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BACKGROUND: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. METHODOLOGY: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. RESULTS: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. CONCLUSIONS: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO.

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El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti. El comportamiento del dengue en Argentina es epidémico; la mayoría de los casos se observan en los meses de mayor temperatura. Hasta la semana epidemiológica (SE) 20/2023, se registraron en Argentina 106 672 casos; se vieron afectadas 18 de las 24 provincias que conforman el país. Dentro de los principales grupos de riesgo, se incluyen los menores de 2 años. Reconocer los signos, síntomas e identificar los factores de riesgo es fundamental para el manejo de casos con mayor riesgo de gravedad. Presentamos el caso de una paciente de 32 días de vida que se internó por síndrome febril sin foco, con diagnósticos diferenciales de meningitis viral y sepsis, evolucionó con leucocitosis, plaquetopenia, hipoalbuminemia, asociado a exantema y edemas. Se llegó al diagnóstico de dengue por la clínica, epidemiologia e IgM positiva.

Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes. In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months.Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of severity. Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis of dengue fever was established based on clinical, epidemiological, and positive IgM data.

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Introducción: La enfermedad de Still del adulto es una enfermedad reumática, inflamatoria, sistémica y crónica cuya prevalencia en la población caucásica se estima en 1 caso por cada 100 000 adultos Objetivo: Presentar un paciente adulto joven, con una fiebre de origen desconocido como forma de presentación de la enfermedad de Still del adulto. Caso clínico: Paciente de 29 años de edad con antecedente de fiebre reumática, con un ingreso hospitalario anterior; que presentó un cuadro febril no infeccioso, de 50 días de duración, al cual no se le determinó la causa. Un año después reapareció la fiebre, de similares características, asociada a poliartralgia, hepatoesplenomegalia, anemia, hiperferritinemia, neutrofilia, factor reumatoideo negativo y se constató un cuadro de pericarditis durante el ingreso. Se realizó el diagnóstico de enfermedad de Still del adulto, por exclusión. Se inició tratamiento con esteroides, desapareció la fiebre en las primeras 24 horas y el paciente tuvo una evolución favorable. Conclusiones: La enfermedad de Still del adulto puede presentarse como una fiebre de origen desconocido y se diagnostica por exclusión, ya que no existen manifestaciones clínicas ni pruebas de laboratorio, patognomónicas. La hiperferritinemia es útil para la sospecha diagnóstica.

Introduction: Adult Still's disease is a rheumatic, inflammatory, systemic and chronic disease whose prevalence in the Caucasian population is estimated at 1 case per 100,000 adults. Objective: To present a young adult patient with a fever of unknown origin as the presentation of adult Still's disease. Clinical case: 29-year-old patient with a history of rheumatic fever, with a previous hospital admission; who presented a non-infectious febrile illness lasting 50 days, for which the cause was not determined. A year later, the fever reappeared, with similar characteristics, associated with polyarthralgia, hepatosplenomegaly, anemia, hyperferritinemia, neutrophilia, negative rheumatoid factor, and pericarditis was noted during admission. The diagnosis of adult Still's disease was made by exclusion. Treatment with steroids was started, the fever disappeared in the first 24 hours and the patient had a favorable evolution. Conclusions: Adult Still's disease can present as a fever of unknown origin and is diagnosed by exclusion, since there are no pathognomonic clinical manifestations or laboratory tests. Hyperferritinemia is useful for diagnostic suspicion.

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Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes. In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months. Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of severity. Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis of dengue fever was established based on clinical, epidemiological, and positive IgM data.

El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti. El comportamiento del dengue en Argentina es epidémico; la mayoría de los casos se observan en los meses de mayor temperatura. Hasta la semana epidemiológica (SE) 20/2023, se registraron en Argentina 106 672 casos; se vieron afectadas 18 de las 24 provincias que conforman el país. Dentro de los principales grupos de riesgo, se incluyen los menores de 2 años. Reconocer los signos, síntomas e identificar los factores de riesgo es fundamental para el manejo de casos con mayor riesgo de gravedad. Presentamos el caso de una paciente de 32 días de vida que se internó por síndrome febril sin foco, con diagnósticos diferenciales de meningitis viral y sepsis, evolucionó con leucocitosis, plaquetopenia, hipoalbuminemia, asociado a exantema y edemas. Se llegó al diagnóstico de dengue por la clínica, epidemiologia e IgM positiva.

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Los fenómenos reaccionales de la lepra son complicaciones inflamatorias que a menudo se presentan como verdaderas emergencias médicas durante el curso del tratamiento o incluso después de culminarlo. A menudo, los síntomas sistémicos como la fiebre pueden aparecer antes que las manifestaciones cutáneas y desconcertar al médico. Se realiza la presentación del caso de un paciente masculino, 39 años, sano, que acude con cuadro de 2 meses de evolución de fiebre, pérdida de peso, con posterior aparición de manchas rojas en todo el cuerpo. Se realizaron biopsia de piel y baciloscopia, con los cuales se pudieron llegar al diagnóstico de lepra.

The reactional phenomena of leprosy are inflammatory complications that often present as true medical emergencies during treatment or even after completion. Often, systemic symptoms such as fever can appear before skin manifestations and baffle the doctor. The case presented is a 39-year male patient, healthy, who consult with a 2-month history of fever, and weight loss, with subsequent appearance of red spots all over the body. A skin biopsy and smear microscopy were performed, with which leprosy was diagnosed.

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Granulomatous hepatitis is a well-defined histopathologic entity characterized by aggregates of modified macrophages (epithelioid in appearance) and other inflammatory cells that accumulate after persistent exposure to antigens. It induces a cellular immune response mediated by the release of various cytokines (including interferon-gamma [INF-γ], tumor necrosis factor-alpha [TNF-α], and interleukin 12 [IL-12]) that stimulate mononuclear cell fusion, culminating in the formation of multinucleated giant cells with a surrounding border of lymphocytes and fibroblasts. It represents between 2% and 15% of all pathological liver studies, usually during an infiltrative or cholestatic biochemical pattern. A practical approach is proposed based on a challenging clinical case of a patient with a fever of unknown origin in an intermediate incidence area for tuberculosis, such as Colombia.

La hepatitis granulomatosa es una entidad histopatológica bien definida que se caracteriza por la presencia de agregados de macrófagos modificados (de aspecto epitelioide) y otras células inflamatorias que se acumulan luego de la exposición persistente a antígenos, lo que induce una respuesta inmunitaria celular mediada por la liberación de varias citocinas (entre las que se destacan el interferón gamma [INF-γ], el factor de necrosis tumoral alfa [TNF-α] y la interleucina 12 [IL-12]) que estimulan la fusión de células mononucleares para culminar en la formación de células gigantes multinucleadas con un borde circundante de linfocitos y fibroblastos. Representa entre el 2 % y el 15 % de todos los estudios anatomopatológicos de hígado, en el curso por lo general de un patrón bioquímico de tipo infiltrativo o colestásico. Se propone un enfoque práctico a partir de un caso clínico retador de un paciente con fiebre de origen desconocido en una zona de incidencia intermedia para tuberculosis, como lo es Colombia.

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BACKGROUND: Antisynthetase syndrome is an inflammatory myopathy that is characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies. Only 30% of those who suffer from the disease can be identified. We present three Hispanic cases of antisynthetase syndrome with unusual clinical pictures were extended myositis panel results enable disease diagnosis and treatment. CASE PRESENTATION: A 57-year-old Hispanic/Latino female with an erythematous scaly plaque, unresolved fever and non-immune haemolytic anaemia in whom inpatient work-up for fever of unknown origin was positive for anti-PL12 positive myositis extended panel. A 72-year-old Hispanic/Latino male with amyopathic weakness syndrome and mechanic hands in whom impatient work-up was relevant for proximal muscle uptake and anti-PM75 and AntiPL-12 myositis extended panel. And a 67-year-old Hispanic/Latino male with progressive interstitial lung disease and unresolved fever ended in myositis extended panel positive for antiPL-7. After systemic immunosuppressor treatment, patients had favourable clinical and paraclinical responses during outpatient follow-up. CONCLUSIONS: The high variability of the antisynthetase syndrome in these cases demonstrates the importance of identification through an expanded panel and highlights the probability that this is a variable disease and that we need to include emerging molecular tests to promote the timely treatment of patients.

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Resumen Presentamos el caso de un hombre de 40 años, HIV positivo con regular adherencia al tratamiento, que consultó por episodios febriles intermitentes de dos años de evolución, agregando en los últimos dos meses dolor abdominal difuso progresivo y adenomegalias ge neralizadas indoloras. En el laboratorio presentó panci topenia, coagulopatía, hipoalbuminemia y reactantes de fase aguda aumentados. La tomografía computarizada (TC) de tórax, abdomen y pelvis únicamente evidenció hepato-esplenomegalia y adenomegalias generalizadas. Se realizaron múltiples exámenes microbiológicos, in cluyendo cultivos para Mycobacterium sp. de distintas muestras, todos con resultados negativos, a excepción de la RT-PCR para VHH-8. Se tomó biopsia escisional de ganglio iliaco izquierdo con hallazgos compatibles con enfermedad de Castleman. A pesar de reiniciar terapia antirretroviral, la sintomatología progresó, iniciando tratamiento con corticoides y ganciclovir. Luego de una semana, desarrolló falla mulitorgánica y anasarca, que contraindicaron los fármacos iniciados. Se realizó nueva TC de tórax que mostró infiltrados con patrón en árbol en brote en lóbulo superior derecho asociado a derra me pleural bilateral, y a nivel abdominal, progresión de hepato-esplenomegalia y ascitis. Pasó a unidad de cui dados intensivos 48 horas después por falla hepática ful minante. El paciente falleció en pocas horas. Se recibió postmortem el cultivo del aspirado traqueal positivo para Mycobacterium tuberculosis y la punción-biopsia hepática con granulomas no necrotizantes. Nuestro objetivo es remarcar la importancia de pesquisar tuberculosis activa en nuestro país frente a la sospecha de enfermedad de Castleman antes de iniciar tratamiento, y resaltar que la TBC también puede presentarse como complicación infecciosa elevando la morbimortalidad.

Abstract We present the case of a 40-year-old man, HIV posi tive with regular adherence to treatment, who consulted for intermittent febrile episodes during a two-years period, progressive diffuse abdominal pain and painless generalized lymphadenopathy in the last two months. Laboratory analysis showed pancytopenia, altered co agulation tests, hypoalbuminemia, and increased acute phase reactants. Computed tomography (CT) of the chest, abdomen and pelvis revealed hepato-splenomegaly and generalized lymphadenopathy. Multiple microbiological tests were performed, including cultures for Mycobacte rium sp. from different samples, with negative results, except for the RT-PCR for HHV-8. An excisional biopsy of the left iliac lymph node was taken with findings compatible with Castleman's disease. Despite restarting antiretroviral therapy, the symptoms progressed, starting treatment with steroids and ganciclovir. After a week, he developed multiple organ failure and anasarca, which contraindicated the drugs previously started. A new CT of the chest showed infiltrates with a tree-in-bud pattern in the right upper lobe with bilateral pleural effusion, and at the abdominal level, progression of hepatospleno megaly and ascites. He was transferred to the intensive care unit 48 hours later due to fulminant hepatic fail ure. The patient died within a few hours. Postmortem recieved culture results of the tracheal aspirate were positive for tuberculosis (TB) and the histopathology of the liver biopsy showed non-necrotizing granulomas. Our objective is to highlight the importance of screening for active TB, in our country, when Castleman's disease is suspected, before starting treatment, and to stand out that TB can also present as an infectious complication, increasing morbidity and mortality.

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We present the case of a 40-year-old man, HIV positive with regular adherence to treatment, who consulted for intermittent febrile episodes during a two-years period, progressive diffuse abdominal pain and painless generalized lymphadenopathy in the last two months. Laboratory analysis showed pancytopenia, altered coagulation tests, hypoalbuminemia, and increased acute phase reactants. Computed tomography (CT) of the chest, abdomen and pelvis revealed hepato-splenomegaly and generalized lymphadenopathy. Multiple microbiological tests were performed, including cultures for Mycobacterium sp. from different samples, with negative results, except for the RT-PCR for HHV-8. An excisional biopsy of the left iliac lymph node was taken with findings compatible with Castleman's disease. Despite restarting antiretroviral therapy, the symptoms progressed, starting treatment with steroids and ganciclovir. After a week, he developed multiple organ failure and anasarca, which contraindicated the drugs previously started. A new CT of the chest showed infiltrates with a tree-in-bud pattern in the right upper lobe with bilateral pleural effusion, and at the abdominal level, progression of hepatosplenomegaly and ascites. He was transferred to the intensive care unit 48 hours later due to fulminant hepatic failure. The patient died within a few hours. Postmortem recieved culture results of the tracheal aspirate were positive for tuberculosis (TB) and the histopathology of the liver biopsy showed non-necrotizing granulomas. Our objective is to highlight the importance of screening for active TB, in our country, when Castleman's disease is suspected, before starting treatment, and to stand out that TB can also present as an infectious complication, increasing morbidity and mortality.

Presentamos el caso de un hombre de 40 años, HIV positivo con regular adherencia al tratamiento, que consultó por episodios febriles intermitentes de dos años de evolución, agregando en los últimos dos meses dolor abdominal difuso progresivo y adenomegalias generalizadas indoloras. En el laboratorio presentó pancitopenia, coagulopatía, hipoalbuminemia y reactantes de fase aguda aumentados. La tomografía computarizada (TC) de tórax, abdomen y pelvis únicamente evidenció hepato-esplenomegalia y adenomegalias generalizadas. Se realizaron múltiples exámenes microbiológicos, incluyendo cultivos para Mycobacterium sp. de distintas muestras, todos con resultados negativos, a excepción de la RT-PCR para VHH-8. Se tomó biopsia escisional de ganglio iliaco izquierdo con hallazgos compatibles con enfermedad de Castleman. A pesar de reiniciar terapia antirretroviral, la sintomatología progresó, iniciando tratamiento con corticoides y ganciclovir. Luego de una semana, desarrolló falla mulitorgánica y anasarca, que contraindicaron los fármacos iniciados. Se realizó nueva TC de tórax que mostró infiltrados con patrón en árbol en brote en lóbulo superior derecho asociado a derrame pleural bilateral, y a nivel abdominal, progresión de hepato-esplenomegalia y ascitis. Pasó a unidad de cuidados intensivos 48 horas después por falla hepática fulminante. El paciente falleció en pocas horas. Se recibió postmortem el cultivo del aspirado traqueal positivo para Mycobacterium tuberculosis y la punción-biopsia hepática con granulomas no necrotizantes. Nuestro objetivo es remarcar la importancia de pesquisar tuberculosis activa en nuestro país frente a la sospecha de enfermedad de Castleman antes de iniciar tratamiento, y resaltar que la TBC también puede presentarse como complicación infecciosa elevando la morbimortalidad.

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La fiebre chikungunya es una enfermedad viral descrita por primera vez en 1952. Actualmente se informan brotes esporádicos de fiebre chikungunya a nivel país (abril 2022). Presentamos el caso de un varón joven con fiebre chikungunya en fase subaguda la cual se presentó al ingreso hospitalario como fiebre de origen desconocido.

Chikungunya fever is a viral disease first described in 1952. Sporadic outbreaks of chikungunya fever are currently reported nationwide (April 2022). We present the case of a young man with chikungunya fever in the subacute phase which presented at hospital admission as fever of unknown origin.