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PODCAST: Angioedema

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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.

                                      • The post PODCAST: Angioedema first appeared on האיגוד הישראלי לרפואה דחופה.

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