Anaphylaxis

{{short description|Life-threatening allergic reaction}} {{cs1 config|name-list-style=vanc}} {{Infobox medical condition | name = Anaphylaxis | types = Anaphylactoid reaction, anaphylactic shock, biphasic anaphylaxis | image = | field = Emergency medicine, allergy and immunology | symptoms = Itchy rash, throat swelling, numbness, shortness of breath, lightheadedness, low blood pressure,<ref name=NIH2015/> vomiting | complications = | onset = Over minutes to hours<ref name=NIH2015/> | duration = | causes = Insect bites, foods, medications,<ref name=NIH2015/> drugs/vaccines | risks = | diagnosis = Based on symptoms<ref name=IAP2003>{{cite book|last1=Caterino|first1=Jeffrey M.|last2=Kahan|first2=Scott|title=In a Page: Emergency medicine|date=2003|publisher=Lippincott Williams & Wilkins|isbn=978-1-4051-0357-2|page=132|url=https://books.google.com/books?id=O0LwFPZDKbsC&pg=PA132|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908184018/https://books.google.ca/books?id=O0LwFPZDKbsC&pg=PA132|archive-date=2017-09-08}}</ref> | differential = Allergic reaction, asthma exacerbation, carcinoid syndrome<ref name=IAP2003/> | prevention = | treatment = Epinephrine, intravenous fluids<ref name=NIH2015/> | medication = Epinephrine, corticosteroids, antihistamines | frequency = 0.05–2%<ref name=World11/> | deaths = }}

'''Anaphylaxis''' is a serious, potentially fatal allergic reaction that can progress rapidly.<ref>{{Cite journal |last1=Dribin |first1=Timothy E. |last2=Muraro |first2=Antonella |last3=Camargo |first3=Carlos A. |last4=Turner |first4=Paul J. |last5=Wang |first5=Julie |last6=Roberts |first6=Graham |last7=Anagnostou |first7=Aikaterini |last8=Halken |first8=Susanne |last9=Liebermann |first9=Jay |last10=Worm |first10=Margitta |last11=Zuberbier |first11=Torsten |last12=Sampson |first12=Hugh A. |last13=Alvaro-Lozano |first13=Montserrat |last14=Arasi |first14=Stefania |last15=Ben-Shoshan |first15=Moshe |date=2025 |title=Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report—a GA2LEN project |journal=Journal of Allergy and Clinical Immunology |volume=156 |issue=2 |pages=406–417.e6 |doi=10.1016/j.jaci.2025.01.021 |issn=0091-6749 |pmc=12301991 |pmid=39880313}}</ref> It typically causes more than one of the following: an itchy rash, throat closing due to swelling that can obstruct or stop breathing; severe tongue swelling that can also interfere with or stop breathing; shortness of breath, vomiting, lightheadedness, loss of consciousness, low blood pressure, and medical shock.<ref name="Overview - Anaphylaxis">{{cite web |author1=NHS |title=Overview – Anaphylaxis |url=https://www.nhs.uk/conditions/anaphylaxis/ |website=NHS (National Health Service) |publisher=British government |access-date=4 March 2022 |location=United Kingdom |language=English |date=29 November 2019}}</ref><ref name="NIH2015" />

These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels.<ref name="NIH2015" /> Urgent medical treatment is required to prevent serious harm and death, even if the patient has used an epinephrine autoinjector or has taken other medications in response, and even if symptoms appear to be improving.<ref name="Overview - Anaphylaxis" />

Common causes include allergies to insect bites and stings, allergies to foods—including nuts, peanuts, milk, fish, eggs; allergies to medications – including some antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs); or allergies to anaesthetics or latex.<ref name="Overview - Anaphylaxis"/> Other causes can include physical exercise, and cases may also occur in some people due to escalating reactions to simple throat irritation or may also occur without an obvious reason.<ref name="Overview - Anaphylaxis"/><ref name=NIH2015>{{cite web|title=Anaphylaxis|url=https://www.niaid.nih.gov/node/7937?404message&requested_url=/topics/anaphylaxis/Pages/default.aspx|publisher=National Institute of Allergy and Infectious Diseases|access-date=4 February 2016|date=April 23, 2015|url-status=live|archive-url=https://web.archive.org/web/20150504041904/http://www.niaid.nih.gov/topics/anaphylaxis/Pages/default.aspx|archive-date=4 May 2015}}</ref> The mast cell disease mastocytosis, along with the mast cell disorder mast cell activation syndrome are both capable of triggering anaphylaxis.<ref>{{Cite journal |last=Gülen |first=Theo |date=2023-10-25 |title=A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis |journal=Diagnostics (Basel, Switzerland) |volume=13 |issue=21 |pages=3307 |doi=10.3390/diagnostics13213307 |doi-access=free |issn=2075-4418 |pmc=10647312 |pmid=37958203}}</ref>

The mechanism involves the release of inflammatory mediators in a rapidly escalating cascade from certain types of white blood cells triggered by either immunologic or non-immunologic mechanisms.<ref name="Khan11">{{cite journal|last=Khan|first=BQ|author2=Kemp, SF|title=Pathophysiology of anaphylaxis|journal=Current Opinion in Allergy and Clinical Immunology|date=August 2011|volume=11|issue=4|pages=319–25|pmid=21659865|doi=10.1097/ACI.0b013e3283481ab6|s2cid=6810542}}</ref> Diagnosis is based on the presenting symptoms and signs after exposure to a potential allergen or irritant.<ref name="Overview - Anaphylaxis" /><ref name="NIH2015" />

The primary treatment of anaphylaxis is epinephrine injection into a muscle, intravenous fluids, then placing the person in a reclining position with feet elevated to help restore normal blood flow.<ref name=NIH2015/><ref name=EAACI2014>{{cite journal|author=The EAACI Food Allergy and Anaphylaxis Guidelines Group|title=Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology.|journal=Allergy|date=August 2014|volume=69|issue=8|pages=1026–45|pmid=24909803|doi=10.1111/all.12437|s2cid=11054771|url=https://kclpure.kcl.ac.uk/portal/en/publications/18fea276-3a30-4c4a-8d90-9d456bb71bb8 }}</ref> Additional doses of epinephrine may be required.<ref name=NIH2015/> Other measures, such as antihistamines and steroids, are complementary.<ref name=NIH2015/> Carrying an epinephrine autoinjector, commonly called an "epipen", and identification regarding the condition is recommended in people with a history of anaphylaxis.<ref name=NIH2015/> Immediately contacting ambulance / EMT services is strongly recommended, regardless of any on-site treatment.<ref name="Overview - Anaphylaxis"/> Getting to a doctor or hospital as soon as possible is important, even if the condition appears to be getting better.<ref name="Overview - Anaphylaxis"/><ref>{{Cite journal |date=2003-08-01 |title=Use of epinephrine in the treatment of anaphylaxis |journal=Current Opinion in Allergy and Clinical Immunology |volume=3 |issue=4 |pages=313–318 |doi=10.1097/00130832-200308000-00013 |issn=1528-4050 |pmid=12865777| vauthors = Lieberman P }}</ref>

Worldwide, 0.05–2% of the population is estimated to experience anaphylaxis at some point in life.<ref name=World11/> Globally, as underreporting declined into the 2010s, the rate appeared to be increasing.<ref name=World11>{{cite journal|last1=Simons|first1=FE|last2=Ardusso|first2=LR|last3=Bilò|first3=MB|last4=El-Gamal|first4=YM|last5=Ledford|first5=DK|last6=Ring|first6=J|last7=Sanchez-Borges|first7=M|last8=Senna|first8=GE|last9=Sheikh|first9=A|last10=Thong|first10=BY|last11=World Allergy|first11=Organization.|title=World allergy organization guidelines for the assessment and management of anaphylaxis.|journal=The World Allergy Organization Journal|date=February 2011|volume=4|issue=2|pages=13–37|pmid=23268454|doi=10.1097/wox.0b013e318211496c|pmc=3500036}}</ref> It occurs most often in young people and females.<ref name=EAACI2014/><ref name=CEA11>{{cite journal|last=Lee|first=JK|author2=Vadas, P|title=Anaphylaxis: mechanisms and management|journal=Clinical and Experimental Allergy|date=July 2011|volume=41|issue=7|pages=923–38|pmid=21668816|doi=10.1111/j.1365-2222.2011.03779.x|s2cid=13218854}}</ref> About 99.7% of people hospitalized with anaphylaxis in the United States survive.<ref>{{cite journal|last1=Ma|first1=L|last2=Danoff|first2=TM|last3=Borish|first3=L|title=Case fatality and population mortality associated with anaphylaxis in the United States.|journal=The Journal of Allergy and Clinical Immunology|date=April 2014|volume=133|issue=4|pages=1075–83|pmid=24332862|doi=10.1016/j.jaci.2013.10.029|pmc=3972293}}</ref>

==Etymology== The word is derived from {{langx|grc|ἀνά|ana|up}}, and {{langx|grc|φύλαξις|phylaxis|protection}}.<ref>{{Cite web |title=Definition of ANA- |url=https://www.merriam-webster.com/dictionary/ana- |access-date=2024-09-05 |website=www.merriam-webster.com |language=en}}</ref><ref>{{cite book|last1=Gylys|first1=Barbara|title=Medical Terminology Systems: A Body Systems Approach|date=2012|publisher=F.A. Davis|isbn=978-0-8036-3913-3|page=269|url=https://books.google.com/books?id=cR5hAQAAQBAJ&pg=PA269|url-status=live|archive-url=https://web.archive.org/web/20160205065649/https://books.google.ca/books?id=cR5hAQAAQBAJ&pg=PA269|archive-date=2016-02-05}}</ref>

==Signs and symptoms== thumb|upright=1.5|Signs and symptoms of anaphylaxis Anaphylaxis typically presents many different symptoms over minutes or hours<ref name=EAACI2014/><ref>{{cite journal |vauthors=Oswalt ML, Kemp SF |title=Anaphylaxis: office management and prevention |journal=Immunol Allergy Clin North Am |volume=27 |issue=2 |pages=177–91, vi |date=May 2007 |pmid=17493497 |doi=10.1016/j.iac.2007.03.004|quote=Clinically, anaphylaxis is considered likely to be present if any one of three criteria is satisfied within minutes to hours}}</ref> with an average onset of 5 to 30 minutes if exposure is intravenous and up to 2 hours if from eating food.<ref name=Rosen2010/> The most common areas affected include: skin (80–90%), respiratory (70%), gastrointestinal (30–45%), heart and vasculature (10–45%), and central nervous system (10–15%)<ref name=Review09>{{cite journal |author=Simons FE |title=Anaphylaxis: Recent advances in assessment and treatment |journal=The Journal of Allergy and Clinical Immunology |volume=124 |issue=4 |pages=625–36; quiz 637–8 |date=October 2009 |pmid=19815109 |doi=10.1016/j.jaci.2009.08.025}}</ref> with usually two or more being involved.<ref name=World11/>

===Skin=== [[File:Rash on the chest of a person with anaphylaxis.jpg|thumb|upright=1.3|Urticaria and flushing on the chest of a person with anaphylaxis]] Symptoms typically include generalized hives, itchiness, flushing, or swelling (angioedema) of the affected tissues.<ref name="Samp2006">{{cite journal |display-authors=etal |vauthors=Sampson HA, Muñoz-Furlong A, Campbell RL |date=February 2006 |title=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 |url=https://www.jacionline.org/article/S0091-6749%2805%2902723-5/fulltext |journal=The Journal of Allergy and Clinical Immunology |volume=117 |issue=2 |pages=391–7 |doi=10.1016/j.jaci.2005.12.1303 |pmid=16461139 |url-access=subscription |doi-access=free}}</ref> Those with angioedema may describe a burning sensation of the skin rather than itchiness.<ref name=Rosen2010/> Swelling of the tongue or throat occurs in up to about 20% of cases.<ref name=Shock10/> Other features may include a runny nose and swelling of the conjunctiva.<ref name=Aus06/> The skin may also be blue tinged because of lack of oxygen.<ref name=Aus06/>

===Respiratory=== Respiratory symptoms and signs that may be present include shortness of breath, wheezes, or stridor.<ref name="Samp2006" /> The wheezing is typically caused by spasms of the bronchial muscles<ref name=Cardio08/> while stridor is related to upper airway obstruction secondary to swelling.<ref name=Aus06>{{cite journal|last=Brown|first=SG|author2=Mullins, RJ |author3=Gold, MS|title=Anaphylaxis: diagnosis and management|journal=The Medical Journal of Australia|date=Sep 4, 2006|volume=185|issue=5|pages=283–9|pmid=16948628|doi=10.5694/j.1326-5377.2006.tb00563.x|hdl=2440/23292|s2cid=39009649|hdl-access=free}}</ref> Hoarseness, pain with swallowing, or a cough may also occur.<ref name=Rosen2010/>

===Cardiovascular=== While a fast heart rate caused by low blood pressure is more common,<ref name=Aus06/> a Bezold–Jarisch reflex has been described in 10% of people, where a slow heart rate is associated with low blood pressure.<ref name=CEA11/> A drop in blood pressure or shock (either distributive or cardiogenic) may cause the feeling of lightheadedness or loss of consciousness.<ref name=Cardio08/> Rarely very low blood pressure may be the only sign of anaphylaxis.<ref name=Shock10/>

Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest.<ref name=World11/><ref name=Review09/> Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis.<ref name=Cardio08/> The coronary spasm is related to the presence of histamine-releasing cells in the heart.<ref name=Cardio08/>

===Other=== Gastrointestinal symptoms may include severe crampy abdominal pain and vomiting.<ref name="Samp2006" /> There may be confusion, a loss of bladder control or pelvic pain similar to that of uterine cramps.<ref name="Samp2006" /><ref name=Aus06/> Dilation of blood vessels around the brain may cause headaches.<ref name=Rosen2010/> A feeling of anxiety or of "impending doom" has also been described.<ref name=World11/>

==Causes== Anaphylaxis can occur in response to almost any foreign substance.<ref name=His11/> Common triggers include venom from insect bites or stings, foods, and medication.<ref name=CEA11/><ref>{{cite book|last=Worm|first=M|title=Anaphylaxis|chapter=Epidemiology of anaphylaxis|series=Chemical Immunology and Allergy|year=2010|volume=95|pages=12–21|pmid=20519879|doi=10.1159/000315935|isbn=978-3-8055-9441-7}}</ref> Foods are the most common trigger in children and young adults, while medications and insect bites and stings are more common in older adults.<ref name=World11/> Less common causes include: physical factors, biological agents such as semen, latex, hormonal changes, food additives and colors, and topical medications.<ref name=Aus06/>

Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells.<ref name=World11/><ref name="APLS07">{{cite book |url=https://books.google.com/books?id=lLVfDC2dh54C&pg=PA69 |title=The pediatric emergency medicine resource |vauthors=Gausche-Hill M, Fuchs S, Yamamoto L |publisher=Jones & Bartlett |year=2007 |isbn=978-0-7637-4414-4 |edition=Rev. 4. |location=Sudbury, Mass. |page=69 |archive-url=https://web.archive.org/web/20161223154615/https://books.google.com/books?id=lLVfDC2dh54C&pg=PA69 |archive-date=2016-12-23 |url-status=live}}</ref><ref>{{cite journal|last1=Feldweg|first1=AM|title=Exercise-Induced Anaphylaxis|journal=Immunology and Allergy Clinics of North America|date=May 2015|volume=35|issue=2|pages=261–75|doi=10.1016/j.iac.2015.01.005|pmid=25841550|type=Review}}</ref> Events caused by exercise are frequently associated with cofactors such as the ingestion of certain foods<ref name=Rosen2010/><ref name=Pravetton2016rev>{{cite journal|last1=Pravettoni|first1=V|last2=Incorvaia|first2=C|title=Diagnosis of exercise-induced anaphylaxis: current insights.|journal=Journal of Asthma and Allergy|date=2016|volume=9|pages=191–198|doi=10.2147/JAA.S109105|pmid=27822074|pmc=5089823|doi-access=free}}</ref> or taking an NSAID.<ref name=Pravetton2016rev/><ref>{{Cite journal |date=2017-01-02 |title=Food-dependent exercise-induced anaphylaxis |journal=Canadian Family Physician |volume=63 |issue=1 |pages=42–43 |issn=1715-5258 |pmc=5257219 |pmid=28115440| vauthors = Minty B }}</ref> Anaphylaxis caused by a combination of exercise and consumption of certain foods is known as food-dependent exercise-induced anaphylaxis (FDEIA).<ref>{{Cite web |title=Understanding Anaphylaxis: Causes, Symptoms, and Treatment |url=https://www.everydayhealth.com/anaphylaxis/guide/ |access-date=2025-10-02 |website=EverydayHealth.com |language=en}}</ref> In aspirin-exacerbated respiratory disease (AERD), alcohol is a common trigger.<ref name= Stevens2015>{{cite journal |vauthors=Stevens W, Buchheit K, Cahill KN |title=Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis |journal=Curr Allergy Asthma Rep |volume=15 |issue=12 |article-number=69 |date=December 2015 |pmid=26475526 |doi=10.1007/s11882-015-0569-2 |s2cid=2827520 }}</ref><ref name= Cardet2014/> During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes.<ref>{{cite journal|last=Dewachter|first=P|author2=Mouton-Faivre, C |author3=Emala, CW|title=Anaphylaxis and anesthesia: controversies and new insights|journal=Anesthesiology|date=November 2009|volume=111|issue=5|pages=1141–50|pmid=19858877|doi=10.1097/ALN.0b013e3181bbd443|doi-access=free}}</ref> The cause remains unknown in 32–50% of cases, referred to as "idiopathic anaphylaxis."<ref name="editor 2010 223">{{cite book |last=Castells |first=Mariana C. |url=https://books.google.com/books?id=bEvnfm7V-LIC&pg=PA223 |title=Anaphylaxis and hypersensitivity reactions |publisher=Humana Press |year=2010 |isbn=978-1-60327-950-5 |location=New York |page=223 |archive-url=https://web.archive.org/web/20161223161731/https://books.google.com/books?id=bEvnfm7V-LIC&pg=PA223 |archive-date=2016-12-23 |url-status=live}}</ref> Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and HPV may cause anaphylaxis as well.<ref>{{cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK190024/ |format=PDF |publisher=U.S. Institute of Medicine |title=Adverse Effects of Vaccines: Evidence and Causality |year=2011 |pmid=24624471 |access-date=2014-01-16 |url-status=live |archive-url=https://web.archive.org/web/20170908184018/https://www.ncbi.nlm.nih.gov/books/NBK190024/ |archive-date=2017-09-08 |isbn=978-0-309-21435-3 |last1=Stratton |first1=K. |last2=Ford |first2=A. |last3=Rusch |first3=E. |last4=Clayton |first4=E. W. |author5=Committee to Review Adverse Effects of Vaccines |author6=Institute of Medicine }}</ref>

===Food and alcohol=== Many foods can trigger anaphylaxis; this may occur upon the first known ingestion.<ref name=CEA11/> Common triggering foods vary around the world due to cultural cuisine. In Western cultures, ingestion of or exposure to peanuts, wheat, nuts, certain types of seafood like shellfish, milk, fruit and eggs are the most prevalent causes.<ref name=World11/><ref name=Review09/> Sesame is common in the Middle East, while rice and chickpeas are frequently encountered as sources of anaphylaxis in Asia.<ref name=World11/> Severe cases are usually caused by ingesting the allergen,<ref name=CEA11/> but some people experience a severe reaction upon contact. Children can outgrow their allergies. By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts can tolerate these foods.<ref name=His11/> Any type of alcohol, even in small amounts, can trigger anaphylaxis in people with AERD.<ref name= Stevens2015/><ref name= Cardet2014>{{cite journal |vauthors=Cardet JC, White AA, Barrett NA, Feldweg AM, Wickner PG, Savage J, Bhattacharyya N, Laidlaw TM |title=Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease |journal=J Allergy Clin Immunol Pract |volume=2 |issue=2 |pages=208–213 |date=2014 |pmid=24607050 |pmc=4018190 |doi=10.1016/j.jaip.2013.12.003 }}</ref>

===Medication=== Any medication may potentially trigger anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin and NSAIDs.<ref name=Review09/><ref name=WHO2015>{{cite journal|vauthors = Simons FE, Ebisawa M, Sanchez-Borges M, Thong BY, Worm M, Tanno LK, Lockey RF, El-Gamal YM, Brown SG, Park HS, Sheikh A |title=2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines.|journal=The World Allergy Organization Journal|date=2015|volume=8|issue=1|article-number=32|pmid=26525001|pmc=4625730|doi=10.1186/s40413-015-0080-1 |doi-access=free }}</ref> Other antibiotics are implicated less frequently.<ref name=WHO2015/> Anaphylactic reactions to NSAIDs are either agent specific or occur among those that are structurally similar meaning that those who are allergic to one NSAID can typically tolerate a different one or different group of NSAIDs.<ref>{{cite journal|last1=Modena|first1=B|last2=White|first2=AA|last3=Woessner|first3=KM|title=Aspirin and Nonsteroidal Antiinflammatory Drugs Hypersensitivity and Management.|journal=Immunology and Allergy Clinics of North America|date=November 2017|volume=37|issue=4|pages=727–749|doi=10.1016/j.iac.2017.07.008|pmid=28965637}}</ref> Other relatively common causes include chemotherapy, vaccines, protamine and herbal preparations.<ref name=World11/> Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.<ref name=CEA11/>

The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties.<ref name=Drug01>{{cite journal|last=Drain|first=KL|author2=Volcheck, GW|title=Preventing and managing drug-induced anaphylaxis|journal=Drug Safety |year=2001|volume=24|issue=11|pages=843–53|pmid=11665871|doi=10.2165/00002018-200124110-00005|s2cid=24840296}}</ref> Anaphylaxis to penicillin or cephalosporins occurs only after it binds to proteins inside the body with some agents binding more easily than others.<ref name=Rosen2010/> Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in fewer than one in every 50,000 courses of treatment.<ref name=Rosen2010/> Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons.<ref name=Rosen2010/> If someone reacts to penicillin, his or her risk of a reaction to cephalosporins is greater but still less than one in 1,000.<ref name=Rosen2010/> The old radiocontrast agents caused reactions in 1% of cases, while the newer, lower osmolar agents cause reactions in 0.04% of cases.<ref name=Drug01/> Avoidance of cephalosporins in those with penicillin allergy creates a significantly greater patient safety risk than the low probability of anaphylaxis.<ref>{{Cite journal |last1=Zagursky |first1=Robert J. |last2=Pichichero |first2=Michael E. |date=January 2018 |title=Cross-reactivity in β-Lactam Allergy |url=https://linkinghub.elsevier.com/retrieve/pii/S2213219817307110 |journal=The Journal of Allergy and Clinical Immunology: In Practice |language=en |volume=6 |issue=1 |pages=72–81.e1 |doi=10.1016/j.jaip.2017.08.027|pmid=29017833 |url-access=subscription }}</ref>

===Venom=== Venom from stinging or biting insects such as Hymenoptera (ants, bees, and wasps) or Triatominae (kissing bugs) may cause anaphylaxis in susceptible people.<ref name=EAACI2014/><ref name="Klotz">{{cite journal|last=Klotz|first=JH|author2=Dorn, PL |author3=Logan, JL |author4=Stevens, L |author5=Pinnas, JL |author6=Schmidt, JO |author7=Klotz, SA |title="Kissing bugs": potential disease vectors and cause of anaphylaxis|journal=Clinical Infectious Diseases |date=Jun 15, 2010|volume=50|issue=12|pages=1629–34|pmid=20462351|doi=10.1086/652769|doi-access=free}}</ref><ref name=2001simonga>{{cite journal |first1=Simon G. A. |last1=Brown |first2=Qi-Xuan |last2=Wu |first3=G. Robert H. |last3=Kelsall |first4=Robert J. |last4=Heddle |first5=Brian A. |last5=Baldo |title=Fatal anaphylaxis following jack jumper ant sting in southern Tasmania |journal=Medical Journal of Australia |year=2001 |volume=175 |issue=11 |pages=644–647 |pmid=11837875 |url=http://www.mja.com.au/public/issues/175_12_171201/brown/brown.html |url-status=live |archive-url=https://web.archive.org/web/20120114054159/http://mja.com.au/public/issues/175_12_171201/brown/brown.html |archive-date=2012-01-14 |doi=10.5694/j.1326-5377.2001.tb143761.x |s2cid=2495334 |url-access=subscription }}</ref> Previous reactions that are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis;<ref>{{cite journal|last=Bilò|first=MB|title=Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment|journal=Allergy|date=July 2011|volume=66|issue=Suppl 95 |pages=35–7|pmid=21668850|doi=10.1111/j.1398-9995.2011.02630.x|s2cid=31238581}}</ref><ref>{{cite journal|last=Cox|first=L|author2=Larenas-Linnemann, D|author3=Lockey, RF |author4=Passalacqua, G|title=Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System|journal=The Journal of Allergy and Clinical Immunology|date=March 2010|volume=125|issue=3|pages=569–74, 574.e1–574.e7|pmid=20144472|doi=10.1016/j.jaci.2009.10.060|doi-access=free}}</ref> however, half of the fatalities have had no previous systemic reaction.<ref>{{cite journal|last=Bilò|first=BM|author2=Bonifazi, F|title=Epidemiology of insect-venom anaphylaxis|journal=Current Opinion in Allergy and Clinical Immunology|date=August 2008|volume=8|issue=4|pages=330–7|pmid=18596590|doi=10.1097/ACI.0b013e32830638c5|s2cid=28384693}}</ref>

===Risk factors=== People with atopic diseases such as asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex, and radiocontrast agents but not from injectable medications or stings.<ref name=World11/><ref name=CEA11/> One study in children found that 60% had a history of previous atopic diseases, and of children who die from anaphylaxis, more than 90% have asthma.<ref name=CEA11/> Those with mastocytosis, mast cell activation syndrome (MCAS) or of a higher socioeconomic status are at increased risk.<ref name=World11/><ref name=CEA11/><ref name="PMID38948000">{{cite journal |vauthors=Özdemir Ö, Kasımoğlu G, Bak A et al. |title=Mast cell activation syndrome: An up-to-date review of literature |journal=World J Clin Pediatr |date=2024-06-09 |volume=13 |issue=2 |doi=10.5409/wjcp.v13.i2.92813 |pmc=11212760 |pmid=38948000 |url=|doi-access=free}}</ref>

==Pathophysiology== Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems.<ref name="Tint10">{{cite book |author=Tintinalli, Judith E. |title=Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)) |publisher=McGraw-Hill Companies |year=2010 |isbn=978-0-07-148480-0 |location=New York |pages=177–182}}</ref><ref name=Khan11/> It is due to the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes non-immunologic mechanism.<ref name=Khan11/>

Interleukin (IL)–4 and IL-13 are cytokines important in the initial generation of antibody and inflammatory cell responses to anaphylaxis.<ref name="v005"/>

===Immunologic=== The vast majority of anaphylaxis is mediated by allergen-specific immunoglobulin E (IgE). In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcεRI receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and compromise circulatory function.<ref name=Khan11/><ref name=Rosen2010/>

Rarely, anaphylaxis may be triggered by immunoglobulin G (IgG) antibodies. Allergen-specific IgG is generally considered to be protective against allergic reactions (including anaphylaxis) because it competes with IgE for binding to the allergen (i.e., it is a blocking antibody) and its immune complexes (lattices of antigen and antibody, or in this case, allergen and IgG) inhibit IgE signaling.<ref>{{Cite journal |last=Strait |first=R. T. |date=2006-03-01 |title=IgG-blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and Fc RIIb cross-linking |journal=Journal of Clinical Investigation |language=en |volume=116 |issue=3 |pages=833–841 |doi=10.1172/JCI25575 |pmid=16498503 |issn=0021-9738|pmc=1378186 }}</ref><ref>{{Cite journal |last1=Shamji |first1=Mohamed H. |last2=Valenta |first2=Rudolf |last3=Jardetzky |first3=Theodore |last4=Verhasselt |first4=Valerie |last5=Durham |first5=Stephen R. |last6=Würtzen |first6=Peter A. |last7=van Neerven |first7=R. J. Joost |date=December 2021 |title=The role of allergen-specific IgE, IgG and IgA in allergic disease |journal=Allergy |volume=76 |issue=12 |pages=3627–3641 |doi=10.1111/all.14908 |issn=1398-9995 |pmc=8601105 |pmid=33999439}}</ref><ref>{{Cite journal |last1=Shaker |first1=Marcus S. |last2=Wallace |first2=Dana V. |last3=Golden |first3=David B.K. |last4=Oppenheimer |first4=John |last5=Bernstein |first5=Jonathan A. |last6=Campbell |first6=Ronna L. |last7=Dinakar |first7=Chitra |last8=Ellis |first8=Anne |last9=Greenhawt |first9=Matthew |last10=Khan |first10=David A. |last11=Lang |first11=David M. |last12=Lang |first12=Eddy S. |last13=Lieberman |first13=Jay A. |last14=Portnoy |first14=Jay |last15=Rank |first15=Matthew A. |date=April 2020 |title=Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis |url=https://linkinghub.elsevier.com/retrieve/pii/S0091674920301056 |journal=Journal of Allergy and Clinical Immunology |language=en |volume=145 |issue=4 |pages=1082–1123 |doi=10.1016/j.jaci.2020.01.017|url-access=subscription }}</ref>

===Non-immunologic=== Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils without ligating the high-affinity IgE receptor. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration.<ref name=Khan11/><ref name=APLS07/> Sulfites may cause reactions by both immunologic and non-immunologic mechanisms.<ref>{{cite book|last1=Lewis|first1=Julius M.|last2=Cruse|first2=Robert E.|title=Atlas of immunology|date=2010|publisher=CRC Press/Taylor & Francis|location=Boca Raton, FL|isbn=978-1-4398-0269-4|page=411|edition=3rd|url=https://books.google.com/books?id=kNI5Lk2z37sC&pg=PA411|url-status=live|archive-url=https://web.archive.org/web/20170320104901/https://books.google.com/books?id=kNI5Lk2z37sC&pg=PA411|archive-date=2017-03-20}}</ref> This is a form of pseudoallergy and is commonly mediated by MRPRX2, a promiscuous receptor that interacts with many substances (especially drugs) to trigger mast cell degranulation without IgE.<ref>{{Cite journal |last1=Ratnayake |first1=Subashini Hemamala |last2=Senarath |first2=Kanishka |last3=Gangani |first3=Dakshika |last4=Dasanayake |first4=Dhanushka |last5=de Silva |first5=Rajiva |last6=Handunnetti |first6=Shiroma |date=August 2025 |title=Mutations of MRGPRX2, drug sensitivity, and genetic markers related to disease |journal=Journal of Allergy and Clinical Immunology: Global |language=en |volume=4 |issue=3 |article-number=100467 |doi=10.1016/j.jacig.2025.100467|doi-access=free |pmid=41631278 |pmc=12861636 }}</ref>

=== Mixed type === A form of anaphylaxis that has both IgE-dependent and non-IgE-dependent features has been observed as a consequence of some chemotherapy and monoclonal antibodies, manifesting alongside cytokine storm-like features.<ref>{{Cite journal |last=Castells |first=Mariana |date=August 2017 |title=Diagnosis and management of anaphylaxis in precision medicine |url=https://linkinghub.elsevier.com/retrieve/pii/S0091674917310849 |journal=Journal of Allergy and Clinical Immunology |language=en |volume=140 |issue=2 |pages=321–333 |doi=10.1016/j.jaci.2017.06.012 |pmid=28780940 }}</ref>

==Diagnosis== Anaphylaxis is diagnosed on the basis of a person's signs and symptoms. When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis:<ref name="v392">{{cite journal | last1=Muraro | first1=Antonella | last2=Worm | first2=Margitta | last3=Alviani | first3=Cherry | last4=Cardona | first4=Victoria | last5=DunnGalvin | first5=Audrey | last6=Garvey | first6=Lene Heise | last7=Riggioni | first7=Carmen | last8=de Silva | first8=Debra | last9=Angier | first9=Elizabeth | last10=Arasi | first10=Stefania | last11=Bellou | first11=Abdelouahab | last12=Beyer | first12=Kirsten | last13=Bijlhout | first13=Diola | last14=Bilò | first14=Maria Beatrice | last15=Bindslev-Jensen | first15=Carsten | last16=Brockow | first16=Knut | last17=Fernandez-Rivas | first17=Montserrat | last18=Halken | first18=Susanne | last19=Jensen | first19=Britt | last20=Khaleva | first20=Ekaterina | last21=Michaelis | first21=Louise J. | last22=Oude Elberink | first22=Hanneke N. G. | last23=Regent | first23=Lynne | last24=Sanchez | first24=Angel | last25=Vlieg-Boerstra | first25=Berber J. | last26=Roberts | first26=Graham | author27=((European Academy of Allergy and Clinical Immunology, Food Allergy, Anaphylaxis Guidelines Group)) | title=EAACI guidelines: Anaphylaxis (2021 update) | journal=Allergy | volume=77 | issue=2 | date=2022 | issn=0105-4538 | doi=10.1111/all.15032 | pages=357–377 | pmid=34343358 | url=https://onlinelibrary.wiley.com/doi/10.1111/all.15032 | access-date=2025-12-10| hdl=11566/297530 | hdl-access=free }}</ref> # Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure causing symptoms # Two or more of the following symptoms after a likely contact with an allergen: #: a. Involvement of the skin or mucosa #: b. Respiratory difficulties #: c. Low blood pressure #: d. Gastrointestinal symptoms # Low blood pressure after exposure to a known allergen

Skin involvement may include: hives, itchiness, or a swollen tongue, among others. Respiratory difficulties may include: shortness of breath, stridor, or low oxygen levels, among others. Low blood pressure is defined as a greater than 30% decrease from a person's usual blood pressure. In adults, a systolic blood pressure of less than 90 mmHg is often used.<ref name=World11/>

During an attack, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications. However these tests are of limited use if the cause is food or if the person has a normal blood pressure,<ref name=World11/> and they are not specific for the diagnosis.<ref name=His11/> Notably, hereditary alpha tryptasemia is an autosomal dominant condition present in about 5.7% of the population, a condition that is generally asymptomatic (but may increase the frequency and intensity of allergic reactions) that causes elevated levels of tryptase at baseline,<ref>{{Cite journal |last1=Chovanec |first1=Jack |last2=Tunc |first2=Ilker |last3=Hughes |first3=Jason |last4=Halstead |first4=Joseph |last5=Mateja |first5=Allyson |last6=Liu |first6=Yihui |last7=O'Connell |first7=Michael P. |last8=Kim |first8=Jiwon |last9=Park |first9=Young Hwan |last10=Wang |first10=Qinlu |last11=Le |first11=Quang |last12=Pirooznia |first12=Mehdi |last13=Trivedi |first13=Neil N. |last14=Bai |first14=Yun |last15=Yin |first15=Yuzhi |date=2023-05-09 |title=Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms |journal=Blood Advances |volume=7 |issue=9 |pages=1796–1810 |doi=10.1182/bloodadvances.2022007936 |issn=2473-9537 |pmc=10164828 |pmid=36170795}}</ref> which means that in some people, a tryptase may be elevated independent of anaphylaxis. To ensure that an elevated tryptase is not the result of hereditary alpha tryptasemia, the EAACI recommends repeating a tryptase level 24 hours after resolution of anaphylaxis.<ref>{{Cite journal |last1=Muraro |first1=Antonella |last2=Worm |first2=Margitta |last3=Alviani |first3=Cherry |last4=Cardona |first4=Victoria |last5=DunnGalvin |first5=Audrey |last6=Garvey |first6=Lene Heise |last7=Riggioni |first7=Carmen |last8=de Silva |first8=Debra |last9=Angier |first9=Elizabeth |last10=Arasi |first10=Stefania |last11=Bellou |first11=Abdelouahab |last12=Beyer |first12=Kirsten |last13=Bijlhout |first13=Diola |last14=Bilò |first14=Maria Beatrice |last15=Bindslev-Jensen |first15=Carsten |date=February 2022 |title=EAACI guidelines: Anaphylaxis (2021 update) |url=https://onlinelibrary.wiley.com/doi/10.1111/all.15032 |journal=Allergy |language=en |volume=77 |issue=2 |pages=357–377 |doi=10.1111/all.15032 |issn=0105-4538|hdl=11566/297530 |hdl-access=free }}</ref> Additionally, a normal tryptase does not rule out anaphylaxis.

===Classification=== There are three main classifications of anaphylaxis. # '''Anaphylactic shock''' is associated with systemic vasodilation that causes low blood pressure, which is by definition 30% lower than the person's baseline or below standard values.<ref name=Shock10>{{cite journal|last=Limsuwan|first=T|author2=Demoly, P|title=Acute symptoms of drug hypersensitivity (urticaria, angioedema, anaphylaxis, anaphylactic shock)|journal=The Medical Clinics of North America|date=July 2010|volume=94|issue=4|pages=691–710, x|pmid=20609858|url=http://smschile.cl/documentos/cursos2010/MedicalClinicsNorthAmerica/Acute%20Symptoms%20of%20Drug%20Hypersensitivity%20(Urticaria,%20Angioedema,%20Anaphylaxis,%20Anaphylactic%20Shock).pdf|doi=10.1016/j.mcna.2010.03.007|archive-url=https://web.archive.org/web/20120426041514/http://smschile.cl/documentos/cursos2010/MedicalClinicsNorthAmerica/Acute%20Symptoms%20of%20Drug%20Hypersensitivity%20%28Urticaria%2C%20Angioedema%2C%20Anaphylaxis%2C%20Anaphylactic%20Shock%29.pdf|archive-date=2012-04-26|access-date=2011-12-09}}</ref> # '''Biphasic anaphylaxis''' is the recurrence of symptoms within 1–72 hours after resolution of an initial anaphylactic episode.<ref name="pmid32001253"/> Estimates of incidence vary between less than 1% and up to 20% of cases.<ref name="pmid32001253"/><ref name=BI05/> The recurrence typically occurs within 8 hours.<ref name=CEA11/> It is managed in the same manner as anaphylaxis.<ref name=EAACI2014/> # '''Anaphylactoid reaction''', '''non-immune anaphylaxis''', or '''pseudoanaphylaxis''', is a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation.<ref name=CEA11/><ref name="His10">{{cite book |last=Ring |first=J |url=http://media.wiley.com/product_data/excerpt/42/04708611/0470861142.pdf |title=History and classification of anaphylaxis |author2=Behrendt, H |author3=de Weck, A |year=2010 |isbn=978-3-8055-9441-7 |series=Chemical Immunology and Allergy |volume=95 |pages=1–11 |doi=10.1159/000315934 |pmid=20519878}}</ref> Non-immune anaphylaxis is the current term, as of 2018, used by the World Allergy Organization<ref name=His10/> with some recommending that the old terminology, "anaphylactoid", no longer be used.<ref name=CEA11/>

===Allergy skin testing=== [[File:Allergy skin testing.JPG|thumb|upright=1.3|Skin allergy testing being carried out on the right arm]] [[File:Epikutanni-test.jpg|thumb|upright=1.3|Patch test]] Allergy testing may help in determining the trigger. Skin allergy testing is available for certain foods and venoms.<ref name=His11/> Blood testing for specific IgE can be useful to confirm milk, egg, peanut, tree nut, and fish allergies.<ref name=His11/>

Skin testing is available to confirm penicillin allergies, but is not available for other medications.<ref name=His11/> Non-immune forms of anaphylaxis can only be determined by history or exposure to the allergen in question, and not by skin or blood testing.<ref name=His10/>

===Differential diagnosis=== It can sometimes be difficult to distinguish anaphylaxis from asthma, syncope, and panic attacks.<ref name=World11/> Asthma however typically does not entail itching or gastrointestinal symptoms, syncope presents with pallor rather than a rash, and a panic attack may have flushing but does not have hives.<ref name=World11/> Other conditions that may present similarly include: scrombroidosis and anisakiasis.<ref name=CEA11/>

===Post-mortem findings=== In a person who died from anaphylaxis, autopsy may show an "empty heart" attributed to reduced venous return from vasodilation and redistribution of intravascular volume from the central to the peripheral compartment.<ref name="v005">{{cite journal | last=Mustafa | first=S Shahzad | title=Anaphylaxis: Practice Essentials, Background, Pathophysiology | website=Medscape Reference | date=2024-02-26 | url=https://emedicine.medscape.com/article/135065-overview#showall | access-date=2024-06-18}}</ref> Other signs are laryngeal edema, eosinophilia in lungs, heart and tissues, and evidence of myocardial hypoperfusion.<ref name=DaBroi/> Laboratory findings could detect increased levels of serum tryptase, an increase in total and specific IgE serum levels.<ref name=DaBroi>{{cite journal|last=Da Broi|first=U|author2=Moreschi, C|title=Post-mortem diagnosis of anaphylaxis: A difficult task in forensic medicine|journal=Forensic Science International|date=Jan 30, 2011|volume=204|issue=1–3|pages=1–5|pmid=20684869|doi=10.1016/j.forsciint.2010.04.039}}</ref>

==Prevention== {{see also|Allergen immunotherapy}} Avoidance of the trigger of anaphylaxis is recommended. In cases where this may not be possible, desensitization may be an option. Immunotherapy with Hymenoptera venoms is effective at desensitizing 80–90% of adults and 98% of children against allergies to bees, wasps, hornets, yellowjackets, and fire ants. Oral immunotherapy may be effective at desensitizing some people to certain food including milk, eggs, nuts and peanuts; however, adverse effects are common.<ref name=World11/> For example, many people develop an itchy throat, cough, or lip swelling during immunotherapy.<ref>{{cite journal|last1=Simons|first1=FE|last2=Ardusso|first2=LR|last3=Dimov|first3=V|last4=Ebisawa|first4=M|last5=El-Gamal|first5=YM|last6=Lockey|first6=RF|last7=Sanchez-Borges|first7=M|last8=Senna|first8=GE|last9=Sheikh|first9=A|last10=Thong|first10=BY|last11=Worm|first11=M|last12=World Allergy|first12=Organization.|title=World Allergy Organization Anaphylaxis Guidelines: 2013 update of the evidence base.|journal=International Archives of Allergy and Immunology|date=2013|volume=162|issue=3|pages=193–204|pmid=24008815|doi=10.1159/000354543|doi-access=free}}</ref> Desensitization is also possible for many medications, however it is usually advised that most people simply avoid the agent in question. In those who react to latex it may be important to avoid cross-reactive foods such as avocados, bananas, and potatoes among others.<ref name=World11/>

Premedications with antihistamines or glucocorticoids does not prevent anaphylaxis, but may be used in specific circumstances, such as rush aeroallergen desensitization or in certain chemotherapy regimens.<ref>{{Cite journal |last1=Shaker |first1=Marcus S. |last2=Wallace |first2=Dana V. |last3=Golden |first3=David B.K. |last4=Oppenheimer |first4=John |last5=Bernstein |first5=Jonathan A. |last6=Campbell |first6=Ronna L. |last7=Dinakar |first7=Chitra |last8=Ellis |first8=Anne |last9=Greenhawt |first9=Matthew |last10=Khan |first10=David A. |last11=Lang |first11=David M. |last12=Lang |first12=Eddy S. |last13=Lieberman |first13=Jay A. |last14=Portnoy |first14=Jay |last15=Rank |first15=Matthew A. |date=April 2020 |title=Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis |url=https://linkinghub.elsevier.com/retrieve/pii/S0091674920301056 |journal=Journal of Allergy and Clinical Immunology |language=en |volume=145 |issue=4 |pages=1082–1123 |doi=10.1016/j.jaci.2020.01.017|url-access=subscription }}</ref>

==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.<ref name=EAACI2014/> Passive leg raise may also be helpful in the emergency management.<ref name="Simons 2010 pp. S161–S181">{{cite journal | last=Simons | first=F. Estelle R. | title=Anaphylaxis | journal=The Journal of Allergy and Clinical Immunology | publisher=Elsevier BV | volume=125 | issue=2 | year=2010 | issn=0091-6749 | pmid=20176258 | doi=10.1016/j.jaci.2009.12.981 | pages=S161–S181| doi-access=free }}</ref>

Administration of intravenous fluid bolus and epinephrine is the treatment of choice with antihistamines used as adjuncts.<ref>{{cite journal |last1=Shaker |first1=Marcus S. |last2=Wallace |first2=Dana V. |last3=Golden |first3=David B.K. |last4=Oppenheimer |first4=John |last5=Bernstein |first5=Jonathan A. |last6=Campbell |first6=Ronna L. |last7=Dinakar |first7=Chitra |last8=Ellis |first8=Anne |last9=Greenhawt |first9=Matthew |last10=Khan |first10=David A. |last11=Lang |first11=David M. |last12=Lang |first12=Eddy S. |last13=Lieberman |first13=Jay A. |last14=Portnoy |first14=Jay |last15=Rank |first15=Matthew A. |date=April 2020 |title=Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis |journal=Journal of Allergy and Clinical Immunology |language=en |volume=145 |issue=4 |pages=1082–1123 |doi=10.1016/j.jaci.2020.01.017|pmid=32001253 |s2cid=215728019 |doi-access=free }}</ref> A period of in-hospital observation for between 2 and 24 hours is recommended for people once they have returned to normal due to concerns of biphasic anaphylaxis.<ref name=CEA11/><ref name=Rosen2010/><ref name=BI05/><ref name=UK08>{{cite web |url=http://www.resus.org.uk/pages/reaction.pdf |title=Emergency treatment of anaphylactic reactions – Guidelines for healthcare providers |date=January 2008 |access-date=2008-04-22 |publisher=Resuscitation Council (UK) |url-status=live |archive-url=https://web.archive.org/web/20081202181557/http://www.resus.org.uk/pages/reaction.pdf |archive-date=2008-12-02 }}</ref>

===Epinephrine=== thumb|upright=1.3|An old version of an EpiPen brand auto-injector Epinephrine (adrenaline) (1:1000) is the primary treatment for anaphylaxis with no absolute contraindication to its use.<ref name=EAACI2014/> It is recommended that an epinephrine solution be given intramuscularly into the mid anterolateral thigh as soon as the diagnosis is suspected. The injection may be repeated every 5 to 15 minutes if there is insufficient response.<ref name=EAACI2014/> A second dose is needed in 16–35% of episodes with more than two doses rarely required.<ref name=EAACI2014/> The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption.<ref name=EAACI2014/><ref name=Epi10>{{cite journal|last=Simons|first=KJ|author2=Simons, FE|title=Epinephrine and its use in anaphylaxis: current issues|journal=Current Opinion in Allergy and Clinical Immunology|date=August 2010|volume=10|issue=4|pages=354–61|pmid=20543673|doi=10.1097/ACI.0b013e32833bc670|s2cid=205435146}}</ref> It is recommended that after diagnosis and treatment of anaphylaxis, the patient should be kept under observation in an appropriate clinical setting until symptoms have fully resolved.<ref name="pmid32001253">{{cite journal | vauthors = Shaker MS, Wallace DV, Golden DK, Oppenheimer J, Bernstein JA, Campbell RL, Dinakar C, Ellis A, Greenhawt M, Khan DA, Lang DM, Lang ES, Lieberman JA, Portnoy J, Rank MA, Stukus DR, Wang J, Riblet N, Bobrownicki AP, Bontrager T, Dusin J, Foley J, Frederick B, Fregene E, Hellerstedt S, Hassan F, Hess K, Horner C, Huntington K, Kasireddy P, Keeler D, Kim B, Lieberman P, Lindhorst E, McEnany F, Milbank J, Murphy H, Pando O, Patel AK, Ratliff N, Rhodes R, Robertson K, Scott H, Snell A, Sullivan R, Trivedi V, Wickham A, Shaker MS, Wallace DV, Shaker MS, Wallace DV, Bernstein JA, Campbell RL, Dinakar C, Ellis A, Golden DK, Greenhawt M, Lieberman JA, Rank MA, Stukus DR, Wang J, Shaker MS, Wallace DV, Golden DK, Bernstein JA, Dinakar C, Ellis A, Greenhawt M, Horner C, Khan DA, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wang J | title = Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis | journal = J Allergy Clin Immunol | volume = 145 | issue = 4 | pages = 1082–1123 | date = April 2020 | pmid = 32001253 | doi = 10.1016/j.jaci.2020.01.017 | doi-access = free }}</ref> Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations.<ref name=World11/> People on β-blockers may be resistant to the effects of epinephrine,<ref name="CEA11" /> but this is less of an issue with "cardioselective" β1-blockers. In this situation, if epinephrine is not effective, intravenous glucagon can be administered, which has a mechanism of action independent of β-receptors.<ref name="CEA11" />

If necessary, it can also be given intravenously using a dilute epinephrine solution. Intravenous epinephrine, however, has been associated both with dysrhythmia and myocardial infarction.<ref name=EAACI2014/> Epinephrine autoinjectors used for self-administration typically come in two doses, one for adults or children who weigh more than 25 kg and one for children who weigh 10 to 25 kg.<ref>{{cite journal|last1=Halbrich|first1=M|last2=Mack|first2=DP|last3=Carr|first3=S|last4=Watson|first4=W|last5=Kim|first5=H|title=CSACI position statement: epinephrine auto-injectors and children < 15 kg.|journal=Allergy, Asthma, and Clinical Immunology|date=2015|volume=11|issue=1|page=20|pmid=26131015|pmc=4485331|doi=10.1186/s13223-015-0086-9|doi-access=free}}</ref>

Most recently, the FDA has approved an intranasal form of epinephrine under the brand name Neffy,<ref>{{Cite web |last=Commissioner |first=Office of the |date=2024-08-12 |title=FDA Approves First Nasal Spray for Treatment of Anaphylaxis |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-nasal-spray-treatment-anaphylaxis |access-date=2025-10-29 |website=FDA |language=en}}</ref> on the basis of its ability to attain levels of epinephrine in people that are believed to be protective against anaphylaxis. There are currently no clinical data on its effectiveness.

Delayed administration of epinephrine in anaphylaxis is associated with increased rates of hospitalization and mortality.<ref>{{Cite journal |last1=Sicherer |first1=Scott H. |last2=Simons |first2=F. Estelle R. |last3=SECTION ON ALLERGY AND IMMUNOLOGY |last4=Mahr |first4=Todd A. |last5=Abramson |first5=Stuart L. |last6=Dinakar |first6=Chitra |last7=Fleisher |first7=Thomas A. |last8=Irani |first8=Anne-Marie |last9=Kim |first9=Jennifer S. |last10=Matsui |first10=Elizabeth C. |date=2017-03-01 |title=Epinephrine for First-aid Management of Anaphylaxis |url=https://publications.aap.org/pediatrics/article/139/3/e20164006/53753/Epinephrine-for-First-aid-Management-of |journal=Pediatrics |language=en |volume=139 |issue=3 |article-number=e20164006 |doi=10.1542/peds.2016-4006 |pmid=28193791 |issn=0031-4005|url-access=subscription }}</ref>

===Adjuncts=== Antihistamines (both H1 and H2), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence.<ref>{{cite journal|last1=Nurmatov|first1=UB|last2=Rhatigan|first2=E|last3=Simons|first3=FE|last4=Sheikh|first4=A|title=H2-antihistamines for the treatment of anaphylaxis with and without shock: a systematic review.|journal=Annals of Allergy, Asthma & Immunology|date=February 2014|volume=112|issue=2|pages=126–31|pmid=24468252|doi=10.1016/j.anai.2013.11.010}}</ref><ref name=She2007/> A 2007 Cochrane review did not find any good-quality studies upon which to base recommendations<ref name=She2007>{{cite journal |vauthors=Sheikh A, Ten Broek V, Brown SG, Simons FE |title=H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review |journal=Allergy |volume=62 |issue=8 |pages=830–7 |date=August 2007 |pmid=17620060 |doi=10.1111/j.1398-9995.2007.01435.x |s2cid=27548046 |doi-access=free }}</ref> and they are not believed to affect airway edema or spasm.<ref name=CEA11/> 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. Their prophylactic effectiveness in these situations is uncertain.<ref name=BI05>{{cite journal |author=Lieberman P |title=Biphasic anaphylactic reactions |journal=Ann. Allergy Asthma Immunol. |volume=95 |issue=3 |pages=217–26; quiz 226, 258 |date=September 2005 |pmid=16200811 |doi= 10.1016/S1081-1206(10)61217-3}}</ref> Nebulized salbutamol may be effective for bronchospasm that does not resolve with epinephrine.<ref name=CEA11/> Methylene blue has been used in those not responsive to other measures due to its presumed effect of relaxing smooth muscle.<ref name=CEA11/>

===Preparedness=== People prone to anaphylaxis are advised to have an allergy action plan. Parents are advised to inform schools of their children's allergies and what to do in case of an anaphylactic emergency. The action plan usually includes use of epinephrine autoinjectors, the recommendation to wear a medical alert bracelet, and counseling on avoidance of triggers.<ref name=Mart08>{{cite journal|last=Martelli|first=A|author2=Ghiglioni, D|author3=Sarratud, T|author4=Calcinai, E|author5=Veehof, S|author6=Terracciano, L|author7=Fiocchi, A|title=Anaphylaxis in the emergency department: a paediatric perspective|journal=Current Opinion in Allergy and Clinical Immunology|date=August 2008|volume=8|issue=4|pages=321–9|pmid=18596589|doi=10.1097/ACI.0b013e328307a067|s2cid=205434577}}</ref> 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.<ref name=Review09/>

==Prognosis== In those in whom the cause is known and prompt treatment is available, the prognosis is good.<ref name="Harris2007">{{cite book|vauthors = Harris JP, Weisman MH|title=Head and Neck Manifestations of Systemic Disease|url=https://books.google.com/books?id=31yUl-V90XoC&pg=PA325|date=2007-07-26|publisher=CRC Press|isbn=978-1-4200-1756-4|pages=325–}}</ref> Even if the cause is unknown, if appropriate preventive medication is available, the prognosis is generally good.<ref name=Rosen2010/> Usually, death occurs due to either respiratory failure (typically involving asphyxia) or cardiovascular complications, such as cardiovascular shock,<ref name=Khan11/><ref name=CEA11/> with 0.7–20% of cases causing death.<ref name=Rosen2010>{{cite book |title=Rosen's emergency medicine: concepts and clinical practice 7th edition |last=Marx |first=John |year=2010 |publisher=Mosby/Elsevier |location=Philadelphia, PA |isbn=978-0-323-05472-0 |pages=1511–1528 }}</ref><ref name=Cardio08>{{cite journal|last=Triggiani|first=M|author2=Patella, V|author3=Staiano, RI|author4=Granata, F|author5=Marone, G|title=Allergy and the cardiovascular system|journal=Clinical and Experimental Immunology|date=September 2008|volume=153 Suppl 1|pages=7–11|pmid=18721322|pmc=2515352 |doi=10.1111/j.1365-2249.2008.03714.x|issue=s1}}</ref> There have been cases of death occurring within minutes.<ref name=World11/> Outcomes in those with exercise-induced anaphylaxis are typically good, with fewer and less severe episodes as people get older.<ref name="editor 2010 223"/>

==Epidemiology== The number of people who get anaphylaxis is 4–100 per 100,000 persons per year,<ref name=CEA11/><ref name=Tej2015>{{cite journal|last1=Tejedor-Alonso M|first1=A|last2=Moro-Moro|first2=M|last3=Múgica-García|first3=MV|title=Epidemiology of Anaphylaxis: Contributions From the Last 10 Years.|journal=Journal of Investigational Allergology & Clinical Immunology|date=2015|volume=25|issue=3|pages=163–75; quiz follow 174–5|pmid=26182682}}</ref> with a lifetime risk of 0.05–2%.<ref>{{cite book|author1=Leslie C. Grammer|title=Patterson's Allergic Diseases|date=2012|publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-4863-3|edition=7|url=https://books.google.com/books?id=MWdT7W4_N8sC&pg=PA199|url-status=live|archive-url=https://web.archive.org/web/20150620140057/https://books.google.ca/books?id=MWdT7W4_N8sC&pg=PA199|archive-date=2015-06-20}}</ref> About 30% of affected people get more than one attack.<ref name=Tej2015/> Exercise-induced anaphylaxis affects about 1 in 2000 young people.<ref name=Pravetton2016rev/>

Rates appear to be increasing: the numbers in the 1980s were approximately 20 per 100,000 per year, while in the 1990s, it was 50 per 100,000 per year.<ref name=Review09/> The increase appears to be primarily for food-induced anaphylaxis.<ref>{{cite journal|last=Koplin|first=JJ|author2=Martin, PE |author3=Allen, KJ|title=An update on epidemiology of anaphylaxis in children and adults|journal=Current Opinion in Allergy and Clinical Immunology|date=October 2011|volume=11|issue=5|pages=492–6|pmid=21760501|doi=10.1097/ACI.0b013e32834a41a1|s2cid=13164564}}</ref> The risk is greatest in young people and females.<ref name=EAACI2014/><ref name=CEA11/>

Anaphylaxis leads to as many as 500–1,000 deaths per year (2.7 per million) in the United States, 20 deaths per year in the United Kingdom (0.33 per million), and 15 deaths per year in Australia (0.64 per million).<ref name=CEA11/> Another estimate from the United States puts the death rate at 0.7 per million.<ref>{{cite journal|last1=Fromer|first1=L|title=Prevention of Anaphylaxis: The Role of the Epinephrine Auto-Injector.|journal=The American Journal of Medicine|date=December 2016|volume=129|issue=12|pages=1244–1250|doi=10.1016/j.amjmed.2016.07.018|pmid=27555092|doi-access=free}}</ref> Mortality rates have decreased between the 1970s and 2000s.<ref>{{cite journal|last=Demain|first=JG|author2=Minaei, AA |author3=Tracy, JM|title=Anaphylaxis and insect allergy|journal=Current Opinion in Allergy and Clinical Immunology|date=August 2010|volume=10|issue=4|pages=318–22|pmid=20543675|doi=10.1097/ACI.0b013e32833a6c72|s2cid=12112811}}</ref> In Australia, death from food-induced anaphylaxis occur primarily in women while deaths due to insect bites primarily occur in males.<ref name=CEA11/> Death from anaphylaxis is most commonly triggered by medications.<ref name=CEA11/>

==History== The conditions of anaphylaxis have been known since ancient times.<ref name="His10" /> French physician François Magendie had described how rabbits were killed by repeated injections of egg albumin in 1839.<ref>{{cite journal |last1=Shampo |first1=Marc A. |last2=Kyle |first2=Robert A. |date=1987 |title=François Magendie: Early French Physiologist |url=https://linkinghub.elsevier.com/retrieve/pii/S0025619612654469 |journal=Mayo Clinic Proceedings |language=en |volume=62 |issue=5 |page=412 |doi=10.1016/S0025-6196(12)65446-9|pmid=3553755 |url-access=subscription }}</ref> However, the phenomenon was discovered by two French physiologists Charles Richet and Paul Portier.<ref name=":1" /> In 1901, Albert I, Prince of Monaco requested Richet and Portier join him on a scientific expedition around the French coast of the Atlantic Ocean,<ref>{{cite journal |last1=Dworetzky |first1=Murray |last2=Cohen |first2=Sheldon |last3=Cohen |first3=Sheldon G. |last4=Zelaya-Quesada |first4=Myrna |date=2002 |title=Portier, Richet, and the discovery of anaphylaxis: A centennial |journal=Journal of Allergy and Clinical Immunology |language=en |volume=110 |issue=2 |pages=331–336 |doi=10.1016/S0091-6749(02)70118-8|pmid=12170279 |doi-access=free }}</ref> specifically to study on the toxin produced by cnidarians (like jellyfish and sea anemones).<ref name=":1">{{cite journal |last=Richet |first=Gabriel |date=2003 |title=The discovery of anaphylaxis, a brief but triumphant encounter of two physiologists (1902) |journal=Histoire des Sciences Médicales |volume=37 |issue=4 |pages=463–469 |pmid=14989211}}</ref> Richet and Portier boarded Albert's ship ''Princesse Alice II'' for ocean exploration to make collections of the marine animals.<ref name=":0">{{cite journal |last1=Androutsos |first1=G. |last2=Karamanou |first2=M. |last3=Stamboulis |first3=E. |last4=Liappas |first4=I. |last5=Lykouras |first5=E. |last6=Papadimitriou |first6=G. N. |date=2011 |title=The Nobel Prize laureate – father of anaphylaxis Charles-Robert Richet (1850–1935) and his anticancerous serum |url=https://jbuon.com/archive/16-4-783.pdf |journal=Journal of BUON |volume=16 |issue=4 |pages=783–786 |pmid=22331744}}</ref>

Richet and Portier extracted a toxin called hypnotoxin from their collection of jellyfish (but the real source was later identified as Portuguese man o' war)<ref>{{cite journal |last=Suput |first=Dusan |title=Interactions of Cnidarian Toxins with the Immune System |url=https://www.eurekaselect.com/article/33767 |journal= Inflammation & Allergy - Drug Targets|year=2011 |language=en |volume=10 |issue=5 |pages=429–437 |doi=10.2174/187152811797200678|pmid=21824078 |url-access=subscription }}</ref> and sea anemone (''Actinia sulcata'').<ref name=":2">{{cite journal |last1=Boden |first1=Stephen R. |last2=Wesley Burks |first2=A. |date=2011 |title=Anaphylaxis: a history with emphasis on food allergy: Anaphylaxis: a history with emphasis on food allergy |journal=Immunological Reviews |language=en |volume=242 |issue=1 |pages=247–257 |doi=10.1111/j.1600-065X.2011.01028.x |pmc=3122150 |pmid=21682750}}</ref> In their first experiment on the ship, they injected a dog with the toxin in an attempt to immunise the dog, which instead developed a severe reaction (hypersensitivity). In 1902, they repeated the injections in their laboratory and found that dogs normally tolerated the toxin at the first injection, but on re-exposure, three weeks later with the same dose, they always developed fatal shock. They also found that the effect was not related to the doses of toxin used, as even small amounts in secondary injections were lethal.<ref name=":2" /> Thus, instead of inducing tolerance (prophylaxis), which they expected, they discovered effects of the toxin as deadly.<ref>{{cite journal |last=May |first=Charles D. |date=1985 |title=The ancestry of allergy: Being an account of the original experimental induction of hypersensitivity recognizing the contribution of Paul Portier |journal=Journal of Allergy and Clinical Immunology |language=en |volume=75 |issue=4 |pages=485–495 |doi=10.1016/S0091-6749(85)80022-1|pmid=3884689 |doi-access=free }}</ref>

In 1902, Richet introduced the term ''aphylaxis'' to describe the condition of lack of protection. He later changed the term to ''anaphylaxis'' on the grounds of euphony.<ref name="His11">{{cite journal |last=Boden |first=SR |author2=Wesley Burks, A |title=Anaphylaxis: a history with emphasis on food allergy |journal=Immunological Reviews |date=July 2011 |volume=242 |issue=1 |pages=247–57 |pmid=21682750 |doi=10.1111/j.1600-065X.2011.01028.x |pmc=3122150}}, citing May CD, "The ancestry of allergy: being an account of the original experimental induction of hypersensitivity recognizing the contribution of Paul Portier", ''J Allergy Clin Immunol.'' 1985 Apr; 75(4):485–495.</ref> The term is from the Greek {{lang|grc-Grek|ἀνά-|italic=no}}, {{lang|grc-latn|ana-}}, meaning "against", and {{lang|grc-Grek|φύλαξις|italic=no}}, {{lang|grc-latn|phylaxis}}, meaning "protection".<ref name="Dict">{{cite web |url=http://www.merriam-webster.com/dictionary/anaphylaxis |title=anaphylaxis |access-date=2009-11-21|publisher=Merriam-Webster |url-status=live |archive-url=https://web.archive.org/web/20100410192354/http://www.merriam-webster.com/dictionary/anaphylaxis |archive-date=2010-04-10}}</ref> On 15 February 1902, Richet and Portier jointly presented their findings before the ''Societé de Biologie'' in Paris.<ref>{{cite web |title=De l'action anaphylactique de certains venins {{!}} Association des amis de la Bibliothèque nationale de France |url=http://sciences.amisbnf.org/fr/livre/de-laction-anaphylactique-de-certains-venins |access-date=2022-06-24 |website=sciences.amisbnf.org |archive-date=2022-12-07 |archive-url=https://web.archive.org/web/20221207042907/http://sciences.amisbnf.org/fr/livre/de-laction-anaphylactique-de-certains-venins |url-status=dead }}</ref><ref name="Ring 2014 54–61">{{Citation |last1=Ring |first1=Johannes |title=Anaphylaxis |date=2014 |url=https://www.karger.com/Article/FullText/358503 |journal=Chemical Immunology and Allergy |volume=100 |pages=54–61 |editor-last=Bergmann |editor-first=K.-C. |publisher=S. Karger AG |language=en |doi=10.1159/000358503 |isbn=978-3-318-02194-3 |access-date=2022-06-24 |last2=Grosber |first2=Martine |last3=Brockow |first3=Knut |last4=Bergmann |first4=Karl-Christian |pmid=24925384 |editor2-last=Ring |editor2-first=J.|doi-access=free }}</ref> The moment is regarded as the birth of allergy (the term invented by Clemens von Pirquet in 1906) study (allergology).<ref name="Ring 2014 54–61"/> Richet continued to study the phenomenon and was eventually awarded the Nobel Prize in Physiology or Medicine for his work on anaphylaxis in 1913.<ref name=":0" /><ref>{{cite journal |last1=Richet |first1=Gabriel |last2=Estingoy |first2=Pierrette |date=2003 |title=The life and times of Charles Richet |journal=Histoire des Sciences Médicales |volume=37 |issue=4 |pages=501–513 |issn=0440-8888 |pmid=15025138}}</ref>

==Research== There are ongoing efforts to develop sublingual epinephrine to treat anaphylaxis. Trials of sublingual epinephrine, currently called AQST-108 (dipivefrin) and sponsored by Aquestive Therapeutics, are in phase 1 trials as of December 2021.<ref name=CEA11/><ref>{{cite web|date=2021-03-25|title=Aquestive Therapeutics Successfully Demonstrates Repeatable and Predictable Oral Sublingual Film Administration of Epinephrine|url=https://aquestive.com/aquestive-therapeutics-successfully-demonstrates-repeatable-and-predictable-oral-sublingual-film-administration-of-epinephrine/|access-date=2021-12-01|website=Aquestive|language=en-US}}</ref> Subcutaneous injection of the anti-IgE antibody omalizumab is being studied as a method of preventing recurrence, but it is not yet recommended.{{update after|2021|3|17}}<ref name=World11/><ref>{{cite journal|last=Vichyanond|first=P|title=Omalizumab in allergic diseases, a recent review|journal=Asian Pacific Journal of Allergy and Immunology |date=September 2011|volume=29|issue=3|pages=209–19|pmid=22053590}}</ref> Omalizumab-associated anaphylaxis has been observed in less than 0.1% of patients treated for moderate to severe persistent allergic asthma using subcutaneous omalizumab injections.<ref>{{Cite journal |last1=Kim |first1=Harold L. |last2=Leigh |first2=Richard |last3=Becker |first3=Allan |date=2010-12-03 |title=Omalizumab: Practical considerations regarding the risk of anaphylaxis |journal=Allergy, Asthma, and Clinical Immunology|volume=6 |issue=1 |page=32 |doi=10.1186/1710-1492-6-32 |doi-access=free |issn=1710-1492 |pmc=3006370 |pmid=21129189}}</ref>

==References== {{Reflist}}

==External links== {{offline|med}} {{wiktionary}} {{Commons category|Anaphylaxis}} * {{NICE|134|Anaphylaxis: assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode|2011}} and [http://pathways.nice.org.uk/pathways/anaphylaxis Anaphylaxis pathway] {{Webarchive|url=https://web.archive.org/web/20171011193830/http://pathways.nice.org.uk/pathways/anaphylaxis |date=2017-10-11 }} * {{cite web | url = https://medlineplus.gov/anaphylaxis.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Anaphylaxis }}

{{Medical condition classification and resources | DiseasesDB = 29153 | ICD11 ={{ICD11|4A84}} | ICD10 = {{ICD10|T|78|2}}, {{ICD10|T|78|0}}, {{ICD10|T|88|6}}, {{ICD10|T|80|5}} | ICD9 = {{ICD9|995.0}} | MedlinePlus = 000844 | eMedicineSubj = med | eMedicineTopic = 128 | MeshID = D000707 }}

{{Consequences of external causes}} {{shock types}} {{Hypersensitivity and autoimmune diseases}} {{Authority control}}

Category:Allergology Category:Complications of surgical and medical care Category:Medical emergencies Category:Respiratory diseases Category:Type I hypersensitivity Category:Urticaria and angioedema Category:Wikipedia medicine articles ready to translate (full) Category:Wikipedia emergency medicine articles ready to translate