TY - JOUR
T1 - 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
AU - Noguera-Julian, Antoni
AU - Calzada-Hernandez, Joan
AU - Brinkmann, Folke
AU - Basu Roy, Robindra
AU - Bilogortseva, Olga
AU - Buettcher, Michael
AU - Carvalho, Isabel
AU - Chechenyeva, Vira
AU - Falcon, Lola
AU - Goetzinger, Florian
AU - Guerrero-Laleona, Carmelo
AU - Hoffmann, Peter
AU - Jelusic, Marija
AU - Niehues, Tim
AU - Ozere, Iveta
AU - Shackley, Fiona
AU - Suciliene, Elena
AU - Welch, Steven B
AU - Scholvinck, Elisabeth H
AU - Ritz, Nicole
AU - Tebruegge, Marc
N1 - © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
PY - 2020/11
Y1 - 2020/11
N2 - BACKGROUND: In adults, anti-tumor-necrosis-factor (TNF)-α therapy is associated with progression of latent tuberculosis infection (LTBI) to tuberculosis (TB) disease. The existing paediatric data are very limited.METHODS: Retrospective multi-centre 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-gamma release assay) was performed in 15 patients before commencing anti-TNF-α therapy, but only identified one 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, predominately miliary TB (n=14;78%). One case was diagnosed post-mortem. 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: The data indicate that 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.
AB - BACKGROUND: In adults, anti-tumor-necrosis-factor (TNF)-α therapy is associated with progression of latent tuberculosis infection (LTBI) to tuberculosis (TB) disease. The existing paediatric data are very limited.METHODS: Retrospective multi-centre 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-gamma release assay) was performed in 15 patients before commencing anti-TNF-α therapy, but only identified one 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, predominately miliary TB (n=14;78%). One case was diagnosed post-mortem. 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: The data indicate that 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.
KW - Tuberculosis
KW - anti-TNF-alpha
KW - children
KW - miliary tuberculosis
KW - reactivation
U2 - 10.1093/cid/ciz1138
DO - 10.1093/cid/ciz1138
M3 - Article
C2 - 31796965
SN - 1058-4838
VL - 71
SP - 2561
EP - 2569
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 10
ER -
