- Clinical science
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.
- Anaphylaxis: a severe type 1 hypersensitivity reaction that can cause life-threatening and multisystem effects due to IgE-mediated mast cell activation
Anaphylactoid reaction: a reaction that is clinically similar to anaphylaxis but is mediated by direct nonimmune-mediated activation of either mast cells or the complement cascade (see “Pseudoallergy”)
- Examples include reactions to radiocontrast media and vancomycin
- Anaphylactic shock: a type of distributive shock that results from anaphylaxis
- Trigger is idiopathic in 20% of patients 
- Most common triggers leading to fatal anaphylaxis 
Onset of symptoms 
In general, the onset of symptoms is acute (within minutes to hours of exposure to a likely antigen).
|Antigen-dependent onset of anaphylaxis |
Median time to circulatory arrest
Affected organ systems 
- Skin or mucous membranes
- Adults: SBP < 90 mm Hg OR decrease ≥ 30% from baseline 
- Children: definition depends on age
- Tachycardia, weak peripheral pulses
- Signs of end-organ dysfunction
Beware of atypical manifestations without skin/mucosal symptoms (10% of patients) to avoid misdiagnosis and treatment delay. 
Diagnostic criteria for anaphylaxis 
If any of the following criteria are fulfilled, anaphylaxis is likely. The onset of symptoms must be acute (minutes to hours).
- 1) Known allergen exposure with hypotension (SBP < 90 mm Hg or ≥ 30% decrease from the baseline)
- 2) Suspected allergen exposure with skin and/or mucosal symptoms (e.g., hives, swollen lips, tongue, and/or uvula) AND ≥ 1 of the following:
- 3) Suspected allergen exposure AND ≥ 2 of the following:
- Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea
- Cardiovascular: systolic BP < 90 mm Hg or ≥ 30% decrease from baseline, and/or altered mental status, syncope, ischemic chest pain, incontinence, anuria
- Respiratory: dyspnea, hypoxia, stridor, hoarseness, wheezing, cough
- Skin/mucosal: hives, angioedema, pruritus, flushing
- Stabilize the patient (ABCDE approach).
- Airway assessment and management (see “Airway management and ventilation in anaphylaxis”)
- Rapid sequence intubation (RSI) for airway compromise
- Oxygen: Provide FiO2 of 100% (e.g., high-flow O2 by nonrebreather mask).
- Aggressive IV fluid resuscitation if hypotension present (large-bore IV access; administer 1–2 L 0.9% saline IV bolus)
- Position the patient supine.
- If anaphylaxis is likely (see diagnostic criteria for anaphylaxis), start initial treatment immediately: 
- Once stabilized, consider adjunctive therapy with antihistamines; , corticosteroids (e.g., methylprednisolone)
- Continuous reassessment and subsequent management
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.
Laboratory studies 
- Not routinely indicated but can be useful to confirm anaphylaxis or screen for bradykinin-mediated angioedema.
- Serum mast-cell tryptase (MCT): if elevated, supports the diagnosis of anaphylaxis
- Normal result does not rule out anaphylaxis
- Low sensitivity in food-triggered reaction
- Complement C4 levels: can be low in hereditary angioedema (see “”)
- Not routinely indicated but can be useful to rule in/out mimics.
- Screening for upper airway foreign bodies and infections (e.g., peritonsillar abscess, deep neck space infection, epiglottitis): neck x-ray, CT neck
- Evaluating for other causes of respiratory distress (e.g., pneumonia, pulmonary embolism, ARDS): CXR, CTA Chest
- Assessing cardiac function and evaluating for other causes of shock (e.g., cardiomyopathy): echocardiogram
- Lethargic patient:
- Rapid decline: Prepare for endotracheal intubation.
Respiratory failure/complete airway obstruction: Perform rapid sequence intubation (RSI).
- Intubation medications
- Additional considerations
- Severe bronchospasm: Administer a bronchodilator.
Obtain early anesthesia or ENT consultation in patients with a rapid decline or anticipated airway compromise.
Refractory anaphylaxis 
- Anaphylactic shock refractory to repeated IM epinephrine and fluids
- Anaphylactic shock refractory to IV epinephrine infusion
- Cardiac arrest: Start protocol.
Adjunctive therapy 
- Antihistamines: Consider a combination of an H1-antagonist and H2-antagonist in severe cases.
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 “ ”).
Monitoring and disposition 
- Monitor in acute-care setting at least 4–8 hours
- Continuous pulse oximetry monitoring
- Continuous cardiac monitoring
- Clinical reassessment for
- Extend monitoring if patient requires ≥ 2 doses of IM epinephrine OR IV epinephrine
- ICU admission for patients needing advanced airway, mechanical ventilation, and/or vasopressor support
- Prior to discharge:
- Administer IM epinephrine and repeat as needed
- Stop offending trigger
- Administer supplemental oxygen.
- Airway management
- Position supine if tolerated.
- IV fluid resuscitation
- Continuous epinephrine infusion for refractory shock
- Consider adjunctive treatment (steroids, antihistamines).
- Continuous telemetry and pulse oximetry
- Close clinical monitoring for biphasic reaction
- Transfer to ICU or medical service.
|Differential diagnoses of anaphylaxis |
|Acute upper airway obstruction/stridor|
Acute respiratory distress/wheezing 
|Loss of consciousness|| |
The differential diagnoses listed here are not exhaustive.
- Biphasic anaphylactic reactions 
- Respiratory failure, cardiac arrest, death
- Drug side effects
- Complications of or
We list the most important complications. The selection is not exhaustive.