Hypersensitivity reactions after intravascular administration of nonionic iodine-based contrast media: evidence on the influence of different sidechains on cross-reactivity

OBJECTIVE: Cross-reactivity (CR) among nonionic iodine-based contrast media (ICM) is a complex phenomenon influenced by the configuration of chemical side chains (SC). This review evaluates CR patterns to guide the empirical selection of safe alternatives when formal allergy workups are unavailable. METHODS: A comprehensive literature search (2010-present) was conducted, focusing on SC chemistry, skin test (ST) results, and clinical switching strategies. RESULTS: Data support a classification into groups based on carbamoyl SC structure. CR is significantly higher in non-immediate than in immediate reactions. The highest CR occurs within Group 1 (iohexol, iomeprol, ioversol, iodixanol), which shares two N-(2,3-dihydroxypropyl) carbamoyl SC. Iopromide, despite its mixed structure, frequently mimics Group 1 behaviour. Conversely, iobitridol (Group 2), characterized by methylated SC, consistently demonstrates low CR and lacks 3D similarity to other agents, potentially inducing "immunological silence." Iopamidol (Group 4) exhibits variable CR, particularly in NIHR. Clinical evidence confirms that switching to an ICM with a different SC configuration-specifically avoiding the N-(2,3-dihydroxypropyl) moiety when the culprit agent belongs to Group 1-significantly reduces recurrent HR risk (pooled OR 0.65). CONCLUSION: While a comprehensive allergy evaluation remains the gold standard, SC-based classifications provide a useful framework for empirical selection. Choosing an alternative from a different structural group appears to be an effective strategy to mitigate recurrence in high-risk scenarios.