Frank Karen M, Hogarth D Kyle, Miller Jonathan L, Mandal Saptarshi, Mease Philip J, Samulski R Jude, Weisgerber Glen A, Hart John
Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637, USA.
N Engl J Med. 2009 Jul 9;361(2):161-9. doi: 10.1056/NEJMoa0801066.
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.)
我们报告一例播散性组织胞浆菌病病例，该患者因类风湿关节炎接受全身免疫抑制治疗且参与了一项基因治疗试验，并发腹膜后出血并导致死亡。该试验旨在评估通过2型腺相关病毒（AAV）递送系统向关节内递送肿瘤坏死因子α（TNF-α）拮抗剂用于治疗炎性关节炎的效果。患者在组织胞浆菌病流行地区生活期间同时接受抗TNF-α治疗和其他免疫抑制治疗，被认为是感染最可能的原因；现有证据表明，这种致命感染不太可能与基因治疗试验中所施用的药物接触有关。该病例强化了在接受TNF-α拮抗剂治疗的患者中考虑感染性并发症（如地方性真菌病所致并发症）的重要性，以及在研究对象患病时制定精心设计的监测计划的重要性。（ClinicalTrials.gov编号，NCT00126724。）
