A Paradoxical Flare of Cryoglobulinemic Vasculitis Following Rituximab Therapy

Introduction: Cryoglobulinemic vasculitis is a disorder where cryoglobulin immune complexes precipitate and deposit in small to medium-sized vessels, and can present with arthralgia, purpura, and kidney disease. Common causes include infections such as hepatitis C, autoimmune diseases like Sjögren’s syndrome, and malignancies. Management typically targets the underlying cause as well as immunosuppressive therapy such as Rituximab and corticosteroids. We present a case of paradoxical vasculitis flare following Rituximab infusion. Case Description: A 67-year-old female with history Sjögren’s syndrome complicated by acute kidney injury with biopsy-proven cryoglobulinemic vasculitis who presented with nausea, vomiting, and periorbital edema. The patient started Rituximab therapy after the initial diagnosis and had received Rituximab 7 days prior to her presentation. The physical exam was notable for a blood pressure of 176/81 mmHg, periorbital and trace lower extremity edema. Labs revealed acute kidney injury with creatinine of 2.6 mg/dL (baseline 0.8–1.0 mg/dL). Urinalysis showed 3+ protein, 1+ blood, and the urine sediment exam showed red blood cell casts. C3 complement level was low at 60 mg/dl (normal range 85.0 - 193.0 mg/dL) and C4 level was < 0.2 mg/dl (12.0 - 36.0 mg/dL). Qualitative cryoglobulins test was positive. She was started on IV Methylprednisolone, but her renal function worsened further, and creatinine peaked at 3.28 mg/dL at which point Plasmapheresis (PLEX) was initiated. This was followed by a drastic improvement in renal function and return to baseline after 3 sessions. The diagnosis of Rituximab related flare of cryoglobulinemic vasculitis was made. The patient completed 7 sessions of PLEX on discharge with consideration of prophylactic PLEX with future Rituximab use. Discussion: Rituximab is used in treating cryoglobulinemic vasculitis. Though rare, paradoxical flares have been reported. This case highlights the risk of post-rituximab flares leading to AKI and nephritic syndrome. It underscores the need for vigilance, monitoring, and potential prophylactic strategies like PLEX with further Rituximab treatment in these patients.