Nonsteroidal Anti-inflammatory Drug Hypersensitivity In Children Research Articles

Characteristics of NSAID-induced hypersensitivity reactions in childhood.

Non-steroidal anti-inflammatory drugs (NSAIDs) are available as over-the-counter drugs, and they are commonly used in children for their antipyretic, analgesic, and anti-inflammatory effects. NSAIDs are among the most frequently reported drugs associated with hypersensitivity reactions and even with anaphylaxis. A complete evaluation of the patients based on reported clinical manifestations, timing of the reaction, the presence of underlying disease, and reactions to other NSAIDs allows clinicians to stratify children with a history of reaction to NSAIDs. Although NSAID-induced hypersensitivity reactions have mainly been investigated in adults, recent studies have aimed to explore their epidemiology in the pediatric population. This review will cover the current understanding of clinical manifestations, the risk factors, and the different phenotypes of NSAID-induced hypersensitivity reactions with a comprehensive overview of the epidemiologic data from past to present and the practical approach to the management of NSAID hypersensitivity in children and adolescents.

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

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the second-most frequent drug type to cause hypersensitivity reactions in children. Asthma is one of the risk factors for NSAID hypersensitivity (NSAID-H) in adult patients. There are limited number of studies evaluating NSAID-H among children with asthma. Our aim was to assess the frequency of confirmed NSAID-H and evaluate the classification of NSAID-H in children with asthma. Methods: Patients followed with a diagnosis of asthma in our Pediatric Allergy Clinic were evaluated for NSAID-H. Patients were questioned whether they had used NSAIDs, and if they experienced any reaction with these drugs. A control group was also questioned for reactions to NSAID use. Results: 976 children with asthma and 2,000 healthy children as a control group were included in this study. The mean age of the patients with asthma was 10.61 ± 4.21 years and 59.5% were male. Ten (1%) had a reaction history to NSAIDs. NSAID-H was confirmed in 9 (0.9%) who were tested with the suspected drugs. Six of these were classified as “single NSAID-induced urticaria/angioedema or anaphylaxis” and 3 were classified as “NSAIDs-exacerbated respiratory disease.” In the control group, only 1 subject had a reaction history to acetylsalicylic acid and no reaction developed in the provocation test. Conclusions: In our study, NSAID-H was found more frequent in children with asthma than in the control group. Children with asthma should be evaluated for reactions to NSAIDs during hospital visits.

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

BackgroundHypersensitivity 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. MethodsAll 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. ResultsWe 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. ConclusionsThis study suggests the presence of different phenotypes which do not fit into the current classifications in children with NSAID hypersensitivity.

Non-steroidal anti-inflammatory drug hypersensitivity in children

IntroductionThere are rather few publications about hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAID) in the paediatric age. In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity. MethodsWe conducted a retrospective analysis of the clinical files from every patient under 18 years old who attended two Portuguese paediatric allergy outpatient clinics, from January 2009 to August 2014, due to a suspected NSAID hypersensitivity. ResultsWe included 119 patients, with a median age of nine years (P25–P75: 5–14). Ibuprofen was the commonest implicated NSAID in the patients’ reports (n=94–79%). After DPT, NSAID hypersensitivity was confirmed in nine (7.6%) patients, excluded in 93 (78.2%) and was inconclusive in 17 (14.3%). In the majority (n=95–79.8%), the reaction occurred in the first 24h after intake. Eighty-four patients (70.6%) reported only cutaneous manifestations and 18 (15.1%) had systemic symptoms. Anaphylaxis represented a relative risk to NSAID hypersensitivity confirmation. No association was found for atopy and the number of previous reactions. ConclusionIn our study, NSAID hypersensitivity was confirmed in a small proportion of the patients with a previous reported reaction. Ibuprofen was the most implicated drug with urticaria/angio-oedema as the commonest manifestation. Anaphylaxis was associated with confirmed drug hypersensitivity. The drug provocation test was essential to establish the diagnosis.

Phenotypical characterization of children with hypersensitivity reactions to NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the main cause of drug-induced hypersensitivity in children. Many classifications have been proposed, focusing on adults. So far, no large study has deeply investigated a pediatric cohort. The aim of the present study was to describe a population of NSAID hypersensitive patients reporting a reaction during their childhood and to verify whether it is possible to classify pediatric patients, following the EAACI/ENDA classification. We conducted a historical prospective study including patients evaluated from 1996 to 2015 in the allergy unit of the Montpellier University Hospital. We included 635 patients. For each patient, we recorded clinical manifestations and possible comorbidities and tried to identify possible risk factors. NSAID hypersensitivity was diagnosed in 107 of 635 patients (16.9%). In this group, 43 patients (40.2%) could not be classified following the ENDA recommendations. The main discrepancies were on the patients' clinical manifestations and on their possible underlying diseases. We identified, on a multivariate analysis, some risk factors for NSAID hypersensitivity: chronic urticaria (OR 7.737, 3.375-18.296 95%CI), atopic status (OR 2.514, 1.504-4.364 95%CI), and allergic rhinoconjunctivitis (OR 1.799, 1.138-2.837 95%CI). On the basis of our results, we are proposing an adapted classification for NSAID hypersensitivity in children. The current ENDA classification does not seem to be adapted for pediatric patients; a modified version does. Our study could help allergists better understand the differences between adults and children in developing hypersensitivity reactions to NSAIDs, but further large-scale prospective longitudinal analyses are required to validate this new classification.

Nonsteroidal anti-inflammatory drug hypersensitivity among children.

Nonsteroidal anti-inflammatory drugs (NSAID) are the second-most frequent drugs that cause hypersensitivity reactions among children. Studies related to NSAIDs hypersensitivity in children are limited. In this study, we aimed to evaluate children admitted with suspicion of NSAIDs reaction. Between January 1, 2011, and November 30, 2014, we included patients with suspicion of NSAIDs hypersensitivity in our clinic. For evaluation, skin tests and oral provocation tests with the drug (suspected or alternative) were proposed. Reactions were classified and defined according to the latest European Academy of Allergy and Clinical Immunology position paper on NSAID hypersensitivity. During the study period, 123 patients (with 136 drug reactions) were admitted to our clinic with suspected NSAID hypersensitivity. The mean (standard deviation) age of the patients, 67 female (55%), was 83.10 ± 56.05 months. Thirteen patients described reactions to more than one chemically unrelated NSAID, and 110 patients described reactions with chemically similar drugs. Eight patients were not included because they did not have provocation tests. Thus, 115 patients were evaluated. A hundred and thirty provocations were performed. Twenty patients (17.4%) were diagnosed with NSAID hypersensitivity (13 patients diagnosed by provocation tests and 7 patients diagnosed according to their history). The most frequently encountered agent was ibuprofen (50% [10/20]). Eighty percent (16 patients) of the reactions were considered "non-cross-reactive type." Fifteen patients (75%) were classified as having single-NSAID-induced urticaria and/or angioedema, three patients were classified as having NSAID-induced urticaria and/or angioedema, one patient was classified as having NSAID-exacerbated respiratory disease, and the other patients were classified as having single-NSAID-induced delayed hypersensitivity reactions. Detailed history and drug provocation tests are important to verify NSAID hypersensitivity. The most common type is the non-cross-reactive type, and, in our study, the most common responsible drug was ibuprofen.

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

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.

Challenge-proven nonsteroidal anti-inflammatory drug hypersensitivity in children.

O Yilmaz, IH Ertoy Karagol, A Bakirtas. Allergy. 2013;68(12):1555–1561 The goal of this study was to determine the frequency of true nonsteroidal antiinflammatory drug hypersensitivity (NSAID-H) and whether there were any factors in the history that could predict NSAID-H in children. The study population included 58 children, aged 4 months through 17.8 years, with suspected NSAID-H based on a history of acute reactions, including urticaria/angioedema, bronchospasm, laryngeal edema, rhinitis, and systemic reactions involving hypotension, laryngeal edema, bronchospasm, and/or shock. All subjects completed a questionnaire detailing the implicated NSAID, their reaction history, and any individual risk factors. Subjects were stratified …

Hypersensitivity Reactions to Paracetamol in Children: A Study of 25 Cases

Purpose of the Study. Reports of paracetamol (acetaminophen) allergic and nonallergic hypersensitivity reactions are rare. However, urticaria, angioedema, dyspnea, and allergic and nonallergic anaphylactic reactions have been reported in both children and adults in association with paracetamol administration. Most reactions to paracetamol occur in patients with a nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs (NSAIDs). Alternatively, reactions may result from an allergic hypersensitivity to paracetamol, with tolerance of NSAIDs. This study reports an investigation of 25 children with suspected paracetamol hypersensitivity. Study Population. Twenty-five children, aged 8 months to 15 years, with a history of adverse reactions associated with paracetamol administration. In 12 of the 25 children studied, paracetamol adverse reactions were associated with concurrent administration of other medications or biological agents. Methods. Diagnosis of paracetamol hypersensitivity was based on either clinical history or the results of an oral challenge test. Reported reactions included urticaria, angioedema, conjunctivitis, dyspnea, and a maculopapular rash. Oral challenge tests with paracetamol were performed in the hospital setting. Paracetamol dosing was initiated at 1 mg and gradually increased until the appropriate cumulative dose for age and weight was achieved. An oral challenge with acetylsalicylic acid was performed in 1 child with a history highly suggestive of paracetamol hypersensitivity. Results. Paracetamol hypersensitivity was diagnosed in 1 patient (4%) on the basis of clinical history. The child reported accelerated reactions on 2 occasions, including facial angioedema, conjunctivitis, and dyspnea with wheezing, after isolated intake of paracetamol. Oral challenge to acetylsalicylic acid in this patient induced urticaria and angioedema. Oral challenges to paracetamol in the 24 other children studied were tolerated. Conclusions. Results of this study of 25 children with suspected paracetamol hypersensitivity concur with those of previous reports: paracetamol hypersensitivity is rare and is associated with hypersensitivity reactions to antiinflammatory medications. Reviewer Comments. Adverse reactions temporally associated with paracetamol may result from reactions to other medications or the underlying conditions for which these medications have been prescribed. Diagnostic evaluation of suspected paracetamol hypersensitivity is complicated further by the lack of validated, available skin or in vitro testing. Adverse reactions to paracetamol can be both allergic and nonallergic in nature. The results of this study underscore the need for careful evaluation for both paracetamol and NSAID hypersensitivity in children with a history suggestive of adverse reactions to paracetamol.