摘要
目的探讨类风湿关节炎(RA)患者利妥昔单抗相关进行性多灶性白质脑病(PML)的临床特点。方法检索国内外相关数据库(截至2021年11月),收集RA患者接受利妥昔单抗治疗后发生PML的病例报告类文献,提取患者的性别、年龄、基础疾病、利妥昔单抗使用情况、联合用药情况、PML发生时间、临床表现、辅助检查(影像学、脑脊液)结果、干预及转归等临床资料,进行描述性统计分析。结果纳入分析的患者共10例,男性1例,女性9例;年龄51~83岁,平均66岁;均为中至重度RA,病程≥3年者9例,1例无病程记录。10例患者利妥昔单抗用法用量均符合规定,均联合使用抗风湿药或糖皮质激素。9例患者有末次使用利妥昔单抗至发生PML的时间记录,7例为2~8个月,2例分别为16和18个月,中位时间6个月。6例患者有临床症状记录,主要为共济失调、言语障碍、认知功能减退和局灶性感觉障碍等。6例患者行头部MRI检查,均符合PML的影像学改变。4例患者行脑脊液乳头多瘤空泡病毒检测,3例病毒DNA阳性,1例阴性者经脑组织活检诊断为PML。诊断PML后1例未进行干预,3例无干预措施记录,5例单用或联用甲氟喹、米氮平治疗(其中2例联合血浆置换,1例加用糖皮质激素),1例联用米氮平和呋喃妥因治疗。7例因治疗无效死亡,2例存活但有严重神经损伤后遗症,1例未报告最终结局。结论利妥昔单抗相关PML多发生于末次应用该药后2~8个月,临床表现和影像学检查与其他原因所致PML相似,通常呈进行性加重,病死率高,幸存者可能有严重的神经损伤后遗症。
Objective To explore the clinical characteristics of rituximab⁃related progressive multifocal leukoencephalopathy(PML)in patients with rheumatoid arthritis(RA).Methods The relevant domestic and international databases(as of November 2021)were searched and case reports on PML in RA patients treated with rituximab were collected.Clinical data such as gender,age,underlying disease,use of rituximab,combination drugs,time to onset of PML,clinical manifestations,results of ancillary examinations(imaging,cerebrospinal fluid),intervention and prognosis were extracted and analyzed descriptively.Results A total of 10 patients were enrolled in the study,including 1 male and 9 females,aged from 51 to 83 years with an average of 66 years.All of the patients were suffering from moderate to severe RA,9 of which had a disease duration of≥3 years and 1 had no disease duration record.The usage and dosage of rituximab in the 10 patients were in accordance with the instructions,and all the patients received combined medication with conventional synthetic disease⁃modifying anti⁃rheumatic drugs or glucocorticoids.The time from the last dose of rituximab to the onset of PML was recorded in 9 patients,which were 2⁃8,16,and 18 months in 7,1,and 1 patient respectively,with a median time of 6 months.Clinical symptoms were recorded in 6 patients,mainly including ataxia,speech disorders,cognitive impairment,and focal sensory deficits,etc.Six patients had head magnetic resonance imaging,and all of the results were consistent with the imaging changes of PML.Four patients had cerebrospinal fluid anti⁃John Cunningham virus test,which were positive for viral DNA in 3 patients and negative in 1 patient(the patient was diagnosed with PML by brain tissue biopsy).After the diagnosis of PML,1 patient received no intervention,3 had no record of intervention measures,5 were treated with mefloquine and mirtazapine alone or in combination(2 of which were combined with plasma exchange and 1 with glucocorticoids),and 1 was treated with mirtazapine and nitrofurantoin in combination.Seven patients died due to ineffective treatment,2 survived but had severe neurological sequelae,and the final outcome of 1 patient was not reported.Conclusions Rituximab⁃related PML mostly occurs 2 to 8 months after the last application of the drug,which has similar clinical manifestations and imaging to that due to other causes and usually aggravate progressively with a high mortality rate.The survivors may have severe neurological sequelae.
作者
刘寄语
赵力
邹和建
薛愉
Liu Jiyu;Zhao Li;Zou Hejian;Xue Yu(Department of Rheumatology&Immunology,Huashan Hospital,Institute of Rheumatology,Immunology and Allergy,Fudan University,Shanghai 200040,China)
出处
《药物不良反应杂志》
CSCD
2022年第10期534-539,共6页
Adverse Drug Reactions Journal