接受克拉屈滨治疗的系统性肥大细胞增多症患者发生进行性多灶性白质脑病。

Progressive multifocal leukoencephalopathy in a patient with systemic mastocytosis treated with cladribine.

作者信息

Alstadhaug Karl B, Fykse Halstensen Randi, Odeh Francis

机构信息

Department of Neurology, Nordland Hospital Trust, Bodø, Norway; Institue Clinical Medicine, UiT The Arctic University of Tromsø, Tromsø, Norway.

Department of Haematology, Nordland Hospital Trust, Bodø, Norway.

出版信息

J Clin Virol. 2017 Mar;88:17-20. doi: 10.1016/j.jcv.2016.12.005. Epub 2016 Dec 14.

DOI:10.1016/j.jcv.2016.12.005

PMID:28095350

Abstract

BACKGROUND

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the human polyomavirus JC (JCPyV). A particular problem with the drug cladribine seems to be prolonged suppression of the CD4+ T-cells, a well-known risk factor for PML.

CASE DESCRIPTION

A 67-year-old male presented with a 3-weeks history of unsteady gait, dysarthria and a dysfunctional right arm. Seven years earlier, he had been diagnosed with urticaria pigmentosa, and 2 years later aggressive systemic mastocytosis. Cladribine treatment was initiated and regarded effective, but the course was complicated with bouts of severe anemia and recurrent episodes of salmonella associated gastroenteritis. His lymphocyte count fell to 0.1×10/L at its lowest level, but gradually rose. Despite this, in the 6 month wake of the last dose of cladribine given, the patient experienced herpetic stomatitis, had CMV present in blood, and ultimately developed the neurological symptoms. An MRI scan revealed a lesion in the right cerebellar hemisphere compatible with PML, and PCR analysis of the CSF showed positive for JCPyV DNA with a load of 323 950 copies/ml. No pathological cells were seen on CSF flow cytometry. The CD4/CD8-ratio was 0.45 (160 CD4+ cells/mm and 360 CD8+ cells/mm). The patient passed away 3 weeks later.

CONCLUSION

PML may be the consequence of prolonged lymphopenia due to the use of cladribine.

摘要

背景

进行性多灶性白质脑病（PML）是一种由人多瘤病毒 JC（JCPyV）引起的罕见机会性脑部感染。药物克拉屈滨的一个特殊问题似乎是对 CD4+ T 细胞的长期抑制，这是 PML 的一个众所周知的危险因素。

病例描述

一名 67 岁男性出现了 3 周的步态不稳、构音障碍和右臂功能障碍病史。7 年前，他被诊断为色素性荨麻疹，2 年后又患上侵袭性系统性肥大细胞增多症。开始使用克拉屈滨治疗，认为治疗有效，但病程中出现了严重贫血发作和沙门氏菌相关性肠胃炎的反复发作。他的淋巴细胞计数最低降至 0.1×10/L，但随后逐渐上升。尽管如此，在最后一剂克拉屈滨给药后的 6 个月里，患者出现了疱疹性口炎，血液中检测到巨细胞病毒（CMV），最终出现了神经症状。磁共振成像（MRI）扫描显示右小脑半球有一个与 PML 相符的病变，脑脊液（CSF）的聚合酶链反应（PCR）分析显示 JCPyV DNA 呈阳性，载量为 323950 拷贝/ml。脑脊液流式细胞术未发现病理性细胞。CD4/CD8 比值为 0.45（160 个 CD4+细胞/mm 和 360 个 CD8+细胞/mm）。患者 3 周后去世。