- \(\bf Objective\)
To report the course of 3 recent Japanese and European cases of fingolimod-associated progressive multifocal leukoencephalopathy (PML) and to analyze its risk factors and increased incidence in Japan.
\(\bf Methods\)
Case series and literature review.
\(\bf Results\)
Fingolimod-associated PML may cause both supratentorial and infratentorial lesions and a pronounced disability. Diagnosis can be challenging because PML lesions (especially infratentorial) can be initially misdiagnosed as extensive MS lesions. Immune reconstitution inflammatory syndrome (IRIS) develops a few weeks after fingolimod discontinuation and is
usually mild. Age factor and therapy duration seem to be relevant because most reported patients were older than 45 years and were treated with fingolimod for more than 3 years.
Combined IgG/IgM deficiency has been identified as a possible further predisposing condition in 1 case. Another patient developed an endogenous fungal skin infection, as a sign of generally compromised cellular immune response, shortly before PML. None of the reported patients had lymphocyte counts below 200/μl. Two of the 3 reported and 4 of the 21 (19%) registered
fingolimod-PML cases occurred in Japan (estimated risk of 0.652 per 1,000 compared with 0.083 per 1.000 worldwide).
\(\bf Conclusions\)
The risk of PML under fingolimod is low, but there are no reliable predictors. Despite a mild IRIS phase, it causes profound disability. Patients older than 45 years, especially with known comorbid immunodeficiencies or manifestation of other opportunistic infections, should be monitored more closely. Increased surveillance and identification of further risk factors are urgently needed in Japan.
MetadatenAuthor: | Jin NakaharaGND, Laura TomaskeGND, Kodai KumeGND, Tadayuki TakataGND, Masaki KamadaGND, Kazushi DeguchiGND, Kenji KufukiharaGND, Ruth SchneiderORCiDGND, Ralf GoldORCiDGND, Ilya AyzenbergORCiDGND |
---|
URN: | urn:nbn:de:hbz:294-71133 |
---|
DOI: | https://doi.org/10.1212/NXI.0000000000000559 |
---|
Parent Title (English): | Neurology : Neuroimmunology & Neuroinflammation |
---|
Subtitle (German): | Is the risk in Japan increased? |
---|
Document Type: | Article |
---|
Language: | English |
---|
Date of Publication (online): | 2020/04/22 |
---|
Date of first Publication: | 2019/04/10 |
---|
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
---|
Tag: | Open Access Fonds |
---|
Volume: | 6 |
---|
Issue: | 3, Artikel e559 |
---|
First Page: | e559-1 |
---|
Last Page: | e559-6 |
---|
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
---|
Institutes/Facilities: | St. Josef-Hospital Bochum, Neurologische Klinik |
---|
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
---|
open_access (DINI-Set): | open_access |
---|
Licence (English): | Creative Commons - CC BY-NC-ND 4.0 - Attribution-NonCommercial-NoDerivatives 4.0 International |
---|