Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.

It typically causes a number of symptoms including an itchy rash, throat swelling, and low blood pressure. Common causes include insect bites/stings, foods, and medications.

Anaphylaxis is caused by the release of mediators from certain types of white blood cells triggered either by immunologic or non-immunologic mechanisms.

It is diagnosed on the basis of the presenting symptoms and signs.

The primary treatment is an injection of epinephrine, the administration of intravenous fluids, and positioning the person flat, with other measures being complementary.

Signs and symptoms

Anaphylaxis typically presents many different symptoms over minutes or hours with an average onset of 5-30 minutes if exposure is intravenous and 2 hours for foods.

The most common areas affected include skin (80–90%), respiratory (70%), gastrointestinal (30–45%), heart and vasculature (10–45%), and central nervous system (10–15%) with usually two or more being involved.

Symptoms typically include generalized hives, itchiness, flushing, or swelling (angioedema) of the afflicted tissues. Those with angioedema may describe a burning sensation of the skin rather than itchiness.

Swelling of the tongue or throat occurs in up to about 20% of cases. Other features may include a runny nose and swelling of the conjunctiva. The skin may also be blue-tinged because of a lack of oxygen.

Respiratory

Respiratory symptoms and signs that may be present include: shortness of breath, wheezes, or stridor.

The wheezing is typically caused by spasms of the bronchial muscles while stridor is related to upper airway obstruction secondary to swelling. Hoarseness, pain with swallowing, or a cough may also occur.

Cardiovascular

Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest. Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis.

Coronary spasm is related to the presence of histamine-releasing cells in the heart.

A drop in blood pressure or shock (either distributive cardiogenic) may cause a feeling of lightheadedness or loss of consciousness. Rarely very low blood pressure may be the only sign of anaphylaxis.

Other

Gastrointestinal symptoms may include crampy abdominal pain, diarrhea, and vomiting.

There may be confusion, a loss of bladder control or pelvic pain similar to that of uterine cramps.

Dilation of blood vessels around the brain may cause headaches. A feeling of anxiety or of “impending doom” has also been described.

Causes

Anaphylaxis can occur in response to almost any foreign substance. Common triggers include venom from insect bites or stings, foods, and medication.

Foods are the most common trigger in children and young adults while medications and insect bites and stings are more common in older adults.

Less common causes include physical factors, biological agents such as semen, latex, hormonal changes, food additives such as monosodium glutamate and food colors, and topical medications.

Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells.

Events caused by exercise are frequently associated with the ingestion of certain foods.

During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes.

The cause remains unknown in 32-50% of cases, referred to as “idiopathic anaphylaxis”.

Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and the HPV may cause anaphylaxis as well.

Food

Many foods can trigger anaphylaxis; this may occur upon the first known ingestion.

Common triggering foods vary around the world. In Western cultures, ingestion of or exposure to peanuts, wheat, nuts, certain types of seafood like shellfish, milk, and eggs are the most prevalent causes.

Severe cases are usually caused by ingesting the allergen, but some people experience a severe reaction upon contact.

Children can outgrow their allergies. By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts can tolerate these foods.

Medication

Any medication may potentially trigger anaphylaxis.

The most common are: penicillin, followed by aspirin and NSAIDs.

Other antibiotics are implicated less frequently and the reactions to NSAIDs are agent-specific meaning that if one is allergic to one NSAID they can typically tolerate a different one.

Other relatively common causes include chemotherapy, vaccines, protamine, and herbal preparations.

Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.

The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties.

Anaphylaxis to penicillins or cephalosporins only occurs after they bind to proteins inside the body with some agents binding more easily than others.

Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in less than one in every 50,000 courses of treatment.

Venom

Venom from stinging or biting insects such as Hymenoptera (bees and wasps) or Triatominae (kissing bugs) may cause anaphylaxis in susceptible people.

Previous systemic reactions, which are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis; however, half of the fatalities have had no previous systemic reaction.

Risk factors

People with atopic diseases such as asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex, and radiocontrast but not from injectable medications or stings.

Diagnosis

Anaphylaxis is diagnosed on the basis of a person’s signs and symptoms. When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis:

Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure

Two or more of the following symptoms after a likely contact with an allergen:

a. Involvement of the skin or mucosa
b. Respiratory difficulties
c. Low blood pressure
d. Gastrointestinal symptoms

Low blood pressure after exposure to a known allergen

During an attack, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications.

However these tests are of limited use if the cause is food or if the person has normal blood pressure, and they are not specific for the diagnosis.

Prevention

Avoidance of the trigger of anaphylaxis is recommended. In cases where this may not be possible, desensitization may be an option.

Immunotherapy with Hymenoptera venoms is effective at desensitizing 80–90% of adults and 98% of children against allergies to bees, wasps, hornets, yellow jackets, and fire ants. Oral immunotherapy may be effective at desensitizing some people to certain food including milk, eggs, nuts, and peanuts; however, adverse effects are common.

Desensitization is also possible for many medications, however, it is advised that most people simply avoid the agent in question. In those who react to latex, it may be important to avoid cross-reactive foods such as avocados, bananas, and potatoes among others.

Management

Anaphylaxis is a medical emergency that may require resuscitation measures such as airway management, supplemental oxygen, large volumes of intravenous fluids, and close monitoring.

Administration of epinephrine is the treatment of choice with antihistamines and steroids (for example, dexamethasone) often used as adjuncts.

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