Histoplasmosis diseminada en una paciente pediátrica inmunocompetente / Disseminated histoplasmosis in an immunocompetent pediatric patient

La histoplasmosis es una micosis endémica producida por el hongo Histoplasma capsulatum. La forma diseminada en pediatría conlleva alta morbimortalidad. Reportamos el caso de una niña inmunocompetente con diagnóstico de histoplasmosis diseminada. Paciente de 3 años de edad con cuadro clínico de síndrome febril prolongado acompañado de hepatoesplenomegalia confirmada por ecografía. Laboratorio con anemia normocítica, normocrómica y leucopenia. Se arribó al diagnóstico por biopsia de ganglio periportal y periesplénico. El cultivo fue positivo para Histoplasma capsulatum y en estudios histopatológicos se observó linfadenitis granulomatosa con elementos levaduriformes intracelulares. Realizó tratamiento con anfotericina B 1 mg/kg/día durante 6 semanas con favorable resolución clínica. Se debe considerar histoplasmosis diseminada en aquellos pacientes provenientes de zonas endémicas que presentan la tríada de fiebre, hepatoesplenomegalia y citopenias, para poder brindar un tratamiento oportuno, mejorar el pronóstico y disminuir la mortalidad de la enfermedad.

Histoplasmosis is an endemic fungal infection caused by the fungus Histoplasma capsulatum. The disseminated form is associated with a high morbidity and mortality in pediatrics. Here we report the case of an immunocompetent female patient diagnosed with disseminated histoplasmosis. She was 3 years old and presented with protracted febrile syndrome and hepatosplenomegaly confirmed by ultrasound. Lab tests showed normocytic anemia and leukopenia. Diagnosis was made by periportal and perisplenic lymph node biopsy. The culture was positive for Histoplasma capsulatum and histopathological studies showed granulomatous lymphadenitis with intracellular yeast-like elements. Amphotericin B was administered at 1 mg/kg/day for 6 weeks, with a favorable clinical course. Disseminated histoplasmosis should be considered in patients from endemic areas who present the triad of fever, hepatosplenomegaly, and cytopenias so as to provide a timely treatment, improve prognosis, and reduce the mortality from this disease.

Factors interfering with the production of Histoplasma capsulatum antigens / Fatores que interferem na produção de antígenos de Histoplasma capsulatum

Histoplasma capsulatum causes systemic mycosis that depends on host susceptibility, fungal virulence, and factors associated with the infectious process. We evaluated the possible interference of the phenotype of 12 samples of H. capsulatum isolated from HIV-positive and negative patients in obtaining antigens, aiming at the serological diagnosis through the gender-specific recognition of the H and M fractions. The antigens were evaluated by double immunodiffusion against H. capsulatum anti-antigen polyclonal antibody and serum samples from patients with histoplasmosis.The phenotypic evaluation revealed differences in the identification of the fungal agent and in the expression of H and M antigens, considered serological markers of the disease, associated with pigmentation and the production of conidia. It was found that antigenic preparations obtained from H. capsulatum isolated from HIV-positive patients may have satisfactory antigenic capacity. The patient's immune status does not seem to interfere with the expression of antigenic proteins secreted by H. capsulatum. However, we suggest that prolonged use of antiretrovirals drugs or steroids can cause important phenotypic alterations. We showed that some fungal samples from patients with a long history of immunosuppressive drugs produced atypical cellular elements and low reactivity against the H and M fractions. (AU)

Histoplasma capsulatum causa micose sistêmica endêmica que depende da suscetibilidade do hospedeiro, da virulência fúngica e de fatores associados ao processo infeccioso. Avaliamos a possível interferência do fenótipo de 12 amostras de H. capsulatumisolados de pacientes HIV positivos e negativos na obtenção de antígenos, visando o diagnóstico sorológico por meio do reconhecimento gênero-específico das frações H e M. Os antígenos foram avaliados por imunodifusão dupla, frente a anticorpo policlonal anti-antígeno de H. capsulatum e frente a amostras de soro de pacientes com histoplasmose. A avaliação fenotípica revelou diferenças, não só na identificação do agente fúngico, mas também na expressão dos antígenos H e M, considerados marcadores sorológicos da doença, associados à pigmentação e produção de conídios. Verificou-se que preparações antigênicas obtidas de H. capsulatum isoladas de pacientes HIV positivos podem ter capacidade antigênica satisfatória. O estado imunológico do paciente parece não interferir na expressão de proteínas antigênicas secretadas por H. capsulatum. No entanto, sugerimos que o uso prolongado de antirretrovirais e/ou esteróides pode causar alterações fenotípicas importantes. Verificou-se que algumas amostras fúngicas isoladas de pacientes com longo histórico de uso de imunossupressores produziram elementos celulares atípicos e baixa reatividade sorológica contra as frações H e M de H. capsulatum. (AU)

Forma aguda de histoplasmose em paciente imunocompetente: relato de caso / Acute form of histoplasmosis in immunocompetent patient: case report

A histoplasmose é uma doença granulomatosa infecciosa sistêmica cuja transmissão é aerógena e a contaminação se dá pelo contato com fezes de aves e morcegos, depende da exposição e da imunidade do paciente. Trata-se de uma doença com difícil diagnóstico, dada a semelhança dos sintomas com os de outras doenças granulomatosas infecciosas, principalmente em pacientes imunocompetentes, visto que a regressão é geralmente espontânea. Um homem de 34 anos, branco, natural e procedente de Atibaia, previamente hígido, iniciou quadro de dor e edema no tornozelo esquerdo, e evoluiu com dispneia progressiva, com piora ao decúbito, acompanhada de sudorese noturna, tosse seca e febre baixa. Foi realizado o exame de tomografia computadorizada (TC) de tórax sem contraste, que evidenciou espessamento difuso das paredes brônquicas, de aspecto inflamatório, micronódulos esparsos bilateralmente. Paciente apresentou PCR elevado, COVID, sorologias, BAAR e hemoculturas negativas, punção articular e ecocardiograma sem alterações. Optado por COXCIP 4, sulfametoxazol-trimetoprim e anfotericina B de forma empírica. Pesquisa de fungos em escarro positivo; leveduras e lavado brônquico sugestivos de histoplasmose. Evoluiu com insuficiência respiratória necessitando de intubação orotraqueal, posteriormente, traqueostomia e apesar do tratamento antifúngico, evoluiu com óbito após 21 dias. A histoplasmose é uma doença grave, com diversas formas clínicas e prognóstico normalmente autolimitado, mas que pode ser fatal, mesmo em pacientes previamente imunocompetentes.

Histoplasmosis is a systemic infectious granulomatous disease whose transmission is airborne, and contamination occurs through contact with bird and bat feces, depending on the exposure and immunity of the patient. It is a disease with difficult diagnosis, given the similarity of symptoms with those of other infectious granulomatous diseases, especially in immunocompetent patients since regression is usually spontaneous. A 34-year-old Caucasian man from Atibaia, previously healthy, developed pain and swelling in his left ankle, progressing to progressive dyspnea, worsening in recumbency, accompanied by night sweats, dry cough and low-grade fever. A non-contrast-enhanced computed tomography (CT) scan of the chest was performed, which showed diffuse thickening of the bronchial walls, with an inflammatory appearance, and bilaterally sparse micronodules. Patient had high C-reactive protein, COVID, serology, BAAR and negative blood cultures, joint puncture, and echocardiogram without changes. Empirically opted for COXCIP 4, trimethoprim-sulfamethoxazole and amphotericin B. Search for fungi in positive sputum, yeasts, and bronchial lavage suggestive of histoplasmosis. He envolved with respiratory failure requiring orotracheal intubation, later tracheostomy and despite antifungal treatment, he died after 21 days. Histoplasmosis is a serious disease, with several clinical forms and a prognosis that is usually self-limiting, but it can be fatal, even in previously immunocompetent patients

Histoplasmosis pulmonar cavitada en un paciente pediátrico: reporte de caso / Acute cavitated pulmonary histoplasmosis in a pediatric patient: a case report

La histoplasmosis es una micosis producida por el Histoplasma capsulatum. Esta condición es endémica en Estados Unidos, Suramérica, América central y África. Suele presentarse en todas las edades, pero en niños; en especial en aquellos inmunodeprimidos, se han descrito presentaciones graves o atípicas. Se presenta el caso de un paciente de 16 años con antecedentes de trasplante renal, que inicia con síntomas respiratorios inespecíficos, tos y alzas térmicas intermitentes. La radiografía de tórax mostró una imagen de condensación cavitada en el lóbulo superior izquierdo, por lo que se realiza una fibrobroncoscopia, lavado broncoalveolar y cultivos para patógenos habituales, micobacterias y hongos, lográndose aislar al Histoplasma capsulatum. EL objetivo de este trabajo es el de resaltar la consideración de histoplasmosis como diagnóstico diferencial de lesiones cavitadas en parénquima pulmonar en pacientes inmunodeprimidos con la presentación de un caso clínico.

Histoplasmosis is a mycosis caused by Histoplasma capsulatum. This condition is endemic in the United States, South America, Central America, and Africa. It usually occurs in all ages, but in children, especially those immunosuppressed, serious or atypical presentations have been described. We present the case of a 16-year-old patient with a history of kidney transplantation that began with nonspecific respiratory symptoms, cough, and intermittent fever peaks. Imaging findings suggestive of cavitation were found, which by means of a fiberoptic bronchoscopy and bronchoalveolar lavage study isolated Histoplasma capsulatum by means of a deep mycosis culture. The main interest of the case presented is the consideration of histoplasmosis in the presence of cavitated lesions in the lung parenchyma in immunosuppressed patients.

Histoplasmosis diseminada en una mujer con artritis seronegativa / Disseminated histoplasmosis in a woman with seronegative arthritis

Resumen Histoplasma capsulatum es un hongo ambiental que se encuentra distribuido comúnmente en los valles de los ríos Ohio y Mississippi, América Central, Sudamérica y Asia. Las zonas más afectadas en Argentina son las cuencas de los ríos Paraná y de La Plata. Los pacientes con histoplasmosis tienen una amplia variedad de manifestaciones clínicas. La mayoría son asintomáticos, mientras que aquellos con com promiso de la inmunidad celular tienen un riesgo aumentado de padecer la forma diseminada. Presentamos el caso de una mujer adulta, en tratamiento con metotrexato por una artritis seronegativa, que desarrolló la forma diseminada de la enfermedad, y que representó un desafío diagnóstico debido a la dificultad para identificar el agente etiológico.

Abstract Histoplasma capsulatum is an environmental fungus commonly found in the Ohio and Mississippi River valleys, Central and South America, and Asia. The most affected areas in Argentina are the Paraná and de La Plata river basins. Patients with histoplasmosis can have a wide range of clinical presentations. Most of them are asymptomatic, while those with compromised cellular immunity are at increased risk for the disseminated form. We present the case of a patient undergoing treatment with methotrexate for seronegative arthritis who developed the disseminated form of the disease, and who represented a diagnostic challenge due to the difficulty in identifying the etiologic agent.

Histoplasmosis diseminada progresiva aguda en un paciente inmunocompetente / Acute progressive disseminated histoplasmosis in an immunocompetent patient

RESUMEN La histoplasmosis diseminada progresiva constituye una expresión singular y rara de la infección por Histoplasma capsulatum. Sus formas agudas de presentación suelen aparecer en pacientes con deficiencias inmunitarias graves (fundamentalmente VIH). Sin embargo, en regiones de alta endemicidad, incluso pacientes sin inmunodeficiencia demostrada pueden desarrollar esta afección. Se presentó un paciente de 47 años de edad, con antecedentes de haber sufrido un cuadro grave de histoplasmosis pulmonar 18 años antes. El paciente fue ingresado por un cuadro de: fiebre, astenia, sudoración nocturna, disnea, tos seca, hepatoesplenomegalia, anemia y trombocitopenia marcada. Progresó a una insuficiencia respiratoria aguda y fue internado en cuidados intensivos con ventilación mecánica invasiva. Se demostró crecimiento de Histoplasma capsulatum en la muestra de lavado bronquioalveolar y reacción granulomatosa no caseificante en médula ósea, confirmándose el diagnóstico de histoplasmosis diseminada progresiva. El paciente recibió tratamiento con anfotericina B y se recuperó totalmente en pocas semanas.

ABSTRACT Progressive disseminated histoplasmosis is a unique and rare expression of the infection cause by Histoplasma capsulatum. Its acute forms of presentation usually appear in patients with severe immunodeficiency disorders (mainly HIV). However, even patients without proven immunodeficiency can develop this condition in regions of high endemicity. We present a 47-year-old male patient with a previous history of severe pulmonary histoplasmosis eighteen years earlier. The patient was admitted due to the presence of fever, asthenia, night sweats, dyspnea, dry cough, hepatosplenomegaly, anemia and marked thrombocytopenia. He progressed to acute respiratory failure and was admitted to the intensive care unit requiring invasive mechanical ventilation. Growth of Histoplasma capsulatum was demonstrated in the bronchoalveolar lavage sample and a non-caseating granulomatous reaction was found in the bone marrow, confirming the diagnosis of progressive disseminated histoplasmosis. The patient received amphotericin B treatment and made a full recovery within a few weeks.

Primary cutaneous histoplasmosis difficult to treat in immunocompetent patient: case report and literature review / Histoplasmose cutânea primária de difícil tratamento em paciente imunocompetente: relato de caso e revisão da literatura

ABSTRACT Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. The disease is endemic in several regions of tropical and temperate climate. The fungus presents opportunistic behavior, causing widespread infection in immunocompromised patients, resulting from complication of primary pulmonary infection, due to exogenous reinfection or reactivation of a quiescent source. In immunocompetent individuals, approximately 95% of pulmonary infections are asymptomatic. However, prolonged exposure to high amount spores may lead to acute or chronic lung infection. Due to the low amount of inoculum, primary cutaneous histoplasmosis caused by traumatic implantation is extremely rare and effectively treated with triazoles. Thus, the present study aims to report a case of primary cutaneous histoplasmosis that is difficult to treat in an immunocompetent patient, and to review the literature on the incidence of drug-resistant Histoplasma capsulatum strains in clinical practice.

RESUMO A histoplasmose é uma infecção causada pelo fungo dimórfico Histoplasma capsulatum. A doença é endêmica em diversas regiões de clima tropical e temperado. O fungo apresenta comportamento oportunístico, causando infecção disseminada em pacientes imunocomprometidos, resultante da complicação da infecção pulmonar primária, por reinfecção exógena ou reativação de um foco quiescente. Em indivíduos imunocompetentes, cerca de 95% das infecções pulmonares são assintomáticas. No entanto, a exposição prolongada à quantidade elevada de esporos pode levar à infecção pulmonar aguda ou crônica. Devido à baixa quantidade de inóculo, a histoplasmose cutânea primária causada por implantação traumática é extremamente rara e efetivamente tratada com triazóis. Assim, o presente estudo tem como objetivos relatar um caso de histoplasmose cutânea primária de difícil tratamento em paciente imunocompetente, e revisar a literatura a respeito da incidência de cepas de Histoplasma capsulatum resistentes aos fármacos utilizados na prática clínica.

Investigação de surto de Histoplasmose pulmonar aguda entre bombeiros em Brazlândia, Distrito Federal, 2017 / Investigation of acute histoplasmosis outbreak among firefighters, Distrito Federal, 2017

Objetivos: Investigar o surto de histoplasmose em bombeiros no Distrito federal/DF, ocorrido em junho de 2017. Métodos: Realizou-se um estudo de coorte por meio das entrevistas realizadas com os bombeiros mediante um questionário semiestruturado. Considerou-se infectado o bombeiro que apresentou tomografia de tórax sugestiva de histoplasmose ou reagente nos testes de imunodifusão e/ou Western blot. Coletou-se amostra ambiental e realizou-se Nested PCR específico para Histoplasma capsulatum. Resultados: Entre 35 bombeiros, 94,3% eram homens; com a mediana de idade de 37 (24-45) anos, 28 foram classificados como infectados. A média de permanência dentro da caverna foi 25 minutos. O fator de risco associado à infecção foi o ato de entrar na caverna (RR=3,86; RA=71,6; p<0,02). Entre 14 amostras ambientais, 50% foram positivas para H. capsulatum. Conclusão: Confirmou-se o surto de histoplasmose de bombeiros em Brazlândia-DF, e foram tomadas ações como a interdição da caverna e o tratamento dos bombeiros.

Objectives: To nvestigate the outbreak of histoplasmosis in firefighters in Federal District/DF, which occurred in June 2017. Methods: A cohort study was conducted through interviews with firefighters by means of a semi-structured questionnaire. Firefighters who presented chest tomography suggestive of histoplasmosis or reacted to immunodiffusion and/or Western blot tests were considered infected. Environmental samples were collected and Nested PCR specific for Histoplasma capsulatum was performed. Results: Among 35 firefighters, 94.3% were men; with a median age of 37 (24-45) years, 28 were classified as infected. The average length of stay inside the cave was 25 minutes. The risk factor associated with infection was the act of entering the cave (RR = 3.86, RA = 71.6, p <0.02). Among 14 environmental samples, 50% were positive for H. capsulatum. Conclusion: The outbreak of histoplasmosis in firefighters in Brazlândia-DF was confirmed, and actions were taken such as banning the cave and treating the firefighters

Linfohistiocitosis hemofagocítica por Histoplasma capsulatum en paciente con trasplante renal / Hemophagocytic Lymphohistiocytosis induced by Histoplasma capsulatum in a kidney transplant patient

La linfohistiocitosis hemofagocítica (LHH) por Histoplasma capsulatum, presentación rara de la histoplasmosis diseminada, es causada por la fagocitosis de las células hematopoyéticas por macrófagos tisulares. Presentamos el caso de un paciente masculino de 44 años con trasplante renal que asiste por fiebre sin otra sintomatología. Inicialmente se obtiene una gota gruesa positiva para P. vivax, iniciando manejo antimalárico. A los 2 días de tratamiento, el paciente presenta disfunción multiórganica, se rectifica diagnóstico en centro de referencia reportando en extendido de sangre periférica la presencia de levaduras de H. capsulatum en polimorfonucleares, resultado confirmado con prueba de inmunodifusión. Se ajusta manejo, pero el paciente fallece. El diagnóstico de infecciones por gérmenes inusuales con presentaciones inespecíficas es un reto en pacientes con inmunosupresión.

Hemophagocytic Lymphohistiocytosis (HLH) induced by Histoplasma capsulatum is a rare entity who is characterized by phagocytosis of hematopoietic cells by tissue macrophages. A 44-year-old male patient with kidney transplantation was admitted to our ambulatory service with fever. Initially, we performed a thick drop test who was positive for P. vivax, so antimalarial therapy was initiated. Patient then progressed to multiple organ dysfunction after 2 days of treatment. Thus, a reference center went back over the blood smear which revealed the presence of yeast cells H. capsulatum within polymorphonuclear cells. This result was confirmed by an immunodifussion assay. Despite of antifungal treatment, patient passed away. The diagnosis for unusual microorganism with unspecific clinical presentation could be a challenge in immunosupressive patients.

Thermotolerance of Histoplasma capsulatum at 40 °C predominates among clinical isolates from different Latin American regions

ABSTRACT The yeast phase of 22 Histoplasma capsulatum clinical isolates from Mexico, Argentina, Colombia, and Guatemala and three reference strains, one from Panama and two from the United States of America (USA), were screened for thermosensitivity characteristics using different analyses. Growth curves at 0, 3, 6, 12, 24, and 30 h of incubation at 37 and 40 °C, the growth inhibition percentage at 40 °C, and the doubling time at 37 and 40 °C were determined for all yeasts studied. Most of the isolates examined exhibited thermotolerant phenotypes at 40 °C, whereas a thermosensitive phenotype at 40 °C was only detected in the Downs reference strain from the USA. Growth inhibition values lower than 33.8% supported the predominance of the thermotolerant phenotype at 40 °C. The doubling time means found for the different isolates were 5.14 h ± 1.47 h at 37 °C and 5.55 h ± 1.87 h at 40 °C. This is the first report to underscore the predominance of thermotolerant and delayed doubling time phenotypes in H. capsulatum clinical isolates from different regions of Latin America.

Postpartum histoplasmosis in an HIV-negative woman: a case report and phylogenetic characterization by internal transcribed spacer region analysis

Abstract The present report describes the first case of postpartum disseminated histoplasmosis in a 24-year-old HIV-negative woman. On the tenth day after vaginal delivery, the patient presented with dyspnea, fever, hypotension, tachycardia, and painful hepatomegaly. Yeast-like Histoplasma capsulatum features were isolated in the buffy coat. The phylogenetic analysis demonstrated that the fungal isolate was similar to other H. capsulatum isolates identified in HIV patients from Ceará and Latin America. Thus, histoplasmosis development in individuals with transitory immunosuppression or during the period of immunological recovery should be carefully examined.

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.

Uso de Anfotericina B: pacientes con linfoma no Hodgkin células B tipos burkitt por histoplasma capsulatum / Use of Amphotericin B: patients with non-Hodgkin lymphoma B cells burkitt type by histoplasma capsulatum

El linfoma no Hodgkin comprende un grupo de enfermedades relacionadas entre sí. Cada variedad histológica de linfoma no Hodgkin se caracteriza por la transformación maligna de las células linfoides, con morfología, inmunofenotipo, genética y clínica diferente. Entre la etiología encontramos: virus de Epstein-Barr, virus linfotrófico humano tipo 1, herpes virus humano 8, Helicobacter pylori. Los linfomas difusos de células B grandes (30 % 40 %) son los más comunes, seguidos de linfoma de células B folicular (22 %). Todos los demás tipos de linfoma tienen una frecuencia menor de 10 %. El diagnóstico de los linfomas es histopatológico. Actualmente se ha observado un incremento de las infecciones causadas por Histoplasma capsulatum, articularmente en pacientes inmunocomprometidos. El objetivo del estudio fue determinar las características de la histoplasmosis y el uso de la anfotericina B en pacientes con linfoma no Hodgkin de células B tipo Burkitt por Histoplasma capsulatum(AU)

The lymphoma non Hodgkin comprises a group of diseases related to each other. Each histological variety of the non-Hodgkin lymphoma is characterized by the malignant transformation of the lymphoid, orphology, the immune, the genetics and the different clinic cells. Among the etiology: The Epstein-Barr virus, the virus lymphotropic human type 1, the human herpes virus 8, the Helicobacter pylori. The diffuse large B-cell lymphomas (30 % 40 %) are the most common, followed by the follicular B-cell lymphoma (22 %). All other types of lymphoma have one less than 10 % of frequency. The diagnosis of lymphomas is histological. Currently there has been an increase in infections caused by the histoplasma capsulatum, particularly in the immunocompromised patients. The objective of the study was to determine the characteristics of histoplasmosis and the use of the amphotericin B in patients with B-cell non-Hodgkin's lymphoma type Burkitt by histoplasma capsulatum.(AU)

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.

Caracterización de los pacientes con diagnóstico de Histoplasmosis en el Hospital Universitario de San Ignacio entre 2012 a 2016 / Characterization of patients with clinical diagnosis of Histoplasmosis in the "Hospital Universitario San Ignacio" between 2012-2016

Introducción: La histoplasmosis diseminada es una forma de presentación común en pacientes inmunosuprimidos. La introducción de nuevos métodos diagnós ticos y la mejoría de la sobrevida de los pacientes con VIH pueden hacer cambiar las características clínicas de los pacientes con esta enfermedad. El objetivo de este estudio es describir las características demográficas, clínicas y métodos diagnósticos para esta enfermedad utilizados en una institución de cuarto nivel de complejidad en Colombia durante los últimos cinco años. Métodos: Se realizó un estudio observacional tipo serie de casos, incluyendo pacientes con diagnóstico de histoplasmosis manejados en el Hospital Universitario San Ignacio en Bogotá (Colombia) entre enero de 2012 y diciembre de 2016. Los casos fueron identificados utilizando una herramienta automatizada a partir de las historias clínicas electrónicas (DISEARCH). Resultados: 34 pacientes fueron incluidos, 73,5% con VIH. La enfermedad fue más sintomática en los pacientes con VIH. Los síntomas más frecuentes fueron fiebre y tos (80%), seguidas por diarrea (47%) y manifestaciones cutáneas (35%). El estudio histopatológico fue el método de confirmación más frecuente. El antígeno urinario, fue positivo en el 92.8% de los pacientes a quienes se les realizó la prueba. Las enfermedades autoinmunes fueron la principal causa asociada en pacientes VIH negativos. Conclusiones: Las características clínicas de los pacientes con histoplasmosis son similares a las descritas en estudios previos en colombia, llamando la atención la alta prevalencia de diarrea y manifestaciones cutáneas. El antígeno urinario para histoplasma y las biopsias cutáneas son excelentes métodos diagnósticos, menos invasivos y con resultados rápidamente disponibles.

Introduction: Disseminated histoplasmosis is a common presentation in immunosuppressed patients. The introduction of new diagnostic methods and the impro vement of the survival of patients with HIV could have changed the clinical characteristics of patients with this disease. The objective of this study is to describe the demographic characteristics, clinical and methods for diagnosis of this disease in a high conplexity institution in Colombia during the last five years. Methods: A serie of cases was conducted, including patients diagnosed with histoplasmosis managed at the San Ignacio University Hospital in Bogotá (Colombia) between January 2012 and December 2016. The cases were selected using an automatic tool for searching in health electronic records (DISEARCH). Results: 34 patients were included, 73.5% with HIV. The disease was more symptomatic in patients with HIV. The most frequent symptoms were fever and cough (80%), followed by diarrhea (47%) and skin manifestations (35%). The histopathological study was the most frequent confirmation method. The urinary antigen was positive in 92.8% of the patients, in whom the test was performed. Autoimmune diseases were the main cause associated in HIV negative patients. Conclusions: The clinical characteristics of patients with histoplasmosis are similar to those described in previous studies in Colombia. It was remarkably the high prevalence of diarrhea and cutaneous manifestations. The urinary antigen for histoplasma and skin biopsies are excellent diagnostic methods, less invasive and with rapidly available results.

Disseminated histoplasmosis in an HIV-positive Filipino

Introduction@#Histoplasmosis is a granulomatous infection caused by the fungus, Histoplasma capsulatum. The disseminated type can be the initial manifestation of HIV/AIDS. It may affect the lungs, skin, gastrointestinal tract, liver, spleen, genitourinary tract, heart, bone marrow, adrenal glands, lymph nodes, and the central nervous system. Cutaneous findings are diverse and most present with few nodules and ulcerative lesions with involvement of the mucosal surface.@*Case summary@#This article describes the case of a 42-year-old male who presented fever, cough, oral ulcers, and multiple brownish nodular papules and plaques on the lips, face, trunk and extremities. Skin biopsy with tissue culture and sensitivity revealed Histoplasma capsulatum which was resistant to the recommended treatment, Amphotericin-B and Itraconazole. The patient was seropositive for HIV.@*Conclusion@#The incidence of HIV in the Philippines is rapidly increasing and we are expected to encounter more cases of opportunistic infections, such as in this case. Having a high index of clinical suspicion is important in establishing a diagnosis. In patients with HIV/AIDS or presumed to have AIDS presenting with multiple cutaneous lesions, skin biopsy for identification, culture, and sensitivity studies are valuable in determining the diagnosis and initiating treatment. Furthermore, the stigma of being diagnosed with HIV/AIDS prevents people from having HIV tests done. This causes delay in the diagnosis and treatment, and results in higher mortality. Public education and patient counseling are therefore vital in addressing the HIV epidemic.

Histoplasmosis diseminada en paciente con infección por VIH / Disseminated Histoplasmosis in a patient with infection

La Histoplasmosis es una infección micóticaoportunista, frecuente en pacientes con infección por virus de inmunodeficiencia humana (VIH) y síndrome de inmunodeficiencia adquirida (SIDA). La mayoría de las veces suele ser asintomática, pudiendo asociarse a hemorragia, destrucción acelerada de las plaquetas y descenso de la hemopoyesis debido a infección de los megacariocitos. Este reporte trata de un paciente con diagnóstico reciente de infección por VIH, por cuadro de 1 mes de evolución caracterizado por fiebre, malestar general y pérdida de peso mayor a 10% de la masa ponderal. Durante su hospitalización se realizaron estudios de imágenes y laboratorio para tamizaje de infecciones oportunistas. La evolución clínica inicialmente estuvo marcada por deterioro progresivo del estado general, con alteraciones persistentes de las plaquetas y de la serie eritroide, por lo que fue evaluado por el servicio de Hematología, que realizó la punción biopsia por aspiración de médula ósea (BAMO) para descartar malignidad hematológica y compromiso medular por agentes oportunistas.

Histoplasmosisis an opportunistic fungal infection, frequent in patients with infection by human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Most of the time it is usually asymptomatic, and it can be associated with hemorrhage, the accelerated destruction of platelets and the decrease in hemopoiesis due to an infection of megakaryocytes. This report is based on a recent diagnosis of HIV infection, in a picture of evolution of fever, malaise and weight loss greater than 10% of body weight.During his hospitalization, imaging and laboratory studies are carried out to screen for opportunistic infections. Clinical evolution remained marked by progressive general state, with persistent alterations of platelets and erythroid series, so it was evaluated by the hematology service, which performed the bone marrow aspiration biopsy (BAMO) to rule out Hematological malignancy and spinal commitment by opportunistic agents.

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.

Histoplasma capsulatum: ¿un agente emergente para Chile? / Histoplasma capsulatum: an emerging agent in Chile?

Resumen En los últimos 11 meses, nuestro laboratorio ha diagnosticado 9 casos de histoplasmosis de presentación clínica en el territorio nacional. Todos los pacientes asociados a los cuadros clínicos son inmigrantes. Por medio del presente trabajo deseamos difundir y alertar a los profesionales de los laboratorios clínicos de nuestro país de la presencia y circulación de cepas de Histoplasma capsulatum en muestras clínicas. Asimismo, deseamos concientizar en el reforzamiento de las medidas de bioseguridad al interior de los laboratorios clínicos.

In the last eleven months, we have diagnosed 9 cases of Histoplasmosis in our country. All patients affected were from endemic areas of South-America. Here, we wish to inform and prevent to all clinical laboratories from Chile about the presence of Histoplasma capsulatum in clinical samples. In the same way we want to prepare and raising awareness of the strengthening of biosecurity measures.