What is Anaphylaxis?
Anaphylaxis is an acute, life-threatening systemic allergic reaction that is rapid in onset and can cause death within minutes to hours if untreated. 1
Core Definition
- Anaphylaxis represents a severe, generalized or systemic hypersensitivity reaction resulting from the sudden systemic release of mediators from mast cells and basophils. 1
- The reaction must be systemic or generalized—minor, localized, or non-systemic reactions are explicitly excluded from the definition. 1
- This is not a homogeneous process; the pathways, mediators, time course, and response to treatment depend on the trigger agent, route of administration, the patient's hypersensitivity mechanism, and underlying health conditions. 1
Two Mechanistic Categories
Anaphylaxis divides into two distinct types based on underlying mechanism:
- Allergic anaphylaxis: Mediated by immunological mechanisms, including IgE antibodies, IgG antibodies, or complement activation by immune complexes. 2, 1
- Non-allergic anaphylaxis (also called anaphylactoid reaction): Produces identical clinical features but is not mediated by immunological mechanisms. 2, 1
Both types present identically and require the same emergency treatment—the mechanistic distinction does not alter acute management. 2
Clinical Presentation
The more rapidly anaphylaxis develops, the more likely the reaction is to be severe and potentially life-threatening. 1
Most Common Manifestations:
- Cutaneous symptoms: Urticaria and angioedema are the most common initial signs, though they may be delayed or completely absent in 10-20% of rapidly progressive cases. 1
- Respiratory compromise: Includes upper airway occlusion from angioedema, bronchospasm with mucus plugging, or both simultaneously—particularly with reactions to foods, latex, beta-lactam antibiotics, or aspirin. 1
- Cardiovascular collapse: Results from intravascular volume redistribution, decreased cardiac output due to reduced coronary perfusion pressure and impaired venous return, and potential coronary artery spasm. 1
Most Dangerous Manifestations:
- Respiratory compromise and cardiovascular collapse are the most concerning because they are the most frequent causes of anaphylactic fatalities. 1
- Myocardial ischemia and ECG changes can occur within minutes of severe anaphylactic shock, with features of acute left or right ventricular failure developing rapidly. 1
- Asphyxia may result from upper airway occlusion or bronchospasm, and both can occur simultaneously. 1
Additional Signs and Symptoms:
The FDA drug label for epinephrine lists the full spectrum of anaphylaxis symptoms: flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with hypotension, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, airway swelling, laryngospasm, bronchospasm, pruritus, urticaria or angioedema, swelling of the eyelids, lips, and tongue. 3
Common Triggers
- In adults: Medications and stinging insects are the leading triggers. 2
- In children and adolescents: Foods and stinging insects are most frequently implicated. 2
- Food allergy impacts 8% to 11% of children and adults in the United States. 2
- Systemic reactions to Hymenoptera venom occur in 0.5% to 3.3% of the US population, with most fatalities occurring in patients who have no prior history of systemic allergic reaction. 2
Time Course and Resolution
- Anaphylaxis usually resolves in 2-8 hours, but secondary pathology from the reaction or its treatment may prolong this duration. 1
- Resolution is typically complete except when cerebral hypoxia at the peak of the reaction has caused significant brain damage, or when disordered clotting leads to bleeding. 1
- Biphasic anaphylaxis (recurrent anaphylaxis occurring 1 to 72 hours after resolution of the initial episode) occurs in 4-5% of cases. 4
Critical Diagnostic Pitfall
Symptoms not immediately life-threatening might progress rapidly unless treated promptly and appropriately. 1 This emphasizes the need for early intervention with epinephrine even with seemingly mild presentations, as there is no way to reliably predict whether a patient's condition will progress quickly and become life-threatening. 5
Risk Factors for Severe Reactions
Risk factors for severe anaphylaxis include cardiovascular disease, asthma, older age, and additional coexisting comorbid conditions. 2 Concurrent medications that increase risk include beta-adrenergic blockers and angiotensin-converting enzyme inhibitors. 2
Diagnosis
Anaphylaxis diagnosis is based upon clinical signs and symptoms and must occur rapidly, as confirmatory testing for anaphylaxis has poor sensitivity. 2 The clinical criteria proposed in 2006 by the National Institute of Allergy and Infectious Diseases provide a helpful framework, with a sensitivity of 95% and specificity of 71% in emergency department settings. 2 However, fulfilling diagnostic criteria is not a prerequisite for epinephrine administration in a patient experiencing an acute allergic reaction. 2
First-Line Treatment
Epinephrine administered intramuscularly into the anterolateral thigh is the first-line treatment for anaphylaxis. 2, 4 The dose is 0.01 mg/kg of a 1:1000 (1 mg/mL) solution to a maximum of 0.5 mg in adults and 0.3 mg in children. 2 There are no absolute contraindications to epinephrine use in anaphylaxis. 4, 6 Delayed epinephrine administration is directly associated with increased hospitalization rates, hypoxic-ischemic encephalopathy, and death. 4