How does the use of TNFα inhibitors contribute to the increased incidence of reactivation of tuberculosis? I know that TNFα is needed for granuloma formation but don't the inhibitors remove TNFα from the cytokine milieu? Wouldn't TB be prevented then?
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I think the key here is to understand that the absence of disease signs (such as granulomas) doesn't mean the absence of disease - it can mean quite the opposite, especially in those with suppressed immune systems. You're correct in noting that TNF alpha plays a key role in the formation of granulomas. However, the body forms normally forms granulomas as a defense (think siege) mechanism against pathogens such as TB. If this mechanism is sufficiently disrupted by a TNF inhibitor (or other form of immunosuppression), TB not only can 'escape' and reactivate, but may also present in a far more serious form, called miliary TB. Miliary TB requires extended treatment compared to 'conventional' TB, and even with early detection and appropriate treatment, carries a far higher mortality rate
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