Anaphylaxis Pathophysiology and Management

Introduction to Anaphylaxis

• Anaphylaxis is an acute, life-threatening systemic reaction resulting from the sudden release of mediators from mast cells and basophils, triggered by either IgE-dependent or IgE-independent mechanisms, requiring urgent treatment 1, 2

Pathophysiological Mechanisms

• The IgE-mediated pathway involves allergen cross-linking IgE bound to FcεRI receptors on mast cells and basophils, causing immediate release of preformed mediators and de novo synthesis of inflammatory mediators 1
• Complement activation can directly activate mast cells and basophils, with elevated serum C3a associated with severe anaphylaxis 1

Clinical Presentation and Diagnosis

• Cutaneous symptoms, such as flushing, pruritus, urticaria, and angioedema, occur in 90% of cases, though their absence does not rule out anaphylaxis 4, 2
• Respiratory symptoms, including bronchospasm, wheezing, and laryngeal edema, are present in 40-60% of cases 4, 5
• Cardiovascular symptoms, such as hypotension, tachycardia, and cardiovascular collapse, occur in 30-35% of cases 4, 5

Immediate Treatment

• Epinephrine is the drug of choice and must be administered promptly at the onset of apparent anaphylaxis, with the intramuscular route preferred 2, 6
• The recommended dose is 0.3-0.5 mg (0.3-0.5 mL of 1:1000 solution) IM for adults and children ≥30 kg, with repeat dosing every 5-15 minutes if symptoms persist or worsen 5, 7, 8

Secondary Interventions

• Antihistamines, such as diphenhydramine, and corticosteroids, such as methylprednisolone, may be used as adjunctive therapy, but should not delay epinephrine administration 10, 7
• Volume resuscitation with rapid IV fluid bolus is recommended for hypotension 8, 10

Observation and Monitoring

• Observation periods must be individualized, with extended observation of at least 6 hours warranted for severe anaphylaxis or patients requiring more than one dose of epinephrine 8, 7
• Biphasic reactions occur in 1-7% of patients, with symptoms recurring hours after initial resolution, and require prolonged observation 8, 5

Post-Acute Management

• After resolution of the acute episode, all patients must be provided with an epinephrine autoinjector and receive proper instruction for self-administration in case of subsequent episodes 8, 9, 2
• Patients should be referred to an allergist-immunologist for detailed history, diagnostic testing, and evaluation of immunotherapy options 9, 2, 6

Common Triggers and Risk Factors

• Foods, such as peanuts, tree nuts, and shellfish, are common triggers of anaphylaxis, especially in children and adults 8
• Insect venoms, particularly Hymenoptera stings, cause 23% of anaphylaxis cases, with a significant risk of fatal outcomes 1
• Medications, including penicillin, beta-lactam antibiotics, and NSAIDs, can also trigger anaphylaxis 8, 3