Hypersensitivity reactions to iodinated radiocontrast media: Cluster analysis reveals distinct clinical phenotypes

Drug hypersensitivity reaction (DHR) to iodinated radiocontrast media (iRCM) is reported in 1%-3% of injections. Risk assessment of patients with suspicion of DHR to iRCM relies solely on clinical phenotyping and drug allergy workup. Using a novel unsupervised TwoStep cluster analysis, we aimed to identify prototypic patterns within a large cohort of patients evaluated for a potential iRCM DHR.

A retrospective study was conducted using data from the Drug Allergy and Hypersensitivity Database of the Allergy Unit, University Hospital of Montpellier, Montpellier, France. All referred patients during February 2001 to December 2019 with suspicion of iRCM DHR with either confirmed positive or confirmed negative skin tests were included in the analysis.

A total of 1439 patients were evaluated. The chronology of the index reaction was immediate and nonimmediate in 77.1% and 22.4%, respectively. Cluster analysis categorized the total study population in 5 clusters. Cluster 1 compiled all nonimmediate and cluster 2-5 almost all immediate reactors. Cluster 1 and 2 had recent reactions (<1 y) with mostly known iRCMs and the highest iRCM allergy prevalence (16-17%). In the other clusters, more remote reactions, unknown iRCMs and a lower allergy prevalence (3-8%) was observed. Chronology and semiology of the index reaction were the factors most strongly differentiated among clusters. History of anaphylactic shock and chronology of immediate hypersensitivity reactions were shown to be independent predictors of allergy with adjusted OR (aOR) of 4.68 (95%CI: 3.01-7.27, p < 0.001) and 2.51 (95%CI: 1.67-3.78, p < 0.001), respectively.

Unsupervised cluster analysis identified 5 prototypic patterns within patients with a suspected DHR to iRCMs. Well-phenotyped patients cluster together in 2 groups in which the prevalence of allergy is approximately 1 in 6. However, this value decreases for patients with reactions dating back to more than a decade.