Rituximab Induced Serum Sickness Masquerading as Septic Shock

Abstract

Purpose We describe a case of serum sickness following rituximab infusion in Waldenström macroglobulinemia. Introduction Rituximab is a chimeric monoclonal anti-CD20 antibody used to treat hematologic malignancies and autoimmune diseases. Infusion reactions are very common with rituximab (77%), occurring within 30-120 min of the beginning of the infusion (rituximab package insert; Genentech, Inc); however, rituximab may cause a delayed serum sickness–like reaction as well. Description Our patient is a 51-year-old Caucasian woman diagnosed with Waldenström macroglobulinemia in 2004. At that time, she was treated with 3 cycles of rituximab therapy followed by plasmapheresis for a hyperviscosity reaction. Over the next 3 years she had an uneventful course. However, beginning in 2007 she started having unexplained severe headaches, painful peripheral sensory neuropathy, and night sweats. After a thorough work-up to rule out other etiological causes, we decided to re-challenge her with rituximab in November 2009. She was to undergo 3 cycles of plasmapheresis followed by rituximab infusions (375 mg/m2/week for 4 weeks). Prior to initiation of rituximab, her IgM level was 2447 mg/dL, and her serum viscosity was 2.0. She underwent 3 uneventful cycles of plasmapheresis, after which she received her first rituximab infusion. During the infusion, she did experience some nausea, abdominal pain, tactile hallucinations, and perioral numbness; however, these resolved with extra doses of steroids and antihistaminics. One week after the administration of the first rituximab infusion, she was found to be hypotensive with her systolic BP in the 60s mmHg and was febrile to 1015. She needed admission to the intensive care unit and was presumptively treated as having a catheter-related sepsis needing Norepinephrine pressor support and broad spectrum antibiotic coverage. Her IgM level at the time of admission was 1049 mg/dL, and her serum viscosity was 1.5. She did not have any skin rashes, thrombocytopenia, or proteinuria. During her hospital stay, all of her chemistries were within normal limits, and her microbiologic cultures were repeatedly negative. She did have elevated inflammatory biomarkers such as ESR (66 mm/hr) and CRP (17.5 mg/dL). On her third day in the intensive care unit, she complained of excruciating joint pains with swelling, particularly of her wrists and knees. At this point, her antibiotics were discontinued, and she was treated with systemic steroids leading to a significant improvement in her symptoms and discharge from the hospital. Conclusion Rituximab may present with a severe serum sickness like reaction masquerading as septic shock when used to treat hematologic malignancies. Almost all of the case reports that we reviewed on rituximab-induced serum sickness documented reactions such as fever, arthralgias, and rashes (Jacobs; Clin Nucl Med; 2007; 32:12, and Helfgott; J Rheumatol; 2007; 34:430-3); however, to our knowledge this is the first documented case of rituximab-induced serum sickness presenting with hypotension necessitating pressor support.