Tuberculosis disease in children and adolescents on therapy with anti-tumor necrosis factor-alpha agents: a collaborative, multi-centre ptbnet study.

Noguera-Julian, Antoni, Calzada-HernÁndez, Joan, Brinkmann, Folke, Basu Roy, Robindra, Bilogortseva, Olga, Buettcher, Michael, Carvalho, Isabel, Chechenyeva, Vira, Falcon, Lola, Goetzinger, Florian, Guerrero-Laleona, Carmelo, Hoffmann, Peter, Jelusic, Marija, Niehues, Tim, Ozere, Iveta, Shackley, Fiona, Suciliene, Elena, Welch, Steven B, SchÖLvinck, Elisabeth H, Ritz, Nicole and Tebruegge, Marc (2019) Tuberculosis disease in children and adolescents on therapy with anti-tumor necrosis factor-alpha agents: a collaborative, multi-centre ptbnet study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. ISSN 1537-6591.

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Abstract

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.

Item Type:	Article
Subjects:	WF Respiratory system. Respiratory medicine WS Paediatrics. Child health
Divisions:	Womens and Childrens > Paediatrics
Related URLs:	https://www.ncbi.nlm.nih.gov/pubmed/3179...
Depositing User:	Mrs Yolande Brookes
Date Deposited:	06 Dec 2019 14:04
Last Modified:	06 Dec 2019 14:04
URI:	http://www.repository.uhblibrary.co.uk/id/eprint/2659

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