We describe a case of primarily bulbar PML in a patient with a history of systemic lupus erythematosus (SLE) and idiopathic CD4+ lymphocytopenia. She was treated with pembrolizumab, resulting in clinical and radiographic improvement. However, she later developed pure red cell aplasia, likely as an autoimmune complication of immune checkpoint inhibition. This case is compelling due to the combination of an atypical PML risk factor, effective off-label treatment of the disease, and uncommon treatment complications.

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A 75-year-old woman with a history of SLE not requiring immunomodulatory treatment presented with three months of progressive brainstem syndrome. Initial examination was notable for left facial weakness, dysarthria, left-sided weakness and decreased sensation, diffuse hyperreflexia, and prominent left-sided and truncal ataxia. Serum testing revealed chronic lymphopenia with CD4+ count of 48 cells/μL. MRI showed T2 hyperintense lesions with patchy enhancement within the paramedian left cerebellum and the medulla. CSF analysis revealed a positive JC virus PCR (123 copies/mL).

A diagnosis of PML secondary to chronic lymphopenia was made, and pembrolizumab was initiated with significant improvement in neurologic exam.  Repeat MRI showed improvement in T2 hyperintensities. She subsequently developed worsening ataxia. Repeat MRI was stable without significant enhancement to suggest IRIS. Repeat LP demonstrated negative JC virus PCR. Workup showed new anemia requiring transfusion. She was diagnosed with pure red cell aplasia after hematologic workup, including bone marrow biopsy. Further treatment of pembrolizumab was held, and the patient had continued stability at 18 months follow-up. 

PML may occur in populations with atypical immunosuppression risk factors, and treatment with pembrolizumab can be effective but can be complicated by hematologic disorders such as pure red cell aplasia.