Disease: Anaphylaxis
(Severe Allergic Reaction)

Anaphylaxis facts

  • Anaphylaxis is the most severe allergic reaction and is potentially life threatening.
  • Anaphylaxis is rare. The vast majority of people will never have an anaphylactic reaction.
  • The most common causes of anaphylaxis include drugs, such as penicillin, insect stings, foods (peanuts, shellfish), X-ray dye, and latex.
  • The symptoms of anaphylaxis may vary and can include hives, tongue swelling, vomiting, and even shock.
  • If someone is at risk, avoidance is the best form of treatment.
  • If one has a history of serious allergic reaction, he or she should always carry an epinephrine kit.

What is anaphylaxis?

Anaphylaxis refers to a rapidly developing and serious allergic reaction that affects a number of different body systems at one time. Severe anaphylactic reactions can be fatal. Although many patients experience minor allergy symptoms, a small number of people are susceptible to a severe reaction that can lead to shock or even death.

Anaphylaxis is often triggered by substances that are injected or ingested and thereby gain access into the bloodstream. An explosive reaction involving the skin, lungs, nose, throat, and gastrointestinal tract can then result. Although severe cases of anaphylaxis can occur within seconds or minutes of exposure and be fatal if untreated, many reactions are milder and can be ended with prompt medical therapy.

What is the history of anaphylaxis?

To fully understand this term, we need to go back almost 100 years. The story begins on a cruise aboard Prince Albert I of Monaco's yacht. The prince had invited two Parisian scientists to perform studies on the toxin produced by the tentacles of a local jellyfish, the Portuguese Man of War. Charles Richet and Paul Portier were able to isolate the toxin and tried to vaccinate dogs in the hope of obtaining protection, or "prophylaxis," against the toxin. They were horrified to find that subsequent very small doses of the toxin unexpectedly resulted in a new dramatic illness that involved the rapid onset of breathing difficulty and resulted in death within 30 minutes. Richet and Portier termed this "anaphylaxis" or "against protection." They rightly concluded that the immune system first becomes sensitized to the allergen over several weeks and upon reexposure to the same allergen may result in a severe reaction. An allergen is a substance that is foreign to the body and can cause an allergic reaction in certain people.

  • The first documented case of presumed anaphylaxis occurred in 2641 BC when Menes, an Egyptian pharaoh, died mysteriously following a wasp or hornet sting. Later, in Babylonian times, there are two distinct references to deaths due to wasp stings.
  • Charles Richet was awarded the Nobel Prize in 1913 for his work on anaphylaxis.

Richet went on to suggest that the allergen must result in the production of a substance, which then sensitized the dogs to react in such a way upon reexposure. This substance turned out to be IgE.

In the first part of the 20th century, anaphylactic reactions were most commonly caused by tetanus diphtheria vaccinations made from horse serum. Today, human serum is used for tetanus prevention, and the most common causes of anaphylaxis are now penicillin and other antibiotics, insect stings, and certain foods.

What are common causes of anaphylaxis?

Although anaphylaxis can be due to different causes, there are four major subtypes of anaphylaxis (reactions to food, drugs, latex, and insect stings).

The causes of anaphylaxis are divided into two major groups:

  • IgE mediated: This form is the true anaphylaxis that requires an initial sensitizing exposure (for example, an exposure to the substance that will later trigger the anaphylaxis) and occurs on a subsequent exposure. It involves the coating of mast cells and basophils (cells in the blood and tissue that secrete the substances that cause allergic reactions, known as mediators) by IgE, and the explosive release of chemical mediators upon reexposure.
  • Non-IgE mediated: These reactions, the so called "anaphylactoid" reactions, are similar to those of true anaphylaxis but do not require an IgE immune reaction. They are usually caused by the direct stimulation of the mast cells and basophils. The same mediators as occur with true anaphylaxis are released and the same effects are produced. This reaction can happen, and often does, on initial as well as subsequent exposures, since no sensitization is required.

The terms anaphylaxis and anaphylactoid (meaning "like anaphylaxis") are both used to describe this severe allergic reaction. Anaphylaxis is used to describe reactions that are initiated by IgE and anaphylactoid is used in reference to reactions that are not caused by IgE. The effects of the reactions are the same, however, and are generally treated in the same manner. Often, they can not be distinguished initially.

Although it may appear that IgE mediated anaphylaxis occurs upon a first exposure to a food, drug, or insect sting, there must have been a prior, and probably unwitting, sensitization from a previous exposure. One may not remember an uneventful sting or be aware of "hidden" allergens in foods.

What are anaphylaxis symptoms and signs?

Anaphylaxis is a severe reaction that affects multiple areas of the body.

  • The severity of the reaction varies from person to person.
  • Subsequent reactions to the same trigger are typically similar in nature.
  • The more rapid the onset of symptoms, the more severe the reaction is likely to be.
  • A history of allergic disease (rhinitis, eczema, asthma) does not increase the risk of developing IgE mediated anaphylaxis, but it does incline the person to a non-IgE-mediated reaction.
  • Underlying asthma may result in a more severe reaction and can be more difficult to treat.

The symptoms of an anaphylactic reaction may occur within seconds of exposure or be delayed 15-30 minutes, or even an hour or more after exposure (typical of reactions to aspirin and similar drugs). Early symptoms are often related to the skin and include

Learn more about: aspirin

  • flushing (warmth and redness of the skin),
  • itching (often in the groin or armpits),
  • hives.

These symptoms are often accompanied by

  • a feeling of "impending doom,"
  • anxiety,
  • sometimes a rapid, irregular pulse.

Frequently following the above symptoms, throat and tongue swelling results in hoarseness, difficulty swallowing, and difficulty breathing.

Symptoms of rhinitis (hay fever) or asthma may occur, causing

  • a runny nose;
  • sneezing, and wheezing, which may worsen the breathing difficulty;
  • vomiting, diarrhea, and stomach cramps may develop.

Some of the time, the mediators flooding the bloodstream cause a generalized opening of capillaries (tiny blood vessels) which results in

  • a drop in blood pressure,
  • lightheadedness,
  • even loss of consciousness.

These are the typical features of anaphylactic shock.

What happens after the symptoms begin?

There are three possible outcomes:

  1. The signs and symptoms may be mild and fade spontaneously or be quickly ended by administering emergency medication. In this outcome, the symptoms do not subsequently recur from this particular exposure.
  2. After initial improvement, the symptoms may recur within four to 12 hours (late phase reaction) and require additional treatment and close observation. Recent evidence suggests that a late-phase reaction occurs in fewer than 10% of cases.
  3. Lastly, the reaction may be persistent and more severe, thus requiring intensive medical treatment and hospitalization.

Epinephrine, which is also known as "adrenaline," is a drug that acts immediately to cause the blood vessels to contract, thereby preventing fluid leakage. It is one of the medications frequently used to treat anaphylaxis. Epinephrine also helps relax the bronchial tubes, thus relieving breathing difficulty. It also lessens stomach cramps and stops itching and hives. More importantly, epinephrine helps prevent the release of more mediators of the allergic reaction.

In addition to epinephrine, other medications and IV fluids and oxygen will probably be administered once one receives care from a health-care professional. The choice of interventions will depend on the severity of the reaction the patient experiences. Epinephrine given to someone who does not have anaphylaxis can lead to a dangerously fast heartbeat and severe hypertension. It should only be administered by medical personnel familiar with its use and indications or patients who were prescribed an EpiPen by their health-care provider.

Are there any disorders that appear similar to anaphylaxis?

Several disorders may appear similar to anaphylaxis. Fainting (vasovagal reaction) is the reaction that is most likely to be confused with anaphylaxis. The key differences are that in a fainting episode, the affected person has a slow pulse, cool and pale skin, and no hives or difficulty breathing. Other conditions, such as heart attacks, blood clots to the lungs, septic shock, and panic attacks can also be confused with anaphylaxis.

How is anaphylaxis diagnosed?

If someone thinks he or she is having an anaphylactic reaction, the first order of business is to seek emergency care. Once the acute reaction has been treated, one should follow up with a doctor who will probably recommend seeing an allergist. The allergist will assess whether or not the reaction was indeed allergic in nature. Usually, a careful and detailed medical history and selected blood or skin tests can identify the cause. Be prepared to recall any activities that preceded the event, the food and medications ingested, and whether or not one had any contact with rubber products.

Table 1: The Common Causes of Anaphylaxis

Causes - IgE MediatedExamplesMedicationsPenicillin, cephalosporin, anesthetics, streptokinase, othersInsect stingsHornet, wasp, yellow jacket, honey bee, fire antFoodsPeanuts, tree nuts, fish, shellfish, eggs, milk, soy, wheatVaccinesAllergy shots, egg and gelatin-based vaccinesHormonesInsulin, possibly progesteroneLatexRubber productsAnimal/human proteinsHorse serum (used in some snake antivenins)

Causes - Non IgE MediatedExampleMedicationNonsteroidal anti-inflammatories (aspirin, Motrin, etc.), morphine, muscle relaxants (Robaxin, Norflex, and others), gamma globulinX-ray dyePreservativesSulfitesPhysicalExercise, heat-induced urticaria (hives), cold-induced urticariaIdiopathicUnknown cause

Two situations deserve special attention at this point since they are not covered elsewhere but are particularly interesting.

  1. In the 1970s, it was noted that exercise could cause anaphylaxis. Exercise-induced anaphylaxis (EIA) usually occurs with prolonged, strenuous exercise. Conditioned athletes such as marathon runners can be affected. The reaction may occur while exercising shortly after eating a meal, after eating specific foods (for example, lettuce, shellfish, or celery), or after taking aspirin. It appears as though food or aspirin loads the gun and exercise pulls the trigger. Early symptoms are usually flushing and itching, which may progress to other typical symptoms of anaphylaxis if the exercise continues. Premedication with antihistamines or other drugs does not consistently prevent EIA. Exercise avoidance is the most effective treatment. If this is not feasible, exercising with a "buddy" and carrying emergency epinephrine kits is mandatory.
  2. When no cause can be found for anaphylaxis, it is termed idiopathic. Recent reports suggest that 25% of all episodes of anaphylaxis are idiopathic. Many of those affected have underlying allergy or asthma conditions. Extensive allergy testing for foods may uncover an unusual food allergy that is responsible for these reactions. For frequent episodes of anaphylaxis, a physician may recommend a combination of antihistamine, cortisone, and a medication to widen the airways of the lungs (bronchial dilator) to help reduce the severity of attacks.

How do we manage anaphylaxis?

The optimal management of anaphylaxis saves lives. An affected or at-risk person must be aware of possible triggers and early warning signs. If someone is prone to these reactions, he or she must be familiar with the use of emergency anaphylaxis treatment kits and always carry them.

If one is aware of what triggers severe reactions and potentially anaphylaxis, a wrist bracelet indicating this can be helpful in case of unresponsiveness. Emergency measures and prevention are central to management. As always, allergic diseases are best treated by avoidance measures, which will be reviewed in detail below.

What are emergency measures used in the treatment of anaphylaxis?

If you suspect that you or someone you are with is having an anaphylactic reaction, the following are important first aid measures. In general, try to perform these in the order that they are presented.

  • Call emergency services or 911 IMMEDIATELY.
  • If the patient has an EpiPen, inject epinephrine immediately. The shot is given into the outer thigh and can be administered through light fabric. Rub the site to improve absorption of the drug.
  • Place a conscious person lying down and elevate the feet if possible.
  • Stay with the person until help arrives.
  • If trained, begin CPR if the person stops breathing or doesn't have a pulse.

Learn more about: EpiPen

Shots of epinephrine can be given through light clothing such as trousers, skirts, or stockings. Heavy garments may have to be removed prior to injecting. Only inject epinephrine if the patient has a history of anaphylactic reactions or under guidance of a health-care provider.

After 10-15 minutes, if the symptoms are still significant, one can inject another dose of epinephrine if available. Even after the reaction subsides, the individual needs to go to an emergency department immediately. Other treatments may be given, such as oxygen, intravenous fluids, breathing medications, and possibly more epinephrine. Steroids and antihistamines may be given, but these are often not helpful initially and do not take the place of epinephrine. However, they may be more useful in preventing a recurrent delayed reaction.

Do not be surprised if epinephrine makes the individual feel shaky and causes a rapid, pounding pulse. These are normal side effects and are not dangerous except for those with severe heart problems.

What is the history of anaphylaxis?

To fully understand this term, we need to go back almost 100 years. The story begins on a cruise aboard Prince Albert I of Monaco's yacht. The prince had invited two Parisian scientists to perform studies on the toxin produced by the tentacles of a local jellyfish, the Portuguese Man of War. Charles Richet and Paul Portier were able to isolate the toxin and tried to vaccinate dogs in the hope of obtaining protection, or "prophylaxis," against the toxin. They were horrified to find that subsequent very small doses of the toxin unexpectedly resulted in a new dramatic illness that involved the rapid onset of breathing difficulty and resulted in death within 30 minutes. Richet and Portier termed this "anaphylaxis" or "against protection." They rightly concluded that the immune system first becomes sensitized to the allergen over several weeks and upon reexposure to the same allergen may result in a severe reaction. An allergen is a substance that is foreign to the body and can cause an allergic reaction in certain people.

  • The first documented case of presumed anaphylaxis occurred in 2641 BC when Menes, an Egyptian pharaoh, died mysteriously following a wasp or hornet sting. Later, in Babylonian times, there are two distinct references to deaths due to wasp stings.
  • Charles Richet was awarded the Nobel Prize in 1913 for his work on anaphylaxis.

Richet went on to suggest that the allergen must result in the production of a substance, which then sensitized the dogs to react in such a way upon reexposure. This substance turned out to be IgE.

In the first part of the 20th century, anaphylactic reactions were most commonly caused by tetanus diphtheria vaccinations made from horse serum. Today, human serum is used for tetanus prevention, and the most common causes of anaphylaxis are now penicillin and other antibiotics, insect stings, and certain foods.

What are common causes of anaphylaxis?

Although anaphylaxis can be due to different causes, there are four major subtypes of anaphylaxis (reactions to food, drugs, latex, and insect stings).

The causes of anaphylaxis are divided into two major groups:

  • IgE mediated: This form is the true anaphylaxis that requires an initial sensitizing exposure (for example, an exposure to the substance that will later trigger the anaphylaxis) and occurs on a subsequent exposure. It involves the coating of mast cells and basophils (cells in the blood and tissue that secrete the substances that cause allergic reactions, known as mediators) by IgE, and the explosive release of chemical mediators upon reexposure.
  • Non-IgE mediated: These reactions, the so called "anaphylactoid" reactions, are similar to those of true anaphylaxis but do not require an IgE immune reaction. They are usually caused by the direct stimulation of the mast cells and basophils. The same mediators as occur with true anaphylaxis are released and the same effects are produced. This reaction can happen, and often does, on initial as well as subsequent exposures, since no sensitization is required.

The terms anaphylaxis and anaphylactoid (meaning "like anaphylaxis") are both used to describe this severe allergic reaction. Anaphylaxis is used to describe reactions that are initiated by IgE and anaphylactoid is used in reference to reactions that are not caused by IgE. The effects of the reactions are the same, however, and are generally treated in the same manner. Often, they can not be distinguished initially.

Although it may appear that IgE mediated anaphylaxis occurs upon a first exposure to a food, drug, or insect sting, there must have been a prior, and probably unwitting, sensitization from a previous exposure. One may not remember an uneventful sting or be aware of "hidden" allergens in foods.

What are anaphylaxis symptoms and signs?

Anaphylaxis is a severe reaction that affects multiple areas of the body.

  • The severity of the reaction varies from person to person.
  • Subsequent reactions to the same trigger are typically similar in nature.
  • The more rapid the onset of symptoms, the more severe the reaction is likely to be.
  • A history of allergic disease (rhinitis, eczema, asthma) does not increase the risk of developing IgE mediated anaphylaxis, but it does incline the person to a non-IgE-mediated reaction.
  • Underlying asthma may result in a more severe reaction and can be more difficult to treat.

The symptoms of an anaphylactic reaction may occur within seconds of exposure or be delayed 15-30 minutes, or even an hour or more after exposure (typical of reactions to aspirin and similar drugs). Early symptoms are often related to the skin and include

Learn more about: aspirin

  • flushing (warmth and redness of the skin),
  • itching (often in the groin or armpits),
  • hives.

These symptoms are often accompanied by

  • a feeling of "impending doom,"
  • anxiety,
  • sometimes a rapid, irregular pulse.

Frequently following the above symptoms, throat and tongue swelling results in hoarseness, difficulty swallowing, and difficulty breathing.

Symptoms of rhinitis (hay fever) or asthma may occur, causing

  • a runny nose;
  • sneezing, and wheezing, which may worsen the breathing difficulty;
  • vomiting, diarrhea, and stomach cramps may develop.

Some of the time, the mediators flooding the bloodstream cause a generalized opening of capillaries (tiny blood vessels) which results in

  • a drop in blood pressure,
  • lightheadedness,
  • even loss of consciousness.

These are the typical features of anaphylactic shock.

What happens after the symptoms begin?

There are three possible outcomes:

  1. The signs and symptoms may be mild and fade spontaneously or be quickly ended by administering emergency medication. In this outcome, the symptoms do not subsequently recur from this particular exposure.
  2. After initial improvement, the symptoms may recur within four to 12 hours (late phase reaction) and require additional treatment and close observation. Recent evidence suggests that a late-phase reaction occurs in fewer than 10% of cases.
  3. Lastly, the reaction may be persistent and more severe, thus requiring intensive medical treatment and hospitalization.

Epinephrine, which is also known as "adrenaline," is a drug that acts immediately to cause the blood vessels to contract, thereby preventing fluid leakage. It is one of the medications frequently used to treat anaphylaxis. Epinephrine also helps relax the bronchial tubes, thus relieving breathing difficulty. It also lessens stomach cramps and stops itching and hives. More importantly, epinephrine helps prevent the release of more mediators of the allergic reaction.

In addition to epinephrine, other medications and IV fluids and oxygen will probably be administered once one receives care from a health-care professional. The choice of interventions will depend on the severity of the reaction the patient experiences. Epinephrine given to someone who does not have anaphylaxis can lead to a dangerously fast heartbeat and severe hypertension. It should only be administered by medical personnel familiar with its use and indications or patients who were prescribed an EpiPen by their health-care provider.

Are there any disorders that appear similar to anaphylaxis?

Several disorders may appear similar to anaphylaxis. Fainting (vasovagal reaction) is the reaction that is most likely to be confused with anaphylaxis. The key differences are that in a fainting episode, the affected person has a slow pulse, cool and pale skin, and no hives or difficulty breathing. Other conditions, such as heart attacks, blood clots to the lungs, septic shock, and panic attacks can also be confused with anaphylaxis.

How is anaphylaxis diagnosed?

If someone thinks he or she is having an anaphylactic reaction, the first order of business is to seek emergency care. Once the acute reaction has been treated, one should follow up with a doctor who will probably recommend seeing an allergist. The allergist will assess whether or not the reaction was indeed allergic in nature. Usually, a careful and detailed medical history and selected blood or skin tests can identify the cause. Be prepared to recall any activities that preceded the event, the food and medications ingested, and whether or not one had any contact with rubber products.

Table 1: The Common Causes of Anaphylaxis

Causes - IgE MediatedExamplesMedicationsPenicillin, cephalosporin, anesthetics, streptokinase, othersInsect stingsHornet, wasp, yellow jacket, honey bee, fire antFoodsPeanuts, tree nuts, fish, shellfish, eggs, milk, soy, wheatVaccinesAllergy shots, egg and gelatin-based vaccinesHormonesInsulin, possibly progesteroneLatexRubber productsAnimal/human proteinsHorse serum (used in some snake antivenins)

Causes - Non IgE MediatedExampleMedicationNonsteroidal anti-inflammatories (aspirin, Motrin, etc.), morphine, muscle relaxants (Robaxin, Norflex, and others), gamma globulinX-ray dyePreservativesSulfitesPhysicalExercise, heat-induced urticaria (hives), cold-induced urticariaIdiopathicUnknown cause

Two situations deserve special attention at this point since they are not covered elsewhere but are particularly interesting.

  1. In the 1970s, it was noted that exercise could cause anaphylaxis. Exercise-induced anaphylaxis (EIA) usually occurs with prolonged, strenuous exercise. Conditioned athletes such as marathon runners can be affected. The reaction may occur while exercising shortly after eating a meal, after eating specific foods (for example, lettuce, shellfish, or celery), or after taking aspirin. It appears as though food or aspirin loads the gun and exercise pulls the trigger. Early symptoms are usually flushing and itching, which may progress to other typical symptoms of anaphylaxis if the exercise continues. Premedication with antihistamines or other drugs does not consistently prevent EIA. Exercise avoidance is the most effective treatment. If this is not feasible, exercising with a "buddy" and carrying emergency epinephrine kits is mandatory.
  2. When no cause can be found for anaphylaxis, it is termed idiopathic. Recent reports suggest that 25% of all episodes of anaphylaxis are idiopathic. Many of those affected have underlying allergy or asthma conditions. Extensive allergy testing for foods may uncover an unusual food allergy that is responsible for these reactions. For frequent episodes of anaphylaxis, a physician may recommend a combination of antihistamine, cortisone, and a medication to widen the airways of the lungs (bronchial dilator) to help reduce the severity of attacks.

How do we manage anaphylaxis?

The optimal management of anaphylaxis saves lives. An affected or at-risk person must be aware of possible triggers and early warning signs. If someone is prone to these reactions, he or she must be familiar with the use of emergency anaphylaxis treatment kits and always carry them.

If one is aware of what triggers severe reactions and potentially anaphylaxis, a wrist bracelet indicating this can be helpful in case of unresponsiveness. Emergency measures and prevention are central to management. As always, allergic diseases are best treated by avoidance measures, which will be reviewed in detail below.

What are emergency measures used in the treatment of anaphylaxis?

If you suspect that you or someone you are with is having an anaphylactic reaction, the following are important first aid measures. In general, try to perform these in the order that they are presented.

  • Call emergency services or 911 IMMEDIATELY.
  • If the patient has an EpiPen, inject epinephrine immediately. The shot is given into the outer thigh and can be administered through light fabric. Rub the site to improve absorption of the drug.
  • Place a conscious person lying down and elevate the feet if possible.
  • Stay with the person until help arrives.
  • If trained, begin CPR if the person stops breathing or doesn't have a pulse.

Learn more about: EpiPen

Shots of epinephrine can be given through light clothing such as trousers, skirts, or stockings. Heavy garments may have to be removed prior to injecting. Only inject epinephrine if the patient has a history of anaphylactic reactions or under guidance of a health-care provider.

After 10-15 minutes, if the symptoms are still significant, one can inject another dose of epinephrine if available. Even after the reaction subsides, the individual needs to go to an emergency department immediately. Other treatments may be given, such as oxygen, intravenous fluids, breathing medications, and possibly more epinephrine. Steroids and antihistamines may be given, but these are often not helpful initially and do not take the place of epinephrine. However, they may be more useful in preventing a recurrent delayed reaction.

Do not be surprised if epinephrine makes the individual feel shaky and causes a rapid, pounding pulse. These are normal side effects and are not dangerous except for those with severe heart problems.

Source: http://www.rxlist.com

To fully understand this term, we need to go back almost 100 years. The story begins on a cruise aboard Prince Albert I of Monaco's yacht. The prince had invited two Parisian scientists to perform studies on the toxin produced by the tentacles of a local jellyfish, the Portuguese Man of War. Charles Richet and Paul Portier were able to isolate the toxin and tried to vaccinate dogs in the hope of obtaining protection, or "prophylaxis," against the toxin. They were horrified to find that subsequent very small doses of the toxin unexpectedly resulted in a new dramatic illness that involved the rapid onset of breathing difficulty and resulted in death within 30 minutes. Richet and Portier termed this "anaphylaxis" or "against protection." They rightly concluded that the immune system first becomes sensitized to the allergen over several weeks and upon reexposure to the same allergen may result in a severe reaction. An allergen is a substance that is foreign to the body and can cause an allergic reaction in certain people.

  • The first documented case of presumed anaphylaxis occurred in 2641 BC when Menes, an Egyptian pharaoh, died mysteriously following a wasp or hornet sting. Later, in Babylonian times, there are two distinct references to deaths due to wasp stings.
  • Charles Richet was awarded the Nobel Prize in 1913 for his work on anaphylaxis.

Richet went on to suggest that the allergen must result in the production of a substance, which then sensitized the dogs to react in such a way upon reexposure. This substance turned out to be IgE.

In the first part of the 20th century, anaphylactic reactions were most commonly caused by tetanus diphtheria vaccinations made from horse serum. Today, human serum is used for tetanus prevention, and the most common causes of anaphylaxis are now penicillin and other antibiotics, insect stings, and certain foods.

Source: http://www.rxlist.com

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