Himedan Mai, Camelo-Piragua Sandra, Mills Elizabeth A, Gupta Avneesh, Aburashed Rany, Mao-Draayer Yang
University of Michigan, Ann Arbor, MI, USA.
Michigan State University, East Lansing, MI, USA.
J Investig Med High Impact Case Rep. 2017 Sep 27;5(3):2324709617734248. doi: 10.1177/2324709617734248. eCollection 2017 Jul-Sep.
Immune reconstitution inflammatory syndrome (IRIS) is a common complication during treatment for natalizumab-associated progressive multifocal leukoencephalopathy (PML). Although severe IRIS can result in acute worsening of disability and is associated with poor prognosis, effective immune reconstitution may account for the high survival rate of this cohort of PML patients. We present pathological evidence of chronic IRIS 3.5 years after diagnosis with natalizumab-associated PML. Our case showed that the IRIS initially developed after plasma exchange therapy and resolved clinically and radiologically following a combination treatment with corticosteroids, maraviroc, and cidofovir. Autopsy 3.5 years later revealed evidence of grey-white matter junction demyelinating lesions characteristic of PML and perivascular leukocyte infiltrates predominated by CD8 T-lymphocytes, and polymerase chain reaction analysis demonstrated the presence of JC viral DNA in this tissue, indicative of persistent PML-IRIS. While clinical symptoms of PML-IRIS typically stabilize within 6 months, our case report suggests that prolonged low-grade inflammation may persist in some patients. Better assays are needed to determine the prevalence of prolonged low-grade IRIS among PML survivors.
免疫重建炎症综合征（IRIS）是那他珠单抗相关的进行性多灶性白质脑病（PML）治疗期间的常见并发症。尽管严重的IRIS可导致残疾急性加重且预后不良，但有效的免疫重建可能是该组PML患者高生存率的原因。我们展示了确诊那他珠单抗相关PML 3.5年后慢性IRIS的病理证据。我们的病例显示，IRIS最初在血浆置换治疗后出现，在联合使用皮质类固醇、马拉维若和西多福韦治疗后临床和影像学表现均得到缓解。3.5年后的尸检发现了具有PML特征的灰白质交界区脱髓鞘病变证据以及以CD8 T淋巴细胞为主的血管周围白细胞浸润，聚合酶链反应分析表明该组织中存在JC病毒DNA，提示持续性PML-IRIS。虽然PML-IRIS的典型症状通常在6个月内稳定下来，但我们的病例报告表明，一些患者可能会持续存在长期的低度炎症。需要更好的检测方法来确定PML幸存者中长期低度IRIS的患病率。
