PML Diagnosed in Autoimmune Rheumatic Diseases, Part Two

Patient Expert

In a 2012 study, researchers examined the incidence of progressive multifocal leukoencephalopathy (PML) in patients diagnosed with autoimmune rheumatic diseases (ARD) such as RA, lupus, or Sjögren's syndrome.   Accessing the FDA's Adverse Event Reporting System (AERS) database from November 1, 1997 to March 31, 2010, researchers identified 34 confirmed cases of PML in patients diagnosed with autoimmune rheumatic diseases.   Eight of these patients also had a diagnosis of a second ARD (Molloy and Calabrese, 2012).

PML is a rare, opportunistic infection of the central nervous system (CNS) caused by a reactivation of the JC (John Cunningham) virus.   PML is a brain disorder that affects the white matter part of the brain, specifically targeting the cells that make myelin (oligodendrocytes).   Symptoms of PML are similar to MS symptoms and may include clumsiness, weakness, sensory alterations, vision loss, impaired speech, cognitive deterioration, or even personality changes.   Symptoms may occur suddenly or evolve slowly over several weeks to months.

Of the aforementioned 34 confirmed cases of PML, 15 cases occurred in patients who received one or more biologic agents for the treatment of an autoimmune rheumatic disease (ARD).   Fourteen patients were treated with rituximab (Rituxan, RTX) and 6 with an anti-tumor necrosis factor (anti-TNF) agent.   RTX was the most recent biologic treatment in all 14 confirmed cases of PML associated with its use; 5 patients had been treated with an anti-TNF prior to RTX.   Rituxan was used to treat RA in 6 patients (3 of whom had secondary Sjögren's syndrome), lupus in 5 patients, vasculitis in 2, and dermatomyositis in 1.

Potential confounding factors in RTX-treated patients included concomitant use of other immunosuppressive drugs at time of PML onset.   However, four patients were receiving no other immunosuppressive drugs; 1 patient was using only hydroxychloroquine (Plaquenil); and 2 patients were receiving only low-dose steroids.   The 7 remaining patients in this group were receiving 1 or more synthetic disease-modifying drug.   Six patients had previously used or were currently using cyclophosphamide at time of PML onset.

The remaining 19 confirmed cases of PML among ARD patients were treated with synthetic (nonbiologic) DMARDs only, such as hydroxychloroquine, methotrexate, or steroids.   Of these patients, 14 had used cyclophosphamide (Cytoxan, Revimmune) or chlorambucil (Leukeran); 6 were still using chemotherapy drugs at PML onset.   Of the total 34 cases of PML, 14 were treated with azathioprine (Imuran) and 6 with mycophenolate mofetil (Cellcept, Myfortic), prior to developing PML.

Authors conclude that PML is a reported complication of a variety of autoimmune inflammatory diseases and is associated with both synthetic and biologic immunosuppressive agents.   PML has been reported with both TNF inhibitors and Rituxan.   However, based on the scarce number of PML cases in patients treated with TNF inhibitors, which are widely used, suggests that a causal relationship is unlikely.   Continued clinical vigilance is recommended in patients using Rituxan, especially in those who have used chemotherapy drugs, to ensure quick diagnosis and treatment as soon as PML is suspected.

In a separate study, the overall risk of PML is reported to be 0.4/100,000 in patients with rheumatoid arthritis.   The increased risk of PML in RA patients using Rituximab is 4/100,000.   In patients with lupus, the risk of PML is higher than in RA (4/100,000) and 40% of cases of PML occur during low-dose glucocorticoid therapy without immunosuppressive therapy.

Read more about PML symptoms, diagnosis, and treatment in Progressive Multifocal Leukoencephalopathy: What is PML? Part One.

NINDS Progressive Multifocal Leukoencephalopathy Information Page.   Accessed May 28, 2013.

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