What is angioedema (Angioneurotic Edema)?

From the Guidelines

Angioedema is a condition characterized by relatively prolonged attacks of swelling involving the extremities, abdomen, genitourinary tract, face, oropharynx, larynx, or a combination of the above, often caused by a deficiency of the serine protease inhibitor C1 inhibitor (C1INH) and mediated by bradykinin 1.

Key Characteristics

• Angioedema can be hereditary, acquired, or associated with angiotensin-converting enzyme inhibitors, with hereditary angioedema (HAE) being an autosomal dominant disease that typically presents with a positive family history of angioedema 1.
• The primary mediator of swelling in patients with HAE is bradykinin, and the disease is characterized by episodic rather than continuous swelling, with a stereotypical pattern of worsening over 24 hours, peaking, and then slowly resolving over the following 48 hours 1.
• HAE attacks are associated with significant potential morbidity and potential mortality, and optimal management depends on early identification of patients and access to effective, on-demand HAE-specific agents 1.

Diagnosis and Treatment

• Diagnosis of HAE requires evidence of a low C1INH antigenic or functional level, as well as decreased C4 levels and generally normal C1q levels, and can be divided into two forms: type I HAE with low C1INH antigenic and functional levels, and type II HAE with normal C1INH antigenic levels but decreased C1INH functional levels 1.
• Treatment of HAE attacks can involve symptomatic treatment based on the region of body swelling, and consensus guidelines recommend that all patients with HAE should have access to an effective, on-demand HAE-specific agent, such as C1INH concentrates, a plasma kallikrein inhibitor, or a bradykinin B2 receptor antagonist 1.
• Short-term prophylaxis can be achieved by using fresh frozen plasma, C1INH replacement, or short-term, high-dose anabolic androgen therapy, and long-term prophylaxis can be achieved with low-to-moderate doses of anabolic androgens or replacement plasma-derived C1INH 1.

From the Research

Definition of Angioedema

• Angioedema is a self-limiting edema of the subcutaneous or submucosal tissues due to localized increase of microvascular permeability whose mediator may be histamine or bradykinin 2.
• It is characterized by localized swelling of sudden onset affecting the skin and/or mucous membranes 3.
• Angioedema can manifest clinically as facial edema, swelling of the extremities and urogenital area, and potential involvement of the larynx, leading to dyspnea and inspiratory stridor, which can become life-threatening 4.

Types of Angioedema

• Hereditary angioedema is a rare disease inherited as an autosomal dominant trait and caused by a deficiency of C1-esterase inhibitor 3.
• Acquired angioedema includes nonhereditary C1-esterase inhibitor deficiency; idiopathic, allergic, and drug-induced forms; angioedema associated with lupus erythematosus and hypereosinophilia; and angioedema caused by physical stimuli 3.
• Angioedema can be classified into histaminergic and non-histaminergic forms, with concomitant urticaria and pruritus suggesting a histaminergic origin 2.

Causes of Angioedema

• Angiotensin-converting enzyme inhibitors (ACEIs) are a class of medications commonly prescribed for hypertension, heart failure, and diabetic nephropathy, and are associated with an increased risk of angioedema 4.
• Other medications, such as angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, and certain antibiotics, can also cause drug-induced angioedema 4.
• Exposure to allergens and drugs should be investigated, as well as a family history of similar symptoms 2.

Treatment of Angioedema

• Allergic angioedema is sensitive to standard therapies such as epinephrine, glucocorticoids, and antihistamines, whereas non-histaminergic angioedema is often resistant to these drugs 2.
• Therapeutic options for angioedema due to C1-inhibitor deficiencies are C1-inhibitor concentrates, icatibant, and ecallantide 2.
• Fresh frozen plasma can be considered as an alternative treatment option for ACEI-induced angioedema that is refractory to conventional treatment 5.