação em cadeia de polimerase (PCR) como ferramenta complementar para o diagnóstico da tuberculose - estudo de 104 pacientes

BACKGROUND: Lymphadenitis is common in HIV-positive patients. Diagnosis of the infections associated with this condition is complex, particularly in the case of tuberculosis. Rapid and specific detection of Mycobacterium tuberculosis (M. tuberculosis) is fundamental in ensuring adequate treatment. In addition, frequent causes of lymphadenitis such as those associated with lymphoma and histoplasmosis, among others, must be eliminated as possible causes. OBJECTIVES: To evaluate the accuracy of polymerase chain reaction as a tool for the diagnosis of lymphadenitis resulting from M. tuberculosis. METHODS: In this study, a protocol was developed using the following procedures: direct microscopy using Ziehl-Neelsen staining, culture in Lowenstein-Jensen medium, histology and polymerase chain reaction. RESULTS: A total of 104 patients were included in the study. According to histopathology, 38 patients (36 percent) were found to have nonspecific chronic lymphadenitis, 27 (26 percent) had tuberculous lymphadenitis, 11 patients (10.5 percent) had lymphoma and 9 (8.7 percent) had histoplasmosis. When Lowenstein-Jensen culture was performed, positive tests for tuberculous lymphadenitis increased by 30 percent. With polymerase chain reaction, M. tuberculosis DNA was detected in 6 out of 38 samples of non-specific chronic lymphadenitis. Three of these patients were followed up, developed symptoms of tuberculosis and were cured following specific treatment. CONCLUSION: The data obtained in this study suggest that all cases of lymphadenopathies should be submitted to histopathology, Lowenstein-Jensen or Ogawa culture and polymerase chain reaction. Polymerase chain reaction may prove to be useful in providing an early and accurate detection of cases of extrapulmonary tuberculosis in HIV-positive patients with lymphadenopathies, avoiding empirical treatment and the possible development of resistant strains.

FUNDAMENTOS: A linfadenite é comum em pacientes HIV-positivos. O diagnóstico das infecções associadas a essa condição é complexo, especialmente em relação à tuberculose. A detecção rápida e específica do Mycobacterium tuberculosis (M. tuberculosis) é essencial para o tratamento adequado. Além disso, frequentes causas de linfadenites tais como as relacionadas a linfoma, histoplasmose, e outras, devem ser afastadas. OBJETIVOS: Avaliar a importância da biópsia cirúrgica excisional das linfadenites e realização dos exames histopatológicos, exames baciloscópicos (Ziehl-Neelsen), cultura (Lowenstein-Jensen) e reação em cadeia da polimerase (PCR) com finalidade diagnostica MÉTODOS: Desenvolveu-se um protocolo para biópsias excisionais de linfonodos, adotando-se os seguintes procedimentos: exame direto de esfregaços corados pelo método de Ziehl-Neelsen, cultura em meio de Lowenstein-Jensen, exame anátomo-patológico e PCR. RESULTADOS: Ao todo foram incluídos 104 pacientes, e o exame histopatológico evidenciou 36 por cento (n = 38 pacientes) de casos de linfadenite crônica inespecífica, 26 por cento (n = 27) de linfadenite tuberculosa, 10,5 por cento (n =11) de linfoma e 8,7 por cento (n = 9) de histoplasmose. Através da cultura no meio de Lowenstein-Jensen, os casos positivos para linfadenite tuberculosa aumentaram para 30 por cento. A PCR detectou M. tuberculosis em 6 das 38 amostras de linfadenite crônica inespecífica. Três desses pacientes foram acompanhados, exibiram sintomas de tuberculose e foram curados após tratamento específico. CONCLUSÃO: Os dados obtidos neste trabalho sugerem que em todos os casos de linfadenopatia deve-se realizar exame histopatológico, cultura em Lowenstein-Jensen ou Ogawa e reação em cadeia da polimerase. A reação em cadeia da polimerase pode ser útil na detecção precoce e acurada de casos de TB extrapulmonar nos pacientes HIV-positivos com linfadenopatias, evitando-se o uso de tratamentos empíricos e o eventual desenvolvimento de cepas resistentes.

Clinical and evolutionary characteristics of four patients with pulmonary histoplasmosis reported in the Paraíba Paulista Valley region / Características clínicas evolutivas de quatro pacientes com histoplasmose pulmonar encontrado na região do Vale do Paraíba

The type of pulmonary histoplasmosis presents limited lesions to the lungs, with symptoms that are clinically and radiological similar to chronic pulmonary tuberculosis. This paper describes the clinical features of four cases of pulmonary histoplasmosis. Aspects of diagnostic and clinical, epidemiological, laboratorial and imaging exams are discussed, in addition to the clinical status of the individuals five years after disease onset. The treatment of choice was oral medication, following which all the patients improved. It is important to understand the clinical status and the difficulties concerning the differential diagnosis of histoplasmosis, to assist the proper indication of cases, thus reducing potential confusion with other diseases.

A histoplasmose do tipo pulmonar apresenta lesões limitadas aos pulmões, cujos sintomas são clínica e radiologicamente similares à tuberculose pulmonar crônica. Esse trabalho descreve as características clínicas de quatro casos de histoplasmose. Os aspectos do diagnósticos clínicos, epidemiológicos, laboratoriais e exames de imagem são relacionados, além da situação clínica dos indivíduos, 5 após o início da doença. O tratamento de escolha foi atravésde medicação oral, aonde todos os pacientes evoluíram bem. É importante conhecer o quadro clínico e da dificuldade em diagnosticar a histoplasmose para ajudar a conduzir as boas indicações dos casos, reduzindo assim o malentendido com outras entidades patológicas.

Capítulo 4: histoplasmose / Chapter 4: histoplasmosis

Histoplasmose é uma micose sistêmica causada por um pequeno fungo, Histoplasma capsulatum var. capsulatum, cujo habitat é o solo rico em excrementos de pássaros e morcegos. A incidência da histoplasmose é mundial. No Brasil, a doença incide em todas as regiões; porém, o estado do Rio de Janeiro é responsável pelo maior número de microepidemias descritas até hoje. A infecção humana ocorre pela inalação de esporos do H. capsulatum. A forma clínica mais freqüente é a assintomática. Na histoplasmose aguda ou epidêmica, os sintomas são febre alta, tosse, astenia, dor retroesternal, acompanhados de aumento dos linfonodos cervicais, fígado e do baço. Os achados radiológicos mais frequentes são o infiltrado reticulonodular difuso em ambos os pulmões, associados a linfonodomegalias hílares e mediastinais. Na forma pulmonar crônica, o quadro clínico e radiológico é idêntico ao da tuberculose pulmonar do adulto. O diagnóstico da histoplasmose é feito pela identificação do fungo ou crescimento em cultura de escarro ou de material obtido por fibrobroncoscopia. A histopatologia identifica o fungo dentro e fora do macrófago em meio à lesão granulomatosa com ou sem necrose caseosa. A imunodifusão em duplo gel de ágar é o teste sorológico mais fácil e disponível para o diagnóstico imunológico. As formas agudas com sintomas prolongados, as formas disseminadas e a forma pulmonar crônica requerem tratamento. A droga de escolha é o itraconazol.

Histoplasmosis is systemic mycosis caused by a small fungus, Histoplasma capsulatum var. capsulatum, whose natural habitat is soil contaminated by bat or bird excrement. The incidence of histoplasmosis is worldwide. In Brazil, the disease is found in all regions; however, the state of Rio de Janeiro is responsible for most of the microepidemics described. Human infection occurs when airborne spores of H. capsulatum are inhaled. The most common clinical presentation is asymptomatic. The symptoms of acute or epidemic histoplasmosis are high fever, cough, asthenia and retrosternal pain, as well as enlargement of the cervical lymph nodes, liver and spleen. The most common radiological findings are diffuse reticulonodular infiltrates in both lungs, as well as hilar and mediastinal lymph node enlargement. In chronic pulmonary histoplasmosis, the clinical and radiological manifestations are identical to those of reinfection with pulmonary tuberculosis. Histoplasmosis is diagnosed by means of the identification or culture growth of the fungus in sputum or fiberoptic bronchoscopy specimens. Histopathological examination reveals the fungus itself within or surrounding macrophages, as well as granulomatous lesions with or without caseous necrosis. Double agar gel immunodiffusion is the most easily used and readily available serologic test for making the immunological diagnosis. Acute histoplasmosis with prolonged symptoms requires treatment, as do the disseminated or chronic pulmonary forms of the disease. The drug of choice is itraconazole.

Histoplasmose: [revisão] / Histoplasmosis: [review]

A histoplasmose é uma micose causada por fungo dimórfico, o Histoplasma capsulatum. É considerada classicamente uma micose endêmica, embora o fungo tenha um comportamento oportunístico em pacientes com depressão da imunidade celular. O homem adquire a infecção através da inalação de conídeos presentes na natureza (cavernas com morcegos, galinheiros, etc). O quadro clínico pode variar, desde infecções assintomáticas até quadros graves disseminados, que acometem pacientes com Aids, transplantados ou com neoplasias hematológicas. O diagnóstico baseia-se no encontro do fungo em fluidos orgânicos (escarro, sangue, líquor) ou tecidos (histopatologia), na cultura de materiais biológicos e na sorologia. O tratamento das formas agudas graves, respiratória crônica ou de formas localizadas pode ser feito com azólicos orais (itraconazol) e nas disseminadas, a Anfotericina B (preferencialmente as formulações lipídicas) constitui a droga da eleição para iniciar a terapia. A histoplasmose representa, hoje uma das micoses sistêmicas mais importantes nas Américas, com ampla distribuição em todas as regiões do Brasil.

Histoplasmosis is a fungal infection caused by the dimorphic fungus Histoplasma capsulatum. It is classically considered an endemic mycosis, even though the fungus has an opportunistic behavior in immunocompromised patients. People acquired the infection through the inhalation of conidial forms present in the environmental, such as caves dwelling bats and soils inhabited by chickens. The clinical features may vary from asymptomatic infections to disseminated severe forms that affect patients with acquired immunodeficiency syndrome or hematological malignancies and allograft recipients. The diagnosis is based on the detection of the fungus in organic fluids (sputum, blood, liquor) or tissues (histopathological assays), in the culture of biological samples and serological assays. The treatment of severe chronic respiratory acute or localized forms can be performed with oral azolic (itraconazol) and in the disseminated forms, the amphotericin B (preferentially the lipidic formulations) consists in the elected drug to initiate the therapy. Nowadays, histoplasmosis represents one of the most important systemic mycosis in the Americas, with broad distribution in all regions of Brazil.

Chronic meningitis by histoplasmosis: report of a child with acute myeloid leukemia

Meningitis is a common evolution in progressive disseminated histoplasmosis in children, and is asymptomatic in many cases. In leukemia, the impaired of the T cells function can predispose to the disseminated form. The attributed mortality rate in this case is 20 percent-40 percent and the relapse rate is as high as 50 percent; therefore, prolonged treatment may be emphasized. We have described a child with acute myeloid leukemia (AML), that developed skin lesions and asymptomatic chronic meningitis, with a good evolution after prolonged treatment with amphotericin B deoxycholate followed by fluconazole.

Histoplasmosis pulmonar diseminada (enfermedad de Darling): a propósito de un caso / Disseminated pulmonary histoplasmosis (Darling's disease): a purpose of a case

La histoplasmosis es una micosis sistémica que afecta al hombre y a los animales, causada por el Hongo Histoplasma capsulatum, se relaciona especialmente con el guano de las aves, y las cuevas habitadas por murciélagos. La infección se produce habitualmente por vía respiratoria, raramente la puerta de entrada es cutánea. El mecanismo de contagio es a través de la inhalación de esporas en el polvo del aire; la población más afectada es la que vive en zonas rurales, especialmente los granjeros; este padecimiento también se ha presentado en forma epidémica. Es una enfermedad de variada, manifestación clínica que puede ir de una simple infección respiratoria asintomática, hasta una enfermedad diseminada, caracterizada por fiebre, anemia progresiva, hepatoesplenomegalía, linfadenopatías, úlceras en el aparato digestivo y necrosis de suprarrenales. Ocurre con mayor frecuencia en individuos del sexo masculino sin distinción de raza. El tratamiento es a base de derivados del imidazol: ketoconazol, itraconazol, fluconazol y anfotericina B.

Histoplasmosis vaginal en una paciente con síndrome de inmunodeficiencia adquirida / Vaginal histoplasmosis in a patient with acquired immunodeficiency syndrome

El Histoplasma capsulatum es un hongo dimórfico que es endémico en Guatemala. Desde que inició la epidemia de SIDA en Guatemala se han reconocido con mayor frecuencia casos de histoplasmosis crónica en pacientes inmunocomprometidos. Se presenta un caso de una mujer de 30 años con historia de dolor vaginal, fiebre y una lesión vaginal que inició 5 meses antes con un cuadro aparente de papilomatosis. Las lesiones vaginales evolucionaron de tal forma que al ingreso se encontró una paciente en malas condiciones generales y nutricionales con una lesión destructiva en genitales externos y vagina. La biopsia fue compatible con Histoplasmoma. Se inició tratamiento con Anfotericina B, la paciente mejoró parcialmente sin embargo al final falleció. Al revisar la literatura se encontraron solamente 3 casos reportados de Histoplamosis vaginal.

Bilateral adrenal histoplasmosis in an immunocompetent man

Histoplasmosis is a fungal disease that is endemic in Brazil. It may present as chronic pulmonary infection or in disseminated form. Disseminated histoplasmosis frequently affects the adrenal gland; however, unilateral involvement in immunosuppressed patients is the usual presentation. We report a case of an elderly immunocompetent male with history of weight loss, fever and bilateral adrenal mass who was successfully treated with itraconazole.

Histoplasmose é uma doença fúngica endêmica no Brasil que pode se apresentar como infecção pulmonar crônica ou na forma disseminada. A histoplasmose disseminada freqüentemente acomete a glândula adrenal; entretanto, ocorre mais em pacientes imunossuprimidos e de forma unilateral. Relatamos um caso de um homem idoso imunocompetente com história de perda de peso, febre e massa adrenal bilateral que foi tratada com itraconazol, com sucesso.

Bilateral afrenal nodules due to histoplasmosis in an elderly

We report a case history of an 84-year-old elderly male patient that presented with a clinical picture suggestive of adrenal failure and bilateral adrenal nodules detected by abdominal computed tomography. A fine needle-guided biopsy was inconclusive for achieving a final diagnosis. The patient died due to septic shock and the autopsy disclosed histoplasmosis with extensive bilateral necrosis of the adrenal glands. Although the adrenal involvement in chronic disseminated histoplasmosis has been described, there have been few reports of the infection being associated with adrenal insufficiency.

Estudio de 40 casos de Histoplasmosis en niños y revisión de la literatura / Study of 40 cases of histoplasmosis in children and literature review

En niños, la histoplasmosis es la micosis profunda más frecuente en nuestro país. No es de denuncia obligatoria, por lo que existe un gran subregistro. El objetivo de este trabajo es reportar los casos de histoplasmosis diagnosticados en niños en la Sección de Micología Médica del Instituto de Medicina Tropical (IMT). Universidad Central de Venezuela (UCV), entre julio 2004 y julio 2005, con la finalidad de dar a conocer los principales aspectos de esta entidad a la población médica, en especial a los pediatras. Se evaluaron los pacientes en edad pediátrica (0-18 años) que fueron traídos a la consulta de la Sección y las muestras biológicas que se recibieron en el lapso antes mencionado. Se realizó examen mitológico y se siguió la evolución con el tratamiento. Se encontraron 40 casos de histoplasmosis con edades comprendidas entre 14 días y 16 años, 15 del genero femenino y 25 del genero masculino. Seis eran menores de 1 año, la mayoría (25 casos) provenientes del Distrito capital. Dieciocho presentaron la forma de histoplasmosis diseminada de los cuales 4 fallecieron. Quince presentaron la forma pulmonar aguda y 5 meningitis crónica. Seis pacientes estaban desnutridos, 4 presentaron VIH y 4 tenían tuberculosis. En 18 pacientes se desconoce comorbilidad. Nueve pacientes tenían aumento de la VSG, 7 anemia, 5 leucopenia y 2 pancitopenia. Los datos epidemiológicos fueron sugestivos de histoplasmosis en todos los casos. Se reportaron 40 casos de histoplasmosis en niños, diagnósticados en la Sección de Micología Médica del IMT-UCV. La forma clínica más frecuente fue la histoplasmosis diseminada. Ante la presencia de niños con las características descritas, debe pensarse en histoplasmosis como diagnóstico diferencial, relacionando la epidemiología, clínica, radiología y exámenes de laboratorio. Es necesario practicar mitológico para confirmar la presencia de esta enfermedad.

Chronic disseminated histoplasmosis with lesions restricted to the mouth: case report

Reportamos um caso raro de histoplasmose crônica disseminada com diversas lesões ulceradas na cavidade oral de um paciente alcoólatra, sem o vírus da imunodeficiência humana, com nenhum outro sinal detectável ou sintomas de doença sistêmica ou manifestações extra-orais. Análise histopatológica revelou processo inflamatório crônico com granulomas contendo organismos fúngicos. O isolamento do Histoplasma capsulatum forneceu o diagnóstico definitivo. Tratamento com itraconazol resultou numa remissão completa das lesões orais. De acordo com nosso conhecimento, este é o segundo caso reportado de histoplasmose oral em um paciente HIV negativo descrito no Brasil.

Histoplasmose pulmonar em clínica privada no Rio de Janeiro / Pulmonary histoplasmosis in a private clinic in Rio de Janeiro city

A histoplasmose é uma infecção fúngica causada pelo H. capsulatum que acomete principalmente os pulmões. Pode apresentar-se como infecção primária assintomática, infecção pulmonar aguda ou crônica, ou sob a forma disseminada. O objetivo é descrever as principais manifestações clínicas e radiológicas numa população de grande centro urbano. Metodologia: foi realizado estudo retrospectivo com análise de prontuários de uma clínica privada na cidade do Rio de Janeiro, sendo incluídos todos os pacientes com diagnóstico de histoplasmose, confirmado por sorologia, cultura ou histopatologia. Foram mostradas as principais manifestações clínicas e radiológicas da histoplasmose, e o aspecto endêmico da doença mesmo em áreas urbanas. Resultados: incluídos 18 pacientes, com média de idade de 46 anos, sendo 10 mulheres. Como principais manifestações clínicas, observamos febre, tosse, astenia e dor torácica. O nódulo pulmonar e linfonodomegalia foram os achados radiológicos mais encontrados. Todos os pacientes eram moradores de área urbana. Não houve casos da forma disseminada da doença. Conclusões: a presença da histoplasmose pulmonar em áreas urbanas é uma realidade, acometendo indivíduos saudáveis, e sendo muitas vezes subdiagnosticada devido aos sintomas inespecíficos e a remissão espontânea em muitos casos. A febre e o nódulo pulmonar são os principais achados clínicos e radiológicos.