Clinical and behavioral determinants in pediatric non‐immediate drug hypersensitivity: Low confirmation but persistent avoidance

BACKGROUND: Non-immediate drug hypersensitivity reactions (DHRs) in children are frequently overdiagnosed, leading to unnecessary drug avoidance. Evidence regarding predictors of more extensive reactions, drug provocation test (DPT) outcomes, and re-exposure behavior and avoidance remains limited. METHODS: This retrospective cohort study included 161 children referred for suspected non-immediate-type DHRs. Clinical characteristics, reaction features, laboratory findings, and DPT outcomes were collected from medical records. Re-exposure behavior and avoidance were assessed at 6 and 12 months. Logistic regression was used to identify predictors of more extensive reactions, DPT outcomes, and avoidance of re-exposure. RESULTS: Beta-lactam antibiotics were the most frequently implicated drugs in 154 (95.7%) cases. Generalized cutaneous reactions occurred in 79 (49.1%) and were associated with male sex (OR: 2.70, 95% CI 1.31-5.56, p = .007), concomitant rhinitis/conjunctivitis (OR: 2.41, 1.02-5.71, p = .045), atopic dermatitis (OR: 2.55, 1.05-6.19, p = .038), and symptom onset after >3.5 days of treatment (OR: 3.21, 1.57-6.49, p = .001). DPT was positive in 9.3% of tested children, with no independent predictors of positivity. A mild maculopapular rash as the index reaction independently predicted a negative DPT result. (OR: 6.74, 1.83-24.83, p = .004). At 6 months, 40.7% avoided re-exposure despite clinical indication, associated with generalized urticaria as the index reaction (OR: 2.60, 1.00-6.72, p = .048) and having received treatment for the reaction (OR: 4.12, 1.08-15.73, p = .038). By 12 months, 86.5% of patients had reused the culprit drug. CONCLUSION: Male sex, atopic comorbidities, and later-onset reactions were associated with an increased risk of more extensive non-immediate-type DHRs. Despite low DPT positivity and good re-exposure tolerance, drug avoidance remains frequent, particularly after treated or generalized reactions.