Palatal perforation due to disseminated histoplasmosis as the first presentation of HIV-AIDS

Histoplasmosis is a systemic fungal infection caused by H. capsulatum usually in immunocompromised individuals such as those with HIV-AIDS. Though oral manifestations are rare, they could be the only and initial manifestation of HIV-AIDS. We report the case of a 23-year-old female who presented with oral ulcer and palatal perforation and detected to be suffering from disseminated histoplasmosis. She also turned out to be HIV positive. Her CD4+ count was undetectable. She responded well to intravenous liposomal Amphotericin B, oral itraconazole and antiretroviral therapy. To the best of our knowledge, histoplasmosis presenting as palatal perforation as the first manifestation of HIV-AIDS has not been reported from South India previously. A high index of suspicion is needed in such cases of exaggerated oral lesions even in states like Kerala to avoid delay in diagnosis and therapy.

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.

Diagnóstico micológico de histoplasmosis en Uruguay, reporte de una serie de casos de la última década

Introducción: La histoplasmosis es una micosis sistémica que afecta a humanos, su agente Histoplasma capsulatum, hongo dimorfo, es ubicuo en la naturaleza. Frecuentemente se presenta como reactivación en personas con infección por VIH/SIDA, con manifestaciones polimórficas y diseminadas. Las lesiones mucocutáneas son una importante llave diagnóstica. Objetivo: Contribuir al conocimiento de esta patología a través del reporte de los diagnósticos de laboratorio de histoplasmosis realizados en Uruguay en los últimos 10 años. Materiales y Métodos: Se realizó un estudio observacional, retrospectivo de las histoplasmosis diagnosticadas en el laboratorio de referencia de Micología de Facultad de Medicina y dos laboratorios clínicos. Se enrolaron los registros clínicos y analíticos asociados. Resultados: Fueron 69 los diagnósticos de histoplasmosis. Más de 80% correspondió a personas con infección por VIH/SIDA. El 62,3% del total presentó lesiones de piel y/o mucosas y en 58% el diagnóstico se realizó mediante el estudio de estas. El 62,3% de los diagnósticos se realizaron mediante la visualización al microscopio óptico de frotis coloreados. Conclusiones: La mayoría de las histoplasmosis se vinculan a la infección por VIH/SIDA. El estudio micológico de las lesiones de piel y/o de mucosas, es accesible, mínimamente invasivo, rápido y presenta una excelente performance diagnóstica.

Background: Histoplasmosis is a systemic mycosis that affects humans, its agent Histoplasma capsulatum, a dimorphic fungus, is ubiquitous in nature. It frequently presents as reactivation in people with HIV/AIDS infection, with polymorphic and disseminated manifestations. Mucocutaneous lesions are characteristic and an important diagnostic key. Aim: To contribute to the knowledge of this pathology through the report of histoplasmosis laboratory diagnosis made in Uruguay in the last 10 years. Methods: We conducted an observational, retrospective study of diagnosed histoplasmosis in the Mycology reference laboratory of the Faculty of Medicine and two clinical laboratories. Associated clinical and analytical records were obtained. Results: There were 69 histoplasmosis diagnoses. More than 80% corresponded to people with HIV/AIDS infection. 62.3% of the total presented skin and/or mucosal lesions and in 58% the diagnosis was made by studying them. 62.3% of the diagnoses were initially made by viewing colored smears under an optical microscope. Conclusions: Most histoplasmosis is linked to HIV/AIDS infection. Exposure to a high fungal load is a constant in cases of immunocompetent individuals. The mycological study of skin and/or mucosal lesions is accessible, minimally invasive, fast and has excellent diagnostic performance.

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)

Brote de histoplasmosis en el contexto de la pandemia por COVID-19 / Histoplasmosis outbreak in the context of the COVID-19 pandemic

La histoplasmosis es una micosis profunda de distribución mundial causada por el Histoplasma capsulatum var. capsulatum. Se caracteriza por una variabilidad clínica que depende principalmente de la carga fúngica, del estado inmunológico del paciente y de la virulencia del germen. Se describe un brote de histoplasmosis pulmonar aguda en militares, producido en el contexto epidemiológico de la COVID-19. El episodio tuvo lugar a partir de actividad laboral en cuevas donde participaron cuatro militares, tres de los cuales desarrollaron síntomas y fueron admitidos en el Hospital Dr. Gustavo Aldereguía Lima de Cienfuegos en enero de 2022. La información fue obtenida a través de la entrevista médica y la historia clínica. Se evidenció que en el contexto epidemiológico de la pandemia por COVID-19 no se debe subestimar el diagnóstico de otras enfermedades respiratorias, incluidas las micosis endémicas(AU)

Histoplasmosis is a deep mycotic infection of worldwide distribution caused by Histoplasma capsulatum var. capsulatum. It is characterized by clinical variability that depends mainly on the fungal load, the patient's immune status and the virulence of the germ. We describe an outbreak of acute pulmonary histoplasmosis among military officers, which occurred in the epidemiological context of COVID-19. The episode occurred during work activities in caves in which four soldiers participated, three of whom developed symptoms and were admitted to the "Dr. Gustavo Aldereguía Lima" Hospital in Cienfuegos in January 2022. The information was obtained through medical interviews and clinical records. It was evidenced that in the epidemiological context of the COVID-19 pandemic, the diagnosis of other respiratory diseases, including endemic mycoses, should not be underestimated(AU)

Histoplasmosis sistémica con lesión cutánea única en paciente con SIDA

La histoplasmosis es una enfermedad causada por el hongo dimorfo Histoplasma capsulatum, que involucra al tejido linfático, pulmones, hígado, bazo, glándulas suprarrenales, riñones y piel. En los últimos años ha emergido como una enfermedad oportunista, principalmente en aquellos individuos con inmunidad celular alterada, como es el caso de los pacientes con SIDA. Cerca de 70% de los pacientes sudamericanos con histoplasmosis y SIDA presenta lesiones cutáneas o mucosas. En Argentina y Paraguay, la histoplasmosis es la micosis sistémica más frecuente en individuos con infección por el VIH. Presentamos el caso de una paciente con diagnóstico de histoplasmosis sistémica cuya única manifestación es la lesión cutánea, confirmado con la anatomía patológica y, fundamentalmente, con el cultivo, constituyendo una presentación clínica inusual.

Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum, which involves lymphatic tissue, lungs, liver, spleen, adrenal glands, kidneys, and skin. In recent years, it has emerged as an opportunistic disease, mainly in individuals with altered cellular immunity, as is the case of AIDS patients. About 70% of South American patients with histoplasmosis and AIDS have cutaneous or mucosal lesions. In Argentina and Paraguay, histoplasmosis is the most common systemic mycosis in individuals with HIV infection. We present the case of an patient diagnosed with systemic histoplasmosis whose only manifestation is a single skin lesion, confirmed by pathology and, fundamentally by culture, constituting an unusual clinic presentation.

Acute pulmonary histoplasmosis: a case series from an outbreak in Southeastern Brazil

ABSTRACT Histoplasmosis is a systemic mycosis prevalent in the Americas. Humans become infected via the respiratory route by inhaling aerosols from soil contaminated with bird and bat excretions. Acute pulmonary histoplasmosis is usually asymptomatic and is more often a self-limiting illness. We report a series of seven acute pulmonary cases in adults during an outbreak in Nova Friburgo city, Rio de Janeiro State, Brazil, in a group of volunteers who were cleaning an old, abandoned house without using personal protective equipment. The patients had a favorable evolution after suitable treatment, but all required hospitalization.

Manifestación cutánea de histoplasmosis diseminada en un paciente con trasplante renal / Cutaneous manifestation of disseminated histoplasmosis in a renal transplant patient

Introducción: La infección por Histoplasma capsulatum ocurre con frecuencia en pacientes con inmunosupresión por VIH o en trasplantados que reciben tratamiento inmunosupresor. La infección primaria se adquiere por vía inhalatoria con afectación pulmonar y posteriormente puede diseminarse a otros órganos como hígado, intestinos, corazón, riñones, piel o tejido óseo. Es muy raro que ocurra en pacientes con trasplante renal, aunque sí es común en el trasplante pulmonar. Objetivo: Presentar el caso de un paciente con antecedente de trasplante renal 9 años antes que ingresó por presentar lesiones cutáneas no típicas de histoplasmosis, quien desarrolló 2 semanas después histoplasmosis diseminada, sin compromiso pulmonar. Caso clínico: Paciente masculino de 65 años de edad postrasplante renal, que desarrolló manifestación cutánea caracterizada por pápulas y placas eritematodescamativas con superficies costrosas y atróficas, acompañado de fiebre persistente y adenopatías. No presentó signos o síntomas pulmonares como manifestación de infección primaria. El diagnóstico definitivo se estableció mediante histopatología de piel y ganglios cervicales, además del crecimiento de H. capsulatum en hemocultivos específicos para hongos. Recibió tratamiento con anfotericina B liposomal y posteriormente con itraconazol de forma ambulatoria con evolución favorable. Conclusión: El caso descrito es importante, ya que no se asemeja a la presentación típica de esta entidad, es decir, con afectación pulmonar primaria y posteriormente cutánea. Se espera haber enriquecido el conocimiento de esta enfermedad en pacientes trasplantados.

Introduction: Histoplasma capsulatum infection frequently occurs in patients with HIV immunosuppression or in transplant recipients receiving immunosuppressive therapy. Primary infection is acquired by inhalation with pulmonary involvement, and may subsequently spread to other organs such as liver, intestines, heart, kidneys, skin or bone tissue. It is very rare in renal transplant patients, although it is common in lung transplantation. Objective: To present the case of a patient with a history of renal transplantation nine years earlier, who was admitted for presenting skin lesions not typical of histoplasmosis, developing disseminated histoplasmosis two weeks later, without pulmonary involvement. Clinical Case: Post-renal transplant male patient, aged 65, who developed cutaneous manifestations characterized by erythematous and scaly papules and plaques with crusty and atrophic surfaces, accompanied by persistent fever and lymphadenopathy. There were no pulmonary signs or symptoms of a primary infection. The definitive diagnosis was made by histopathology of skin and cervical nodes, in addition to the growth of H. capsulatum in specific blood cultures for fungi. The patient was treated with liposomal amphotericin B and later with itraconazole on an outpatient basis with favorable evolution. Conclusion: The case described is important since it does not resemble the typical presentation of this entity, that is, with primary pulmonary and subsequently cutaneous involvement. It is expected to have enriched the knowledge of this disease in transplanted patients.

COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient / COVID-19 asociado a histoplasmosis diseminada en un paciente trasplantado renal

Abstract We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS-CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient's progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis.

Resumen Se presenta un caso de histoplasmosis diseminada e infección por COVID-19 en un paciente trasplantado renal en Argentina. El paciente presentó un cuadro clínico respiratorio, y la tomografía computarizada (TC) de tórax mostró múltiples opacidades centrolobulillares bilaterales con patrón de árbol en brote. El paciente fue tratado inicialmente con antibióticos para agentes causantes de neumonía bacteriana adquirida en la comunidad y luego como tuberculosis. Un mes después se le diagnosticó una histoplasmosis diseminada y el hongo fue aislado del esputo, la piel y la mucosa oral. El hongo fue tipificado molecularmente como Histoplasma capsulatum clado LAmB. El paciente fue hospitalizado y se inició tratamiento con anfoteric-ina B liposomal vía intravenosa. Durante el transcurso de la terapia antifúngica los síntomas respiratorios del paciente empeoraron, una nueva TC de tórax mostró una lesión unilateral con apariencia de vidrio esmerilado y se detectó SARS-CoV-2 en el hisopado nasofaríngeo. El paciente fue tratado con plasmoterapia y se modificó el régimen de inmunosupresión (se interrumpió everolimus, se redujo micofenolato de mofetilo y se incrementó la meprednisona). La evolución del paciente fue favorable y fue dado de alta con tratamiento oral con itraconazol.

Histoplasmosis masquerading as tuberculosis: A report of three cases in immunocompetent children

The most common cause of granulomatous lymphadenitis in countries like ours is mycobactrium tuberculosis followed by atypical mycobacterial infection, fungal infections, parasitic infection, cat scratch disease, lymphogranuloma venereum (inguinal lymphadenopathy), and leprosy Here, we present three cases of lymphadenopathy due to histoplasmosis in immunocompetent children. Two of them presented with fever, lymphadenopathy, initially diagnosed as granulomatous lymphadenitis consistent with tuberculosis on FNAC and were put on antitubercular drugs. However, their condition gradually became worse. As the patients continued to deteriorate, subsequent lymph node biopsies were done and diagnosed as histoplasmosis. Third case presented with acute loss of vision with hepatosplenomegaly and lymphadenopathy. Initially considered as acute leukemia, but eventually established as histoplasmosis. Histoplasmosis should be considered as one of the possible causes of granulomatous lymphadenitis in children.

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.

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 en pacientes con infección por VIH en Paraguay: Casuística del Laboratorio Central del Ministerio de Salud Pública en el período 1993-2017

Resumen Introducción: La histoplasmosis es una micosis sistémica en pacientes inmunodeprimidos y su epidemiología es desconocida en el país. Objetivo: Describir los datos demográficos y clínicos de pacientes con infección por VIH (IpVIH) e histoplasmosis diagnosticadas en el Laboratorio Central de Salud Pública, Asunción-Paraguay. Pacientes yMétodos: Estudio retrospectivo y transversal de pacientes con muestras positivas a Histoplasma capsulatum diagnosticados en el período 1993-2017. Resultados: Fueron diagnosticados 162 pacientes con IpVIH e histoplasmosis. El origen de los pacientes en orden de prevalencia fue: la capital Asunción, Central, Cordillera y San Pedro. La relación hombre/mujer fue 4:1 y la edad media 34,1 ± 7,7 años con un rango de 18 a 61 años. La fiebre, las lesiones en piel y las úlceras en mucosa fueron los síntomas y manifestaciones más frecuentes. Los métodos para diagnósticos más utilizados fueron las escarificaciones de piel, úlceras muco-cutáneas y las punciones de médula ósea. Conclusión: Por ser el primer reporte nacional de histoplasmosis en pacientes con IpVIH, consideramos este trabajo relevante para la base de otros estudios de micosis profunda.

Abstract Background: Histoplasmosis is a systemic mycosis in immunosuppressed patients and its epidemiology is unknown in the country. Aim: To describe the demographic and clinical data of patients with HIV infection and histoplasmosis diagnosed in the Central Public Health Laboratory, Asunción-Paraguay. Methods: Retrospective and cross-sectional study of patients with Histoplasma capsulatum positive samples diagnosed in the period 1993-2017. Results: 162 patients with HIV infection were diagnosed as histoplasmosis. The origin of the patients in order of prevalence were the capital Asunción, Central, Cordillera and San Pedro departments. The male/female ratio was 4: 1 and the mean age was 34.1 ± 7.7 years with a range of18 to 61 years. Fever, skin lesions and mucosal ulcers were the most frequent symptoms and manifestations. The most widely used diagnostic methods were scarification of skin, mucocutaneous ulcers and bone marrow punctures. Conclusion: As it is the first national report of histoplasmosis in patients with HIV infection, we consider this work relevant for the basis of other studies of deep mycosis.

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.

Histoplasmosis cerebral / Cerebral histoplasmosis

RESUMEN La histoplasmosis cerebral primaria es poco frecuente, en la mayoría de los casos se presenta en forma secundaria a la diseminación desde un foco primario pulmonar. El histoplasma es un hongo dimórfico y endémico que ha sido identificado en Estados Unidos, Canadá, México, Centro y Sudamérica, y es menos común en África, Asia y Europa. La infección se produce por la inhalación inadvertida de las conidias contenidas en los cuerpos fructíferos; el pulmón es el sitio de infección primaria. De las infecciones documentadas por histoplasma en individuos inmunocompetentes, entre el 50 % y el 90 % son asintomáticas, y de las infecciones sintomáticas, el 80 % no requiere terapia y resuelve en forma espontánea; sin embargo, el histoplasma puede diseminarse por toda la economía, incluyendo el sistema nervioso central (SNC). La presentación clínica de histoplasmosis con compromiso del SNC es inespecífica y puede simular otras patologías más comunes. El diagnóstico es particularmente difícil en casos en los que solamente se presenta compromiso aislado del SNC. La histoplasmosis diseminada conlleva un alto riesgo de mortalidad; el tratamiento consta de una fase de inducción seguida de una fase de mantenimiento.

SUMMARY Primary cerebral histoplasmosis is rare and in the majority of cases presents in secondary to dissemination from a primary pulmonary focus. Histoplasma is a dimorphic and endemic fungus. It has been identified in the United States, Canada, central Mexico and South America and is less common in Africa, Asia, and Europe. The infection is caused by inadvertent inhalation of the conidia contained in the fruiting bodies, the lung is the site of primary infection. Of documented histoplasma infections in individuals immunocompetent, between 50 % and 90 % are asymptomatic, and of symptomatic infections, 80 % do not require therapy and resolve spontaneously, however, histoplasma can spread throughout the economy including the central nervous system (CNS). The presentation Histoplasmosis with CNS involvement is nonspecific and can mimic other most common pathologies. Diagnosis is particularly difficult in cases where it only presents isolated CNS involvement. Disseminated histoplasmosis carries a high risk of mortality; treatment consists of an induction phase followed by a maintenance.

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.

Características clínicas, epidemiológicas, diagnóstico y tratamiento de los pacientes pediátricos con histoplasmosis en el Hospital Materno infantil José Domingo de Obaldía, desde enero 2008 a diciembre 2018 / Clinical, epidemiological characteristics, diagnosis and treatment of pediatric patients with histoplasmosis at the Hospital Materno Infantil José Domingo de Obaldia, since January 2008 to December 2018

Introducción: La histoplasmosis es una enfermedad causada por el hongo Histoplasma capsulatum descrita por primera vez por Samuel Taylor Darling en un trabajador de la zona del canal de Panamá. La exposición al hongo es frecuente en áreas tropicales y subtropicales, la mayoría son infecciones asintomáticas o ligeramente sintomáticas Los pacientes pediátricos son más vulnerables a padecer formas graves de histoplasmosis, especialmente menores de dos años. Materiales y métodos: Se realizó un estudio transversal retrospectivo, en pacientes diagnosticados con histoplasmosis en el Hospital Materno Infantil José Domingo de Obaldía de enero de 2008 a diciembre 2018. Resultados:Se analizaron 8 casos en 11 años (2008-2018), El principal grupo afectado fueron los menores de 2 años (n=7). Las características clínicas encontradas fueron: hepatomegalia y esplenomegalia en todos los pacientes, además, fiebre, adenopatías, anorexia, y astenia Se encontró trombocitopenia en todos los casos, seguido de anemia y leucopenia; e infiltrado alveolo intersticial en la radiografía de tórax de 6 pacientes. No se encontraron pacientes con infección por VIH. El método diagnóstico fue a través de estudios histopatológicos en el aspirado de médula ósea. El tratamiento utilizado fue anfotericina B, seguido de Itraconazol. De los 8 pacientes, 6 fallecieron con una letalidad del 75%. Conclusiones: Es una entidad poco frecuente en nuestra institución. Tiene una alta letalidad, siendo los más vulnerables los menores de 2 años; representando el 89% de las defunciones. Los pacientes presentaron datos de infección diseminada. Se debe sospechar histoplasmosis en pacientes con hepatomegalia, esplenomegalia, trombocitopenia, anemia y/o leucopenia.

Introduction: Histoplasmosis is a disease caused by the Histoplasma capsulatum fungus, first described by Samuel Taylor Darling in a worker in the Panama Canal area. Exposure to the fungus is common in tropical and subtropical areas, most are asymptomatic or slightly symptomatic (self-limited) infections. Pediatric patients are more vulnerable to severe forms of histoplasmosis, especially under two years. Materials and methods: A retrospective cross-sectional study was carried out in patients diagnosed with histoplasmosis at Hospital Materno Infantil José Domingo de Obaldía from January 2008 to December 2018. Results: 8 cases were analyzed in 11 years (2008-2018), mostly of the male sex (n = 5). The main age group affected were those under 2 years of age (n = 7). The clinical features found were hepatomegaly and splenomegaly in all patients, in addition, fever, lymphadenopathy, anorexia, and asthenia. In the complementary studies thrombocytopenia was found in all cases, followed by anemia and leukopenia, in addition to alveolo-interstitial infiltrate on the chest radiograph of 6 patients. The diagnostic method was histopathological studies in bone marrow aspirate. The treatment used was amphotericin B, followed by Itraconazole. Of the 8 patients, 6 died with a lethality of 75%. Conclusions: It is a rare entity in our institution. It has a high lethality, the most vulnerable being those under 2 years. Patients presented disseminated infection data. Histoplasmosis should be suspected in patients with hepatomegaly, splenomegaly, thrombocytopenia, anemia and (or ) leukopenia.

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.

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.

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.