60例人类免疫缺陷病毒感染者/获得性免疫缺陷综合征合并神经梅毒患者临床和实验室特征

Clinical and laboratory characteristics of neurosyphilis in 60 patients with human immunodeficiency virus infection/acquired immune deficiency syndrome

目的分析人类免疫缺陷病毒(HIV)感染者/获得性免疫缺陷综合征(AIDS)合并无症状神经梅毒(ANS)和症状性神经梅毒(SNS)患者的临床及实验室特征,并探讨SNS的危险因素。方法收集2014年1月至2021年8月首都医科大学附属北京地坛医院住院确诊为神经梅毒的60例HIV/AIDS患者的临床资料,采用Spearman相关分析患者CD4^(+)T细胞计数与脑脊液指标的相关性;并根据临床症状或体征分为ANS组(23例)和SNS组(37例),分析两组患者的临床特征、血清学及脑脊液指标,并采用多因素Logistic回归分析ANS患者进展为SNS的危险因素。结果入组患者均为男性,中位年龄32.5岁,SNS组驱梅治疗和抗逆转录病毒治疗(ART)者均为6例(16.22%),显著低于ANS组[18例(78.26%)和16例(69.57%)](χ^(2)=22.750、P=0.001,χ^(2)=17.383、P<0.001);CSF TRUST滴度分布差异有统计学意义(P=0.030),SNS组CSF TRUST阳性患者29例(78.38%),显著高于ANS组[9例(39.13%)](χ^(2)=8.013、P=0.005)。入院时血清TRUST滴度分布差异有统计学意义(P=0.026),SNS组患者入院时血清TRUST滴度[1︰128(1︰32,1︰256)vs.1︰32(1︰8,1︰64):Z=-3.303、P=0.001]和CSF-WBC计数[45(18.5,92)个/μl vs.15(6,22)个/μl:Z=-3.613、P<0.001]均显著高于ANS组;而CSF葡萄糖浓度[2.9(2.5,3.5)mmol/L vs.3.3(3.0,4.0)mmol/L:Z=-2.266、P=0.023]显著低于ANS组。两组患者年龄、CSF蛋白含量、CSF蛋白异常率、CSF氯化物浓度、CD4^(+)T细胞计数以及CD4^(+)T细胞计数<200个/μl患者比例差异均无统计学意义。CD4^(+)T细胞计数与脑脊液蛋白含量(r=-0.498、P<0.001)、脑脊液葡萄糖浓度(r=0.442、P<0.001)、脑脊液氯化物浓度(r=0.289、P=0.025)均有一定相关性。多因素Logistic回归分析显示,有驱梅治疗史(OR=0.060、P=0.001)为ANS进展为SNS的保护性因素;入院时血清TRUST滴度(OR=1.489、P=0.039)、ln脑脊液白细胞计数(OR=2.690、P=0.007)为ANS进展为SNS的危险性因素。血清TRUST滴度每升高1个滴度,ANS进展为SNS的风险增加1.489倍;脑脊液白细胞计数每增加1个ln值,ANS进展为SNS的风险增加2.690倍。结论患者CD4^(+)T细胞计数越低,脑脊液蛋白含量越高,而脑脊液葡萄糖浓度、脑脊液氯化物浓度则越低;驱梅治疗可降低SNS发生率,血清TRUST滴度及脑脊液白细胞计数升高可能增加ANS进展为SNS的风险。

Objective To investigate the clinical and laboratory characteristics of asymptomatic neurosyphilis(ANS)and symptomatic neurosyphilis(SNS)in patients with human immunodeficiency virus infection/acquired immune deficiency syndrome(HIV/AIDS),and to analyze the risk factors of SNS.Methods Total of 60 HIV/AIDS inpatients with neurosyphilis were enrolled in Beijing Ditan Hospital,Capital Medical University from January 2014 to August 2021.The correlation between CD4^(+)T cell count and cerebrospinal fluid(CSF)-related factors were analyzed by Spearman correlation analysis.The enrolled patients were divided into SNS group(23 cases)and ANS group(37 cases)according to clinical symptoms or signs,the clinical characteristics,serology and CSF examination were compared,respectively.The risk factors for progression to symptomatic neurosyphilis were analyzed by multivariate Logistic regression.Results All the 60 patients were male,with a median age of 32.5 years old.Patients who received antisyphilitic treatment or antiretroviral therapy(ART)were both 6 cases(16.22%)in SNS group,which were significantly lower than those of ANS group for 18 patients(78.26%)and 16 patients(69.57%),with significant differences(χ^(2)=22.750,P=0.001;χ^(2)=17.383,P<0.001).There was a statistical difference in CSF TRUST titer distribution(P=0.03),and there were 29 cases(78.38%)with positive CSF TRUST in SNS group,which was significantly higher than that of ANS group[9 cases(39.13%)],with significant difference(χ^(2)=8.013,P=0.005).There was a statistical difference in serum TRUST titer distribution at admission(P=0.023),and the serum TRUST titer,CSF-WBC count of patients in SNS group were[1︰128(1︰32,1︰256)]and[45(18.5,92)]cells/μl,which were significantly higher than those of ANS group[1︰32(1:8,1︰64)and 15(6,22)cells/μl],with significant differences(Z=-3.303,P=0.001;Z=-3.613,P<0.001);but the CSF glucose concentration was significantly lower than that of ANS group[2.9(2.5,3.5)mmol/L vs.3.3(3.0,4.0)mmol/L],with significant difference(Z=-2.266,P=0.023).Age,serum TRUST titer distribution at admission,CSF TRUST titer distribution,CSF protein concentration,CSF protein abnormal rate,CSF chloride,count of CD4^(+)T cells and proportion of patients with CD4^(+)T cells count<200 cells/μl were all without significant differences between the two groups.CD4^(+)T cells counts were correlated with CSF protein concentration(r=-0.498,P<0.001),CSF glucose concentration(r=0.442,P<0.001),CSF chloride concentration(r=0.289,P=0.025).Multivariate Logistic regression analysis showed that a history of antisyphilistic therapy(OR=0.060,P=0.001)was the protective factor of ANS progression to SNS;Serum TRUST titer at admission(OR=1.489,P=0.039)and ln CSF-WBC count(OR=2.690,P=0.007)were risk factors of ANS progression to SNS.The risk of ANS progression to SNS increased 1.489 times for every increase in serum TRUST titer,and 2.690 times for every ln increase in CSF WBC count.Conclusions The lower the count of CD4^(+)T cells,the higher the protein concentrations in CSF,while the lower the concentrations of glucose and chloride in CSF.Treatment with benzylpenicillin could reduce the occurrence of SNS,and the increase of current serum TRUST titer and CSF WBC count may increase the risk of asymptomatic neurosyphilis developing into symptomatic neurosyphilis.