Working Diagnosis:
Exercise-induced (cholinergic) urticaria (“ChoIU”) with features of exercise-induced anaphylaxis (“EIA”)

Treatment:
Patient was referred to Allergy and Immunology. She was initiated on maximum dose fexofenadine (360 mg BID) and prescribed albuterol and an epinephrine pen to use with cardiovascular exercise.

Outcome:
The athlete reported improvement of symptoms with treatment (360 mg fexofenadine BID) and was able to continue distance running. She was instructed to carry an epinephrine pen for all cardiovascular exercise.

Author's Comments:
Exercise-induced anaphylaxis and cholinergic urticaria are conditions that occur in response to physical exertion. The pathophysiology for both conditions is not fully understood but are thought to be IgE mediated type I hypersensitivities. It is important to recognize these symptoms early in the athlete population as these two conditions represent a continuum of symptomology. Exercise-induced anaphylaxis can become quickly life-threatening with the speed at which laryngeal inflammation occurs during exercise. The diagnosis for these conditions is based heavily on clinical history and physical exam. For cholinergic urticaria, second-generation antihistamines are the mainstay of treatment (such as fexofenadine 360mg BID or cetirizine 10-20mg BID). If there is a concern for exercise-induced anaphylaxis, an epinephrine autoinjector should be prescribed for the athlete to have with them during all cardiovascular exercise. Additionally, if respiratory symptoms are present, an albuterol inhaler can provide symptomatic relief. In refractory cases, omalizumab can be tried with some success reported in the literature (typically dosed every 2-4 weeks at 75-600mg based on IgE levels).

Editor's Comments:
Cholinergic urticaria (ChoIU) and exercise-induced anaphylaxis (EIA) are both physical
allergies caused by mast cell degranulation. ChoIU can be triggered by increases in
core body temperature due to exercise, hot baths, or emotional stress. EIA symptoms
are specifically due to physical exertion and may or may not be food dependent. Since
both conditions can be triggered by exercise, the morphological characteristics of the
resulting urticaria can help distinguish between the two. ChoIU results in small, punctate
wheals (1-3 mm) accompanied by intense pruritus and erythema. EIA is characterized
by larger urticarial wheals, generalized pruritus, and potentially life-threatening
symptoms such as angioedema. With regards to treatment, avoiding known triggers is
crucial for both conditions. This includes avoiding exercise during extreme
temperatures, abstaining from food or medications that may function as cofactors (e.g.
wheat), and modifying exercise routines. Induction of tolerance through regular exercise
can also be considered. Pharmacologic management includes antihistamines and mast
cell stabilizers, with prophylactic use indicated for long-term care. If symptoms are
severe, injectable epinephrine, airway maintenance, and cardiovascular support may be
necessary.

References:
Brockow, K., Feldweg, A., Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis. In: UpToDate TePas E (Ed), Wolters Kluwer. (Accessed on March 7, 2024.)
Gal, K. (2023, February 19). Mast cell stabilizing foods. Dr.BeckyCampbell. https://drbeckycampbell.com/mast-cell-stabilizing-foods
Geller M. Clinical Management of Exercise-Induced Anaphylaxis and Cholinergic Urticaria. J Allergy Clin Immunol Pract. 2020 Jul-Aug;8(7):2209-2214. doi: 10.1016/j.jaip.2020.01.025. PMID: 32620433.
Gonzalez et al. 2017. Exercise-induced anaphylaxis DermNet. https://dermnetnz.org/topics/exercise-induced-anaphylaxis
Sheffer AL, Soter NA, McFadden ER Jr, Austen KF. Exercise-induced anaphylaxis: a distinct form of physical allergy. J Allergy Clin Immunol. 1983 Mar;71(3):311-6. doi: 10.1016/0091-6749(83)90085-4. PMID: 6826991.
Sports Medicine Review. (2023, September 19). Exercise Induced Anaphylaxis: A Brief Review. https://www.sportsmedreview.com/blog/exercise-induced-anaphylaxis-a-brief-review
Sanchez-Borges M, Gonzalez-Aveledo L, Caballero-Fonseca F, Capriles-Hulett A. Review of Physical Urticarias and Testing Methods. Curr Allergy Asthma Rep. 2017 Aug;17(8):51. doi: 10.1007/s11882-017-0722-1. PMID: 28634900
Hosey, R. G., Carek, P. J., & Goo, A. (2001). Exercise-Induced Anaphylaxis and
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Nichols, A. W. (1992). Exercise-Induced Anaphylaxis and Urticaria. Clinics in
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