Causes and Risk Factors of Anaphylaxis

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Anaphylaxis is a life-threatening allergic reaction that can be triggered by exposure to many different substances (allergens). The most common allergies that can produce anaphylaxis are to drugs, insects stings, foods, and latex.

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Immunological Causes

Your immune system protects you foreign substances. Histamine and other mediator chemicals that promote the inflammatory response are stored in mast cells and basophils that are in tissues throughout your body. After exposure to foreign substances, your body's immune cells (lymphocytes) begin to produce antibodies that will recognize those substances the next time they are in the body.

On future exposures, these antibodies bind to the substances and also to receptors on mast cells and basophils. This triggers the release of the mediator chemicals that promote an inflammatory reaction.

Histamine and other mediators cause the blood vessels to dilate so more fluid enters the tissues, leading to swelling. In anaphylaxis, the chemicals are released throughout the body and affect many different systems. Low blood pressure, hives, and difficulty breathing are seen.

An anaphylactic reaction does not usually occur the first time you are exposed to an allergen. The next time you are exposed to the allergen you may have an allergic reaction. Anaphylaxis is rare but can occur anytime after you are sensitized.

Sometimes these chemicals are directly triggered to be released, without prior exposure or development of antibodies. This is called an anaphylactoid reaction and is more often seen in reactions to IV contrast medium and opioids.

Common Triggers

Anaphylaxis can occur in response to almost any allergen. However, common respiratory allergies such as hay fever and animal dander rarely cause anaphylaxis.

A large percentage of cases of anaphylaxis can't be linked to a specific allergen and are called idiopathic.

Food Allergies

Food allergies are the most common triggers of anaphylaxis in children, and among the top causes for adults. The foods most often responsible are peanuts, tree nuts (walnuts, hazelnuts, pecans), fish, shellfish, chicken eggs, and cow's milk. It may also be seen with wheat, soy,  sesame seeds, kiwi fruit, and lupin flour.

Insect Venom Allergies

Wasp and bee stings are frequent causes of anaphylactic reactions in children and adults. These insects include yellow jackets, honeybees, paper wasps, and hornets. Fire ants can also produce the reaction.

Medication Allergies

Medication allergies are a common cause of anaphylaxis in all age groups. The most common drugs that produce anaphylaxis are penicillin, aspirin, and non-steroidal anti-inflammatory drugs such as Advil (ibuprofen) and Aleve (naproxen).

Anaphylactoid reactions can occur after intravenous administration of the drugs given during general anesthesia, iodine-containing IV contrast dyes used in imaging studies, opioids, and monoclonal antibodies.

Less common medication-induced anaphylaxis is seen with:

  • Insulin, especially from non-human sources or when not used recently or regularly
  • Sulfa drugs
  • Drugs used to treat seizures
  • Drugs applied to the skin, including antibiotics
  • Local anesthetics, such as used in dental procedures 

Latex Allergies

Latex is a natural rubber product that is found in many items used in health care as well as many consumer products. The demand for latex soared in the 1980s as glove use was required in more areas of health care. The latex used was high in the protein that triggers latex allergy. The gloves currently produced are lower in protein. However, the people who have been sensitized and have a severe latex allergy can be affected even being in a room with latex gloves or balloons.

Exercise-Induced Anaphylaxis

Exercise-induced anaphylaxis (EIA) is a rare cause of anaphylaxis that occurs as a result of physical activity. The triggering exercise can be of any form, including jogging, tennis, swimming, walking, or even strenuous chores such as shoveling snow. Symptoms may start with tiredness, warmth, itching, and redness, usually within a few minutes of starting exercise.

The cause of exercise-induced anaphylaxis is unknown, although it tends to occur in people with allergic responses to medications, foods, alcohol, weather (hot, cold, or humid), and menstruation. Typically, exercise or the trigger alone will not cause symptoms. But, if the person is exposed to the trigger and exercise, then symptoms of EIA may occur.

Medications that have reported to cause EIA include aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs (NSAIDs). Many groups of foods (if eaten 24 hours before exercising) have been associated with EIA, including cereal grains, seafood, nuts, fruits, vegetables, dairy, and alcohol.

Some people with EIA associate it with eating, but there is no specific food that triggers the symptoms.

Oral Mite Anaphylaxis (Pancake Syndrome)

People allergic to dust mites have experienced anaphylaxis as a result of eating foods contaminated with dust mite particles. This rare syndrome has been given the name oral mite anaphylaxis (OMA), or pancake syndrome. Dust mites are a common cause of allergic diseases. They are most commonly found in bedding material, carpeting, and upholstered furniture, but may also contaminate foods made from wheat flour and other cereal grains. Symptoms of OMA typically occur within a few minutes to hours after eating a food contaminated with dust mites.

OMA is most often reported in younger people who have other allergic conditions, although it may occur in people of all ages. It's not clear why more people don't experience this condition, given how common dust mite allergy is and how often flour is likely contaminated with the mites.

In people reported to have experienced the pancake syndrome, 44 percent had a history of allergy to NSAIDs.

Cold-Induced Urticaria/Anaphylaxis

Rarely, exposure to cold can produce anaphylaxis. People who may be sensitive are more likely to have had cold-induced urticaria (hives) produced in cold conditions.

Delayed Allergy to Red Meat

A rare type of anaphylaxis can occur in people who were bitten by a tick that has recently fed on blood from a farm animal. These people become sensitized to alpha-gal, a type of carbohydrate found in meat from mammals (beef, lamb, pork, and goat). They then can develop anaphylaxis when they eat red meat.

Role of Genetics

Allergies and asthma tend to run in families and there is believed to be a genetic predisposition to them. People with allergies to the common triggers of anaphylaxis are more at risk. You could develop anaphylaxis in future exposures to the allergen even if your usual reaction is mild, such as a rash. 

If you previously had an anaphylactic reaction, you are at greater risk of having one again. Future reactions may be even more severe.

People with even mild asthma are more at risk of severe allergic reactions, including anaphylaxis. If you are allergic to foods, medications, or insects, you need to take extra precautions if you also have asthma. The same is true for people with other chronic lung diseases as the respiratory symptoms will be more severe during anaphylaxis. Poorly-controlled asthma raises the risk that you could die during anaphylaxis.

Mastocytosis is a rare condition that develops due to a mutation in a gene. In most cases, this mutation happens during the production of mast cells in an individual and is not inherited or passed on to their children. With mastocytosis, you have more mast cells, which are the immune cells that store histamine and other chemicals. These cells can accumulate in the skin, internal organs, and bones. If triggered by an allergen, you are more at risk of anaphylaxis because of the number of cells releasing these chemicals.

Cardiovascular Risk

If you have a poorly-controlled cardiovascular disease you are more at risk of death if you have an episode of anaphylaxis. People with cardiovascular disease who are taking beta-blockers or alpha-adrenergic blockers are at further risk if they develop anaphylaxis because those medications reduce the effects of epinephrine, which is given to stop the anaphylactic reaction.

Anaphylaxis treatment with epinephrine carries more risk for people over age 50 as it can produce heart complications including atrial fibrillation and myocardial infarction.

Allergic Reaction vs. Anaphylaxis

Unlike an allergic reaction, which may affect one or two organ systems, anaphylaxis is a cascading response that affects multiple organ systems.

Anyone with a history of anaphylaxis should carry an epinephrine auto-injector (EpiPen) to respond quickly to the onset of symptoms. A medical ID bracelet is also recommended.

Frequently Asked Questions

  • What is anaphylaxis?

    Anaphylaxis is a potentially life-threatening allergy affecting the body as a whole. It occurs when the immune system overreacts to an allergy-causing substance (allergen) and floods the body with inflammatory substances that can cause the body to go into shock. Around 5% of people will experience anaphylaxis at some point in their lives.

  • What is the main cause of anaphylaxis?

    As with all allergies, anaphylaxis occurs when the immune system regards an otherwise harmless substance as harmful. The immune overreaction triggers the release of histamine and other mediators of the immune response, causing blood vessels to dilate and tissues to swell.

  • What are common triggers for anaphylaxis?

    Food allergies to nuts, shellfish, milk, and eggs are the most common triggers in children. In addition to food, adults commonly experience anaphylaxis in response to insect stings, certain medications (like antibiotics), and natural latex.

  • What are the signs and symptoms of anaphylaxis?

    The signs and symptoms of anaphylaxis commonly include:

    • Shortness of breath
    • Wheezing
    • Rash or hives
    • Stomach pain or cramps
    • Nausea or vomiting
    • Swelling of the lips, face, tongue, or neck
    • Lightheadedness or fainting
    • A feeling of impending doom
  • How long does it take for anaphylaxis to occur?

    Anaphylaxis usually occurs within 20 minutes to two hours of exposure to an allergen, although some people have delayed reactions that take several days to develop. Others have biphasic anaphylaxis in which an initial, mild anaphylactic reaction is followed hours or days later by a severe and potentially devastating anaphylactic event.

  • How do you treat anaphylaxis?

    Anaphylaxis requires emergency medical care. The first-line response involves an intramuscular injection of epinephrine (adrenaline) and cardiopulmonary resuscitation (CPR) if breathing has stopped. Intravenous antihistamines and steroids can quickly relieve inflammation, while beta-agonists like albuterol can help ease breathing.

  • What can I expect after anaphylaxis treatment?

    If treated quickly and appropriately, many people with anaphylaxis will improve within hours (although an overnight hospital stay may be recommended). If treatment is delayed or a person has a pre-existing condition like heart failure or COPD, recovery may take longer and require a prolonged hospital stay.

  • Can you die from anaphylaxis?

    Yes. If anaphylaxis isn't treated, death can occur within minutes or hours. Death occurs mainly as a result of anaphylactic shock in which a person's blood pressure drops so low that organs are deprived of oxygen, leading to coma, major organ failure, and death. Anaphylaxis can also cause suffocation if the swelling of the throat blocks the airways. Even so, only around 1% of anaphylactic events end in death.

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