Incidence and nature of infectious disease in patients treated with anti-TNF agents Siba P. Raychaudhuri a,c, ⁎, Caroline T. Nguyen b , Smriti K. Raychaudhuri a , M. Eric Gershwin c a VA Medical Center, Sacramento, United States b University of California at Davis School of Medicine, Davis, CA 95616, United States c Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, United States abstract article info Article history: Accepted 16 August 2009 Available online 27 August 2009 Keywords: TNF TNF-α inhibitors Opportunistic infection Tuberculosis Rheumatic diseases Tumor necrosis factor α (TNF-α) inhibitors offer a targeted therapeutic strategy that contrasts with the nonspecific immunosuppressive agents traditionally used to treat most inflammatory diseases. These biologic agents have had a significant impact in ameliorating the signs and symptoms of inflammatory rheumatoid disease and improving patient function. From the onset of clinical trials, a central concern of cytokine blockade has been a potential increase in susceptibility to infections. Not surprisingly, a variety of infections have been reported in association with the use of TNF-α inhibitor agents. In particular, there is evidence suggesting an increased rate of granulomatous infections in patients treated with monoclonal TNF-α inhibitors. This review provides the incidence and nature of infections in patients treated with TNF-α inhibitor agents and reminds the clinician of the required vigilance in monitoring patients. Published by Elsevier B.V. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 2. TNF-α inhibitor types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 3. Pathophysiological role of TNF-α . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 4. Increased risk of infections by TNF-α inhibitor treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 5. Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 5.1. Variation of risk of reactivation among different TNF-α inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 5.2. Screening and prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 6. Risk of non-tuberculous mycobacterial infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 7. Opportunistic infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 8. Histoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 9. Coccidioidomycosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 10. Cryptococcus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 11. Aspergillosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 12. Listeriosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 13. Pneumocystis carinii (jirovecii). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 14. Sepsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 15. Viral infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 15.1. Hepatitis B infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 16. Hepatitis C infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 17. Human immunodeficiency virus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 18. Other infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 19. Site specific infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 20. Vaccinations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 21. Final comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 22. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 . Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 Autoimmunity Reviews 9 (2009) 67–81 ⁎ Corresponding author. VA Medical Center, Sacramento, United States. E-mail address: sraychaudhuri@ucdavis.edu (S.P. Raychaudhuri). 1568-9972/$ – see front matter. Published by Elsevier B.V. doi:10.1016/j.autrev.2009.08.006 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev