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.