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

Abstract

To the Editor: We describe a fatal case of progressive multifocal leukoencephalopathy (PML) in a patient with polymyositis (PM) and antisynthetase syndrome treated with conventional immunosuppressive drugs. PML is a rare and fatal demyelinating disease caused by the ubiquitous John Cunningham virus (JCV)1,2. JCV infection is usually an asymptomatic event in childhood and about 60%–80% of the normal adult population are seropositive for antibodies against JCV3,4. After primary infection, the virus remains in a latent form in the bone marrow, lymphoid organs, and kidney and some studies have demonstrated that it also can establish latency in healthy brain tissue although this is a matter of debate5,6. The virus may later reactivate, undergoing genomic rearrangement in the non-coding regulatory region, and migrate to the brain, where it infects glial cells and causes a lytic infection known as PML7,8. Reactivation usually occurs during conditions of immunosuppression but there are also reports of PML development in immunocompetent individuals9. The mechanisms behind the pathway leading to viral reactivation remain insufficiently defined. 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 drugs9,11,12,13,14,15,16, but also in patients during off-label treatment with RTX17. The increased risk for PML associated with the new biologics has raised … Address correspondence to Dr. E. Iacobaeus; E-mail: ellen.iacobaeus{at}karolinska.se