For example, rituximab can cause profound first-dose toxicity related to the rapid lysis of normal and malignant B cells that bear the target antigen, CD20.507 Acute reactions can be caused by a variety of mechanisms, including acute IgE-mediated hypersensitivity and anaphylactoid reactions against the antibodies, serum sickness, tumor lysis syndrome (TIS) and CRS.508,509 Clinical manifestations include local skin reactions at the injection site, fever and influenza-like syndrome and potentially fatal acute anaphylaxis and systemic inflammatory response syndrome (SIRS). Here, IGHE is linked to systemic inflammatory response syndrome.