Appearance of food-dependent exercise-induced anaphylaxis as an inflammatory disease: a pediatric case report and differential diagnosis

Main Article Content

Antonio Scarcella
Simona Barni
Mattia Giovannini
Lucrezia Sarti
Giulia Liccioli
Erika Paladini
Leonardo Tomei
Sandra Trapani
Francesca Mori


anaphylaxis, exercise, food-dependent exercise-induced anaphylaxis, wheat-dependent exercise-induced anaphylaxis


Anaphylaxis is the most serious of all allergic reactions. Despite advances in the knowledge of anaphylaxis, its clinical manifestations continue to be under-recognized. Indeed, proper diagnosis of anaphylaxis is often missed, and the treatment is delayed. The underlying causes are still under investigation globally. Inflammation represents the cornerstone of pathophysiology of anaphylaxis. Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare clinical manifestation characterized by a chronological sequence in which food ingestion followed by physical exercise leads to anaphylaxis. Its mechanisms are yet to be fully explained. We report the case of a 14-year-old Chinese male who lost consciousness while undergoing physical activity at school. Several differential diagnoses were considered such as hypovolemic shock, septic shock, anaphylactic shock or neurological adverse event. Finally, the diagnosis of FDEIA was made. This case highlights the difficulties in diagnosing FDEIA and its management, especially when the clinical history is not complete and detailed.

Abstract 103 | PDF Downloads 118 HTML Downloads 10 XML Downloads 5


1. Turner PJ, Worm M, Ansotegui IJ, et al. Time to revisit the definition and clinical criteria for anaphylaxis? World Allergy Organ J. 2019;12:100066. 10.1016/j.waojou.2019.100066

2. Yu JE, Lin RY. The Epidemiology of anaphylaxis. Clin Rev Allergy Immunol. 2018;54:366–74. 10.1007/s12016-015-8503-x

3. Sicherer SH, Simons FER, Mahr TA, et al. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139(3):e20164006. 10.1542/peds.2016-4006

4. Cianferoni A, Muraro A. Food-induced anaphylaxis. Immunol Allergy Clin North Am. 2012;32:165–95. 10.1016/j.iac.2011.10.002

5. Toit G Du. Food-dependent exercise-induced anaphylaxis in childhood. Pediatr Allergy Immunol. 2007;18:455–63. 10.1111/j.1399-3038.2007.00599.x

6. Gupta RS. Anaphylaxis in the young adult population. Am J Med. 2014;127:S17–24. 10.1016/j.amjmed.2013.09.010

7. Tang R, Xu H-Y, Cao J, et al. Clinical characteristics of inpatients with anaphylaxis in China. Biomed Res Int. 2015;2015: 1–6. 10.1155/2015/429534

8. Riedel S. Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis. Diagn Microbiol Infect Dis. 2012;73:221–7. 10.1016/j.diagmicrobio.2012.05.002

9. Meisner M. Update on procalcitonin measurements. Ann Lab Med. 2014;34:263–73. 10.3343/alm.2014.34.4.263

10. Tang BM, Eslick GD, Craig JC, et al. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: Systematic review and meta-analysis. Lancet Infect Dis. 2007;7:210–7. 10.1016/S1473-3099(07)70052-X

11. Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: A systematic review and meta-analysis. Lancet Infect Dis. 2013;13:426–35. 10.1016/S1473-3099(12)70323-7

12. Kim YJ, Kang SW, Lee JH, et al. Marked elevation of procalcitonin level can lead to a misdiagnosis of anaphylactic shock as septic shock. Int J Infect Dis. 2015;37:93–4. 10.1016/j.ijid.2015.06.012

13. Hounoki H, Yamaguchi S, Taki H, et al. Elevated serum procalcitonin in anaphylaxis. J Antimicrob Chemother. 2013;68: 1689–90. 10.1093/jac/dkt076

14. Mann J, Cavallazzi R. Marked serum procalcitonin level in response to isolated anaphylactic shock. Am J Emerg Med. 2015;33:125.e5–125.e6. 10.1016/j.ajem.2014.05.053

15. Joo Shiang A. Elevated procalcitonin levels in anaphylaxis. Hong Kong J Emerg Med. 2020;27:241–4. 10.1177/1024907919825748

16. Nguyen SMT, Rupprecht CP, Haque A, et al. Mechanisms governing anaphylaxis: Inflammatory cells, mediators, endothelial gap junctions and beyond. Int J Mol Sci. 2021;22:7785. 10.3390/ijms22157785

17. Stone SF, Cotterell C, Isbister GK, et al. Elevated serum cytokines during human anaphylaxis: Identification of potential mediators of acute allergic reactions. J Allergy Clin Immunol. 2009;124:786–92.e4. 10.1016/j.jaci.2009.07.055

18. Maulitz R, Pratt D, Schocket A. Exercise-induced anaphylactic reaction to shellfish. J Allergy Clin Immunol. 1979;63:433–34. 10.1016/0091-6749(79)90218-5

19. Silveira LS, Antunes B de MM, Minari ALA, et al. Macrophage polarization: Implications on metabolic diseases and the role of exercise. Crit Rev Eukaryot Gene Expr. 2016;26: 115–32. 10.1615/CritRevEukaryotGeneExpr.2016015920

20. Allen J, Sun Y, Woods JA. Exercise and the Regulation of Inflammatory Responses. Prog Mol Biol Transl Sci. 2015;135:337-54 10.1016/bs.pmbts.2015.07.003

21. Hennigar SR, McClung JP, Pasiakos SM. Nutritional interventions and the IL-6 response to exercise. FASEB J. 2017;31: 3719–28. 10.1096/fj.201700080R

22. Peake JM, Neubauer O, Walsh NP, et al. Recovery of the immune system after exercise. J Appl Physiol. 2017;122: 1077–87. 10.1152/japplphysiol.00622.2016

23. Shaw DM, Merien F, Braakhuis A, et al. T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise. Cytokine. 2018;104:136–142. 10.1016/j.cyto.2017.10.001

24. Cerqueira É, Marinho DA, Neiva HP, et al. Inflammatory effects of high and moderate intensity exercise—A systematic review. Front Physiol. 2020;10:1550. 10.3389/fphys.2019.01550

25. Kim CW, Figueroa A, Park CH, et al. Combined effects of food and exercise on anaphylaxis. Nutr Res Pract. 2013;7:347. 10.4162/nrp.2013.7.5.347

26. Wu AYY. Drug allergy: Diagnosis and management. Hong Kong Pract. 2000;22:61–70.

27. Kounis NG. Coronary hypersensitivity disorder: The Kounis syndrome. Clin Ther. 2013;35:563–71. 10.1016/j.clinthera.2013.02.022

28. Giovannini M, Koniari I, Mori F, et al. Kounis syndrome: Towards a new classification. Int J Cardiol. 2021;341:13–14. 10.1016/j.ijcard.2021.04.018

29. Jayamali WD, Herath HMMTB, Kulathunga A. Myocardial infarction during anaphylaxis in a young healthy male with normal coronary arteries—Is epinephrine the culprit? BMC Cardiovasc Disord. 2017;17:237. 10.1186/s12872-017-0670-7

30. Shaver KJ, Adams C, Weiss SJ. Acute myocardial infarction after administration of low-dose intravenous epinephrine for anaphylaxis. CJEM. 2006;8:289–94. 10.1017/S1481803500013890

31. Cunnington C, McDonald JE, Singh RK. Epinephrine-induced myocardial infarction in severe anaphylaxis: Is nonselective β-blockade a contributory factor? Am J Emerg Med. 2013;31:759.e1–759.e2. 10.1016/j.ajem.2012.11.022

32. Ferry DR, Henry RL, Kern MJ. Epinephrine-induced myocardial infarction in a patient with angiographically normal coronary arteries. Am Heart J. 1986;111:1193–95. 10.1016/0002-8703(86)90023-2

33. Rubio Caballero JA, Oteo Domínguez JF, Maicas Bellido C, et al. An adrenaline-induced vasospasm as the form of presentation of variant angina. Rev Esp Cardiol. 1999;52: 273–6. 10.1016/S0300-8932(99)74911-0

34. Saff R, Nahhas A, Fink JN. Myocardial infarction induced by coronary vasospasm after self-administration of epinephrine. Ann Allergy. 1993;70:396–8.

35. Bilò MB, Martini M, Tontini C, et al. Idiopathic anaphylaxis. Clin Exp Allergy. 2019;49:942–52. 10.1111/cea.13402

36. Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13:100472. 10.1016/j.waojou.2020.100472

37. Keshavarz B, Platts-Mills TAE, Wilson JM. The use of microarray and other multiplex technologies in the diagnosis of allergy. Ann Allergy asthma Immunol. 2021;127(1):10–18. 10.1016/j.anai.2021.01.003

38. Heaps A, Carter S, Selwood C, et al. The utility of the ISAC allergen array in the investigation of idiopathic anaphylaxis. Clin Exp Immunol. 2014;177:483–90. 10.1111/cei.12334

39. Benito-Garcia F, Ansotegui IJ, Morais-Almeida M. Diagnosis and prevention of food-dependent exercise-induced anaphylaxis. Expert Rev Clin Immunol. 2019;15:849–56. 10.1080/1744666X.2019.1642747

40. Asaumi T, Ebisawa M. How to manage food-dependent exercise-induced anaphylaxis (FDEIA). Curr Opin Allergy Clin Immunol. 2018;18:243–7. 10.1097/ACI.0000000000000442

41. 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;108:1035–9. 10.1067/mai.2001.119914

42. Manabe T, Oku N, Aihara Y. Food-dependent exercise-induced anaphylaxis among junior high school students: A 14-year epidemiological comparison. Allergol Int. 2015;64:285–6. 10.1016/j.alit.2015.01.007

43. Manabe T, Oku N, Aihara Y. Food-dependent exercise-induced anaphylaxis in Japanese elementary school children. Pediatr Int. 2018;60:329–33. 10.1111/ped.13520