From the Guidelines
Isolated angioedema is caused by several distinct mechanisms, including hereditary angioedema due to C1-inhibitor deficiency or dysfunction, acquired angioedema, allergic reactions, and idiopathic angioedema, with the most recent evidence suggesting that hereditary angioedema results from mutations in the C1INH gene, leading to unregulated bradykinin production 1.
Causes of Isolated Angioedema
The causes of isolated angioedema can be broadly categorized into:
- Hereditary angioedema, which results from C1 esterase inhibitor deficiency or dysfunction, leading to unregulated bradykinin production 1
- Acquired angioedema, which can develop from autoimmune disorders, lymphoproliferative diseases, or certain cancers that affect complement pathways 1
- Allergic reactions to foods, medications, and environmental allergens 1
- Idiopathic angioedema, which occurs without identifiable triggers 1
- Physical factors like pressure, vibration, temperature changes, and UV radiation can trigger angioedema in some individuals 1
- Infections, particularly viral infections like hepatitis, can also cause angioedema through immune system activation 1
- Hormonal fluctuations, especially estrogen changes during menstruation or pregnancy, may exacerbate angioedema in susceptible individuals 1
- Stress and emotional factors can trigger or worsen episodes through unclear mechanisms involving mast cell activation 1
Diagnosis and Treatment
Diagnosis of isolated angioedema involves identifying the underlying cause, with options ranging from laboratory tests to assess C1INH levels and function, to physical examination and medical history 1. Treatment depends on identifying and addressing the specific cause, with options ranging from antihistamines for allergic reactions to C1 inhibitor replacement for hereditary forms 1.
Recent Evidence
The most recent evidence suggests that hereditary angioedema results from mutations in the C1INH gene, leading to unregulated bradykinin production, and that acquired angioedema can develop from autoimmune disorders, lymphoproliferative diseases, or certain cancers that affect complement pathways 1. In summary, isolated angioedema is a complex condition with multiple causes, and diagnosis and treatment should be guided by the most recent evidence, with a focus on identifying and addressing the underlying cause 1.
From the Research
Causes of Isolated Angioedema
The causes of isolated angioedema can be broadly categorized into several types, including:
- Mast cell-mediated angioedema, which is often associated with histamine release and may be accompanied by urticaria or other symptoms of type I hypersensitivity reactions 2
- Bradykinin-mediated angioedema, which can be hereditary, acquired, or drug-induced, such as with angiotensin-converting enzyme (ACE) inhibitors 3, 4, 5
- Idiopathic angioedema, which has an unknown mechanism and can be challenging to diagnose and treat 2
Bradykinin-Mediated Angioedema
Bradykinin-mediated angioedema is a significant cause of isolated angioedema and can be further divided into:
- Hereditary angioedema (HAE), which is an autosomal dominant disorder characterized by a deficiency of functional C1 esterase inhibitor (C1-INH) 3, 6
- Acquired angioedema (AAE), which is caused by either consumption or inactivation of C1-INH 6
- Drug-induced angioedema, which can be caused by medications such as ACE inhibitors, and is often associated with elevated bradykinin levels 5
Other Causes
Other possible causes of isolated angioedema include: