Anaphylaxis

Anaphylaxis is an acute systemic (multi-system) and severe Type I Hypersensitivity allergic reaction in humans and other mammals. The term comes from the Greek words ανα ana (against) and φύλαξις phylaxis (protection).^[1] Anaphylaxis occurs when a person or animal is exposed to a trigger substance, called an allergen, to which they have already become sensitized. Minute amounts of allergens may cause a life-threatening anaphylactic reaction. Anaphylaxis may occur after ingestion, skin contact, injection of an allergen or, in rare cases, inhalation.^[2]

Anaphylactic shock, the most severe type of anaphylaxis, occurs when an allergic response triggers a quick release from mast cells of large quantities of immunological mediators (histamines, prostaglandins, leukotrienes) leading to systemic vasodilation (associated with a sudden drop in blood pressure) and edema of bronchial mucosa (resulting in bronchoconstriction and difficulty breathing). Anaphylactic shock can lead to death in a matter of minutes if left untreated.

An estimated 1.24% to 16.8% of the population of the United States is considered "at risk" for having an anaphylactic reaction if they are exposed to one or more allergens, especially penicillin and insect stings. Most of these people successfully avoid their allergens and will never experience anaphylaxis. Of those people who actually experience anaphylaxis, up to 1% may die as a result.^[3] Anaphylaxis results in fewer than 1,000 deaths per year in the U.S. (compared to 2.4 million deaths from all causes each year in the U.S.^[4]). The most common presentation includes sudden cardiovascular collapse (88% of reported cases of severe anaphylaxis).

Researchers typically distinguish between "true anaphylaxis" and "pseudo-anaphylaxis or an anaphylactoid reaction." The symptoms, treatment, and risk of death are identical, but "true" anaphylaxis is always caused directly by degranulation of mast cells or basophils that is mediated by immunoglobulin E (IgE), and pseudo-anaphylaxis occurs due to all other causes.^[5] The distinction is primarily made by those studying mechanisms of allergic reactions.

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Symptoms

Symptoms of anaphylaxis are related to the action of (IgE) and other anaphylatoxins, which act to release histamine and other mediator substances from mast cells (degranulation). In addition to other effects, histamine induces vasodilation of arterioles and constriction of bronchioles in the lungs, also known as bronchospasm (constriction of the airways).

Symptoms can include the following:

• polyuria
• respiratory distress
• hypotension (low blood pressure)
• encephalitis
• fainting
• unconsciousness
• urticaria (hives)
• flushed appearance
• angioedema (swelling of the lips, face, neck and throat)
• tears (due to angioedema and stress)
• vomiting
• itching
• diarrhea
• abdominal pain
• anxiety

The time between ingestion of the allergen and anaphylaxis symptoms can vary for some patients depending on the amount of allergen consumed and their reaction time. Symptoms can appear immediately, or can be delayed by half an hour to several hours after ingestion.^[6] However, symptoms of anaphylaxis usually appear very quickly once they do begin.

Causes

Anaphylaxis is a severe, whole-body allergic reaction. After an initial exposure to a substance like bee sting toxin, the person's immune system becomes sensitized to that allergen- Shocking dose. On a subsequent exposure, an allergic reaction occurs. This reaction is sudden, severe, and involves the whole body.

Tissues in different parts of the body release histamine and other substances. This causes constriction of the airways, resulting in wheezing, difficulty breathing, and gastrointestinal symptoms such as abdominal pain, cramps, vomiting, and diarrhea. Histamine causes the blood vessels to dilate (which lowers blood pressure) and fluid to leak from the bloodstream into the tissues (which lowers the blood volume). These effects result in shock. Fluid can leak into the alveoli (air sacs) of the lungs, causing pulmonary edema.

Hives and angioedema (hives on the lips, eyelids, throat, and/or tongue) often occur. Angioedema may be severe enough to block the airway. Prolonged anaphylaxis can cause heart arrhythmias.

Some drugs (polymyxin, morphine, x-ray dye, and others) may cause an "anaphylactoid" reaction (anaphylactic-like reaction) on the first exposure.^[7] This is usually due to a toxic reaction, rather than the immune system mechanism that occurs with "true" anaphylaxis. The symptoms, risk for complications without treatment, and treatment are the same, however, for both types of reactions.

Anaphylaxis can occur in response to any allergen. Common causes include insect bites/stings, horse serum (used in some vaccines), food allergies, and drug allergies. Pollens and other inhaled allergens rarely cause anaphylaxis. In opthamology, the dye fluorescein used in some eye exams is a well known trigger. Some people have an anaphylactic reaction with no identifiable cause.

Anaphylaxis occurs infrequently. However, it is life-threatening and can occur at any time. Risks include prior history of any type of allergic reaction.

Treatment

Emergency treatment

  Anaphylaxis is a life-threatening medical emergency because of rapid constriction of the airway, often within minutes of onset, which can lead to respiratory failure and respiratory arrest. Brain and organ damage rapidly occurs if the patient cannot breathe. Due to the severe nature of the emergency, patients experiencing or about to experience anaphylaxis require the help of advanced medical personnel. First aid measures for anaphylaxis include rescue breathing (part of CPR). Rescue breathing may be hindered by the constricted airways, but if the victim stops breathing on his or her own, it is the only way to get oxygen to him or her until professional help is available.

Another treatment for anaphylaxis is administration of epinephrine (adrenaline). Epinephrine prevents worsening of the airway constriction, stimulates the heart to continue beating, and may be life-saving. Epinephrine acts on Beta-2 adrenergic receptors in the lung as a powerful bronchodilator (i.e. it opens the airways), relieving allergic or histamine-induced acute asthmatic attack or anaphylaxis. If the patient has previously been diagnosed with anaphylaxis, he or she may be carrying an EpiPen (or TWINJECT TM) for immediate administration of epinephrine. However, use of an EpiPen or similar device only provides temporary and limited relief of symptoms.

Tachycardia (rapid heartbeat) results from stimulation of Beta-1 adrenergic receptors of the heart increasing contractility (positive inotropic effect) and frequency (chronotropic effect) and thus cardiac output.^[8] Repetitive administration of epinephrine can cause tachycardia and occasionally ventricular tachycardia with heart rates potentially reaching 240 beats per minute, which itself can be fatal. Extra doses of epinephrine can sometimes cause cardiac arrest. This is why some protocols advise intramuscular injection of only 0.3–0.5mL of a 1:1,000 dilution.

Some patients with severe allergies routinely carry preloaded syringes containing epinephrine, diphenhydramine (Benadryl), and dexamethasone (Decadron) whenever they go to an unknown or uncontrolled environment.

Clinical care

Paramedic treatment in the field includes administration of epinephrine IM, antihistamines IM (e.g. chlorphenamine, diphenhydramine), steroids such as hydrocortisone, IV Fluid administration and in severe cases, pressor agents (which cause the heart to increase its contraction strength) such as dopamine for hypotension, administration of oxygen, and intubation during transport to advanced medical care.

In severe situations with profuse laryngeal edema (swelling of the airway), cricothyrotomy or tracheotomy may be required to maintain oxygenation. In these procedures, an incision is made through the anterior portion of the neck, over the cricoid membrane, and an endotracheal tube is inserted to allow mechanical ventilation of the victim.

The clinical treatment of anaphylaxis by a doctor and in the hospital setting aims to treat the cellular hypersensitivity reaction as well as the symptoms. Antihistamine drugs such as diphenhydramine or chlorphenamine (which inhibit the effects of histamine at histamine receptors) are continued but are usually not sufficient in anaphylaxis, and high doses of intravenous corticosteroids such as dexamethasone or hydrocortisone are often required. Hypotension is treated with intravenous fluids and sometimes vasopressor drugs. For bronchospasm, bronchodilator drugs (e.g. salbutamol, known as Albuterol in the United States) are used. In severe cases, immediate treatment with epinephrine can be lifesaving. Supportive care with mechanical ventilation may be required.

It is also possible to undergo a second reaction prior to medical attention or using an Epipen. It is suggested to seek one to two days of medical care.

The possibility of biphasic reactions (recurrence of anaphylaxis) requires that patients be monitored for four hours after being transported to medical care for anaphylaxis.^[9]

Planning for emergency treatment

The Asthma and Allergy Foundation of America advises patients prone to anaphylaxis to have an "allergy action plan" on file at school, home, or in their office to aid others in case of an anaphylactic emergency, and provides a free "plan" form.^[10] Action plans are considered essential to quality emergency care. Many authorities advocate immunotherapy to prevent future episodes of anaphylaxis.^[11]

Beta-blockers may aggravate anaphylactic reactions and interfere with treatment.

Prevention

Immunotherapy with Hymenoptera venoms is especially effective and widely used throughout the world and is accepted as an effective treatment for most patients with allergy to bees, wasps, hornets, yellow jackets, white faced hornets, and fire ants.^[12]

The greatest success with prevention of anaphylaxis has been the use of allergy injections to prevent recurrence of sting allergy. The risk to an individual from a particular species of insect depends on complex interactions between likelihood of human contact, insect aggression, efficiency of the venom delivery apparatus, and venom allergenicity. According to most authorities, venom immunotherapy has been demonstrated to reduce the risk of systemic reactions below 1% to 3%. One simple method of venom extraction has been electrical stimulation to obtain venom, instead of dissecting the venom sac. An allergist will then provide venom immunotherapy which is highly efficacious in preventing future episodes of anaphylaxis.

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