Service de médecine interne, Fondation A. de Rothschild, 25-29, rue Manin, 75019 Paris, France; Inserm UMR 1125, 74, rue Marcel-Cachin, 93017 Bobigny, France; Sorbonne Paris Cité, université Paris 13, 74, rue Marcel-Cachin, 93017 Bobigny, France.
Service de neurologie, Fondation A. de Rothschild, 75019 Paris, France.
Joint Bone Spine. 2017 Dec;84(6):671-675. doi: 10.1016/j.jbspin.2017.03.002. Epub 2017 Mar 18.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood. However, a consistent feature is the presence of a predisposing factor, most notably immunosuppression. The risk of developing PML varies with the underlying disease (e.g., HIV infection or autoimmune disease) and with the drugs used to treat them. Biologics have been ranked according to the risk of PML during their use. Natalizumab, a monoclonal antibody given to treat multiple sclerosis, is among the drugs associated with a high risk of PML. Patients given natalizumab are now closely monitored based on anti-JCV antibody titers and index values. In rheumatology, the expanding use of biologics has led to an increase in cases of PML, with rituximab being associated with the highest risk. Given the absence of specific recommendations, exhaustive registries and postmarketing observational studies are urgently needed to gauge the risk of PML according to the underlying disease and drug treatments, with the goal of defining optimal monitoring protocols.
进行性多灶性白质脑病（PML）是一种中枢神经系统脱髓鞘疾病，由 JC 病毒（JCV）再激活引起。尽管该病毒在普通人群中的流行率很高，但 PML 极为罕见。目前尚无特异性治疗方法，预后较差。诊断基于脑部影像学发现、脑脊液样本中 JCV 基因组的检测，以及在某些情况下，对脑部病变的组织学研究。导致 PML 发展的病理生理机制尚未完全阐明。然而，一个一致的特征是存在诱发因素，最常见的是免疫抑制。发生 PML 的风险因基础疾病（例如 HIV 感染或自身免疫性疾病）和用于治疗这些疾病的药物而有所不同。生物制剂根据使用过程中发生 PML 的风险进行了分类。那他珠单抗是一种用于治疗多发性硬化症的单克隆抗体，是与 PML 高风险相关的药物之一。接受那他珠单抗治疗的患者现在根据抗 JCV 抗体滴度和指数值进行密切监测。在风湿病学中，生物制剂的广泛使用导致 PML 病例增加，利妥昔单抗与最高风险相关。由于缺乏具体建议，迫切需要进行详尽的登记和上市后观察性研究，根据基础疾病和药物治疗来评估 PML 的风险，以确定最佳监测方案。
