Key result
A fatal case of disseminated histoplasmosis in a gene-therapy trial participant was likely caused by concurrent systemic immunosuppressive therapy and endemic exposure, rather than the study agent.
Case Report (n=1)
Fatal disseminated histoplasmosis in a gene-therapy trial participant was likely due to concurrent systemic immunosuppression rather than the intraarticular gene therapy itself.
Emphasizes histoplasmosis prophylaxis in immunosuppressed gene-therapy recipients from endemic areas; leaves open agent causality for controlled trials.
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 alpha (TNF-alpha) antagonist, through an adeno-associated virus (AAV) type 2 delivery system, for inflammatory arthritis. The patient's receipt of concurrent anti-TNF-alpha 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-alpha antagonist and the importance of having a well-designed monitoring plan when subjects in a research study become ill. (ClinicalTrials.gov number, NCT00126724.)
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Frank et al. (2009) conducted a case report in Rheumatoid arthritis (n=1). Intraarticular delivery of a TNF-alpha antagonist via an AAV type 2 delivery system was evaluated on Cause of death. A fatal case of disseminated histoplasmosis in a gene-therapy trial participant was likely caused by concurrent systemic immunosuppressive therapy and endemic exposure, rather than the study agent.
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