What is the initial workup for a patient presenting with angioedema?

Initial Workup for Angioedema

The initial workup for angioedema should include documenting true angioedema with photos or imaging, measuring C4 and C1-inhibitor levels and function, evaluating medication history (especially ACE inhibitors), and assessing for family history of angioedema. 1

Confirming True Angioedema

• Obtain photographic evidence or imaging documentation of swelling episodes
• Laryngoscopic examination for oropharyngeal/laryngeal involvement
• Abdominal imaging during attacks if gastrointestinal symptoms present (to detect bowel wall edema)
• Differentiate from mimics such as factitious angioedema 2

Essential Laboratory Testing

1. First-line laboratory tests:

   • C4 level (typically low in hereditary angioedema)
   • C1-inhibitor antigen level
   • C1-inhibitor functional activity 2, 1

2. Additional testing for suspected acquired C1-inhibitor deficiency:

   • C1q level (typically low in acquired angioedema)
   • Anti-C1-inhibitor antibodies 2

Medication History Assessment

• Identify and discontinue potential causative medications:

  • ACE inhibitors (most common drug cause)
  • Angiotensin II receptor blockers (sartans)
  • Dipeptidyl peptidase IV inhibitors (gliptins)
  • Neprilysin inhibitors
  • NSAIDs 2, 1

• Observe for 1-3 months after medication discontinuation to determine if angioedema resolves 1

Clinical History Elements

1. Angioedema characteristics:

   • Duration of individual episodes (typically 24-72 hours)
   • Frequency and pattern of attacks
   • Associated symptoms (pain, nausea, vomiting)
   • Presence or absence of urticaria/hives (suggests histaminergic vs. bradykinin-mediated) 2

2. Trigger identification:

   • Physical trauma or procedures (dental work, surgery)
   • Emotional stress
   • Infections
   • Hormonal fluctuations (estrogen) 2, 1

3. Family history:

   • Document any relatives with recurrent angioedema or HAE diagnosis 2, 1

Distinguishing Angioedema Types

Histaminergic Angioedema

• Often associated with urticaria/hives
• Typically responds to antihistamines
• May have associated pruritus 1, 3

Bradykinin-Mediated Angioedema

• No associated urticaria
• Does not respond to antihistamines/corticosteroids
• Often includes abdominal attacks with severe pain
• May have family history (hereditary forms) 2, 4

ACE Inhibitor-Induced Angioedema

• Typically occurs within first weeks of therapy but can occur after years
• Predominantly affects face, lips, tongue, and upper airway
• May persist for weeks after drug discontinuation 1, 5

Special Considerations

• For patients with predominant gastrointestinal symptoms, obtain abdominal imaging during attacks to evaluate for bowel wall edema 2
• Consider genetic testing if there is a strong family history of angioedema 2, 6
• In cases of recurrent angioedema with normal C1-inhibitor levels and function, consider hereditary angioedema with normal C1-inhibitor 2, 6

Common Pitfalls to Avoid

• Failing to document true angioedema with objective evidence
• Misdiagnosing abdominal pain as other gastrointestinal disorders
• Continuing ACE inhibitors in patients with angioedema
• Relying solely on antihistamines for bradykinin-mediated angioedema
• Overlooking family history due to variable penetrance or de novo mutations 2, 1

By following this systematic approach to the initial workup of angioedema, clinicians can accurately diagnose the specific type and implement appropriate management strategies to reduce morbidity and mortality.