Diagnostic Accuracy of QuantiFERON-TB Gold Plus Assays in Children and Adolescents with Tuberculosis Disease.

In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We conducted a cross-sectional multicenter study, involving 158 children and adolescents with tuberculosis disease. The overall sensitivity of the assay was 82.9% (IQR 77.0%-88.8%), indicating that in children this test does not have higher sensitivity than previous generation interferon-gamma release assays.

Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study.

BACKGROUND: In adults, anti-tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. METHODS: Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti-TNF-α therapy. RESULTS: Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn's disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti-TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti-TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1-20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46-66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. CONCLUSIONS: LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti-TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.

Encefalopatía por virus herpes 6 como complicación de exantema súbito / Encephalopathy due to human herpesvirus 6 infection as exanthema subitum complication

La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

[Encephalopathy due to human herpesvirus 6 infection as exanthema subitum complication]. / Encefalopatía por virus herpes 6 como complicación de exantema súbito.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

Infecciones por Serratia, ¿debemos pensar en mmunodeficienaas primarias? / Serratia infections, should we think about primary immunodeficiencies?

La enfermedad granulomatosa crónica es una inmunodeficiencia primaria, con una incidencia de 1/200 000-250 000recién nacidos vivos. Afecta, principalmente, a varones; la mayoría de las mutaciones son ligadas al cromosoma X y las formas autosómicas recesivas ocurren, con más frecuencia, en comunidades con mayor número de matrimonios consanguíneos. Se caracteriza por sensibilidad a infecciones recurrentes y graves, bacterianas y fúngicas, con formación de granulomas, debido a la incapacidad de los fagocitos para generar compuestos reactivos de oxígeno, necesarios para la muerte intracelular de microorganismos fagocitados. Se presentan tres casos de enfermedad granulomatosa crónica en los que se aisló Serratia marcescens y, tras una anamnesis minuciosa y obtener resultados de pruebas de funcionalidad de neutrófilos, se llegó a un diagnóstico molecular de la enfermedad. La enfermedad granulomatosa crónica puede manifestarse de formas muy variadas, por lo que el alto índice de sospecha y una buena anamnesis son fundamentales para alcanzar un diagnóstico.

Chronic granulomatous disease (CGD) is a primary immunodeficiency with an incidence of 1/200,000-250,000 live births. CGD affects mainly male patients, most of the mutations being X-linked, and autosomal recessive forms occur more frequently in communities with greater numbers of consanguineous marriages. CGD is characterized by sensitivity to recurrent and severe bacterial and fungal infections, with formation of granulomas due to the inability of phagocytes to generate reactive oxygen compounds, necessary for the intracellular death of phagocytic microorganisms. We report three cases of CGD in which Serratia marcescens was isolated, and after detailed anamnesis and performance of neutrophil function tests, a molecular diagnosis of the disease was reached. CGD can be manifested in a wide variety of ways, so that high suspicion and a meticulous anamnesis are essential to reach a diagnosis.

Reacción paradójica al tratamiento antituberculosis en una niña inmunocompetente afectada de tuberculosis ganglionar pulmonar / Paradoxical reaction to antituberculosis treatment in an immunocompetent girl with pulmonary tuberculosis

La reacción paradójica al tratamiento antituberculoso es una entidad poco frecuente en pediatría. Se presenta el caso de una niña de 9 años con fiebre, tos y expectoración de tres semanas de evolución. La prueba de tuberculina y Quantiferon fueron positivos; la velocidad de sedimentación era de 64 mm/h; el cultivo y la reacción en cadena de la polimerasa para M. tuberculosis fueron negativos. La radiografía de tórax mostró ensanchamiento mediastínico derecho. Ante el diagnóstico de tuberculosis, se inició un tratamiento con rifampicina, isoniacida, pirazinamida y etambutol en dosis estándar. A los 21 días, reapareció la fiebre elevada sin otra sintomatología, empeoramiento radiológico junto con normalidad de serologías, analítica sanguínea y resonancia cerebral. Se diagnosticó una reacción paradójica; se inició 1 mg/kg/día de prednisona oral, y quedó afebril a las 24 horas. Es importante considerar esta entidad cuando otras causas de empeoramiento clínico y/o radiológico se han descartado para evitar pruebas complementarias y modificaciones de tratamiento innecesarias.

Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started. Twenty-one days later she presented high fever with no other symptoms, worsening of radiological findings and normal blood tests, serologies and brain magnetic resonance imaging. The patient presented a paradoxical reaction and was given prednisone 1 mg/kg/day, fever disappeared in 24 hours. It is important to consider a paradoxical reaction when other causes of clinical and/or radiological worsening have been ruled out, to avoid unnecessary tests and treatment modifications.

[Serratia infections, should we think about primary immunodeficiencies?] / Infecciones por serratia, ¿debemos pensar en inmunodeficiencias primarias?

Chronic granulomatous disease (CGD) is a primary immunodeficiency with an incidence of 1/200,000-250,000 live births. CGD affects mainly male patients, most of the mutations being X-linked, and autosomal recessive forms occur more frequently in communities with greater numbers of consanguineous marriages. CGD is characterized by sensitivity to recurrent and severe bacterial and fungal infections, with formation of granulomas due to the inability of phagocytes to generate reactive oxygen compounds, necessary for the intracellular death of phagocytic microorganisms. We report three cases of CGD in which Serratia marcescens was isolated, and after detailed anamnesis and performance of neutrophil function tests, a molecular diagnosis of the disease was reached. CGD can be manifested in a wide variety of ways, so that high suspicion and a meticulous anamnesis are essential to reach a diagnosis.

La enfermedad granulomatosa crónica es una inmunodeficiencia primaria, con una incidencia de 1/200 000-250 000 recién nacidos vivos. Afecta, principalmente, a varones; la mayoría de las mutaciones son ligadas al cromosoma X y las formas autosómicas recesivas ocurren, con más frecuencia, en comunidades con mayor número de matrimonios consanguíneos. Se caracteriza por sensibilidad a infecciones recurrentes y graves, bacterianas y fúngicas, con formación de granulomas, debido a la incapacidad de los fagocitos para generar compuestos reactivos de oxígeno, necesarios para la muerte intracelular de microorganismos fagocitados. Se presentan tres casos de enfermedad granulomatosa crónica en los que se aisló Serratia marcescens y, tras una anamnesis minuciosa y obtener resultados de pruebas de funcionalidad de neutrófilos, se llegó a un diagnóstico molecular de la enfermedad. La enfermedad granulomatosa crónica puede manifestarse de formas muy variadas, por lo que el alto índice de sospecha y una buena anamnesis son fundamentales para alcanzar un diagnóstico.

[Paradoxical reaction to antituberculosis treatment in an immunocompetent girl with pulmonary tuberculosis]. / Reacción paradójica al tratamiento antituberculosis en una niña inmunocompetente afectada de tuberculosis ganglionar pulmonar.

Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started. Twenty-one days later she presented high fever with no other symptoms, worsening of radiological findings and normal blood tests, serologies and brain magnetic resonance imaging. The patient presented a paradoxical reaction and was given prednisone 1 mg/kg/day, fever disappeared in 24 hours. It is important to consider a paradoxical reaction when other causes of clinical and/or radiological worsening have been ruled out, to avoid unnecessary tests and treatment modifications.

La reacción paradójica al tratamiento antituberculoso es una entidad poco frecuente en pediatría. Se presenta el caso de una niña de 9 años con fiebre, tos y expectoración de tres semanas de evolución. La prueba de tuberculina y Quantiferon fueron positivos; la velocidad de sedimentación era de 64 mm/h; el cultivo y la reacción en cadena de la polimerasa para M. tuberculosis fueron negativos. La radiografía de tórax mostró ensanchamiento mediastínico derecho. Ante el diagnóstico de tuberculosis, se inició un tratamiento con rifampicina, isoniacida, pirazinamida y etambutol en dosis estándar. A los 21 días, reapareció la fiebre elevada sin otra sintomatología, empeoramiento radiológico junto con normalidad de serologías, analítica sanguínea y resonancia cerebral. Se diagnosticó una reacción paradójica; se inició 1 mg/kg/día de prednisona oral, y quedó afebril a las 24 horas. Es importante considerar esta entidad cuando otras causas de empeoramiento clínico y/o radiológico se han descartado para evitar pruebas complementarias y modificaciones de tratamiento innecesarias.

[Lymphadenitis due to non-tuberculous mycobacteria: Experience over 15 years]. / Linfadenitis por micobacterias no tuberculosas: experiencia de 15 años.

OBJECTIVE: To study the epidemiology, clinical features, diagnosis, therapeutic management, and outcome of non-tuberculous mycobacterial lymphadenitis in a paediatric population of Aragón (Spain). MATERIAL AND METHODS: A retrospective study was conducted on patients under 15 years-old diagnosed with non-tuberculous mycobacterial lymphadenitis between the years 2000 and 2015. INCLUSION CRITERIA: patients with lymphadenitis and positive culture. Quantitative values are shown as mean, rank, and standard deviation, and qualitative data as frequencies. RESULTS: Twenty-seven cases were registered, with a mean age of presentation of 39.9 months (range 10 months-8 years). The mean time between the symptoms onset and first consultation was 1.7±1.1 months. The most frequent location was sub-maxilar in 17/27 cases (63%), on the right side in 59.3%, and size 2.96±1.26cm. Fistulae were observed in 16/27 cases. Tuberculin test was greater than 10mm in 7/24 (29.1%). Microbiological cultures were positive for Mycobacterium avium in 14/27 (51.9%), Mycobacterium intracellulare 3/27 (11.1%), and Mycobacterium lentiflavum 3/27 (11.1%). Combined treatment of antibiotics and surgery was given in 16/27 cases (59.8%), medical treatment only in7/27 (25.9%), and surgical exeresis alone in 4/27 (14.8%). Two patients required a new surgery, and one showed severe neutropenia secondary to rifabutin. Only one case (3.7%) suffered from temporary facial palsy as sequel. CONCLUSIONS: The most frequent treatment was the combination of antibiotics and surgery. Delay in diagnosis seemed to be responsible for the limited number of exeresis as first option, only one for every seven patients.

Disseminated Tuberculosis Resulting From Reinfection in a Pediatric Patient Sequentially Treated With Etanercept and Adalimumab.

Treatment with tumor necrosis factor α inhibitors is a risk factor for tuberculosis (TB). Despite previous treatment with isoniazid for latent TB, a 9-year-old girl with juvenile idiopathic arthritis developed disseminated TB after changing therapy with etanercept to adalimumab and after new contact with a smear-positive relative. Genotyping strain matches and susceptibility to isoniazid make reinfection more likely than reactivation in our patient.

Linfadenitis por Mycobacterium lentiflavum: Reporte de dos casos / Mycobacterium lentiflavum lymphadenitis: Two case reports

La linfadenitis es la manifestación clínica más frecuente de la infección por micobacterias no tuberculosas en niños inmunocompetentes. Se presentan dos casos de linfadenitis por M. lentiflavum diagnosticados en un hospital de tercer nivel en los últimos 10 años. Se realizaron pruebas complementarias de rutina ante adenopatía persistente y se obtuvo una muestra mediante drenaje para el cultivo, que resultó positivo para este germen. Ambos pacientes recibieron tratamiento antibiótico oral durante varias semanas. El caso 1 precisó exéresis completa al quinto mes de evolución, mientras que el caso 2 presentó resolución completa de la lesión a los 4 meses. M. lentiflavum es considerado, de entre las nuevas especies de micobacterias no tuberculosas recientemente descritas, un germen emergente en nuestro medio. Posee unas características microbiológicas y clínicas especiales, diferentes del resto de las micobacterias no tuberculosas. Son pocos los casos publicados hasta la fecha desde que se describió por primera vez la infección en 1997.

Lymphadenitis is the most common clinical feature in nontuberculous mycobacterium infection in immunocompetent children. We present two case reports of M. lentiflavum lymphadenitis diagnosed in a tertiary hospital in the last 10 years. Routine tests were performed after persistent adenopathy, and a sample for culture was obtained, being positive for this microorganism. Both patients received oral antibiotics during several weeks. Case 1 needed complete excision after five months of treatment, whilst Case 2 was cured by medical therapy. M. lentiflavum is considered, among the newly described nontuberculous mycobacterial species, an emergent pathogen in our environment. It has its own microbiological and clinical characteristics, different from the rest of nontuberculous mycobacteria. Case reports are limited in the literature since the infection was described for the first time in 1997.

[Mycobacterium lentiflavum lymphadenitis: two case reports]. / Linfadenitis por Mycobacterium lentiflavum: reporte de dos casos.

Lymphadenitis is the most common clinical feature in nontuberculous mycobacterium infection in immunocompetent children. We present two case reports of M. lentiflavum lymphadenitis diagnosed in a tertiary hospital in the last 10 years. Routine tests were performed after persistent adenopathy, and a sample for culture was obtained, being positive for this microorganism. Both patients received oral antibiotics during several weeks. Case 1 needed complete excision after five months of treatment, whilst Case 2 was cured by medical therapy. M. lentiflavum is considered, among the newly described nontuberculous mycobacterial species, an emergent pathogen in our environment. It has its own microbiological and clinical characteristics, different from the rest of nontuberculous mycobacteria. Case reports are limited in the literature since the infection was described for the first time in 1997.

La linfadenitis es la manifestación clínica más frecuente de la infección por micobacterias no tuberculosas en niños inmunocompetentes. Se presentan dos casos de linfadenitis por M. lentiflavum diagnosticados en un hospital de tercer nivel en los últimos 10 años. Se realizaron pruebas complementarias de rutina ante adenopatía persistente y se obtuvo una muestra mediante drenaje para el cultivo, que resultó positivo para este germen. Ambos pacientes recibieron tratamiento antibiótico oral durante varias semanas. El caso 1 precisó exéresis completa al quinto mes de evolución, mientras que el caso 2 presentó resolución completa de la lesión a los 4 meses. M. lentiflavum es considerado, de entre las nuevas especies de micobacterias no tuberculosas recientemente descritas, un germen emergente en nuestro medio. Posee unas características microbiológicas y clínicas especiales, diferentes del resto de las micobacterias no tuberculosas. Son pocos los casos publicados hasta la fecha desde que se describió por primera vez la infección en 1997.