What are the causes of angioedema (Angioneurotic Edema)?

From the Guidelines

Angioedema is caused by a variety of factors, including hereditary and acquired conditions, that trigger rapid swelling in the deeper layers of the skin and mucous membranes, with the most recent and highest quality study suggesting that hereditary angioedema with normal C1 inhibitor levels is a distinct form of the disease 1. The causes of angioedema can be broadly categorized into:

• Hereditary angioedema, which results from genetic mutations affecting C1 inhibitor protein, leading to uncontrolled bradykinin production 1
• Acquired angioedema, which can develop from autoimmune disorders, certain cancers, or infections that affect complement proteins 1
• Physical triggers, such as pressure, vibration, temperature changes, or UV exposure, which can induce angioedema in some individuals
• Stress and anxiety, which may worsen symptoms or trigger episodes in susceptible people
• Idiopathic angioedema, which occurs when no specific cause can be identified despite thorough evaluation
• Medications, such as ACE inhibitors, NSAIDs, and antibiotics, which can cause angioedema in some individuals 1 The most recent study on hereditary angioedema with normal C1 inhibitor levels suggests that this form of the disease is caused by increased bradykinin signaling and can be treated with specialized medications like icatibant or C1 inhibitor concentrates 1. It is essential to identify and avoid triggers to prevent angioedema episodes, and severe cases with throat swelling require immediate emergency care as they can be life-threatening 1. The management of angioedema includes on-demand treatment, short-term prophylaxis, and long-term prophylaxis, with the goal of reducing the frequency and severity of attacks and improving quality of life 1.

From the Research

Causes of Angioedema

The causes of angioedema can be classified into several categories, including:

• Hereditary angioedema, which is a rare disease inherited as an autosomal dominant trait and caused by a deficiency of C1-esterase inhibitor 2
• Acquired angioedema, which includes nonhereditary C1-esterase inhibitor deficiency, idiopathic, allergic, and drug-induced forms 2
• Drug-induced angioedema, which can be caused by medications such as:

• Angiotensin-converting enzyme inhibitors (ACEIs) 3, 4
• Angiotensin receptor blockers 3, 4
• Nonsteroidal anti-inflammatory drugs (NSAIDs) 3, 5, 6
• Fibrinolytic agents 3
• Estrogens 3
• Antihypertensive drugs other than ACE inhibitors 3
• Psychotropic drugs 3

• Other causes, such as:

• Physical stimuli 2
• Lupus erythematosus 2
• Hypereosinophilia 2

Mechanisms of Angioedema

The mechanisms of angioedema can involve:

• Histamine-mediated reactions, which are associated with urticaria and pruritus 4
• Bradykinin-mediated reactions, which are often familial (hereditary angioedema) and are more often associated with gastrointestinal symptoms and a lack of urticaria and pruritus 4
• Inhibition of the first component of the complement (C1-INH) 3
• Inhibition of cyclo-oxygenases (COX) and the resulting increase in synthesis and release of cysteinyl leukotrienes 6