Anaphylaxis

Anaphylaxis is a serious allergic reaction.  It begins suddenly. In some reactions there is a second wave which happens minutes or even hours after the first. It may cause death.Tintinalli, Judith E. 2010. Emergency medicine: a comprehensive study guide. New York: McGraw-Hill, 177–182.   Anaphylaxis has many symptoms (signs of being sick), such as an itchy rash, throat swelling, breathing problems, and low blood pressure. Common causes include insect bites, foods, and medications.

Anaphylaxis happens when a person eats, breathes in, or ingests an allergen (something they are allergic to).  Their immune system over-reacts.  It sends out special proteins from inside certain white blood cells.  These proteins can start an allergic reaction or make the reaction worse.

Anaphylaxis is diagnosed (found to be sick with something) from a person’s signs and symptoms.  The best treatment is an injection (a shot) of epinephrine (adrenaline).  Sometimes doctors give other medicines along with epinephrine.

Worldwide, about 0.05–2% of people have anaphylaxis at some point in their lives.  Anaphylaxis appears to be getting more common. Half of the people who die of anaphylaxis have had no anaphylactic reaction before.

 History 
Cases of anaphylaxis have been reported since ancient times.

The condition was originally named "aphylaxis" by Charles Richet in 1902.  In 1913, Richet was awarded the Nobel Prize in Medicine and Physiology for his work on anaphylaxis.

Later, the name was changed to "anaphylaxis" because it sounded nicer.  The word "anaphylaxis" comes from the Greek words ἀνά (ana), against, and φύλαξις (phyla's), protection.

 Signs and symptoms 

Anaphylaxis can cause many different signs and symptoms over minutes or hours.  If the anaphylaxis is caused by something that entered the body directly through the bloodstream  symptoms appear within an average of 5 to 30 minutes.  If it is caused by a food the person ate symptoms appear up to 2 hours later.

The most common body systems affected by anaphylaxis include:
 Skin (affected in 80–90% of cases)
 Lungs and breathing pathways (70%)
 Stomach and intestines (30–45%)
 Heart and blood vessels (10–45%)
 Central nervous system (10–15%)

People with anaphylaxis usually have problems with two or more of these body systems.

Skin symptoms
Skin symptoms usually include:
 Hives (raised, itchy bumps on the skin)
 Itchiness
 Flushing (a red face or skin)
 Swollen lips 
 Runny nose
 Swelling of the mucous membrane on the surface of the eye and eyelid (conjunctiva)
 Angioedema (swelling under the skin).  People with angioedema may feel like their skin is burning instead of itching. 
In 20% of cases, the tongue or throat may swell up, which can cause breathing problems.Limsuwan T; Demoly P 2010. Acute symptoms of drug hypersensitivity (urticaria, angioedema, anaphylaxis, anaphylactic shock)." The Medical clinics of North America 94 (4): 691–710, x.    If a person is having breathing problems, the skin may turn blue because the body is not getting enough oxygen.  This is called cyanosis.

Respiratory (breathing) symptoms
Respiratory signs and symptoms include: 
 Trouble breathing (also called dyspnea or shortness of breath)
 Bronchoconstriction (when the bronchi, the tubes that bring air to the lungs, get narrower; this makes it harder for air to get to the lungs)
 Hoarseness, pain with swallowing, or a cough
 When a medical professional listens to the patient's lungs with a stethoscope, they may hear:
 Low-pitched sounds called wheezes, caused by bronchoconstriction
 High-pitched sounds called stridor, caused by swelling in the upper airway

Cardiovascular symptoms
When a person has anaphylaxis, some of the cells in the heart may release histamine. Histamine is a chemical made by the body. It can cause the heart’s blood vessels to get narrower suddenly (this is called "coronary artery spasm").  If the heart's blood vessels get too narrow, the heart cannot get enough blood.  This can cause many serious problems:Simons F.E. 2009. Anaphylaxis: recent advances in assessment and treatment. J. Allergy Clin. Immunol. 124 (4): 625–36; quiz 637–8.
 Heart cells can die.  This is called a myocardial infarction, or a heart attack
 The heart may beat too slowly or too quickly (these are called cardiac arrhythmias)
 The heart may stop beating altogether.  This is called cardiac arrest.

Anaphylaxis can also cause low blood pressure.  This may be caused by distributive shock, where the body's blood vessels get much wider because of the chemicals released by the immune system.  It can also be caused by cardiogenic shock, where the heart is not getting enough blood to pump out to the rest of the body.

Low blood pressure can cause many problems, including:
 A fast heart rate
 A slow heart rate.  This is not very common.  It happens in about 10% of cases.  It is called the Bezold-Jarisch reflexLee J.K. & Vadas. P. 2011. Anaphylaxis: mechanisms and management". Clinical and experimental allergy. 41 (7): 923–38.
 Syncope (fainting)

In rare cases, very low blood pressure may be the only sign of anaphylaxis.

People who already have heart disease are at greater risk of having heart problems from anaphylaxis.

Other symptoms
Anaphylaxis can also cause problems with other body systems:
 Stomach and intestines: A person may have abdominal pain, diarrhea, or vomiting (throwing up) 
 Urinary and genital systems: Women may have pain in the pelvis that feels like cramps in the uterus.  Men and women may lose control of their bladder.  
 Central nervous system: A person may have confused thoughts.  They may have headaches caused by blood vessels in the brain getting wider.  They may feel anxious (very worried) and believe they are going to die.

Causes
Anaphylaxis can be caused by the body’s response to almost any foreign substance (anything that is outside the body). Common causes include venom from insect bites or stings; foods; and medications.  In children and young adults, foods are the most common trigger (or cause) of anaphylaxis.  In older adults, medications and insect bites or stings are more common triggers.

 Food 
Many foods can trigger anaphylaxis, even when the food is eaten for the first time. In the Western world, the most common causes are eating or touching peanuts, wheat, tree nuts, shellfish, milk, and eggs.  In the Middle East, sesame is a common trigger food.  In Asia, rice and chickpeas often cause anaphylaxis.

Severe cases of anaphylaxis usually happen when a person eats the trigger food.  However, some people have severe anaphylaxis when the trigger food touches some part of their body.

Children can outgrow their allergies.  For example, by age 16:
 80% of children with anaphylaxis to milk or eggs can eat these foods with no problems
 20% of children who had only one case of anaphylaxis to peanuts can eat peanuts with no problems
Infants can have reactions too. There is a list of foods babies can't eat. A common cause of harm for babies (especially with new parents) is raw milk or animal milk, which their body can not handle. Breastmilk and Formulae won't cause anaphylaxis.

Allergic reactions are especially dangerous for young children, because they can't talk, or might not know what's happenening. 

 Medication 
Any medication may cause anaphylaxis. The most common are β-lactam antibiotics (such as penicillin), then aspirin and NSAIDs.

Venom
Venom from stinging or biting insects, like bees and wasps (Hymenoptera) or kissing bugs (Triatominae), may cause anaphylaxis.  If a person has a bad allergic reaction to venom once, they have a greater risk of having anaphylaxis if they are stung or bitten again.  

Risk factors
Certain diseases, called atopic diseases, can make a person more likely to have allergies.  Atopic diseases include asthma, eczema, and allergic rhinitis.  People with these diseases have a high risk of anaphylaxis from food, latex, and radiocontrast agents.  However, these people do not have a higher risk from injected medications or stings. One study of children with anaphylaxis found that 60% had a history of previous atopic diseases.  More than 90% of children who die from anaphylaxis have asthma. The risk of having another anaphylactic reaction decreases as a person avoids the trigger for longer and longer.

 How anaphylaxis happens 
Anaphylaxis usually happens because the immune system over-reacts to an allergen.  The immune system releases mast cells and basophils, which are types of white blood cells.  The immune system sees the trigger as something bad and sends out white blood cells to kill it.  The mast cells and basophils attach to the allergen to try to kill it.  However, because the system is over-reacting, the mast cells and basophils explode and dump out chemicals that cause inflammation, like histamine.  Histamine causes many of the symptoms of anaphylaxis.  For example:
 Bronchoconstriction (where the tubes that carry air to the lungs get narrower)
 Vasodilation (where the blood vessels get wider)
 Fluid leaks out of blood vessels
 The heart muscle does not work as well

 Diagnosis 
Anaphylaxis is diagnosed based on signs, symptoms, and knowing that a person has been exposed to an allergen.  It is very likely that a person has anaphylaxis if any of these three things happen within minutes or hours after they were exposed to an allergen:
 Problems with the skin or mucosal tissue, plus either breathing problems or a low blood pressure
 Two or more of these symptoms:
 Problems with the skin or mucosa
 Breathing problems
 Low blood pressure
 Gastrointestinal symptoms
 Low blood pressure after exposure to an allergen

If a person has a bad reaction to an insect sting or a medication, blood tests for tryptase or histamine might be useful in diagnosing anaphylaxis. However, these tests are not very useful if the cause is food, or if the person has a normal blood pressure.  Also, these tests cannot say for sure that a person does not have anaphylaxis.

Allergy testing
Allergy testing may help to identify what caused a person’s anaphylaxis. Skin allergy tests (such as patch tests) can be done for certain foods and venoms.  Skin tests can diagnose an allergy to penicillin, but there are no skin tests for other medications.  Blood tests can diagnose milk, egg, peanut, tree nut and fish allergies.

 Differential diagnosis 
Sometimes it is difficult to tell the difference between anaphylaxis; asthma; fainting caused by not having enough oxygen; and panic attacks.  However, there are some important differences between these conditions:
 People with asthma usually do not have itching, swelling, or problems with their stomach or intestines. 
 After fainting, a person's skin is pale, and they will not have a rash or swelling.  Their breath sounds will be normal.
 A person who is having a panic attack may have flushed skin, but will not have hives or swelling.  Usually their blood pressure will not be low.  Their breath sounds will be normal.

 Prevention 
The best way to prevent anaphylaxis is to avoid the trigger that caused anaphylaxis in the past.  When this is not possible, there may be treatments to make the body stop reacting to the trigger.  This is called desensitization.  For example, treatment of the immune system (immunotherapy) with Hymenoptera venoms is able to make 80–90% of adults and 98% of children stop having allergic reactions to bees, wasps, hornets, yellow jackets, and fire ants.  Most people who are allergic to certain medicines can just avoid those medicines.  However, desensitization is possible for many medications (for example, many chemotherapies) if the person has to take those medicines.

People with latex allergies may have to avoid "cross-reactive foods."  These are foods that have ingredients that are similar to latex.  Examples of these foods include avocados, bananas, and potatoes.Simons F.E. 2010. World Allergy Organization survey on global availability of essentials for the assessment and management of anaphylaxis by allergy-immunology specialists in health care settings". Annals of allergy, asthma & immunology 104 (5): 405–12.  

 Management 
Anaphylaxis is a medical emergency that may require emergency medical treatment.  Some patients need help keeping their airways open so they can breathe.   Other patients need to be given extra oxygen or large amounts of intravenous fluids (fluids given through a needle into a vein).

Epinephrine is the best treatment for anaphylaxis.  Doctors often give antihistamines (which destroy histamine) and steroids along with epinephrine.  Once a person has returned to normal, they should be watched in the hospital for 2 to 24 hours to make sure their symptoms do not return.Lieberman P 2005. Biphasic anaphylactic reactions. Ann. Allergy Asthma Immunol. 95 (3): 217–26; quiz 226, 258. thumb|An old version of an EpiPen auto-injector
Epinephrine is the best and first treatment used for anaphylaxis.  It reverses many of the symptoms of anaphylaxis.  It makes the bronchi (the passages to the lungs) get wider. It makes the blood vessels go back to their normal size and it raises blood pressure.

Epinephrine comes in an "auto-injector," usually called an "EpiPen."  Once its safety cap is taken off, the EpiPen just has to be pressed into the thigh, and the right amount of epinephrine will automatically be injected into the person's body.  Doctors can prescribe EpiPens to people who know they have allergies, so they can treat themselves for anaphylaxis.  Many ambulances also carry EpiPens to treat anaphylaxis. The EpiPen is meant to be injected into the thigh muscle, on the outside of the leg, as soon as anaphylaxis is suspected.  There is no reason why it should not be used if a person is having an anaphylactic reaction.  The injection may be repeated every 5 to 15 minutes if the person is still having breathing problems or other major symptoms. A second dose is needed in 16 to 35% of cases. More than two doses are rarely needed.

Epinephrine can cause minor side effects, including tremors, anxiety, headaches, and palpitations.

Epinephrine may not work in people who are taking β-blockers.  In these people, if epinephrine does not work, doctors can give intravenous glucagon.

 Being prepared 
People who are at risk for anaphylaxis are advised to have an "allergy action plan."  These plans often include:
 Knowing how to use an EpiPen properly and what the signs of an attack look like
 Parents telling schools about their children's allergies and what to do in case of an anaphylactic emergency
 Wearing a medical alert bracelet that says what the person is allergic to 
 Planning for how to avoid triggers

 Outlook 
If anaphylaxis is diagnosed and the person is treated quickly, there is a good chance that they will recover.  Even if nobody knows what caused the anaphylaxis, the person usually makes a good recovery as long as they get medication to stop the reaction.

When people die from anaphylaxis, they usually die from respiratory (breathing) problems, usually the airway closing up, or cardiovascular problems, like shock. About 0.7% to 20% of people with anaphylaxis die from it.  Some people die within minutes.

Very rarely, people have exercise-induced anaphylaxis - anaphylaxis that is caused by exercise.  These people usually do well.  They usually have fewer anaphylactic episodes, which are less severe, as they get older.Demain JG; Minaei AA, Tracy JM 2010. Anaphylaxis and insect allergy. Current Opinion in Allergy and Clinical Immunology 10 (4): 318–22.

References

Category:Medical emergencies
Category:Allergies