Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children.

BACKGROUND: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently encountered in daily clinical practice. The aim of this study was to determine the confirmation rates, risk factors of NSAID hypersensitivity in children and to try to classify them with a standardized diagnostic protocol. METHODS: All patients with a suspicion of NSAID-induced hypersensitivity were evaluated with European Network for drug Allergy (ENDA) recommendations. The children were classified as selective responders (SRs) or cross-intolerant (CI) depending on the drug provocation test (DPT) results. RESULTS: We evaluated 106 children with a suspicion of NSAID hypersensitivity. NSAID hypersensitivity was confirmed with tests in 31 patients; 4 (12.9%) were diagnosed by skin tests and 27 (87.1%) by DPTs and two patients with a history of anaphylaxis by medical records. Eleven patients (33.3%) were classified as SRs, whereas twenty-two (66.6%) children as CIs. SRs and CIs were further classified as NSAID-induced urticaria/angioedema (n = 8), NSAID-exacerbated cutaneous disease (n = 6) and NSAID-exacerbated respiratory disease (n = 1) and single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 11). Eight (24.2%) patients could not be categorized according to ENDA/GA2LEN classification; one CI patient could not be classified based on pathomechanisms, seven CIs could not be categorized based on the underlying disease and clinical manifestations. A reaction within an hour of drug intake (aOR:3.0, 95% confidence interval: 1.18-7.67, p = 0.021), a history with multiple NSAIDs hypersensitivity (aOR:2.9, 95% confidence interval: 1.16-7.60, p = 0.022), and family history of atopy (aOR:4.0, 95% confidence interval: 1.50-10.82, p = 0.006) were found as the independent risk factors related to confirmed NSAID hypersensitivity. CONCLUSIONS: This study suggests the presence of different phenotypes which do not fit into the current classifications in children with NSAID hypersensitivity.

Diagnostic evaluation and risk factors for drug allergies in children: from clinical history to skin and challenge tests.

BACKGROUND: Parent or self-reported drug allergy claims frequently overestimate the real incidence of hypersensitivity reactions. A detailed and algorithmic diagnostic evaluation of drug reactions may allow a proper diagnosis. OBJECTIVE: The aim of this study was to determine the confirmation rates and risk factors for confirmed allergic drug reactions in children. SETTING: Mersin University Hospital in Turkey. METHOD: The study consisted of children between ages of 8 months and 18 years with the history of suspected drug allergy as reported by the clinician or the patients. Parents were interviewed by a clinician to complete questionnaires that included questions about demographic data and characteristics of index drug reaction. Immediate reactions (IRs) were assessed with immediate-reading skin prick (SPT) and intradermal tests (IDT). Nonimmediate reactions (NIRs) were assessed with SPT, both early and delayed reading of IDT and patch tests. In case of negative skin tests, drug provocation tests were performed. The possible risk factors for confirmed drug allergy in univariate analysis (p < 0.1) were entered into the multivariate logistic regression analysis to determine independent predictors. MAIN OUTCOME MEASURE: (1) Confirmation rates of drug allergy (2) Risk factors related to confirmed drug allergy in children. RESULTS: We evaluated a total of 180 suspected drug allergy reactions in 97 children, mainly to antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and anticonvulsants. Among all suspected allergic drug reactions, 97 (53.9 %) were immediate type and 83 (46.1 %) were non-immediate type. The average time interval between the reaction and allergologic work-up was 5 months. Drug allergy confirmation rates were 30.1 % for beta-lactams, 27.2 % for non-betalactams, 21.1 % for NSAIDs and 30 % for anticonvulsants. Eight of 54 confirmed NIRs showed positivity on immediate skin tests. Regulatory T cells, TGF-ß and IL-10 levels were not different between groups with and without confirmed drug allergy. A strong family and personal history of drug allergy were found to be significantly related to the confirmed allergic drug reactions. CONCLUSION: Parent or self-reported drug allergy should be evaluated with a standardized diagnostic work-up before strict prohibitions are made. In addition, family and personal histories of drug allergy were significant risk factors related to allergic drug reactions in children.