Diagnostic Approaches to Suspected Drug Hypersensitivity in Children: A Five-year Single-center Real-world Study

Drug hypersensitivity reactions are a frequent cause of referral to pediatric allergy clinics; however, confirmed drug allergy is considerably less common than reported suspicion. This retrospective study evaluated real-life diagnostic approaches in children with suspected drug hypersensitivity reactions in a tertiary pediatric allergy center over a five-year period. Patients aged 1-17 years who underwent in vivo and/or in vitro diagnostic testing for suspected drug hypersensitivity reactions between January 2018 and December 2022 were included. Demographic characteristics, clinical findings, suspected drugs, serum specific immunoglobulin E measurements, skin prick tests, intradermal tests, and drug provocation test (DPT) results were retrospectively analyzed. A total of 168 drug allergy evaluations from 148 unique children were included. The median age was 7 years (interquartile range: 5-12), and 54.8% of evaluations involved female patients. Beta-lactam antibiotics were the most frequently suspected drug group (53.6%), followed by non-steroidal anti-inflammatory drugs and other analgesic/antipyretic drugs (24.4%). Urticaria was the most common reaction phenotype (31%). DPT was performed in 148 evaluations. Culprit-drug DPT was performed in 99 evaluations, with positive reactions in 9 (9.1%). In 49 evaluations, DPT was performed with a selected alternative drug, of which 45 (91.8%) were tolerated and 4 (8.2%) were not tolerated. In the patient-level sensitivity analysis, evaluations undergoing selected alternative-drug DPT more frequently involved index anaphylaxis and reaction onset <2 h; these findings were exploratory and did not remain significant after adjustment for multiple comparisons. No statistically significant differences were observed between positive and negative culprit-drug DPT groups in exploratory univariate comparisons. Anaphylaxis occurred in 5 of 148 DPTs (3.4%); all patients achieved complete clinical recovery, with no fatalities or intensive care unit admissions. Real-life pediatric drug hypersensitivity practice involves heterogeneous diagnostic approaches shaped by clinical characteristics, risk assessment, and the suspected drug class. Appropriate diagnostic reassessment may help clarify suspected drug hypersensitivity and reduce unnecessary drug avoidance in children.