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Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis

Anna M Feldweg, MD
Section Editor
John M Kelso, MD
Deputy Editor
Elizabeth TePas, MD, MS


Exercise-induced anaphylaxis (EIAn) is a disorder in which anaphylaxis occurs in association with physical exertion. The clinical manifestations, theories of pathogenesis, evaluation, and diagnosis of EIAn and food-dependent, exercise-induced anaphylaxis (FDEIAn) will be reviewed here. The management and prognosis of EIAn and FDEIAn are discussed elsewhere. (See "Exercise-induced anaphylaxis: Management and prognosis" and "Food-induced anaphylaxis".)


Anaphylaxis, from any cause, is defined as a serious allergic or hypersensitivity reaction that is rapid in onset and may cause death [1,2]. The diagnostic criteria for anaphylaxis are reviewed in detail separately. (See "Anaphylaxis: Acute diagnosis", section on 'Diagnostic criteria'.)

The following terms are used in this topic review:

Exercise-induced anaphylaxis (EIAn) – EIAn is a disorder in which anaphylaxis occurs only in association with physical exertion.

Food-dependent, exercise-induced anaphylaxis (FDEIAn) – FDEIAn is a disorder in which symptoms develop only if exercise takes place within a few hours of eating and, in most cases, only if a specific food to which the patient is sensitized is eaten in the pre-exercise period. This definition has been used for several decades, although work in the pathophysiology of FDEIAn has raised the question of whether exercise is absolutely necessary for the development of symptoms. (See 'Theories of pathogenesis' below.)


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Literature review current through: Sep 2016. | This topic last updated: Jan 4, 2016.
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  1. Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006; 117:391.
  2. Sampson HA, Muñoz-Furlong A, Bock SA, et al. Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol 2005; 115:584.
  3. Romano A, Di Fonso M, Giuffreda F, et al. Food-dependent exercise-induced anaphylaxis: clinical and laboratory findings in 54 subjects. Int Arch Allergy Immunol 2001; 125:264.
  4. Maulitz RM, Pratt DS, Schocket AL. Exercise-induced anaphylactic reaction to shellfish. J Allergy Clin Immunol 1979; 63:433.
  5. Sheffer AL, Austen KF. Exercise-induced anaphylaxis. J Allergy Clin Immunol 1980; 66:106.
  6. Shadick NA, Liang MH, Partridge AJ, et al. The natural history of exercise-induced anaphylaxis: survey results from a 10-year follow-up study. J Allergy Clin Immunol 1999; 104:123.
  7. Ausdenmoore RW. Fatality in a teenager secondary to exercise-induced anaphylaxis. Pediatr Asthma Allergy Immunol 1991; 5:21.
  8. Noma T, Yoshizawa I, Ogawa N, et al. Fatal buckwheat dependent exercised-induced anaphylaxis. Asian Pac J Allergy Immunol 2001; 19:283.
  9. Drouet M, Sabbah A, Le Sellin J, et al. [Fatal anaphylaxis after eating wild boar meat in a patient with pork-cat syndrome]. Allerg Immunol (Paris) 2001; 33:163.
  10. Flannagan LM, Wolf BC. Sudden death associated with food and exercise. J Forensic Sci 2004; 49:543.
  11. Pérez-Rangel I, Gonzalo-Garijo MA, Pérez-Calderón R, et al. Wheat-dependent exercise-induced anaphylaxis in elderly patients. Ann Allergy Asthma Immunol 2013; 110:121.
  12. Dohi M, Suko M, Sugiyama H, et al. Food-dependent, exercise-induced anaphylaxis: a study on 11 Japanese cases. J Allergy Clin Immunol 1991; 87:34.
  13. Kano H, Juji F, Shibuya N, et al. [Clinical courses of 18 cases with food-dependent exercise-induced anaphylaxis]. Arerugi 2000; 49:472.
  14. Orhan F, Karakas T. Food-dependent exercise-induced anaphylaxis to lentil and anaphylaxis to chickpea in a 17-year-old boy. J Investig Allergol Clin Immunol 2008; 18:465.
  15. Sánchez-Borges M, Iraola V, Fernández-Caldas E, et al. Dust mite ingestion-associated, exercise-induced anaphylaxis. J Allergy Clin Immunol 2007; 120:714.
  16. Bito T, Kanda E, Tanaka M, et al. Cows milk-dependent exercise-induced anaphylaxis under the condition of a premenstrual or ovulatory phase following skin sensitization. Allergol Int 2008; 57:437.
  17. Beaudouin E, Renaudin JM, Morisset M, et al. Food-dependent exercise-induced anaphylaxis--update and current data. Eur Ann Allergy Clin Immunol 2006; 38:45.
  18. Asero R, Mistrello G, Roncarolo D, et al. Exercise-induced egg anaphylaxis. Allergy 1997; 52:687.
  19. Romano A, Scala E, Rumi G, et al. Lipid transfer proteins: the most frequent sensitizer in Italian subjects with food-dependent exercise-induced anaphylaxis. Clin Exp Allergy 2012; 42:1643.
  20. Pastorello EA, Farioli L, Stafylaraki C, et al. Wheat-dependent exercise-induced anaphylaxis caused by a lipid transfer protein and not by ω-5 gliadin. Ann Allergy Asthma Immunol 2014; 112:386.
  21. Hanakawa Y, Tohyama M, Shirakata Y, et al. Food-dependent exercise-induced anaphylaxis: a case related to the amount of food allergen ingested. Br J Dermatol 1998; 138:898.
  22. Brockow K, Kneissl D, Valentini L, et al. Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis. J Allergy Clin Immunol 2015; 135:977.
  23. Kidd JM 3rd, Cohen SH, Sosman AJ, Fink JN. Food-dependent exercise-induced anaphylaxis. J Allergy Clin Immunol 1983; 71:407.
  24. Aihara Y, Kotoyori T, Takahashi Y, et al. The necessity for dual food intake to provoke food-dependent exercise-induced anaphylaxis (FEIAn): a case report of FEIAn with simultaneous intake of wheat and umeboshi. J Allergy Clin Immunol 2001; 107:1100.
  25. Adachi A, Horikawa T, Shimizu H, et al. Soybean beta-conglycinin as the main allergen in a patient with food-dependent exercise-induced anaphylaxis by tofu: food processing alters pepsin resistance. Clin Exp Allergy 2009; 39:167.
  26. Wade JP, Liang MH, Sheffer AL. Exercise-induced anaphylaxis: epidemiologic observations. Prog Clin Biol Res 1989; 297:175.
  27. Harada S, Horikawa T, Ashida M, et al. Aspirin enhances the induction of type I allergic symptoms when combined with food and exercise in patients with food-dependent exercise-induced anaphylaxis. Br J Dermatol 2001; 145:336.
  28. Matsuo H, Morimoto K, Akaki T, et al. Exercise and aspirin increase levels of circulating gliadin peptides in patients with wheat-dependent exercise-induced anaphylaxis. Clin Exp Allergy 2005; 35:461.
  29. Fujii H, Kambe N, Fujisawa A, et al. Food-dependent exercise-induced anaphylaxis induced by low dose aspirin therapy. Allergol Int 2008; 57:97.
  30. Aihara M, Miyazawa M, Osuna H, et al. Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin administration on skin testing and provocation. Br J Dermatol 2002; 146:466.
  31. Eggleston PA, Kagey-Sobotka A, Proud D, et al. Disassociation of the release of histamine and arachidonic acid metabolites from osmotically activated basophils and human lung mast cells. Am Rev Respir Dis 1990; 141:960.
  32. Wolańczyk-Medrala A, Barg W, Radlińska A, et al. Food-dependent exercise-induced anaphylaxis-sequence of causative factors might be reversed. Ann Agric Environ Med 2010; 17:315.
  33. Aihara Y, Takahashi Y, Kotoyori T, et al. Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students. J Allergy Clin Immunol 2001; 108:1035.
  34. Du Toit G. Food-dependent exercise-induced anaphylaxis in childhood. Pediatr Allergy Immunol 2007; 18:455.
  35. Barg W, Wolanczyk-Medrala A, Obojski A, et al. Food-dependent exercise-induced anaphylaxis: possible impact of increased basophil histamine releasability in hyperosmolar conditions. J Investig Allergol Clin Immunol 2008; 18:312.
  36. Caminiti L, Passalacqua G, Vita D, et al. Food-exercise-induced anaphylaxis in a boy successfully desensitized to cow milk. Allergy 2007; 62:335.
  37. Pourpak Z, Ghojezadeh L, Mansouri M, et al. Wheat anaphylaxis in children. Immunol Invest 2007; 36:175.
  38. Longley S, Panush RS. Familial exercise-induced anaphylaxis. Ann Allergy 1987; 58:257.
  39. Grant JA, Farnam J, Lord RA, et al. Familial exercise-induced anaphylaxis. Ann Allergy 1985; 54:35.
  40. Sheffer AL, Tong AK, Murphy GF, et al. Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation. J Allergy Clin Immunol 1985; 75:479.
  41. Lewis J, Lieberman P, Treadwell G, Erffmeyer J. Exercise-induced urticaria, angioedema, and anaphylactoid episodes. J Allergy Clin Immunol 1981; 68:432.
  42. Sheffer AL, Soter NA, McFadden ER Jr, Austen KF. Exercise-induced anaphylaxis: a distinct form of physical allergy. J Allergy Clin Immunol 1983; 71:311.
  43. Oyefara BI, Bahna SL. Delayed food-dependent, exercise-induced anaphylaxis. Allergy Asthma Proc 2007; 28:64.
  44. Schwartz HJ. Elevated serum tryptase in exercise-induced anaphylaxis. J Allergy Clin Immunol 1995; 95:917.
  45. Sheffer AL, Austen KF. Exercise-induced anaphylaxis. J Allergy Clin Immunol 1984; 73:699.
  46. Casale TB, Bowman S, Kaliner M. Induction of human cutaneous mast cell degranulation by opiates and endogenous opioid peptides: evidence for opiate and nonopiate receptor participation. J Allergy Clin Immunol 1984; 73:775.
  47. Lin RY, Barnard M. Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis. Ann Allergy 1993; 70:475.
  48. Tharp MD, Thirlby R, Sullivan TJ. Gastrin induces histamine release from human cutaneous mast cells. J Allergy Clin Immunol 1984; 74:159.
  49. Yano H, Kato Y, Matsuda T. Acute exercise induces gastrointestinal leakage of allergen in lysozyme-sensitized mice. Eur J Appl Physiol 2002; 87:358.
  50. Oshima T, Miwa H, Joh T. Aspirin induces gastric epithelial barrier dysfunction by activating p38 MAPK via claudin-7. Am J Physiol Cell Physiol 2008; 295:C800.
  51. Lichtenberger LM, Zhou Y, Dial EJ, Raphael RM. NSAID injury to the gastrointestinal tract: evidence that NSAIDs interact with phospholipids to weaken the hydrophobic surface barrier and induce the formation of unstable pores in membranes. J Pharm Pharmacol 2006; 58:1421.
  52. Mastalerz L, Setkowicz M, Szczeklik A. Mechanism of chronic urticaria exacerbation by aspirin. Curr Allergy Asthma Rep 2005; 5:277.
  53. Palosuo K, Alenius H, Varjonen E, et al. A novel wheat gliadin as a cause of exercise-induced anaphylaxis. J Allergy Clin Immunol 1999; 103:912.
  54. Daengsuwan T, Palosuo K, Phankingthongkum S, et al. IgE antibodies to omega-5 gliadin in children with wheat-induced anaphylaxis. Allergy 2005; 60:506.
  55. Fukutomi Y, Itagaki Y, Taniguchi M, et al. Rhinoconjunctival sensitization to hydrolyzed wheat protein in facial soap can induce wheat-dependent exercise-induced anaphylaxis. J Allergy Clin Immunol 2011; 127:531.
  56. Fukutomi Y, Taniguchi M, Nakamura H, Akiyama K. Epidemiological link between wheat allergy and exposure to hydrolyzed wheat protein in facial soap. Allergy 2014; 69:1405.
  57. Loibl M, Schwarz S, Ring J, et al. Definition of an exercise intensity threshold in a challenge test to diagnose food-dependent exercise-induced anaphylaxis. Allergy 2009; 64:1560.
  58. Kleiman J, Ben-Shoshan M. Food-dependent exercise-induced anaphylaxis with negative allergy testing. BMJ Case Rep 2014; 2014.
  59. Guinnepain MT, Eloit C, Raffard M, et al. Exercise-induced anaphylaxis: useful screening of food sensitization. Ann Allergy Asthma Immunol 1996; 77:491.
  60. Hofmann SC, Fischer J, Eriksson C, et al. IgE detection to α/β/γ-gliadin and its clinical relevance in wheat-dependent exercise-induced anaphylaxis. Allergy 2012; 67:1457.
  61. Matsuo H, Dahlström J, Tanaka A, et al. Sensitivity and specificity of recombinant omega-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis. Allergy 2008; 63:233.
  62. Park HJ, Kim JH, Kim JE, et al. Diagnostic value of the serum-specific IgE ratio of ω-5 gliadin to wheat in adult patients with wheat-induced anaphylaxis. Int Arch Allergy Immunol 2012; 157:147.
  63. Romano A, Di Fonso M, Giuffreda F, et al. Diagnostic work-up for food-dependent, exercise-induced anaphylaxis. Allergy 1995; 50:817.
  64. Kaplan AP, Natbony SF, Tawil AP, et al. Exercise-induced anaphylaxis as a manifestation of cholinergic urticaria. J Allergy Clin Immunol 1981; 68:319.
  65. Casale TB, Keahey TM, Kaliner M. Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features. JAMA 1986; 255:2049.
  66. Morimoto K, Sanada S, Hara T, Hide M. [Two cases of food-dependent exercise-induced anaphylaxis difficult to evoke symptoms by provocation test]. Arerugi 2006; 55:1433.
  67. Ii M, Sayama K, Tohyama M, Hashimoto K. A case of cold-dependent exercise-induced anaphylaxis. Br J Dermatol 2002; 147:368.
  68. Wanderer AA, Hoffman HM. The spectrum of acquired and familial cold-induced urticaria/urticaria-like syndromes. Immunol Allergy Clin North Am 2004; 24:259.
  69. Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy 2008; 63:226.
  70. Schondorf R, Low PA. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia? Neurology 1993; 43:132.
  71. Johnson JN, Mack KJ, Kuntz NL, et al. Postural orthostatic tachycardia syndrome: a clinical review. Pediatr Neurol 2010; 42:77.
  72. Shibao C, Arzubiaga C, Roberts LJ 2nd, et al. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension 2005; 45:385.