Comparison of paediatric NSAID hypersensitivity studies to EAACI/ENDA 2018 consensus.
| Study | Study design & population | Alignment with EAACI/ENDA 2018 | Notes/Contributions |
|---|---|---|---|
| Dogan et al. [12], 2024—Assessment of paediatric patients with suspected NSAID hypersensitivity | Prospective assessment of children referred for suspected NSAID reactions: detailed history, skin testing, and oral challenge | Supports EAACI/ENDA recommendation for systematic evaluation and controlled drug challenges; reinforces phenotype classification | Adds recent real-world data on the prevalence of true NSAID hypersensitivity in children |
| Podlecka et al. [13], 2023—Practical approach to NSAID hypersensitivity in children | Narrative review/expert opinion on paediatric NSAID reactions | Directly aligns with EAACI/ENDA guidance for structured assessment | Useful as practical guidance for clinicians; emphasises outpatient safety |
| Yilmaz Topal et al. [14], 2020—Results of NSAID provocation tests and classification challenges | Retrospective cohort of children undergoing oral provocation tests | Highlights limitations noted in EAACI/ENDA 2018 regarding classification and co-factors | Provides data supporting careful interpretation of drug challenges and phenotype assignment |
| Li et al. [15], 2022—Safety, outcomes, and recommendations for two-step outpatient NSAID challenges | Prospective outpatient two-step challenge in children | Reinforces EAACI/ENDA recommendation for supervised graded challenges | Strengthens evidence for outpatient risk stratification and procedural safety |
| Aytekin Güvenir et al. [16], 2024—Alternative drug safety in children with nonsteroidal anti-inflammatory drug hypersensitivity | Observational study; children with confirmed NSAID hypersensitivity undergoing alternative drug provocation | Strong alignment with guideline emphasis on drug provocation testing (DPT) as the gold standard and identification of safe alternatives | Supports safety of paracetamol and selective COX-2 inhibitors; reinforces the need for individualized testing rather than assumption of cross-reactivity |
| Mori et al. [17], 2020—Multicentre retrospective study, ENDA group | Multicentre retrospective European cohort of children | Directly validates EAACI/ENDA classification (cross-reactive vs. selective) | Offers multicentre evidence supporting the international applicability of classification |
| Hadley et al. [19], 2023—NSAID hypersensitivity in severe paediatric asthma | Observational cohort of children with severe asthma | Aligns with EAACI/ENDA risk stratification recommendations; highlights asthma as a co-factor | Supports tailored assessment in high-risk subgroups |
| Metbulut et al. [20], 2025—Evaluation of drug-related anaphylaxis in children | Multicentre retrospective anaphylaxis registry | Reinforces EAACI/ENDA emphasis on severe reaction recognition | Provides data on severe outcomes, informing emergency preparedness and management |
| González Moreno et al. [22], 2025—Natural history of cross intolerance to NSAIDs in the paediatric population | Longitudinal cohort; paediatric patients with CI followed over time | Aligns with the classification of cross-intolerant phenotypes (CI) but extends beyond the guidelines by examining natural history | Demonstrates that some children may outgrow CI, which is not well addressed in EAACI/ENDA 2018; adds prognostic insight |
| Tekcan et al. [23], 2025—Comparison of negative predictive values of single- and two-day provocation tests with suspected nonsteroidal anti-inflammatory drug and paracetamol allergy in children | Diagnostic accuracy study; children undergoing 1-day vs. 2-day DPT for NSAIDs/paracetamol | Strong alignment with the recommendation for DPT to confirm/exclude hypersensitivity | Suggests shorter (1-day) protocols may be sufficient in many cases; contributes to optimizing and standardizing testing protocols |
| Uluc et al. [24], 2025—Evaluation of nonsteroidal anti-inflammatory drug hypersensitivity in children: is age the crucial factor? | Observational cohort; evaluates NSAID tolerance across different paediatric age groups | Partially aligned; supports guideline focus on individual variability, but introduces age as a modifying factor not emphasized in the 2018 paper | Suggests younger children may have higher tolerance or different phenotypes; proposes an age-stratified approach to evaluation |
| Arikoglu et al. [25], 2024—Alternative drug safety in children with nonsteroidal anti-inflammatory drug hypersensitivity. | Comparative study of classification protocols in children with NSAID hypersensitivity | Challenges: strict application of EAACI/ENDA classification; proposes refinement of phenotypes | Highlights that children with underlying atopy/asthma may represent a distinct subgroup; suggests the need to adapt adult-derived classifications for paediatrics |
CI: cross-intolerance; COX: cyclooxygenase; NSAID: non-steroidal anti-inflammatory drug.