title: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pediatric Allergy, Hacettepe University School of Medicine, Ankara, Turkey.
authors: Ozlem
authors: O
authors: Cavkaytar
authors: Ebru
authors: E
authors: Arik Yilmaz
authors: Betul
authors: B
authors: Karaatmaca
authors: Betul
authors: B
authors: Buyuktiryaki
authors: Cansın
authors: C
authors: Sackesen
authors: Bulent E
authors: BE
authors: Sekerel
authors: Ozge
authors: O
authors: Soyer
mesh_terms: D000367:Age Factors; D000707:Anaphylaxis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000145:classification; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D012882:Skin Tests; D014421:Turkey / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal