Progressive multifocal leukoencephalopathy associated with fumaric acid esters treatment in psoriasis patients

Abstract

Background

Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favorable 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 February, 25^th 2016 for reports of PML in psoriasis patients treated with FAEs.

Results

Eight cases (4 male, 4 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 dimethylfumarate (DMF) and monoethylfumarates, and 2 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 mm³. 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, 2 had stable disease, 2 had residual symptoms, and 1 patient died to an immune reconstitution inflammatory syndrome.

Conclusion

PML 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 are recommended to minimize the risk for PML.

This article is protected by copyright. All rights reserved.

http://ift.tt/2o06RKf