Exercise-Induced Urticaria: When People are Allergic to Physical Activity

Imagine going for a run. The first mile feels great: energy rising, blood pumping. Until a rash creeps up, giving way to itchy, red welts, flushed skin, and hives. For people with such a condition—called exercise-induced urticaria—a jog can turn into a battle against their own immune system.

First described in the 1970s, exercise-induced urticaria is a relatively rare condition likely due to a sudden increase in the body’s core temperature.¹ Scientists propose that mast cell degranulation and a rise in plasma histamine levels are involved. In extreme cases, people may experience a systemic reaction where tissues beyond the skin are involved, such as anaphylaxis. The condition can be managed with a regimen of antihistamines and epinephrine administration if required.

Pathophysiology Underlying Exercise-Induced Urticaria and Anaphylaxis

Exercises such as running or strength training increase the body’s core temperature. This can result in blood rushing into the skin, carrying some immune cells with it. Indeed, histological studies from people who experienced such urticaria symptoms revealed increased neutrophils in the skin.²

Scientists hypothesize that an increase in body temperature triggers mast cell degranulation: a rapid release of bioactive mediators like histamines from the granules within the cells. Consistent with this, researchers observed increased serum histamine in people with this condition after exercising and proposed that mast cell degranulation after increased temperature is likely mediated by antibodies.³

“We [previously] thought that there were antibodies against the [immunoglobulin] receptor that sits on allergy cells like mast cells and basophils, that was being triggered to make the allergy cells explode and cause hives,” said Sarita Patil, a translational physician scientist who specializes in allergies at Massachusetts General Hospital.

However, she thinks that there are additional mechanisms involved in this process. “There's probably a lot of different ways that you can get to activating allergy cells accidentally,” she said. “And we are still working on it. We’re not there yet.”

Another working theory is that an increase in temperature activates the sympathetic nervous system, which is involved in the fight-or-flight response. This stimulates nerve fibers to release the neurotransmitter acetylcholine, leading to mast cell degranulation, and consequently secrete histamine.⁴

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Despite the condition being documented in the 1970s for the first time, scientists do not fully understand the exact mechanisms behind it. According to Patil, this is because it is difficult to study the condition, in part due to the variability of symptoms.

While most of her patients experience urticaria while they are exercising, some get a rash when they are done exercising and are cooling down, which is called cholinergic urticaria. For some, consuming certain foods and then exercising can result in breaking out into hives.⁵

“Exercise is actually what we call a cofactor in allergy, which is that it can lower your threshold for having a reaction,” explained Patil. “In other words, it can make it easier to have a reaction to a food.”

Diagnosis and Management of Exercise-Induced Urticaria and Anaphylaxis

In some extreme but rare cases, people may experience wheezing after exercising, pointing towards exercise-induced anaphylaxis. Scientists still do not fully understand when such an extreme reaction might happen. “I have patients who only have exercise-induced hives and who never developed the anaphylaxis portion of it,” said Patil. “And I have patients who skipped [that stage and] went right past the hives into anaphylaxis.”

People may not experience such an allergic reaction every single time they exercise. “[This makes] it hard to have diagnostic criteria for it,” said Patil. Doctors rely on a careful recording of the patient’s history and physical examination.

Those that may have experienced such reactions upon exercising can follow certain tips to ensure they can still be physically active. Patil puts her patients with such a history on a standing regimen of antihistamines. She also advises her patients to carry an epinephrine pen and antihistamine while exercising and not to be alone. “[Because] we want people to exercise,” she said. “[It] is really important for your overall health, your heart health, and your overall metabolism.”