风湿免疫病患者结核分枝杆菌潜伏感染率及相关影响因素的多中心横断面研究

Latent tuberculosis infection rate and risk factors in patients with rheumatic diseases:a multi-center,cross-sectional study

目的:以结核感染T细胞斑点试验(T-SPOT.TB)检测作为筛查结核分枝杆菌潜伏感染(latent tuberculosis infection,LTBI)的工具,调查我国风湿免疫病患者结核分枝杆菌潜伏感染率,并分析影响T-SPOT.TB检测结果的相关因素。方法:纳入自2014年9月至2016年3月我国东、中、西部13家三级甲等综合医院接诊的风湿免疫病患者作为研究对象,共计3715例。应用T-SPOT.TB对研究对象进行LTBI筛查。收集研究对象的基本信息,包括性别、年龄、地区、体质量指数、病程、吸烟史、基础疾病、结核病患者密切接触史、结核病既往史,以及糖皮质激素、免疫抑制剂及生物制剂的使用情况,实验室化验结果,风湿免疫病诊断结果等。采用单因素及多因素logistic回归模型分析影响T-SPOT.TB检测结果的因素。结果:3715例研究对象T-SPOT.TB检测阳性者有672例(18.1%,95%CI:16.9%~19.3%)。不同风湿免疫病病种患者T-SPOT.TB检测阳性率差异有统计学意义(χ^(2)=79.003,P<0.001),白塞综合征患者检测阳性率最高(44.4%,32/72),混合性结缔组织病患者检测阳性率最低(8.9%,4/45)。男性风湿免疫病患者T-SPOT.TB检测阳性率为23.6%(168/711),明显高于女性(16.8%,504/3004),差异有统计学意义(χ^(2)=18.213,P<0.001)。不同年龄组风湿免疫病患者T-SPOT.TB检测阳性率差异有统计学意义(χ^(2)=67.189,P<0.001),51~60岁组检测阳性率最高(24.8%,143/577),16~20岁组检测阳性率最低(8.1%,13/160)。多因素logistic回归分析显示:年龄≥41岁(aOR=1.81,95%CI:1.48~2.23),吸烟≥21支/d(aOR=1.66,95%CI:1.15~2.40),有结核病既往史(aOR=3.88,95%CI:2.71~5.57),患白塞综合征(aOR=3.00,95%CI:1.70~5.28)是T-SPOT.TB检测阳性结果的独立相关因素;使用大剂量激素(aOR=0.67,95%CI:0.47~0.96)或生物制剂(aOR=0.55,95%CI:0.36~0.84),淋巴细胞计数偏低(aOR=0.39,95%CI:0.25~0.62),低蛋白血症(aOR=0.72,95%CI:0.52~0.99),以及患多发性肌炎/皮肌炎(aOR=0.54,95%CI:0.29~0.99)、系统性红斑狼疮(aOR=0.75,95%CI:0.57~0.99)是T-SPOT.TB检测阴性结果的独立相关因素。结论:风湿免疫病患者总体结核分枝杆菌潜伏感染率为18.1%,各病种T-SPOT.TB检测阳性率差异明显。当患者有大剂量糖皮质激素、生物制剂的使用,淋巴细胞计数偏低,低蛋白血症,以及罹患系统性红斑狼疮时警惕假阴性结果。

Objective:This study aimed to screen latent tuberculosis infection(LTBI)among patients with rheumatic diseases in China using the T-SPOT.TB assay and investigate factors affecting the results of T-SPOT.TB.Methods:Rheumatic diseases patients(n=3715)were enrolled from 13 tertiary hospitals in Eastern,Middle,and Western China from September 2014 to March 2016 and were screened by the T-SPOT.TB assay to detect LTBI.Basic information about the subjects were collected,including gender,age,region,body mass index,course of disease,smoking history,underlying disease,close contact history of tuberculosis patients,evidence of previous tuberculosis,the use of glucocorticoids,immunosuppressants and biologics,laboratory tests,and diagnosis of rheumatic disease,etc.Univariate analysis and multivariable logistic regression were performed to identify factors affecting the results of T-SPOT.TB.Results:out Of the 3715 patients,672 were positive in T-SPOT.TB,the positive rate was 18.1%(95%CI:16.9%-19.3%).There was a statistically significant difference in the positive rate of T-SPOT.TB test among patients with different types of rheumatic immune diseases(χ^(2)=79.003,P<0.001),patients with Behcet’s syndrome had the highest positive rate(44.4%,32/72),while patients with mixed connective tissue disease had the lowest positive rate(8.9%,4/45).The positive rate of T-SPOT.TB test in male patients with rheumatic immune disease was 23.6%(168/711),which was significantly higher than that in females(16.8%,504/3004,χ^(2)=18.213,P<0.001).There was a statistically significant difference in the positive rate of T-SPOT.TB test among patients with rheumatic immune disease in different age groups(χ^(2)=67.189,P<0.001),the 51-60 years old group had the highest positive rate(24.8%,143/577),while the 16-20 years old group had the lowest positive rate(8.1%,13/160).Multivariate logistic regression analysis showed that age≥41 years(aOR=1.81,95%CI:1.48-2.23),smoking≥21 cigarettes/d(aOR=1.66,95%CI:1.15-2.40),previous history of tuberculosis(aOR=3.88,95%CI:2.71-5.57),and Behcet’s syndrome(aOR=3.00,95%CI:1.70-5.28)were independent related factors of T-SPOT.TB positive results;using high-dose hormones(aOR=0.67,95%CI:0.47-0.96)or biological agents(aOR=0.55,95%CI:0.36-0.84),low lymphocyte count(aOR=0.39,95%CI:0.25-0.62),hypoalbuminemia(aOR=0.72,95%CI:0.52-0.99),and multiple myositis/dermatomyositis(aOR=0.54,95%CI:0.29-0.99),systemic lupus erythematosus(aOR=0.75,95%CI:0.57-0.99)were independent correlation factors for negative T-SPOT.TB test results.Conclusion:Among patients with rheumatic diseases,the overall prevalence of LTBI is 18.1%.There is a significant difference in the positive rate of T-SPOT.TB test among different diseases.When patients are treated with high-dose glucocorticoids or biologics,have low lymphocyte counts,hypoalbuminemia,or suffer from systemic lupus erythematosus,more attention should be paid to potential false-negative results.