Angioedema: Definition and Clinical Characteristics
Angioedema is characterized by localized, non-pitting, non-pruritic swelling of the subcutaneous and/or submucosal tissue caused by increased vascular permeability, which can be life-threatening when affecting the upper respiratory tract. 1
Types of Angioedema
Angioedema can be classified into two main categories based on underlying mechanisms:
1. Histaminergic (Mast Cell-Mediated) Angioedema
- Often associated with urticaria/hives
- Responds to antihistamines
- Usually resolves within 24 hours
- May be part of allergic reactions to foods, medications, or insect stings 1, 2
2. Bradykinin-Mediated Angioedema
- Not associated with urticaria
- Does not respond to antihistamines, corticosteroids, or epinephrine
- Episodes typically last 24-72 hours
- Includes several subtypes:
Clinical Presentation
Angioedema presents with:
- Sudden onset of swelling
- Asymmetric, non-dependent swelling
- Commonly affects face, lips, tongue, throat, extremities, genitalia, and intestinal wall
- May involve multiple sites simultaneously or sequentially
- Episodes are self-limiting, typically lasting 2-5 days without treatment 3, 1
Severity varies significantly between patients and even within the same patient over time. The most dangerous presentations involve:
- Laryngeal edema (potentially fatal due to airway obstruction)
- Severe abdominal attacks (can mimic acute abdomen with severe pain, vomiting, and hypotension) 3
Pathophysiology
The underlying mechanism of all angioedema is increased vascular permeability leading to plasma extravasation and tissue swelling. This occurs through two main pathways:
- Histamine pathway: Mast cell activation and histamine release
- Bradykinin pathway: Excessive bradykinin production or reduced degradation 3, 7
Diagnosis
Diagnosis of angioedema involves:
- Documenting true angioedema with photos or imaging
- Distinguishing between histaminergic and bradykinin-mediated forms
- Laboratory testing when hereditary or acquired forms are suspected:
- C4 level (typically low in HAE)
- C1-inhibitor antigen level
- C1-inhibitor functional activity 1
Management
Treatment depends on the type of angioedema:
Histaminergic Angioedema
- First-line: Second-generation H1 antihistamines (up to 4× standard dose)
- Second-line: Add montelukast
- Third-line: Omalizumab (4-6 month course) 1
Bradykinin-Mediated Angioedema
- Acute attacks: Icatibant (bradykinin B2 receptor antagonist), C1 inhibitor concentrate, or ecallantide
- ACE inhibitor-induced: Immediate discontinuation of the ACE inhibitor (cornerstone of therapy)
- Prophylaxis: C1 inhibitor concentrate before procedures or long-term for frequent attacks 1
Special Considerations
ACE Inhibitor-Induced Angioedema
- Accounts for 30-40% of angioedema cases seen in US emergency departments
- Can occur even after years of uneventful use
- Swelling may persist for weeks after discontinuation
- Higher risk in African Americans, smokers, older patients, and women 1, 4
Hereditary Angioedema
- Rare genetic disorder with variable penetrance
- Attacks may be triggered by trauma, stress, infection, or estrogen
- Requires specialized treatment with C1 inhibitor concentrate or other targeted therapies 3
Prognosis and Follow-up
- Regular follow-up is necessary to assess treatment efficacy
- Patients with history of laryngeal involvement should be prescribed epinephrine auto-injectors
- Medical identification jewelry or wallet cards are recommended
- Airway management education is essential 1
Common Pitfalls to Avoid
- Failing to provide epinephrine auto-injectors to high-risk patients
- Continuing ACE inhibitors in patients with angioedema
- Relying solely on antihistamines for bradykinin-mediated angioedema
- Inadequate follow-up planning
- Misdiagnosing abdominal angioedema as other causes of acute abdomen 1