Episode 212: Angioedema

Aug 2, 2025

Dr. Maria Mulligan-Buckmiller, a rock star chief resident, shares her expertise on angioedema management in the emergency department. She dives into the different types of angioedema, highlighting the crucial distinctions between histamine and bradykinin-mediated responses. The podcast discusses clinical presentations, including upper airway swelling and abdominal symptoms. Mulligan-Buckmiller emphasizes the importance of timely interventions and effective airway management, as well as key treatments like Icatabant and C1 esterase inhibitors to address potential complications.

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ANECDOTE

Hereditary Angioedema Case

A patient with progressive facial swelling and shortness of breath was initially treated with epinephrine.
Further history revealed hereditary angioedema with a family history and lack of itching or redness.

INSIGHT

Angioedema Mechanisms Differ

Angioedema causes localized swelling through increased vascular permeability from vasodilation.
Histamine-mediated angioedema features itching and hives; bradykinin-mediated lacks these and involves C1 esterase inhibitor deficiency.

INSIGHT

Angioedema Clinical Presentations

Angioedema can cause asymmetric, non-pitting swelling in mucous membranes, including lips and GI tract.
Bowel wall angioedema may cause symptoms mimicking acute abdomen, such as pain and ischemia.

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Angioedema – Recognition and Management in the ED

Hosts:
Maria Mulligan-Buckmiller, MD
Brian Gilberti, MD

Download Leave a Comment Tags: Airway

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.

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.