NSAID-Induced Urticaria and Angioedema
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Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in urticaria and angioedema, is being observed with increasing frequency. Prevalence rates range from 0.1–0.3%, which is partly due to the large size of the exposed (at risk) population. Some predisposing factors for these cutaneous reactions have been identified, among them atopic diathesis, female sex, young adulthood, a history of chronic urticaria and the use of the NSAID for the relief of acute pain.
The description of two different arachidonic acid cyclo-oxygenases (COX) about a decade ago, designated COX-1 and COX-2, and the incorporation into the therapeutic armamentarium of more selective enzyme inhibitors for the control of inflammation and pain, has led to an improved understanding of the pathogenesis of adverse reactions to NSAIDs. This has allowed investigators to study ‘sensitive’ individuals to see if they can safely receive these new pharmaceutical compounds.
The reasons why some people react to NSAIDs are not completely clarified. The prevalent theory about the pathogenesis of urticaria and angioedema due to NSAIDs in cross-reactive patients assumes that the inhibition of COX-1 leads to a shunting of arachidonic acid metabolism towards the 5-lipoxygenase pathway, which results in an increased synthesis and release of cysteinyl leukotrienes.
Although COX-2 inhibitors are well tolerated by the majority of classic NSAID-sensitive patients, cutaneous reactions to highly selective inhibitors of COX-2 have been described in some of these individuals, casting some doubts about the relevance of such hypotheses.
On the other hand, in patients who react to a single NSAID and chemically similar products (single-reactors), specific immunoglobulin E antibodies to haptenated NSAID metabolites have been suspected, although these metabolites are not easily demonstrated by means of routine in vivo or in vitro techniques.
Facial (periorbital) angioedema constitutes the most common form of clinical presentation, and one-third of the patients show a mixed clinical pattern of cutaneous (urticaria and/or angioedema) and respiratory symptoms which include upper respiratory tract edema, rhinorrhea, cough, breathlessness and tearing.
When necessary, diagnosis is confirmed by means of controlled peroral drug challenges done by experienced physicians in the hospital setting and test results are helpful for clinical management, which will be based on strict avoidance, and the use of alternative tolerated medications. This approach is specially indicated in hypersensitive patients with chronic medical conditions who require continuous NSAID therapy, such as those with arthritis and coronary heart disease.
The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.
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