神经精神性狼疮的最新治疗进展

摘要
神经精神性狼疮（NPSLE）是指与系统性红斑狼疮相关的一系列神经和精神症状。神经精神性狼疮包括累及中枢神经系统和外周神经系统的各种表现和少见的神经精神症状。由于缺乏金标准，确定神经精神症状为系统性红斑狼疮所致必须严格除外其他可能的原因，这的确是个临床挑战。在急性期，这些患者的治疗管理与其他有同样神经精神症状的非系统性红斑狼疮患者无差别。之后必须开始进行根据临床表现和症状严重程度制定的个性化治疗方案。神经精神性狼疮的治疗尚缺乏临床试验，数据主要来自病例系列研究和个案报道。考虑到炎症和潜在的自身免疫参与发病，对于症状严重的病例最主要的治疗仍然是大剂量激素和静脉用环磷酰胺。若治疗效果不佳可应用利妥昔单抗、静脉用丙种球蛋白或血浆置换。对于轻中度神经精神性表现的患者及维持治疗时，可选用硫唑嘌呤或霉酚酸酯。当症状由血栓性疾病所致，则抗凝和抗血小板制剂为主要的治疗药，尤其存在抗磷脂抗体或合并抗磷脂综合征时。基于对系统性红斑狼疮发病机制的理解，最近应用生物制剂治疗系统性红斑狼疮的临床试验显示了非常好的结果。根据我们目前对其发病机制的理解，可以推测到这些新的治疗方法可能会影响到神经精神性狼疮的治疗。本文对神经精神性狼疮的流行病学、病理生理、诊断和治疗进行详细的综述。基于文献检索和专家意见阐述了神经精神性狼疮最常用的药物治疗方法。并将对最新的治疗药物和新靶点的阻断剂对神经精神性狼疮未来治疗的影响进行讨论。

附原文：
Abstract Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most common pharmacological treatments used in NPSLE, based on both a literature search and our expert opinion. The extent to which new drugs in the advanced development of SLE, or the blockade of new targets, may impact future treatment of NPSLE will also be discussed.

引自：
Magro-Checa C, Zirkzee EJ,Huizinga TW, et al. Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives.Drugs. 2016;76(4):459-83.