Singh Nina, Lortholary Olivier, Alexander Barbara D, Gupta Krishan L, John George T, Pursell Kenneth, Munoz Patricia, Klintmalm Goran B, Stosor Valentina, del Busto Ramon, Limaye Ajit P, Somani Jyoti, Lyon Marshall, Houston Sally, House Andrew A, Pruett Timothy L, Orloff Susan, Humar Atul, Dowdy Lorraine, Garcia-Diaz Julia, Kalil Andre C, Fisher Robert A, Husain Shahid
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. nis5+@pitt.edu
Clin Infect Dis. 2005 Jun 15;40(12):1756-61. doi: 10.1086/430606. Epub 2005 Apr 29.
We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients.
The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study.
In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy.
This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.
我们描述了器官移植受者新型隐球菌感染病程中一种类似免疫重建综合征(IRS)的情况。
研究人群包括一组连续的83例患有隐球菌病的器官移植受者,在一项国际多中心研究中对他们进行了中位时间为2年的观察。
在83例患者中的4例(4.8%)中,在开始适当的抗真菌治疗后中位5.5周观察到一种类似IRS的情况。尽管新型隐球菌培养阴性,但仍记录到临床表现恶化。与所有其他患者相比,这些患者接受他克莫司、霉酚酸酯和泼尼松作为免疫抑制治疗方案的可能性显著更高(P = 0.007)。这种现象的推测基础是由于接受了有效的抗真菌治疗以及免疫抑制治疗的减少或停止,感染开始时主要的Th2反应转变为Th1促炎反应。
本研究表明,类似IRS的情况发生在患有新型隐球菌感染的器官移植受者中。此外,这种情况可能被误解为治疗失败。免疫调节药物在这种情况下可能作为辅助治疗发挥作用。