Development of Central Nervous System Vasculitis in a Patient with Waldenstrom Macroglobulinemia: A Rare Presentation with Poor Prognosis.

Waldenstrom macroglobulinemia (WM) is a rare lymphoproliferative disorder characterized by the presence of monoclonal immunoglobulin M in serum. WM may present with neurologic complications involving the peripheral and central nervous systems (CNS) though CNS complications associated with WM are rare. We present a case of a 72-year-old male with an 18-month history of WM who experienced neurologic and constitutional symptoms indicative of WM progression over a three-week period while on rituximab maintenance therapy. The patient's symptoms were initially attributed to rituximab-induced asthenia though his clinical condition did not improve with rituximab discontinuation. Due to progressively worsening neurologic symptoms, the patient was re-evaluated and found to have multiple cerebral infarcts and increased serum cryoglobulin levels indicative of cryoglobulinema. The patient was promptly initiated on a combination regimen of high dose steroids, intravenous immunoglobulin (IVIG), and plasmapheresis but had a poor response. Brain biopsy revealed necrotizing vasculitis with dense intra- and peri-vascular CD3 positive T-cell infiltrates with mural necrosis. This is a unique case of WM complicated by type 1 cryoglobulinemia associated with CNS vasculitis that was unresponsive to active rituximab therapy; this case illustrates a poor prognosis of patients with CNS involvement in WM.