Case Presentation:
A 68 year old female presented with confusion, left hand paresthesias, and unsteadiness with one fall. Her past medical history was significant for alcoholism and rheumatoid arthritis (RA) treated for six years with rituximab. Exam revealed stable vital signs in an alert, cooperative, well‐nourished patient. She had no joint swelling, nodules, ulnar deviation, scarring or other findings consistent with prior severe RA. Neurologically she had mild disorientation and subtle apraxia, but attention, memory, speech, motor function, reflexes, gait and sensation were intact. Labs including complete blood count, comprehensive metabolic panel, toxicology screen, HIV, and serum protein electrophoresis were normal. MRI of the brain showed prominent right frontal lobe vasogenic edema (image below). Dexamethasone was initiated and the patient experienced significant improvement. Subsequent brain biopsy demonstrated a demyelinating process consistent with progressive multifocal leukoencephalopathy (PML). CSF studies confirmed diagnosis with 777 copies/ml JC viral DNA by PCR. Over the next six months patient suffered left‐sided weakness, but her decline then stabilized off rituximab and all other immunosuppressives.
Discussion:
PML is a rare demyelinating central nervous system disease caused by reactivation of JC polyoma virus endemic to 80% of healthy adults. PML is found in those with profound immunosupression such as AIDS patients. PML has also been seen after use of rituximab, a monoclonal antibody targeting B cell CD20 antigen. In a review of 57 cases of HIV‐negative patients who developed PML after rituximab use, only one had RA. Hypogammaglobulinemia, hematologic malignancy, cytopenias, and use of chemotherapies or alternate immunosuppressives increase the risk, yet our patient lacked all of these factors. The use of rituximab in RA patients is efficacious in those with moderate to severe disease who have previously failed other treatment modalities. However, despite the extreme rarity of PML cases seen in RA patients, the potential for this disease is cautioned by both drug manufacturer and the American College of Rheumatology. We postulate that prolonged duration of rituximab therapy and alcoholism put our patient at greater risk. That she survives at 6 months post‐diagnosis with stabilization of neurologic deficit is consistent with both the uncertain prognosis in these patients, and the presumption of immune reconstitution.
Conclusions:
We present a rare case of PML after rituximab therapy in a patient with RA of unclear severity, who lacked additional risk factors for PML development. Though rituximab has been shown to be efficacious in RA unresponsive to other treatment, patient selection should be made with caution.
