Tolerance Evaluation of Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Children: Is Age the Crucial Factor?

Introduction: Little is known about the natural history of pediatric nonsteroidal anti-inflammatory drug hypersensitivity (NSAID-H). The aim of this prospective study was to evaluate tolerance development in pediatric patients with confirmed, immediate NSAID-H and to determine the risk factors for NSAID-H persistence. Methods: Children with a confirmed diagnosis of NSAID-H were assessed for tolerance by drug provocation test (DPT) at least 3 years after diagnosis. Factors associated with developing tolerance in NSAID-H were investigated. Results: Of the 34 cases with confirmed NSAID-H diagnosis, 23 (67.65%) were included. The median (range) age at the last DPT was 16.5 (13.2–20.4) years. Tolerance developed in 12 (52.1%) of the 23 patients evaluated. Survival analysis showed that median duration to develop tolerance was 6.16 years from the initial reaction (SE = 18.6). Receiver operating characteristic curve analysis gave a cutoff value for initial reaction age as ≤11.75 years in predicting NSAID-H tolerance with specificity of 83.3%, sensitivity of 81.8% (AUC = 0.830, 95% CI: 0.616–0.952, p < 0.001). Univariate logistic regression analysis showed that the risk of persistence of NSAID-H was 1.3-fold higher with each additional year from the initial reaction (1/odds ratio [OR]) (OR = 0.754, 95% CI: 0.964–0.590; p = 0.024). At the diagnostic DPT, in the tolerant group, urticaria (42.7%) was more common (p = 0.006) and the persistent group reacted at a significantly lower cumulative dose (p = 0.044). Conclusion: Half of the patients with NSAID-H developed tolerance, around 6 years after the initial reaction. The probability of tolerance rises if the initial reaction occurs before the age of 11.75 years and if urticaria was observed at presentation. Reaction at low doses on diagnostic DPT may be a predictor of persistence. Plain Language Summary: There have been reports that adult patients with nonsteroidal anti-inflammatory drug-induced urticaria/angioedema may eventually become tolerant; however, prospective studies investigating the natural history of nonsteroidal anti-inflammatory drug hypersensitivity in children have not yet been conducted. Our results showed that half of the patients with nonsteroidal anti-inflammatory drug hypersensitivity developed tolerance around 6 years after the initial reaction. Young age and presence of urticaria at diagnosis were associated with tolerance. Moreover, reactions with low doses at diagnosis appear to be a predictor of persistence in this population. To the best of our knowledge, this is the first study to prospectively elucidate the natural history of children with proven NSAID hypersensitivity. This study highlights that, just as clinical presentation in children varies, tolerance development may also differ from that in adults. Age should be a particular consideration when evaluating a patient with nonsteroidal anti-inflammatory drug hypersensitivity. [ABSTRACT FROM AUTHOR]