Screening for latent tuberculosis before anti-TNF therapy
Before an anti-TNF drug (one that blocks tumour necrosis factor alpha, TNF) starts, patients are screened for latent tuberculosis (TB): bacteria present in the body but causing no symptoms.
Remember
Blocking TNF weakens granulomas, the tight balls of immune cells that wall off TB, so latent TB can escape and cause active disease. Screen for it before any anti-TNF drug, even in a patient who feels well and was born in the UK.
Memory aid
TNF is the mortar that holds the granuloma wall together, so remove the mortar and the dormant TB can get out.
Think of the granuloma as a wall around the TB bacteria and TNF as the mortar, so blocking TNF is like removing the mortar.
Tumour necrosis factor alpha (TNF) is a messenger protein released by immune cells that drives inflammation. It is also needed to form and maintain granulomas, the tight balls of immune cells that wall off bacteria the body has not managed to clear, such as Mycobacterium tuberculosis.
In latent tuberculosis the bacteria are present but dormant, meaning they cause no symptoms, because the granulomas hold the infection in check. Anti-TNF drugs, among them infliximab (an antibody against TNF alpha), adalimumab and etanercept, block TNF. That weakens the wall, so the bacteria can escape and the TB can reactivate, which means it wakes up and becomes active, often outside the lungs or as widespread disease, usually soon after the drug is started.
That is why patients are screened before the first dose. Screening normally combines a risk assessment, a chest X-ray and an interferon-gamma release assay (a blood test that detects the immune system's response to TB), with a tuberculin skin test (a skin test used to find latent TB) where indicated. If latent TB is found, it is treated before the anti-TNF drug is begun. Feeling well and being born in the UK do not remove the need to test: in the report that first alerted doctors to this problem with infliximab, 64 of 70 cases came from countries with a low incidence of TB.
Chronic hepatitis B is also screened for, because anti-TNF therapy can reactivate it, but TB is the defining concern.
Key facts
- Mechanism
- TNF is needed to form and maintain granulomas, so anti-TNF drugs can break down granulomas and reactivate latent TB.
- Drug class
- infliximab, adalimumab, golimumab, etanercept and certolizumab all target TNF alpha.
- Timing
- screen before the first dose, and treat latent TB that is found before the anti-TNF drug is begun.
- Blood test
- an interferon-gamma release assay looks for latent TB, which anti-TNF therapy can reactivate.
- Who is screened
- patients before any anti-TNF drug, and patients born in the UK with no significant past medical history too.
- Also screened
- chronic hepatitis B, which anti-TNF therapy can reactivate.
Exam traps
- A bone density scan is not the screen for an anti-TNF drug: it suits long-term oral steroids, but the defining pre-treatment risk of an anti-TNF drug is reactivation of latent infection, not bone loss.
- Thiopurine methyltransferase (TPMT) is an enzyme that breaks down azathioprine, so testing its activity is mandatory before azathioprine, but that is a different drug and it is not an anti-TNF screen.
- An echocardiogram (an ultrasound scan of the heart) matters when heart failure is known or suspected, but in a well patient with no cardiac history it is not the screening test that anti-TNF therapy calls for.
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