弥漫性结缔组织病患者侵袭性真菌感染的回顾性病例对照研究

Invasive fungal infection in diffuse connective tissue diseases： a retrospective case-control study

目的研究弥漫性结缔组织病（DCTD）住院患者合并侵袭性真菌感染的临床特征、危险因素及预后影响因素。方法回顾性收集2007年1月至2011年1月，上海仁济医院风湿科住院的DCTD合并侵袭性真菌感染患者33例。对照患者来自同期住院的67例其他感染患者，包括活动性结核感染患者33例和其他细菌感染患者34例。同时，历史对照为2002年1月至2006年12月11例系统性红斑狼疮（SLE）合并侵袭性真菌感染的住院患者。按数据分布类型选用相应的统计方法：单因素方差分析，秩和检验∥检验，确切概率法；多元分析采用Logistic逐步回归方法和Log—rank生存分析。结果DCTD患者中发生侵袭性真菌感染，主要的基础疾病为SLE（18例，55％），系统性血管炎（4例，12％）和炎症性肌病（4例，12％）。最常见的病原致病菌为念珠菌属（13例，39％），隐球菌属（10例，30％）和曲霉菌属（3例，9％）。感染部位则包括肺部（19例，58％），中枢神经系统（9例，27％）和血液播散型（4例，12％）。6例（18％）患者死于侵袭性真菌感染。相对于其他感染患者，侵袭性真菌感染患者的基础疾病的病程较短、感染前暴露的激素量较多、肝酶增高、空腹血糖增高及C反应蛋白水平增高。历史生存对照分析，发现近几年的SLE合并侵袭性真菌感染患者的短期生存率提高（历史组和近期组分别为64％和83％）。结论熟悉DCTD患者并发侵袭性真菌感染的疾病谱及相关的危险因素将有助于临床医生及时恰当地干预；侵袭性真菌感染认识的进步和抗真菌药物的进展最终有望改善该类患者的预后。

Objective Invasive fungal infection （IFI） can be a lethal complication in patients With diffuse connective tissue diseases （DCTD）. The aim of this study was to determine the characteristics of hospitalized DCTD patients with IFI, and identify the risk factors. Methods Data from 33 DCTD in patients with IFI at Shanghai Renji Hospital between Jan 2007 and Jan 2011 were collected retrospectively. DCTD patients with either active M. tuberculosis （n=33） or other bacterial infections （n=34） at the same period wer~ taken as controls. Systemic lupus erythematosus （SLE） inpatients with IFI （n= 11 ） from Jan 2002 to Dec 2006 were also considered as a historical control group. The method of univariate analysis of data depended on the data distribution type. Variables that suggested association in the univariate analysis P〈0.1 were entered into ：a stepwise logistic regression model Results The leading underlying diseases of DCTD with IFI were SLE （n7 18, 55%）, systemic vasculitis （n=4, 12%）, and inflammatory myopathy （n=4, 12%）. The most frequent pathogen was Candida spp （n=13, 39% ）, fallowed by Cryptococcus neoformans （n=10, 30% ）, and Aspergillus （n=3, 9%）. The infection locations included lung （n=19, 58%）, central nervous system （n=9, 27% ）, and disseminated IFI （n=4, 12% ）. Six patients （18%） died from IFI. Compared with non-IFI infections, patients with IFI infection had a shorter duration of underlying disease and were exposed to high doses of prednisolone prior to infection.More patients with IFI infection had elevated alanine aminotransferase, higher fasting glucose and lower C-reactive protein levels when compared to patients with non-IFI infections. Compared with the two historical SLE-IFI groups, the short-term survival improved in lupus patients complicated with IFI infection over time （64% vs 83%）. Conclusion Understanding disease spectrums andrisk factors of IFI in DCTD, along with advances in antifungal treatment, will help clinicians to manage those patients with invasive fungal infection effectively to achieve favourable prognosis.