title: [Special features of NSAID intolerance in children].
abstract: Adverse reactions to acetylsalicylic acid (aspirin, ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) are the second most important cause of adverse drug reactions (ARDs) after beta-lactams. They produce various clinical manifestations and can affect different organs. Gastrointestinal reactions (pyrosis, vomiting, gastralgia), neurological reactions (tinnitus, deafness, vertigo), blood dyscrasias, and nephrotoxic and hepatotoxic reactions are well known.NSAIDs are the drugs of choice in the treatment of chronic arthropathies and other childhood connective-tissue diseases and are also commonly used in the treatment of febrile and acute inflammatory processes. Not all NAIDs are authorized for use in the pediatric population but their spectrum of use varies according to the entity for which they are indicated and the legislation of the country. Published studies on the prevalence of aspirin intolerance in patients with bronchial asthma show a fair amount of disagreement. This may be due to (i) the method of selecting asthmatic patients for the study, which differs according to whether all asthmatic patients are included or only those dependent on corticoids; (ii) the diagnostic method used, whether based on clinical criteria or oral provocation tests, which will affect the number of patients with a diagnosis of intolerance. In children aged less than 10 years, including children with asthma, the prevalence is low, while among children and young adults aged 10-20 years old, the prevalence is estimated at 10 %. Some hypotheses attempt to explain the mechanisms through which adverse reactions to NAIDs take place. One hypothesis attributes the reaction to a reaginic immunological mechanism but this hypothesis has only been confirmed in exceptional cases. The theory of the cyclooxygenase pathway, currently the most widely accepted, is based on the ability of NSAIDs to inhibit the cyclooxygenase pathway of arachidonic acid metabolism, leading to prostaglandin depletion and an increase in leukotrienes. The discovery of two isoforms of the cyclooxygenase enzymes, COX-1 and COX-2, has represented a great advance in our understanding of the mechanism of action of NSAIDs and has also elucidated the problem of cross-reactivities. According to the theory of viral infection, aspirin-induced asthma could be caused by chronic viral infection since, after initial exposure to the virus, cytotoxic lymphocytes are produced. Their activity is inhibited by prostaglandin E2 (PGE2); aspirin and other NSAIDs block PGE2 production and allow cytotoxic lymphocytes to attack and eliminate the respiratory tract cells infected by the virus. During this reaction lysosomal enzymes and mediators are released, which could precipitate an asthmatic crisis.Clinically, five types of reaction have been identified: 1. Respiratory illness with aspirin sensitivity. 2. Aspirin-induced urticarial disease. 3. Allergic reactions to NSAIDs and aspirin. 4 and 5. Aseptic meningitis and pneumonitis due to hypersensitivity. The latter are exceptional and are published as case reports. They have never been associated with aspirin or acetaminophen and usually occur in patients undergoing prolonged treatment. Diagnosis is based on a detailed history. Skin tests are not valid and in vitro tests are not widely used. Provocation tests with aspirin and NSAIDs definitively identify sensitized patients but their indications and limitations should be kept in mind. In children, certain features of adverse reactions to NSAIDs are observed in relation to their incidence and clinical manifestations. Acetaminophen is considered the drug of choice but further studies of other alternatives in children are required.
authors.affiliation: Servicio de Pediatría. Hospital Clínico. Santiago de Compostela. La Coruna. Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Porto Arceo
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000145:classification; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D003888:Desensitization, Immunologic; D015232:Dinoprostone / Q000502:physiology; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology; D007223:Infant; D015289:Leukotrienes / Q000502:physiology; D018448:Models, Immunological; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D015995:Prevalence; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014777:Virus Diseases / Q000150:complications
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin