The discrepancy between perceived and proven drug hypersensitivity in a well-defined cohort of patients with inborn errors of immunity

Abstract

Background: Inborn errors of immunity (IEI) are genetic disorders characterized by recurrent and/or severe infections, autoimmunity, autoinflammation, allergies, and cancer. Despite frequent drug exposures due to recurrent infections and comorbidities, the prevalence and characteristics of drug hypersensitivity reactions (DHR) in pediatric patients with IEI remain understudied. Methods: This multicenter, cross-sectional study evaluated 264 pediatric patients with IEI along with a control group (CG) comprising 443 age-matched controls using a stepwise diagnostic approach, including the patient-reported Study Questionnaire (Study-Q), the European Network for Drug Allergy Questionnaire (ENDA-Q), and confirmatory diagnostic testing, including skin testing and drug provocation tests (DPT). The demographic, clinical, and allergic profiles of the IEI patients and CG were compared. Results: IEI patients (57.6% male) had a median current age of 10 years, with combined immunodeficiencies being the most common phenotype (53.4%). The number of courses for antibiotic use and hospitalization was more frequent in IEI patients compared to CG (p < 0.001). DHR was more common in IEI patients according to Study-Q (p < 0.001) and ENDA-Q (p = 0.002), although proven DHR as a result of confirmatory testing was comparable with CG (1.1% vs. 0.4%, p = 0.368). Despite the fact that suspected DHR in IEI patients was most frequently associated with beta-lactams (47.6%), with 73.9% presenting with urticaria, proven DHR mainly included reactions to radiocontrast agents (n = 2) and ibuprofen (n = 1). Conclusion: Although drug hypersensitivity is often suspected in patients with IEI, proven cases are rare. Standardized protocols, including DPT in drug allergy centers, are essential to differentiate proven allergies from nonallergic reactions, ensure effective treatment, and avoid unnecessary drug restrictions in this unique population.