Anaphylaxis, Exercise-Induced

Epidemiology

The age of onset ranges from childhood through adulthood. This condition affects males and females equally, and about half the patients have a history of atopy. Attacks can range from a few times per month to once a year. Most cases have been reported in athletes who exercise regularly. There are some studies that suggest that the severity of the anaphylactic events may decrease over time.

Pathogenesis

The exact mechanism is not known, but mast cells are known to be a factor because studies have shown elevated levels of serum histamine and tryptase during attacks. Studies have also shown mast cell degeneration on skin biopsies done after an attack. There may be a priming phenomenon at work, where one stimulus acts as a cofactor for the reaction to occur. Food, medication, or other factors (see below) may act as the primer, and then the exercise triggers the event. Exercise alone does not cause anaphylaxis, and eating the food without exercise also does not cause an anaphylactic event. An individual must first be “primed” by eating the food, and when this is followed up by exercising (the “trigger”), it has the potential to cause an anaphylactic event.

Triggers/Associated Factors

Exercise-induced anaphylaxis can be triggered by any physical activity, but it is more common in aerobic sports and running. Factors that have been associated with this condition include menstruation, use of aspirin and NSAIDs (nonsteroidal anti-inflammatory drugs), and exposure to cold weather or hot, humid weather. Some patients have a food-dependent variant, where they need to ingest a certain food, then exercise, which provokes an anaphylactic response. Common foods associated with these reactions are celery, wheat, shellfish, cheese, eggs, chicken, hazelnuts, oranges, apples, peaches, grapes, and cabbage.

Clinical Signs and Symptoms

Within several minutes of exercising, patients experience a prodromal phase that consists of fatigue, warmth, pruritus, and redness of the skin (erythema). These symptoms then progress to large hives that become confluent and eventually appear as angioedema. If the patient continues to exercise, the attack progresses to systemic anaphylaxis with cardiovascular (hypotension, tachycardia, syncope), respiratory (wheezing, stridor), and gastrointestinal (nausea, vomiting, abdominal pain) symptoms. Once the attack occurs, it can last from 30 minutes to 4 hours. There can also be a later-phase reaction that causes headache, fatigue, and warmth, lasting from 24 to 72 hours.

Testing

The diagnosis can often be made based on history. Exercise testing can be performed, but it is cumbersome. Testing needs to be done in a controlled environment with medical personnel, epinephrine, and resuscitative equipment present. Vital signs and spirometry should be monitored. It is also recommended that an intravenous (IV) line be in place both to draw serum markers and to administer medications if necessary. False-negative [Page 43]challenges are common, so testing may need to be repeated on multiple occasions.

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