结缔组织病合并新型隐球菌感染的临床分析  

Clinical analysis of cryptococcosis neoformans infection in patients with connective tissue disease

作　　者：苏晖莹 金月波[2] 王乃迪 安媛[2] Su Huiying;Jin Yuebo;Wang Naidi;An Yuan(Department of Rheumatology and Immunology,PuYang People's Hospital,Henan 457000,China;Department of Rheumatology and Immunology,Peking University People's Hospital,Beijing 100044,China)

机构地区：[1]河南省濮阳市人民医院风湿免疫科,濮阳457000 [2]北京大学人民医院风湿免疫科,北京100044

出　　处：《中华风湿病学杂志》2022年第9期577-582,共6页Chinese Journal of Rheumatology

基　　金：国家自然科学基金(81701607)。

摘　　要：目的分析CTD合并新型隐球菌感染患者临床特点及相关因素,提高对该病的认识和临床诊疗水平。方法回顾性分析2010年1月至2021年4月在北京大学人民医院住院治疗的12例CTD并发新型隐球菌感染患者的临床特点、实验室检查结果、治疗、预后,并复习相关文献。采用独立样本t检验或秩和检验。结果12例患者均为女性,年龄18~85岁,平均(51±23)岁;均无明确鸟类接触史。其中3例RA,7例SLE,1例pSS,1例未分化CTD;4例隐球菌脑膜炎,8例肺隐球菌病;12例均无人类免疫缺陷病毒感染,起病前均曾单用或联合应用激素、免疫抑制剂、生物制剂治疗;血隐球菌抗原检测均阳性;6例行脑脊液检查,2例脑脊液墨汁染色阳性,2例脑脊液培养阳性,3例颅内压明显增高[最高>600 mmH2O)(1 mmH2O=0.0098 kPa)];7例行肺穿刺活检,7例肺组织病理学检查确诊阳性;6例发病时淋巴细胞<1.0×10^(9)/L,共2例检测了外周血CD4^(+)T细胞且水平明显降低。治疗方面,12例均静脉应用抗真菌药物治疗(4~6周),12例应用氟康唑,2例氟康唑联合两性霉素,1例氟康唑联合氟胞嘧啶,1例氟康唑联合两性霉素、氟胞嘧啶,均改为口服氟康唑序贯治疗,总疗程4~21个月,11例均痊愈,1例隐球菌脑膜炎症状缓解。结论CTD合并新型隐球菌感染临床症状不典型,发病可能与免疫抑制剂和糖皮质激素的应用有关,外周血淋巴细胞尤其是CD4^(+)T细胞降低更易感染,早期诊断早治疗是提高此病治愈率、改善预后的关键。Objective To improve the level of clinical diagnosis and treatment by analyzing the clinical features and relevant factors of cryptococcosis neoformans in patients with connective tissue disease(CTD).Methods Twelve patients with CTD and cryptococcosis neoformans infection in Peking University People's Hospital from January 2010 to April 2021 were retrospectively enrolled.Clinical and laboratory data,treatment and outcome were collected and analyzed.Independent sample t-test or Rank-sum test was used.Results The age of the patients ranged from 18 to 85 years old(mean 51 years old),all of whom were female.None of them were exposed to pigeons and their feces.Of the 12 patients,3 patients suffered from rheumatoid arthritis,7 patients had systemic lupus erythematosus,1 patient was diagnosed with primary Sjögren's syndrome,and 1 patient was diagnosed as undifferentiated connective tissue disease.Four cases were cryptococcal meningitis,8 were pulmonary cryptococcosis.None of the 12 patients had immunodeficiency virus infection.All 12 patients were given glucocorticoid alone or combined with immunosuppressive or biological agents.All were detected with positive cryptococcus neoformans antigen in serum;6 got lumbar puncture,2 cases were positive for ink stain,cerebrospinal fluid(CSF)culture were positive in 2,in whom 3 had high intracranial pressure,in which the highest one was more than 600 mmH2O(1 mmH2O=0.0098 kPa);7 cases underwent lung biopsy.Among these patients,all were positive for cryptococcosis neoformans in lung tissue pathological examination;6 had the number of peripheral lymphocytes less than 1.0×10^(9)/L,and 2 were detected for the number of CD4^(+)T cell,which was significantly decreased.As for the initial anti-fungal drug therapy,all cases were treated with fluconazole intravenously;2 were treated with combined amphotericin,1 was treated with combined fluorocytosine,1 was treated with amphotericin and fluorocytosine.Then oral flu-conazole was prescribed as sequential therapy.The whole treatmentcourse ran

关 键 词：结缔组织病 肺隐球菌病 隐球菌脑膜炎 

分 类 号：R593.2[医药卫生—内科学] R519.4[医药卫生—临床医学]