干燥综合征继发隐球菌性脑膜脑炎一例报告及相关自身免疫病文献复习

doi:10.16150/j.1671-2870.2021.05.006

摘要/Abstract

摘要：

目的：分析报道1例干燥综合征（Sjögren syndrome,SS）继发隐球菌性脑膜脑炎（cryptococcal meningoencephalitis, CM）患者,结合文献探讨自身免疫病继发CM的临床、病理特征及诊治方法。 方法：分析2019年上海交通大学附属第六人民医院收治的1例SS继发CM患者的临床资料,并在国内外数据库中检索相关文献,汇总分析自身免疫病继发CM病例的临床、病理特征和诊治方法。 结果：本例患者有SS病史,本次以头痛、发热及颅内压升高起病,经脑脊液墨汁染色涂片明确诊断为CM。患者经抗真菌治疗后,因疾病复发死于两性霉素B导致的药物不良反应。回顾分析文献和本例患者后发现,9%~18%的CM患者罹患有自身免疫病,且不同研究中患者的发热症状表现及发热率差异较大（33%~82%）;患者的临床表现以脑脊液压力增高引起的头痛（38%~100%）为多见。目前,CM的诊断仍依赖于脑脊液检查。联合两性霉素B和氟胞嘧啶的治疗方案疗效并不令人满意,安全性差。患者预后不佳,死亡率高（5%~42%）。 结论：包括SS在内的自身免疫病患者继发CM时,其临床表现不典型,而脑脊液压力异常增高是其特点,目前其治疗方法缺乏,患者的死亡率高、预后不佳。

关键词: 干燥综合征, 自身免疫病, 新型隐球菌, 脑膜脑炎

Abstract:

Objective: To investigate a case of cryptococcal meningoencephalitis (CM) secondary to Sjögren′s syndrome (SS), and to analyze the clinical, pathological features, diagnosis and treatment of the diseases combined with literature review. Methods: Clinical data of 1 case of CM secondary to SS patient were collected, and literatures online were reviewed. Results: The main clinical manifestation consisted of headache, fever and intracranial hypertension. CM was confirmed by cerebrospinal fluid ink stain smear, but the patient still died of complication of amphotericin B treatment. Literature review indicated 9%-18% CM may had a history of autoimmune diseases. Headache because of increased cerebrospinal fluid pressure ocuured in 38%-100%. The efficacy of amphotericin B combined with fluorocytosine in recommended treatment was not satisfactory, and mortality was high (5%-42%). Conclusions: The clinical manifestation of CM secondary to autoimmune diseases is not typical, the abnormal increase of cerebrospinal fluid pressure is its characteristic. The efficacy of treatment is not satisfactory, and the mortality rate is high.

Key words: Sjögren′s syndrome, Autoimmune diseases, Cryptococcus neoformans, Meningoencephalitis

中图分类号:

R593.2

陆弘逾, 顾俊, 王静, 曹亚峰, 宋陆茜, 范俊, 陈梅. 干燥综合征继发隐球菌性脑膜脑炎一例报告及相关自身免疫病文献复习[J]. 诊断学理论与实践, 2021, 20(05): 456-461.

LU Hongyu, GU Jun, WANG Jing, CAO Yafeng, SONG Luxi, FAN Jun, CHEN Mei. Sjögren′s syndrome secondary to cryptococcal meningoencephalitis: a case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2021, 20(05): 456-461.

图/表 2

参考文献 19

[1]	Thorne I, Sutcliffe N. Sjögren′s syndrome[J]. Br J Hosp Med (Lond), 2017,78(8):438-442. doi: 10.12968/hmed.2017.78.8.438 URL
[2]	Margaretten M. Neurologic Manifestations of Primary Sjögren Syndrome[J]. Rheum Dis Clin North Am, 2017,43(4):519-529. doi: 10.1016/j.rdc.2017.06.002 URL
[3]	Moosa MY, Coovadia YM. Cryptococcal meningitis in Durban, South Africa: a comparison of clinical features, laboratory findings, and outcome for human immunodeficiency virus (HIV)-positive and HIV-negative patients[J]. Clin Infect Dis, 1997,24(2):131-134. pmid: 9114135
[4]	Pappas PG, Perfect JR, Cloud GA, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy[J]. Clin Infect Dis, 2001, 33(5):690-699. pmid: 11477526
[5]	Chau TT, Mai NH, Phu NH, et al. A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam - high prevalence of Cryptococcus neoformans var grubii in the absence of underlying di-sease[J]. BMC Infect Dis, 2010,10:199. doi: 10.1186/1471-2334-10-199 URL
[6]	Lee YC, Wang JT, Sun HY, et al. Comparisons of clinical features and mortality of cryptococcal meningitis between patients with and without human immunodeficiency virus infection[J]. J Microbiol Immunol Infect, 201144(5):338-345.
[7]	Zheng H, Chen Q, Xie Z, et al. A retrospective research of HIV-negative cryptococcal meningoencephalitis patients with acute/subacute onset[J]. Eur J Clin Microbiol Infect Dis, 2016,35(2):299-303. doi: 10.1007/s10096-015-2545-0 URL
[8]	Li M, Chen Z, Xu L, et al. A Comparison of the clinical characteristics and outcomes of cryptococcal meningitis in HIV-negative individuals with and without immunosuppression[J]. Neurologist, 2019,24(1):1-5. doi: 10.1097/NRL.0000000000000221 URL
[9]	Marr KA, Sun Y, Spec A, et al. A multicenter, longitu-dinal cohort study of cryptococcosis in human immuno-deficiency virus-negative people in the United States[J]. Clin Infect Dis, 2020,70(2):252-261. doi: 10.1093/cid/ciz193 URL
[10]	常艳宇, 胡学强. 新型隐球菌性脑膜炎和(或)脑炎102例诊断与治疗经验[J]. 中国现代神经疾病杂志, 2014,14(8):687-692.
[11]	Beardsley J, Hoang NLT, Kibengo FM, et al. Do intrace-rebral cytokine responses explain the harmful effects of dexamethasone in human immunodeficiency virus-associated cryptococcal meningitis?[J]. Clin Infect Dis, 2019,68(9):1494-1501. doi: 10.1093/cid/ciy725 pmid: 30169607
[12]	Boulware DR, Rolfes MA, Rajasingham R, et al. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast[J]. Emerg Infect Dis, 2014,20(1):45-53. doi: 10.3201/eid2001.130906 pmid: 24378231
[13]	Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america[J]. Clin Infect Dis, 2010,50(3):291-322. doi: 10.1086/649858 pmid: 20047480
[14]	刘正印, 王贵强, 朱利平, 等. 隐球菌性脑膜炎诊治专家共识[J]. 中华内科杂志, 2018,57(5):317-323.
[15]	Tseng HK, Liu CP, Ho MW, et al. Microbiological, epidemiological, and clinical characteristics and outcomes of patients with cryptococcosis in Taiwan, 1997-2010[J]. PLoS One,2013, 8(4):e61921. doi: 10.1371/journal.pone.0061921 URL
[16]	Pappas PG. Cryptococcal infections in non-HIV-infected patients[J]. Trans Am Clin Climatol Assoc, 2013,124:61-79. pmid: 23874010
[17]	Fang W, Chen M, Liu J, et al. Cryptococcal meningitis in systemic lupus erythematosus patients: pooled analysis and systematic review[J]. Emerg Microbes Infect, 2016, 5(9):e95.
[18]	Dixon WG, Abrahamowicz M, Beauchamp ME, et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis[J]. Ann Rheum Dis, 2012,71(7):1128-1133. doi: 10.1136/annrheumdis-2011-200702 URL
[19]	Liao TL, Chen YM, Chen DY. Risk factors for cryptococcal infection among patients with rheumatoid arthritis receiving different immunosuppressive medications[J]. Clin Microbiol Infect, 2016,22(9):815,e1.