Tuberculosis in children and adolescents with rheumatic diseases using biologic agents: an integrative review / Tuberculose em crianças e adolescentes com doenças reumáticas em uso de medicamentos biológicos: revisão integrativa

ABSTRACT Objective: To conduct a bibliographic review on tuberculosis (TB) disease in children and adolescents with rheumatic diseases, being managed with biologic therapy. Data source: An integrative review with a search in the U.S. National Library of Medicine and the National Institutes of Health (PubMed) using the following descriptors and Boolean operators: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis factor-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), between January 2010 and October 2021. Data synthesis: Thirty-seven articles were included, with the total number of 36,198 patients. There were 81 cases of latent tuberculosis infection (LTBI), 80 cases of pulmonary tuberculosis (PTB), and four of extrapulmonary tuberculosis (EPTB). The main rheumatic disease was juvenile idiopathic arthritis. Among LTBI cases, most were diagnosed at screening and none progressed to TB disease during follow-up. Of the TB cases using biologics, most used tumor necrosis factor-alpha inhibitors (anti-TNFα) drugs. There was only one death. Conclusions: The study revealed a low rate of active TB in pediatric patients using biologic therapy. Screening for LTBI before initiating biologics should be done in all patients, and treatment, in cases of positive screening, plays a critical role in preventing progression to TB disease.

RESUMO Objetivo: Fazer um levantamento bibliográfico referente à tuberculose (TB) em crianças e adolescentes com doenças reumáticas, em uso de imunobiológicos. Fonte de dados: Revisão integrativa com busca na base United States National Library of Medicine (PubMed) utilizando os descritores e operadores booleanos: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis fator-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), entre janeiro de 2010 e outubro de 2021. Síntese de dados: Trinta e sete artigos foram incluídos, com o total de 36.198 pacientes. Houve 81 casos de tuberculose latente (ILTB), 80 casos de tuberculose pulmonar (TBP) e quatro casos de tuberculose extrapulmonar (TBEP). A principal doença reumática foi a artrite idiopática juvenil. Entre os casos de ILTB, a maioria foi diagnosticada no rastreio e nenhum evoluiu para a TB. Dos casos de TB em uso de imunobiológicos, a maioria utilizava fármacos antiTNFα. Houve somente um caso de óbito. Conclusões: O estudo demonstrou baixa taxa de TB nos pacientes pediátricos em uso de imunobiológicos. O rastreio para ILTB antes do início da terapia com agentes biológicos deve ser realizado em todos os pacientes, e o tratamento, nos casos de rastreio positivo, é importante para evitar a progressão para TB doença.

Clinical forms and diagnosis of tuberculosis in children and adolescents during the COVID-19 pandemic / Formas clínicas e diagnóstico da tuberculose em crianças e adolescentes durante a pandemia de COVID-19

ABSTRACT Objective: The present study aimed to describe the clinical forms and the time taken to diagnose new tuberculosis cases and to statistically analyze the isolated and combined forms of the disease in children and adolescents treated at a university hospital in Rio de Janeiro during the first year of the COVID-19 pandemic in Brazil. Methods: This was a cross-sectional study that used retrospective data on children (0-9 years old) and adolescents (10-18 years old) with pulmonary (PTB), extrapulmonary (EPTB), and combined tuberculosis (PTB + EPTB) followed up at the outpatient clinic from January 2019 to March 2021. Categorical data were analyzed by descriptive statistics and expressed as frequency and proportions. Categorical variables were compared using the Chi-square test, and numerical variables using Student's T-test. Results: A total of 51 cases were included, 63% (32/51) of which comprised patients in the year of the pandemic (group A), while 37% (19/51) were patients attended in previous years (group B). In group A, 19% (6/32) of the patients presented PTB, 59% (16/32) had EPTB, and 31% (10/32) had PTB+EPTB. In group B, 42% (8/19) of the patients presented PTB, 42% (8/19) had EPTB, and 16% (3/19) had PTB+EPTB. Conclusion: Our study revealed more tuberculosis cases in the first year of the pandemic than in the same period of the previous year, with greater variation of sites affected by the disease, including rarer and more severe forms.

RESUMO Objetivo: O presente estudo teve como objetivo descrever as formas clínicas e o tempo de diagnóstico de novos casos de tuberculose e analisar estatisticamente as formas isoladas e combinadas da doença em crianças e adolescentes atendidos em um hospital universitário do Rio de Janeiro durante o primeiro ano da pandemia de COVID-19 no Brasil. Métodos: Este estudo transversal utilizou dados retrospectivos de crianças (0-9 anos) e adolescentes (10-18 anos) com tuberculose pulmonar (TBP), extrapulmonar (TBEP) e combinada (TBP + TBEP) acompanhados no ambulatório de janeiro de 2019 a março de 2021. Os dados categóricos foram analisados por estatística descritiva e expressos em frequência e proporções. As variáveis categóricas foram comparadas pelo teste Qui-quadrado e as variáveis numéricas pelo teste T de Student. Resultados: Foram incluídos 51 casos, sendo 63% (32/51) pacientes no ano da pandemia (grupo A) e 37% (19/51) pacientes atendidos em anos anteriores (grupo B). No grupo A, 19% (6/32) dos pacientes apresentavam TBP, 59% (16/32) TBEP e 31% (10/32) TBP+TBEP. No grupo B, 42% (8/19) dos pacientes apresentavam TBP, 42% (8/19) TBEP e 16% (3/19) TBP+TBEP. Conclusão: Nosso estudo evidenciou mais casos de tuberculose no primeiro ano da pandemia do que no mesmo período do ano anterior, com maior variação de locais acometidos pela doença, incluindo formas mais raras e mais graves.

Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis in children and adolescents

ABSTRACT This prospective study describes the use of Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis (EPTB) in children and adolescents, in Rio de Janeiro, Brazil. Eighteen patients were studied; the final diagnosis of EPTB was established in 13 (72%). Gene-Xpert Ultra results showed detection in 10/13 (77%) of EPTB cases (7 of these 10 with trace-positive results). Gene-Xpert Ultra proved to be a promising method for the diagnosis of childhood EPTB.

Diagnosis of tuberculosis: a consensus statement from the Brazilian Thoracic Association / Consenso sobre o diagnóstico da tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

RESUMO O diagnóstico precoce e adequado da tuberculose é um dos pilares mais importantes no controle da doença. A proposta deste consenso brasileiro é apresentar aos profissionais da área de saúde um documento com as evidências mais atuais e úteis para o diagnóstico da tuberculose. Para tanto, a Comissão de Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia reuniu 14 membros da Sociedade com reconhecida experiência em tuberculose no Brasil. Foi realizada uma revisão não sistemática dos seguintes tópicos: diagnóstico clínico, diagnóstico bacteriológico, diagnóstico radiológico, diagnóstico histopatológico, diagnóstico da tuberculose na criança e diagnóstico da tuberculose latente.

Clinical profile of children with and without comorbidities hospitalized with community-acquired pneumonia / Perfil clínico de crianças com e sem comorbidades hospitalizadas com pneumonia adquirida na comunidade

ABSTRACT Objective: To describe the clinical profile of children and adolescents hospitalized with community-acquired pneumonia (CAP). They were divided into two groups: those with and those without comorbidities. Methods: An observational, cross-sectional, descriptive study with prospective data collection, was carried out in a cohort of patients aged zero to 11, who were hospitalized with a clinical and radiological diagnosis of community-acquired pneumonia, from January 2010 to January 2012. As an exploratory study, the two groups were compared through logistic regression for possible risk factors associated with community-acquired pneumonia. Relative risk (RR) was used with a 95% confidence interval (95%CI). The process of selection for independent variables was stepwise forward, with a significance level of 5%. Results: There were 121 cases of community-acquired pneumonia evaluated, and 47.9% had comorbidities. In the bivariate analysis, patients with comorbidities demonstrated higher chances for: age >60 months (p=0.005), malnutrition (p=0.002), previous use of antibiotics (p=0.008) and previous hospitalization for community-acquired pneumonia in the last 24 months (p=0.004). In the multivariate analysis, these variables were independent predictors of community-acquired pneumonia in patients with the comorbidities: age >60 months (p=0.002; RR=5.39; 95%CI 1.89-15.40); malnutrition (p=0.008; RR=1.75; 95%CI 1.75-44.60); previous use of antibiotics (p=0.0013; RR=3.03; 95%CI 1.27-7.20); and previous hospitalization for community-acquired pneumonia (p=0.035; RR=2.91; 95%CI 1.08-7.90). Conclusions: Most patients with community-acquired pneumonia and comorbidities were aged >60 months, were malnourished, had used antibiotics and had been hospitalized for community-acquired pneumonia. Comorbidities were associated with a higher chance of malnutrition and hospitalizations for community-acquired pneumonia in an older age group, compared to children without comorbidities. Knowledge of this clinical profile may contribute to better assist pediatric patients with community-acquired pneumonia hospitalized in referral centers.

RESUMO Objetivo: Descrever o perfil clínico de crianças e adolescentes hospitalizados com pneumonia adquirida na comunidade, separando-os em dois grupos: com e sem comorbidades. Métodos: Estudo observacional, transversal, descritivo, com coleta prospectiva de dados, realizado na coorte de pacientes de zero a 11 anos, hospitalizados com diagnósticos clínico e radiológico de pneumonia adquirida na comunidade de janeiro de 2010 a janeiro de 2012. De modo exploratório, buscou-se comparar os dois grupos por regressão logística quanto a possíveis fatores de risco para pneumonia adquirida na comunidade, por meio de risco relativo (RR) com intervalo de confiança de 95% (IC95%). O processo de seleção das variáveis independentes foi o de stepwise forward, a 5%. Resultados: Foram avaliados 121 casos; 47,9% tinham comorbidades. Na análise bivariada, pacientes com comorbidades mostraram maiores chances de apresentar: idade >60 meses (p=0,005), desnutrição (p=0,002), uso prévio de antibióticos (p=0,008) e hospitalização por pneumonia adquirida na comunidade nos últimos 24 meses (p=0,004). Na análise multivariada, estas foram variáveis preditoras independentes para pneumonia adquirida na comunidade, nos pacientes com comorbidades: idade >60 meses (p=0,002; RR=5,39; IC95% 1,89-15,40); desnutrição (p=0,008; RR=1,75; IC95% 1,75-44,60); uso prévio de antimicrobianos (p=0,0013; RR=3,03; IC95% 1,27-7,20) e hospitalização prévia por pneumonia adquirida na comunidade (p=0,035; RR=2,91; IC95% 1,08-7,90). Conclusões: A maioria dos pacientes com pneumonia adquirida na comunidade e comorbidades tinha idade >60 meses, desnutrição, fizera uso prévio de antibióticos e havia sido hospitalizado por pneumonia adquirida na comunidade. As comorbidades relacionam-se à maior chance de desnutrição e a hospitalizações por pneumonia adquirida na comunidade em faixa etária mais elevada do que crianças sem comorbidades. O conhecimento desse perfil clínico pode contribuir para melhor assistência da pneumonia adquirida na comunidade em pacientes pediátricos hospitalizados em serviços de referência.

The clinical and molecular diagnosis of childhood and adolescent pulmonary tuberculosis in referral centers

Abstract INTRODUCTION: The diagnostic accuracy of Xpert MTB/RIF (Xpert) in pulmonary tuberculosis (PTB) in children is lower than in adults. In Brazil, the diagnosis of PTB is based on a diagnostic score system (DSS). This study aims to study the role of Xpert in children and adolescents with PTB symptoms. METHODS: A cross-sectional study was conducted in 3 referral centers to TB. Children and adolescents (0-19 years old) whose respiratory samples were submitted to Xpert were included. Statistical analysis (bivariate and logistic regression) to assess the simultaneous influence of TB-related variables on the occurrence of Xpert detectable in TB cases was done. To evaluate the agreement or disagreement between Xpert results with acid-fast bacillus (AFB) and cultures, κ method was used (significancy level of 5%). RESULTS: Eighty-eight patients were included in the study and PTB occurred in 43 patients (49%) and Xpert was detectable in 21 patients (24%). Adolescents and positive culture results were independent predictive variables of Xpert positivity. DSS sensitivity compared with the final diagnosis of TB was 100% (95% CI, 88.1-100%), specificity was 97.2% (95% CI, 85.5-99.9%). The accuracy of the method was 98.5% (95% CI, 91.7-99.9%). CONCLUSIONS: Xpert contributed to diagnosis in 9% of patients with AFB and in culture negative cases. DSS indicated relevance for this diagnostic approach of intrathoracic TB (ITB) in reference centers for presenting data both with high sensitivity and specificity.

The use of Gene-Xpert MTB RIF in the diagnosis of extrapulmonary tuberculosis in childhood and adolescence

Abstract INTRODUCTION: Gene-Xpert MTB RIF (Xpert) is based on nucleic acid amplification by real-time polymerase chain reaction, which allows for the identification of Mycobacterium tuberculosis and rifampin resistance. We describe the use of Xpert for extrapulmonary tuberculosis (EPTB) in children and adolescents. METHODS: A case series of two reference centers in Rio de Janeiro from 2014-2019. RESULTS: The final diagnosis of EPTB was established in 11/36 (31%) patients, with five cases detectable by Xpert. For lymph node evaluation (9/11), diagnosis by Xpert occurred in 5/9 patients, all with caseous aspects. CONCLUSIONS: Xpert can facilitate the rapid diagnosis of lymph node tuberculosis.