Summary

Anaphylaxis is a life-threatening, systemic hypersensitivity reaction characterized by rapid onset and potential for airway compromise and cardiovascular collapse. It involves sudden IgE-mediated release of mediators from mast cells and basophils in response to triggers like food, insect stings, or medications. Key features include acute onset of symptoms involving multiple organ systems, often with skin/mucosal changes. Immediate recognition, administration of intramuscular epinephrine, and supportive care are critical. Risk factors include prior anaphylaxis and atopic conditions. Anaphylactoid reactions, though IgE-independent, present similarly and are managed the same way.

Etiology

Anaphylaxis is primarily caused by an IgE-mediated immunologic reaction, though non-IgE-mediated and non-immunologic mechanisms can also occur. Common triggers include:

• Foods: Peanuts, tree nuts, shellfish, fish, eggs, milk, soy, wheat
• Medications: β-lactam antibiotics, NSAIDs, neuromuscular blocking agents, chemotherapeutics, radiocontrast media
• Insect stings: Hymenoptera (bees, wasps, hornets, fire ants)
• Latex: Common in healthcare settings
• Exercise: Can be food-dependent or independent
• Idiopathic: No identifiable cause in up to 20% of cases

Most common triggers for fatal anaphylaxis:

• Younger patients: Food allergies, insect stings
• Older patients: Drug reactions, radiocontrast media
• Hospitalized patients: Food, medications (e.g., antibiotics, NSAIDs), latex

Risk factors:

• Prior anaphylaxis
• Atopic conditions (asthma, allergic rhinitis, atopic dermatitis)
• Mastocytosis or elevated baseline tryptase
• Use of β-blockers or ACE inhibitors (can exacerbate anaphylaxis)

Pathophysiology

Anaphylaxis involves a massive release of mediators from mast cells and basophils, triggered by allergen cross-linking of IgE antibodies on cell surfaces. Key mediators and their effects include:

1. Histamine: Vasodilation, increased vascular permeability, bronchoconstriction
2. Leukotrienes: Potent bronchoconstrictors, increase vascular permeability
3. Prostaglandins: Vasodilation, bronchial smooth muscle contraction
4. Platelet-activating factor: Platelet aggregation, vasodilation, increased vascular permeability
5. Tryptase: Marker of mast cell activation, useful in diagnosis

These mediators lead to:

• Systemic vasodilation → hypotension
• Increased vascular permeability → angioedema, urticaria
• Bronchial smooth muscle contraction → wheezing, respiratory distress
• Increased mucus production → airway obstruction

The rapid onset and multi-system involvement distinguish anaphylaxis from other allergic reactions. Anaphylactoid reactions, while IgE-independent, result from direct mast-cell activation and present similarly.

Signs and Symptoms

Symptoms typically develop within minutes to 2 hours after exposure to the trigger. Multi-system involvement is characteristic. Onset can be antigen-dependent:

• Food: Median time to circulatory arrest is 30 minutes
• Insect stings: 15 minutes
• Medications: 5 minutes

Common symptoms:

• Cutaneous (80-90% of cases):
  • Urticaria (hives), pruritus (itching)
  • Flushing, erythema
  • Angioedema (including eyelids)
• Respiratory (70% of cases):
  • Dyspnea, wheezing, cough
  • Stridor, hoarseness
  • Upper airway edema
  • Nasal congestion, sneezing
• Cardiovascular (45% of cases):
  • Hypotension
  • Tachycardia, weak peripheral pulses
  • Dizziness, syncope
  • Chest tightness or pain
• Gastrointestinal (45% of cases):
  • Nausea, vomiting (especially in food allergies)
  • Abdominal pain, diarrhea

Physical exam findings:

• Hypotension (SBP < 90 mmHg or >30% decrease from baseline)
• Tachycardia
• Respiratory distress (wheezing, stridor, accessory muscle use)
• Cutaneous signs (urticaria, angioedema)
• Altered mental status
• Signs of end-organ dysfunction (e.g., decreased urine output, skin mottling, delayed capillary refill)

Beware of atypical presentations without skin/mucosal symptoms, which occur in 10% of cases.

Diagnostic Workup

Anaphylaxis is primarily a clinical diagnosis based on history and physical examination. No single test can confirm anaphylaxis in real-time.

Key diagnostic criteria (WAO 2020 Anaphylaxis Criteria):

1. Acute onset of illness (minutes to hours) with involvement of skin, mucosal tissue, or both AND at least one of:a) Respiratory compromiseb) Reduced blood pressure or symptoms of end-organ dysfunction
2. Two or more of the following occurring rapidly after exposure to a likely allergen:a) Involvement of skin/mucosal tissueb) Respiratory compromisec) Reduced blood pressure or associated symptomsd) Persistent gastrointestinal symptoms
3. Reduced blood pressure after exposure to a known allergen for that patient

Laboratory tests (not necessary for immediate management):

• Serum tryptase: Elevated levels support diagnosis (peak at 1-2 hours, return to baseline within 24 hours)
• Specific IgE testing: Useful for identifying triggers (not for acute diagnosis)
• Complement C4 levels: Can be low in hereditary angioedema

Imaging (not routinely indicated but can be useful to rule out mimics):

• Neck X-ray or CT: To screen for upper airway foreign bodies or infections
• Chest X-ray or CT angiography: To evaluate for other causes of respiratory distress
• Echocardiogram: To assess cardiac function and evaluate for other causes of shock

Treatment

Immediate management is critical and should not be delayed for diagnostic confirmation.

1. First-line treatment:
   • Epinephrine 0.3-0.5 mg IM (1:1000 concentration) in anterolateral thigh
   • Can be repeated every 5-15 minutes if needed
   • Pediatric dose: 0.01 mg/kg up to 0.3 mg
2. Supportive measures:
   • Remove trigger if identifiable
   • Position patient supine with legs elevated (unless respiratory distress)
   • Supplemental oxygen (FiO2 100%, e.g., high-flow O2 by non-rebreather mask)
   • IV fluids (crystalloids) for hypotension: 1-2 L rapidly in adults
3. Airway management:
   • Basic airway maneuvers and adjuncts (e.g., head-tilt/chin-lift, jaw-thrust, NPA, OPA)
   • Prepare for difficult airway; consider early anesthesia or ENT consult
   • If intubation necessary, consider ketamine for induction; use paralytics with caution
   • Consider inhaled racemic epinephrine while preparing for intubation
4. Second-line treatments:
   • H1 antihistamines (e.g., diphenhydramine 25-50 mg IV/IM)
   • H2 antihistamines (e.g., cimetidine 300 mg IV)
   • Glucocorticoids (e.g., methylprednisolone 125 mg IV)
   • Inhaled β2-agonists for bronchospasm (e.g., albuterol nebulizer or MDI)
5. Refractory cases:
   • IV epinephrine infusion (0.1-1 μg/kg/min)
   • Vasopressors (norepinephrine, vasopressin)
   • Glucagon for patients on β-blockers (1-5 mg IV bolus, then infusion)
6. Post-acute care:
   • Observe for biphasic reactions (6-24 hours)
   • Prescribe epinephrine auto-injector
   • Refer to allergist for follow-up