Episode 212: Angioedema

Definition & Pathophysiology

Angioedema = localized swelling of mucous membranes and subcutaneous tissues due to increased vascular permeability.

Triggers increased vascular permeability → fluid shifts into tissues.

Etiologies

• Histamine-mediated (anaphylaxis)
  • Associated with urticaria/hives, pruritus, and redness.
  • Triggered by allergens (foods, insect stings, medications).
  • Rapid onset (minutes to hours).
• Bradykinin-mediated
  • Hereditary angioedema (HAE): C1 esterase inhibitor deficiency (autosomal dominant).
  • Acquired angioedema: Associated with B-cell lymphoma, autoimmune disease, MGUS.
  • Medication-induced: Most commonly ACE inhibitors; rarely ARBs.
  • Typically lacks urticaria and itching.
  • Gradual onset, can last days if untreated.
• Idiopathic angioedema
  • Unknown cause; diagnosis of exclusion.

Clinical Presentations

• Swelling
  • Asymmetric, non-pitting, usually non-painful.
  • May involve lips, tongue, face, extremities, GI tract.
• Respiratory compromise
  • Upper airway swelling → stridor, dyspnea, sensation of throat closure.
  • Airway obstruction is the most feared complication.
• Abdominal manifestations
  • Bowel wall angioedema can mimic acute abdomen:
    • Nausea, vomiting, diarrhea, severe pain, increased intra-abdominal pressure, possible ischemia.

Key Differentiating Features

• Histamine-mediated: rapid onset, hives/itching, resolves quickly with epinephrine, antihistamines, and steroids.
• Bradykinin-mediated: slower onset, lacks urticaria, prolonged duration, less responsive to standard anaphylaxis medications.

Diagnostic Approach in the ED

• Focus on airway (ABCs) and clinical assessment.
• Labs (e.g., C4 level) useful for downstream diagnosis (esp. HAE) but not for acute management.
• Imaging: only if symptoms suggest abdominal involvement or to rule out other causes.

Treatment Strategies

• Airway protection is always priority:
  • Early consideration of intubation if worsening obstruction or inability to manage secretions.
• Histamine-mediated (anaphylaxis):
  • Epinephrine (IM), antihistamines, corticosteroids.
• Bradykinin-mediated:
  • Epinephrine may be tried if unclear etiology (no significant harm, lifesaving if histamine-mediated).
  • Targeted therapies:
    • Icatibant: bradykinin receptor antagonist.
    • Ecallantide: kallikrein inhibitor (less available).
    • C1 esterase inhibitor concentrate: replenishes deficient protein.
    • Fresh frozen plasma (FFP): contains C1 esterase inhibitor.
    • Tranexamic acid (TXA): off-label, less evidence, considered if no other options.

Complications to Watch For

• Airway compromise: rapid deterioration possible.
• Abdominal compartment syndrome from bowel edema (rare, surgical emergency).

Take-Home Points

• Secure the airway if in doubt.
• Differentiate histamine-mediated vs bradykinin-mediated by presence/absence of hives/itching and speed of onset.
• Use epinephrine promptly if suspecting histamine-mediated angioedema or if uncertain.
• Consider bradykinin-targeted therapies for confirmed hereditary, acquired, or ACE-inhibitor–related angioedema.
• Recognize ACE inhibitors as the most frequent medication trigger; ARBs rarely cause it.
• Labs and imaging generally don’t change initial ED management but aid diagnosis for follow-up care.