Presentación atípica de histoplasmosis diseminada / Atypical presentation of disseminated histoplasmosis

La histoplasmosis es una micosis sistémica producida por una variedad de hongo dimorfo perteneciente al complejo Histoplasma capsulatum. Es una enfermedad prevalente en nuestro medio y sobre todo en pacientes viviendo con HIV con recuento de <200 linfocitos CD4/ml y con cargas virales mayores a 100.000 copias/ml. La presentación de la forma diseminada raramente suele afectar al aparato reproductor; siendo la forma más frecuente pulmonar

Histoplasmosis in the anal canal: case report and literature review

We herein present the case of a patient with anal condylomatosis concomitant with histoplasmosis, whose diagnosis was only possible through the collection of material and the subsequent evidence of a primary pulmonary focus. Histoplasmosis is a fungal disease whose contamination occurs through the respiratory route, and it can spread to the digestive tract, but the anus is rarely affected. It is important to have a high degree of suspicion to make the diagnosis, especially in immunosuppressed patients.

Thrombotic Microangiopathy Due to Progressive Disseminated Histoplasmosis in a Child With Down Syndrome and Acute Lymphoblastic Leukemia.

Histoplasmosis, a common mycosis in the south-central United States, may be life threatening in immunocompromised patients. We describe a 4-year-old female with Down syndrome and acute lymphoblastic leukemia who developed hemolytic anemia, thrombocytopenia, and renal failure, consistent with thrombotic microangiopathy. Bone marrow biopsy revealed non-necrotizing granulomas with GMS staining demonstrating budding yeast. Serum Histoplasma antigen testing was positive, providing further evidence for the diagnosis of progressive disseminated histoplasmosis. Treatment with amphotericin B, plasma exchange, and ventilator, vasopressor, and renal replacement support led to a full recovery. Providers should have a low threshold for histoplasmosis testing in ill immunocompromised patients, who are at greater risk for infection-related morbidity.

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.

Endemic Fungi Presenting as Community-Acquired Pneumonia: A Review.

In endemic areas, dimorphic fungal infections due to Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii/immitis account for up to 30% of cases of community-acquired pneumonia. Because respiratory manifestations are often indistinguishable from common bacterial causes of pneumonia, the diagnosis of pulmonary histoplasmosis, blastomycosis, and coccidioidomycosis is often delayed and associated with antibiotics overuse. In addition to being highly endemic to certain regions of North America, dimorphic fungi have global significance due to established areas of endemicity in all six inhabited continents, an increasingly interconnected world of travelers and transported goods, and a changing epidemiology as a result of global heating and anthropomorphic land utilization. In this review, we discuss the epidemiology, pathogenesis, clinical presentation, diagnostic modalities, and treatment strategies for histoplasmosis, blastomycosis, and coccidioidomycosis.

Urine antigen-negative disseminated histoplasmosis mimicking post-transplant lymphoproliferative disorder.

A 50-year-old woman with a history of kidney transplant presented with 2 days of abdominal pain after 6 months of recurrent streptococcal pharyngitis, fevers, weight loss and a new rash on her chest and back. Her examination was notable for a unilateral tonsillar exudate and 2-3 mm pink papules with a fine scale over her chest and back. CT of the abdomen and chest demonstrated several large lymph nodes, and laboratory investigation revealed new cytopenias and elevated transaminases. Urine antigen testing for Histoplasma capsulatum was negative, but a fungal complement fixation panel was reactive for Histoplasma antibodies. Skin biopsy revealed intracellular organisms consistent with H. capsulatum She underwent treatment with liposomal amphotericin B but due to nephrotoxicity, drug interactions and worsening transaminitis, therapy was changed to itraconazole. The diagnosis and management of disseminated histoplasmosis presents multiple challenges, which are of particular importance in patients with a history of renal transplantation.

Presumed ocular histoplasmosis syndrome in a commercially insured population, United States.

PURPOSE: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN: Retrospective cohort study. METHODS: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM® MarketScan® Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES: Data related to testing, treatment, and direct medical costs. RESULTS: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV. CONCLUSIONS: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies.

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.

Hypercalcaemia, adrenal insufficiency and bilateral adrenal histoplasmosis in a middle-aged man: a diagnostic dilemma.

A 45-year-old man presented with a 3-month history of involuntary weight loss, anorexia, postural dizziness and intermittent fever. On investigation, he was found to have parathyroid hormone (PTH)-independent hypercalcaemia, with negative workup for 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D excess, thyrotoxicosis, multiple myeloma and bony metastases. On further evaluation, he was detected to have primary hypoadrenalism with bilateral adrenal enlargement, secondary to adrenal histoplasmosis. Hypercalcaemia improved with hydration and physiological steroid replacement even before initiation of antifungal therapy, confirming adrenal insufficiency as the cause for hypercalcaemia. Hypercalcaemia resulting from hypoadrenalism secondary to adrenal histoplasmosis is rare and should be suspected whenever evaluating a patient with PTH-independent hypercalcaemia.

Disseminated pulmonary histoplasmosis in immunocompetent patients: a common epidemiological exposure.

We describe the initial presentation, diagnostic work-up and treatment of three adult immunocompetent men who presented within a short time frame of each other to an academic medical centre with acute respiratory distress syndrome. Their presentation was found to be secondary to a large inoculum of histoplasmosis from remodelling a building with bat droppings infestation. We discuss the pathophysiology of histoplasmosis and highlight the importance of exposure history in patients with acute respiratory failure and why patients with the occupational risk of exposure to fungal inoculum should wear protective respirator gear.

Catheter based treatments for fibrosing mediastinitis.

Fibrosing mediastinitis is a rare, often debilitating and potentially lethal disease characterized by an exuberant fibroinflammatory response within the mediastinum. Patients typically present with insidious symptoms related to compression of adjacent structures including the esophagus, heart, airways, and cardiac vessels. Fibrosing mediastinitis is most often triggered by Histoplasmosis infection; however, antifungal and anti-inflammatory therapies are largely ineffective. While structural interventions aimed at alleviating obstruction can provide significant palliation, surgical interventions are challenging with high mortality and clinical experience with percutaneous interventions is limited. Here, we will review the presentation, natural history, and treatment of fibrosing mediastinitis, placing particular emphasis on catheter-based therapies.

MANAGEMENT OF NEOVASCULAR OCULAR HISTOPLASMOSIS: Past and Present.

PURPOSE: To review the wide variety of treatment modalities available for choroidal neovascularization secondary to the presumed ocular histoplasmosis syndrome. METHODS: A literature search was performed to review the multitude of studies conducted to investigate the efficacy and safety of treatment modalities available for choroidal neovascularization secondary to the presumed ocular histoplasmosis syndrome. RESULTS: Each treatment modality is reviewed, with the studies summarized and presented to support or refute the method of treatment. Two case reports are presented to demonstrate the treatment regimens. CONCLUSION: This is a comprehensive review of the treatment modalities available to address choroidal neovascularization secondary to the presumed ocular histoplasmosis syndrome. Investigators will continue to strive toward higher efficacy and safety with future innovations in the field.

A case of Histoplasma capsulatum variety capsulatum septic arthritis successfully treated with surgery, systemic antifungals, and local amphotericin cement beads.

Histoplasma capsulatum variety capsulatum (H. capsulatum) is a thermally dimorphic fungus that is endemic to the Mississippi River and Ohio River valley regions. Of the hundreds of thousands of patients exposed to this fungus, less than 1% develop a severe illness most commonly manifesting as pulmonary disease. Septic arthritis from hematogenous seeding with H. capsulatum or from direct inoculation has been reported only rarely in the literature. The first case of septic arthritis of the shoulder due to H. capsulatum occurring in an immunocompromised patient, treated successfully with irrigation and debridement, systemic antifungals, and local delivery of amphotericin B with cement beads, is reported here. Importantly, the addition of local amphotericin B delivery by cement beads to conventional treatment likely led to clinical cure in this patient.

Environmental and Wilderness-Related Risk Factors for Histoplasmosis: More Than Bats in Caves.

INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus that causes histoplasmosis, a sporadic endemic mycosis with environmental, occupational, and wilderness exposure-related risk factors. The objectives of this review are to describe these risk factors, to alert clinicians to the different presenting manifestations of histoplasmosis, and to recommend effective management and prevention strategies. METHODS: Internet search engines were queried with keywords to select articles for review over the study period, 1950 to 2018. Articles selected for review included case series, epidemiologic analyses of surveillance data, clinical and laboratory updates, immunologic investigations, and observational and longitudinal studies. Articles excluded from review included systemic mycosis reviews and clinicopathologic conference reports. RESULTS: The principal transmission mechanism of histoplasmosis is by inhalation of spores aerosolized by soil disruption, resulting in pneumonic infections ranging from asymptomatic to disseminated. Although histoplasmosis is more common in endemic regions, nonendemic regions have reported increasing autochthonous and imported cases. Immunocompromised persons are at significantly increased risks of contracting histoplasmosis. Environmental and wilderness-related risk factors for histoplasmosis include bird and bat watching, cave and cave entrance exploration, and bamboo removal and burning. Occupational risk factors for histoplasmosis include road construction, roofing, bridge and water tower work, demolition, and masonry. CONCLUSIONS: Histoplasmosis can result in considerable morbidity. Increased awareness of disease risk factors among the public and the international healthcare community will improve the timely diagnosis and treatment of histoplasmosis and prevent disease progression and dissemination.

Caso Clínico: Histoplasmosis Cutánea Diseminada en un Paciente Inmunocomprometido / Case Report: Cutaneous Histoplasmosis Disseminated in an Immunocompromised Patient

INTRODUCCIÓN: La histoplasmosis es una micosis sistémica frecuente en pacientes inmunocomprometidos. La clínica es variable y se considera la micosis respiratoria más frecuente a nivel mundial, presentando mayor prevalencia en zonas tropicales incluida Sur América. Se estima que existen cuarenta millones de enfermos, calculándose doscientos mil nuevos casos anualmente. En Ecuador se desconoce la epidemiología de la enfermedad pero se calcula que el 11.1 % de pacientes con SIDA tienen histoplasmosis. CASO CLÍNICO: Paciente masculino de 23 años, procedente del Oro - Ecuador, con antecedentes de SIDA diagnosticado hace cuatro años, con mala adherencia al tratamiento antirretroviral y tuberculosis pulmonar, es ingresado por presentar fiebre de dos semanas de evolución, astenia, tos productiva, pérdida de peso, pápulas eritemato-violáceas costrosas diseminadas en todo el tegumento, con afectación mucosa. Los factores de riesgo que presentó el paciente para histoplasmosis la falta de cumplimiento al tratamiento antirretroviral y vivir en un área rural con exposición a excrementos de aves de corral. EVOLUCIÓN: El paciente fue hospitalizado con diagnóstico de histoplasmosis cutánea diseminada, SIDA, tuberculosis pulmonar, candidiasis oral y herpes anal. Se continuó con el tratamiento antirretroviral, antituberculoso e inició Anfotericina-B e Itraconazol; posteriormente el paciente fue dado de alta con mejoría clínica. CONCLUSIÓN: Las dermatosis juegan un papel importante para realizar el diagnóstico precoz de histoplasmosis. Cuando existen comorbilidades asociadas a la enfermedad, como el SIDA y tuberculosis pulmonar, es necesario replantear el tratamiento, por la interacción medicamentosa que puede existir entre el Itraconazol y la Rifampicina. El paciente recibió Anfotericina­B hasta presentar mejoría clínica. Para la prevención de enfermedades oportunistas una correcta adhesión al tratamiento antirretroviral, evitar el hábitat del hongo como criaderos de aves o cuevas y ante el riesgo de exposición, el uso adecuado de mascarilla.

BACKGROUND: Histoplasmosis is a frequent systemic mycosis in immunocompromised patients. The clinic is variable and is considered the most common respiratory mycosis worldwide, presenting a higher prevalence in tropical areas including South America. It is estimated that there are forty million patients, calculating two hundred thousand new cases annually. In Ecuador, the epidemiology of the disease is unknown, but it is estimated that 11.1% of patients with AIDS have histoplasmosis. CASE REPORT: Male patient of 23 years old, from Oro - Ecuador, with a history of AIDS diagnosed four years ago, with poor adherence to antiretroviral treatment and pulmonary tuberculosis, is admitted for presenting fever of two weeks evolution, asthenia, productive cough, weight loss, scaly erythematous-violaceous papules spread throughout the integument, with mucosal involvement. The risk factors presented by the patient for histoplasmosis were the lack of compliance with antiretroviral treatment and living in a rural area with exposure to poultry excrement. EVOLUTION: The patient was hospitalized with diagnosis of disseminated cutaneous histoplasmosis, AIDS, pulmonary tuberculosis, oral candidiasis and anal herpes. Antiretroviral, antituberculous treatment was continued and Amphotericin-B and itraconazole were started; later the patient was discharged with clinical improvement. CONCLUSION: Dermatoses play an important role in the early diagnosis of histoplasmosis. When there are comorbidities associated with the disease, such as AIDS and pulmonary tuberculosis. It is necessary to rethink the treatment, due to the drug interaction that may exist between Itraconazole and Rifampicin. The patient received Amphotericin-B until clinical improvement. For the prevention of opportunistic diseases, a correct adherence to the antiretroviral treatment, avoid the habitat of the fungus as bird or cave farms and before the risk of exposure, the adequate use of a mask.

Tuberculosis and Other Granulomatous Diseases of the Airway.

Granulomatous diseases of the airway are challenging lesions to diagnose and effectively manage not only because they are uncommon but also because they can occur in different forms, each with unique clinical and radiological characteristics. Most such lesions can be effectively managed conservatively with repeated airway dilatation, use of intraluminal stents, and specific antimicrobial treatment. The only exception is those lesions presenting with localized airway obstruction wherein surgical resection may be indicated and beneficial.