Most Common Allergic Diseases: Historical Reflections in Understanding Bergmann K-C, Ring J (eds): History of Allergy. Chem Immunol Allergy. Basel, Karger, 2014, vol 100, pp 132–139 DOI: 10.1159/000358618

Aspirin Hypersensitivity Mario Sánchez-Borges Allergy and Clinical Immunology Department, Centro Médico-Docente ‘la Trinidad’ and Clínica El Avila, Caracas, Venezuela

Hypersensitivity reactions to acetylsalicylic acid and non-steroidal anti-inflammatory drugs constitute a major medical concern worldwide. This article presents an overview of the observations that led to the discovery of cyclooxygenase inhibitors, as a prerequisite to better understand the basic concepts supporting seminal investigations carried out in order to elucidate the clinical features, pathogenic mechanisms, diagnosis and modern management of these common conditions. There are some unmet needs in this clinical area which will have to be solved in the future, especially concerning the pathogenesis of these reactions and the availability of novel in vitro diagnostic methods sparing both patient and physician of the risks inherent to in vivo provocation tests. © 2014 S. Karger AG, Basel

Aspirin is one of the most widely used drugs in the world and hypersensitivity reactions to aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) are, after β-lactam antibiotics, the second

most common cause of drug hypersensitivity. Natural salicylates such as salicin and salicylic acid are present in the bark and leaves of willow and poplar trees, and these compounds constitute the ancestry to aspirin. Since a knowledge of the pharmacology of aspirin and NSAIDs is relevant to the understanding of adverse reactions to these drugs, we will first present an overview of the observations that resulted in the discovery of aspirin, the first synthetic drug available for use in human beings, and will then review the most important findings allowing us to obtain a better understanding of these common adverse reactions.

The Discovery of Aspirin Ancient Times Natural salicylates present in the bark of white willow and other trees are mentioned in texts from ancient Sumer, Egypt, Mesopotamia, Lebanon and Assyria. Around 3000 BC, ancient Egyptians recorded the medicinal value of willow bark and myrtle. Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

Abstract

From Willow Bark to Salicin to Salicylic Acid The first clinical trial on the therapeutic use of willow bark against fever was reported to the Royal Society of Medicine on April 25, 1763, by Reverend Edward (Edmund) Stone, a vicar from Chipping Norton in Oxfordshire, England. This investigator noted that it was effective in reducing malarial fever (‘agues’). Stone had tasted the bark in 1758 and noticed an astringent taste reminiscent of the standard ague cure of Peruvian bark. He collected, dried and powdered a substantial amount of willow bark, and over the next 5 years tested it on a number of people sick with fever and agues, involving an ill-defined constellation of symptoms, including intermittent fever, pain and fatigue that primarily referred to malaria. Lewis and Clark used willow bark tea for fever in 1803–1806. In 1824, Bartolomeo Rigartelli used a

Aspirin Hypersensitivity

willow bark extract as a therapeutic agent, denominating it ‘salino amarissimo antifebrile’ (very bitter antipyretic salts). In 1828, Johann Andreas Buchner, professor of pharmacology at the University of Munich, isolated a tiny amount of bitter-tasting yellow needle-like crystals from willow tree which he called ‘salicina’ (salicin). Brugnatelli and Fontana had obtained salicin in a highly impure form in 1826. In 1829, French pharmacist Henri Leroux isolated salicin in crystalline form. He boiled the powder of white willow bark in water and, while trying to concentrate the preparation, obtained the soluble crystals that he named salicylic acid. At around the same time, Löwig, a German chemist, found salicylic acid in meadowsweet. This compound had an unpleasant taste and caused gastric irritation and nausea. In 1830, the Swiss pharmacist Johann Pagenstecher discovered what he thought was a new painreducing substance isolated from meadowsweet (Spiraea ulmaria), and in 1838 Rafaelle Piria, an Italian chemist then working at the Sorbonne in Paris, was able to convert salicin to salicylic acid. He split salicin into a sugar and an aromatic component (salicylaldehyde) and converted the latter by hydrolysis and oxidation to an acid of crystalized colorless needles which he named salicylic acid.

2

From Natural to Synthetic Acetylsalicylic Acid A major breakthrough occurred in 1853 when Charles Frédéric Gerhardt, a French chemist, first synthesized acetylsalicylic acid (ASA) by buffering salicylic acid with acetyl chloride and sodium salicylate. The resulting product was unstable and impure, and Gerhardt called it acetosalicylic anhydride. In 1859, Hermann Kolbe, a chemistry professor at Marburg University, prepared salicylic acid from sodium phenate and carbon dioxide, and in the same year von Gilm created ASA again, calling it acetylated salicylic acid. In 1869, Schröder, Prinzhorn and Kraut were the first to assign the correct structure of ASA with the acetyl group connected to phenolic oxygen. In 1876, the antirheumatic effect of salicin was described by Thomas MacLagan, a Scottish physician from Dundee, and that of salicylic acid by S. Stricker and L. Riess. In 1880, the German chemical industry was investigating the potential of new tar-derived medi-

133

Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

The decoction of sheets of willow is mentioned in a famous Egyptian papyrus, Ebers Papyrus, a medical text from around 1543 BC. The Romans also knew its medical properties, and Chinese and Greek civilizations employed willow bark more than 2,000 years ago. Hippocrates of Kos, the Greek physician considered as the father of modern medicine, described ‘a bitter powder that came from the bark and leaves of the willow tree which eases pain and reduces fever’. The active extract of the bark was called salicin after the Latin name of the white willow tree (Salix alba), a member of the Salicaceae family, salicin being the glycoside of salicylic acid. Celsus, Pliny the Elder, Dioscorides and Galen also used these natural remedies. The Roman encyclopedist Celsus, in his De Medicina of circa 30 BC suggested willow leaf extracts to treat inflammation. Willow treatments also appeared in the Greek physician Dioscorides’ De Materia Medica, and Pliny the Elder’s Natural History. By the time of Galen, willow was commonly used throughout the Roman and Arab worlds. In the Middle Ages Hildegard of Bingen, a nun, and Henrik Harpestreng used salicylates for fever and rheumatism. The Cherokee and other Native Americans and the Hottentots of South Africa used an infusion of the bark for fever and other medicinal purposes for centuries.

Mechanisms of Action In regard to its mechanisms of action, Heinrich Dreser proposed that aspirin relieved pain by acting on the central nervous system. In 1958, Harry Collier, a biochemist in the London Laboratory of Parke Davis & Co., began investigating the relationship be-

134

tween kinins and the effects of aspirin. In tests in guinea pigs he found that pretreatment with aspirin inhibited the bronchoconstriction induced by bradykinin. Cutting the vagus nerve did not affect the action of bradykinin or the inhibitory effect of aspirin, evidence that ASA worked locally to inhibit pain and inflammation, rather than on the central nervous system. John Robert Vane, a British pharmacologist and his graduate student Priscilla Piper, from London’s Royal College of Surgeons, found that aspirin inhibited the release of an unidentified chemical generated by guinea pig lungs that caused rabbit tissue to contract. By 1971, Vane had identified the chemical (which he called ‘rabbit-aorta contracting substance’ or RCS) as a prostaglandin. In June 1971, Vane and Piper suggested that aspirin and similar drugs (the NSAIDs) worked by blocking the production of prostaglandins. Later on it was shown that NSAIDs worked by inhibiting cyclooxygenase, the enzyme responsible for converting arachidonic acid into a prostaglandin, which was described in 1976. For this discovery, Vane received the Nobel Prize in Physiology and Medicine in 1982 and was knighted in 1984 for his contributions to science. Cyclooxygenase Isoenzymes Other than cyclooxygenase-1 (COX-1), the constitutive enzyme present in all cells, there are at least two other COX isoforms, designated as COX-2 and COX-3. COX-2, the inducible isoenzyme, was discovered in 1988 by Daniel Simmons and his team at Brigham Young University. The mouse COX-2 gene was cloned by UCLA scientist Harvey Herschman. COX-3 was discovered due to the observation that the COX-1/COX-2 model did not explain the antipyretic and analgesic properties of acetaminophen. Although its effects could be due to inhibition of COX-2, it was clear that paracetamol is not an effective anti-inflammatory. Simmons and his team suggested that a variant of COX-1, which they named COX-3, was especially sensitive to acetaminophen and related compounds (phenacetin, antipyrine, dipyrone).

Sánchez-Borges

Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

cines and, in 1886, Kalle & Co. discovered by accident the antipyretic properties of the dye derivative acetanilide, which was called Antifebrin. Afterwards, Carl Duisberg, head of research at the small dye firm Friedrich Bayer & Co., Elberfeld, Germany, developed phenacetin (acetophenetidin). On August 10, 1897, Felix Hoffman, a German chemist working at Friedrich Bayer & Co., discovered a better method for synthesizing pure, stable and palatable ASA, the first modern, truly synthetic drug. He neutralized salicylic acid by buffering it with sodium and acetyl chloride. He was looking for a medicine for his father who suffered with chronic rheumatism. The disgusting sweet taste of sodium salicylate was refined by acetylation of the free phenolic hydroxyl group of salicylic acid through substitution of the hydrogen atom with a methyl group. Hoffman clearly understood that aspirin was an effective pain reliever that did not have the unpleasant side effects of salicylic acid. Apparently, Arthur Eichengrün, Hoffman’s boss, was the one that envisioned the idea to synthesize the drug. In 1899, Heinrich Dreser, Bayer’s head of pharmacology laboratories, set up animal experiments and showed the anti-inflammatory and analgesic effects of ASA, and Bayer & Co. patented it on March 6, 1899. The beneficial effect of ASA on pain and rheumatic fever was then recognized by K. Witthauer and Julius Wohlgemuth. Aspirin was first sold as a powder, and in 1900 aspirin tablets were produced. In 1915, the tablets became available to the public without a prescription. The name aspirin comes from ‘a’ in acetyl chloride, ‘spir’ from Spirsäure (salicylic acid) in S. ulmaria (the plant they derived the salicylic acid from) and ‘in’, a familiar name ending for medicines. In fact, ASA had been manufactured by the Chemische Fabrik von Heyden & Co. since 1897 without a brand name. Aspirin’s popularity declined after the development of acetaminophen/ paracetamol in 1956 and ibuprofen in 1962.

Table 1. Historical chronology of aspirin discovery

Date

Discovery

Around 1543 BC 460 BC

Egyptians mention the medicinal value of a decoction of willow bark and myrtle leaves in the Ebers Papyrus Hippocrates prescribes the bark and leaves of the white willow tree (S. alba) for pain, including labor pain, and fever 100 AD Dioscorides, a Greek surgeon, uses willow leaves for pain relief 200 Pliny the Elder alludes to willow leaves in his writings 1763 Edward (Edmund) Stone reports the successful treatment of malarial fever (agues) with willow bark 1826 Brugnatelli and Fontana obtained impure salicin 1828 Johann Andreas Buchner, a pharmacologist from Munich, isolated pure salicin from willow bark 1829 Henri Leroux, a French pharmacist, isolates salicin 1830 Johann Pagenstecher, a Swiss pharmacist, discovers a new analgesic isolated from meadowsweet (S. ulmaria) 1835 Karl Löwig, a German chemist, finds salicylic acid in meadowsweet flowers 1838 Raffaele Piria, an Italian chemist, converts salicin (salicoside) into salicylic acid 1853 Charles Frédéric Gerhardt, a French chemist, synthesizes impure ASA 1859 H. von Gilm also prepares impure ASA 1869 Kraut, Schröder and Prinzhorn describe the molecular structure of ASA 1874 Herman Kolbe prepares salicylic acid from coal tar 1876 Thomas MacLagan, a Scottish physician, describes the antirheumatic effect of salicin, and S. Stricker and L. Riess that of salicylic acid 1897 Felix Hoffman, a German chemist, prepares the first pure and stable sample of ASA on August 10. He realizes that ASA is devoid of the gastric side effects of salicylic acid 1899 Heinrich Dreser shows the anti-inflammatory and analgesic effects of ASA 1900 Bayer & Co. introduces aspirin in water-soluble tablet form 1915 Aspirin becomes available to the public without prescription 1969 Aspirin is included in the self-medication kits taken to the moon by the Apollo astronauts 1948 Lawrence Craven, a family physician from California, describes the potential of aspirin to prevent heart attacks 1971 John Vane, a British pharmacologist, discovers the mechanism of action of aspirin as an inhibitor of the cyclooxygenase pathway 1980 US FDA approves the use of aspirin to reduce the risk of stroke 1982 John Vane is awarded the Nobel Prize in Physiology and Medicine 1985 US FDA approves the use of aspirin for prevention of heart attacks and strokes 1999 COX-3 is discovered by Simmons and co-workers

Aspirin Hypersensitivity

of aspirin’s effectiveness for the prevention of myocardial infarction. The chronology of aspirin development is summarized in table 1.

Hypersensitivity Reactions to ASA and NSAIDs Early Observations The first description of a hypersensitivity reaction triggered by aspirin was made only 3 years after the introduction of the drug for therapeutic use, by Hirschberg [1] in 1902. This author described a pa-

135

Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

Antithrombotic Effects of Aspirin The antiplatelet effects of aspirin were first noticed by Lawrence Craven, a family doctor from California. He gave his tonsillectomy patients chewable Aspergum, an aspirin-laced chewing gum, and found that an unusual number of patients had to be hospitalized for severe bleeding. In the 1960s, Harvey Weiss found that aspirin had an antiaggregation effect on blood platelets. John O’Brien and Peter Elwood showed in 1973 a modest but not statistically significant reduction in heart attacks among patients taking aspirin. A meta-analysis by Richard Peto convinced the US Food and Drug Administration (FDA)

2

Samter’s Disease In 1968, Max Samter proposed the concept of aspirin triad (Samter’s triad) as a distinct clinical entity [4]. This disease has also been mentioned in the literature as the Widal-Abrami-Lermoyez triad, Widal-Lermoyez syndrome and Widal’s syndrome. Different terminologies are used by various authors for aspirin-induced asthma, including the following: aspirin-intolerant asthma, aspirin sensitivity, aspirin-sensitive asthma, aspirin-exacerbated asthma. Presently, the designation of aspirin-exacerbated respiratory disease (AERD) is the most commonly accepted because it includes the wider involvement of both the upper and lower airways, and also due to the fact that the disease progresses independently of any aspirin or NSAID exposure. In order to harmonize the nomenclature, we have recently proposed that cross-reactive urticaria/angioedema observed in patients with underlying chronic spontaneous urticaria be designated aspirin-exacerbated cutaneous disease, AECD [5]. In 1997, we reported the association of cutaneous aspirin sensitivity (urticaria/angioedema) with allergic rhinitis and severe systemic reactions to mite-contaminated foods, and we proposed this clinical picture as a ‘new aspirin triad’ [6]. Classification of Hypersensitivity Reactions to ASA and NSAIDs Since there were discrepancies in the literature in regard to the terminology used by different investigators, Stevenson [7] proposed the first classification

136

system for ASA hypersensitivity in 1993. A further step followed in 2001 when Stevenson et al. [8] published a second classification system for reactions that inhibit cyclooxygenase enzymes. Recently, a more comprehensive classification including immediate and delayed reactions to NSAIDs has been proposed by EAACI/ENDA and GA2LEN/HANNA [9]. Pathogenesis Aspirin and NSAIDs that inhibit COX-1 cross react to induce reactions in all patients with AERD and AECD, and in patients with multiple NSAID-induced urticaria and angioedema, as recognized early by Vanselow [10]. Reactions, including asthma, are observed when NSAIDs are administered by diverse routes, including oral, parenteral, topical in the skin or even conjunctival [11]. In the 1970s, the link between precipitation of asthma attacks and inhibition of cyclooxygenase by aspirin and other NSAIDs was described. Later on, other alterations in arachidonic acid metabolism were discovered, and also found to be common in aspirin-induced angioedema and urticaria [12]. This observation led Szczeklik [13] to propose the cyclooxygenase theory. Overproduction of cysteinyl leukotrienes, increased expression of CysLTR1 in the airways mucosa [14], decreased production of prostaglandin E2, which acts like a break on the uncontrolled synthesis of cysteinyl leukotrienes, and reduced lipoxin synthesis are also involved in the pathogenesis of ASA/NSAIDs reactions. In this regard, Picado et al. [15] found a decreased expression of COX-2 mRNA in nasal polyps from subjects suffering from AERD. The hypothesis that aspirin-induced asthma results from a persistent, latent rhinovirus infection of the respiratory tract giving origin to alterations in arachidonate metabolism, as proposed by Szczeklik [16], has not been substantiated. Reactions to a single NSAID, where drug-specific immunoglobulin (Ig) E antibodies are thought to be involved, are rarely observed. These allergic reactions have been reported more often for the pyrazolone group of NSAIDs [17].

Sánchez-Borges

Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

tient with acute angioedema and urticaria occurring immediately after aspirin intake [1]. Gilbert recognized for the first time an asthmatic reaction to ASA in 1911 [2], whereas Reed and Cookes repeated the same observation in 1919. In 1920, Van der Veer described the first ASA-induced fatal asthmatic reaction. M. Fernand Widal, Pierre Abrami and Jacques Lermoyez observed in 1922 the association between aspirin sensitivity, aspirin-induced asthma and nasal polyposis, the ASA triad, which was rediscovered more than 40 years later by Samter (see below) [3]. In modern times this disease is designed as a tetrad that also includes chronic hyperplastic eosinophilic sinusitis. These investigators also described for the first time the phenomenon of aspirin desensitization.

Table 2. Milestones in the history of aspirin hypersensitivity

Date

Discovery

1902 1911 1919 1920 1922

Hirschberg describes the first case of aspirin hypersensitivity Gilbert recognizes aspirin-induced asthmatic reaction Reed and Cookes again observe that aspirin could provoke asthma attacks Van der Veer describes the first aspirin-induced fatal asthmatic reaction M. Fernand Widal, Pierre Abrami and Jacques Lermoyez observe the association of aspirin sensitivity, aspirin-induced asthma and nasal polyposis Samter and Beers propose the concept of aspirin triad Vanselow reports on asthma induced by indomethacin Zeiss and Lockey propose that aspirin-induced asthma is inherited as autosomal recessive Stevenson develops oral aspirin challenges for aspirin-sensitive asthma Stevenson implements aspirin desensitization as a treatment for aspirin-induced asthma Bianco introduces the aspirin inhalation test Milewski describes the nasal provocation test with lysine-aspirin Settipane reports respiratory reactions to increased doses of acetaminophen Szczeklik [13] proposes the cyclooxygenase theory to explain aspirin-intolerant asthma A new aspirin triad of allergic rhinitis, severe allergic reaction to ingested aeroallergens and aspirin sensitivity is proposed by Sánchez-Borges et al. [6] IgE-mediated reactions to pyrazolones reported by Kowalski et al. [26] Sánchez-Borges and co-workers show that atopy is a risk factor for NSAID hypersensitivity reactions Picado demonstrates a decrease of COX-2 mRNA in nasal polyps from patients with aspirin triad A new classification of reactions to NSAIDs is proposed by Stevenson, Sánchez-Borges and Szczeklik Selective COX-2 inhibitors are tolerated by patients with ASA-intolerant asthma and urticaria Mastalerz et al. [12] propose that the pathogenesis of aspirin-induced urticaria is due to inhibition of cyclooxygenase Intravenous desensitization with aspirin is proposed Sánchez-Borges et al. [30] propose the concept of the ‘high-risk’ phenotype for reactions to NSAIDs The concept of AECD is proposed A new classification system for NSAID-induced hypersensitivity reactions is developed by Kowalski et al. [9]

1999 2000 2000 2001 2001 2004 2006 2009 2010 2011

Genetics In 1973, Lockey et al. [18] described four members of a Mennonite family who suffered with ASAinduced asthma, three of whom were first cousins. The presence of the disease in relatives, influenced by the presence of consanguinity, suggested an autosomal recessive mode of inheritance. More recently, progress in molecular genetics has permitted the study of a number of genetic polymorphisms associated with reactions to NSAIDs [reviewed in 19]. In AERD the following genetic variants have been recognized: HLADPB1*0301, LTC4S444A>C, ALOX5, CysLTR1 and CysLTR2, PGE2 receptor subtype 2 (EP2), TBXA2R and TBX21. For aspirin-induced urticaria and angioedema the following genetic variants have been reported: HLADRB1*1302 and HLA-DQB1*0609, LTC4S-444A>C

Aspirin Hypersensitivity

2

and FcεRIα-344C>T. It has to be mentioned that these genetic markers are applicable only for the populations under study, and sometimes are not reproducible in other populations of a different genetic background. Presently, its usefulness for diagnostic purposes has not been validated. Developments in Diagnostic Methods Provocation tests with aspirin and other NSAIDs constitute the gold standard to confirm the diagnosis of NSAID hypersensitivity. Challenges can be performed by different routes, such as oral [20], bronchial [21] and nasal [22]. For reactions to a single NSAID, presumably IgE-mediated, immediatetype prick and intradermal skin tests have been recommended, although sensitivity and specificity are variable [23].

137

Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

1967 1967 1973 1976 1977 1977 1977 1989 1990 1997

In vitro methods to avoid the undesirable and potentially risky effects of in vivo challenges have been proposed, but presently they are not widely used and require further validation. They include the sulfidoleukotriene release assay [24], the basophil activation test [25], and the 15-HETE generation assay (ASPITest) [26].

been performed with lysine-aspirin by other routes, such as bronchial [34], nasal [35] and intravenous [36]. The milestones in the study of aspirin and NSAID hypersensitivity reactions are shown in table 2.

Conclusions

138

Adverse hypersensitivity reactions to aspirin and NSAIDs are a major cause of consultation in general medical practice as well as in specialized allergy clinics. Major advances in the understanding of the clinical features of these reactions have permitted to design better diagnostic and management efforts for patients suffering from these conditions. This has been possible thanks to the dedication of a number of pioneer clinical and basic investigators led by Prof. Max Samter, Prof. Sir John Vane, Prof. Donald D. Stevenson, Prof. Andrej Szczeklik, Prof. Alain De Weck and Prof. Richard Lockey, and a whole new generation of professionals that includes Marek Kowalski, Cesar Picado and Hae Sim Park, among others. In spite of the huge amount of knowledge presently available on these reactions there are some loopholes in the understanding of their pathogenesis. New and improved in vitro diagnostic methods sparing the affected patients of the risks of challenge tests are dearly needed at the present time.

References

1 Hirschberg SR: Mitteilung über einen Fall von Nebenwirkung des Aspirin. Dtsch Med Wochenschr 1902;28:416. 2 Gilbert GB: Unusual idiosyncrasy to aspirin. J Am Med Assoc 1911;56:1262. 3 Widal MF, Abrami P, Lermoyez J: Anaphylaxie et idiosyncrasie. Presse Med 1922; 30: 189–192. 4 Samter M, Beers RF: Intolerance to aspirin: clinical studies and consideration of its pathogenesis. Ann Intern Med 1968; 68: 975–983. 5 Sánchez-Borges M: NSAID hypersensitivity (respiratory, cutaneous and generalized, anaphylactic symptoms). Med Clin North Am 2010;94:853–864. 6 Sánchez-Borges M, Capriles-Hulett A, Capriles-Behrens E, Fernandez-Caldas E: A new triad: sensitivity to aspirin, allergic rhinitis, and severe allergic reaction to ingested aeroallergens. Cutis 1997;59:311–314.

Sánchez-Borges

Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

Advances in Patient Management The avoidance of all classic COX-1 inhibitors is usually recommended for patients with cross-reactive NSAID hypersensitivity, together with the use of weak COX inhibitors, especially acetaminophen. However, Settipane and Stevenson [27] observed more than 20 years ago that acetaminophen can cause bronchoconstriction at doses greater than 1,000 mg in 34% of individuals with AERD. With the incorporation of new drugs that are highly selective for COX-2, the safety of such NSAIDs in patients with respiratory or cutaneous disease was investigated. Stevenson and Simon [28] found that selective COX-2 inhibitors may be used safely in the majority of aspirin-sensitive patients with asthma. Similar results were observed in patients with aspirin-induced urticaria and angioedema [29]. It is worth mentioning that a small number of NSAIDsensitive patients will not tolerate the above-mentioned alternative drugs (weak COX inhibitors and selective COX-2 inhibitors). We have proposed that these patients are considered as the ‘high-risk phenotype’ of NSAID hypersensitivity [30]. In patients who require NSAIDs for chronic conditions such as rheumatic diseases and ischemic coronary disease, desensitization is an option. In 1976, Zeiss and Lockey [31] described the paradoxical finding that ASA-intolerant patients revealed a 3-day refractory period after oral aspirin challenge resulted in respiratory symptoms. This observation constituted the basis for the oral desensitization protocols that have been preconized by Stevenson et al. [32], who demonstrated that oral administration by means of an initial desensitization with gradually ascending doses of aspirin could be followed safely by a daily maintenance dose. The first randomized, double-blind, placebo-controlled crossover trial of oral desensitization was published by the same investigators in 1984 [33]. Desensitization has also

7 Stevenson DD: Challenge procedures in detection of reactions to aspirin and nonsteroidal anti-inflammatory drugs. Ann Allergy 1993;71:417–418. 8 Stevenson DD, Sánchez-Borges M, Szczeklik A: Classification of allergic and pseudoallergic reactions to drugs that inhibit cyclooxygenase enzymes. Ann Allergy Asthma Immunol 2001;87:177–180. 9 Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, Bousquet P, Celik G, Demoly P, Gomes ER, Nizankowska-Mogilnicka E, Romano A, Sánchez-Borges M, Sanz M, Torres MJ, De Weck A, Szczeklik A, Brockow K: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) – classification, diagnosis and management: review of the EAACI/ENDA and GA2LEN/HANNA. Allergy 2011;66:818–829. 10 Vanselow H: Bronchial asthma induced by indomethacin. Ann Intern Med 1967; 66: 568–572. 11 Sitenga GL, Ing EB, Van Dellen RG, Younge BR, Leavitt JA: Asthma caused by topical application of ketorolac. Ophthalmology 1996;103:890–892. 12 Mastalerz L, Setkowicz M, Sanak M, Szczeklik A: Hypersensitivity to aspirin: common eicosanoid alterations in urticaria and asthma. J Allergy Clin Immunol 2004;113:771– 775. 13 Szczeklik A: The cyclooxygenase theory of aspirin-induced asthma. Eur Respir J 1990; 3:588–593. 14 Souza AR, Parikh A, Scadding G, Corrigan CJ, Lee TH: Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med 2002;347:1493–1499. 15 Picado C, Fernandez-Morata JC, Juan M, Roca-Ferrer J, Fuentes M, Xaubet A, Mullol J: Cyclooxygenase-2 mRNA is down-expressed in nasal polyps from aspirin-sensitive asthmatics. Am J Respir Crit Care Med 1999;160:291–296. 16 Szczeklik A: Aspirin-induced asthma as a viral disease. Clin Allergy 1988;18:15–20.

17 Kowalski ML, Bienkiewicz B, Wosczek G, Iwaszkiewicz J, Poniatowska M: Diagnosis of pyrazolone drug sensitivity: clinical history versus skin testing and in vitro testing. Allergy Asthma Proc 1999;20:347–352. 18 Lockey RF, Rucknagel DL, Vanselow NA: Familial occurrence of asthma, nasal polyps and aspirin intolerance. Ann Intern Med 1973;78:57–63. 19 Kim S-H, Park H-S: Genetic markers for differentiating aspirin-hypersensitivity. Yonsei Med J 2006;47:15–21. 20 Stevenson DD, Arroyave CM, Bhat KN, Tan EM: Oral aspirin challenges in asthmatic patients: a study of plasma histamine. Clin Allergy 1976;6:493–505. 21 Bianco S, Robuschi M, Petrigni G: Aspirin induced tolerance in aspirin-asthma detected by a new challenge test. J Med Sci 1977; 5:129–130. 22 Schapowal A, Schmitz-Schuman M, Szczeklik A, Bruijnzeel P, Hansel T, Virchow C: Lysine-aspirin nasal provocation and anterior rhinomanometry for the diagnosis of aspirin-sensitive asthma. Atemw Lungenkrkh 1990;16:S1–S5. 23 Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F, Ebner H, Ebner C: IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. J Allergy Clin Immunol 2003;111:882–888. 24 Sanz ML, Gamboa P, De Weck AL: A new combined test with flowcytometric basophil activation and determination of sulfidoleukotrienes is useful for in vitro diagnosis of hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. Int Arch Allergy Immunol 2005;136:58–72. 25 Gamboa P, Sanz ML, Caballero MR, Urrutia I, Antepara I, Esparza R, de Weck AL: The flow-cytometric determination of basophil activation induced by aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) is useful for in vitro diagnosis of the NSAID hypersensitivity syndrome. Clin Exp Allergy 2004;34:1448–1457.

26 Kowalski ML, Bienkiewicz B, Woszczek G: Diagnosis of pyrazolone drug sensitivity: clinical history versus skin testing and in vitro testing. Allergy Asthma Proc 1999; 20: 347–352. 27 Settipane RA, Stevenson DD: Cross-sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. J Allergy Clin Immunol 1989;84:26–33. 28 Stevenson DD, Simon RA: Lack of cross reactivity between rofecoxib and aspirin-sensitive patients with asthma. J Allergy Clin Immunol 2001;108:47–51. 29 Sánchez-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;87:201–204. 30 Sánchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F: A novel phenotype of nonsteroidal anti-inflammatory drug hypersensitivity: the high-risk patient. World Allergy Organ J 2009;2:17–19. 31 Zeiss CR, Lockey RF: Refractory period to aspirin in a patient with aspirin-induced asthma. J Allergy Clin Immunol 1976; 57: 440–448. 32 Stevenson DD, Simon RA, Mathison DA: Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges. J Allergy Clin Immunol 1980;66:82–88. 33 Stevenson DD, Pleskow WW, Simon RA, Mathison DA, Lumry WR, Schatz M: Aspirin-sensitive rhinosinusitis asthma: a double-blind crossover study of treatment with aspirin. J Allergy Clin Immunol 1984; 73: 500–507. 34 Schmitz-Schumann M, Schaub E, Virchow C: Inhalation provocation test with lysineacetylsalicylic acid in patients with analgetics-induced asthma (in German). Prax Klin Pneumol 1982;36:17–21. 35 Patriarca G, Schiavino D, Nucera E, Papa G, Schinco G, Fais G: Prevention of relapse in nasal polyposis. Lancet 1991;337:1488. 36 Pfaar O, Spielhaupter M, Wrede H: Aspirin desensitization on patients with aspirin intolerance and nasal polyps: a new therapeutic approach by the intravenous route. Allergologie 2006;8:322–331.

2

Aspirin Hypersensitivity

139

Downloaded by: University of South Australia 198.143.35.1 - 8/2/2015 4:33:21 AM

Dr. Mario Sánchez-Borges Allergy and Clinical Immunology Department Centro Médico-Docente ‘la Trinidad’ 6a transversal Urbanización Altamira, piso 8, consultorio 803 Caracas 1060 (Venezuela) E-Mail sanchezbmario @ gmail.com

Aspirin hypersensitivity.

Hypersensitivity reactions to acetylsalicylic acid and non-steroidal anti-inflammatory drugs constitute a major medical concern worldwide. This articl...
482KB Sizes 4 Downloads 3 Views