From the Guidelines
Angioedema is primarily caused by hereditary factors, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme (ACE) inhibitor-associated mechanisms.
Causes of Angioedema
- Hereditary Angioedema (HAE): Caused by a deficiency of the serine protease inhibitor C1 inhibitor (C1INH) due to mutations in the C1INH gene, resulting in a C1INH functional deficiency 1. HAE is an autosomal dominant disease, and most patients have a positive family history of angioedema 1.
- Acquired C1 Inhibitor Deficiency: Results from enhanced catabolism of C1INH, which might be associated with C1INH autoantibodies, with or without an underlying condition such as lymphoma 1.
- Angiotensin-Converting Enzyme (ACE) Inhibitor-Associated Angioedema: Occurs in approximately 0.1% to 0.7% of patients taking ACE inhibitors, likely due to impaired degradation of bioactive peptides such as bradykinin 1.
Other Factors
- Bradykinin Signaling: Increased bradykinin signaling can cause HAE with normal C1INH levels 1.
- Estrogen Therapy: Estrogen therapy can increase the frequency and severity of HAE attacks, particularly in patients with HAE and normal C1INH levels 1.
- Stress and Trauma: Recognized as precipitants of HAE attacks 1.
- Pregnancy: Can be associated with an increase in the frequency and severity of HAE episodes 1.
From the Research
Causes of Angioedema
The causes of angioedema can be classified into several categories, including:
- Hereditary causes: Hereditary angioedema is a rare form of angioedema that can be diagnosed by screening with a C4 level 2
- Acquired causes: Acquired angioedema can be caused by various factors, including allergic reactions and drug intake, such as angiotensin-converting-enzyme inhibitors and NSAIDs 3, 4
- Iatrogenic causes: Iatrogenic angioedema can be caused by medical treatments, such as the use of ACE inhibitors 3, 4
- Idiopathic causes: In some cases, the cause of angioedema may not be identified 4
Pathophysiological Causes
Angioedema can be divided into two pathophysiological forms:
- Histaminergic angioedema: This form is characterized by the release of histamine and is often associated with allergic reactions and urticaria 3, 4
- Non-histaminergic angioedema: This form is characterized by the release of bradykinin and is often associated with hereditary angioedema and ACE inhibitor-induced angioedema 3, 4
Common Triggers
Common triggers of angioedema include: