Multifocal leukoencephalopathy in a patient medicated with etanercept and methotrexate for rheumatoid arthritis

Methotrexate (MTX) and etanercept are commonly used in the treatment of rheumatoid arthritis (RA). Several important adverse events, including central nervous system lesions, have been reported during RA treatment. Among them, MTX-induced leukoencephalopathy is a recognized complication that is often observed following intrathecal or intravenous MTX administration. Herein, we report a case of a RA patient who was diagnosed with multifocal leukoencephalopathy during etanercept and MTX therapy. A 77-year-old Chinese woman with a 3-year history of RA had been taking subcutaneous etanercept and low-dose oral MTX since February 2021. Five months after the initial administration, she developed cognitive impairment and experienced a dropped attack. She was then admitted to our hospital in June 2021. T2-weighted magnetic resonance imaging (MRI) images revealed disseminated lesions in the white matter of the brain. Based on these MRI findings and extensive clinical investigation that excluded other possible causes of white matter lesions, she was suspected of having a demyelinating disorder. There was no evidence suggesting other neurological disorders. High-dose corticosteroid was administered, which resulted in improved cognitive impairment. This case report illustrates an important example of multifocal leukoencephalopathy induced by the combined use of etanercept and MTX, which resolved with high-dose corticosteroid. With the recent emphasis on various biologic agents for treatment of RA, our case highlights the importance of identifying leukoencephalopathy that may be induced by various biologics.