Intended for healthcare professionals

Practice Rational Testing

Screening tests for tuberculosis before starting biological therapy

BMJ 2015; 350 doi: (Published 05 March 2015) Cite this as: BMJ 2015;350:h1060
  1. Richard J Hewitt, core medical trainee1,
  2. Marie Francis, clinical respiratory research nurse1,
  3. Aran Singanayagam, academic clinical lecturer1,
  4. Onn Min Kon, consultant respiratory physician adjunct professor and reader in respiratory medicine12
  1. 1Chest and Allergy Department, St Mary’s Hospital, Imperial College NHS Trust, London W2 1NY, UK
  2. 2Imperial College London, St Mary’s Campus, London, UK
  1. Correspondence to: O M Kon onn.kon{at}
  • Accepted 19 February 2015

The bottom line

  • Biological drugs are associated with an increased risk of progression from latent to active tuberculosis

  • Before starting treatment, exclude active tuberculosis by asking about symptoms (such as cough, fever, weight loss, and night sweats) and possible exposure to or history of tuberculosis, and with a chest radiograph

  • Check for latent tuberculosis with the tuberculin skin test or an interferon γ release assay; a combination of both tests may be the most sensitive approach

A 27 year old white woman born in the United Kingdom presented with diarrhoea and rectal bleeding. A diagnosis of Crohn’s disease was made after urgent flexible sigmoidoscopy and she was treated with high dose intravenous corticosteroid. She relapsed on conversion to oral drugs and was start on infliximab, a tumour necrosis factor α (TNF-α) inhibitor.


Biological drugs that target components of the immune system, such as TNF-α antagonists, interleukin 1 receptor antagonists, and interleukin 6 receptor antagonists, are licensed for the treatment of immune mediated inflammatory conditions such as rheumatoid arthritis and Crohn’s disease. These agents suppress the host immune response, so are associated with increased risk of opportunistic infections including viral infections (odds ratio 1.91, 95% confidence interval 1.02 to 3.58), such as herpes simplex virus and varicella zoster virus, and mycobacterial infections (3.73, 1.72 to 8.13), although risk varies with different agents.1

In about 95% of people infected with Mycobacterium tuberculosis the infection is controlled by the immune system. This results in a state of “latent tuberculosis infection,” with no features of active disease.2 However 5% of those with latent tuberculosis later develop reactivation of tuberculosis and active disease.2 TNF-α antagonists can cause such reactivation of latent infection and active disease.3 People with reactivation have a significantly higher risk of disseminated tuberculosis, and deaths have been recorded.3 Crucially, screening …

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