Infectious complications of treatment with biologic agents.
OBJECTIVE
There are three tumor necrosis factor-alpha inhibitors on the US and European markets today, and uncommon but devastating infectious complications accompany their use. This review describes the most important pathogen-specific infections and their relative frequency. Recent literature is summarized that has helped elucidate the pathophysiologic basis for their occurrence. Finally, evolving sets of recommendations for prevention, diagnosis, and treatment of infectious complications of their use are explored.


RESULTS
Tuberculosis has continued to be the most common pathogen reported in association with infliximab, and less so with etanercept and adalimumab. Determining treated population case rates depends on having an accurate denominator and reflects the local population's latent infection rate. The same is true for histoplasmosis. Other pathogens requiring intact cellular immunity for control of latent infection have also been reported. Specific recommendations for preventive therapy are being made, but prospective clinical trials are needed to assess the risk-benefit of any particular approach.


CONCLUSIONS
Microorganisms responsible for the infectious complications associated with anticytokine therapy are generally intracellular pathogens or pathogens that commonly exist in a chronic, latent state and are normally held in check by cell-mediated immunity. Diagnosis requires a high index of suspicion and prompt acquisition of appropriate tissue for microscopic examination and microbiologic culture. Prompt empiric therapy that focuses on the most likely infections is necessary to prevent mortality.
Hamilton
Carol Dukes
CD
Duke University Medical Center, Durham, North Carolina 27710, USA. dukes002@mc.duke.edu
D001691:Biological Therapy / Q000009:adverse effects*; D006801:Humans; D007239:Infections / Q000209:etiology*; D014376:Tuberculosis / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha