Anaphylaxis

What is anaphylaxis?

Anaphylaxis (pronounced anna-fill-axis) is an extreme form of allergic reaction. Typically, it occurs very suddenly and without warning. It usually occurs within minutes of being exposed to an allergen. The symptoms affect many parts of the body.

Anaphylaxis can cause swelling of the lips and tongue, breathing problems, collapse and loss of consciousness. The symptoms become rapidly worse and, without treatment, can cause death.

Adrenaline (epinephrine), given as soon as possible, is the most important treatment for anaphylaxis.

What happens during anaphylaxis?

An allergy is a response by the body's immune system to something (called an allergen) that is not necessarily harmful in itself. Certain people are sensitive to this allergen and have a reaction when exposed to it.

During an allergic reaction, a complex series of events occurs within the body. These events are co-ordinated by the immune system. Sometimes the immune system 'goes into overdrive'. If this happens, the body can lose control of its vital functions, with catastrophic results. Such a severe reaction can cause death. This is anaphylaxis.

On a more detailed level, changes happen within the walls of capillaries, the smallest blood vessels in the body. The capillaries become leaky, and fluid leaks from the blood into the tissues (blood is comprised of blood cells as well as fluid called serum). So much fluid is lost from the blood (vascular) system, that blood pressure falls. As the blood pressure drops, there is a lack of blood to the major organs. This is known as shock - and in this case is anaphylactic shock.

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Anaphylaxis symptoms

Classic early symptoms of anaphylaxis include:

• Wheezing and hoarseness. This happens as the airways narrow.

• Swelling of the lips, tongue and throat. It is known as angio-oedema. The swelling involves the deeper layers of the skin. Whilst it can occur around the eyes, and in the hands and feet, it is more significant when it affects the lips, tongue and throat. Without emergency treatment, this results in suffocation (asphyxiation).

• An itchy rash, like nettle rash - commonly called hives. Urticaria is the medical term. The rash is raised and generally pale pink in colour. The raised areas are called wheals. Not everyone having an anaphylactic reaction gets this rash.

Other symptoms include:

• Feeling faint - due to dropping of your blood pressure.

• A sense of impending doom.

• A fast heart rate (tachycardia) or the sensation of a 'thumping' heart (palpitations) as your heart tries to pump faster to maintain your blood pressure.

• Symptoms involving the gut (gastrointestinal tract). These include feeling sick (nausea), being sick (vomiting) and tummy (abdominal) pain.

Classic advancing symptoms of anaphylaxis include:

• Stridor. This is a noise created by trying to breathe in when the upper airways (namely the mouth, throat and upper windpipe (trachea)) are partially obstructed. This is due to swelling in these tissues.

• Respiratory collapse. This means that the breathing (respiratory) system of the body is failing. There might be fast, shallow breathing and the skin of the lips and tongue may become bluish (called cyanosis). If you cannot breathe air into the lungs, the blood cannot be oxygenated. Oxygenated blood is needed so that the cells in our body, and therefore the organs in our body, can work.

• Confusion, agitation, anxiety and loss of consciousness. These symptoms soon follow. Low oxygen levels (hypoxia) can make you confused. If you are unable to breathe properly due to angio-oedema, you will feel restless and anxious - you are effectively suffocating. Eventually, loss of consciousness occurs.

• Low blood pressure (hypotension) and eventual circulatory collapse are the end events.

What causes anaphylaxis?

Anaphylaxis can potentially be caused by any allergen. Most allergens are proteins, but some (such as medications) are not. Some cases of anaphylaxis have no known cause. This is referred to as idiopathic anaphylaxis.

Causes of anaphylaxis:

• Idiopathic (unknown).

• Food allergies - common examples include nuts (for example, peanut, Brazil), shellfish and eggs.

• Venom (for example, bee or wasp stings).

• Medicines - common examples include:

  • Antibiotics - for example, penicillin.

  • Painkillers - for example, opioids such as morphine or codeine, or non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin.

Can pollen cause anaphylaxis?

Inhaled pollen can cause anaphylaxis, but this is very rare. Pollen allergies usually cause much milder symptoms (hay fever).

Rarely, some people with pollen-food allergy syndrome (oral allergy syndrome) develop anaphylaxis, but this happens after eating a food allergen, and not on exposure to pollen.

There are also some reports of people developing anaphylaxis after eating pollen, such as in supplements or certain types of honey that contain pollen, but again this is rare.

How common is anaphylaxis?

Approximately 3 in 4,000 people in England have experienced anaphylaxis at some point in their lives. There are approximately 20 deaths from anaphylaxis reported each year in the UK, with around half the deaths having no identifiable cause for anaphylaxis.

In the UK it is estimated that:

• About half a million people in the UK have had an anaphylactic reaction to venom (bee or wasp stings).

• Almost a quarter of a million people under 44 years of age have had anaphylaxis due to nuts.

Who is at risk of anaphylaxis?

Some people with allergies are at risk of anaphylaxis.

People who are at higher risk of anaphylaxis include:

• People who have already had anaphylaxis before.

• People who have asthma alongside an allergy, especially if the asthma is poorly controlled.

• People with allergies to things that are difficult to avoid completely; for example, people with food allergies can sometimes be accidentally exposed to an allergen if they are unaware that the food they are eating contains it, or a mistake has been made in food preparation, which can lead to severe allergic reactions.

• People who have had previously had significant allergic reactions, such as widespread hives (urticaria) with wheezing.

• People who have had allergic reactions in response to a very small amount of an allergen.

Food is a particularly common trigger for anaphylaxis in children, and medications are much more common triggers in adults.

How is anaphylaxis diagnosed?

Anaphylaxis is diagnosed based on the presence of typical symptoms and signs, particularly if someone has recently been exposed to a known allergic trigger.

Blood tests can be useful to help confirm the diagnosis. Tryptase is a chemical released by mast cells (a type of cell in the immune system). In anaphylaxis, blood tryptase levels rise within about an hour and then stay elevated for hours to days. A raised blood tryptase level can help to confirm that someone did have anaphylaxis.

The results of tryptase blood tests take time to come back, so they are not useful for diagnosing anaphylaxis whilst it is happening. But they can sometimes be useful to confirm that anaphylaxis did happen, after initial emergency treatment has been given and someone has recovered.

Anaphylaxis does need to be distinguished from other medical conditions that may have some similar symptoms. These include a life-threatening asthma attack, or a severe blood infection (septic shock). There are also other conditions that are not life-threatening but that can initially seem similar to anaphylaxis. Examples include panic attacks, fainting (vasovagal episode) or idiopathic (non-allergic) urticaria or angio-oedema. Other tests might be used to look for these conditions, depending on the situation.

Anaphylaxis treatment

Anaphylaxis is a life-threatening emergency and needs immediate treatment.

First aid measures for anaphylaxis (out of hospital)

The most important treatment for anaphylaxis is adrenaline (epinephrine), given as soon as possible.

This is why it's important for people at risk of anaphylaxis to carry adrenaline auto-injectors at all times, and to use them at the first signs of anaphylaxis.

Treatments such as antihistamines and steroid tablets do not work fast enough to treat anaphylaxis.

Even if someone feels completely better after injecting adrenaline, they still need to go to hospital. This is because anaphylactic reactions can sometimes return several hours later, which may require further treatment.

Hospital treatment

People with suspected anaphylaxis are treated in the resuscitation room of an emergency department.

Hospital treatment for anaphylaxis involves:

• Adrenaline (epinephrine) - which is still the main and most important treatment.

  • Adrenaline is given as an injection into a muscle (usually the thigh) as soon as possible, with another dose given if there is no improvement after five minutes.

  • If two doses of intramuscular adrenaline haven't worked, an intravenous infusion of adrenaline is used.

• Other treatment aims to treat life-threatening complications of anaphylaxis, and can include:

  • Treatment to keep the airway (mouth, throat, and windpipe) open, to allow air to get in and out of the lungs. This might involve placing a tube in the airway to keep it open.

  • Support with breathing, such as oxygen via a mask, or ventilation (assisted breathing).

  • Support to keep blood flowing and to stop blood pressure from dropping too low, such as intravenous fluids, and medicines to increase blood pressure.

• Other things might be given in certain situations, such as:

  • A nebuliser to help open up the small airways of the lungs. This can be useful if someone is having an asthma attack as well as anaphylaxis, or if it's not clear which one is happening, and emergency treatment is being given for both.

  • Antihistamines to treat allergic skin reactions. They are not an emergency treatment for anaphylaxis, but may help to treat other, less serious, allergic reactions.

  • Steroids (tablets or intravenously). Steroids used to be part of the standard treatment of anaphylaxis, but are no longer used routinely as there is little evidence that they help. They are more useful if someone is also having an asthma attack.

• Whilst treatment is ongoing, a person with anaphylaxis will be closely monitored. This involves (amongst other things) blood pressure monitoring, heart monitoring and a heart tracing (electrocardiogram, or ECG) and measurement of the oxygen levels in the blood (using a pulse oximeter to measure oxygen saturation - sats).

• If you have had an anaphylactic reaction, you will be kept in hospital for observation. This can be anything from two to twelve hours after the reaction has subsided, depending on the circumstances. For example:

  • Someone who has had a good response to a single dose of adrenaline, is feeling completely back to normal, already has adrenaline auto-injectors and knows how to use them, and has someone who can monitor them at home, might be able to go home after two hours of observation.

  • In most cases, though, people will kept in for longer, and sometimes overnight.

  • There is a possibility of a second anaphylactic reaction occurring about 6 to 12 hours after the first one (a 'biphasic' reaction), which is why it's important to monitor people closely for some time, even if they have recovered fully.

  • People who require treatment on intensive care for very severe anaphylactic reactions will need to stay in hospital longer.

What should I do if I think someone is having an anaphylactic reaction?

• Check if it's anaphylaxis. Anaphylaxis is likely when:

  • There is a sudden onset of symptoms.

  • Symptoms get rapidly much worse.

  • There are life-threatening airway and/or breathing problems and/or circulation problems.

  • There are skin changes such as swelling of the lips and tongue (angio-oedema), hives (urticaria) and flushing.

  • The person may have had a severe allergic reaction or anaphylaxis in the past. However, this may be the first time.

• A person having difficulty breathing may prefer to sit up in a chair. It is best for a person feeling faint, to lie down.

• Look to see if the person is wearing a medical emergency bracelet or necklace. Are they carrying an adrenaline (epinephrine) pen? These are also called adrenaline (epinephrine) auto-injectors. Brands include EpiPen®, Emerade® and Jext®. If they are, you could save their life by administering it. Techniques for injection vary slightly, according to the device prescribed, and the instructions are printed on the side of the device. Each device is designed to be used only once - you cannot repeat the procedure with a used auto-injector.

• Call 999/112/911 for an ambulance - act quickly as anaphylaxis is a medical emergency.

• If they are not feeling any better within 5 minutes after the first injection of adrenaline, give a second injection using another auto-injector, if it's available.

Should I carry an adrenaline (epinephrine) pen?

People who are at risk of anaphylaxis (see above) should carry two adrenaline (epinephrine) pens at all times. You should be prescribed an adrenaline (epinephrine) auto-injector and taught how to use it. Parents and carers should also be shown how to use the auto-injectors. If for any reason you would be unable to use such a device (for example, young children, and those with some physical disabilities or a learning difficulty), parents or carers should be instructed.

One of the most important things is that you carry the auto-injectors with you at all times - in your bag or about your person.

Check the expiry dates on your auto-injectors, and speak to a pharmacist if you need a new one.

How many adrenaline (epinephrine) pens do I need?

The UK's Medicines & Healthcare products Regulatory Agency (MHRA) recommends that people at risk of anaphylaxis should have two adrenaline auto-injectors with them at all times.

This is in case a second dose of adrenaline is required before the ambulance can arrive, or if the first auto-injector malfunctions or isn't injected into the right place.

Children may need a total of four auto-injectors (two to be kept at school, and two to be carried at all other times). Once they are able to use the auto-injectors themselves, and are allowed to carry the auto-injectors on their own at school, they can go back to having two auto-injectors in total, which they should keep with them at all times.

The British Society for Allergy and Clinical Immunology (BSACI) recommends that doctors try to avoid prescribing more than two (or four, for a child) adrenaline auto-injectors at once. This is because they want to encourage people to carry their auto-injectors with them at all times, instead of keeping sets in different locations which might not always be accessible at once.

How to use an adrenaline auto-injector

Note: the following is a guide. It is not intended as a substitution for proper training and instruction. Dummy devices exist that can be practised with (they do not contain any adrenaline (epinephrine) or have a needle).

To use Emerade®

• Remove the cap protecting the needle.

• Hold Emerade® against the outer side of your thigh and press it against your leg. You will hear a click when the adrenaline (epinephrine) is injected.

• Keep holding the pen against your leg for about 5 seconds. This allows the full dose of adrenaline (epinephrine) to be injected.

• Massage the area for 10 seconds. This helps the adrenaline (epinephrine) to work more quickly.

• Make sure you tell the paramedics that you have used an adrenaline (epinephrine) pen.

For more information on how to give Emerade®, see www.emerade-bausch.co.uk.

NB: in May 2023, the MHRA advised that all batches of Emerade® 150 microgram, 300 microgram, and 500 microgram auto-injector pens be recalled from patients due to an error in one component of the auto-injector, believed to cause the failure of some pens to activate. Emerade® is not currently available in the UK, and other brands should be prescribed instead. See Further Reading below for more information.

To use EpiPen®

• Pull off the blue safety release cap at the end.

• Hold the pen firmly and swing your arm from about 10 cm (4 inches) away, pushing the orange tip against your outer thigh.

• The adrenaline (epinephrine) will be released automatically into your thigh muscle.

• Hold the pen in place for 10 seconds.

• As soon as you release pressure, a protective cover will extend over the needle tip.

• Massage the area for 10 seconds.

• Make sure you tell the paramedics that you have used an adrenaline (epinephrine) pen.

For more information on how to give EpiPen®, see www.epipen.com.

To use Jext®

• Grasp the pen in your writing hand, with your thumb closest to the yellow cap.

• Pull off the yellow cap.

• Push the black tip firmly against your outer thigh. You will hear a click which means the injection has started.

• Hold the injector in place against your thigh for 10 seconds; then remove it.

• The needle shield will automatically cover the needle when you remove the pen.

• Massage the area for 10 seconds.

• Make sure you tell the paramedics that you have used an adrenaline (epinephrine) pen.

For more information on how to give Jext®, see www.jext.co.uk.

What is the outlook (prognosis) for anaphylaxis?

If you have had a confirmed anaphylactic reaction, you should be referred to an allergy specialist. Generally you would be seen in a hospital outpatient clinic by a consultant immunologist.

As an outpatient, further blood tests and other tests for allergies may be done. An example would be skin prick testing. See the separate leaflet called Skin prick allergy test for more details.

Adrenaline auto-injectors should be prescribed to anyone who has had anaphylaxis or is thought to be at risk of anaphylaxis, even if they are still waiting to see an allergy specialist.

Sometimes, if doctors are not sure whether someone is at risk of anaphylaxis, they may prescribe an auto-injector anyway as a safety measure.

Everyone who has been prescribed an adrenaline auto-injector should be seen by an allergy specialist. They might recommend continuing to carry auto-injectors, but sometimes may say that it isn't necessary.

It is a good idea to have a medical emergency identification bracelet or equivalent if you have a history of anaphylaxis. Any medically trained person, including paramedics, will check to see if a collapsed patient is wearing such an item.