Substance Info: (and synonyms)
Aspirin / Acetylsalicylic acid / Acetyl salicylic acid

Background Info:

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Immune Reactions I Non-Immune Reactions I Occupational

Salicylates include acetyl salicylate (Aspirin/Disprin) and sodium salicylate (see). Acetyl salicylate, a painkilling drug, is mainly synthetically manufactured and may be found naturally in the bark of the willow tree. Acetyl salicylic acid is absent or found in extremely low levels in 30 foods examined using HPLC with fluorescence detection. (Janssen 1997 ref.3179 5) On the other hand, sodium salicylate occurs naturally in a wide range of foods. (Swain 1985 ref.226 43)

Although acetylsalicylic acid was first synthesised in the laboratory in 1899, it had long been extracted from the Willow tree (bark) and used in traditional medicine. Salicylic acid can be obtained from the oils of the birch tree or wintergreen, or made synthetically in several ways. It is used to manufacture the other salicylates and on its own is a keratoloytic (softens skin, e.g., corns).

Salicylic acid is an essential component in the signal transduction pathway in many plants leading to systemic acquired resistance.




No Allergens characterised

Immune Reactions:

Clinical features of AIA are characteristic. Naso-sinus complications, (often chronic) such as rhinitis, chronic sinusitis, nasal polyposis, asthma, chronic urticaria, laryngeal oedema, and anosmia, are commonly found in patients with AIA. Peak incidence is around 35 years of age (Sanak 1999 ref.3277 9) and usually persists for life. Some allergic individuals react severely to acetyl salicylate. This study reported that 8% of their aspirin-intolerant patients were also affected by tartrazine (Samter) whereas Settipane found that 15% of their aspirin-sensitive asthmatics reacted to tartrazine. Small doses (frequently less than 80mg) may precipitate symptoms. (Sanak 1999 ref.3277 9) Aspirin-induced asthma as an important type of bronchial asthma. It is estimated to affect 9.8% adults with chronic asthma (Sakakibara). In this study, 15 of 33 subjects (33 of whom were non-allergic asthmatics and 3 allergic asthmatics who had a history of aspirin sensitivity) challenged with aspirin developed bronchoconstriction. (Hong 1989 ref.2221 9) This study presents 6 atopic children with urticaria and/or angioedema related to ASA. (Botey 1988 ref.2225 7) Dermatographism, chronic urticaria, antibiotic and metal allergy, food allergy may be the conditions accompanying analgesic intolerance in asthmatics. (Kalyoncu 1999 ref.3248 7) Aspirin-sensitive rhinosinusitis is a non-allergic, non-infectious perennial eosinophilic rhinitis starting in middle age and rarely seen in children. (Schapowal 1995 ref.973 92) Adult asthmatics, particularly in their 3rd or 4th decade, are more prone to develop a salicylate intolerance than children. Initially an intense rhinitis with very watery and intermittent rhinorrhoea is experienced, and this is followed after a few months by chronic nasal congestion. Nasal polyposis may be found. Asthma and occasionally conjunctivitis develops later on. Symptoms can occur up to 1 hour after aspirin ingestion. Asthma and polyposis follows a protracted course thereafter, even if aspirin is avoided. Paradoxically, aspirin has been reported to relieve asthma in some individuals. Of 6 children with severe atopic dermatitis who underwent DBPCC with additives, 2 reacted to tartrazine, 3 to sodium benzoate, 2 to sodium glutamate, 2 to sodium metabisulfite, 4 to acetylsalicylic acid and 1 to tyramine. (Van Bever 1989 ref.2222 8) 3 cases of food-dependent exercise-induced anaphylaxis in which aspirin intake exacerbated anaphylactic symptoms. (Dohi 1990 ref.2017 4) Some patients with AIA are hypersensitive to some agents in addition to NSAID, e.g., tartrazine (15.1%), sodium benzoate (14.3%), and parabens (12.0%). Patients with latent AIA are in danger of having fatal or near-fatal asthma attacks if they take NSAID. (Sakakibara) The result of this study suggests that sodium salicylate may cross-react with aspirin in aspirin-and tartrazine-sensitive patients. (Park 1991 ref.2219 8) In this patient, ingestion of 60 ml freshly squeezed carrot juice two hours after intake of 100 mg aspirin induced striking angioedema and shortness of breath after three further hours, whereas challenged with each on separate occasions did not result in any reaction. (Schöpf 2000 ref.3575 7) 5 types of pseudo allergic and allergic reactions to aspirin and nonsteroidal anti-inflammitory drugs have been identified. (Stevenson 2000 ref.3688 7) Aspirin intolerance manifests itself as two clinical symptoms, urticaria/angioedema and asthma. There is seldom patient of aspirin intolerance who has the both symptoms, urticaria and asthma. The authors suspect that the pathogenic mechanism for aspirin urticaria differs from that for aspirin asthma. In this study, 18 patients with aspirin urticaria were tested. None had symptoms of asthma. Threshold dose to evoke urticaria/angioedema was 100 to 500 mg of aspirin (average, 311 mg). Urticaria/angioedema occurred within 50 minutes to 14 hours (average, 3 hours 16 minutes) after ingesting aspirin. The dose and the time of onset of symptoms for these 18 patients are more than for those with aspirin asthma. These results support the opinion that aspirin urticaria has the different pathogenic mechanism from aspirin asthma. In addition, we experienced one patient of aspirin intolerance which caused hyperemia and edema of the bulbar conjunctiva. She had no symptom of urticaria and asthma, and had the both character of aspirin urticaria and asthma as to aspirin challenge test. (Nakamura 2001 ref.4857 7) Eosinophilic arthritis and intolerance to aspirin (Widal's syndrome) (Le Quintrec 1991 ref.5051 8) Widal syndrome (muco-ciliary chronic sinusitis), presenting as a posterior catharrh that can be confirmed by computerized tomography and by prolonged sinuso-nasal saccharine clearance, a problem of mucus ciliary transport syndrome may be associated with other disorders (rhinitis, otitis, bronchitis, irritable colon, sterility and dextrocardia), and aspirin and intolerance to other drugs or chemicals especially anti-inflammatory drugs, has been implicated. (Mathe 1988 1988 ref.5052 7) (Widal 1987 ref.5053 6) In this study, 65 patients (35 females and 30 males mean age 38.5 yrs) affected by perennial asthma, underwent double blind challenge placebo controlled with food additives and acetyl salicylic acid (ASA). 62 % of the patients were positive to 1 additive, 22 % to two additives and 16% to three additives. 42% of them were positive to ASA, 18% to E 211 (Sodium benzoate), 15% to E127 (Erythrosine), 12 % to E 223 (Sodium metabisulphite), 10% to E 102 (Tartrazine) and 3% to 214-219 (Benzoates). The authors conclude that these results indicate that ASA is the most important additive in asthma due to food additives. (Pacor 2001 ref.4037 4) Some patients with AIA are hypersensitive to some agents in addition to NSAID, e.g., tartrazine (15.1%), sodium benzoate (14.3%), and parabens (12.0%). (Sakakibara) Administration of aspirin before ingestion of food allergens (wheat or shrimp) induced urticaria in one patient and urticaria and hypotension in another, while aspirin alone or food alone elicited no response. The third patient developed urticaria only when he took all three items, i.e. aspirin, food and additional exercise, whereas provocation with any one or or two of these did not induce any symptoms. These findings suggest that aspirin upregulates type I allergic responses to food in patients with food-dependent exercise-induced anaphylaxis (FDEIA), and further shows that aspirin synergizes with exercise to provoke symptoms of FDEIA. (Harada 2001 ref.5639 8) In a study of anaphylaxis after ingestion of wheat flour contaminated with mites, the study population showed respiratory allergies to dust mites (100%) and intolerance to acetylsalicylic acid (87%).(Blanco 1997 ref.5653 7)

Reorganization process. Data in process of being reorganized. Editorial staff 2014


Fifteen cases of systemic allergic reactions to ingcslant antigens arc reported. penicillin, pinto bean, halibut, rice, potato, Brazil nut, shrimp, milk, a cereal mix, garbanzo bean, tangerine, salicylsalicylic acid, and demethylchlortetracycline. Case A 37-year-old woman with dyspnea, generalized urticaria and angioedema, and syncope. She was unconscious with laryngeal stridor, pulmonary wheezing, cyanosis, angioedema of the face and oropharynx, and generalized urticaria. Subsequently, 4 reactions of varying severity occurred. Pinto bean became apparent from a diet diary. A prick test with extract prepared from fresh, raw pinto bean caused a large local cutaneous reaction and was followed by mild generalized symptoms of dyspnea, wheezing, pruritus, and flushing. Case A 27-year-old man, while ingesting halibut and toast, abruptly developed dyspnea, generalized urticaria, facial angioedema, dizziness, "faintness," diarrhea, nausea, and emesis. He was hypotensive. Wheezing, generalized urticaria, and facial angioedema were present. A similar reaction occurred several months earlier while ingesting halibut. A cutaneous prick test was strongly positive to halibut extract. Case A 21-year-old woman experienced dyspnea, dizziness, pruritus, swelling of the face, weakness, headache, and abdominal cramps. These symptoms developed while ingesting rice. Similar reactions, including syncope, had previously occurred during ingestion of rice. She had facial angioedema, generalized urticaria, cyanosis, and wheezing. A cutaneous prick test was strongly positive with a dilute solution of rice extract. Case A 17-year-old boy with wheezing, dyspnea, angioedema, dizziness, weakness, and chest pain described as "tightness" which occurred repeatedly after ingestion of potato. Cutaneous scratch tests were positive to potato extract. Case A 28-year-old man who experienced immediate systemic allergic reactions numerous times after ingestion of Brazil nut, pistachio nut, and cashew. Reactions were characterized by rhinorrhea, dyspnea; cyanosis; angioedema of face, tongue, and pharynx; abdominal cramps; weakness; and dizziness. A cutaneous scratch test with Brazil nut extract was performed elsewhere and caused a large local reaction and wheezing. Case A 24-year-old with a history of ingestion of shrimp and lobster which had repeatedly caused rhinorrhea, angioedema of face and oropharynx, urticaria, dyspnea, wheezing, dizziness, and syncope. A cutaneous prick test with shrimp extract was markedly positive. He later ingested shrimp casserole to avoid insulting a girl friend despite knowledge of his sensitivity to this food. Pruritus, generalized urticaria, swelling of the face and neck, dyspnea, dysphagia, laryngeal stridor, weakness, and dizziness developed immediately. Case A 5-month-old with reactions which invariably followed ingestion of pasteurized but otherwise uncooked milk. Reactions were characterized by pallor, cyanosis, muscle flaccidity, and generalized urticaria.. On one occasion, milk was accidentally spilled on him; urticaria developed at all sites of contact. Further cutaneous testing was deferred. He tolerated milk in baked foods. Case A 49-year-old man with dyspnea, swelling of the face and oropharynx, pruritus, urticaria, and dyspnea which developed while he was ingesting a cereal mix. Angioedema of the face, generalized urticaria, cyanosis, and wheezing were present. Cutaneous prick tests were positive with the specific lot of cereal mix which the patient was ingesting. Cutaneous tests with individual ingredients of the cereal mix were negative. The reaction is attributed to the specific lot of cereal mix and may have been caused by a contaminant. Case 10 A 39-year-old with dizziness, dyspnea, wheezing, generalized pruritus, and swelling of the face and oropharynx. Positive findings included rhinorrhea, lacrimation, generalized urticaria, and angioedema of the face and oropharynx. Partially cooked garbanzo bean (chick-pea) was ingested immediately prior to his reaction. A cutaneous prick test with this food was positive. He tolerated well-cooked beans. Case 11 A 33-year-old woman suddenly developed generalized pruritus, dyspnea, abdominal "cramps," nausea, and dizziness while eating a meal. Physical findings included generalized urticaria, angioedema of face and oropharynx, and wheezing. Tangerine was among the foods ingested before the reaction. A cutaneous prick test with fresh tangerine juice was positive. She subsequently ingested lemonade and fresh orange without adverse effect. Cutaneous tests with fresh orange juice were negative. Case A 37-year-old man with adverse effects to salicylsalicylic acid and acetylsalicylic acid. Case A 34-year-old male physician experienced within 20 minutes of ingestion of demethylchlortetracycline, headache, transient syncope, dyspnea, "tightness in the chest," angioedema of the face and hands, and generalized urticaria developed. Findings were generalized urticaria, periorbital edema, and edema of the hands and feet. Case A 22-year-old man with chest pain dyspnea, swelling of the face, generalized pruritus, and syncope developed while lie was ingesting a meal. Similar reactions had occurred 5 times previously. The causative antigen was undetermined, but all reactions followed ingestion of various foods containing a large mold content. (Golbert, 1969 ref.286 73)

Golbert, T, Patterson, R, Pruzansky, JJ. Systemic allergic reactions to ingested antigens. J Allergy 1969


Causes increase in variety of cancers in female rats. No conclusive evidence for human carcinogenicity. Allergic reactions: urticaria, asthma, and other allergic manifestations in some allergic individuals. Anaphylaxis. Angioedema. Bronchospasm. Hypotension. GIT symptoms. Hyperactivity controversial. Some studies, but not all, show a clear relationship. Link between those allergic to aspirin and tartrazine. Patients with the aspirin classic triad reaction (asthma, urticaria, and rhinitis) or anaphylactoid reactions may develop similar reactions to this dye. (Lockey 1977 ref.927 89) (Michaelsson 1973 ref.454 89) (Weber 1979 ref.456 89)

Weber RW, Hoffman M, Raine DA, Nelson HS. Incidence of bronchoconstriction due to aspirin, azo dyes, non-azo dyes and preservatives in a population of perennial asthmatics. J Allergy Clin Immunol 1979


Link between those allergic to aspirin and tartrazine. Patients with the aspirin classic triad reaction (asthma, urticaria, and rhinitis) or anaphylactoid reactions may develop similar reactions to this dye. (Bell 1990 ref.921 89) (Weber 1979 ref.456 89) (Lockey 1977 ref.927 89)

Bell RT, Fishman S. Eosinophilia from food dye added to enteral feeding. N Engl J Med 1990


Link between those allergic to aspirin and tartrazine. Patients with the aspirin classic triad reaction (asthma, urticaria, and rhinitis) or anaphylactoid reactions may develop similar reactions to this dye. (Lockey 1977 ref.927 89) (Michaelsson 1973 ref.454 89) (Weber 1979 ref.456 89)

Lockey SD Sr. Hypersensitivity to tartrazine (FD&C Yellow No.5) and other dyes and additives present in foods and pharmaceutical products. Ann Allergy 1977


In this study, 65 patients (35 females and 30 males mean age 38.5 yrs) affected by perennial asthma, underwent double blind challenge placebo controlled with food additives and acetyl salicylic acid (ASA). 62 % of the patients were positive to 1 additive, 22 % to two additives and 16% to three additives. 42% of them were positive to ASA, 18% to E 211 (Sodium benzoate), 15% to E127 (Erythrosine), 12 % to E 223 (Sodium metabisulphite), 10% to E 102 (Tartrazine) and 3% to 214-219 (Benzoates). The authors conclude that these results indicate that ASA is the most important additive in asthma due to food additives. (Pacor 2001 ref.4037 5)

Pacor M.L., Di Lorenzo G., Biasi D., Corrocher R. Prevalence of food additives in patients affected by mild and moderate perennial asthma [Poster] 8th International Symposium on Problems of Food Allergy, Venice. 2001


This report describes a 39-year-old female patient who presented with an intense allergic reaction and shock after ingesting sunflower seeds and simultaneously acetylsalicylic acid (ASA). Skin tests and CAP specific IgE demonstrated IgE-mediated sensitisation to sunflower seeds. When sunflower seeds were eaten alone, only discrete paresthesia of the oral mucosa occurred. Surprisingly, an oral challenge with ASA was well tolerated. The supplementary contribution of ASA to the allergic reaction was dose-dependent. (Moller 1996 ref.5110 8)

Moller R, Paul E. Acetylsalicylic acid as an augmentation factor in food allergy. [German] Hautarzt 1996


A 45-year-old woman developed chronic urticaria anaphylactoid reactions after (1) ingestion of coffee and (2) taking an analgesic drug. Prick testing in the patient and passive cutaneous anaphylaxis with coffee extract in the monkey Macacus nemestrinus were positive. With regard to further prick tests and oral provocation tests there is conclusive evidence that anaphylactic hypersensitivity to coffee was co-existing with idiosyncrasy to acetylsalicylic acid, indomethacne, metamizole (dipyrone), and caffeine. (Przybilla 1983 ref.9620 5)

Przybilla B, Ring J, Burg G. Anaphylaxis following ingestion of coffee, chronic urticaria and analgesics idiosyncrasy. [German] Hautarzt 1983


A 23-year-old woman experienced generalized urticaria and loss of consciousness during walking after ingestion of wheat. Skin prick test and CAP-RAST were positive for gluten. An oral challenge test using 100g wheat was positive without exercise. The patient was given diagnosis of wheat allergy. In addition, not only exercise but also administration of 500mg aspirin were found to exacerbate her symptoms after the ingestion of wheat, suggesting that acetylsalicylic acid could be an augmentation factor in wheat allergy. (Fujita 2005 ref.13225 8)

Fujita H, Osuna H, Kanbara T, Inomata N, Ikezawa Z. Wheat anaphylaxis enhanced by administration of acetylsalicylic acid or by exercise. [Japanese] Arerugi 2005


A 25-year-old woman with wheeze, dyspnea, nasal obstruction, epiphora, and ear fullness occurring 30 minutes after the intake of 200 mg of ibuprofen and 100 mg of norfloxacin. The patient had kept 20 hamsters indoors and a dog outside for 1 year and a half. During the 9 months prior to admission, she had experienced nocturnal asthmatic symptoms, which were controlled by oral theophylline on an as-needed basis. Serum total IgE was 98 U/ml, and tests for specific IgE antibodies to hamster epithelium and dog epithelium were both positive (class 2). After removal of the hamsters from her home, the patient became asymptomatic without further medication, and her airway hyper-responsiveness was also alleviated. The diagnosis of aspirin-induced asthma was confirmed by single-blind oral challenge with 100 mg of ibuprofen. (Kawai 2000 ref.13942 8)

Kawai K, Shirai T, Suzuki K, Chida K, Nakamura H. Mild intermittent aspirin-induced asthma in a patient who became asymptomatic after removal of pet hamsters from home. [Japanese] Nihon Kokyuki Gakkai Zasshi 2000


This study reports on a 5-year-old girl who suffered from recurrent reactions accompanied by urticaria, angioedema, headaches, dyspnea, loss of consciousness, and abdominal pain that were not eradicated, but were instead exacerbated, by various treatments with antihistamines and intravenous corticosteroids. Her diet diary revealed that symptoms occurred after ingestion of colorful sweets such as candies and jellybeans. Open challenge tests with food additives and nonsteroidal anti-inflammatory drugs (NSAIDs) were performed after elimination of these items. Skin prick tests using additives and NSAIDs, which were dissolved in saline, and prick- prick tests using candies and jellybeans, were carried out. Open challenge tests with Tartrazine, brilliant blue, p-hydroxybenzoate, aspirin, lidocaine, theophylline and acetaminophen were positive, whereas skin prick tests using additives and NSAIDs and prick-prick tests using candies and jellybeans were all negative. Consequently, intolerance to azo dyes and NSAIDs such as aspirin was diagnosed. However, she appeared to react to multiple chemical odors such as those of cigarette smoke, disinfectant, detergent, cleaning compounds, perfume, and hairdressing, all while avoiding additives and NSAIDs. On the basis of her history and the neuro-ophthalmological abnormalities, a diagnosis of severe MCS was made and she was prescribed multiple vitamins and glutathione. (Naoko 2006 ref.14118 8)

Naoko Inomata, Hiroyuki Osuna, Hiroyuki Fujita, Toru Ogawa and Zenro Ikezawa Multiple chemical sensitivities following intolerance to azo dye in sweets in a 5-year-old girl. Allergol International 2006


A case of wheat allergy dramatically enhanced by aspirin in a dose-dependent manner. A 68-year-old man experienced recurrent episodes of generalized urticaria after eating foods that contained wheat for several years. Skin prick tests for wheat and water-soluble gluten extract was positive. Serum specific IgE were 0.78 and 0.55 UA/mL for wheat and gluten. Challenge tests, including wheat ingestion, drug intake, exercise, and a combination of these challenges, were conducted as a clinical procedure. In all combined challenges, aspirin was administered 1 hour before wheat ingestion, whereas exercise was challenged 1 hour after wheat ingestion. As a result, several wheals developed on the patient’s shoulders after ingestion of 100 g of wheat, whereas he had no symptoms after ingestion of 20 g of wheat, administration of 0.5 or 1.5 g of aspirin, or exercise alone. No symptoms occurred after ingestion of 20 g of wheat combined with 0.5 g of aspirin or exercise. Finally, 1.5 g of aspirin intake before ingestion of 20 g of wheat drastically induced generalized urticaria but did not induce any extracutaneous symptoms.

Nakamura K, Inomata N, Ikezawa Z. Dramatic augmentation of wheat allergy by aspirin in a dose-dependent manner. Ann Allergy Asthma Immunol 2006


A 30-year-old man was seen with generalized urticaria. He had been suffering with repeated episodes which were getting worse. On all occassions he had visited his mother-in-law on the day, or the day before, urticaria developed. A detailed food dairy and SPT for the foods ingested there, was unhelpful. Details of the recipes revealed that the mother-in-law had been adding acetyl-salicylic acid as a preservative to her house-canned fruits, berries and vegetables. Provocation test with this was positive. (Kurbacheva 2007 ref.20008 7)

Kurbacheva O, Zuberbier T. A visit to the mother in law - a hidden cause for urticaria. Allergy 2007


The prevalence of AI is approximately 0.3% to 0.9%, but AI is often overlooked. It can display a wide range of clinical pictures, such as acute asthma attacks, urticaria, angioedema, chronic rhinitis, myocardial ischemia, and anaphylactic shock. Regarding the pathogenesis of AI, modifications of eicosanoid metabolism are supposed to underlie AI, including aspirin-induced asthma and aspirin-induced urticaria. However, the pathogenesis of AI has not yet been clearly elucidated. Associations of several HLA alleles with subtypes of AI, such as aspirin-induced urticaria and aspirin-induced asthma, and single nucleotide polymorphisms in genes encoding enzymes involved in arachidonic acid metabolism have been shown. (Jenneck 2007 ref.20249 7)

Jenneck C, Juergens U, Buecheler M, Novak N. Pathogenesis, diagnosis, and treatment of aspirin intolerance. Ann Allergy Asthma Immunol 2007


Food-dependent exercise induced anaphylaxis (FDEIA) is a distinct form of food allergy induced by physical exercise. Symptoms are typically generalized urticaria and severe allergic reactions such as shock or hypotension. Whereas various food items are responsible for the development of FDEIA, wheat is reported to be the allergen with the highest frequency in Japan. Recently aspirin has been known to be an additional exacerbating factor. Skin tests and in vitro serum food-specific IgE assays are currently used, however their sensitivity and specificity are not always satisfactory. A challenge test consisting of ingestion of assumed food followed by intense physical exercise is the only reliable method to determine the causative food and to diagnose the disease. The challenge test is not always safe because in some cases the test induces an anaphylactic shock. So a reliable in vitro diagnostic method is necessary for the patients with FDEIA. We revealed that wheat omega-5 gliadin and high molecular weight glutenin subunit are major allergens in wheat-dependent exercise-induced anaphylaxis (WDEIA). A simultaneous detection of specific IgE to epitope sequences of both omega-5 gliadin and high molecular weight glutenin is found to achieve higher sensitivity and specificity compared with the in vitro serum food-specific IgE assays currently used for diagnosis of WDEIA. On the other hand, immunoreactive gliadins appeared in the sera of patients during the provocation test with both wheat-exercise and wheat-aspirin challenges in parallel with allergic symptoms. These findings suggest that FDEIA is IgE-mediated hypersensitivity reaction to foods and both exercise and aspirin facilitate allergen absorption from the gastrointestinal tract. (Morita 2007 ref.20811 7)

Morita E, Kunie K, Matsuo H. Food-dependent exercise-induced anaphylaxis… J Dermatol Sci 2007


Food-dependent exercise-induced anaphylaxis induced by low dose aspirin therapy. (Fujii 2008 ref.21383 2)

Fujii H, Kambe N, Fujisawa A, Kohno K, Morita E, Miyachi Y. Food-dependent exercise-induced anaphylaxis induced by low dose aspirin therapy. Allergol Int 2008


A 25-year-old white woman presented with anaphylaxis requiring resuscitation. She had ingested 2 capsules of Stacker 2, a dietary supplement promoted for weight loss, prior to experiencing her initial symptoms. Among other active ingredients, this product contains willow bark. Of significance is that this patient also reported a history of allergy to acetylsalicylic acid. (Boullata 2003 ref.22086 5)

Boullata JI, McDonnell PJ, Oliva CD. Anaphylactic reaction to a dietary supplement containing willow bark. Ann Pharmacother 2003


NSAIDs-including aspirin (ASA)-that inhibit cyclooxygenase (COX)-1 induce nonallergic hypersensitivity reactions consisting of attacks of rhinitis and asthma. Such reactions occur exclusively in a subset of asthmatic patients who also have underlying nasal polyps and chronic hyperplastic eosinophilic sinusitis. We now refer to their underlying inflammatory disease of the entire respiratory tract as aspirin-exacerbated respiratory disease. This review focuses on descriptions of these patients; methods available to diagnose ASA-exacerbated respiratory disease; the unique ability of all NSAIDs that inhibit COX-1 to cross-react with ASA; lack of cross-reactivity with selective COX-2 inhibitors; an update on pathogenesis; and current thoughts about treatment, including ASA desensitization and daily ingestion of ASA itself. (Stevenson 2009 ref.23318 7)

Stevenson DD. Aspirin sensitivity and desensitization for asthma and sinusitis. Curr Allergy Asthma Rep 2009


A case of food-dependent exercise-induced anaphylaxis due to ingestion of peach. An 11-year-old boy experienced anaphylactic symptoms (dyspnea, pruritus, diffuse erythematous rash) during exercise after having had lunch. He ate peach approximately 2 hours before playing football. Similar symptoms closely related to exercise had been experienced 2 months earlier. 2.5 hours after eating peach, but exercise alone had never generated a reaction. Total serum IgE was1070 U/mL and peach-specific IgE 8.08 kUA/mL. Open-labeled oral challenge tests, which were performed using 50 g (wet weight) of peach, failed to induce any allergic reactions. He showed no symptoms after ingestion of the peach, and a 20-minute treadmill test was performed. Sixty minutes after food intake, after ingestion of the peach challenge, followed by exercise, led to mild pruritus and small urticaria on the left arm but no change in his lung function. He was given 500 mg of oral aspirin followed by peach 30 minutes later and a treadmill test 6 minutes after peach intake. Aspirin and peach induced anaphylactic reactions (dyspnea, pruritus, diffuse erythematous rash). Aspirin loading did not induce an allergic reaction. (Sato 2009 ref.23857 7)

Sato S, Nagao R, Hujioka T, Suzuki K, Tsuyuki K, Hoshika A. A case of food-dependent exercise-induced anaphylaxis due to ingestion of peach. J Investig Allergol Clin Immunol 2009


Three patients who developed urticaria while taking an enteric formulation of aspirin, confirmed on a second exposure. The patients did not exhibit any underlying history of atopy. Two of the patients were able to tolerate a soluble formulation. These symptoms might be caused by pharmaceutical excipients, present in very small amounts in the enteric coating, rather than the active ingredient acetylsalicylate. (Hebron 2009 ref.24624 7)

Hebron BS, Hebron HJ. Aspirin sensitivity: acetylsalicylate or excipients. Intern Med J 2009


This review focuses on aspirin-exacerbated asthma (AEA). The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. Although AEA affects adults and children with physician-diagnosed asthma, in some cases there is no history of asthma and AEA often goes unrecognized and underdiagnosed. (Varghese 2008 ref.25641 2)

Varghese M, Lockey RF. Aspirin-exacerbated asthma. Allergy Asthma Clin Immunol 2008


A 29-year-old woman had an episode of urticaria at the age of 17 while exercising after eating fried cuttlefish. For years thereafter, she experienced several episodes of urticaria after eating seafood. At the age of 29, she ate grilled seafood, including cuttlefish for supper after taking loxoprofen for lumbago. One hour later, she developed generalized urticaria accompanied by nausea, abdominal pain, swelling of the lips, and dyspnea while walking. Specific IgE was negative for all kinds of foods, including cuttlefish. Skin prick test was positive for raw and cooked cuttlefish. A provocation test of cuttlefish resulted only in slight itching of the oral mucosa. The combination of cuttlefish and 1.5 g of aspirin resulted in generalized urticaria. She was diagnosed with food-dependent exercise-induced anaphylaxis (FDEIA) caused by cuttlefish. These results indicate that in provocation tests for the diagnosis of FDEIA, allergic reactions could be enhanced by aspirin in a dose-dependent manner. (Nakamura 2010 ref.25717 2)

Nakamura K, Inomata N, Okawa T, Maeda N, Kirino M, Shiomi K, Ikezawa Z. A case of food-dependent exercise-induced anaphylaxis diagnosed by the provocation test with cuttlefish after the pretreatment with 1.5 g of aspirin. [japanese] Arerugi 2010


A case of chlorpheniramine maleate-induced hypersensitivity with aspirin intolerance. (Kim 2011 ref.27614 8)

Kim MH, Lee SM, Lee SH, Kwon HS, Kim SH, Cho SH, Min KU, Kim YY, Chang YS. A case of chlorpheniramine maleate-induced hypersensitivity with aspirin intolerance. Allergy Asthma Immunol Res 2011


Aspirin as a cause of pancreatitis in patients with aspirin-exacerbated respiratory disease. (Stevenson 2012 ref.27732 7)

Stevenson DD, White AA, Simon RA. Aspirin as a cause of pancreatitis in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 2012


The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Eighty-one children with a history of CSU were enrolled over a 3-year period. Nearly a quarter of children and adolescents with CSU were hypersensitive to aspirin. Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P < 0.016, P = 0.024, respectively). SBPCPTs with aspirin revealed that 14 of 58 patients (24%) with CPU and one of 10 patients with CRU (10%) were aspirin hypersensitive. Aspirin hypersensitivity rate was 26.5% in patients <12 years of age. All of the 15 aspirin-hypersensitive patients (aged between 6.6 and 17.4 years), except for three, experienced an unequivocal angioedema of the lips as a positive reaction in SBPCPT. (Cavkaytar 2015 ref.30441 3)

Cavkaytar O, Arik YE, Buyuktiryaki B, Sekerel BE, Sackesen C, Soyer OU. Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria. Allergy 2015


DRESS syndrome developed related to acetylsalicylic acid use. (Terlemez 2016 ref.31845 7)

Terlemez S, Demir F, Bulut Y, Carti O, Gokdogan D, Tokgoz Y, Yenigun A. DRESS syndrome developed related to acetylsalicylic acid use. Pediatr Allergy Immunol 2016


Current knowledge and management of hypersensitivity to aspirin and nsaids. (Laidlaw 2017 ref.32844 7)

Laidlaw TM, Cahill KN. Current knowledge and management of hypersensitivity to aspirin and nsaids. J Allergy Clin Immunol Pract 2017


Non-Immune Reactions:

Hyperactivity remains controversial. Gastric irritation, ulceration. Should be avoided if alcohol or caffeine has been taken. Tinnitus (ringing in ears) at toxic doses. Blood in stool from gastric erosion. Metabolic acidosis. Reyes syndrome. Skin irritation. Eriksson found a correlation between acetylsalicylic acid intolerance and sensitivity to some foods, e.g., nuts, strawberry, almond, green pepper, hip, chocolate, egg, cabbage, milk and wine. Exacerbation of asthma in a steroid-dependant individual. (Chafee 1967 ref.3025 3) 5 types of pseudo allergic and allergic reactions to aspirin and nonsteroidal anti-inflammitory drugs have been identified. (Stevenson 2000 ref.3688 7)

Reorganization process. Data in process of being reorganized. Editorial staff 2014


Eriksson found a correlation between acetylsalicylic acid intolerance and sensitivity to some foods, e.g., nuts, strawberry, almond, green pepper, chocolate, egg, cabbage, milk and wine. (Eriksson 1978 ref.1247 7)

Eriksson NE. Food sensitivity reported by patients with asthma and hay fever. Allergy 1978


Swain et al. suggested (Swain 1985 ref.226 78) that a normal mixed Western diet provides 72-1448 pmol (10-200 mg) of natural salicylates, and 17 pmol (3 mg) acetylsalicylate daily. This study measured levels of total salicylates and acetylsalicylate in 30 foods using a specific and sensitive HPLC method with fluorescence detection. Levels of total salicylate were 10-100 times lower than published previously: the authors found total salicylate levels of 0-0.7 umol/100 g in vegetables and fruits, and 2-20 umol/100 g in herbs and spices. Levels of acetylsalicylate were lower than the limit of detection in all foods. Based on these results, the authors estimate that a Western diet provides about 0-15 umol/day of total salicylates. The authors conclude that levels of total salicylates and acetylsalicylate in diets are low, and probably insufficient to affect disease risk. (Janssen 1997 ref.3179 8)

Janssen PL, Katan MB, van Staveren WA, Hollman PC, Venema DP Acetylsalicylate and salicylates in foods. Cancer Lett 1997



No Records


CCS: Proximal

No Panallergen CCS

CCS: Similar allergens

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Allergy Advisor - Zing Solutions

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Allergy Advisor  - Food Additive and Preservative Allergy and Intolerance Database