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Previous Volume 361:161-169 July 9, 2009 Number 2 Next

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SUMMARY

We present a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding and leading to death, in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene-therapy trial. This trial was designed to evaluate intraarticular delivery of a tumor necrosis factor (TNF-) antagonist, through an adeno-associated virus (AAV) type 2 delivery system, for inflammatory arthritis. The patient's receipt of concurrent anti–TNF- therapy and other immunosuppressive therapy while she was living in an area where histoplasmosis was endemic was thought to be the most likely explanation for the infection; the evidence presented suggests that this fatal infection was unlikely to have been related to exposure to the agent administered in the gene-therapy trial. This case reinforces the importance of considering infectious complications, such as those from endemic mycoses, in patients receiving treatment with a TNF- antagonist and the importance of having a well-designed monitoring plan when subjects in a research study become ill. (ClinicalTrials.gov number, NCT00126724 [ClinicalTrials.gov] .)

Source Information

From the Department of Pathology (K.M.F., J.L.M., S.M., J.H.) and the Division of Pulmonary and Critical Care, Department of Medicine (D.K.H.), University of Chicago Medical Center, Chicago; Seattle Rheumatology Associates, Division of Rheumatology Research, Swedish Medical Center, University of Washington School of Medicine, Seattle (P.J.M.); the Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill (R.J.S.); and St. John's Hospital, Springfield, IL (G.A.W.).

Address reprint requests to Dr. Frank at the University of Chicago Medical Center, 5841 S. Maryland Ave., MC 0001, Chicago, IL 60637, or at kfrank{at}uchicago.edu.

Full Text of this Article

Related Letters:

Death in a Gene-Therapy Trial
Zaia J. A., Federoff H. J., Hage C. A., Bowyer S., Kleiman M. B.
Extract | Full Text | PDF  
N Engl J Med 2009; 361:1811-1812, Oct 29, 2009. Correspondence

This article has been cited by other articles:

• Zaia, J. A., Federoff, H. J., Hage, C. A., Bowyer, S., Kleiman, M. B. (2009). Death in a gene-therapy trial.. NEJM 361: 1811-1812 [Full Text]  
• Hohmann, E. L. (2009). Gene Therapy -- Still a Work in Clinical and Regulatory Progress. NEJM 361: 193-195 [Full Text]