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Progressive multifocal leukoencephalopathy associated with fumaric acid esters treatment in psoriasis patients
Author(s) -
Balak D.M.W.,
Hajdarbegovic E.,
Bramer W.M.,
Neumann H.A.M.,
Thio H.B.
Publication year - 2017
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.14236
Subject(s) - medicine , progressive multifocal leukoencephalopathy , dimethyl fumarate , lymphocytopenia , natalizumab , immunosuppression , psoriasis , leukoencephalopathy , immune reconstitution inflammatory syndrome , dermatology , multiple sclerosis , gastroenterology , pediatrics , disease , immunology , lymphocyte , viral load , human immunodeficiency virus (hiv) , antiretroviral therapy
Background Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favourable long‐term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment. Objective To assess clinical features and outcomes of FAE‐associated PML cases. Methods Systematic literature search in multiple databases up to 25th February 2016 for reports of PML in psoriasis patients treated with FAEs. Results Eight cases (four male, four female) of FAE‐associated PML were identified. Median age was 64 years (range 42–74 years); median FAE treatment duration was 3 years (range 1.5–5 years). Six patients were treated with a formulation containing dimethyl fumarate (DMF) and monoethyl fumarates, and two patients with a DMF formulation. Patients exhibited neurological symptoms, such as aphasia, hemiparesis and dysarthria. PML diagnosis was based on MRI findings and presence of JC virus in cerebrospinal fluid and/or brain tissue. All cases were linked to moderate‐to‐severe reductions in absolute lymphocyte counts, with nadirs ranging from 200 to 792 cells per mm 3 . Median exposure to lymphocytopenia was 2 years (range 1–5 years). In all cases, FAE treatment was discontinued; PML was treated with mefloquine plus mirtazapine. Three patients improved, two had stable disease, two had residual symptoms, and one patient died to an immune reconstitution inflammatory syndrome. Conclusion Progressive multifocal leukoencephalopathy is infrequently linked to FAE treatment, but underreporting cannot be excluded. Physicians treating patients with FAEs should be vigilant for the occurrence of PML, and both clinicians and patients should be alert for onset of new neurological symptoms. Periodic monitoring of lymphocyte counts and FAE discontinuation in case of moderate‐to‐severe lymphocytopenia is recommended to minimize the risk for PML.