Urticaria angioedema, NSAIDs

Aspirin and NSAIDs can induce allergic and pseudoallergic reactions. Because these drugs are used so widely, with much over-the-counter use, the health care professional must have a basic understanding of the types of reactions that can occur and how to prevent them. Three types of reactions occur bron-chospasm with rhinoconjunctivitis, urticaria/angioedema, and anaphylaxis. Remember that patients with gastric discomfort... 

Hypersensitivity to dipyridamole, aspirin, or any of the other product components. Allergy Aspirin is contraindicated in patients with a known allergy to NSAIDs and in patients with asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasms (asthma). 

Contraindications fc>r nonsalicylate NSAID therapy are the same as those for aspirin (see Box 7-I).The formation of a gastric ulcer or erosion that may bleed profusely is a serious potential problem with NSAIDs. Consequently, the nonsalicylate NSAIDs should be avoided or used with great caution in patients with active peptic ulcer disease. NSAIDs may increase the risk of GI complications even when used in conjunction with low-dose aspirin for cardioprotection. In addition, because of potential crosssensitivity to other NSAIDs, the nonsalicylate NSAIDs should not be given to patients in whom aspirin or other NSAIDs have caused symptoms of asthma, rhinitis, urticaria, angioedema, hypotension, bronchospasm, or of symptoms of hypersensitivity reactions. Opioids, tramadol, or acetaminophen may be suitable alternatives for patients with known or suspected susceptibility. 

Among the anaphylactic reactions to NSAIDs that result in different types of reaction (urticaria, angioedema, asthma, or hypotension), there have been very few reports of anaphylactic shock. However, anaphylaxis has been described in patients taking celecoxib (135,136) or rofecoxib (137). Rofecoxib caused anaphylaxis in a patient who had had a similar reaction to diclofenac, suggesting that COX-2 inhibitors may be not safe in all individuals who have adverse reactions to non-selective COX inhibitors. It also suggests that different mechanisms may be involved in patients with asthma and in those with anaphylactoid reactions to NSAIDs. 

There was even better tolerability of rofecoxib in another study in 33 patients with documented urticaria/angioedema after ingestion of two different NSAIDs (145). The patients underwent provocative tests with increasing doses of rofecoxib (from 6.25 to 25 mg) at the end of the challenge aU tolerated rofecoxib 25 mg. 

Other single case reports have supported the evidence of better tolerability of COX-2-selective inhibitors (in particular rofecoxib) in patients with a history of urticaria/angioedema (64,146). However, contrasting data have shown cross-reactivity of celecoxib with other NSAIDs and between celecoxib and rofecoxib (147). 

Meloxicam may be relatively safe when given to patients with NSAID-induced urticaria/angioedema (14,15). Of 148 NSAID-sensitive subjects with an unequivocal history of urticaria with or without angioe-dema, who were challenged with increasing oral doses of meloxicam (1-7 mg/day) in a single-blind placebo-controlled trial, only two had a positive test (urticaria in one and urticaria/angioedema in the other) both had chronic idiopathic urticaria (16). 

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can produce two general types of reactions, urticaria/angioedema and rhinosinusitis/asthma, in susceptible patients. Approximately 20% of asthmatics are sensitive to aspirin and other NSAIDs. 

Single NSAID-Induced Urticaria, Angioedema, and/or Anaphyiaxis... 

Some patients with chronic idiopathic urticaria develop wheals and even angioedema after aspirin or NSAIDs. In others, aspirin causes an obvious increase in the underlying urticaria. The reaction may occur in just 15 min or up to 24 h following aspirin ingestion, but on average it develops within 1-4 h. Most cases resolve within a few hours, but in severe reactions bouts of multiform skin eruptions, covering most of the body, may continue for 10 days after aspirin intake [8,16,17]. 

IgE -mediated urticarial/angioedema reactions and anaphylaxis are associated with aspirin and NSAIDs. Urticaria is the most common form of IgE-mediated reaction. This class is second only to fi-lactams in causing anaphylaxis. The potential for cross-reactivity between agents in IgE-mediated reactions appears small, but caution is advised. Because aspirin therapy is highly beneficial in primary and secondary prevention in... 

NSAID hypersensitivity Because of potential cross-sensitivity to other NSAIDs, do not give these agents to patients in whom aspirin or other NSAIDs have induced symptoms of asthma, rhinitis, urticaria, nasal polyps, angioedema, bronchospasm. 

Urticaria and angioedema e.g. penicillins, ACE inhibitors, gold, NSAIDs, e.g. aspirin, codeine. 

The tolerability of rofecoxib in patients with cutaneous allergic and pseudoallergic adverse reactions to non-selective NSAIDs has been confirmed in a study in 139 patients with NSAID-induced adverse reactions 60 with urticaria alone (43%), 34 with angioedema (25%), 34 with angioedema plus urticaria (2.9%), and 2 with Stevens-Johnson syndrome (1.4%) (134). They aU underwent a single-blind, placebo-controlled oral challenge with increasing doses of rofecoxib, and 138 of them tolerated it without adverse reactions. Only one had mild urticaria on the arms. Rofecoxib may be a useful alternative in patients with NSAID hypersensitivity. 

In another study, 34 patients with a history of urticaria and/or angioedema after ingestion of at least two chemically unrelated non-selective NSAIDs, 22 of whom also had chronic urticaria, all underwent a single-blind, placebo-controlled oral tolerance test with rofecoxib (12 and 25 mg 1 hour apart) (144). Rofecoxib caused urticaria and/or angioedema in 6/34 patients (18%), with no difference between patients with or without a history of chronic urticaria. 

Certain individuals display hypersensitivity to aspirin and NSAIDs, as manifested by symptoms that range from vasomotor rhinitis with profuse watery secretions, angioedema, generalized urticaria, and bronchial asthma to laryngeal edema, bronchoconstriction, flushing, hypotension, and shock. Aspirin intolerance is a contraindication to therapy with any other NSAID because cross-sensitivity can provoke a life-threatening reaction. 

Immunologic The safety of meloxicam has been studied in 116 patients with aspirin/ NSAID-associated urticaria or angioedema, who underwent a single-blind, placebo-controlled oral challenge with meloxicam (7.5 mg cumulative dose) [40 ]. There were no reactions in 106 patients. Five patients developed pruritus or erythema and five developed localized angioedema with erythema. Reactions to meloxicam were milder than the patients previous reactions. 

Urticaria is the second most common cutaneous reaction induced by drugs, often in association with angioedema and anaphylaxis. Many drugs are implicated including p-lactams, NSAIDs, sulfonamides, vancomycin, and contrast media. ACE inhibitors are responsible for approximately one in six patients admitted to hospital with angioedema. 

Of the drugs implicated in provoking urticaria and angioedema, the NSAIDs are perhaps the most important. What is currently understood of their proposed mechanisms of action together with a review of the arachidonic acid cascade is considered in Chap. 9. Formation of the cysteinyl leukotiienes is detailed in Sect 3.2.S.2 (above) and is also referred to in Chap. 9. 

Cross-Reacting NSAID-Induced Urticaria and Angioedema... 

Successful desensitization of otherwise healthy individuals with multiple NSAID-induced urticaria and angioedema but no underlying skin disorder does not appear to have been reported. 

NSAID-induced cutaneous reactions occur in a number of different clinical patterns—cross-reacting NSAID-induced urticaria and angio-edema multiple NSAID-induced urticaria and angioedema single NSAID-induced urticaria and angioedema or anaphylaxis. 

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