D1.27 - Delayed Hypersensitivity Reactions to Iodinated Contrast Media: Diagnostic Outcomes and Alternative Selection

Iodinated contrast media (ICM) are indispensable in oncology and cardiology, yet delayed drug hypersensitivity reactions (DHRs) often lead to indefinite avoidance, compromising patient care. Given high cross-reactivity and the difficulty of performing drug provocation tests (DPTs), precise diagnostic strategies are essential. We evaluated diagnostic outcomes and skin test (ST) patterns to guide alternative ICM selection.

We retrospectively analyzed 30 patients consecutively referred for a history of delayed DHR to ICM. The allergy workup followed EAACI guidelines.

The cohort was predominantly female (76.7%), with a mean age of 57.8 years; 50% of the patients required contrast-enhanced imaging for malignancy surveillance. Maculopapular exanthema (MPE) was the primary phenotype (56.7%), with symptoms developing within 48 hours after the ICM exposure in 76.7% of cases. Systemic corticosteroids were administered in 53.3% of the patients, and symptoms lasted ≥7 days in half of the cases. No bullous eruptions or hepatic involvement were observed, though skin desquamation and facial edema were reported in four patients each.

Iohexol was the most frequent culprit. Patch tests were positive in 21.7% of cases (n=5/23), whereas intradermal tests (IDTs) confirmed T-cell-mediated sensitization in 43.3% (n=13/30). Interestingly, multiple drug hypersensitivity was observed in two patients, including one case of Meropenem-induced DRESS with co-administered ICM; subsequent Iohexol reexposure caused MPE, with STs confirming the ICM as an independent trigger in this patient.

Positive STs to multiple ICMs occurred in 20% of the patients. Cross-reactivity was most prevalent between Iohexol and Iodixanol (16%), followed by Ioversol and Iodixanol or Iopamidol (13%).  Surprisingly, Iomeprol yielded negative ST results in all 16 patients tested, identifying it as a potential lower-risk alternative available in our country. Furthermore, 13.3% suffered multiple reactions before referral due to underestimated cross-reactivity or unidentified culprits.

Skin testing, specifically IDTs, is a high-yield diagnostic tool that confirmed delayed hypersensitivity in nearly half of suspected cases. Beyond culprit identification, STs are essential for mapping cross-reactivity: while Iohexol and Iodixanol showed frequent overlap, Iomeprol emerged as a promising alternative. In the absence of standardized DPTs, comprehensive ST panels are critical for safely resuming life-saving imaging.