Favourable outcome of progressive multifocal leucoencephalopathy in two patients with dermatomyositis

Abstract

Progressive multifocal leucoencephalopathy (PML), a demyelinating disease caused by the JC virus (JCV), occurs in immunosuppressed patients and carries a poor prognosis. A favourable outcome is reported in two patients with PML and dermatomyositis. Immunosuppressive drugs were stopped in patient 1 but could only be partially tapered in patient 2. The JCV-specific CD8+ T cell response was strong in patient 1 and weak in patient 2. Both were treated with cytosine-arabinoside, and patient 2 was also treated with mirtazapine, a 5HT2A receptor antagonist. Combination of these drugs might be helpful to treat HIV-negative patients with PML.

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

“…Several rheumatic disease patients have survived after withdrawal of immunosuppressive therapy and initiation of cidofovir, interferon, or cytarabine treatment, but in no case was there a clear therapeutic response. Recovery was generally, but not invariably, associated with significant sequelae (3,6,12,17,25,27,31). Clearance of JCV from the CSF and/or development of enhancement around existing white matter lesions on neuroimaging may be indicators of recovery.…”

“…PML has been described mainly in patients infected with the human immunodeficiency virus (HIV). However, other immunosuppressed patient populations, including those with malignancies, organ transplants, and systemic lupus erythematosus (SLE) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and other rheumatic diseases (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), are at risk of developing this complication.…”

Progressive Multifocal Leukoencephalopathy in a Patient with Polymyositis: Case Report and Literature Review

“…The antimalarial drug mefloquine was shown to inhibit JCV replications in vitro 25 , but a subsequent clinical study was discontinued due to lack of significant efficacy (www.clinicaltrials.gov). There are case reports and series that have reported favorable outcomes of PML after treatment with cytosine-arabinoside, including a few patients with rheumatic diseases 13,14 ; however, a large placebo-controlled trial on the effect of cytosine-arabinoside for HIV-associated PML failed to demonstrate any effect of the drug 26 . A recent study on the first 35 postmarketing cases of PML in patients with MS treated with natalizumab identified several factors associated with improved survival, including shorter time from symptom onset to diagnosis of PML, younger age at diagnosis, less disability before PML, and more localized disease on MRI 27 .…”

“…The risk of PML in autoimmune diseases has recently been highlighted because of an increasing number of PML cases occurring during treatment with new biological immunosuppressive agents including natalizumab (for multiple sclerosis, MS), rituximab (RTX; for rheumatic diseases), and efalizumab (for psoriasis) and also with the newer immunosuppressant agent mycophenolate mofetil (MMF) 10 . In the more rare autoimmune diseases polymyositis/dermatomyositis (PM/DM) there are a few reports of PML developing in patients treated with conventional disease-modifying antirheumatic drugs 9,11,12,13,14,15,16 , but also in patients during off-label treatment with RTX 17 . The increased risk for PML associated with the new biologics has raised the question of whether these treatments involve a biological explanation for the increased risk.…”

“…Five patients had supratentorial white-matter lesions on MRI, which is the most typical localization of PML; 3 patients had only infratentorial white-matter lesions, including our case, and gadolinium enhancement was seen in 2 patients. One female patient had a negative PCR analysis for JCV DNA in 2 repeated cerebrospinal fluid (CSF) analyses despite multiple supratentorial white-matter PML lesions, and the PML diagnosis was instead confirmed by brain biopsy 13 . That case demonstrates the importance of repeating the PCR analysis for JCV in CSF with ultrasensitive techniques or proceeding to a brain biopsy if suspicion of PML persists.…”