anaphylaxis

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Definition

Anaphylaxis is a rapidly progressing, life-threatening allergic reaction.

Description

Anaphylaxis is a type of allergic reaction, in which the immune system responds to otherwise harmless substances from the environment. Unlike other allergic reactions, however, anaphylaxis can kill. Reaction may begin within minutes or even seconds of exposure, and rapidly progress to cause airway constriction, skin and intestinal irritation, and altered heart rhythms. In severe cases, it can result in complete airway obstruction, shock, and death.

— Richard Robinson

1. Hypersensitivity especially in animals to a substance, such as foreign protein or a drug, that is caused by exposure to a foreign substance after a preliminary exposure.
2. See anaphylactic shock.

[ANA– + (PRO)PHYLAXIS.]

A generalized or localized tissue reaction occurring within minutes of an antigen-antibody reaction. Similar reactions elicited by nonimmunologic mechanisms are termed anaphylactoid reactions. In humans, the clinical manifestations of anaphylaxis include reactions of the skin with itching, erythema, and urticaria; the upper respiratory tract with edema of the larynx; the lower respiratory tract with dyspnea, wheezing, and cough; the gastrointestinal tract with abdominal cramps, nausea, vomiting, and diarrhea; and the cardiovascular system with hypotension and shock. Individuals undergoing anaphylactic reactions may develop any one, a combination, or all of the signs and symptoms. Anaphylaxis may be fatal within minutes, or may occur days or weeks after the reaction, if the organs sustained considerable damage during the hypotensive phase.

Anaphylaxis in humans is most often the result of the interaction of specific IgE antibody fixed to mast cells and antigen. Two molecules of IgE are bridged by the antigen, which may be a complex protein or chemical (hapten) bound to protein. The antigen-antibody interaction leads to increased cell-membrane permeability, with influx of calcium and release of either preformed or newly formed pharmacologic mediators from the granules. Preformed mediators include histamine and eosinophilic or neutrophilic chemotactic factors. Newly formed molecules include leukotrienes or slow-reacting substance of anaphylaxis and prostaglandins. The mediator action induces bronchoconstriction, vasodilation, cellular infiltration, and increased mucus production.

Another mechanism for induction of anaphylaxis in humans occurs when antigen binds to preformed IgG antibody and complement components interact with the antigen-antibody complex. The early components of the complement system bind to the antibody molecule, leading to activation of other complement components. During the activation, components known as anaphylatoxins (C3a and C5a) are released which may directly cause bronchoconstriction with respiratory impairment, and vasodilation with hypotension or shock. See also Complement; Eicosanoids.

Anaphylaxis due to IgE mechanisms has been associated with foreign proteins such as horse antitoxins, insulin, adrenocorticotropic hormone (ACTH), protamine, and chymopapain injected into herniated discs; drugs such as penicillin and its derivatives; foods such as shellfish, nuts, and eggs; and venom of stinging insects. Anaphylaxis mediated by IgG is seen in blood-transfusion reactions and following the use of cryoprecipitate, plasma, or immunoglobulin therapy.

After the identification of the inciting agent for the anaphylactic reaction, prevention is the best mode of therapy. Immunotherapy with insect venom and desensitization with certain drugs are effective prophylactic measures. Individuals with recurrent episodes of anaphylaxis, when the etiological cause is unknown and preventive measures are impractical, should be provided with epinephrine in a form that can be self-administered whenever symptoms occur. See also Epinephrine.

The treatment of anaphylaxis is aimed at reducing the effect of the chemical mediators on the end organs and preventing further mediator release. The drug of choice for this is epinephrine given subcutaneously in repeated doses. Additionally, a clear airway and appropriate oxygenation must be maintained; hypotension should be treated, as should any cardiac arrhythmia. See also Antigen-antibody reaction; Hypersensitivity; Shock syndrome.

Hypersensitivity to certain agents, resulting in pain, swelling, and feverishness. A form of anaphylaxis occurs in individuals suffering from nettle rash (urticaria) or asthma, and those who eat foods to which their bodies are allergic (see food allergy).

A condition called exercise-induced anaphylaxis is triggered in some people by combinations of exercise and particular foods. Typically, symptoms occur five minutes into a bout of intense exercise. Itching is the most common symptom, but others include rashes and difficulty in breathing. The most common food associated with exercise-induced anaphylaxis is raw celery, but other foods including shellfish, peaches, grapes, wheat, and alcohol may increase the risk of an attack. Medications, such as aspirin and antibiotics, have also been linked with the condition. In the USA, there have been over 1000 documented cases of exercise-induced anaphylaxis but no reports of death. However, other forms of anaphylaxis can be more serious (see anaphylactic shock).

A violent allergic reaction characterized by sudden collapse, shock, or respiratory and circulatory failure after injection of an allergen.

Definition

Anaphylaxis is a severe, sudden, and potentially fatal allergic reaction to a foreign substance or antigen that affects multiple systems of the body.

Description

Anaphylaxis is a severe, whole-body allergic reaction. After initial exposure to a substance such as wasp sting toxin, the allergic child's immune system becomes sensitized to that allergen. On a subsequent exposure to the specific allergen, an allergic reaction, which can involve a number of different areas of the body, occurs. Anaphylaxis is thought to result from antigen-antibody interactions on the surface of mast cells, connective tissue cells that are believed to contain a number of regulatory, or mediator, chemicals. Specifically, an immunoglobulin antibody protein, IgE, is produced in response to the presence of the allergen. IgE binds to the mast cells, causing them to suddenly release a number of chemicals, including histamine, heparin, serotonin, and bradykinin. Once released, these chemicals produce the bodily reactions that characterize anaphylaxis: constriction of the airways, causing wheezing and difficulty in breathing; and gastrointestinal symptoms, such as abdominal pain, cramps, vomiting, and diarrhea. Shock can occur when the released histamine causes the blood vessels to dilate, which lowers blood pressure; histamine also causes fluids to leak from the bloodstream into the tissues, lowering the blood volume. Pulmonary edema can result from fluids leaking into the alveoli (air sacs) of the lung.

Substances that can trigger an anaphylactic reaction include:

• insect stings from hornets, wasps, yellow jackets, honey bees, or fire ants
• medications, including penicillin, cephalosporin, anesthetics, streptokinase, and others
• foods (ingesting even tiny amounts or simply being near the offending food), including peanuts, tree nuts (such as walnuts or almonds), fish, shellfish, eggs, milk, soy, and wheat
• vaccines, including allergy shots and egg- and gelatin-based vaccines
• hormones, including insulin and possibly progesterone
• rubber latex products
• animal and human proteins, including seminal fluid and horse serum (which is used as snake anti-venom)

Anaphylactoid (meaning "anaphylactic-like") reactions are similar to those of true anaphylaxis but do not require an IgE immune reaction. These are usually caused by direct stimulation of the mast cells. The same chemicals as with anaphylaxis are released, with the same effects, so the symptoms are treated the same way. However, an anaphylactoid reaction can occur on initial exposure to an allergen as well as on subsequent exposures, since no sensitization is required.

There is also a rare kind of food allergy, called exercise-induced allergy, that is caused by eating a specific food and then exercising. It can produce itching, lightheadedness, hives, and anaphylaxis. The offending food does not cause a reaction without exercise, and, alternately, exercise does not cause a reaction without ingesting the food beforehand.

Demographics

Although likely an underestimate, about 10,000 cases of anaphylaxis occur per year in North America, with about 750 fatalities a year. The exact prevalence of anaphylaxis is unknown, because milder reactions may be attributed to asthma attacks or sudden cases of hives, and more serious or fatal episodes might be reported as heart attacks, as the initial symptoms of hives, asthma, and swollen throat can fade quickly.

Causes and Symptoms

The symptoms of anaphylaxis may occur within seconds of exposure, or be delayed 15 to 30 minutes and sometimes even an hour or more later, if the allergen is aspirin or other similar drugs. The sooner the symptoms occur after exposure, the more severe the anaphylactic reaction is likely to be.

The first symptoms of an anaphylactic reaction are associated with the skin: flushing (warmth and redness), itching (often in the groin or armpits), and hives. These symptoms are often accompanied by anxiety; a rapid, irregular pulse; and a sense of impending doom. Then the throat and tongue swell, the voice becomes hoarse, and swallowing and breathing become labored. Symptoms of rhinitis or asthma may also occur, causing a runny nose, sneezing, wheezing, and abnormal high-pitched breathing sounds, further worsening the breathing problems. Gastrointestinal effects may also develop, including vomiting, diarrhea, and stomach cramps. The child may be confused and have slurred speech. In about 25 percent of the cases, the chemicals flooding the blood stream will cause a generalized opening of capillaries (tiny blood vessels), resulting in a drop in blood pressure, lightheadedness, and even a loss of consciousness, which are typical symptoms of anaphylactic shock. The child may exhibit blueness of the skin (cyanosis), lips, or nail beds.

After the original symptoms occur, there are three possible outcomes:

• The symptoms may be mild and fade spontaneously or be quickly ended by administering emergency medication. The anaphylactic episode is over for that particular exposure.
• After initial improvement, the symptoms may reoccur after four to 12 hours (a late phase recurrent reaction) and require additional treatment and monitoring. Late phase reactions occur in about 10 percent of cases.
• The reaction may be persistent and severe, requiring extensive medical treatment and hospitalization. This condition occurs in about 20 percent of cases.

When to Call the Doctor

The child should be given immediate emergency care, if possible, and then taken to the emergency room or the local emergency number (e.g., 911) should be called if symptoms of anaphylaxis develop.

Diagnosis

A child having an anaphylactic reaction will exhibit typical symptoms of anaphylaxis, such as hives and swelling of the eyes or face, blue skin from lack of oxygen, or pale skin from shock. The airway may be blocked, and the child may be wheezing as well as confused and weak. The pulse will be rapid and the blood pressure may be low. Anaphylaxis is an emergency condition that requires immediate professional medical attention.

Once a child has had an anaphylactic reaction, an allergist should be consulted to identify the specific allergen that caused the reaction. The allergist will take a detailed medical history and use blood or skin tests to identify the allergen. The allergist will ask about activities that the child participated in before the event, food and medications the child may have ingested, and whether the child had contact with any rubber products.

Treatment

Because of the severity of these reactions, treatment must begin immediately. The most common emergency treatment involves injection of epinephrine (adrenaline) to stop the release of histamines and relax the muscles of the respiratory tract. The injection is given in the outer thigh and can be administered through light fabric such as trousers, skirts, or stockings. Heavier clothing may have to be removed prior to the injection. After the injection, emergency services or 911 should be called immediately. A child with known severe allergic reactions should be carrying an allergy kit with epinephrine; if not, treatment will have to be delayed until emergency personnel can provide the required medication. For reactions to insect stings or allergy shots, a tourniquet should be placed between the puncture site and the heart; the tourniquet should be released every 10 minutes. If the child is conscious, he or she should lie down and elevate the feet. If trained, the parents or others present should administer CPR if the child stops breathing or does not have a pulse. After 10 to 15 minutes, if symptoms are still significant, another dose of epinephrine can be injected. Even after the reaction subsides, the child should still be taken to the emergency room immediately and monitored for three to four hours, since symptoms can redevelop. Other treatments may be given by medical personnel, including oxygen, intravenous fluids, breathing medications, and possibly more epinephrine. The epinephrine may make the child feel shaky and have a rapid, pounding pulse, but these are normal side effects and are only dangerous to those with heart problems. Steroids and antihistamines may also be given but are usually not as helpful initially as epinephrine. However, they may be useful in preventing a recurrent delayed reaction.

If the child is being treated with beta blocker medications commonly used to treat high blood pressure, angina, thyroid disorders, migraines, or glaucoma, it may be difficult to reverse an anaphylactic reaction.

Prognosis

Anaphylaxis is a severe disorder that has a poor prognosis without prompt treatment. Symptoms are usually resolved with appropriate therapy; therefore, immediate emergency care is essential.

Prevention

For children with known reactions to antibiotics, foods, insect stings, specific foods, or any of the allergens that can induce an anaphylactic reaction, avoidance of the symptom-inducing agent is the best form of prevention.

Specific avoidance measures that are recommended include:

Drugs/medications:

• Parents should advise healthcare personnel of the childs allergies.
• Parents should ask the doctor whether prescribed medications could contain the drug(s) to which the child is allergic.
• The child should take all medications by mouth, if possible, since the risk of anaphylaxis is greater with injections.
• Any child should stay in a doctors office or near medical care for a period of time after receiving injections of an antibiotic or vaccine.

Insect stings:

• The child should avoid areas where insects breed and live.
• The child should not wear bright clothing, perfume, hair spray, or lotions that might attract insects.
• If possible the child should wear long sleeves, long trousers, and shoes when out of doors.

Food:

• The child must be instructed to never again eat that kind of food that causes an anaphylactic reaction.
• Parents should carefully read all ingredient labels of foods that the child might eat and be aware of the different terms used for various foods, such as caseinate for milk or albumin for eggs.
• Parents should ask about ingredients in foods while eating out with the child, bring safe substitutes from home, and bring an allergy kit.
• Parents should be aware of possible cross-contamination, such as when an ice cream scoop is used for Rocky Road ice cream, which contains peanuts, and then for vanilla ice cream.
• School kitchen personnel should be notified of the childs condition.
• The child should avoid eating foods that might cross-react with foods that the child is allergic to, for example, if the child is allergic to shrimp, the child may also be allergic to crab or lobster.
• When traveling to other countries, parents should learn the appropriate words for foods that trigger their childs allergy; in addition, parents can request that air carriers serve peanut-free snacks to all passengers when their child is traveling; also the child should avoid eating airline meals.

Latex:

• The child should avoid all latex rubber products.
• If the child has to be hospitalized, the parents should alert the hospital personnel to the childs allergy to latex.
• A child with a latex allergy may also have allergies to kiwi fruit, passion fruit, papayas, bananas, avocados, figs, peaches, nectarines, plums, tomatoes, celery, and chestnuts.

In addition, children with a history of allergic reactions should carry an emergency kit containing injectable epinephrine and chewable antihistamine and be instructed in its use. A child who is not prepared to deal with an anaphylactic reaction is at an increased risk of dying. The allergy kit should include simple instructions on when and how to use the kit; sterilizing swabs to cleanse the skin before and after the injection; epinephrine in a preloaded syringe, as prescribed by the childs doctor in doses appropriate for children; and antihistamine tablets. The expiration date on the medications in the allergy kit should be checked and medications replaced as needed. Also, the epinephrine solution should be clear; if it is pinkish brown, it should be discarded and replaced.

There are many brands of allergy kits. The simplest kit to use is the Ana-kit, which contains a sterile syringe preloaded with two doses of epinephrine with a stop between. Another commonly used kit is the Epi-Pen, which carries a single self-injecting, spring-loaded syringe of epinephrine. Two Epi-Pen kits should be carried, so that two doses are available. Allergy kits should be kept at home, school, and day care; and the school administrator, teachers, and friends should be made aware of the childs allergies. Adults associated with the child should be trained in giving an injection and have a plan to transport the child to the hospital. Older children should be taught to give self-injections. Children at risk for anaphylaxis should also wear a Medic Alert bracelet or necklace or carry a medical emergency card with them at all times that clearly describes their allergy.

A consultation with an allergist can help to identify the substances that trigger the reaction; the allergist can also provide information on how to best avoid the triggering substance. The allergist may also be able to give allergy shots to children with wasp, yellow jacket, hornet, honey bee, or fire ant allergies. These shots provide 90 percent protection against the first four insect reactions, but less protection against fire ant reactions. Premedication is also helpful in preventing anaphylaxis from x-ray dyes; also there may be alternative dyes available for use that are less likely to cause reactions. Desensitization to medications has also been successful in some cases. The process involves gradually increasing the amount of medication given under controlled conditions. The procedure has worked for sensitivities to penicillin, sulfa drugs, and insulin.

The risk of anaphylaxis sometimes diminishes over time if there are no repeated exposures or reactions. However, the child at risk should also expect the worst and be prepared with preventive medication.

Parental Concerns

Parents caring for children who are at risk for life-threatening anaphylactic reactions may experience high stress levels, for they have to maintain vigilance in order to protect the child while creating a sense of normalcy as the child grows up. Parents can reduce their stress by using social support groups, accepting their childs condition, and maintaining a positive attitude.

See also Allergies.

Resources

Books

Barber, Marianne S. The Parents Guide to Food Allergies: Clear and Complete Advice from the Experts on Raising Your Food-Allergic Child. New York: Owl Books, 2001.

Coss, Linda Marienhoff. How to Manage Your Childs Life-Threatening Food Allergies: Practical Tips for Daily Life. Lake Forest, CA: Plumtree Press, 2004.

Jevon, Philip. Anaphylaxis: A Practical Guide. London, UK: Butterworth-Heinemann, 2004.

Smith, Nicole. Allie the Allergic Elephant: A Childrens Story of Peanut Allergies. San Francisco: Jungle Communications, 2002.

Organizations

American Academy of Allergy, Asthma, and Immunology. 611 E. Wells Street, Milwaukee, WI 53202. Web site: www.aaaai.org

Food Allergy and Anaphylaxis Network. 10400 Eaton Place, Suite 107, Fairfax, VA 220302208. Web site: www.foodallergy.org

Web Sites

American College of Allergy, Asthma, and Immunology. Available online at (accessed October 10, 2004).

[Article by: Judith Sims]

For more information on anaphylaxis, visit Britannica.com.

A condition that occurs in individuals who are hypersensitive to some substance (e.g. a bee sting) to which they have an abnormal allergic reaction. Histamine, a powerful vasodilator, is released from tissues causing either local or widespread reactions. A severe, widespread reaction can be life-threatening. It is characterized by nausea, lowered blood pressure, irregular heart beat, vomiting, and respiratory distress. See also exercise-induced anaphylaxis.

Resembling anaphylaxis, but not involving an immunological mechanism.

• a. purpura — see anaphylactoid purpura.

Anaphylaxis
Classification and external resources
ICD-10	T78.2
DiseasesDB	29153
eMedicine	med/128
MeSH	D000707

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] Minute amounts of allergens may cause a life-threatening anaphylactic reaction. Anaphylaxis may occur after ingestion, skin contact, injection of an allergen or, in some 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.

Due in part to the variety of definitions, 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 approximately 1,500 deaths per year in the U.S.^[4] (one out of every 1,600 of the 2.4 million deaths from all causes each year in the U.S.;^[5]). 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.^[6] The distinction is primarily made by those studying mechanisms of allergic reactions.

Contents 1 Causes 2 Symptoms 3 Diagnosis 4 Treatment 4.1 Emergency treatment 4.2 Clinical care 4.3 Planning for emergency treatment 4.4 Prevention 5 Pathophysiology 5.1 Compared to pseudoanaphylaxis 6 References 7 External links

Causes

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

Hives and angioedema (swelling of 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. Some vaccinations are also known to cause "anaphylactoid" reactions.^[8] Antitoxins and antivenins may cause similar reactions. In certain individuals, strenuous physical activity can induce anaphylaxis.

Anaphylaxis can occur in response to any allergen. Common causes include insect bites/stings, food allergies (peanuts and tree nuts are the most common, though not the only), 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 (idiopathic).

Symptoms

Symptoms of anaphylaxis are related to the action of Immunoglobulin E (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).

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.

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): this can be life threatening
• 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.^[9] However, symptoms of anaphylaxis usually appear very quickly once they do begin.

Diagnosis

This section requires expansion.

Apart from its clinical features, blood tests for tryptase (released from mast cells) might be useful in diagnosing anaphylaxis.^[10]

In some cases, it is unclear from the patient interview what triggered the anaphylaxis. In this setting, skin allergy testing (with or without patch testing) or RAST blood tests can sometimes identify the cause.

Treatment

Emergency treatment

A woman being treated in an emergency department after going into anaphylactic shock

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 patient stops breathing on his or her own, it is the only way to get oxygen to him or her until professional help is available.

The primary treatment for anaphylaxis is administration of epinephrine (adrenaline). Epinephrine prevents worsening of the airway constriction, stimulates the heart to continue beating, causes vasoconstriction in order to increase blood pressure, and may be life-saving. Epinephrine acts on Beta-2 adrenergic receptors in the lung as a powerful bronchodilator (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 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.^[11] 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 very small amounts of epinephrine.

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 (such as chlorphenamine or diphenhydramine); steroids, such as hydrocortisone or dexamethasone; 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 patient.

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.^[11]

Many anaphylactic patients will be sent home or released after the initial reaction is declared over. Yet, rebound reactions are almost always bound to happen. Most people with anaphylaxis have a rebound a few hours after the initial reaction, yet there are cases where a rebound would occur after as much time as a week.

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.^[12] Action plans are considered essential to quality emergency care. Many authorities advocate immunotherapy to prevent future episodes of anaphylaxis.^[13]

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.^[14]

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.

A vaccine has been in the works to prevent anaphylaxis from peanuts and tree nuts. Despite showing significant promise to prevent individuals with the allergy from developing anaphylaxis if eating a small amount of the food, the FDA has not yet approved the vaccine.^[15]

Pathophysiology

Classified as a type I hypersensitivity, anaphylaxis is triggered when an antigen binds to IgE antibodies on mast cells based in connective tissue throughout the body, which leads to degranulation of the mast cells (the release of inflammatory mediators).^[16] These immune mediators cause many symptoms, including common symptoms of allergic reactions, such as itching, hives, and swelling. Anaphylactic shock is an allergic reaction to an antigen that causes circulatory collapse and suffocation due to bronchial and tracheal swelling.

Different classes of antibodies are produced by B cells to bind and destroy substances that the immune system has identified as potentially dangerous pathogens. Each B cell produces thousands of identical antibodies that can attack a single, small part of a pathogen. In susceptible individuals, antibodies may be produced against innocuous antigens or allergens, such as components of common foods or plants. One class, the IgE antibodies, can trigger anaphylaxis. Production of IgE antibodies may persist for months, even in the complete absence of the allergen. These IgE antibodies associate with a receptor on the surface of mast cells. If the antibody binds to its specific antigen, then the antibody triggers degranulation of the mast cell.

Mast cells become the major effector cells for immediate hypersensitivity and chronic allergic reactions.^[17]

Mast cells are large cells found in particularly high concentrations in vascularized connective tissues just beneath epithelial surfaces, including the submucosal tissues of the gastrointestinal and respiratory tracts, and the dermis that lies just below the surface of the skin.^[16] They contain large granules that store a variety of mediator molecules including the vasoactive amine, histamine. Histamine causes dilation of local blood vessels and smooth-muscle contraction. Other molecules in the mast cell granules include lipid inflammatory mediators such as prostaglandin D2¬ and leukotriene C4 as well as tumor necrosis factor-α (TNF-α), a cytokine.^[16] The importance of TNF-α is most noted in the activation of the endothelium. TNF-α, the prototype of the TNF family cytokines, can induce endothelial cells to present E-selectin and ICAM-1, both of which are cell adhesion molecules (CAM) that mediate the “roll and stick” mechanism of leukocyte extravasation, termed diapedesis. While this process is essential for the recruit of leukocytes to a localized area during an inflammatory response, it can be catastrophic in cases of systemic infection. Point in case, the presence of said infection in the bloodstream, or sepsis, is accompanied by the release of TNF-α by macrophages in liver, spleen, and other systemic sites. The systemic release of TNF-α causes vasodilatation, which leads to a loss of blood pressure and increased vascular permeability, leading to a loss of plasma volume and eventually to shock.^[16]

TNF-α, along with the other aforementioned mast cell granule contents become exocytosed upon activation of the mast cell. Activation is achieved only when IgE, bound to the high-affinity Fcε receptors (FcεR1), are cross-linked by multivalent antigen. The FcεR1 is a tetrameric receptor composed of a single α chain, responsible for binding the IgE, associated with a single β chain and a disulfide linked homodimer of γ chains that initiate the cell signal pathway.^[18] Once the FcεR1 are aggregated by the cross-linking process, the immunoreceptor tryrosine-based activation motifs (ITAMs) in both the β and γ chains are phosphorylated by LYN, a protein tryrosine kinase (PTK) belonging to the Src family. The ITAM domain is simply conserved sequence motif generally composed of two YXXL/I sequences separated by about six to nine amino acids, where Y is tyrosine, L is leucine, I isoleucine and X any amino acid.^[16] Their phosphorylation in the β and γ chains provide high-affinity docking sites for the SH2 domains of additional LYN and the SYK (spleen tyrosine kinasse), respectively.^[19] These SH2 domains (Src homology 2 domian) are found in a numerous cell-signaling proteins and bind to phosphotyrosine through a very specific sequence.^[16] As the signal continues to propagate through the pathway, the membrane bound molecule, named linker for activation of T cells (LAT), is phosphoyraleted by the LYN and SYK and acts as a scaffold protein, organizing other molecules that complete the degranulation of mast cells, as well as promote further cytokine production.^[20] The most notable of these LAT affected molecules is Phospholipase C (PLC). As in many cell signaling pathways PLC hydrolyzes the phosphodiester bond in phosphoatidylinositol-4,5-bisphosphate [PI(4,5)P¬¬2] to yield diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP¬¬3)¬. A well-characterized second messenger, IP¬3¬, signals the release of calcium from the endoplasmic reticulum. The influx of cytosolic Ca2+ and phosphoatidylserine further active Phosphokinase C (PKC) bound to DAG. Together, it is the cytosolic Ca2+ and PKC signal the degranulation of the mast cell.4

Although less well mapped, similarly prevailing cell signaling molecules, such as Ras, a monomeric G protein, SOS (son of sevenless homologue) and MAPK (mitogen-activated protein kinase) lead to the upregulation of cytokines and the previously mentioned eicosanoids, prostaglandin D2¬ and leukotriene C4.^[19]

While this cell single pathway is sufficient to induce degraluation, it is not the only effective mechanism. Studies with LYK deficient mice have shown that degranulation is still inducible.^[20] Consequently, several alternative pathways leading to mast cell degranulation have been mapped. The first of which, dubbed the “complementary” pathway, determined that the crosstalk between LYK and another Src family PTK, called FYN, is an essential interaction to degranulation, along with the preferential activity of Phosphoatidylinositol 3-kinase (PI-3K) over PLC. Studies have also elucidated subsequent pathways that utilize the integration of G-protein-coupled receptors to mediate the degranulation and cytokine production mechanism of activated mast cells.^[19]

IgE binding to FcεR1 in the absence of a specific antigen still induces the up-regulation of FcεR1 surface expression in mast cells through autocrine signaling of cytokines.^[21] However, not all IgE are equally capable of inducing such as secretion. Therefore, researchers have divided all invariant IgEs into two major categories: highly cytokinergic(HC), where the production and secretion of various cytokines and other activation events including degranulation is inducible, and poorly cytokinergic (PC) in which no autocrine signaling is observed. The former, HC IgE, brings forward a reaction in which cytokines are exocytosed and act as autocrine and paracrine signaling molecules. As such, mast cells with bound HC IgE attract other mast cells even in the absence of antigen crosslinking.^[18] While the exact structural features that account for the function differences between HC and PC IgE has yet to be determined their effects are thought to be the result of intracellular cell signaling.^[21] IgE binding to FcεR1 leads to a greater stability of the mast cell and increased production of surface receptors. The newly expressed FcεR1 then aggregate on the surface, independent of antigen binding. The cell signaling pathway then initiates and appears to involve components used in the alternative mechanisms. Mast cell migration is dependent on soluble factors such as adenosine, leukotriene B¬4 and other chemokines, whose secretion is dependent upon the activity of LYN and SYK. The degranulation of mast cells in the absence of antigen, can then be initiated by G-protein-couple receptors (GPCR) stimulated by soluble factors agonists and completed by downstream activity of PI3K.^[18]

Compared to pseudoanaphylaxis

Pseudoanaphylaxis presents with the same clinical signs and symptoms as true anaphylaxis, but it does not involve IgE antibodies. Instead, mast cell degranulation is triggered either by the activation of the complement system or by a pharmacological reaction on the mast cell's surface.^[22] Histamine, which is released in both true IgE-based allergic reactions and in these anaphylactoid reactions, is responsible for the resulting signs and symptoms, which are consequently identical.

The complement system contains three proteins (C3a, C4a, and C5a) that are called anaphylatoxins because of their role in triggering pseudoanaphylaxis.^[22] The most common trigger for this mechanism is an intravenous infusion of an iodine-containing radiological contrast medium.^[22]

The mechanism by which other substances, commonly called histamine liberators, trigger mast cell degranulation, is poorly understood. Some substances are known to be effective liberators in susceptible people, including egg white, strawberries, and a variety of medications.^[23]

References

1. ^ "Anaphylaxis." Etymology. Oxford English Dictionary. http://dictionary.oed.com.
2. ^ "Anaphylaxis". Health. AllRefer.com. 2002-01-17. http://health.allrefer.com/health/anaphylaxis-info.html. Retrieved on 2007-01-29. 
3. ^ Neugut AI, Ghatak AT, Miller RL (January 2001). "Anaphylaxis in the United States: an investigation into its epidemiology". Arch. Intern. Med. 161 (1): 15–21. doi:10.1001/archinte.161.1.15. PMID 11146694. http://archinte.ama-assn.org/cgi/content/full/161/1/15. 
4. ^ Matasar MJ, Neugut AI (January 2003). "Epidemiology of anaphylaxis in the United States". Curr Allergy Asthma Rep 3 (1): 30–5. PMID 12542990. 
5. ^ "Deaths/Mortality". National Center for Health Statistics. http://www.cdc.gov/nchs/fastats/deaths.htm. Retrieved on 2008-04-22. 
6. ^ Limmer D, Mistovich JJ, Krost WS (November 17, 2005). "Anaphylactic and Anaphylactoid Reactions -- Prehospital Pathophysiology". EMSResponder.com. http://publicsafety.com/article/article.jsp?id=2165&siteSection=6. Retrieved on 2007-11-27. 
7. ^ "Mastocytosis: Allergic Reactions: Merck Manual Home Edition". http://www.merck.com/mmhe/sec16/ch185/ch185e.html. Retrieved on 2007-11-27. 
8. ^ National Advisory Committee on Immunization (NACI) - SUPPLEMENTARY STATEMENT MMR VACCINE AND ANAPHYLACTIC HYPERSENSITIVITY TO EGG OR EGG-RELATED ANTIGENS - CCDR Volume 22
9. ^ "Food Allergies". Asthma and Allergy Foundation of America. March 28, 2007. http://www.aafa.org/display.cfm?id=9&sub=20&cont=286. 
10. ^ Schwartz LB (August 2006). "Diagnostic value of tryptase in anaphylaxis and mastocytosis". Immunology and allergy clinics of North America 26 (3): 451–63. doi:10.1016/j.iac.2006.05.010. PMID 16931288. 
11. ^ ^{a b} "Emergency treatment of anaphylactic reactions -- Guidelines for healthcare providers" (PDF). Resuscitation Council (UK). January 2008. http://www.resus.org.uk/pages/reaction.pdf. Retrieved on 2008-04-22. 
12. ^ "Asthma and Allergy Foundation of America - Information About Asthma, Allergies, Food Allergies and More!". http://www.aafa.org/display.cfm?id=4&sub=81&cont=392. Retrieved on 2007-11-27. 
13. ^ "Fact Sheet - ACAAI". http://www.acaai.org/public/patients/factSheet.htm. Retrieved on 2007-11-27. 
14. ^ Bousquet J, Müller UR, Dreborg S, et al. (1987). "Immunotherapy with Hymenoptera venoms. Position paper of the Working Group on Immunotherapy of the European Academy of Allergy and Clinical Immunology". Allergy 42 (6): 401–13. doi:10.1111/j.1398-9995.1987.tb00355.x. PMID 3310714. 
15. ^ Peanut Allergy. Website of the Allergic Child Publishing Group.
16. ^ ^{a b c d e f} Murphy, Kenneth (November 27, 2007). Janeway's Immunobiology (7th edition ed.). New York: Garland Science. ISBN 0-8153-4123-7. 
17. ^ Kitaura J, Kinoshita T, Matsumoto M, et al. (April 2005). "IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion". Blood 105 (8): 3222–9. doi:10.1182/blood-2004-11-4205. PMID 15637135. http://bloodjournal.hematologylibrary.org/cgi/content/full/105/8/3222. 
18. ^ ^{a b c} Paolini R, Jouvin MH, Kinet JP (October 1991). "Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement". Nature 353 (6347): 855–8. doi:10.1038/353855a0. PMID 1834946. 
19. ^ ^{a b c} Gilfillan AM, Tkaczyk C (March 2006). "Integrated signalling pathways for mast-cell activation". Nat. Rev. Immunol. 6 (3): 218–30. doi:10.1038/nri1782. PMID 16470226. 
20. ^ ^{a b} Parravicini V, Gadina M, Kovarova M, et al. (August 2002). "Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation". Nat. Immunol. 3 (8): 741–8. doi:10.1038/ni817. PMID 12089510. 
21. ^ ^{a b} Kitaura J, Song J, Tsai M, et al. (October 2003). "Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI". Proc. Natl. Acad. Sci. U.S.A. 100 (22): 12911–6. doi:10.1073/pnas.1735525100. PMID 14569021. http://www.pnas.org/cgi/content/full/100/22/12911. 
22. ^ ^{a b c} Joris, Isabelle; Majno, Guido (2004). Cells, tissues, and disease: principles of general pathology. Oxford [Oxfordshire]: Oxford University Press. pp. 538-539. ISBN 0-19-514090-7. 
23. ^ Arnaldo Cantani (2008). Pediatric Allergy, Asthma and Immunology. Berlin: Springer. pp. 710-713. ISBN 3-540-20768-6. 

External links

Information

• Anaphylaxis information from the American Academy of Allergy and Immunology
• Patient information: Anaphylaxis from UpToDate
• How to use an Epipen - training video
• How to use Twinject - training video
• Emergency treatment of anaphylactic reactions - Resuscitation Council (UK)

Charities

• The Food Allergy & Anaphylaxis Network
• The Anaphylaxis campaign, a UK national registered charity for people at risk from anaphylaxis
• Asthma and Allergy Foundation of America (US)
• Australia - Australian national registered charity for the support of those at risk of Anaphylaxis.
• Anaphylaxis Canada
• whyriskit.ca, a site for teens at risk for anaphylaxis

v • d • e Consequences of external causes (T66-T88, 990-999) Temperature/radiation elevated: Hyperthermia · Heat syncope · Radiation poisoning reduced: Hypothermia · Immersion foot · Chilblain Air Hypoxia/Asphyxia · Barotrauma (Aerosinusitis, Decompression sickness) · Altitude sickness/Chronic mountain sickness Food Starvation Maltreatment Physical abuse · Sexual abuse · Psychological abuse Emesis Motion sickness · Seasickness · Airsickness · Space adaptation syndrome Other Electric shock · Anaphylaxis · Angioedema Hypersensitivity (Allergy, Arthus reaction) Subcutaneous emphysema Certain early complications of trauma embolism (Air, Fat) Crush syndrome/Rhabdomyolysis Contracture/Volkmann's contracture/Compartment syndrome Complications of surgical and medical care transfusion reactions: Transfusion hemosiderosis · TRALI · TACO · TA-GvHD · FNHTR · Acute/Delayed hemolytic transfusion reaction other: Serum sickness · Malignant hyperthermia · Herxheimer reaction · Graft-versus-host disease · Tumor lysis syndrome

v • d • e Immune disorders: hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign Atopic dermatitis · Allergic urticaria · Hay fever · Allergic asthma · Anaphylaxis · Food allergy (Milk, Egg, Peanut, Tree nut, Seafood, Soy, Wheat) Autoimmune none Type II/ADCC (IgM, IgG) Foreign Pernicious anemia · Hemolytic disease of the newborn · Penicillin allergy Autoimmune Cytotoxic Autoimmune hemolytic anemia · Idiopathic thrombocytopenic purpura  · Bullous pemphigoid  · Pemphigus vulgaris · Rheumatic fever · Goodpasture's syndrome "Type 5"/receptor Graves' disease · Myasthenia gravis Type III (Immune complex) Foreign Henoch-Schönlein purpura · Hypersensitivity vasculitis · Reactive arthritis · Rheumatoid arthritis · Farmer's lung · Post-streptococcal glomerulonephritis · Serum sickness · Arthus reaction Autoimmune Systemic lupus erythematosus · Subacute bacterial endocarditis Type IV/cell-mediated (T-cells) Foreign Contact dermatitis · Mantoux test Autoimmune Diabetes mellitus type 1 · Hashimoto's thyroiditis · Guillain-Barré syndrome  · Multiple sclerosis  · Coeliac disease · Giant cell arteritis GVHD Transfusion-associated graft versus host disease Unknown/ multiple Foreign Hypersensitivity pneumonitis (Allergic bronchopulmonary aspergillosis) · Transplant rejection · Latex allergy (I+IV) Autoimmune Sjögren's syndrome · Autoimmune hepatitis · Autoimmune polyendocrine syndrome (APS1, APS2) · Autoimmune adrenalitis

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