fumarates and Leukoencephalopathy--Progressive-Multifocal

Progressive multifocal leukoencephalopathy (PML) is a rare and potentially fatal condition caused by a brain infection with JC polyomavirus (JCV). PML develops almost exclusively in immunocompromised patients and has recently been associated with use of fumaric acid esters (FAEs), or fumarates. We reviewed the literature and the Dutch and European pharmacovigilance databases in order to identify all available FAE-associated PML cases and distinguish possible common features among these patients. A total of 19 PML cases associated with FAE use were identified. Five cases were associated with FAE use for multiple sclerosis and 14 for psoriasis. Ten patients were male and nine were female. The median age at PML diagnosis was 59 years. The median duration of FAE therapy to PML symptom onset or appearance of first PML lesion on brain imaging was 31 months (range 6-110). In all cases a certain degree of lymphocytopenia was reported. The median duration of lymphocytopenia to PML symptom onset was 23 months (range 6-72). The median lymphocyte count at PML diagnosis was 414 cells/µL. CD4 and CD8 counts were reported in ten cases, with median cell count of 137 and 39 cells/µL, respectively. Three patients died (16% mortality). The association between occurrence of PML in patients with low CD4 and CD8 counts is reminiscent of PML cases in the HIV population and suggests that loss of T cells is the most important risk factor.

Topics: Adult; Aged; Aged, 80 and over; Female; Fumarates; Humans; Image Processing, Computer-Assisted; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Male; Middle Aged; Treatment Outcome

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.. To assess clinical features and outcomes of FAE-associated PML cases.. Systematic literature search in multiple databases up to 25th February 2016 for reports of PML in psoriasis patients treated with FAEs.. 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. 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.

Topics: Adult; Aged; Female; Fumarates; Humans; Leukoencephalopathy, Progressive Multifocal; Lymphocyte Count; Male; Middle Aged; Psoriasis; Risk Factors; Treatment Outcome

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal

Topics: Dimethyl Fumarate; Fatal Outcome; Female; Fumarates; Humans; Immunosuppressive Agents; Leukocyte Count; Leukoencephalopathy, Progressive Multifocal; Lymphocyte Count; Lymphopenia; Middle Aged; Opportunistic Infections; Psoriasis

Topics: Delayed-Action Preparations; Dimethyl Fumarate; Fatal Outcome; Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Lymphocyte Count; Lymphopenia; Middle Aged; Multiple Sclerosis; Opportunistic Infections

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Lymphopenia

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Lymphopenia

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cerebellum; Dimethyl Fumarate; Fumarates; Humans; Leukoencephalopathy, Progressive Multifocal; Male; Psoriasis; Treatment Outcome

Topics: Aged; Brain; Dermatologic Agents; Fumarates; Humans; Immune Reconstitution Inflammatory Syndrome; Immunologic Deficiency Syndromes; Leukoencephalopathy, Progressive Multifocal; Male; Psoriasis

Topics: Adult; Dermatologic Agents; Dimethyl Fumarate; Drug Compounding; Female; Fumarates; Humans; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Paresis; Pharmacies; Psoriasis

Topics: Dermatologic Agents; Dimethyl Fumarate; Female; Fumarates; Humans; Immunologic Deficiency Syndromes; Leukoencephalopathy, Progressive Multifocal; Male

Topics: Dermatologic Agents; Female; Fumarates; Humans; Immunologic Deficiency Syndromes; Leukoencephalopathy, Progressive Multifocal; Male

Topics: Dermatologic Agents; Female; Fumarates; Humans; Immunologic Deficiency Syndromes; Leukoencephalopathy, Progressive Multifocal; Male

Topics: Dermatologic Agents; Female; Fumarates; Humans; Immunologic Deficiency Syndromes; Leukoencephalopathy, Progressive Multifocal; Male

Topics: Dermatologic Agents; Female; Fumarates; Humans; Immunologic Deficiency Syndromes; Leukoencephalopathy, Progressive Multifocal; Male

Topics: Dermatologic Agents; Female; Fumarates; Humans; Immunologic Deficiency Syndromes; Leukoencephalopathy, Progressive Multifocal; Male