What is Angioedema?

From the Guidelines

Angioedema is a condition characterized by recurrent episodes of non-pruritic, non-pitting swelling of the skin and mucous membranes, often involving the extremities, abdomen, genitourinary tract, face, oropharynx, or larynx.

Key Features of Angioedema

• Angioedema results from increased vascular permeability, with leakage of plasma into the superficial skin or deeper skin layers 1
• The swelling is always episodic and not continuous daily swelling, with a typical attack worsening over 24 hours and then slowly remitting over the following 48 to 72 hours 1
• Disease severity is highly variable, both between patients and within a single patient over time, with some patients experiencing frequent attacks and others experiencing few or no attacks 1

Types of Angioedema

• Hereditary Angioedema (HAE): a rare genetic disorder caused by a deficiency of the serine protease inhibitor C1 inhibitor (C1INH), characterized by recurrent episodes of skin and mucosal edema 1
• Acquired C1 Inhibitor Deficiency: a condition characterized by a deficiency of C1INH, often associated with lymphoproliferative disorders or autoimmune diseases 1
• Angiotensin-Converting Enzyme (ACE) Inhibitor-Associated Angioedema: a condition caused by the use of ACE inhibitors, characterized by recurrent episodes of angioedema without urticaria, often involving the face and tongue 1

Diagnosis and Treatment

• Diagnosis of angioedema involves a combination of clinical evaluation, laboratory tests (such as C4 and C1INH levels), and exclusion of other conditions 1
• Treatment of angioedema depends on the underlying cause, with options including C1INH replacement, bradykinin B2 receptor antagonists, and other medications 1
• Access to treatment is limited in low-income countries, highlighting the need for global equity and access to essential measures for the management of angioedema 1

From the Research

Definition and Characteristics of Angioedema

• Angioedema is characterized by localized swelling of subcutaneous tissues or mucosa of the upper respiratory or gastrointestinal tract 2
• It 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 3
• The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera 4

Types and Pathophysiology of Angioedema

• There are several distinct subtypes of angioedema, caused by different pathological processes involving a range of proinflammatory mediators 2
• Angioedema may be allergic or nonallergic, and the overall lifetime incidence of AE is reported to be as high as 15% 4
• Pathophysiologically, angioedemas are divided into histaminergic and non-histaminergic forms 5
• The kallikrein-kinin system plays a key role in the pathophysiology of certain types of angioedema, such as hereditary and acquired angioedema 4

Clinical Presentation and Diagnosis

• Patients present to emergency department when angioedema involves oral cavity and larynx (life-threatening conditions) or gut (mimicking an acute abdomen) 3
• Concomitant urticaria and pruritus suggest a histaminergic origin, while exposure to allergens and drugs (mainly ACE inhibitors and non steroidal anti-inflammatory drugs) should be investigated 3
• A simple approach can be applied for a correct diagnosis and treatment, including initial evaluation of consciousness and vital signs to manage breathing and to support circulation if necessary 3

Treatment and Management

• Securing the airway remains the most important intervention, followed by administration of both established and more novel pharmacologic interventions based on disease pathology 6
• Allergic angioedema is sensitive to standard therapies such as epinephrine, glucocorticoids and antihistamines, whereas non histaminergic angioedema is often resistant to these drugs 3
• Therapeutic options for angioedema due C1-inhibitor deficiencies are C1-inhibitor concentrates, icatibant and ecallantide, and fresh frozen plasma can be considered if these drugs are not available 3