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Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases

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An Erratum to this article was published on 15 July 2017

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Abstract

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.

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  • 15 July 2017

    An erratum to this article has been published.

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Authors and Affiliations

  1. Department of Medical Microbiology and Infection Control, University Medical Center Utrecht, Utrecht, The Netherlands

    Robbert-Jan Gieselbach & Frank E. Coenjaerts

  2. Netherlands Pharmacovigilance Centre Lareb, ‘s Hertogenbosch, The Netherlands

    Annemarie H. Muller-Hansma

  3. Department of Neurology, Neuroscience Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands

    Martijn T. Wijburg & Bob W. van Oosten

  4. Department of Radiology and Nuclear Medicine, Neuroscience Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands

    Martijn T. Wijburg & Mike P. Wattjes

  5. Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands

    Marjolein S. de Bruin-Weller

  6. Department of Neurology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands

    Dennis J. Nieuwkamp

  7. Laboratory of Medical Microbiology and Immunology, St. Elisabeth Hospital Tilburg, Tilburg, The Netherlands

    Jean-Luc Murk

  8. Laboratory of Medical Microbiology and Immunology, St. Elisabeth TweeSteden ziekenhuis (ETZ), Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands

    Jean-Luc Murk

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  1. Robbert-Jan Gieselbach
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  2. Annemarie H. Muller-Hansma
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Correspondence to Jean-Luc Murk.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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All procedures performed were in accordance with the ethical standards stated in the Declaration of Helsinki.

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The opinions and conclusions of the authors do not necessarily reflect those of the various National Pharmacovigilance Centers or the European Medicines Agency (EMA).

An erratum to this article is available at https://doi.org/10.1007/s00415-017-8557-1.

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Gieselbach, RJ., Muller-Hansma, A.H., Wijburg, M.T. et al. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases. J Neurol 264, 1155–1164 (2017). https://doi.org/10.1007/s00415-017-8509-9

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