Abstract
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.
Zusammenfassung
Methotrexat (MTX) und Etanercept werden weithin zur Behandlung der rheumatoiden Arthritis (RA) eingesetzt. Verschiedene wesentliche Nebenwirkungen, einschließlich Läsionen des zentralen Nervensystems, wurden während einer RA-Behandlung beschrieben. Darunter findet sich auch die MTX-induzierte Leukenzephalopathie als anerkannte Komplikation, die oft nach intrathekaler oder i.v.-Applikation von MTX beobachtet wird. In der vorliegenden Arbeit wird der Fall einer RA-Patientin vorgestellt, bei der die Diagnose multifokale Leukenzephalopathie unter Therapie mit Etanercept und MTX gestellt wurde. Eine 77-jährige chinesische Frau mit einer seit 3 Jahren bestehenden RA in der Anamnese hatte seit Februar 2021 Etanercept s.c. und MTX in niedriger Dosierung p.o. angewandt. Bei ihr kam es 5 Monate nach der initialen Anwendung zu kognitiver Beeinträchtigung und zu einem anfallsartigen Sturz. Daraufhin wurde sie im Juni 2021 in das Krankenhaus der Autoren aufgenommen. In Aufnahmen der T2-gewichteten Magnetresonanztomographie (MRI) zeigten sich disseminierte Läsionen in der weißen Substanz des Gehirns. Auf der Grundlage dieser MRT-Befunde und einer ausgedehnten klinischen Untersuchung, durch die andere mögliche Ursachen für Läsionen der weißen Substanz des Gehirns ausgeschlossen wurden, wurde bei ihr der Verdacht auf eine demyelinisierende Erkrankung gestellt. Es bestand kein Hinweis auf andere neurologische Erkrankungen. Unter der Gabe einer Hochdosistherapie mit Kortikosteroiden trat eine Besserung der kognitiven Beeinträchtigung auf. Dieser Fallbericht stellt ein wichtiges Beispiel einer multifokalen Leukenzephalopathie dar, die durch die kombinierte Gabe von Etanercept und MTX induziert und durch Kortikosteroide in hoher Dosierung gebessert wurde. Angesichts des aktuellen Schwerpunkts auf unterschiedlichen biologischen Agenzien zur Behandlung der RA stellt der vorliegende Fall die Bedeutung der Erkennung einer Leukenzephalopathie heraus, die durch verschiedene Biologika ausgelöst worden sein kann.
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This work was supported by the Natural Science Foundation of Ningbo (grant number 202003N4243).
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T. Yu and C. Yang declare that they have no competing interests.
For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case. For images or other information within the manuscript which identify patients, consent was obtained from them and/or their legal guardians.
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Mike Oliver Becker, Zürich
Paula Hoff, Berlin
Axel Hueber, Nürnberg
Frank Moosig, Neumünster
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The data that support the findings of this study are available upon reasonable request.
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Yu, T., Yang, C. Multifocal leukoencephalopathy in a patient medicated with etanercept and methotrexate for rheumatoid arthritis. Z Rheumatol 83, 297–302 (2024). https://doi.org/10.1007/s00393-023-01430-6
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DOI: https://doi.org/10.1007/s00393-023-01430-6