Last updated: September 15, 2023

Summarytoggle arrow icon

Anaphylaxis is an acute, potentially life-threatening, type 1 hypersensitivity reaction, involving the sudden IgE-mediated release of histamine mediators from mast cells and basophils in response to a trigger (e.g., food, insect stings, medication). Anaphylactoid reactions (a subtype of pseudoallergy) are IgE-independent reactions that result from direct mast-cell activation (e.g., in response to opioids); the clinical presentation and management are the same as for anaphylaxis. Typical signs and symptoms of both reactions include the acute onset of urticarial rash, angioedema, stridor, dyspnea, bronchospasm, circulatory failure (distributive shock), vomiting, and diarrhea. The diagnosis is clinical and is based on combinations of typical symptoms, plus the presence of a known or suspected trigger. Rapid recognition and treatment are key to prevent death from airway loss, respiratory failure, or cardiovascular collapse. Management consists of initial resuscitation measures that focus on administering IM epinephrine, removing triggers, securing the airway, and giving IV fluid boluses, which take precedence over adjunctive treatment like steroids and antihistamines.

Definitiontoggle arrow icon

Etiologytoggle arrow icon

  • Trigger is idiopathic in 20% of patients [1]
  • Most common triggers leading to fatal anaphylaxis [1][2][3]

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Onset of symptoms [2][4]

In general, the onset of symptoms is acute (within minutes to hours of exposure to a likely antigen).

Antigen-dependent onset of anaphylaxis [2][4]

Median time to circulatory arrest

Food 30 min
Insect 15 min
Medication 5 min

Affected organ systems [2][4]

Beware of atypical manifestations without skin/mucosal symptoms (10% of patients) to avoid misdiagnosis and treatment delay. [1]

Diagnostic criteria for anaphylaxis [1][4][6]

If any of the following criteria are fulfilled, anaphylaxis is likely. The onset of symptoms must be acute (minutes to hours).

If anaphylaxis diagnostic criteria are met, empiric treatment should be given without delay.

Managementtoggle arrow icon

The most important measures in anaphylaxis are to remove the inciting allergen and administer epinephrine as soon as possible. Delay can lead to airway compromise, respiratory failure, refractory shock, and death.

Epinephrine injections for anaphylaxis should always be given intramuscularly in a concentration of 1:1,000 (as opposed to the 1:10,000 solution used in cardiac arrest). Injecting the 1:1,000 solution into a vein can lead to cardiac arrhythmia/arrest.

Diagnosticstoggle arrow icon

Anaphylaxis is a clinical diagnosis (see “Diagnostic criteria for anaphylaxis”).

Laboratory studies [2][8][9]

Imaging [2][9]

Airway management and ventilationtoggle arrow icon

See also “Airway management” and “Mechanical ventilation” for more details.

Obtain early anesthesia or ENT consultation in patients with a rapid decline or anticipated airway compromise.

Subsequent managementtoggle arrow icon

Refractory anaphylaxis [2][4][7]

Adjunctive therapy [2][4][7]

Antihistamines and steroids should be administered in anaphylaxis only after the initial resuscitation measures (IM epinephrine, fluids and/or vasopressors) have been given.

A lack of response to epinephrine, antihistamines, and steroids should raise suspicion of differential diagnoses such as bradykinin-mediated angioedema, which requires its own specific treatment (see “Treatment of angioedema”).

Monitoring and disposition [2][4][7]

Acute management checklisttoggle arrow icon

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Preventiontoggle arrow icon

Pretreatment for in-hospital triggers [15][16][17]

Referencestoggle arrow icon

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  2. Walls R, Hockberger R, Gausche-Hill M. Rosen's Emergency Medicine. Elsevier Health Sciences ; 2018
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  5. Świeczkowski D, Zdanowski S, Merks P, Szarpak Ł, Vaillancourt R, Jaguszewski MJ. The plague of unexpected drug recalls and the pandemic of falsified medications in cardiovascular medicine as a threat to patient safety and global public health: A brief review.. Cardiology journal. 2022; 29 (1): p.133-139.doi: 10.5603/CJ.a2020.0168 . | Open in Read by QxMD
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  7. Long B, Koyfman A, Gottlieb M. Evaluation and Management of Angioedema in the Emergency Department. Western Journal of Emergency Medicine. 2019; 20 (4): p.587-600.doi: 10.5811/westjem.2019.5.42650 . | Open in Read by QxMD
  8. Moellman JJ, Bernstein JA, Lindsell C, et al. A Consensus Parameter for the Evaluation and Management of Angioedema in the Emergency Department. Academic Emergency Medicine. 2014; 21 (4): p.469-484.doi: 10.1111/acem.12341 . | Open in Read by QxMD
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  13. International Collaborative Study of Severe Anaphylaxis.. Risk of anaphylaxis in a hospital population in relation to the use of various drugs: an international study.. Pharmacoepidemiol Drug Saf. 2003; 12 (3): p.195-202.doi: 10.1002/pds.822 . | Open in Read by QxMD
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  21. Kemp SF. Pathophysiology of anaphylaxis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: February 23, 2017. Accessed: March 9, 2017.
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