Anaphylaxis

Anaphylaxis is an acute multi-system severe type I hypersensitivity allergic reaction. The term comes from the Greek words ἀνά ana, against, and φύλαξις phylaxis, protection.

Due in part to the variety of definitions, between 1% and 15% of the population of the United States can be considered "at risk" for having an anaphylactic reaction if they are exposed to one or more allergens. Of those people who actually experience anaphylaxis, up to 1% may die as a result. Anaphylaxis results in approximately 1,500 deaths per year in the U.S. In the United Kingdom, mortality rates for anaphylaxis have been reported as up to 0.05 per 100,000 population, or around 10-20 a year. Anaphylactic reactions requiring hospital treatment appear to be increasing, with authorities in the UK reporting a threefold increase between 1994 and 2004.

Based on the pathophysiology, anaphylaxis can be divided into "true anaphylaxis" and "pseudo-anaphylaxis" or "anaphylactoid reaction." The symptoms, treatment, and risk of death are the same; however, "true" anaphylaxis is caused by degranulation of mast cells or basophils mediated by immunoglobulin E (IgE), and pseudo-anaphylaxis occurs without IgE mediation.

Classification

Biphasic anaphylaxis

Biphasic anaphylaxis is the recurrence of symptoms within 72 hours with no further exposure to the allergen. It occurs in between 1–20% of cases depending on the study examined. This can result from morphine, radiocontrast, aspirin and muscle relaxants.

Active anaphylaxis

Active anaphylaxis is what is naturally observed. Two weeks or so after an animal, including humans, is exposed to certain allergens, active anaphylaxis (which is simply called "anaphylaxis") would be elicited upon exposure to the same allergens.

Passive anaphylaxis

Passive anaphylaxis is induced in native animals that receive transfer of the serum experimentally from sensitized animals with certain allergens. Passive anaphylaxis would be provoked in the recipient animals after exposure to the same allergens.

Signs and symptoms

Anaphylaxis can present with many different symptoms due to the systemic effects of histamine release. These usually develop over minutes to hours.

Causes

Anaphylaxis can occur in response to any allergen. Common triggers include insect bites or stings, foods, medication, and latex rubber.

Food

Many foods can trigger anaphylaxis. The most common are peanuts, wheat, tree nuts, shellfish, fish, milk, and eggs. 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.

Venom

Venom from stinging or biting insects such as Hymenoptera or Hemiptera may induce anaphylaxis in susceptible people. 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.

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. 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. These SH2 domains (Src homology 2 domian) are found in a numerous cell-signaling proteins and bind to phosphotyrosine through a very specific sequence. 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. 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. # Symptom onset within minutes to several hours of allergen exposure with involvement of the skin or mucosal tissue and any of the following: hives, itchiness, or swelling of the airway; plus either respiratory difficulty or a low blood pressure. # Any two or more of the following symptoms within minutes to several hours of allergen exposure: a. Involvement of the skin or mucosa b. Respiratory difficulties c. Low blood pressure d. Gastrointestinal symptoms # Low blood pressure within minutes to several hours after exposure to known allergen

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

Allergy testing may help in determining what triggered the anaphylaxis. In this setting, skin allergy testing (with or without patch testing) or RAST blood tests can sometimes identify the cause.

Prevention

Immunotherapy with Hymenoptera venoms is effective against allergies to bees, wasps, hornets, yellow jackets, white faced hornets, and fire ants.

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. Venom immunotherapy reduces risk of systemic reactions below 3%. One simple method of venom extraction has been electrical stimulation to obtain venom, instead of dissecting the venom sac.

A potential vaccine has been developed to prevent anaphylaxis due to peanut and tree nut allergies if they are exposed to a small amount of peanuts or nuts. Although it shows some promise to reduce the likelihood of anaphylaxis in affected individuals, the vaccine has not yet been approved for marketing and distribution. Desensitization techniques are also being studied for peanut allergies.

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.

Epinephrine

Epinephrine (adrenaline) is the primary treatment for anaphylaxis with no absolute contraindication to its use. Epinephrine autoinjector is provided for self-prescription.

Intravenous fluids

Anaphylaxis can lead to massive losses of intravascular fluids. Thus, large amounts of intravenous fluids maybe required.

;Steroids Corticosteroids are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. How effective they are at achieving this, however, is uncertain.

Preparedness

People prone to anaphylaxis are advised to have an "allergy action plan", and parents are advised to inform schools, etc. of their children's allergies and what to do in case of an anaphylactic emergency. The action plan usually includes use of epinephrine auto-injectors, the recommendation to wear a medical alert bracelet, and counseling on avoidance of triggers. Immunotherapy is available for certain triggers to prevent future episodes of anaphylaxis. A multi–year course of subcutaneous desensitization has been found effective against stinging insects, while oral desensitization is effective for many foods. The risk is greatest in young people and females. The trigger in the young is usually food related while in adults, medications and insect venoms are more common causes.

Due in part to the variety of definitions, between 1% and 15% of the population of the United States can be 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. Anaphylaxis results in approximately 1,500 deaths per year in the U.S. (one out of every 1,600 of the 2.4 million deaths from all causes each year in the U.S.;). The most common presentation includes sudden cardiovascular collapse (88% of reported cases of severe anaphylaxis). In England, mortality rates for anaphylaxis have been reported as up to 0.05 per 100,000 population, or around 10-20 a year. Anaphylactic reactions requiring hospital treatment appear to be increasing, with authorities in England reporting a threefold increase between 1994 and 2004.

References

External links

Anaphylaxis information from the American Academy of Allergy and Immunology

Patient information: Anaphylaxis from UpToDate

Emergency treatment of anaphylactic reactions - Resuscitation Council (UK)

First aid for anaphylactic shock from the British Red Cross

Category:Allergology Category:Pulmonology Category:Urticaria and angioedema Category:Medical emergencies Category:Complications of surgical and medical care