Anaphylaxis: An Allergic Reaction That Can Kill

by Food and Drug Administration (FDA)

One spring day in 1972, Jacki Kwan was quietly working on her research calculations and munching pistachio nuts a co-worker had brought back from the Middle East. After stuffing her body full of pistachios, as she put it, she decided to take a break and go downstairs to pick up her paycheck. Kwan rode the elevator from the 4th floor to the basement and was walking down the hall when she began to feel uncomfortably warm. Then she started to itch. "At that point," she said, "I knew it was the pistachio nuts, because the reaction triggered a vague memory of a problem I had as a child once when I ate pistachio ice cream."

Kwan got her check and went back upstairs. In another 10 minutes she was back at her desk, feeling "really miserable." No wonder: "The itching had become severe and I was getting hives all over my body," Kwan said. "I was flushed and puffy, and started to vomit and have diarrhea at the same time. Everything was getting progressively worse. Finally, I could feel my throat swell up and start to close, and I was having trouble breathing."

Kwan was indeed having an allergic reaction to the pistachio nuts. But her response was not the usual runny nose, watery eyes, sneezing, or itching so many allergy sufferers endure. She was having an anaphylactic reaction — an acute, life-threatening medical emergency. Her symptoms were classic.

Anaphylaxis typically comes on within minutes of exposure to the offending substance, peaks within 15 to 30 minutes, and is over within hours. The first symptom is usually a sensation of warmth followed by intense itching — especially on the soles of the feet and the palms of the hand. The skin flushes, hives may appear, and the face may swell. Breathing becomes difficult, and the patient may feel faint and anxious. It's not surprising that patients often describe, as Kwan did, a sense of impending doom. Blood pressure may drop precipitously. Convulsions, shock, unconsciousness, even death may follow. Roughly 60 percent to 80 percent of anaphylactic deaths are caused by an inability to breathe because swollen airway passages obstruct airflow to the lungs. The second most common cause of anaphylactic deaths — about 24 percent by one estimate — is shock, caused by insufficient blood circulating through the body.

In the March 1986 Western Journal of Medicine, Lawrence M. Lichtenstein, M.D., of Johns Hopkins University School of Medicine, described anaphylaxis as "a dramatic problem which generally has a yes or no outcome: The patient either recovers completely or dies. Fortunately, death is rare." For Kwan, it was a case of being in the right place at the right time. She was working as a medical technologist in an anesthesiology laboratory at the Washington Hospital Center in Washington, D.C. The doctors in the lab rushed her to a nearby room to lie down and gave her an injection of epinephrine (adrenalin). Kwan recovered quickly and hasn't eaten a pistachio since.

The frightening and life-threatening symptoms of anaphylaxis are caused by the release of substances known as mediators from mast cells and from basophils, a type of white blood cell. Since the skin and the respiratory and digestive tracts are rich in mast cells, the organs of these systems are the ones primarily affected in the reaction.

The cause of anaphylaxis was first explored in the 1920s when horse serum — being used to make antitoxin for diphtheria, scarlet fever, tetanus, and tuberculosis — was found to induce the reaction. Scientists have since discovered that the explosive reaction of anaphylaxis is the culmination of a complicated sequence of events.

Anaphylaxis — like less severe allergic reactions — is an abnormal response to an antigen (a foreign substance, usually a protein) that doesn't bother most people but elicits symptoms in those who have an inherited hypersensitivity to it. Well-known antigens that can cause anaphylaxis include penicillin, insect venom, pollen extracts, fish, shellfish and nuts.

Initial exposure to the antigen prompts the hypersensitive person to produce immunoglobulin E (IgE) antibodies. Whereas most antibodies (IgG, IgM, IgA, IgD) are primarily protective — helping to fight harmful bacteria, viruses, fungi, and other toxic substances — IgE antibodies are more likely to work against the body, "sensitizing" the affected person for a future allergic response.

IgE antibodies attach themselves to mast cells and basophils, priming the body for the allergic reaction. Subsequent exposure to the antigen completes the linkage needed to set off the sequence of events that leads to that "sense of impending doom": The antigen hooks up to the IgE antibodies bound to the mast cells, causing the cells to "degranulate" — the scientists' term for an explosive discharge of histamine and other substances from the cell granules. The released mediators cause blood vessels to dilate and leak fluid into the surrounding tissues and cause smooth muscle in the airways to contract. All this activity results in the familiar symptoms of allergy or — in extreme cases — anaphylaxis.

Since the middle of the 20th century, penicillin has been by far the most common cause of anaphylaxis. (Fortunately, most allergic responses to the drug are far less serious. Some involve only localized skin reactions — hives, rashes or inflammation caused by direct topical administration of the drug. Others are systemic reactions, with wheezing, swelling, redness, and vasculitis — inflammation of blood vessels — but not the life-threatening symptoms of anaphylaxis).

Allergic reactions to insect stings are another major cause of anaphylactic death, almost always caused by the order Hymenoptera — honeybees, bumblebees, wasps, hornets, yellow jackets, and fire ants. Nevertheless, although many millions of people in the United States are allergic to insect venom, and hundreds of thousands of them have allergic reactions to stings each year, the number of deaths reported from these reactions is estimated at only 50 to 100 per year.

Some substances can cause a reaction just like anaphylaxis, but the mast cell degranulation is triggered without IgE. (Some experts refer to these as "anaphylactoid" reactions to distinguish them from true IgE-mediated anaphylaxis. By any name, though, the outcome is the same.) Dyes used in certain diagnostic X-ray tests are the most common cause.

Anaphylactoid reactions can also be incited by physical stimuli, such as cold temperatures or exercise — good news for couch potatoes in search of an excuse to avoid jogging. The reason for mast cell degranulation in these circumstances is not thoroughly understood.

Some people with exercise-induced anaphylaxis develop symptoms only if they've eaten before exercising. This is called "food-dependent exercise-induced" anaphylaxis. Writing in the March 1986 issue of the Western Journal of Medicine, Gildon N. Beall, M.D., and his colleagues at Harbor UCLA Medical Center in Torrence, Calif., described the case of a 25-year-old woman who had episodes of food-dependent exercise-induced anaphylaxis. The incidents "only occurred Friday evenings on the dance floor after her escort had treated her to dinner. The patient's problem resolved when she ate dinner after dancing rather than before." Some people are susceptible to this form of anaphylaxis only if they've eaten certain foods (most commonly celery or shellfish).

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.