Show Notes

Definition & Pathophysiology

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

Triggers increased vascular permeability → fluid shifts into tissues.

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.

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.

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.

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.

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.

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.