Allergy to non-steroidal anti-inflammatories in children: a narrative review of the current models of care

Abstract

Drug allergies are reported in 10% of children, with non-steroidal anti-inflammatory drugs (NSAIDs) and β-lactam antibiotics being the most frequently implicated; while antibiotic allergy is more commonly reported in early childhood, NSAIDs are the leading cause of confirmed drug hypersensitivity in older children and adolescents. Paracetamol and ibuprofen are widely used in paediatrics for their analgesic, anti-pyretic, and anti-inflammatory effects via their inhibitory action on cyclooxygenase (COX) enzymes. Whilst considered generally safe, hypersensitivity reactions (HSR) to NSAIDs are the leading causes of drug-induced hypersensitivity in children and the most frequent cause of anaphylaxis. NSAID hypersensitivity is classified into immunologic (allergic) and non-immunologic (non-allergic) reactions, typically occurring in selective responders who react to a single NSAID or structurally related group without cross-intolerance. Reactions may be immediate (within one hour with urticaria, angioedema, anaphylaxis), or delayed (hours to days later). Paediatric presentations overlap with adult but pose unique diagnostic and management challenges, compounded by limited paediatric-specific evidence and variable international practice. In 2018, the European Network of Drug Allergy and the European Academy of Allergy and Clinical Immunology published a consensus-based position paper outlining recommendations for diagnosis and management in children and adolescents. A review of 12 recent paediatric studies supports current classification frameworks and reinforces oral provocation testing as the diagnostic gold standard, with prospective study designs and multicentre recruitment that enhance validity and generalisability, highlighting that cutaneous symptoms were the most common presentation and supervised graded drug challenges shown to be safe and clinically informative. Despite these advances, significant global variability persists, and current approaches are still largely guided by expert consensus rather than robust, standardised evidence. This highlights the need for internationally harmonised guidelines, large prospective studies, improved risk stratification, and the development of reliable adjunctive diagnostic tools, particularly given the limited utility and validation of skin testing in this population.

Keywords

paediatric / non-steroidal anti-inflammatory medication / hypersensitivity

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