Anaphylaxis (Anaphylactic Shock)

What happens in anaphylaxis

In a typical allergic reaction, the immune system has already made IgE antibodies to a harmless substance (an allergen). These antibodies sit on mast cells and basophils in the skin, airways and gut. On re-exposure, the allergen binds to them and the cells burst open, releasing histamine, tryptase, leukotrienes and other chemicals within seconds.

These chemicals:

• widen blood vessels and make them leaky, so blood pressure falls and tissues swell
• tighten the muscles of the airways, causing wheeze
• make the gut contract, causing cramps and vomiting
• cause itching and hives in the skin

Some reactions bypass IgE. Certain medicines (opioids, IV contrast, vancomycin) and NSAIDs can activate mast cells directly. Doctors treat them the same way. For a checklist of warning signs and step-by-step first aid, see anaphylaxis symptoms.

Causes and triggers

Foods

The leading cause in children and young adults. In the US, the major allergens are peanut, tree nuts, milk, egg, wheat, soy, fish, shellfish and sesame. Peanut and tree nut allergies cause most fatal food reactions. See food allergy.

Alpha-gal syndrome is a delayed reaction to red meat (beef, pork, lamb) that develops after certain tick bites, notably the lone star tick. Symptoms start 3 to 6 hours after eating.

Insect stings

Bees, wasps, hornets, yellow jackets and fire ants. Sting reactions are the main cause in middle-aged and older adults.

Medicines

Antibiotics (especially penicillins and cephalosporins), NSAIDs such as ibuprofen and aspirin, anesthetic drugs, chemotherapy, biologic medicines and IV contrast dye. See drug allergy. Medicines are the leading cause of fatal anaphylaxis in older adults in many countries.

Other triggers

• Latex: gloves, balloons and medical devices.
• Exercise: alone or after eating a specific food (food-dependent exercise-induced anaphylaxis).
• Idiopathic anaphylaxis: no trigger is found despite testing. Some of these people have a mast cell disorder.

Cofactors that make reactions worse

Exercise, alcohol, NSAIDs, fever or infection, menstruation, lack of sleep and stress can turn a usually mild reaction into anaphylaxis.

Risk factors for severe or fatal reactions

• uncontrolled asthma
• delayed epinephrine, or no auto-injector available
• age 10 to 24 with food allergy, or older age with heart disease
• mastocytosis or a raised baseline tryptase
• beta blockers and ACE inhibitors
• standing up or walking during a reaction

Diagnosis

Anaphylaxis is diagnosed clinically. Doctors use criteria from the World Allergy Organization: a sudden illness with skin or mucosal symptoms plus breathing problems, low blood pressure or severe gut symptoms, or breathing or blood pressure problems straight after exposure to a known allergen, even without skin signs.

Tests after the reaction:

• Serum tryptase: best taken 30 minutes to 2 hours after symptoms start, with a baseline level at least 24 hours later. A rise supports anaphylaxis and a high baseline suggests a mast cell disorder.
• Skin prick tests and specific IgE blood tests: identify food, venom, latex or some drug allergies. They are done by an allergist, usually at least 4 weeks after the reaction.
• Supervised oral challenge: eating small, increasing amounts under medical observation when tests are unclear.
• Drug allergy testing: penicillin skin tests and graded challenges can remove incorrect allergy labels.

Treatment

Emergency treatment

1. Epinephrine into the outer thigh muscle is the first and most important treatment. It raises blood pressure, opens the airways and reduces swelling within minutes. The dose can be repeated every 5 to 15 minutes. Auto-injectors and a nasal spray are available.
2. Lie flat with legs raised, or sit up if breathing is hard. Never stand up suddenly.
3. Oxygen and IV fluids in the ambulance or ER.
4. Additional medicines: inhaled bronchodilators for wheeze, and antihistamines for itch and hives. Steroids are no longer routinely recommended to prevent late reactions, though some clinicians still use them. None of these replace epinephrine.
5. Refractory anaphylaxis: an epinephrine infusion and intensive care for reactions that do not respond to two doses.

Observation

Most people are observed for 4 to 6 hours after symptoms resolve. Longer observation, often overnight, is advised for severe reactions, those needing more than one dose of epinephrine, people with severe asthma, or those who live far from emergency care.

Biphasic anaphylaxis

A biphasic reaction is a return of symptoms, usually within 12 hours (sometimes up to 72 hours), without new exposure. It occurs in about 5% of cases and is more likely after severe reactions or delayed epinephrine.

Long-term management

• Allergist referral to confirm the trigger and assess risk.
• Two epinephrine devices carried at all times, checked for expiry, with everyone close to you trained to use them.
• A written anaphylaxis action plan for home, school and work.
• Strict trigger avoidance: read food labels every time, tell restaurants, and check medicine ingredients.
• Medical ID bracelet or phone record.
• Control asthma with regular preventer treatment.
• Venom immunotherapy: a course of injections over 3 to 5 years reduces the risk of anaphylaxis from a future sting to under 10% in most people.
• Oral immunotherapy and biologics: peanut oral immunotherapy and omalizumab (for multiple food allergies) can raise the amount of allergen needed to cause a reaction in selected patients.
• Drug desensitization: allows a needed medicine to be given safely under supervision.

Complications

Anaphylaxis can cause airway obstruction, cardiac arrest, heart attack from reduced blood flow, brain injury from low oxygen, and death. Anxiety about future reactions is common and can be addressed with education and, if needed, psychological support.

Outlook

With rapid epinephrine, the vast majority of people recover fully within hours. Fatal anaphylaxis is rare and is most often linked to delayed epinephrine, asthma or being upright during the reaction. Some allergies, such as milk and egg in children, are often outgrown. Peanut, tree nut, fish, shellfish and venom allergies are more often lifelong, though venom immunotherapy is highly effective.

Frequently asked questions

What is the difference between anaphylaxis and anaphylactic shock?

Anaphylaxis is the severe allergic reaction itself. Anaphylactic shock is anaphylaxis with a dangerous drop in blood pressure, so organs are not getting enough blood. Not every anaphylactic reaction includes shock, but every case needs epinephrine and emergency care.

Why is epinephrine the main treatment for anaphylaxis?

Epinephrine reverses the key dangers: it tightens blood vessels to raise blood pressure, relaxes airway muscles, and reduces swelling and further release of allergy chemicals. Antihistamines only relieve itch and hives. Studies link delays in epinephrine to most deaths from anaphylaxis.

What causes anaphylaxis?

The most common triggers are foods (peanut, tree nuts, shellfish, fish, milk, egg, sesame), insect stings, and medicines such as antibiotics, NSAIDs and anesthetic drugs. Latex and exercise are less common. In some people no cause is found, which is called idiopathic anaphylaxis.

Can you develop anaphylaxis later in life?

Yes. Shellfish allergy, insect venom allergy, drug allergy and alpha-gal syndrome often appear in adulthood. A mild reaction does not guarantee future reactions will be mild, so anyone with a reaction involving breathing or circulation should see an allergist.

How long should you stay in the hospital after anaphylaxis?

Most people are observed for 4 to 6 hours after symptoms resolve. Severe reactions, those needing repeated epinephrine, people with severe asthma, or those who live far from help may be observed overnight, because symptoms can return.