Hypersensitivity reactions to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs

Although epidemiological studies indicate that the prevalence of suspected allergic reactions to nonopioid analgesics, antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs) is low in children and adolescents, these drugs are the second cause of suspected hypersensitivity (HS) reactions in young patients. Most frequent reactions are cutaneous (urticaria, angicedema) and respiratory (rhinitis, asthma). Other reactions (anaphylaxis, potentially harmful toxidermias) are rare, although NSAIDs are the 1st or 2nd cause of drug-induced anaphylaxis, and the 3rd cause of severe cutaneous adverse reactions (SCARs) induced by drugs, either in children or in adults. Reactions may result from a specific (allergic) HS, either IgE-mediated (immediate and very early reactions) or mediated by T-lymphocytes (delayed reactions). In those patients, diagnosis is usually based on a convincing clinical history and/or drug provocation tests (DPT) showing that the patients react to the suspected drug (+ other drugs in the same chemical family), but tolerate other (families of) drugs. Positive responses in prick and intradermal (ID) tests (anaphylaxis, immediate reactions) and in ID and patch tests (non-immediate reactions) with the suspected drugs may also be observed. However, although these tests have a good specificity, provided they are performed with non-irritant concentrations of the drugs, they have a very low sensitivity (usually < 25-30 %) and are not validated. Reactions may also result from a non-specific (non-allergic) HS (pharmacological "intolerance"), with a frequent cross-reactivity between the various chemical families of drugs, including paracetamol. Non-allergic HS to NSAIDs can occur in non-predisposed patients (NSAID-induced reactions), but also in patients with underlying pathologies (chronic/relapsing urticaria/angicedema; rhinitis, asthma, and/or polyposis) exacerbated by NSAIDs (NSAID-exacerbated reactions). In patients with non-allergic HS, diagnosis is based on a convincing clinical history and/or responses in DPT. Based on a convincing clinical history and/or positive responses in DPT, HS (allergic or non-allergic) to non-opioid analgesics, antipyretics and NSAIDs has been diagnosed in 13 to 50 % of the patients with allergic-like reactions to these drugs. Risk factors are a personal atopy and age. In adult patients, most (>= 70-75 %) of the reactions to NSAIDs are attributed to non-allergic mechanisms. However, several studies, including studies performed in several hundred of patients, strongly suggest that most HS reactions in children and adolescents result from allergic HS (>= 50-70 %). Prevention of relapses is based on administration of other (families of) analgesics, antipyretics and NSAIDs in children and adults with allergic HS to these drugs. In patients with non-allergic HS, prevention is based on administration of drugs with a low cyclo-oxygenasel inhibitory activity (if tolerated, based on clinical history or responses in DPT). Desensitization (tolerance induction) is efficient in patients with respiratory reactions, but does not perfectly work in patients with mucocutaneous reactions and anaphylaxis. Finally, results of a recent study performed in adults strongly suggest that non-allergic HS reactions to NSAIDs could resolve within years, especially in patients reporting non-severe index reactions. (C) 2020 Elsevier Masson SAS. All rights reserved.