# Anaphylaxis
**Anaphylaxis** is a serious, systemic hypersensitivity reaction that is usually rapid in onset and may cause death, characterized by potentially life-threatening compromise of respiration, circulation, or both[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext). It is a medical emergency: the NHS advises calling emergency services immediately when a reaction is suspected[2](https://www.nhs.uk/conditions/anaphylaxis/). The reaction typically involves the whole body and develops within minutes of exposure to a trigger such as food, a drug, or insect venom[3](https://medlineplus.gov/ency/article/000844.htm). It can occur without typical skin features and without circulatory shock, and it is driven primarily by mast-cell activation, usually through IgE-mediated pathways[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext).
| Key fact | Detail |
|---|---|
| Definition | Serious, systemic hypersensitivity reaction, usually rapid in onset, potentially fatal; may occur without skin features or shock[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext) |
| First-line treatment | Intramuscular epinephrine 0.01 mg/kg (max 0.3 mg children, 0.5 mg adults) into the anterolateral thigh, repeated every 5–15 minutes as needed[5](https://link.springer.com/article/10.1186/s13223-024-00926-3) |
| Incidence | Approximately 46 cases per 100,000 people per year (95% CI 21–103), rising about 7.4% annually[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext) |
| Lifetime prevalence | Estimated 0.3%–5.1%[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext) |
| Mortality | Below 1 death per million population per year; case fatality under 0.5% among hospitalized or emergency department patients[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext) • [5](https://link.springer.com/article/10.1186/s13223-024-00926-3) |
| Biphasic reactions | Median 6.5% of adult patients (range 0.4%–20%) relapse after apparent recovery, typically 10.5 hours later[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext) |
| Leading triggers | Food, drugs, and insect venom; foods dominate in children, beta-lactam antibiotics and NSAIDs in adults[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext) |
## Signs and symptoms
Anaphylaxis often produces a systemic response involving multiple organ systems, such as the skin, the upper and lower airways, and the cardiovascular system[6](https://bestpractice.bmj.com/topics/en-us/501). Skin findings include urticaria and angioedema (swelling deep under the skin, often lips and eyes) from vasodilation with plasma leakage; airway findings include bronchoconstriction; gastrointestinal involvement includes vomiting and diarrhea from diffuse smooth-muscle contraction[7](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis).
Symptoms typically develop within minutes of exposure but may appear as late as 2 hours afterward, and up to 4 hours after red-meat ingestion in alpha-gal syndrome[5](https://link.springer.com/article/10.1186/s13223-024-00926-3). Because severe anaphylaxis is defined by life-threatening respiratory or circulatory compromise, a reaction limited to hives alone does not meet the definition[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext).
## Causes and triggers
The three most important triggers are food, drugs, and insect venom[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext). In children and adolescents, food was the trigger in 66% of cases and insect venom in 19%, with prevalence higher until the second decade of life; trigger frequencies differ across geographic areas[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC11250555/). Cow's milk, peanuts, and tree nuts are the leading food triggers in children, while beta-lactam antibiotics and NSAIDs are the main drug triggers in adults; [Hymenoptera](https://www.edgepedia.org/hymenoptera) (stinging) insects are leading causes in some countries[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext).
Cofactors can amplify the severity of a reaction. These include exercise, infections, psychological burden, sleep deprivation, alcohol intake, and medications such as NSAIDs, beta-blockers, and angiotensin-converting enzyme inhibitors[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext).
## Mechanism
Most episodes are triggered through an immunologic mechanism involving immunoglobulin E (IgE): allergen binds IgE attached to the FcεRI receptor on mast cells and basophils, causing activation and degranulation and the release of inflammatory mediators including histamine, platelet-activating factor, leukotrienes, tryptase (enzyme released by mast cells, blood test marker), and prostaglandins[5](https://link.springer.com/article/10.1186/s13223-024-00926-3) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/). These mediators act within minutes: histamine and leukotrienes cause diffuse smooth-muscle contraction (bronchoconstriction, vomiting, diarrhea) and vasodilation with plasma leakage (urticaria, angioedema), which can contribute to a fall in blood pressure and, in severe cases, shock[7](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis).
Not all anaphylaxis is IgE-mediated. Non-IgE reactions, previously called anaphylactoid, are clinically indistinguishable, do not require prior sensitization, and occur through direct mast-cell stimulation, sometimes via the MRGPRX2 receptor, or through immune complexes that activate complement[7](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis). The GA2LEN 2024 consensus describes anaphylaxis classically as a type 1 hypersensitivity reaction driven by IgE-mediated mediator release, while noting that non-IgE-mediated anaphylaxis is well described, particularly to some drugs[10](https://www.jacionline.org/article/S0091-6749(25)00072-7/fulltext).
## Diagnosis
Diagnosis is clinical, based on rapid multisystem involvement; first measures are removal of the allergen and appropriate patient positioning[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext). The differential diagnosis includes acute asthma, localized angioedema, syncope, and anxiety or panic attacks[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/). Treatment with epinephrine should be provided even when the diagnosis is uncertain, since there is no contraindication to its use[5](https://link.springer.com/article/10.1186/s13223-024-00926-3).
The formal definitions differ across frameworks. WAO tabulates definitions from NIAID 2006, EAACI 2013, AAAAI/ACAAI 2010, ASCIA 2016, WAO 2011, and WHO ICD-11 2019, which vary in wording and emphasis[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/). The WAO definition, shared in substance by the 2023 US practice parameter, is a serious systemic hypersensitivity reaction, usually rapid in onset, that may cause death, with life-threatening airway, breathing, or circulatory compromise possibly occurring without typical skin features[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/) • [1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext).
Laboratory testing has a limited acute role. An acute serum total tryptase level at least 20% plus 2 ng/mL above the patient's own baseline can support the diagnosis, since many cases show no elevation above the laboratory normal (for example, >11.4 ng/mL)[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext).
## By the numbers
Reported global incidence ranges from 50 to 112 episodes per 100,000 person-years, and a recent meta-analysis estimates approximately 46 cases per 100,000 people per year (95% CI 21–103), increasing annually by about 7.4% (95% CI 7.3–7.6)[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext). In children, reported incidence ranges widely, from 1 to 761 per 100,000 person-years[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext). Lifetime prevalence is estimated at 0.3%–5.1%[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext). Up to 1–2% of patients in the emergency unit of a maximal-care hospital present because of anaphylactic reactions[11](https://link.springer.com/article/10.1007/s40629-020-00158-y).
Mortality is low but the denominator matters. Deaths are estimated below 1 per million population per year, with trigger-specific estimates of 0.05–0.51 per million per year for drugs, 0.03–0.32 for food, and 0.09–0.13 for venom[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/). A German guideline estimates one to three fatalities per year per million population[11](https://link.springer.com/article/10.1007/s40629-020-00158-y). Among patients hospitalized or presenting to an emergency department, the case fatality rate is under 0.5%[5](https://link.springer.com/article/10.1186/s13223-024-00926-3). Incidence has risen in recent decades, particularly food-induced anaphylaxis in children and [drug-induced anaphylaxis](https://www.edgepedia.org/drug-induced-anaphylaxis) in adults, while mortality has remained unchanged[11](https://link.springer.com/article/10.1007/s40629-020-00158-y).
Biphasic reactions, in which symptoms recur after apparent recovery without new antigen exposure, occur in 0.4% to 15% of reactions, after an asymptomatic period of at least 1 hour and up to 48 hours[5](https://link.springer.com/article/10.1186/s13223-024-00926-3). In a meta-analysis of 2890 adult patients, the median biphasic rate was 6.5% (range 0.4%–20%), with a median interval of 10.5 hours (range 1.75–17 hours) between resolution and recurrence[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext). A 1-hour symptom-free observation period after resolution carried a 95% negative predictive value (95% CI, 90.9%–97.3%) for biphasic anaphylaxis[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext). Beyond biphasic relapse, recurrence of new anaphylactic reactions over longer follow-up occurs in 26.5%–54.0% of patients over 1.5 to 25 years[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/).
## Management
Immediate intramuscular epinephrine injected into the lateral thigh is the first-line treatment, with repeat dosing as needed[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext). The recommended dose is 0.01 mg/kg (maximum 0.5 mg) every 5–15 minutes as necessary[5](https://link.springer.com/article/10.1186/s13223-024-00926-3); standard practice caps the dose at 0.3 mg for children and teenagers and 0.5 mg for adults[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext). In solution terms, adults receive 0.3 to 0.5 mL of a 1:1000 (0.1%) solution, or 0.01 mL/kg in children[7](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis). The anterolateral thigh is preferred because it allows more rapid absorption and higher plasma epinephrine levels than subcutaneous injection or intramuscular injection in the upper arm[5](https://link.springer.com/article/10.1186/s13223-024-00926-3). FDA-approved auto-injectors deliver 0.3 mg for patients ≥30 kg, 0.15 mg for 15–30 kg, and 0.1 mg (Auvi-Q) for 7.5–15 kg, with several organizations supporting a switch to the 0.3 mg device at 25 kg[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext).
Among the additional treatments that may be given are H-1 and H-2 receptor blockers, bronchodilators taken by inhalation, extra oxygen, epinephrine delivered by inhalation, fluids given intravenously, and corticosteroids administered systemically; none of these should ever postpone or take the place of epinephrine injected intramuscularly.[10](https://www.jacionline.org/article/S0091-6749(25)00072-7/fulltext) Recent evidence shows corticosteroids have no benefit in preventing severe or refractory reactions or reducing biphasic-reaction risk[5](https://link.springer.com/article/10.1186/s13223-024-00926-3). Glucagon may be considered for refractory anaphylaxis in patients taking beta-blockers, while pregnancy alone is not an indication, as epinephrine remains first-line treatment during pregnancy[5](https://link.springer.com/article/10.1186/s13223-024-00926-3) • [12](https://cpr.heart.org/en/resuscitation-science/cpr-and-ecc-guidelines/adult-and-pediatric-special-circumstances-of-resuscitation). Intravenous epinephrine is reserved for settings with cardiac monitoring and clinical expertise, and repeat epinephrine is indicated when patients do not respond to initial dosing[10](https://www.jacionline.org/article/S0091-6749(25)00072-7/fulltext). After acute treatment, patients should be observed for an individualized period[5](https://link.springer.com/article/10.1186/s13223-024-00926-3).
There are no validated risk-stratification algorithms in the research literature to guide epinephrine auto-injector prescription; expert opinion identifies higher-risk groups including prior systemic reactions to the food allergen, venom allergy with honey bee as the trigger, elevated baseline tryptase, older age, and cardiovascular disease[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext).
## Prevention and what has changed since 2023
Two treatment changes are notable. Omalizumab can be used to prevent type 1 allergic reactions, including anaphylaxis, from accidental food exposure in patients aged 1 year or older with IgE-mediated food allergy[7](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis). An intranasal epinephrine formulation is indicated for emergency treatment of type I hypersensitivity reactions including anaphylaxis in patients aged 4 years or older weighing at least 15 kg: one 2 mg spray for patients ≥30 kg and one 1 mg spray for those 15–30 kg, with repeat doses in the same nostril starting 5 minutes after the first[7](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis). Intranasal epinephrine provides blood levels and cardiovascular effects comparable to traditional intramuscular injections, but no head-to-head studies comparing injectable and non-injectable epinephrine have been published, and regulatory approval was based on pharmacokinetic and pharmacodynamic data[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext). The WAO 2026 White Book update and the 2024 GA2LEN consensus reflect these developments, and neither adjunct replaces epinephrine as first-line treatment[4](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext) • [10](https://www.jacionline.org/article/S0091-6749(25)00072-7/fulltext).
## Prognosis and risk of fatal episodes
Overall case fatality is extremely low, under 0.5% among hospitalized or emergency department patients[5](https://link.springer.com/article/10.1186/s13223-024-00926-3). Refractory anaphylaxis, which persists despite appropriate treatment, accounts for less than 0.5% of severe cases per the European Anaphylaxis Registry but sharply increases fatality risk: 26.2% versus 0.35% in a 2019 European registry (P < .0001)[1](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext).
Several factors predict severe or fatal reactions. Data from the European anaphylaxis registry confirm that beta-adrenoceptor antagonists are associated with increased risk of severe anaphylaxis (odds ratio 1.86); elicitor-independent risk factors include advanced age, severe cardiovascular disease, inadequately treated bronchial asthma, NSAID use, and mastocytosis (rare excess of mast cells, causing severe allergic reactions)[11](https://link.springer.com/article/10.1007/s40629-020-00158-y). Uncontrolled, severe asthma is a recognized risk factor for fatal anaphylaxis, and a personal history of atopy does not increase the risk of anaphylaxis but can increase the risk of death when anaphylaxis occurs[7](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis). Recurrent episodes may suggest underlying systemic mastocytosis or mast cell activation syndrome[5](https://link.springer.com/article/10.1186/s13223-024-00926-3).
## References
1. [Anaphylaxis: A 2023 practice parameter update, Annals of Allergy, Asthma & Immunology](https://www.annallergy.org/article/S1081-1206(23)01304-2/fulltext)
2. [Anaphylaxis, NHS](https://www.nhs.uk/conditions/anaphylaxis/)
3. [Anaphylaxis, MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000844.htm)
4. [Overview of allergic disease: Anaphylaxis – WAO White Book on Allergy 2026, World Allergy Organization Journal](https://www.worldallergyorganizationjournal.org/article/S1939-4551(26)00171-7/fulltext)
5. [Anaphylaxis, Allergy, Asthma & Clinical Immunology (2024 review)](https://link.springer.com/article/10.1186/s13223-024-00926-3)
6. [Anaphylaxis, BMJ Best Practice](https://bestpractice.bmj.com/topics/en-us/501)
7. [Anaphylaxis, Merck Manual Professional Edition](https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/anaphylaxis)
8. [Diagnosis and management of anaphylaxis (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11250555/)
9. [World Allergy Organization anaphylaxis guidance 2020](https://pmc.ncbi.nlm.nih.gov/articles/PMC7607509/)
10. [Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report – a GA2LEN project, Journal of Allergy and Clinical Immunology](https://www.jacionline.org/article/S0091-6749(25)00072-7/fulltext)
11. [Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update, Allergo Journal International](https://link.springer.com/article/10.1007/s40629-020-00158-y)
12. [Adult and Pediatric Special Circumstances of Resuscitation, cpr.heart.org](https://cpr.heart.org/en/resuscitation-science/cpr-and-ecc-guidelines/adult-and-pediatric-special-circumstances-of-resuscitation)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Immune-system dysfunction and generalized hypersensitivity*
*Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; Sep 30, 2026; Oct 25, 2026 · Edited: Sep 30, 2026; Oct 25, 2026 · Last review: Oct 25, 2026*
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