Fournier Anna, Martin-Blondel Guillaume, Lechapt-Zalcman Emmanuèle, Dina Julia, Kazemi Apolline, Verdon Renaud, Mortier Emmanuel, de La Blanchardière Arnaud
Department of Infectious and Tropical Diseases, CHU Côte de Nacre, Caen, France.
Department of Infectious and Tropical Diseases, CHU Toulouse, Toulouse, France.
Front Immunol. 2017 May 23;8:577. doi: 10.3389/fimmu.2017.00577. eCollection 2017.
Incidence of progressive multifocal leukoencephalopathy (PML) in HIV-infected patients has declined in the combined antiretroviral therapy (cART) era although a growing number of acquired immunodeficiency syndrome (AIDS)-related PML-immune reconstitution inflammatory syndromes (PML-IRIS) have been published during the same period. Therapeutic management of PML-IRIS is not consensual and mainly relies on corticosteroids. Our main aim was, in addition to provide a thoughtful analysis of published PML-IRIS cases, to assess the benefit of corticosteroids in the management of PML-IRIS, focusing on confirmed cases. We performed a literature review of the 46 confirmed cases of PML-IRIS cases occurring in HIV-infected patients from 1998 to September 2016 (21 unmasking and 25 paradoxical PML-IRIS). AIDS-related PML-IRIS patients were mostly men (sex ratio 4/1) with a median age of 40.5 years (range 12-66). Median CD4 T cell count before cART and at PML-IRIS onset was 45/μl (0-301) and 101/μl (20-610), respectively. After cART initiation, PML-IRIS occurred within a median timescale of 38 days (18-120). Clinical signs were motor deficits (69%), speech disorders (36%), cognitive disorders (33%), cerebellar ataxia (28%), and visual disturbances (23%). Brain MRI revealed hyperintense areas on T2-weighted sequences and FLAIR images (76%) and suggestive contrast enhancement (87%). PCR for John Cunningham virus (JCV) in cerebrospinal fluid (CSF) was positive in only 84% of cases; however, when performed, brain biopsy confirmed diagnosis of PML in 90% of cases and demonstrated histological signs of IRIS in 95% of cases. Clinical worsening related to PML-IRIS and leading to death was observed in 28% of cases. Corticosteroids were prescribed in 63% of cases and maraviroc in one case. Statistical analysis failed to demonstrate significant benefit from steroid treatment, despite spectacular improvement in certain cases. Diagnosis of PML-IRIS should be considered in HIV-infected patients with worsening neurological symptoms after initiation or resumption of effective cART, independently of CD4 cell count prior to cART. If PCR for JCV is negative in CSF, brain biopsy should be discussed. Only large multicentric randomized trials could potentially demonstrate the possible efficacy of corticosteroids and/or CCR5 antagonists in the management of PML-IRIS.
在联合抗逆转录病毒治疗（cART）时代，HIV感染患者中进行性多灶性白质脑病（PML）的发病率有所下降，尽管同期有越来越多与获得性免疫缺陷综合征（AIDS）相关的PML免疫重建炎症综合征（PML-IRIS）被报道。PML-IRIS的治疗管理尚无共识，主要依赖于皮质类固醇。我们的主要目的，除了对已发表的PML-IRIS病例进行深入分析外，还在于评估皮质类固醇在PML-IRIS管理中的益处，重点关注确诊病例。我们对1998年至2016年9月期间在HIV感染患者中发生的46例确诊PML-IRIS病例进行了文献综述（21例揭露型和25例矛盾型PML-IRIS）。与AIDS相关的PML-IRIS患者大多为男性（性别比4/1），中位年龄为40.5岁（范围12 - 66岁）。cART前及PML-IRIS发病时CD4 T细胞计数的中位数分别为45/μl（0 - 301）和101/μl（20 - 610）。开始cART后，PML-IRIS发生的中位时间为38天（18 - 120天）。临床症状包括运动障碍（69%）、言语障碍（36%）、认知障碍（33%）、小脑共济失调（28%）和视觉障碍（23%）。脑部MRI显示T2加权序列和液体衰减反转恢复（FLAIR）图像上有高信号区（76%）以及提示性的对比增强（87%）。脑脊液（CSF）中针对约翰·坎宁安病毒（JCV）的聚合酶链反应（PCR）仅在84%的病例中呈阳性；然而，进行脑活检时，90%的病例确诊为PML，95%的病例显示有IRIS的组织学迹象。28%的病例观察到与PML-IRIS相关并导致死亡的临床恶化。63%的病例使用了皮质类固醇，1例使用了马拉维若。统计分析未能证明类固醇治疗有显著益处，尽管某些病例有显著改善。对于开始或恢复有效的cART后出现神经症状恶化的HIV感染患者，无论cART前的CD4细胞计数如何，都应考虑PML-IRIS的诊断。如果CSF中JCV的PCR检测为阴性，应讨论是否进行脑活检。只有大型多中心随机试验有可能证明皮质类固醇和/或CCR5拮抗剂在PML-IRIS管理中的可能疗效。
