Different Phenotypes of Non-Steroidal Anti-Inflammatory Drug Hypersensitivity during Childhood

Abstract

Background: Although non-steroidal anti-inflammatory drug hypersensitivity (NSAID-H) has been widely studied in adults, there is still a lack of data regarding the features and phenotypes of NSAID-H in children. Our aim was to define risk factors and different phenotypes according to clinical patterns. Methods: Patients with a history of reaction to any NSAIDs referred between January 2012 and October 2014 were included. After completing a European Network for Drug Allergy (ENDA) questionnaire, initial skin and/or oral provocation tests (OPTs) were performed for the offending drug. Additional OPTs were done with aspirin in case of NSAID-H to determine cross-reactivity. NSAID-hypersensitive patients were defined as being either a selective responder (SR) or cross-intolerant (CI) and further categorized according to either the ENDA/GA²LEN classification or an alternative scheme by Caimmi et al. [Int Arch Allergy Immunol 2012;159:306-312]. Results: Among 121 patients [58.7% male, average age 7.8 years (4.7-10.8)] with 161 NSAID-related reactions, 110 patients with 148 reactions were assessed. NSAID-H was diagnosed in 30 (27%) patients with 37 (25%) reactions. Multivariate regression analysis revealed that an immediate-type reaction and respiratory symptoms during the reaction increased the risk of a reproducible NSAID-related reaction (OR 3.508, 95% CI 1.42-8.7, p = 0.007; OR 3.951, 95% CI 1.33-11.77, p = 0.014, respectively). Additional OPTs revealed 13 SRs and 14 CIs. A family history of allergic disease was more frequent in CIs compared to SRs (57.1 vs. 15.4%, p = 0.031). Reactions belonging to CIs were more frequently characterized by angioedema compared to those of SRs (81.3 vs. 46.2%, p = 0.019). SRs and CIs were further classified as single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 13), NSAID-induced urticaria/angioedema (n = 7), NSAID-exacerbated cutaneous disease (n = 2) and NSAID-exacerbated respiratory disease (n = 1). Four CIs could not be categorized according to either classification system. One SR could not be categorized according to ENDA/GA²LEN. Conclusion: During childhood, NSAID-H exhibits different phenotypes and the majority of them can be categorized with current classification systems; however, classifications based on adult data may not exactly fit NSAID-H in paediatric patients.

Non-steroidal anti-inflammatory drug hypersensitivity in children

“…3 In patients evaluated due to a possible NSAID-H, the investigation confirmed this suspicion in a minority of them. 4,5 The drug provocation test (DPT) with the culprit drug is considered the gold standard to diagnose NSAID hypersensitivity. 6,7 The prevalence of immunologically mediated reactions to NSAIDs ranges from 0.1% to 3.6%.…”

“…Atopy, immediate-type reactions or respiratory symptoms as previous manifestations have been identified as risk factors by some authors. 5 The aim of our study was to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID, to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity.…”

Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs among Adults: Clinical Features and Risk Factors for Diagnosis Confirmation

“…Different classification of reactions to NSAIDs and phenotypes have been described over the last decades based on clinical presentation, culprit drugs, onset of reactions and preexisting respiratory or cutaneous diseases [11,17,18,19,20,21]. An updated classification of reactions was published in a consensus paper by the European Academy of Allergy and Clinical Immunology (EAACI) in 2013 [22], and we adopted it in this work.…”

The Frequency of Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Children with Asthma

“…The other 6 patients had urticaria and/or angioedema with the suspected drug during OPT and did not have a reaction with ASA; they were thus classified as SNIUAA (66.7%). In previous studies from our country, 3.7-5% of confirmed NSAID-H in children was classified as NERD and 25-48% as SINUUA [21,22].…”

“…Paracetamol is not a frequent cause of NSAID-H, and low doses of paracetamol are usually used as an alternative drug for patients with NSAID-H [21][22][23]. However, 1 of our patients had a reaction to paracetamol during OPT.…”