Tuberculosis y síndrome inflamatorio de reconstitución inmunológica. Caso pediátrico / Tuberculosis and immune reconstitution inflammatory syndrome. Pediatric case

La tuberculosis es una enfermedad muy frecuente en nuestro medio. A pesar de que la detección precoz y el tratamiento adecuado logran la curación en la mayoría de los pacientes, la dificultad en el diagnóstico, el abandono del tratamiento y la aparición de resistencia a los fármacos tradicionales generan que, en la actualidad, continúe siendo un importante problema de salud pública. En la Argentina, la tasa de morbilidad es de 25/100 000 habitantes, con un leve aumento en la mortalidad.Se presenta el caso de una paciente pediátrica con tuberculosis, que tuvo múltiples complicaciones asociadas a la enfermedad y a su tratamiento, entre las cuales se incluye el síndrome in-flamatorio de reconstitución inmunológica, también conocido como reacción paradojal al tratamiento antituberculoso. Este representa una consecuencia clínica adversa al restablecimien-to de la inmunidad en el paciente que padece una infección sistémica grave, como la tuberculosis miliar.

Tuberculosis is a very frequent disease in our environment. Although early detection and adequate treatment achieve cure in most patients, the difficulty in diagnosis, the abandonment of treatment and the appearance of resistance to traditional drugs generate that at present it continues to represent an im-portant public health problem. In Argentina, the morbidity rate is 25/100,000 inhabitants, with a slight increase in mortality.We present the case of a pediatric patient with tuberculosis and multiple complications associated with the disease and its treatment. One of these complications was the immune re-constitution inflammatory syndrome or paradoxical reaction to antituberculosis treatment. It represents an adverse clinical con-sequence of the restoration of immunity in the patient suffering from a serious systemic infection such as miliary tuberculosis.

Síndrome de Job asociado a tuberculosis miliar

El síndrome de hiper IgE también denominado síndrome de Job, es una inmunodeficiencia primaria poco frecuente, cuyo modo de herencia puede ser autosómico recesivo o dominante. Se caracteriza por altos niveles de IgE, eosinofilia, abscesos cutáneos, eccema, candidiasis mucocutánea crónica e infecciones pulmonares recidivantes que contribuyen al desarrollo de neumatoceles y bronquiectasias. El germen más frecuentemente aislado es el Staphylococcus aureus. En la actualidad, ante la mayor supervivencia de los pacientes se han comunicado infecciones oportunistas y linfomas. Existen escasas publicaciones de pacientes con enfermedad por Mycobacterium tuberculosis asociada a síndrome de hiper IgE, por lo que consideramos relevante comunicar el caso de un paciente con antecedentes de una tuberculosis pulmonar, que presentó una tuberculosis miliar con grave compromiso respiratorio, con buena respuesta al tratamiento estándar con drogas de primera línea.

The hyper Immunoglobulin E syndrome, also known as Job´s syndrome, is a rare primary immunodeficiency, its mechanisms of inheritance maybe recessive or dominant autosomal. It is characterized by high levels of IgE, eosinophilia, skin abscesses, eczema, chronic mucocutaneous candidiasis and recurrent pulmonary infections all of which contribute to the development of pneumatoceles and bronchiectasis. The most frequently isolated bacteria is Staphylococcus aureus. Currently, despite the highest survival of patients, lymphomas and other opportunistic infections have been reported. There are few reports of patients with Mycobacterium tuberculosis infection associated with hyper IgE syndrome. Therefore it is relevant that we report a case history of a patient with pulmonary tuberculosis, presenting miliary tuberculosis and severe respiratory compromise, who responded positively to standard anti-tuberculous treatment with first line drugs.

Primary pulmonary diffuse large B-cell non-Hodgkin's lymphoma in a child.

A 3-year-old girl presented with a history of intermittent fever of six months duration associated with respiratory symptoms consisting of recurrent cough, fever, wheeze and a suspected history of contact with tuberculosis (TB). Chest radiograph revealed pulmonary infiltrates mimicking miliary TB. She was started on anti-tuberculous treatment, but in view of clinical deterioration, a further work-up including a lung biopsy revealed non-Hodgkin’s lymphoma (NHL). This case documents the extremely rare occurrence of pulmonary involvement and miliary infiltrates on the chest radiograph in NHL.

Challenges in the diagnosis & treatment of miliary tuberculosis.

Miliary tuberculosis (TB) is a potentially lethal disease if not diagnosed and treated early. Diagnosing miliary TB can be a challenge that can perplex even the most experienced clinicians. Clinical manifestations are nonspecific, typical chest radiograph findings may not be evident till late in the disease, high resolution computed tomography (HRCT) shows randomly distributed miliary nodules and is relatively more sensitive. Ultrasonography, CT and magnetic resonance imaging (MRI) are useful in discerning the extent of organ involvement by lesions of miliary TB in extra-pulmonary locations. Fundus examination for choroid tubercles, histopathological examination of tissue biopsy specimens, conventional and rapid culture methods for isolation of Mycobacterium tuberculosis, drug-susceptibility testing, along with use of molecular biology tools in sputum, body fluids, other body tissues are useful in confirming the diagnosis. Although several prognostic markers have been described which predict mortality, yet untreated miliary TB has a fatal outcome within one year. A high index of clinical suspicion and early diagnosis and timely institution of anti-tuberculosis treatment can be life-saving. Response to first-line anti-tuberculosis drugs is good but drug-induced hepatotoxicity and drug-drug interactions in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients pose significant problems during treatment. However, sparse data are available from randomized controlled trials to define the optimum regimen and duration of treatment in patients with drug-sensitive as well as drug-resistant miliary TB, including those with HIV/AIDS.

Tuberculosis miliar en paciente inmunocompetente: caso clínico y revisión de la literatura / Miliary tuberculosis in immunocompetent patient: case report and literature review

La tuberculosis en Chile ha tenido un considerable descenso en incidencia y mortalidad, encontrándonos en la etapa de eliminación como problema de salud pública. Sin embargo, a medida que la tuberculosis pulmonar disminuye en frecuencia, la proporción de tuberculosis extrapulmonar se incrementa. Como es conocido, el pulmón es el órgano diana por excelencia, pero cualquier órgano puede ser afectado. Dentro de las tuberculosis extrapulmonares, la forma miliar corresponde sólo a un 5 por ciento de los casos. La diseminación miliar es rara en pacientes inmunocompetentes, estando prácticamente restringida a grupos de riesgo. El diagnóstico de la tuberculosis miliar requiere de un alto índice de sospecha, ya que su clínica es inespecífica, y el aislamiento del bacilo de Koch difícil.

Prueba de cosintropina en tuberculosis activa grave / Cosyntropin test in severe active tuberculosis

BACKGROUND: Frequency of adrenal insufficiency in patients with tuberculosis varies from 0 to 58%; however, all published series excluded severely ill patients. Our objective was to investigate adrenal insufficiency with the low-dose cosyntropin test in patients with severe active tuberculosis. METHOD: From two large university affiliated hospitals, 18 patients with tuberculosis and criteria of sepsis or severe sepsis according to SCCM/ACCP criteria, defined by the present authors as severe active tuberculosis, participated in the study. A low-dose ACTH test with 10 mg of ACTH was performed. After ACTH test, all patients received a stress dose of hydrocortisone (240 mg/day) during their entire hospitalization along with four antituberculous drugs. Abnormal response was considered when elevation of serum cortisol was <7 microg/dl with respect to basal level, 60 min after ACTH administration. RESULTS: Adrenal insufficiency was found in seven patients (39%); no clinical or laboratory data were associated with the presence of abnormal adrenal response. Except in one patient with HIV infection, all the signs and symptoms improved after antituberculous and hydrocortisone treatment. The increment in serum cortisol value post-ACTH test was lower in patients with hypoalbuminemia. CONCLUSIONS: Adrenal insufficiency is frequent in severe active tuberculosis. The efficacy and security of supplemental steroid treatment in severe active tuberculosis should be established by a randomized clinical trial.

Effect of antituberculosis treatment on cardiopulmonary responses to exercise in miliary tuberculosis.

BACKGROUND & OBJECTIVES: Tuberculosis (TB) is a major health problem in the developing world. In this preliminary study, we report the effect of antituberculosis treatment (ATT) on cardiopulmonary responses to exercise in patients with miliary tuberculosis (MTB). METHODS: The prospective study of cardiopulmonary responses to exercise in patients with MTB within one month of starting (n=14), on completion of ATT (n=7) and in 15 healthy subjects using the incremental exercise test was performed on a bicycle ergometer. RESULTS: In MTB patients, mean body mass index (BMI), exercise duration (3.1 vs 4.6 min), work load (63 vs 91.4 watts), resting tachycardia, tachypnoea and the mean oxygen saturation improved significantly (P<0.05) with ATT. Mean oxygen consumption (V . O(2)) at anaerobic threshold (546.7 vs 580.9 ml/min) and maximum exercise (1008.1 vs 1022 ml/min) were similar before and after ATT. In MTB patients, post-treatment mean body weight, BMI, resting heart rate, respiratory rate and oxygen saturation during maximum exercise were similar, but exercise duration (4.6 vs 6.2 min, P<0.05), work load (91.4 vs 145.5 watts, P<0.05), V . O(2) and oxygen pulse were significantly lower as compared to healthy subjects. INTERPRETATION & CONCLUSION: In MTB patients, though there was significant improvement in clinical parameters, functional abnormalities persisted on exercise testing after completion of ATT. As most patients with MTB are young and economically active, these observations obviously have long-term implications for these individuals.

Tuberculosis miliar en paciente inmunocompetente como causa rara de fiebre nosocomial / Miliary tuerculoosis an uncommon cause of nosocomial fever in an immunocompetent patient

A progresive decrease of tuberculosis incidence has been shown in the last years in Chile. Presently Chile is considered as a country with a low incidence of tuberculosis (< 20 cases per 10(5) inhabitants). Miliary tuberculosis is an uncommon form of tuberculosis in immunocompetent patients. Miliary tuberculosis is tipically observed in immunocompromised patients. It is an infrequent cause of nosocomial fever. We report a case of miliary tuberculosis in an immunocompetent patient, that caused intrahospitalary fever, in the course of a long term hospitalization.

La tuberculosis ha disminuido su incidencia en los últimos años en Chile, siendo considerado actualmente como un país con baja incidencia de tuberculosis (< 20 casos por 10(5) habitantes). Dentro de las diferentes formas de presentación clínica de la tuberculosis, la diseminación miliar es rara en pacientes inmunocompetentes, estando restringida prácticamente a determinados grupos de riesgo. Más excepcional aún es considerar a la tuberculosis miliar como causa de fiebre intrahospitalaria. Comunicamos un caso de tuberculosis miliar en un paciente inmunocompetente, como causa de fiebre nosocomial, durante una hospitalización prolongada.

Multidrug resistant miliary tuberculosis and Pott's disease in an immunocompetent patient

In a high tuberculosis TB prevalence country, mortality due to miliary TB is not unknown but the treatment outcome in general is good. We describe a previously healthy man with miliary TB who did not respond to 2-months antituberculous therapy with 4 drugs. Persistent complaints of backache, which antedated chest symptoms, resulted in a diagnosis of Pott's disease. Culture of bronchial aspirate yielded multidrug resistant Mycobacterium tuberculosis that responded slowly to streptomycin, ethionamide, cycloserine, clofazimine, ofloxacin, paraaminosalicylic acid and isoniazid. The association of multidrug resistant miliary TB with Pott's disease in an immunocompetent patient is yet to be highlighted

Breakthrough neurological manifestation during appropriate antituberculous therapy of miliary tuberculosis.

We report a 20-month-old girl with miliary pulmonary tuberculosis and normal neurological findings. While on treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol for 1 month, she developed weakness of the lower extremities without meningism or altered consciousness. A computerized tomogram revealed tuberculomas and basal arachnoiditis. The cerebrospinal fluid findings were compatible with tuberculous meningitis. She responded well to systemic corticosteroids.

Múltiplos tuberculomas intracerebrais na vigência de terapia específica para tuberculose pulmonar: a propósito de um caso / Multiple intracranial tuberculomas developing during specific treatment of pulmonary tuberculosis: case report

A forma clássica de apresentação da neurotuberculose é a meningite. Os tuberculomas cerebrais são formas raras de neurotuberculose e resultam da disseminação hematogênica de focos distantes de infecção pelo Mycobacterium tuberculosis. Aproximadamente 1 por cento dos pacientes com tuberculose do sistema nervoso central desenvolve tuberculomas intracranianos, poucas semanas ou meses após o início da quimioterapia tuberculostática. A involução das lesões é lenta e não necessariamente significa resistência medicamentosa ou falta de aderência ao tratamento. Descrevemos o caso, diagnosticado e tratado na 25ª Enfermaria da Santa Casa da Misericórdia do Rio de Janeiro, de um paciente imunocompetente que apresentou meningite e tuberculomas múltiplos do sistema nervoso central, durante o tratamento específico de tuberculose miliar. A literatura é revisada e o diagnóstico, terapêutica e possíveis mecanismos imunológicos são discutidos.

Tuberculosis hematógena tardía / Late tuberculosis

La tuberculosis hematógena tardía es una forma de tuberculosis miliar que se presenta mucho tiempo después de la infección primaria, a partir de un foco extrapulmonar, por lo general silente. Es forma de tuberculosis se produce debido a una disminución de la inmunidad celular y humoral, generada por una causa intercurrente. Entre estas se pueden citar las terapias inmunosupresoras, neoplasias, diabetes, insuficiencia renal crónica y enfermedades virales. Tiene una alta mortalidad, que se estima en un 85 por ciento de los afectados. Se presenta un paciente de sexo masculino, de 56 años de edad que ingresa al Servicio de Clínica Médica para ser estudiado con diagnóstico de síndrome febril prolongado. Se concluye señalando que, para disminuir la alta mortalidad de esta entidad, debe realizarse su diagnóstico y tratamiento en forma precoz, y para ello hay que tenerla presente en el diagnóstico diferencial del síndrome febril prolongado

Tuberculosis congénita / Congenital tuberculosis

La tuberculosis congénita es una entidad patológica rara, cuya incidencia es variable según la prevalencia de la enfermedad de la población. Se presenta un caso clínico correspondiente a un recién nacido prematuro, hijo de madre portadora de tuberculosis miliar, que en el período neonatal mostró signos clínicos sugerentes de sepsis y en cuyo contenido gástrico se aisló Mycobacterium tuberculosis, habiéndose descartado la exposición materna extrauterina o con personal infectado. La forma de infección materno-fetal, en este caso, probablemente fue hematógena (vía vena umbilical). La respuesta clínica del paciente al tratamiento antituberculoso fue satisfactoria. Este caso es un ejemplo de una enfermedad que, aunque poco frecuente, debe ser sospechada en toda infección neonatal de etiología no precisada, debido a la importancia de instalar el tratamiento específico precozmente para mejorar el pronóstico vital del neonato

Tuberculosis miliar en niños: aspectos terapeuticos / Miliar tuberculosis in children : therapeutical aspects

Se revisó las historias del HEMBT entre Enero de 1971 a Diciembre de 1985; reuniendo sólo 63 historias los criterios para el diagnóstico de Tuberculosis Miliar. las drogas de elección fueron la Isoniazida y Estreptomicina en el 100% y la tercera droga fue el Ethambutol en el 44.4% seguido por la Rifampicina en el 38%. El esquema de tratamiento mas usado fue el triple asociado a cortico esteroides en 71.4%, siendo eficaz con un p<0.005. Al ser dado de alta el paciente la combinación mas usado fue INH y EM en el 51%. De los 47 sobrevivientes 16 tuvieron controles de los cuales el 31% recibieron un año de tratamiento. Hubo 11 reingresos de los cuales 9 salieron con diagnóstico de tuberculosis avanzada. Es importante educar al paciente y la familia para que cumpla su tratamiento adecuado

T-cell subpopulations in tuberculosis and the effects of rifampicin.

T-cell subpopulations were evaluated by several recent methods in 38 tuberculosis patients (24 active and 10 quiescent cases of pulmonary tuberculosis; two of miliary and two of active extra-pulmonary tuberculosis) before and during rifampicin (RMP) treatment. There was a significant reduction in the total number of T cells (E-RFC and OKT3+ cells) and of helper T cells (OKT4+) coinciding with an increase in the number of suppressor T cells when the 38 tuberculosis patients were compared with 21 healthy control subjects. When the changes of T-cell subpopulations in groups of subjects and patients with different clinical forms of the disease were analysed, these changes could be clearly shown with both sets of assays (receptor assays and monoclonal antibody assays) among those with the active pulmonary form of tuberculosis while similar changes could be demonstrated only by one or the other assay among those with the other forms of the disease. The effects of one month of RMP treatment on these parameters were much more obvious among the clinically active patients than the quiescent patients, i.e. a recovery of total T cells from a low pre-treatment to a near normal level accompanied by a significant reduction in the number of suppressor cells (OKT8+). In fact, among quiescent patients the number of suppressor cells (as TG) appeared to rise further with RMP treatment.