The use of selective cyclooxygenase-2 (COX-2) inhibitors as an alternative to other nonsteroidal anti-inflammatory drugs (NSAID) is suggested for patients with aspirin-induced asthma. The safety of Rofecoxib (1, 2) and of Celecoxib (3) was demonstrated in these patients with double-blind, placebo-controlled oral challenges.
We present the case of a 64-year-old woman with aspirin-sensitive asthma and a history of severe anaphylactic reactions to different NSAID, who developed an asthmatic reaction after a single-blind, placebo-controlled oral challenge with Etoricoxib. She reported that 30 years ago, she had developed bronchial asthma with sensitization to house dust mites. Initially, there were some moderate asthmatic reactions to aspirin, one severe anaphylactic reaction to two tablets of Copyrkal® (400-mg paracetamol and 50-mg caffeine) and one nearly life-threatening anaphylactic reaction after an i.v. injection of metamizole, a pyrazolone drug. Ten years ago, she had surgery on nasal polyps and, to date, she has noticed a moderate relapse of nasal polyposis. In the past few years, the asthma has been difficult to treat and for nearly the whole of the year prior to presentation an oral prednisolone therapy between 20 and 50 mg a day was necessary. At the time of presentation her medication was a high-dose inhalative and topical nasal corticosteroid, a long-acting β-agonist, oral low-dose theophylline and an H1-antihistamine. At least three times a week she needed a short-acting β-agonist at night. After the last severe exacerbation of her asthma, the oral prednisolone therapy was now stopped 2 weeks before admission. Blood tests and leukocyte differential count were within normal limits. Total serum IgE was 227 kU/l, specific IgE to Dermatophagoides pteroniss was 0.63 kU/l (RAST class 1). The physical examination and lung function were normal. Before starting an adaptive desensitization with aspirin, a single-blind, placebo-controlled oral challenge with Etoricoxib as an alternative analgetic drug was conducted. At 1-h intervals, first two dosages of placebo and then 30 and 60 mg of Etoricoxib were administered. Thirty minutes after the 60 mg Etoricoxib dosage she complained about moderate dyspnoea. The clinical examination revealed severe rhinorrhoea and a shortness of breath with wheezing. The lung function showed a fall in forced expiratory volume in 1 s (FEV1) of 24% from baseline, and an increase in specific resistance of 120% to 3.5 kPA × s (Fig. 1). After the administration of a short-acting β-agonist and 50 mg prednisolone i.v. the symptoms resolved. A single-blind, placebo-controlled oral challenge with paracetamol was tolerated well up to a dosage of 500 mg. Then, an adaptive desensitization with aspirin was initiated. The patient reacted to 20-mg aspirin with moderate rhinorrhoea and a fall in FEV1 of 22% from baseline. With the administration of a short-acting β-agonist and repeating the 20 mg dosage twice, the adaptive desensitization could be finished without any further adverse effects up to 500 mg/day aspirin.
Etoricoxib is a second-generation COX-2 inhibitor with the highest in vitro selectivity for COX-2. In a double-blinded, placebo-controlled trial comparing Etoricoxib (120 mg) and Celecoxib (200 mg) in patients with NSAID-induced urticaria or angioedema, the reaction rate was 11% for Celecoxib and 7% for Etoricoxib, but without any asthmatic reaction (4). In 31 patients with intolerance to NSAIDs, manifested as cutaneous, respiratory or anaphylactic symptoms, none reacted to Etoricoxib (5). In 16 subjects with aspirin-sensitive asthma all tolerated a 90-mg dosage of Etoricoxib without any adverse effects (6). This is the first report of an Etoricoxib-induced asthmatic reaction in a patient with aspirin-sensitive asthma. For these patients we recommend an oral challenge with Etoricoxib in a specialized centre because adverse reactions may occur.