Progressive multifocal leukoencephalopathy in rheumatoid arthritis and biological therapies: a case report and review of the literature

Abstract

Background: Progressive multifocal leukoencephalopathy is a rare but potentially fatal disease caused by infection of the central nervous system with John Cunningham polyomavirus. Progressive multifocal leukoencephalopathy mainly occurs in immunocompromised patients, including patients on biological and targeted synthetic therapies, such as multiple sclerosis and rheumatoid arthritis patients. Early diagnosis of progressive multifocal leukoencephalopathy is crucial for patient survival. We describe a case of progressive multifocal leukoencephalopathy with significant diagnostic delay in a rheumatoid arthritis patient using rituximab. Additionally, we give an overview of available literature on progressive multifocal leukoencephalopathy in rheumatoid arthritis patients using biologicals, focusing on the diagnostic difficulties and delays, to raise awareness of this adverse event among physicians treating rheumatoid arthritis patients with immunosuppressants.

Case presentation: A 69-year-old white man of Dutch descent with rheumatoid arthritis treated with rituximab presented to a neurology outpatient clinic, complaining of difficulties in word-finding and reading without problems in visual acuity, several weeks after a mild traumatic head injury (patient's delay). Brain computed tomography-scan showed two hypodense white-matter lesions, initially considered to be of vascular origin (doctor's delay). However, magnetic resonance imaging, performed more than a week later, showed lesions consistent with progressive multifocal leukoencephalopathy. Immunosuppressants were then immediately discontinued. The patient agreed to repeat magnetic resonance imaging and lumbar puncture. Initial John Cunningham polyomavirus polymerase chain reaction on cerebrospinal fluid was negative. However, a subsequent lumbar puncture confirmed the diagnosis. The patient rejected experimental treatment with pembrolizumab and passed away a month after the initial presentation.

Conclusions: This case report emphasizes the need for increased awareness and importance of timely recognition of potential progressive multifocal leukoencephalopathy in rheumatoid arthritis patients using immunosuppressive therapies. A total of 26 other cases of rheumatoid arthritis patients using biologicals who developed progressive multifocal leukoencephalopathy were identified from the literature, and we reviewed their cases. Most (24; 92%) cases occurred during rituximab or TNF-alpha inhibitor use. There was a mean delay of 2.5 months between symptom onset and diagnosis. Information on predisposing risk factors such as lymphopenia was often not reported. Physicians and patients should be aware of the symptoms of progressive multifocal leukoencephalopathy, as early diagnosis and immediate withdrawal of immunosuppressants is crucial to improve the chance of survival. This case report highlights the importance of awareness in recognizing progressive multifocal leukoencephalopathy symptoms in nontraditional populations.

Keywords: Biological; Case report; Diagnostic delay; Progressive multifocal leukoencephalopathy; Rheumatoid arthritis.