DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p = 0.0067) and an age of at least 68 years (p = 0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.

Background/Objectives: Hypersensitivity reactions (HSRs) to iodinated contrast media (ICM), both immediate and non-immediate, pose clinical challenges despite using low-osmolality agents. This review aims to summarize current diagnostic approaches, cross-reactivity patterns, and the debated role of premedication. Methods: A narrative review was conducted using PubMed (2014–2024), selecting studies on ICM-related HSRs, focusing on skin and in vitro testing, drug provocation tests (DPTs), cross-reactivity, and premedication. Results: Skin tests show limited sensitivity, especially for non-immediate reactions. Cross-reactivity among ICMs is common but unpredictable. DPTs are the diagnostic gold standard but lack standardized protocols. Premedication is frequently used, though its efficacy remains uncertain. Conclusions: The management of ICM hypersensitivity is limited by diagnostic gaps and insufficient evidence on premedication. Standardized protocols and prospective studies are needed to improve patient safety and guide clinical decisions.