First Case of Food-dependent, Exercise-induced Angioedema Identified in Case Study

Researchers reported the first case of exercise-induced angioedema that is dependent on food in a new case study from Israel.

The report, “A case of food-dependent exercise-induced angioedema,” appeared in the Journal of Allergy and Clinical Immunology: In Practice.

Angioedema is a swelling of the skin often triggered by food or medications. It most commonly occurs in the area around the eyes, lips, tongue, hands, feet, or genitals.

Severe forms of angioedema may also cause other symptoms of allergic reactions, such as hives (urticaria), and can lead to fainting, dizziness, and collapse.

If swelling occurs in the gastrointestinal system, it can cause vomiting and abdominal pain, and if it affects the neck and throat, it can restrict breathing.

When an allergic reaction is involved, IgE — an antibody involved in allergic reactions — activates a type of cell known as mast cells, which release chemicals including histamines, that increase the leakiness of small blood vessels and cause swelling.

Sometimes, even after many tests, the cause of angioedema attacks is not identified; these patients are diagnosed with idiopathic (unknown cause) angioedema. Among these patients, angioedema without rash/urticaria that responds to antihistamine medications is called idiopathic histaminergic angioedema.

Researchers in Israel reported the case of a 26-year-old woman who complained of swelling of the eyelids, lips, face, and extremities, consistent with angioedema.

These episodes occurred when she jogged one hour after drinking milk, and the symptoms disappeared within two to four days. In the past year and a half, she had 11 episodes, seven while running, and four within two hours after jogging.

The angioedema episodes were not accompanied by hives, rash, nausea, vomiting, or diarrhea, and the patient reported no past allergic diseases. After physical and blood tests, the researchers found abnormally high levels of IgE, suggesting the presence of an allergic reaction.

Skin allergy tests to a variety of allergy-associated foods showed positive allergic reactions to cow’s milk and milk proteins’ lactalbumin and casein. Also, blood tests showed that specific antibodies against cow’s milk were present at higher levels than those against other foods.

Since she never complained of allergic reactions to cow’s milk before, an open oral challenge test was performed to evaluate whether cow’s milk induced an allergic reaction. Cows’ milk was given to the patient every 15 minutes in increasing doses, and no allergic reaction was observed.

Then, to reproduce the conditions that induced the patient’s angioedema events, an exercise test — consisting of a 15-minute run on a treadmill — was conducted on three different days.

The first was performed in a fasting state (with no previous food), the second one an hour after a meal without cow’s milk, and the third an hour after drinking one cup (250 mL) of cow’s milk.

Angioedema symptoms, including swelling of the eyelids, lips, and hands, were only induced when the young woman ran after drinking cow’s milk. Again, rash or other signs of allergic reaction were not observed.

Treatment with an antihistamine medicine resolved her angioedema symptoms within five hours, indicating the reaction was mediated by IgE. However, its underlying mechanisms are still unclear.

The team of researchers noted the evidence indicated that the patient had angioedema induced by exercise, dependent on the consumption of cow’s milk, and mediated by IgE.

The woman was advised to avoid exercise within six hours after eating or drinking milk products, and an antihistamine was prescribed to treat potential future angioedema attacks. Since then, she has not had any angioedema events.

The researchers believe this food-dependent, exercise-induced angioedema might be the case of some idiopathic histaminergic angioedema patients, and a detailed recall of the conditions surrounding the patient’s angioedema events may help its diagnosis.