What are the causes and treatments of anaphylaxis?

Anaphylaxis: Causes and Treatment

Common Causes of Anaphylaxis

The most common triggers of anaphylaxis vary by age: in children, foods (especially peanuts, tree nuts, milk, eggs, fish, and shellfish) predominate, while in adults, medications and stinging insects are the leading causes. 1

Food Triggers

• Pediatric population: Peanuts, tree nuts, milk, eggs, fish, and shellfish are the most frequent culprits 1
• Adult population: Shellfish causes the greatest number of anaphylactic episodes 1
• Food reactions almost always occur immediately after exposure, though symptoms may subside and recur several hours later (biphasic reaction) 1

Medication Triggers

• Antibiotics: Penicillin and other β-lactam antibiotics are the most common drug triggers 1, 2
• Cancer chemotherapy: Platinum-containing drugs (cisplatin, carboplatin) are increasingly recognized causes, with some reactions due to the solvent Cremophor-L 1
• NSAIDs and aspirin: These reactions appear medication-specific, allowing patients to tolerate other NSAIDs 1
• Radiographic contrast material (RCM): Causes anaphylactoid reactions in 5-8% of patients with conventional high-osmolality agents, though newer low-osmolality agents reduce this risk by approximately 80% 1

Insect Venom

• Hymenoptera (bees, wasps, hornets) stings cause systemic reactions in 0.5-3.3% of the US population 1
• Most fatalities occur in patients with no prior history of systemic allergic reactions 1

Other Triggers

• Latex: Particularly affects healthcare workers, patients with spina bifida, and those with frequent medical procedures 1
• Physical factors: Exercise, cold, heat, and sunlight can trigger anaphylaxis 1
• Idiopathic: Up to one-fifth of anaphylaxis cases have no identifiable trigger 1, 3

Risk Factors for Severe or Fatal Anaphylaxis

Major risk factors include prior history of anaphylaxis, β-adrenergic blocker therapy, cardiovascular disease, poorly controlled asthma, older age, and atopic background (for venom and latex). 1

• β-blocker use: Increases severity and may reduce epinephrine responsiveness 1
• Asthma: Especially if severe or poorly controlled, significantly increases risk of fatal reactions 1
• Cardiovascular disease: Associated with more severe outcomes 1
• Adolescence: Fatal anaphylaxis is often associated with this age group, particularly when combined with delayed epinephrine administration 1
• Previous RCM reaction: Risk of repeat reaction ranges from 16-44% without prophylaxis 1

Immediate Treatment of Anaphylaxis

Epinephrine administered intramuscularly into the anterolateral thigh is the first-line, life-saving treatment and must be given immediately at the onset of anaphylaxis—when in doubt, give epinephrine. 1, 4, 5

Epinephrine Administration

• Dosing: 0.01 mg/kg of 1:1000 solution (1 mg/mL) intramuscularly
  • Maximum 0.3 mg in prepubertal children
  • Maximum 0.5 mg in adolescents and adults 1, 4
• Route: Intramuscular injection into the mid-outer thigh (vastus lateralis muscle) provides optimal absorption 1, 4
• Repeat dosing: 10-20% of patients require a second dose; repeat every 5-15 minutes if symptoms persist or worsen 1, 4, 5
• No absolute contraindications: Even patients on β-blockers should receive epinephrine (though they may require glucagon as adjunctive therapy if refractory) 4

Critical Pitfall to Avoid

Delayed epinephrine administration is directly associated with increased hospitalization, hypoxic-ischemic encephalopathy, and death—never substitute antihistamines as first-line treatment. 4

Supportive Measures (After Epinephrine)

• Patient positioning: Place supine with legs elevated, or in position of comfort if respiratory distress or vomiting present 1
• Oxygen: Administer supplemental oxygen 1
• IV fluids: Rapid volume replacement with crystalloids or colloids for hypotension (up to 50% of intravascular volume can shift to extravascular space within 10 minutes) 5
• Adjunct medications (only after epinephrine):
  • H1 and H2 antihistamines
  • Corticosteroids
  • β2 agonists for bronchospasm
  • Glucagon for patients on β-blockers 1, 3

Observation Period

All patients must be transferred to an emergency department for observation, even if symptoms resolve, due to risk of biphasic reactions. 4, 5

• Biphasic anaphylaxis occurs in 4-5% of cases, typically 1-72 hours after initial resolution 1, 4
• Higher risk in patients requiring multiple epinephrine doses 4
• Observation period should be 4-12 hours depending on severity and risk factors 3

Prevention Strategies

Avoidance and Education

Patient education is the most important preventive strategy, including instruction on hidden allergens, cross-reactions, and proper use of self-administered epinephrine. 1

• Prescribe epinephrine auto-injector for all patients with history of anaphylaxis 1, 5
• Patients should wear medical alert identification 1
• Refer to allergist-immunologist for comprehensive evaluation 5

Specific Prophylaxis Strategies

• Insect venom immunotherapy: Highly effective (90-98%) for patients with systemic sensitivity to stinging insects 1
• RCM reactions: Pretreatment with corticosteroids and antihistamines markedly reduces recurrent reactions; use low-osmolality agents 1
• Medication desensitization: Can be effective for drugs that previously caused anaphylaxis, though effect is temporary and must be repeated if medication needed again 1