NSAIDs cutaneous reactions

Patients with chronic idiopathic urticaria, who develop cutaneous reactions in response to aspirin, display certain similarities in eicosanoid profile with AIA. The mechanism of the reactions is often related to COX-1 inhibition [18]. Therefore, aspirin and all drugs that inhibit COX-1 should be avoided in patients who already have had cutaneous reactions to NSAID. Coxibs are usually well tolerated, although occasional adverse reactions have been reported [19, 20]. For treatment of the reactions, antihistamines are usually sufficient, but in more severe cases adrenaline and corticosteroids may be warranted. 

Sanchez Borges M, Capriles-Hulett A, Caballero-Fonseca F, Perez CR. Tolerability to new COX-2 inhibitors in NSAID-sensitive patients with cutaneous reactions. Ann Allergy Asthma Immunol 2001 87(3) 201. ... 

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. 

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. 

Theoretically, the risk of serious GI adverse events should be less than with oral NSAIDs, but long-term studies evaluating these events are lacking.38 Studies comparing topical NSAIDs with other topical products, including counterirritants, are also needed.35 Local cutaneous adverse reactions (e.g., erythema, pruritus, and irritation) occur in 1% to 2% of patients and may be due in part to the vehicle used.38... 

Fever, rigors, chills, malaise headaches, myalgia Nausea, emesis Neutropenia Hepatic enzyme elevation Cutaneous—alopecia, transient, mild rashlike reaction Acetaminophen (APAP). NSAID if APAP is not effective. Meperidine for severe chills and rigors. Bedtime administration. 5-HT3 antagonist, prochlorperazine, metoclopramide, fluids Weekly complete blood count reduce dose by 30-50% Liver function tests (LFTs) weekly withhold treatment until LFTs normalize restart at 30-50% dose reduction reversible on dose reduction or cessation. Interferon is contraindicated in patients with psoriasis because exacerbation of psoriasis has been noted during IFN therapy. 

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. 

About 5% of patients have itching, rashes, or erythema multiforme (3). Circulating immune complexes have been found (4). The UK s Committee on Safety of Medicines issued a warning about the high rate of cutaneous adverse reactions with fenbufen and noted that some are followed by severe illnesses (SEDA-13,72) (SEDA-14, 94) (SEDA-15, 100). Toxic epidermal necrolysis, a life-threatening reaction, has also been reported (SEDA-6, 96) (SEDA-8, 106) and a 1981-85 review on its incidence in France identified fenbufen as the third most common NSAID, after isoxicam and oxyphenbutazone, as a causal factor (5). Another severe skin reaction with laboratory evidence of hepatotoxicity has been described (SEDA-22,115). 

C. Toxicity Cutaneous flushing is a common adverse effect. Pretreatment with aspirin or other NSAIDs reduces the intensity of this flushing, suggesting that it is mediated by prostaglandin release. Tolerance to the flushing reaction usually develops within a few days. Dose-dependent nausea and abdominal discomfort often occur. Pruritus and other skin conditions are reported. Moderate elevations of liver enzymes and even severe hepatotoxicity may occur. Hyperuricemia occurs in about 20% of patients, and carbohydrate tolerance may be moderately impaired. 

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