Exercise induced anaphylaxis
Question:
4/21/2025
I recently saw a 29-year-old patient who has had longstanding exercise-induced anaphylaxis (since age 13). She denies any episodes that were not provoked by exercise. She followed with an allergist for years, just moved, and established care with me. (I see a previous post inquiring about labor/childbirth and I report that interestingly, although she has anaphylaxis from even very light aerobic exercise, my patient was pre-medicated and tolerated labor/childbirth without any problems). She was evaluated multiple times for food sensitizations, including skin tests and serum IgE which included omega -5 -gliadin IgE and alpha-gal IgE. She reports that she consistently had anaphylaxis with exercise on a completely empty stomach, no NSAID or drug exposures, so it does not seem as though there is any food or drug dependent component, and she is not affected by heat or cold.
She tolerates yoga but is becoming frustrated with inability to exercise and would like to trial some type of aerobic exercise again to improve her fitness and lose weight. We discussed biologic therapy, and she is considering this. For now, we have initiated daily high dose antihistamine therapy (H1 and H2) and montelukast.
Based upon the literature I’ve reviewed, it appears that less vigorous exercise is possibly safer, and that walking or cycling as opposed to running may be less likely to precipitate anaphylaxis. Does this seem correct? I am wondering if there is any evidence to suggest that some type “desensitization” to exercise is possible? Is anyone aware of a successful “protocol” for this?
Answer:
Exercise-induced anaphylaxis (EIA) is rare and has been described at all levels of physical exertion. As you know most cases are food dependent. While wheat (omega -5 -gliadin) is most common, many foods have been identified, such as shellfish, legumes, tree nuts, tomato, carrot and celery. It appears that you have adequately ruled out food as a co-factor. Other reported co-factors include cold exposure, drinking cold beverages, alcohol, NSAIDs and possibly stress.
If you have not already, measure the basal tryptase when she is asymptomatic and then repeat tryptase within three hours of a symptomatic event. Measuring mast cell markers, such as spot urine LTE4, PGD2 and n-methylhistamine may also be helpful. If basal tryptase is >6.5, consider measuring high sensitivity PCR for TPSAB1 gene to assess for hereditary alpha tryptasemia. In patients with recurrent anaphylaxis, I often measure high sensitivity PCR D816V to assess systemic mastocytosis, regardless of the tryptase level.
An exercise challenge test may be helpful to assess your patient. This test can be carried out on a treadmill or an exercise bicycle in a manner like a graded exercise stress test.
I agree that she might benefit from omalizumab. There are several case reports of successful treatment of EIA with omalizumab. (1,2,3) Exercising with a partner would be recommended and of course always have self-administered epinephrine available.
I am unaware of a desensitization protocol for EIA.
1) Jiang N, Xiang L, Huang H, Zhang X. The management of exercise-induced anaphylaxis in a Chinese child with biologics: a case report. Front Allergy. 2024 Sep 19;5:1453873. PMID: 39364293; PMCID: PMC11446895.
2) Jones JD, Marney SR, Jr, Fahrenholz JM. Idiopathic anaphylaxis successfully treated with omalizumab. Ann Allergy Asthma Immunol 101:550–551, 2008. [DOI] [PubMed] [Google Scholar]
3) Christensen MJ, Bindslev-Jensen C. Successful treatment with omalizumab in challenge confirmed exercise-induced anaphylaxis. J Allergy Clin Immunol Pract 5:204–206, 2017.
Jeffrey G. Demain, MD, FAAAAI