The study aims to evaluate the persistence of IgE-mediated allergy to contrast media (CM) after a second exposure in patients who tested positive at both the first and second evaluations for CM allergy. It also aims to analyze the risk factors associated with the persistence of IgE-mediated sensitization after the second allergological assessment.

Drug allergy is often overdiagnosed, as only about 25% of cases labeled as allergic are confirmed. IgE-mediated drug allergy, responsible for immediate reactions up to anaphylaxis, carries inherent risks and relies primarily on in vivo testing, supplemented by in vitro assays in selected cases. In vivo assessment includes skin tests (ST), which, when positive, detect drug-specific IgE bound to mast cells, and drug provocation tests (DPT), which involve controlled re-exposure to the suspected drug.

When IgE-mediated allergy is confirmed, drugs with positive ST are strictly contraindicated for life. Drugs with negative ST are generally considered safe, and tolerance is often verified through DPT performed in specialized settings using stepwise dose escalation up to near-therapeutic doses. In some cases, drugs are reintroduced directly in real-life conditions without prior DPT.

Contrast media (CM) can trigger systemic reactions even at very low doses. In such cases, in vitro testing should ideally precede DPT to minimize systemic exposure. However, its use is limited by the small number of commercially available drug allergens, the need for specialized expertise for techniques such as the basophil activation test, and variable sensitivity depending on the drug, which remains largely unknown for CM. Skin testing for CM allergy has a very high negative predictive value (>95%), indicating that most patients with negative ST tolerate subsequent CM exposure. As a result, many centers do not systematically perform DPT after negative ST.

Evidence suggests that IgE-mediated drug allergy, including CM allergy, may decline over time, with conversion from positive to negative ST occurring after several years. However, it is unclear whether this reflects a true loss of clinical allergy, as documented re-exposures are rare and mostly anecdotal. Clinical experience shows that allergy may either resolve or persist despite negative follow-up tests.

Finally, the severity of drug-induced allergic reactions may be increased in patients with mast cell activation syndrome or mastocytosis, conditions characterized by elevated mast cell burden or reactivity and often suspected in the presence of elevated baseline serum tryptase levels.

Inclusion Criteria:

- Adult patients (≥18 years) with confirmed IgE-mediated allergy to contrast media products after a first exposure.

Exclusion Criteria:

• Patients receiving H1 antihistamines for an allergic condition at the time of evaluation.
• Patients with active eczema and/or uncontrolled asthma.
• Pregnant or breastfeeding women, or women who have recently given birth.
• Individuals under legal protection (e.g., guardianship).
• Individuals deprived of liberty or involved in judicial proceedings.
• Individuals without health insurance coverage.
• Absence of clear, written informed consent.

Drug Allergy and Hypersensitivity Database of the Allergy Exploration Unit, Montpellier University Hospital (CHU Montpellier).