儿童结核性脑膜炎抗结核治疗中发生类赫反应的危险因素

Risk factors of paradoxical response during anti-tuberculosis treatment in children with tuberculous meningitis

目的探讨儿童结核性脑膜炎(TBM)抗结核治疗中出现类赫反应(PR)的临床特征、危险因素及对预后的影响。方法回顾性分析2013年1月至2018年12月在遵义医科大学附属医院儿科收治的TBM患儿的临床资料及随访情况;根据是否发生PR分组,采用单因素分析选出PR的影响因素后,引入多因素Logistic回归分析找出PR的独立危险因素;评估PR对随访≥9个月预后的影响。结果纳入87例TBM,其中31例(35.6%)发生PR,男16例,女15例,中位年龄92个月(8~168个月)。在抗结核治疗中位时间33 d(15~180 d)出现PR,表现为原有症状加重或复现(22/31例,71.0%),脑脊液(CSF)恶化(25/31例,80.6%)及脑影像恶化(16/31例,51.6%)。单因素分析显示PR与临床分期Ⅱ期、肢体瘫痪、颅神经损害、结核感染检测(T-SPOT)阳性、CSF乳酸脱氢酶(LDH)水平升高、基底脑膜强化、中枢神经系统外结核有关(均P<0.05);多因素Logistic回归分析显示肢体瘫痪、颅神经损害、LDH水平升高及T-SPOT阳性是PR的独立危险因素(均P<0.05)。PR与预后无关(P=0.165)。结论TBM患儿抗结核治疗中35.6%发生PR,与肢体瘫痪、颅神经损害、CSF-LDH水平升高、T-SPOT阳性有关,与预后无关。识别PR极其重要,可避免一些临床误区。

Objective To investigate clinical features,risk factors and prognostic effects of paradoxical response(PR)in children with tuberculous meningitis(TBM)during anti-tuberculosis treatment.Methods The clinical and follow-up data of TBM children admitted to the Department of Pediatrics,the Affiliated Hospital of Zunyi Medical University between January 2013 and December 2018 were retrospectively analyzed.The children were divided into the PR group and the non-PR group.Influencing factors of PR were selected by the univariate analysis,and independent risk factors were screened from these influencing factors by using the multivariate Logistic regression model.The effect of PR on long-term prognosis(≥9 months)of TBM was evaluated.Results There were 31 cases(35.6%)with PR among the 87 TBM children enrolled,including 16 boys and 15 girls,with median age of 92(8-168)months.The median time for PR occurrence during the anti-tuberculosis treatment was 33(15-180)days.PR could present dete-rioration or recurrence of original symptoms,cerebrospinal fluid(CSF)deterioration and neuroimaging deterioration,accounting for 71.0%(22/31 cases),80.6%(25/31 cases)and 51.6%(16/31 cases),respectively.Univariate analysis showed that stageⅡ,limb paralysis,cranial nerve palsy,positive tests of tuberculosis infection(T-SPOT),an increased lactate dehydrogenase(LDH)level in CSF,basilar meningeal enhancement,and tuberculosis infection outside the central nervous system were the influencing factors of the PR(all P<0.05).Multivariate analysis showed that limb paralysis,cranial nerve palsy,an increased CSF-LDH level,and positive T-SPOT were independent risk factors of PR(all P<0.05).PR was not associated with prognosis(P=0.165).Conclusions PR occurs in 35.6%of children with TBM.Limb paralysis,cranial nerve palsy,an increased CSF-LDH level and positive T-SPOT are independent risk factors of PR.PR does not adversely affect the outcome.Identifying PR is extremely important for the prevention of some clinical misunderstandings.