What are the signs and treatment of anaphylaxis?

Signs and Symptoms of Anaphylaxis

Anaphylaxis presents with a combination of characteristic findings across multiple organ systems, with cutaneous manifestations being most common but potentially absent in rapidly progressive cases, and the more rapidly symptoms develop after exposure, the more likely the reaction is severe and life-threatening. 1, 2

Clinical Manifestations by Organ System

Cutaneous Signs (Most Common)

• Diffuse erythema, pruritus, urticaria, and/or angioedema are the most frequent manifestations 1, 2
• Swelling of eyelids, lips, and tongue 3
• Important caveat: Cutaneous manifestations may be delayed or completely absent in rapidly progressive anaphylaxis, particularly when cardiovascular collapse occurs 2

Cardiovascular Signs

• Hypotension with or without syncope 1
• Tachycardia (the rule in anaphylaxis) 1
• Thready or unobtainable pulse 3
• Cardiac arrhythmias 1
• Critical feature: Increased vascular permeability can transfer up to 50% of intravascular fluid into extravascular space within 10 minutes, causing rapid hemodynamic collapse 2

Respiratory Signs

• Upper airway: Dysphonia, stridor, airway swelling, laryngospasm 1, 3
• Lower airway: Cough, wheezing, bronchospasm, shortness of breath 1, 3
• Throat tightness or sensation of choking 3

Gastrointestinal Signs

• Nausea, vomiting, diarrhea 1, 3
• Abdominal cramps 3
• Involuntary voiding 3

Neurological Signs

• Altered level of consciousness (suggests hypoxia) 1, 2
• Lightheadedness, headache 1
• Feeling of impending doom 1
• Apprehension, syncope, convulsions 3

Diagnostic Approach

Anaphylaxis is a clinical diagnosis that must be made rapidly; confirmatory testing has poor sensitivity and should never delay treatment. 2 The history is the most important diagnostic tool 1

Key Diagnostic Principles

• Prompt recognition is crucial—if there is any doubt, it is generally better to administer epinephrine 1, 4
• The more rapidly anaphylaxis develops, the more severe and life-threatening it is likely to be 1, 2
• Laboratory tests (such as serum tryptase) can help confirm diagnosis but proper timing is essential and should not delay treatment 1

Critical Differential Diagnosis

Vasodepressor (vasovagal) reaction is the condition most commonly confused with anaphylaxis 1

Distinguishing Features of Vasovagal Reaction:

• Urticaria is absent 1
• Heart rate is typically bradycardic (not tachycardic) 1
• Bronchospasm or breathing difficulty is generally absent 1
• Blood pressure is usually normal or increased 1
• Skin is typically cool and pale 1

Other Conditions to Consider:

• Acute anxiety (panic attack, hyperventilation syndrome) 1
• Myocardial dysfunction, pulmonary embolism 1
• Systemic mast cell disorders 1
• Foreign-body aspiration, acute poisoning 1
• Hypoglycemia, seizure disorder 1
• Hereditary angioedema, isolated asthma 1

Treatment of Anaphylaxis

Epinephrine is the first-line, life-saving drug for anaphylaxis and should be administered immediately at the onset of apparent anaphylaxis—delayed injection is associated with poor outcomes including fatality. 1, 2, 5

Immediate Treatment Algorithm

1. Assess and Position

• Assess airway, breathing, circulation, and level of consciousness 1
• Position patient supine or in position of comfort if respiratory distress/vomiting present 1, 5
• Call for help immediately (911/EMS) 1, 5

2. Administer Epinephrine (First-Line Treatment)

Dosing:

• Adults: 0.2-0.5 mL (0.3-0.5 mg) of 1:1000 dilution intramuscularly 1, 2, 5, 3
• Children: 0.01 mg/kg intramuscularly (maximum 0.3 mg in prepubertal children) 1, 2, 5

Route and Site:

• Intramuscular injection into the mid-anterolateral thigh (vastus lateralis) is the method of choice 1, 5, 6
• Intramuscular thigh injections provide more rapid absorption and higher plasma levels than arm injections 1
• Can be given through clothing, but avoid seams or pockets with objects 7

Repeat Dosing:

• Repeat every 5-15 minutes as necessary to control symptoms and increase blood pressure 1, 2, 5
• Between 7-18% of patients require more than one dose 7
• A second dose should be given if symptoms persist or if EMS arrival will exceed 5-10 minutes 7

3. Adjunctive Treatments (Second-Line Only)

H1-Antihistamines:

• Diphenhydramine can be administered as second-line therapy 5
• Should never be used alone or as initial treatment 1, 5
• Combination of H1 and H2 antihistamines is superior to H1 alone 5

Glucocorticoids:

• Can be considered for patients with history of idiopathic anaphylaxis, asthma, or severe/prolonged anaphylaxis 5
• Have no role in treating acute anaphylaxis due to slow onset of action 5
• If given: IV glucocorticoids every 6 hours at 1.0-2.0 mg/kg/day equivalent 5
• Do not demonstrate significant reduction in biphasic reactions 8

4. Refractory Cases

For hypotension refractory to epinephrine and fluids:

• Vasopressor infusion (dopamine) 5
• Appropriate volume replacement with crystalloids initially, then colloids for severe shock 1

For bronchospasm resistant to epinephrine:

• Nebulized albuterol 5

For patients on β-blockers:

• Consider glucagon infusion 5

For cardiopulmonary arrest:

• High-dose IV epinephrine may be required 5
• IV epinephrine should only be used in monitored settings for cardiac arrest or profound hypotension unresponsive to IM epinephrine 5, 8

Critical Pitfalls to Avoid

• Using subcutaneous instead of intramuscular injection (delays absorption) 5
• Administering IV epinephrine outside monitored settings 5, 8
• Relying solely on antihistamines or glucocorticoids 5
• Delaying epinephrine administration (associated with increased hospitalization risk, hypoxic-ischemic encephalopathy, and death) 7, 8
• Accidental digital injection (can cause vasoconstriction and necrosis) 7

Post-Acute Management

All patients who experience anaphylaxis require transport to emergency department for monitoring 1, 5, 7, 8

Observation Period:

• Patients should be observed for 4-10 hours according to severity 9
• Biphasic reactions may affect 1-7% of patients 8
• Risk factors for biphasic reaction include severe initial presentation and repeated epinephrine doses 8

Discharge Requirements:

• Prescription of epinephrine auto-injector with training on use 1, 2, 5
• Written personalized anaphylaxis emergency action plan 1
• Education on trigger avoidance and risk of recurrence 2, 5
• Referral to allergist-immunologist 2
• Medical identification jewelry or wallet card 1

High-Risk Populations Requiring Special Attention:

• Teenagers (high-risk behaviors, failure to carry auto-injectors) 1
• Patients with severe uncontrolled asthma 9
• Patients on β-adrenergic blockade 9