系统性红斑狼疮患者应用靶向B细胞治疗后发生中枢神经系统病变文献病例分析

Literature case analysis of central nervous system lesions in patients with systemic lupus erythematosus after targeted B cell therapy

目的探讨系统性红斑狼疮(SLE)患者经靶向B淋巴细胞生物制剂治疗后发生中枢神经系统不良反应的临床特征。方法检索国内外相关数据库(截至2023年5月),收集系统性红斑狼疮患者经贝利尤单抗、利妥昔单抗治疗后发生中枢神经系统病变的病例报告类文献,提取患者的基本信息、贝利尤单抗或利妥昔单抗用药情况(用法用量、单用或联用、联用方案等)、中枢神经系统病变发生时间、临床表现、影像学特征、临床治疗及转归等,并进行描述统计分析。结果检索到进行性多灶性脑白质病(PML)患者14例,发病年龄(50.71±11.45)岁;可逆性后部脑病综合征(PRES)患者24例,发病年龄(30.67±14.93)岁。纳入有详细病例报道的患者共7例,7例患者均未合并HIV感染、恶性肿瘤及其他自身免疫性疾病。7例患者均经磁共振检查确诊,均未行脑组织活检。临床表现:癫痫5例,视物模糊或视力丧失3例,构音障碍或失语2例,头痛2例,昏迷1例,血压升高4例。最终7例患者中1例死亡。结论应用靶向B细胞治疗后,SLE患者中枢神经系统副作用多发生在疾病活动期且合并使用其他免疫抑制剂时。患者的临床表现容易与神经精神狼疮混淆,导致病情延误,提示在使用靶向B细胞生物制剂治疗时,应评估SLE患者发生中枢神经系统副作用的潜在风险。

Objective To investigate the clinical features of side effects of central nervous system in patients with systemic lupus erythematosus(SLE)treated with B lymphocyte targeted biologic agents.Methods By searching domestic and foreign databases(up to May 2023),case reports on patients with systemic lupus erythematosus who developed central nervous system diseases after treatment with belimumab and rituximab were collected.The basic information of patients,the medication of belimumab or rituximab(usage and dosage,single or combined use,combined use plan,etc.),time of onset,symptoms,imaging features,treatment and outcome of the lesions of central nervous system were extracted,and descriptive statistical analysis was conducted.Results A total of 14 progressive multifocal leukoencephalopathy(PML)patients with onset age of(50.71±11.45)years old and 24 posterior reversible encephalopathy syndrome(PRES)patients with onset age of(30.67±14.93)years old were searched.A total of 7 patients with detailed case reports were included.None of the 7 patients had HIV infection,malignant tumor or other autoimmune diseases.All 7 patients were confirmed by magnetic resonance examination without brain biopsy.Clinical manifestations:5 cases of epilepsy,3 cases of blurred vision or vision loss,2 cases of dysplasia or aphasia,2 cases of headache,1 case of coma,4 cases of elevated blood pressure.One of the seven patients died.Conclusion The side effects of central nervous system in SLE patients after targeted b-cell therapy occur frequently in the active stage and when used in combination with other immunosuppressants.Patients with neuropsychiatric lupus can easily be confused with their clinical manifestations,resulting in delayed condition.This suggests that the potential risk of side effects of central nervous system in SLE patients should be assessed when b-cell targeted biologics are used.