Okazaki Tomoko, Kodama Daichi, Yamadera Misaki, Sugiyama Yasuko, Tsuji Hiromi, Nishida Fukuko, Ooka Yoko, Nakamichi Kazuo, Hashikawa Kazuo, Yanagihara Takehiko
Department of Neurology, Osaka Police Hospital.
Department of Pathology, Osaka Police Hospital.
Rinsho Shinkeigaku. 2021 Dec 22;61(12):833-838. doi: 10.5692/clinicalneurol.cn-001622. Epub 2021 Nov 18.
Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by JC virus (JCV) activation. We report an 85-years old man who had been diagnosed to have rheumatoid arthritis (RA) 1.5 years prior to diagnosis of PML, and had been treated with salazosulfapyridine (SASP). He developed weakness of the left upper limb, which progressed gradually for two months. A neurological examination on admission revealed severe palsy of the left upper limb without sensory disturbance, cognitive decline or gait disturbance. Brain MRI revealed white matter lesions in the right frontal lobe around the precentral gyrus. Cerebrospinal fluid (CSF) examination and peripheral lymphocyte counts were normal. HIV was ruled out serologically. There were no findings suggestive of malignancy. We suspected PML and stopped SASP. JCV-DNA was detected in CSF. There were enlarged nuclei positive with VP-1 immunostaining in the brain biopsy materials. Thus, the diagnosis of PML was definitive. Paralysis of the left upper limb began to improve one week after discontinuing SASP. Treatment with mefloquine and mirtazapine was initiated, but he developed severe interstitial pneumonia, which might be caused by mefloquine. Therefore, he underwent rehabilitation without medication. JCV-DNA became undetectable and white matter lesions decreased 6 months later. Paralysis improved and he had no problem with activities of daily living a year later. The risk factor for PML has changed over the last decade, and drugs such as biologics became significant risk factors for patients with autoimmune diseases. There are reports suggesting that systemic lupus erythematosus (SLE) and RA themselves might be independent risk factors for PML. Although there is no previous report of SASP inducing PML, SASP might be the culprit in our case. However, there is another possibility that SAPS and RA worked synergistically for the onset of PML.
进行性多灶性白质脑病(PML)是由JC病毒(JCV)激活引起的一种罕见的机会性感染。我们报告一名85岁男性,在诊断为PML前1.5年被诊断患有类风湿关节炎(RA),并一直使用柳氮磺胺吡啶(SASP)治疗。他出现左上肢无力,持续两个月逐渐加重。入院时的神经系统检查显示左上肢严重麻痹,无感觉障碍、认知衰退或步态障碍。脑部MRI显示中央前回周围右额叶白质病变。脑脊液(CSF)检查和外周淋巴细胞计数正常。血清学检查排除了HIV。未发现提示恶性肿瘤的迹象。我们怀疑是PML并停用了SASP。在脑脊液中检测到JCV-DNA。脑活检材料中可见VP-1免疫染色阳性的核肿大。因此,PML的诊断明确。停用SASP一周后,左上肢麻痹开始改善。开始使用甲氟喹和米氮平治疗,但他出现了严重的间质性肺炎,可能是由甲氟喹引起的。因此,他未用药接受了康复治疗。6个月后,JCV-DNA检测不到,白质病变减少。一年后,麻痹改善,他日常生活无问题。在过去十年中,PML的危险因素发生了变化,生物制剂等药物成为自身免疫性疾病患者的重要危险因素。有报告表明,系统性红斑狼疮(SLE)和RA本身可能是PML的独立危险因素。虽然以前没有SASP诱发PML的报告,但在我们的病例中SASP可能是罪魁祸首。然而,另一种可能性是SAPS和RA协同作用导致了PML的发生。