INTRODUCTION
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed, over-the-counter drugs that have analgesic, anti-inflammatory, antipyretic, and anti-platelet properties.1 Today, potential indications for NSAIDs include the prevention of colon cancer2,3 and Alzheimer's disease.
4,5,6 However, the increasing use of NSAIDs has produced a number of adverse effects, including cutaneous reactions.
NSAIDs principal mechanism of action is the inhibition of prostaglandin
production through the blockade of cyclo-oxygenase (COX) enzymes.7 There are at least two isoforms of COX—COX-1 and COX-2. COX-1 is expressed under physiologic conditions in almost all tissues, including gut, respiratory, kidney, endothelial cells, and platelets, and it is highly inducible by pro-inflammatory mediators such as cytokines and growth factors. COX-2 is concentrated in inflammatory
cells, and it has a 60% homology with COX-1.1,8
Conventional NSAIDs are nonspecific COX inhibitors, but they are more potent inhibitors of COX-1 than COX-2. Conversely, the new selective COX-2 inhibitors are potent and specific inhibitors of the COX-2 enzyme.9 Acetaminophen (paracetamol), the most commonly used antipyretic drug, is also an inhibitor of prostaglandin
synthesis,10 and some authors suggest that it is a weak COX inhibitor,11 but it is not an NSAID because it possesses almost
no anti-inflammatory effects.
The most commonly reported cutaneous reactions to NSAIDs are angioedema and urticaria,12 and two different pathways have been identified in their NSAID-induced pathogenesis. The first is an immediate hypersensitivity reaction or “allergic reaction” to specific NSAIDs mediated through the IgE pathway.1 In the second,
“pseudoallergic” cutaneous reactions occur because NSAID COX-1 inhibition results in a decrease of prostaglandin E2, which prevents mast and basophil cells from releasing histamine.13,14 In addition, this blockade results in the shunting of arachidonic acid metabolism toward the 5-lipoxygenase pathway, and causes the increased production and release of cysteinyl leukotrienes, which are involved in the inflammatory cascade.15
The prevalence of urticaria and/or angioedema from NSAIDs in the general population has been reported to be 0.1 percent to 3.0 percent.13,16 Predisposing factors for NSAID-induced urticaria and angioedema include a history of atopy, female sex, young adulthood,
and chronic urticaria.17,18 Strom et al. also reported that the use of NSAIDs for the treatment of acute pain increases the rate of cutaneous reactions.19
