Excercise-Intuced Anaphylaxis (EIA)

Background
Exercise-induced anaphylaxis (EIA) is a syndrome in which patients experience the symptoms of anaphylaxis, which occur only after increased physical activity. The symptoms include pruritus and urticaria (typically with giant hives), and, without emergency intervention, the patient may develop hypotension and collapse. Now increasingly recognized as more children and teenagers participate in physical activities and sports, exercise-induced anaphylaxis may become more common in the future. Those affected by the syndrome are typically accomplished athletes and have a history of atopy, but anyone can be affected.
The types of physical activities that have triggered episodes of exercise-induced anaphylaxis have included walking, dancing, racquet sports, swimming, jogging, bicycling, skiing, basketball, and sprinting. Hot humid weather and cold weather can precipitate episodes in some patients. If a patient has recurrent exercise-induced anaphylaxis, the episodes tend to be worse in the summer months. The first reported case of exercise-induced anaphylaxis was in 1979 by Maulitz and coworkers and was food-related, occurring in a 31-year-old patient who had ingested shellfish prior to long-distance running.1 Since then, many different allergens have been reported in the literature to have caused exercise-induced anaphylaxis, including shrimp, oyster, celery, cheese sandwiches, pizza, wheat gliadin,2 eggs, peaches, grapes, pomegranites,3 chick peas,4 pears, poppy seeds, soybean,5 and snails (which have been reported to have cross-reactivity with dust mites).
In 1980, Sheffer and Austen provided the first report of patients with exercise-induced anaphylaxis.6 Sixteen patients, aged 12-54 years, experienced exercise-induced anaphylaxis without a specific allergen exposure. Ten of these patients had onset of exercise-induced anaphylaxis in their teenage years, indicating that those who care for pediatric patients should be aware of this syndrome.
Exercise-induced anaphylaxis has been categorized in a few different ways in the literature. Classic exercise-induced anaphylaxis is the most common type. Sheffer and Austen (1980) originally described 4 phases in the sequence of symptomatology of classic exercise-induced anaphylaxis.6 A prodromal phase is characterized by fatigue, warmth, pruritus, and cutaneous erythema. The early phase follows, with the urticarial eruption that progresses from giant hives (about 10-15 mm in diameter) to become confluent and may include angioedema of the face, palms, and soles. Then, the fully established phase occurs, which can include hypotension, syncope, loss of consciousness, choking, stridor, nausea, and vomiting and can last 30 minutes to 4 hours. The final phase is the late or postexertional phase, which is characterized by prolonged urticaria and headache persisting for 24-74 hours.
Another type of exercise-induced anaphylaxis is variant-type exercise-induced anaphylaxis, which is similar to classic exercise-induced anaphylaxis, except the typical giant hives are not observed. In their place are small punctate skin lesions, more typical of cholinergic urticaria, but the syndrome does lead to hypotension and collapse if allowed to progress. The variant type of exercise-induced anaphylaxis accounts for approximately 10% of cases.
Familial exercise-induced anaphylaxis has been described involving patients with a family history of exercise-induced anaphylaxis and atopy. No inheritance pattern has been established.
Two forms of food-dependent exercise-induced anaphylaxis have been described. Inherent in the definition of food-dependent exercise-induced anaphylaxis is that the food or exercise alone does not produce symptoms. First, specific-food exercise-induced anaphylaxis in which a specific food is known to be the offending allergen is recognized. Second, nonspecific-food exercise-induced anaphylaxis in which no specific food is known, but eating any food prior to exercise causes symptoms of exercise-induced anaphylaxis is also recognized.7
The last type of exercise-induced anaphylaxis described is medication-dependent or drug-dependent exercise-induced anaphylaxis. This category includes patients who develop the syndrome only after ingesting a specific medication and then exercising. The offending medications that have been reported include nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, antibiotics, and cold remedies.

Pathophysiology
In exercise-induced anaphylaxis, an exercise-induced lowering of the mast cell degranulation threshold occurs, which causes the release of histamine and other mediators and leads to the progression from pruritus and urticarial rash to the symptoms of anaphylaxis. In the food-dependent subset, this process is influenced by immunoglobulin E (IgE) mast cell sensitization by a known or unknown food. If the offending food is known, the amount of the specific food ingested has an effect on whether the patient has symptoms. The mechanism by which exercise lowers the mast cell degranulation threshold is unknown. Previous observations suggest that increased physical activity has a direct effect on mast cell releasability and does not result in an increased sensitivity to histamine.
Once the histamine and other mast cell mediators, including leukotrienes, are released, they cause the smooth muscle contraction responsible for the wheezing and GI symptoms. The histamine and other mast cell mediators also cause the vascular dilatation that leads to the escape of plasma into the tissues, causing urticaria and angioedema, and results in hypotension and shock.8,9

Frequency
United States
Prevalence is not well established. In one study, 9% of total episodes of childhood anaphylaxis and 20% of episodes in children older than 8 years were triggered by exercise.
International Case reports from Germany, Italy, Japan, United States, and Thailand are provided in the literature.

Mortality/Morbidity
Deaths of children have been reported, but they are rare. Infrequently, patients must alter their lifestyle and physical activity significantly; in some patients, the syndrome causes them to be unable to perform daily activities without the risk of anaphylactic syndrome.

Race
No racial predilection is known.

Sex
One study showed a slight male predominance, but most other studies show no overwhelming difference between sexes.

Age
Exercise-induced anaphylaxis has been reported from as young as 4 years into adulthood. In a study of 16 patients, 10 patients (63%) had onset in their teenage years.

Clinical History
Pediatric patients with exercise-induced anaphylaxis (EIA) typically are athletic or involved in school or otherwise organized sports, and they typically have a history of atopy and/or a family history of atopy or possibly of exercise-induced anaphylaxis.
Typical episodes occur after exercise on a particularly hot, humid, or cold day.
History of ingesting aspirin or other nonsteroidal anti-inflammatory drug (NSAID), a meal, or a specific food prior to exercising may be noted.

In women, the episodes can be more frequent and more severe before and during menstrual cycles.

The history of an episode most likely includes the initial pruritus and giant hives associated with the onset of the symptoms.

As the syndrome progresses, the patient may report nausea, cramping, diarrhea, vomiting, tinnitus, vertigo, pruritus, difficulty breathing, chest tightness, and wheezing; a syncopal episode may occur.

The history may be obtained from a paramedic who responded to the collapse of a child. In this case, the patient's history may include loss of consciousness or variable consciousness.
In several minutes or hours after the episode, the patient may report only a headache that can persist for as long as 3 days.

Physical
The physical examination should start with the airway, breathing, and circulation (ABCs).
The most emergent assessments are those of airway maintenance and level of consciousness. One must rule out laryngeal obstruction.
Simultaneously assess for hypotension.
The rest of the physical examination should include looking for the typical features of exercise-induced anaphylaxis, including urticaria and giant hives, angioedema, wheezing, and stridor.

Causes
Risk factors for exercise-induced anaphylaxis include personal or family history of exercise-induced anaphylaxis or atopy, male sex (in one study), exposure to food allergen, and extremes of weather.

Beta-blocker medications can aggravate anaphylactic episodes.

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