Causes and Risk Factors of Anaphylaxis

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.

Immunological Causes

Your immune system protects you from 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.

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.

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 (e.g.,walnuts, hazelnuts, pecans, pistachios, cashews), fish, shellfish, chicken eggs, cow's milk, wheat soy, and sesame). 

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 and non-steroidal anti-inflammatory drugs such as aspirin, 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
• 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, 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.

Medications can be another trigger for EIA and include aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs (NSAIDs).

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.

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 lone star tick. 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. 

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.