51例系统性红斑狼疮合并真菌感染临床分析
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摘要
目的 探讨系统性红斑狼疮(systemic lupus erythcmatosus，SLE)合并真菌感染的易患因素、临床特征、诊断、治疗及预后。
方法 应用回顾性调查的方法对北京协和医院2000—2005年51例SLE合并真菌感染患者进行分析。
结果 1466例SLE病人中，51例合并真菌感染，发病率为3.5％。感染的常见诱因分别为长期使用糖皮质激素、免疫抑制剂、广谱抗生素，侵入性操作和白细胞减低。感染的病原菌仍以白色念珠菌为主，其次为隐球菌和曲霉菌。真菌感染最常见的部位是肺，其次为口腔、脑膜和血液。SLE合并真菌感染的临床表现无特异性，发热占90.2％，白细胞增高者占11.8％，白细胞减低者占52.9％，肺真菌感染与细菌感染和狼疮活动累及肺难以鉴别。抗真菌治疗单用氟康唑21例，两性霉素B(包括两性霉素B脂质体3例)7例，依曲康唑4例，其余均为联合用药，其中两性霉素B+5-氟胞嘧啶+氟康唑12例，先用氟康唑后换为依曲康唑2例，依曲康唑+SMZco1例。两性霉素B+氟康唑3例。本组治愈26例，好转12例，未愈3例，死亡10例，死亡率达19.6％。肺曲霉菌感染死亡率高达80％。低蛋白血症、低氧血症、多部位真菌感染、曲霉菌感染和真菌血症可能是导致死亡的危险因素。
结论 近年来真菌感染有逐年增加的趋势，与长期使用糖皮质激素、免疫抑制剂、广谱抗生素、侵入性操作的增多及白细胞减低相关。真菌感染的死亡率仍然高，尤以肺曲霉菌感染的死亡率最高(80％)，临床应重视SLE患者肺曲霉菌感染的预防、早期诊断和治疗。
Objective To investigate the major predisposing factor, clinical features, diagnosis, antifungal therapy and prognosis of fungal infection (FI) in patients with systemic lupus erythcmatosus(SLE).
Methods 51 cases of fungal infection in patients SLE admitted in the PUMC hospital from 2000 to 2005 were reviewed retrospectively. Results FI was found in 3.5%(51/1466) patients . The predisposing factor for FI included use of steroids/immunosuppressant/broad spectrum antibiotics over a long period, invasive manipulation and leucopenia. Candida albicans was ranked the first pathogen, thereafter were neoformans and Aspergillus species. The infective site were lung, oral cavity, cerebral meninges and blood etc. All the clinical manifestations of FI in SLE were not specific, included fever(90.2%),leucocytosis (11.8%).It was difficult to differentiate fungal infection with bacterial infection and SLE disease involved in lung. In antifungal drugs, fluconazole was used alone in 21 patients, amphotericin B in 7 patients, flucytosine in 4 patients, other patients used them in combination. Out of 51 patients, 26 were cured, 12 made improvement.The overall mortality was 19.6%( 10/51). Mortality in Aspergillus species infection was 80%(4/5). Hypoalbuminemia, hypoxia, Aspergillus species infection, and more than two infectious site might be the risk factors for mortality.
Conclusion The incidence of fungal infection is increasing in recently years ,which is correlated with use of high dose steroid/immunosuppressant/ broad-spectrum antibiotics over a long period, invasive manipulation and
方法 应用回顾性调查的方法对北京协和医院2000—2005年51例SLE合并真菌感染患者进行分析。
结果 1466例SLE病人中，51例合并真菌感染，发病率为3.5％。感染的常见诱因分别为长期使用糖皮质激素、免疫抑制剂、广谱抗生素，侵入性操作和白细胞减低。感染的病原菌仍以白色念珠菌为主，其次为隐球菌和曲霉菌。真菌感染最常见的部位是肺，其次为口腔、脑膜和血液。SLE合并真菌感染的临床表现无特异性，发热占90.2％，白细胞增高者占11.8％，白细胞减低者占52.9％，肺真菌感染与细菌感染和狼疮活动累及肺难以鉴别。抗真菌治疗单用氟康唑21例，两性霉素B(包括两性霉素B脂质体3例)7例，依曲康唑4例，其余均为联合用药，其中两性霉素B+5-氟胞嘧啶+氟康唑12例，先用氟康唑后换为依曲康唑2例，依曲康唑+SMZco1例。两性霉素B+氟康唑3例。本组治愈26例，好转12例，未愈3例，死亡10例，死亡率达19.6％。肺曲霉菌感染死亡率高达80％。低蛋白血症、低氧血症、多部位真菌感染、曲霉菌感染和真菌血症可能是导致死亡的危险因素。
结论 近年来真菌感染有逐年增加的趋势，与长期使用糖皮质激素、免疫抑制剂、广谱抗生素、侵入性操作的增多及白细胞减低相关。真菌感染的死亡率仍然高，尤以肺曲霉菌感染的死亡率最高(80％)，临床应重视SLE患者肺曲霉菌感染的预防、早期诊断和治疗。
Objective To investigate the major predisposing factor, clinical features, diagnosis, antifungal therapy and prognosis of fungal infection (FI) in patients with systemic lupus erythcmatosus(SLE).
Methods 51 cases of fungal infection in patients SLE admitted in the PUMC hospital from 2000 to 2005 were reviewed retrospectively. Results FI was found in 3.5%(51/1466) patients . The predisposing factor for FI included use of steroids/immunosuppressant/broad spectrum antibiotics over a long period, invasive manipulation and leucopenia. Candida albicans was ranked the first pathogen, thereafter were neoformans and Aspergillus species. The infective site were lung, oral cavity, cerebral meninges and blood etc. All the clinical manifestations of FI in SLE were not specific, included fever(90.2%),leucocytosis (11.8%).It was difficult to differentiate fungal infection with bacterial infection and SLE disease involved in lung. In antifungal drugs, fluconazole was used alone in 21 patients, amphotericin B in 7 patients, flucytosine in 4 patients, other patients used them in combination. Out of 51 patients, 26 were cured, 12 made improvement.The overall mortality was 19.6%( 10/51). Mortality in Aspergillus species infection was 80%(4/5). Hypoalbuminemia, hypoxia, Aspergillus species infection, and more than two infectious site might be the risk factors for mortality.
Conclusion The incidence of fungal infection is increasing in recently years ,which is correlated with use of high dose steroid/immunosuppressant/ broad-spectrum antibiotics over a long period, invasive manipulation and
引文
1 高东田，董海新，孙卓祥，等．360例深部真菌感染患者医院感染的调查[J]．中华医院感染学杂志，2006，2：146-148．
2 刘正印，盛瑞媛，李旭丽，等．院内真菌感染149例分析，中华医学杂志，2003，83：399—402．
3 钱小顺，朱元珏，许文兵，等．127例肺部真菌感染的临床分析．中华结核和呼吸杂志，2000，23：417—419．
4 Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1992, 25:1271-1277.
5 中华内科杂志编辑委员会．血液病／恶性肿瘤侵袭性真菌感染的诊断标准与治疗原则(草案)．中华内科杂志，2005，23：554-556．
6 孙传兴 主编．临床疾病诊断依据治愈好转标准(第2版)．北京：人民军医出版社，2002：
7 杜斌，张海涛，陈德昌，等．3447例尸检病例的深部真菌感染分析．中华医??学杂志，1996，76：352—354．
8 FallerM,WenzelR .Impact of the changing epidemiology of fungal infections in the 1990' s Eur J Clin Microbiol Infect Dis, 1992,11:2870452-2870461.
9 马军．侵袭性真菌感染的流行病学．中华医学杂志，2005，85：1443—1444．
10 Edmond MB, Wallace SE, McClish DK, et al. Nosocomial blood-stream infections in United States hospitals : a three-year analysis [J]. Clin Infect Dis, 1999, 29:239-244.
11 Rees JR, Pinner RW, Haijjeh RA,et al.The epidemiological features of invasive mycotic infections in the San Francisco Bay area,1992-1993 :results of population-based laboratory active surveillance [J] .Clin Infect Dis ,1998,27:1138-1147.
12 徐英春，王澎，陈民钧．辉瑞公司全球多心酵母菌敏感性监测结果．中国抗感染化疗杂志，2003，3：187—190．
13 Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis :the last 30 year[J].Arch Intern Med, 1999, 159:1301-1309.
14 Farrhurst RM, Pegues DA. Images in clinical medicine.Pulmonary cryptococal granulomas, N Engl J Med,2002,347:426-431.
15 Dean DA,Burchard KW. Surgical perspective on invasive Candida infections. World J Surg, 1998,22:127-134.
16 Fraser VJ,Jones M,Dunkel J,et al. Candidemia in a tertiary care hospital:epidemiology, risk factors,and predictors of mortality. Cli Infect Dis,1992;15:414-421.
17 翟介明，於强，何礼贤等．结缔组织疾病经糖皮质激素治疗并发肺部感染的病原学诊断．中华风湿病学杂志，1998，2：29—31．
18 李若瑜．侵袭性真菌感染实验室诊断的现状及展望．中华医学杂志．2005，85：1449—1450．
19 Ascioglu S, Rex JH, dePauw B, etal. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants:an international consensus. Clin Infect Dis,2002,34:7-14.20 应用抗菌药物防治外科感染的指导意见(草案)—外科患者深部真菌感染的防治．中华外科杂志，2005，43：1030—1033．
21 Helmi M,Love RB,Welter D,et al.Aspergillus infection in lung transplant recipients with systic fibrosis:risk factors and outcomes comparison to other types of transplant recipients.Chest,2003, 123:800-808.
22 Mckinsey DS. Making best use of the newer antifungal drugs.Infect Med,2003,20:392-399.1 杜斌，张海涛，陈德昌，等．3447例尸检病例的深部真菌感染分析．中华医学杂志，1996，76：352—354．
2 Failer M, Wenze 1R .Impact of the changing epidemiology of fungal infections in the 1990' s Eur J Clin Microbiol Infect Dis, 1992,11:2870452 -2870461.
3 马军．侵袭性真菌感染的流行病学．中华医学杂志，2005，85：1443—1444．
4 刘正印，盛瑞媛，李旭丽，等．院内真菌感染149例分析，中华医学杂志，2003，83：399—402．
5 Edmond MB, Wallace SE, McClish DK, et al. Nosocomial blood-stream infections in United States hospitals : a three-year analysis [J]. Clin Infect Dis, 1999, 29:239-244.
6 赵蓓蕾，施毅，桑红主编．现代肺部真菌病学．北京：人民军医出版社，2004，18—20．
7 章涛，宋绍辉，滕维亚．深部真菌感染临床特点及防治对策．中华医院感染学杂??志，2001，11(6)：473-474．
8 钱小顺，朱元珏，许文兵，等．127例肺部真菌感染的临床分析．中华结核和呼吸杂志，2000，23：417—419．
9 陈文彬．深部真菌感染病原学诊断概述．中国实用内科杂志，2002，22(1)：5～6．
10 刘代红，黄晓军，郭乃榄．异基因造血干细胞移植后肺炎的病因分析，北京大学学报(医学版)，2005，3712：130—133．
11 Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis :the last 30 year[J].Arch Intern Med, 1999, 159:1301-1309.
12 翟介明，於强，何礼贤等．结缔组织疾病经糖皮质激素治疗并发肺部感染的病原学诊断．中华风湿病学杂志，1998，2：29—31．
13 Richardson MD,Kokki MH.New perspective in the diagnosis of systemic fungal infections .Ann Med, 1999,31(2):3274.
14 Ascioglu S, Rex JH, dePauw B, etal. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants:an international consensus. Clin Infect Dis,2002,34: 7-14.
15 李若瑜．侵袭性真菌感染实验室诊断的现状及展望．中华医学杂志，2005，85：1449—1450．
16 Richardson MD,Kokki M.Therapeutic guidelines in systemic Fungal infections[M] 2ed.London: Current Medical Literature Ltd.2001.2-87
17 应用抗菌药物防治外科感染的指导意见(草案)一外科患者深部真菌感染的防治．中华外科杂志，2005，43：1030—1033．
18 中华内科杂志编辑委员会．血液病／恶性肿瘤侵袭性真菌感染的诊断标准与治疗原则(草案)．中华内科杂志，2005，23：554-556．
2 刘正印，盛瑞媛，李旭丽，等．院内真菌感染149例分析，中华医学杂志，2003，83：399—402．
3 钱小顺，朱元珏，许文兵，等．127例肺部真菌感染的临床分析．中华结核和呼吸杂志，2000，23：417—419．
4 Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1992, 25:1271-1277.
5 中华内科杂志编辑委员会．血液病／恶性肿瘤侵袭性真菌感染的诊断标准与治疗原则(草案)．中华内科杂志，2005，23：554-556．
6 孙传兴 主编．临床疾病诊断依据治愈好转标准(第2版)．北京：人民军医出版社，2002：
7 杜斌，张海涛，陈德昌，等．3447例尸检病例的深部真菌感染分析．中华医??学杂志，1996，76：352—354．
8 FallerM,WenzelR .Impact of the changing epidemiology of fungal infections in the 1990' s Eur J Clin Microbiol Infect Dis, 1992,11:2870452-2870461.
9 马军．侵袭性真菌感染的流行病学．中华医学杂志，2005，85：1443—1444．
10 Edmond MB, Wallace SE, McClish DK, et al. Nosocomial blood-stream infections in United States hospitals : a three-year analysis [J]. Clin Infect Dis, 1999, 29:239-244.
11 Rees JR, Pinner RW, Haijjeh RA,et al.The epidemiological features of invasive mycotic infections in the San Francisco Bay area,1992-1993 :results of population-based laboratory active surveillance [J] .Clin Infect Dis ,1998,27:1138-1147.
12 徐英春，王澎，陈民钧．辉瑞公司全球多心酵母菌敏感性监测结果．中国抗感染化疗杂志，2003，3：187—190．
13 Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis :the last 30 year[J].Arch Intern Med, 1999, 159:1301-1309.
14 Farrhurst RM, Pegues DA. Images in clinical medicine.Pulmonary cryptococal granulomas, N Engl J Med,2002,347:426-431.
15 Dean DA,Burchard KW. Surgical perspective on invasive Candida infections. World J Surg, 1998,22:127-134.
16 Fraser VJ,Jones M,Dunkel J,et al. Candidemia in a tertiary care hospital:epidemiology, risk factors,and predictors of mortality. Cli Infect Dis,1992;15:414-421.
17 翟介明，於强，何礼贤等．结缔组织疾病经糖皮质激素治疗并发肺部感染的病原学诊断．中华风湿病学杂志，1998，2：29—31．
18 李若瑜．侵袭性真菌感染实验室诊断的现状及展望．中华医学杂志．2005，85：1449—1450．
19 Ascioglu S, Rex JH, dePauw B, etal. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants:an international consensus. Clin Infect Dis,2002,34:7-14.20 应用抗菌药物防治外科感染的指导意见(草案)—外科患者深部真菌感染的防治．中华外科杂志，2005，43：1030—1033．
21 Helmi M,Love RB,Welter D,et al.Aspergillus infection in lung transplant recipients with systic fibrosis:risk factors and outcomes comparison to other types of transplant recipients.Chest,2003, 123:800-808.
22 Mckinsey DS. Making best use of the newer antifungal drugs.Infect Med,2003,20:392-399.1 杜斌，张海涛，陈德昌，等．3447例尸检病例的深部真菌感染分析．中华医学杂志，1996，76：352—354．
2 Failer M, Wenze 1R .Impact of the changing epidemiology of fungal infections in the 1990' s Eur J Clin Microbiol Infect Dis, 1992,11:2870452 -2870461.
3 马军．侵袭性真菌感染的流行病学．中华医学杂志，2005，85：1443—1444．
4 刘正印，盛瑞媛，李旭丽，等．院内真菌感染149例分析，中华医学杂志，2003，83：399—402．
5 Edmond MB, Wallace SE, McClish DK, et al. Nosocomial blood-stream infections in United States hospitals : a three-year analysis [J]. Clin Infect Dis, 1999, 29:239-244.
6 赵蓓蕾，施毅，桑红主编．现代肺部真菌病学．北京：人民军医出版社，2004，18—20．
7 章涛，宋绍辉，滕维亚．深部真菌感染临床特点及防治对策．中华医院感染学杂??志，2001，11(6)：473-474．
8 钱小顺，朱元珏，许文兵，等．127例肺部真菌感染的临床分析．中华结核和呼吸杂志，2000，23：417—419．
9 陈文彬．深部真菌感染病原学诊断概述．中国实用内科杂志，2002，22(1)：5～6．
10 刘代红，黄晓军，郭乃榄．异基因造血干细胞移植后肺炎的病因分析，北京大学学报(医学版)，2005，3712：130—133．
11 Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis :the last 30 year[J].Arch Intern Med, 1999, 159:1301-1309.
12 翟介明，於强，何礼贤等．结缔组织疾病经糖皮质激素治疗并发肺部感染的病原学诊断．中华风湿病学杂志，1998，2：29—31．
13 Richardson MD,Kokki MH.New perspective in the diagnosis of systemic fungal infections .Ann Med, 1999,31(2):3274.
14 Ascioglu S, Rex JH, dePauw B, etal. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants:an international consensus. Clin Infect Dis,2002,34: 7-14.
15 李若瑜．侵袭性真菌感染实验室诊断的现状及展望．中华医学杂志，2005，85：1449—1450．
16 Richardson MD,Kokki M.Therapeutic guidelines in systemic Fungal infections[M] 2ed.London: Current Medical Literature Ltd.2001.2-87
17 应用抗菌药物防治外科感染的指导意见(草案)一外科患者深部真菌感染的防治．中华外科杂志，2005，43：1030—1033．
18 中华内科杂志编辑委员会．血液病／恶性肿瘤侵袭性真菌感染的诊断标准与治疗原则(草案)．中华内科杂志，2005，23：554-556．