Department of Internal Medicine, 38006National Taiwan University Hospital, National Taiwan University Hospital, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin County, Taiwan.
Lupus. 2021 Oct;30(11):1849-1855. doi: 10.1177/09612033211035443. Epub 2021 Jul 29.
Progressive multifocal leukoencephalopathy (PML) is one of the rare but lethal infectious complication in patients with SLE, manifesting progressive central nervous demyelination caused by JC virus (JCV). There have been no effective antiviral agents so far; however, immune checkpoint inhibitors (ICI) have been demonstrated as potential treatments by reinvigorating antiviral T-cell activity against JC virus. To date, sixteen PML cases treated with anti-PD-1 have been reported; however, there was no report addressing the use of ICI in patients with concomitant PML and rheumatic disease, possibly due to the concern for possible autoimmune disease flare-up. In addition, treatment outcomes of these ICI-treated cases were heterogeneous. Experiences from these cases suggested that high disease burden, JC viral load in CSF, and severe immunosuppression status at baseline may predict poor response to treatment. Our case, a 62-year-old woman with long-standing SLE, turned out to have a delayed but effective response to prolonged ICI treatment despite of her high JC viral load and immunosuppressed status caused by high-dose steroid and rituximab. To our knowledge, this is the first case report with SLE complicated with PML clinically improved by pembrolizumab treatment without consequent immune related adverse events (irAE). Considering the lethal nature of PML and absence of effective medication, ICI is a reasonable consideration in patients with SLE and progressive PML.
进行性多灶性白质脑病（PML）是系统性红斑狼疮（SLE）患者罕见但致命的感染性并发症之一，表现为由 JC 病毒（JCV）引起的进行性中枢脱髓鞘病变。目前尚无有效的抗病毒药物；然而，免疫检查点抑制剂（ICI）通过重新激活针对 JCV 的抗病毒 T 细胞活性，已被证明为潜在的治疗方法。迄今为止，已有 16 例接受抗 PD-1 治疗的 PML 病例报告；然而，由于对可能的自身免疫疾病发作的担忧，尚无报告涉及在伴有 PML 和风湿性疾病的患者中使用 ICI。此外，这些接受 ICI 治疗的病例的治疗结果存在异质性。这些病例的经验表明，高疾病负担、CSF 中的 JC 病毒载量以及基线时严重的免疫抑制状态可能预示着对治疗的反应不佳。我们的病例是一位 62 岁的女性，患有长期的 SLE，尽管她的 JC 病毒载量高且因大剂量类固醇和利妥昔单抗而处于免疫抑制状态，但她对 ICI 治疗的反应出现了延迟但有效的反应。据我们所知，这是首例 SLE 合并 PML 经 pembrolizumab 治疗后临床改善而无继发免疫相关不良事件（irAE）的病例报告。鉴于 PML 的致命性质和缺乏有效的药物治疗，ICI 是 SLE 合并进行性 PML 患者的合理考虑。
