Aspirin intolerance

AIA runs a characteristic clinical course [9]. It is more frequent in women than men, and is unusual in children, beginning in adulthood, on average at the age of 30 years. Rhinorrhea and nasal congestion are usually the first symptoms, subsequently complicated by polyposis. Asthma and aspirin hypersensitivity develop 2-15 years later. Once developed, aspirin intolerance remains through life, although sporadic disappearance of intolerance has been reported. Asthma, characterized by blood and nasal eosinophilia, rims a protracted course despite avoidance of analgesics. In about half the patients, the course of asthma is severe, necessitating use of systemic corticosteroids. 

Malmgren, R., Unge, G. and Zetterstrom, O. (1986). Ix)wered glutathione peroxidase activity in asthmatic patients with food and aspirin intolerance. Allergy 41, 43-45. 

Sanak M, Pierzchalska M, Bazan-Socha S, Szczeklik A. Enhanced expression of the leukotriene C(4) synthase due to overactive transcription of an allelic variant associated with aspirin-intolerant asthma. Am J Respir Cell Mol Biol 2000 23 290-296. 

Yoshida, S., Sakamoto, H., Ishizaki, Y., et al. (2000) Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma. Clin. Exp. Allergy. 30, 64-70. 

Obase, Y., Shimoda, T., Tomari, S., et al. (2001) Effects of pranlukast on aspirin-induced bronchoconstiiction differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients. Ann. Allergy. Asthma. Immunol. 87, 74-79. 

Kim SH, Oh JM, Kim YS, et al. (2006) Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin-intolerant asthma in males. Clin Exp Allergy. 36, 433-439. 

Park JS, Chang HS, Park CS, et al. (2005) Association analysis of cysteinyl-leukotriene receptor 2 (CY SLTR2) polymorphisms with aspirin intolerance in asthmatics. Pharmacogenet Genomics. 15, 483 92. 

Kim SH, Choi JH, Holloway JW, et al. (2005) Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma differing contributions of ALOX5 polymorphism in Korean population. J Korean Med Sci. 20, 926-931. 

Van SR, Stevenson DD, Baldasaro M, et al. (2000) 5 Flanking region polymorphism of the gene encoding leukotriene C4 synthase does not correlate with the aspirin-intolerant asthma phenotype in the United States. J Allergy Clin Immunol. 106(1 pt. 1), 72-76. 

Sampson AP, Cowbum AS, Sladek K, et al. (1997) Profound overexpression of leukotriene C4 synthase in bronchial biopsies from aspirin-intolerant asthmatic patients. Int Arch Allergy Immunol. 113, 355-357. 

Hypersensitivity reactions Aspirin intolerance, manifested by acute bronchospasm, generalized urticaria/angioedema, severe rhinitis, or shock occurs in 4% to 19% of asthmatics. Symptoms occur within 3 hours after ingestion. Have epinephrine 1 1,000 immediately available. 

Forty minutes after a first dose of prednisone 25 mg, a 17-year-old girl with a history of aspirin intolerance had generalized flushing, hives, hypogastric pain, and abdominal cramps, followed by vomiting and diarrhea... 

A small number of individuals exhibit aspirin intolerance or supersensitivity.84 These individuals comprise approximately 1 percent of the general population, but the incidence is considerably higher (10%-25%) in people with asthma or other hypersensitivity reactions.84,94 People with aspirin intolerance will display allergiclike reactions, including acute bronchospasm, urticaria, and severe rhinitis, within a few hours after taking aspirin and aspirinlike NSAIDs.45,76 These reactions may be quite severe, and cardiovascular shock may occur. Likewise, sensitivity to aspirin often indicates a concomitant sensitivity to other NSAIDs, including COX-2 selective drugs.92 Consequently, the use of all NSAIDs is contraindicated in these individuals.84... 

Szczeklik A, Sanak M, Nizankowska-Mogilnicka E, Kielbasa B. Aspirin intolerance and the cyclooxygenase-leukotriene pathways. Curr Opin Pulm Med. 2004 10 51-56. 

Aspirin hypersensitivity is also a potential concern and can occur in two ways (1) a respiratory reaction, which is more profitimd in patients with rhinitis, asthma, or nasal polyps, or (2) a typical type I hypersensitivity reaction, including urticaria, wheals, angioedema, itching, rash, bronchospasm, laryngeal edema, hypotension, shock, or syncope. This latter response generally occurs within 1 hour of aspirin ingestion. Such aspirin intolerance may manifest itself in 4% to 19% of patients with asthma and may approach 40% of steroid-dependent asthmatics. 

Azo dyes e.g., tartrazine (dyes) Anaphylactoid reaction. Contraindicated for aspirin-intolerant individuals [7,23,70]... 

Settipane RA, Constantine HP, Settipane GA. Aspirin intolerance and recurrent urticaria in normal adults and children. Epidemiology and review. Allergy 1980 35(2) 149-54. 

Patients with aspirin intolerance often also react to many other NSAIDs. Azapropazone seems to be a safe alternative in these patients, according a study that showed good tolerance of the drug in patients with aspirin intolerance (5). 

Gutgesell C, Fuchs T. Azapropazone in aspirin intolerance. Allergy 1999 54(8) 897-8. 

Most people tolerate aspirin well, but not patients with asthma, of whom there is a subgroup in whom aspirin precipitates asthmatic attacks (61,62). This is a distinct clinical syndrome, called aspirin-induced asthma, which affects about 10% of adults with asthma (63). Aspirin-induced asthma is usually accompanied by naso-ocular symptoms and can be triggered not only by aspirin, but by several NSAIDs, a fact that makes immunological cross-reactivity most unlikely. The propensity of an NSAID to precipitate an attack of asthma is probably related to inhibition of COX (63). There is evidence that potent inhibitors of COX-1 (such as ibuprofen, indometacin, and naproxen) are more likely to precipitate bronchoconstriction than NSAIDs that inhibit COX-2 preferentially (such as meloxicam and nime-sulide) (64,65). A widely accepted hjrpothesis is that in patients with asthma and aspirin intolerance, NSAJD-induced COX inhibition results in increased products from the 5-lipoxygenase pathway, the leukotrienes, which are both potent bronchoconstrictors and also inducers of... 

Dahlen B, Szczeklik A, Murray JJ Celecoxib in Aspirin-Intolerant Asthma Study Group. Celecoxib in patients with asthma and aspirin intolerance. N Engl J Med 2001 344(2) 142. 

TBXA2R gene variability may also contribute to interindividual differences in the efficacy of pharmaceutical agents that act on this system. A positive association between a polymorphism in the TBXA2R gene and risk of asthma, atopy, and the aspirin-intolerant... 

Kim SH, Ye YM, Hur GY et al (2007) Cys-LTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients. Pharmacogenomics 8 1143-1150... 

The classic description of the aspirin-intolerant asthmatic includes the triad of severe asthma, nasal polyps, and aspirin intolerance. The typical patient experiences intense vasomotor rhinitis, which may or may not be associated with aspirin exposure, beginning during the third or fourth decade of life." Over a period of months, nasal polyps begin to appear, followed by severe asthma exacerbated by aspirin. 

Dahlen S, Malmstrom K, Nizankowska E, et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist A randomized, double-blind, placebo-controlled trial. Am J Respir Crit care Med 2002 165 9-14. 

Gyllfors P, Bochenek G, Overholt J, et al. Biochemical and clinical evidence that aspirin-intolerant asthmatic subjects tolerate the cyclooxygenase 2-selective analgesic celecoxib. J Allerg Clin Immunol 2003 111 1116-1121. 

Other toxic effects of NSAIDs include hypersensitivity reactions, rash, and central nervous system complaints of drowsiness, dizziness, headaches, depression, confusion, and tinnitus. Although NSAIDs are generally avoided in patients with asthma who are aspirin-intolerant, studies indicate that celecoxib and rofecoxib are well tolerated in aspirin-sensitive asthma, providing a viable option for these patients. Celecoxib and valdecoxib are sulfonamides and are thus contraindicated for those with sulfa allergies. 

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