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Classification and external resources

Swelling of the face such that the boy is unable to open his eyes. This reaction was due to an allergen exposure.
ICD-10 T78.2
ICD-9 995.0
DiseasesDB 29153
MedlinePlus 000844
eMedicine med/128
MeSH D000707

Anaphylaxis is a serious allergic reaction which begins suddenly and may cause death.[1] Anaphylaxis has a number of symptoms, such as an itchy rash, throat swelling, and low blood pressure. Common causes include insect bites, foods, and medications.

Anaphylaxis is caused by the release of mediator proteins from certain types of white blood cells. Mediator proteins are substances that can start an allergic reaction or make the reaction more severe. Their release can be caused either by an immune system reaction or by another cause. Anaphylaxis is diagnosed from a person’s symptoms and signs. The primary treatment is injection of epinephrine, which is sometimes combined with other medications.

Worldwide, about 0.05–2% of people have anaphylaxis at some point in their lives. Rates appear to be increasing. The term comes from the Greek words ἀνά ana, against, and φύλαξις phylaxis, protection.

Signs and symptoms[change | change source]

Signs and symptoms of anaphylaxis.

Anaphylaxis produces many different symptoms over minutes or hours.[2] Symptoms appear within an average of 5 to 30 minutes if the cause is a substance that enters the body directly into the blood stream (intravenously). The average is 2 hours if the cause is a food the person ate.[3] The most common areas affected include: skin (80–90%), lungs and breathing pathways (70%), stomach and intestines (30–45%), heart and blood vessels (10–45%), and central nervous system (10–15%). Two or more of these systems are usually involved.

Skin[change | change source]

Hives and flushing on the back of a person with anaphylaxis

Symptoms typically include raised bumps on the skin (hives), itchiness, red face or skin (flushing), or swollen lips.[4] Those with swelling under the skin (angioedema) may feel that their skin is burning instead of itching.[3] The tongue or throat may swell in up to 20% of cases.[5] Other features may include a runny nose and swelling of the mucous membrane on the surface of the eye and eyelid (conjunctiva).[6] The skin may also have a blue color (cyanosis) due to a lack of oxygen.[6]

Respiratory[change | change source]

Respiratory symptoms and signs include shortness of breath, low-pitched difficult breathing (wheezes), or high-pitched difficult breathing (stridor).[4] Low-pitched breathing is typically due to spasms of the muscles in the lower part of the airway (bronchial muscles).[7] High-pitched breathing is due to swelling in the upper airway, which narrows the breathing passages.[6] Hoarseness, pain with swallowing, or a cough may also occur.[3]

Cardiac[change | change source]

The heart’s blood vessels may contract suddenly (coronary artery spasm) because of the release of histamine from certain cells in the heart.[7] This interrupts the blood flow to the heart, which may cause heart cells to die (myocardial infarction), or the heart may beat too slowly or too quickly (cardiac dysrhythmia), or the heart may stop beating altogether (cardiac arrest).[8][9] People who already have heart disease are at greater risk of cardiac effects from anaphylaxis.[7] While a fast heart rate due to low blood pressure is more common,[6] 10% of people who suffer from anaphylaxis may have a slow heart rate (bradycardia) with low blood pressure. (The combination of a slow heart rate and low blood pressure is known as Bezold–Jarisch reflex).[10] The person may feel lightheaded or may lose consciousness due to a drop in blood pressure. This low blood pressure may be caused by the widening of blood vessels (distributive shock) or by a failure of the heart’s ventricles (cardiogenic shock).[7] In rare cases, very low blood pressure may be the only sign of anaphylaxis.[5]

Other[change | change source]

Symptoms from the stomach and intestines may include crampy abdominal pain, diarrhea, and vomiting (throwing up).[4] The person may have confused thoughts, may lose control of their bladder, and may have pain in the pelvis that feels like cramps in the uterus.[4][6] Widening of blood vessels around the brain may cause headaches.[3] The person may also feel anxious or imagine that they are about to die.[9]

Causes[change | change source]

Anaphylaxis can be caused by the body’s response to almost any foreign substance.[11] Common triggers include venom from insect bites or stings, foods, and medication.[10][12][12] Foods are the most common trigger in children and young adults. Medications and insect bites and stings are more common triggers in older adults.[9]

Food[change | change source]

Many foods can trigger anaphylaxis, even when the food is eaten for the first time. In Western cultures, the most common causes are eating or being in contact with peanuts, wheat, tree nuts, shellfish, milk, and eggs. In the Middle East, sesame is a common trigger food. In Asia, rice and chickpeas often cause anaphylaxis. Severe cases are usually caused by eating the food, but some people have a severe reaction when the trigger food touches some part of the body. Children can outgrow their allergies. By age 16, 80% of children with anaphylaxis to milk or eggs and 20% with a single case of anaphylaxis to peanuts are able to eat these foods without problems.[11]

Medication[change | change source]

Any medication may cause anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin and NSAIDs.[13]

Venom[change | change source]

Venom from stinging or biting insects such as bees and wasps (Hymenoptera) or kissing bugs (Triatominae) may cause anaphylaxis.[8][14] If a person had a reaction to venom in the past, and it was more than a local reaction around the site of the sting, they have a greater risk for anaphylaxis in the future.[15][16] However, half of the people who die of anaphylaxis have had no previous widespread (systemic) reaction.[17]

Risk factors[change | change source]

People with atopic diseases such as asthma, eczema, or allergic rhinitis have a high risk of anaphylaxis from food, latex, and radiocontrast agents. These people do not have a higher risk from injectable medications or stings. One study in children with anaphylaxis found that 60% had a history of previous atopic diseases. More than 90% of children who die from anaphylaxis have asthma. People who have disorders caused by too many mast cells in their tissues (mastocytosis) or who are wealthier are at increased risk. The longer the time since the last exposure to the agent that caused anaphylaxis, the lower the risk of a new reaction.[3]

Mechanisms[change | change source]

Anaphylaxis is a severe allergic reaction that starts suddenly and affects many body systems.[1][18] It is due to the release of inflammatory mediators and cytokines from mast cells and basophils. Their release is typically due to an immune system reaction, but may be caused by damage to these cells not caused by an immune reaction.[18]

Immunologic[change | change source]

When anaphylaxis is caused by an immune response, immunoglobulin E (IgE) binds to the foreign material that starts the allergic reaction (the antigen). The combination of IgE bound to the antigen activates FcεRI receptors on mast cells and basophils. The mast cells and basophils react by releasing inflammatory mediators such as histamine. These mediators increase the contraction of bronchial smooth muscles, cause blood vessels to widen (vasodilation), increase the leakage of fluid from blood vessels, and depress the actions of the heart muscle.[3][18] There is also an immunologic mechanism that does not rely on IgE, but it is not known if this occurs in humans.[18]

Diagnosis[change | change source]

Anaphylaxis is diagnosed based on clinical facts. When any one of the following three occurs within minutes/hours of exposure to an allergen, it is very likely that the person has anaphylaxis:

  1. Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure
  2. Two or more of the following symptoms:
    a. Involvement of the skin or mucosa
    b. Respiratory difficulties
    c. Low blood pressure
    d. Gastrointestinal symptoms
  3. Low blood pressure after exposure to a known allergen

If a person has a bad reaction to an insect sting or a medication, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis. However these tests are not very useful if the cause is food or if the person has a normal blood pressure,[9] and they cannot rule out a diagnosis of anaphylaxis.[11]

Allergy testing[change | change source]

Skin allergy testing being carried out on the right arm

Allergy testing may help to determine what caused a person’s anaphylaxis. Skin allergy tests (such as patch tests) are available for certain foods and venoms.[11] Blood tests for specific antibodies can be useful to confirm milk, egg, peanut, tree nut and fish allergies.[11] Skin tests can confirm penicillin allergies, but there are no skin tests for other medications.[11] Non-immune forms of anaphylaxis can only be diagnosed by checking the person’s history or by exposing the person to an allergen that may have caused a reaction in the past. There are no skin or blood tests for non-immune anaphylaxis.[19]

Differential diagnosis[change | change source]

It can sometimes be difficult to distinguish anaphylaxis from asthma, fainting due to lack of oxygen (syncope), and panic attacks. People with asthma typically do not have itching or stomach or intestine symptoms. When a person faints, the skin is pale and does not have a rash. A person who is having a panic attack may have flushed skin but does not have hives. Other conditions that may have similar symptoms include food poisoning from spoiled fish (scombroidosis) and infection from certain parasites (anisakiasis).

Prevention[change | change source]

The recommended way to prevent anaphylaxis is to avoid whatever caused the reaction in the past. When this is not possible, there may be treatments to make the body stop reacting to a known allergen (desensitization). Treatment of the immune system (immunotherapy) with Hymenoptera venoms is effective at desensitizing 80–90% of adults and 98% of children against allergies to bees, wasps, hornets, yellow jackets, and fire ants. Oral immunotherapy may be effective at desensitizing some people to certain foods including milk, eggs, nuts and peanuts; however, these treatments often have bad side effects. Desensitization is also possible for many medications; however, most people should simply avoid the problem medication. In those who react to latex, it may be important to avoid foods that contain substances that are similar to the one that caused the immune response (cross-reactive foods), such as avocados, bananas, and potatoes among others.[9]

Management[change | change source]

Anaphylaxis is a medical emergency that may require lifesaving measures such as airway management, supplemental oxygen, large volumes of intravenous fluids, and close monitoring.[8] Epinephrine is the treatment of choice. Antihistamines and steroids are often used in addition to epinephrine.[9] Once a person has returned to normal, they should be watched in the hospital for 2 to 24 hours to make sure symptoms do not return, as they might if the person has biphasic anaphylaxis.[3][10][20][21]

Epinephrine[change | change source]

An old version of an EpiPen auto-injector

Epinephrine (adrenaline) is the primary treatment for anaphylaxis. There is no reason why it should not be used (no absolute contraindication).[8] It is recommended that an epinephrine solution be injected into the muscle of the mid anterolateral thigh as soon as anaphylaxis is suspected.[9] The injection may be repeated every 5 to 15 minutes if the person is not responding well to the treatment.[9] A second dose is needed in 16 to 35% of cases.[10] More than two doses are rarely needed.[9] Minor problems from epinephrine include tremors, anxiety, headaches, and palpitations.[9]

Epinephrine may not work in people who are taking B-blockers.[10] In this situation, if epinephrine is not effective, intravenous glucagon can be administered. Glucagon has a mechanism of action that does not involve β-receptors.[10]

Preparing[change | change source]

People who are at risk for anaphylaxis are advised to have an "allergy action plan". Parents should inform schools of their children's allergies and what to do in case of an anaphylactic emergency.[22] The action plan usually includes use of epinephrine auto-injectors, the recommendation to wear a medical alert bracelet, and counseling on how to avoid triggers.[22] Treatment to make the body less sensitive to the substance that is causing the allergic reaction (allergen immunotherapy) is available for certain triggers. This type of therapy may 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.[8]

Outlook[change | change source]

There is a good chance of recovery when the cause is known and the person is treated quickly.[23] Even if the cause is unknown, if medication is available to stop the reaction, the person usually makes a good recovery.[3] If death occurs, it is usually due to either a respiratory cause (typically closing off of the airway) or a cardiovascular cause (shock).[10][18] Anaphylaxis causes death in 0.7–20% of cases.[3][7] Some deaths have happened within minutes.[9] People who have exercise-induced anaphylaxis typically have good outcomes, with fewer and less severe episodes as they get older.[24]

History[change | change source]

The term "aphylaxis" was coined by Charles Richet in 1902 and later changed to "anaphylaxis" because it sounded nicer.[11] He was later awarded the Nobel Prize in Medicine and Physiology for his work on anaphylaxis in 1913.[3] The reaction itself, however, has been reported since ancient times.[19]

References[change | change source]

  1. 1.0 1.1 Tintinalli, Judith E. 2010. Emergency medicine: a comprehensive study guide. New York: McGraw-Hill, 177–182. ISBN 0-07-148480-9
  2. Oswalt M.L. & Kemp S.F. (May 2007). "Anaphylaxis: office management and prevention". Immunol Allergy Clin North Am 27 (2): 177–91, vi. doi:10.1016/j.iac.2007.03.004. PMID 17493497. "Clinically, anaphylaxis is considered likely to be present if any one of three criteria is satisfied within minutes to hours".
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 Marx, John (2010). Rosen's emergency medicine: concepts and clinical practice 7th edition. Philadelphia, PA: Mosby/Elsevier. p. 15111528. ISBN 9780323054720.
  4. 4.0 4.1 4.2 4.3 Sampson HA, Muñoz-Furlong A, Campbell RL, et al. (February 2006). "Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium". J. Allergy Clin. Immunol. 117 (2): 391–7. doi:10.1016/j.jaci.2005.12.1303. PMID 16461139.
  5. 5.0 5.1 Limsuwan T; Demoly P 2010. Acute symptoms of drug hypersensitivity (urticaria, angioedema, anaphylaxis, anaphylactic shock)." The Medical clinics of North America 94 (4): 691–710, x. [1]
  6. 6.0 6.1 6.2 6.3 6.4 Brown, SG; Mullins, RJ, Gold, MS (2006 Sep 4). "Anaphylaxis: diagnosis and management.". The Medical journal of Australia 185 (5): 283–9. PMID 16948628.
  7. 7.0 7.1 7.2 7.3 7.4 Triggiani, M; Patella, V, Staiano, RI, Granata, F, Marone, G (2008 Sep). "Allergy and the cardiovascular system.". Clinical and experimental immunology 153 Suppl 1: 7–11. PMC 2515352. PMID 18721322.
  8. 8.0 8.1 8.2 8.3 8.4 Simons F.E. 2009. Anaphylaxis: recent advances in assessment and treatment. J. Allergy Clin. Immunol. 124 (4): 625–36; quiz 637–8.
  9. 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 Simons F.E. 2010. World Allergy Organization survey on global availability of essentials for the assessment and management of anaphylaxis by allergy-immunology specialists in health care settings". Annals of allergy, asthma & immunology 104 (5): 405–12. [2]
  10. 10.0 10.1 10.2 10.3 10.4 10.5 10.6 Lee J.K. & Vadas. P. 2011. Anaphylaxis: mechanisms and management". Clinical and experimental allergy. 41 (7): 923–38.
  11. 11.0 11.1 11.2 11.3 11.4 11.5 11.6 Boden, SR; Wesley Burks, A (2011 Jul). "Anaphylaxis: a history with emphasis on food allergy.". Immunological reviews 242 (1): 247–57. PMID 21682750.
  12. 12.0 12.1 Worm, M (2010). "Epidemiology of anaphylaxis.". Chemical immunology and allergy 95: 12–21. PMID 20519879.
  13. Volcheck, Gerald W. (2009). Clinical allergy : diagnosis and management. Totowa, N.J.: Humana Press. pp. 442. ISBN 9781588296160.
  14. Klotz, J.H. et al (2010 Jun 15). ""Kissing bugs": potential disease vectors and cause of anaphylaxis.". Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 50 (12): 1629–34. PMID 20462351.
  15. Bilò, MB (2011 Jul). "Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment.". Allergy 66 Suppl 95: 35–7. PMID 21668850.
  16. Cox, L. et al (2010 Mar). "Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System.". The Journal of allergy and clinical immunology 125 (3): 569–74, 574.e1-574.e7. PMID 20144472.
  17. Bilò, BM; Bonifazi, F (2008 Aug). "Epidemiology of insect-venom anaphylaxis.". Current opinion in allergy and clinical immunology 8 (4): 330–7. PMID 18596590.
  18. 18.0 18.1 18.2 18.3 18.4 Khan, BQ; Kemp, SF (2011 Aug). "Pathophysiology of anaphylaxis.". Current opinion in allergy and clinical immunology 11 (4): 319–25. PMID 21659865.
  19. 19.0 19.1 Ring, J; Behrendt, H, de Weck, A (2010). "History and classification of anaphylaxis.". Chemical immunology and allergy 95: 1–11. PMID 20519878.
  20. Lieberman P 2005. Biphasic anaphylactic reactions. Ann. Allergy Asthma Immunol. 95 (3): 217–26; quiz 226, 258. [3]
  21. "Emergency treatment of anaphylactic reactions – Guidelines for healthcare providers" (PDF). Resuscitation Council (UK). January 2008. Retrieved 2008-04-22.
  22. 22.0 22.1 Martelli, A; Ghiglioni D. et al (2008 Aug). "Anaphylaxis in the emergency department: a paediatric perspective.". Current opinion in allergy and clinical immunology 8 (4): 321–9. PMID 18596589.
  23. Harris, edited by Jeffrey; Weisman, Micheal S. (2007). Head and neck manifestations of systemic disease. London: Informa Healthcare. pp. 325. ISBN 9780849340505.
  24. Demain JG; Minaei AA, Tracy JM 2010. Anaphylaxis and insect allergy. Current Opinion in Allergy and Clinical Immunology 10 (4): 318–22.