Introduction: Treatment of rheumatoid arthritis (RA) has changed with the release of more efficient disease-modifying anti-inflammatory drugs (DMARDs) and biologicals, such as methotrexate, leflunomide and TNF blockers, respectively. However they are prone to trigger potential pulmonary side effects. STATE OF KNOWLEDGES: Diffuse interstitial pneumonitis with alveolar lymphocytosis are induced by methotrexate. This drug increases also the risk of opportunistic infections (Pneumocyctis carinii) and of delayed lymphomas. Many intracellular bacterial infections, about 80 cases of diffuse pneumonitis, and rare vasculitis are attributable to leflunomide.
Perspectives: The TNF blocking agents (infliximab, etanercept and adalimumab) trigger immunization and consequently, rare type I and III hypersensitivity pneumonitis, serological lupus-like reactions usually without any clinical manifestations. Indeed the risk of infection with intracellular agents remains the first concern. Several hundreds of cases of pulmonary and non pulmonary tuberculosis (TB) have been described. They present as disseminated forms, with pulmonary manifestations present in half cases; of note, other sites are atypical, namely meningitis, lymph node, and digestive involvement. Pathological diagnosis can be difficult since granulomas are sparse or absent. Therefore TB can be lethal because of delayed diagnosis and treatment.
Conclusion: To prevent this major risk when using TNF blockers, the French agency AFFSAPS recommends to screen and treat susceptible patients such as latent tuberculosis. Specifically, antituberculous drugs have to be started three weeks before anti-TNF agents. During biological therapy, physicians must regularly look for usual and unusual symptoms of TB. When TB is diagnosed, anti -TNF agents have to be discontinued, probably definitively, and appropriate antituberculosis treatment started in order to achieve an uneventful course.