D3.321 - Cardiac arrest after Iodixanol: a case of non-IgE mediated mast cell activation

Immediate hypersensitivity reactions to iodinated contrast media remain an important cause of severe adverse events in clinical practice. Although most reactions are mild, life-threatening presentations- including cardiovascular collapse and cardiac arrest- have been reported even with non-ionic, iso-osmolar agents such as iodixanol. Increasing evidence indicates that both IgE-mediated and non-IgE-mediated mechanisms coexist. Direct mast cell activation, potentially via the Mas-related G protein-coupled receptor X2 (MRGPRX2), can trigger rapid and severe mediator release, explaining fulminant reactions with negative skin tests and the limited predictive value of conventional allergy evaluation.

We present the case of a 77-year-old female patient with well-controlled asthma and chronic kidney disease, undergoing urological evaluation for hematuria. Five minutes after initiating a multiphase abdominopelvic CT scan with intravenous iodinated contrast (iodixanol) using a urography protocol, she developed cardiac arrest secondary to severe bronchospasm and hypoxia. Advanced CPR was performed, including IV adrenaline, intubation, and mechanical ventilation. Recovery was achieved after intratracheal adrenaline administration. The patient had previously received iodinated contrast without adverse events.

Skin prick tests (SPT) were performed with iodinated contrast agents including iodixanol, iohexol, ioversol, iobitridol, ioxaglate, iopromide, meglumine and povidone iodine. Serum tryptase levels were measured 2 hours after the reaction and at baseline, 24 hours later.

SPT to all tested iodinated contrast agents were negative (histamine control: 4 mm papule). Serum tryptase peaked at 54  ug/L 2 hours post-reaction and returned to a baseline value of 9.87 ug/L at 24 hours.

This case illustrates that immediate reactions to iodinated contrast media can occur in the absence of IgE sensitization, highlighting the potential role of non-IgE-mediated mast cell activation, including pathways involving MRGPRX2. This underscores the need for novel biomarkers to characterize these mechanisms and allow endophenotyping of contrast media–induced anaphylaxis. Recognition of alternative endotypes is essential for risk stratification, patient counseling, and prevention of future events.