Drug Updates

Have there been reports of PML in patients treated with tumor necrosis–a antagonists? According to Furst, there have been unconfirmed reports documenting PML associated with both etanercept and infliximab therapy.¹¹ In addition, there was a case reported in a patient with refractory RA who was treated with etanercept.¹² In this case, an elderly woman had failed many therapies for RA, including prednisolone, auranofin, penicillamine, methotrexate (MTX), leflunomide, cyclophosphamide, and others. She also received daily isoniazid (INH) due to a possible history of tuberculosis. She ultimately received etanercept 25 mg twice weekly with rapid symptom resolution. During the subsequent month, the INH was changed to rifampin, and the etanercept was continued. Five months later, she was admitted to the hospital for severe malaise and appetite loss with subsequent incontinence, a gradual decline in her ability to communicate, and dementia. Eventually she developed seizures and loss of consciousness.

Upon work-up, the patient had neck rigidity, and the cerebrospinal fluid (CSF) showed an elevated protein concentration of 84 mg/dL (normal, 10–40 mg/dL) and a cell count of 30/3 mL (normal, 0/3–10/3 mL). An MRI showed high-intensity lesions disseminated bilaterally throughout the white matter. The patient was initially inaccurately diagnosed and treated for encephalomeningitis. After consulting with a neurologist, she was clinically diagnosed with PML. Attempts to detect JC virus via polymerase chain reaction (PCR) were unsuccessful, leading to two negative results. The patient generally stayed in bed, but with supportive treatment she improved enough to sit up to have meals. She was subsequently transferred to another facility to undergo rehabilitation. The authors noted that PML can be diagnosed by examining the CSF and by evaluating clinical symptoms. Examining MRI scans is also useful. The sensitivity of JC virus-DNA PCR in CSF is reported to be approximately 74% to 92%. The authors also noted that this patient had most of the PML features minus the JC virus in the CSF.

Calabrese and Molloy reported that vigilance is warranted in the rheumatology community when it comes to recognizing and pursuing a diagnosis of PML, especially when it is suspected via identifying clinical signs and symptoms and MRI findings.¹³ Rheumatologists need to know about PML, be aware of its symptoms, be able to assist patients in making informed treatment decisions, and educate them about the risks and benefits of immunosuppressive therapies.

Michele Kaufman is a freelance medical writer based in New York City.

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