Successful Use of Rituximab in Severe, Nonviral Cryoglobulinemic Vasculitis Complicated by Recurrent Infections and Macrophage Activation Syndrome: A Case Report

Nonviral mixed cryoglobulinemic vasculitis (CV) is a rare small-vessel vasculitis, frequently associated with connective tissue diseases. Its management is particularly challenging when severe systemic manifestations occur in patients with a high infectious risk or life-threatening complications. We report the case of a 42-year-old male with long-standing seropositive rheumatoid arthritis (RA) and secondary Sjögren syndrome (SS) presenting with severe CV (skin ulcers and multineuritis). Diagnosis was confirmed by the presence of type II mixed cryoglobulinemia, profound C4 consumption, and leukocytoclastic vasculitis on skin biopsy. Initial immunosuppressive therapy with cyclophosphamide was interrupted due to recurrent bacterial sepsis. Subsequent plasmapheresis was complicated by the development of macrophage activation syndrome (MAS), diagnosed based on HLH-2004 criteria. After stabilization with high-dose corticosteroids and intravenous immunoglobulin, rituximab (RTX) was introduced as salvage therapy. Following induction, a maintenance dose of 500 mg every 6 months was initiated to target both the high risk of vasculitis relapse and the rheumatoid arthritis. This approach led to durable clinical and biological remission with no recurrence of infection. This case highlights the challenges of managing nonviral CV in the context of autoimmune overlap and severe complications. Rituximab proved to be an effective and safe steroid-sparing strategy, even in a patient with a history of recurrent sepsis and MAS.