DIAGNOSIS AND MANAGEMENT OF EXERCISE-INDUCED ANAPHYLAXIS: A LITERATURE REVIEW
Abstract
Background: Exercise-induced anaphylaxis (EIA) is a rare, potentially life-threatening allergic reaction triggered by physical activity, with food-dependent (FDEIA) and food-independent forms. Understanding its pathophysiology, triggers, and co-factors is essential for accurate diagnosis and prevention.
Aim: To summarize current evidence on the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of EIA.
Methodology: A literature review was conducted using PubMed and Google Scholar.
Results: EIA accounts for 2.3-5% of anaphylaxis cases. It is mediated by IgE-triggered mast cell degranulation, with exercise altering gastrointestinal permeability, osmolarity, and pH, thereby lowering the threshold for allergic reactions. Common triggers include wheat, shellfish, and nuts, with co-factors such as NSAIDs, alcohol, and environmental extremes. Diagnosis is based on detailed history, targeted allergy testing, and, when needed, supervised exercise challenges. Management involves immediate epinephrine administration for acute episodes and long-term prevention through trigger avoidance, co-factor management, and patient education.
Conclusions: EIA is an under-recognized but preventable cause of severe allergic reactions. Early recognition, appropriate diagnostic work-up, and a personalized management plan allow most patients to continue safe physical activity.
References
Maulitz, R., Pratt, D., & Schocket, A. (1979). Exercise-induced anaphylactic reaction to shellfish. Journal of Allergy and Clinical Immunology, 63(6), 433–434. https://doi.org/10.1016/0091-6749(79)90218-5
Minty, B. (2017). Food-dependent exercise-induced anaphylaxis. Canadian Family Physician / Médecin de famille canadien, 63(1), 42–43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5257219
Geller, M. (2020). Clinical management of exercise-induced anaphylaxis and cholinergic urticaria. Journal of Allergy and Clinical Immunology: In Practice, 8(7), 2209–2214. https://doi.org/10.1016/j.jaip.2020.01.025
Ansley, L., Bonini, M., Delgado, L., Del Giacco, S. R., Du Toit, G., Khaitov, M., ... & Carlsen, K. H. (2015). Pathophysiological mechanisms of exercise‐induced anaphylaxis: An EAACI position statement. Allergy, 70(10), 1212–1221. https://doi.org/10.1111/all.12677
Feldweg, A. M. (2017). Food-dependent, exercise-induced anaphylaxis: Diagnosis and management in the outpatient setting. Journal of Allergy and Clinical Immunology: In Practice, 5(2), 283–288. https://doi.org/10.1016/j.jaip.2016.11.022
Giannetti, M. P. (2018). Exercise-induced anaphylaxis: Literature review and recent updates. Current Allergy and Asthma Reports, 18(12), 72. https://doi.org/10.1007/s11882-018-0830-6
Fiedler, E.-M., Zuberbier, T., & Worm, M. (2002). A combination of wheat flour, ethanol, and food additives inducing FDEIA. Allergy, 57(11), 1090–1091. https://doi.org/10.1034/j.1398-9995.2002.23836_12.x
Povesi Dascola, C., & Caffarelli, C. (2012). Exercise-induced anaphylaxis: A clinical view. Italian Journal of Pediatrics, 38(1), 43. https://doi.org/10.1186/1824-7288-38-43
Castells, M. C., Horan, R. F., & Sheffer, A. L. (2003). Exercise-induced anaphylaxis. Current Allergy and Asthma Reports, 3(1), 15–21. https://doi.org/10.1007/s11882-003-0005-x
Carlisle, A., & Lieberman, J. A. (2024). Getting in shape: Updates in exercise anaphylaxis. Current Allergy and Asthma Reports, 24(11), 631–638. https://doi.org/10.1007/s11882-024-01176-4
Barg, W., Medrala, W., & Wolanczyk-Medrala, A. (2011). Exercise-induced anaphylaxis: An update on diagnosis and treatment. Current Allergy and Asthma Reports, 11(1), 45–51. https://doi.org/10.1007/s11882-010-0150-y
Srisuwatchari, W., Kanchanaphoomi, K., Nawiboonwong, J., Thongngarm, T., & Sompornrattanaphan, M. (2023). Food-dependent exercise-induced anaphylaxis: A distinct form of food allergy—An updated review of diagnostic approaches and treatments. Foods, 12(20), 3768. https://doi.org/10.3390/foods12203768
Asaumi, T., Yanagida, N., Sato, S., Shukuya, A., Nishino, M., & Ebisawa, M. (2016). Provocation tests for the diagnosis of food‐dependent exercise‐induced anaphylaxis. Pediatric Allergy and Immunology, 27(1), 44–49. https://doi.org/10.1111/pai.12489
Yano, H., Kato, Y., & Matsuda, T. (2002). Acute exercise induces gastrointestinal leakage of allergen in lysozyme-sensitized mice. European Journal of Applied Physiology, 87(4–5), 358–364. https://doi.org/10.1007/s00421-002-0653-x
Lindinger, M. I., & Grudzien, S. P. (2003). Exercise‐induced changes in plasma composition increase erythrocyte Na+, K+‐ATPase, but not Na+–K+–2Cl− cotransporter activity to stimulate net and unidirectional K+ transport in humans. Journal of Physiology, 553(3), 987–997. https://doi.org/10.1113/jphysiol.2003.052860
Nguyen, S. M. T., Rupprecht, C. P., Haque, A., Pattanaik, D., Yusin, J., & Krishnaswamy, G. (2021). Mechanisms governing anaphylaxis: Inflammatory cells, mediators, endothelial gap junctions and beyond. International Journal of Molecular Sciences, 22(15), 7785. https://doi.org/10.3390/ijms22157785
Niggemann, B., & Beyer, K. (2014). Factors augmenting allergic reactions. Allergy, 69(12), 1582–1587. https://doi.org/10.1111/all.12532
Motomura, C., Nakamura, K., Kudo, K., Takahashi, T., & Matsuo, H. (2017). Aspirin is an enhancing factor for food‐dependent exercise‐induced anaphylaxis in children. Clinical and Experimental Allergy, 47(11), 1497–1500. https://doi.org/10.1111/cea.13026
Versluis, A., Van Os‐Medendorp, H., Kruizinga, A. G., Blom, W. M., Houben, G. F., & Knulst, A. C. (2016). Cofactors in allergic reactions to food: Physical exercise and alcohol are the most important. Immunity, Inflammation and Disease, 4(4), 392–400. https://doi.org/10.1002/iid3.120
Jo, E.-J., Kim, M. Y., Choi, Y. S., Lee, S. Y., Kim, Y. S., & Park, H. S. (2012). Food-dependent exercise-induced anaphylaxis occurred only in a warm but not in a cold environment. Asia Pacific Allergy, 2(2), 161–164. https://doi.org/10.5415/apallergy.2012.2.2.161
Casale, T. B., Keahey, T. M., & Kaliner, M. (1986). Exercise-induced anaphylactic syndromes: Insights into diagnostic and pathophysiologic features. JAMA, 255(15), 2049–2053. https://pubmed.ncbi.nlm.nih.gov/3514973
Volcheck, G. W., & Li, J. T. C. (1997). Exercise-induced urticaria and anaphylaxis. Mayo Clinic Proceedings, 72(2), 140–147. https://doi.org/10.4065/72.2.140
Kleiman, J., & Ben-Shoshan, M. (2014). Food-dependent exercise-induced anaphylaxis with negative allergy testing. BMJ Case Reports, 2014, bcr2013202057. https://doi.org/10.1136/bcr-2013-202057
Mohamed, S., Thalappil, S., & Mohamed Ali, R. (2024). A case report of food-dependent exercise-induced anaphylaxis (FDEIA) treated with omalizumab. Frontiers in Allergy, 5, 1472320. https://doi.org/10.3389/falgy.2024.1472320
Beck, S. C., Wilding, T., Buka, R. J., Baretto, R. L., Huissoon, A. P., & Krishna, M. T. (2019). Biomarkers in human anaphylaxis: A critical appraisal of current evidence and perspectives. Frontiers in Immunology, 10, 494. https://doi.org/10.3389/fimmu.2019.00494
Beyens, M., Toscano, A., Ebo, D., Gülen, T., & Sabato, V. (2023). Diagnostic significance of tryptase for suspected mast cell disorders. Diagnostics, 13(24), 3662. https://doi.org/10.3390/diagnostics13243662
Romano, A., Di Fonso, M., Giuffreda, F., Palma, R., & Artesani, M. C. (1995). Diagnostic work‐up for food‐dependent, exercise‐induced anaphylaxis. Allergy, 50(10), 817–824. https://doi.org/10.1111/j.1398-9995.1995.tb05055.x
Dohi, M., Suko, M., Sugiyama, H., Yamashita, T., Kato, M., & Nakagawa, T. (1991). Food-dependent, exercise-induced anaphylaxis: A study on 11 Japanese cases. Journal of Allergy and Clinical Immunology, 87(1), 34–40. https://doi.org/10.1016/0091-6749(91)90210-F
Fiocchi, A., Mirri, G. P., Santini, I., Bernardo, L., Ottoboni, F., & Riva, E. (1997). Exercise-induced anaphylaxis after food contaminant ingestion in double-blinded, placebo-controlled, food-exercise challenge. Journal of Allergy and Clinical Immunology, 100(3), 424–425. https://doi.org/10.1016/S0091-6749(97)70258-6
Dribin, T. E., Waserman, S., & Turner, P. J. (2023). Who needs epinephrine? Anaphylaxis, autoinjectors, and parachutes. Journal of Allergy and Clinical Immunology: In Practice, 11(4), 1036–1046. https://doi.org/10.1016/j.jaip.2023.02.002
Hearrell, M., & Anagnostou, A. (2020). Diagnosis and management of anaphylaxis. Journal of Food Allergy, 2(1), 64–68. https://doi.org/10.2500/jfa.2020.2.200001
Soyer, O., & Sekerel, B. (2008). Food-dependent exercise-induced anaphylaxis or exercise-induced anaphylaxis? Allergologia et Immunopathologia, 36(4), 242–243. https://doi.org/10.1157/13127050
Christensen, M. J., Eller, E., Mortz, C. G., Brockow, K., & Bindslev-Jensen, C. (2019). Wheat-dependent cofactor-augmented anaphylaxis: A prospective study of exercise, aspirin, and alcohol efficacy as cofactors. Journal of Allergy and Clinical Immunology: In Practice, 7(1), 114–121. https://doi.org/10.1016/j.jaip.2018.06.018
Kulthanan, K., Tuchinda, P., Chularojanamontri, L., & Srisawat, C. (2022). Food-dependent exercise-induced wheals, angioedema, and anaphylaxis: A systematic review. Journal of Allergy and Clinical Immunology: In Practice, 10(9), 2280–2296. https://doi.org/10.1016/j.jaip.2022.06.008
Pravettoni, V., & Incorvaia, C. (2016). Diagnosis of exercise-induced anaphylaxis: Current insights. Journal of Asthma and Allergy, 9, 191–198. https://doi.org/10.2147/JAA.S109105
Morita, E., Kunie, K., & Matsuo, H. (2007). Food-dependent exercise-induced anaphylaxis. Journal of Dermatological Science, 47(2), 109–117. https://doi.org/10.1016/j.jdermsci.2007.03.004
Benhamou, A. H., Vanini, G., Lantin, J. P., & Eigenmann, P. A. (2007). Antihistamine and sodium cromoglycate medication for food cold water exercise‐induced anaphylaxis. Allergy, 62(12), 1471–1472. https://doi.org/10.1111/j.1398-9995.2007.01484.x
Peroni, D. G., Piacentini, G. L., Piazza, M., Cametti, E., & Boner, A. L. (2010). Combined cetirizine–montelukast preventive treatment for food-dependent exercise-induced anaphylaxis. Annals of Allergy, Asthma & Immunology, 104(3), 272–273. https://doi.org/10.1016/j.anai.2009.12.002
Choi, J. H., Lee, H. B., Ahn, I. S., Park, C. W., & Lee, C. H. (2009). Wheat-dependent, exercise-induced anaphylaxis: A successful case of prevention with ketotifen. Annals of Dermatology, 21(2), 203. https://doi.org/10.5021/ad.2009.21.2.203
Gon, Y., Maruoka, S., & Mizumura, K. (2022). Omalizumab and IgE in the control of severe allergic asthma. Frontiers in Pharmacology, 13, 839011. https://doi.org/10.3389/fphar.2022.839011
Sugimura, T., Matsuo, H., Kaneko, S., Yokozeki, H., & Morita, E. (2009). Effect of oral sodium cromoglycate in two children with food-dependent exercise-induced anaphylaxis (FDEIA). Clinical Pediatrics, 48(9), 945–950. https://doi.org/10.1177/0009922809337528
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