Angioedema: Understanding, Diagnosis, and Management

Angioedema is a condition characterized by rapid swelling of the deeper layers of the skin and mucous membranes. This swelling can affect various body parts, including the face, lips, throat, and extremities. Angioedema can be life-threatening if it leads to airway obstruction. It can be classified into different types based on its underlying cause and mechanism.

Types of Angioedema

Angioedema can be broadly categorized into the following types:

  • Allergic Angioedema: Triggered by allergens such as food, insect stings, or medications. It is often associated with other allergic reactions like urticaria (hives).

  • Hereditary Angioedema (HAE): A rare genetic disorder caused by mutations in the C1 inhibitor (C1-INH) gene, leading to recurrent episodes of severe swelling.

  • Acquired Angioedema: Can occur due to autoimmune conditions, malignancies, or medications, particularly angiotensin-converting enzyme inhibitors (ACE inhibitors).

  • Idiopathic Angioedema: Occurs without a known cause and is diagnosed when other types have been ruled out.

Pathophysiology

The pathophysiology of angioedema varies depending on the type:

  • Allergic Angioedema: Involves the release of histamines and other mediators from mast cells and basophils in response to allergens. This leads to increased vascular permeability and fluid leakage into tissues.

  • Hereditary and Acquired Angioedema: Caused by a deficiency or dysfunction of C1-INH, leading to unregulated activation of the complement and contact system pathways. This results in the overproduction of bradykinin, a potent vasodilator, causing increased vascular permeability and swelling.

  • Drug-Induced Angioedema: Particularly associated with ACE inhibitors, which block the degradation of bradykinin, leading to its accumulation and subsequent angioedema.

Symptoms

The symptoms of angioedema include:

  • Swelling of the face, lips, tongue, throat, hands, and feet.

  • Abdominal pain, nausea, and vomiting (particularly in HAE).

  • Difficulty breathing and swallowing if the throat or airways are involved.

  • Sudden onset of swelling, which can be painful and disfiguring.

Diagnosis

Diagnosing angioedema involves a thorough medical history, physical examination, and specific laboratory tests:

1. Medical History and Physical Examination: Assessing the timing, frequency, triggers, and associated symptoms of swelling.

2. Blood Tests:

  • C4 Levels: Often low in cases of HAE and some forms of acquired angioedema.

  • C1-INH Levels and Function: To diagnose HAE or acquired C1-INH deficiency.

  • Tryptase Levels: To assess for mast cell activation in allergic angioedema.

3. Genetic Testing: For confirming HAE by identifying mutations in the SERPING1 gene encoding C1-INH.

4. Challenge Tests: In suspected drug-induced angioedema, discontinuing the suspected drug and observing for improvement.

Management and Treatment

The management of angioedema depends on its type and severity:

1. Acute Management:

  • Allergic Angioedema: Antihistamines, corticosteroids, and epinephrine for severe cases.

  • Hereditary and Acquired Angioedema: C1-INH concentrates, bradykinin receptor antagonists (e.g., icatibant), and kallikrein inhibitors (e.g., ecallantide).

2. Long-Term Management:

  • Avoidance of Triggers: Identifying and avoiding known triggers, particularly in allergic and drug-induced angioedema.

  • Prophylactic Treatment:

  • HAE: Long-term prophylaxis with C1-INH concentrates, androgens (e.g., danazol), or antifibrinolytics (e.g., tranexamic acid).

  • Idiopathic Angioedema: Ongoing antihistamine therapy to prevent attacks.

3. Patient Education:

  • Self-Administration of Medication: Training patients with HAE on self-administration of acute treatments.

  • Emergency Action Plan: Ensuring patients have an action plan in case of severe attacks, including access to emergency medical services.

Prognosis

The prognosis for patients with angioedema varies based on the underlying cause and the effectiveness of management strategies. With appropriate treatment and avoidance of triggers, many patients can lead normal lives. However, recurrent and severe episodes, particularly those affecting the airways, can pose significant risks and require ongoing medical supervision.

Conclusion

Angioedema is a multifaceted condition requiring a nuanced approach to diagnosis and management. Understanding the underlying mechanisms and triggers is crucial for effective treatment and improving patient outcomes. Advances in therapeutic options have significantly enhanced the quality of life for individuals affected by this condition.

Editorial History

Written By:

Nikita Kewalramani

Reviewed By:

Dr. Sachin Kadoo

MBBS, MD.

Last updated: Aug 2, 2024

References:

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  2. Farkas, H., Varga, L., Szeplaki, G., Visy, B., Harmat, G., & Bowen, T. (2007). Management of hereditary angioedema in pediatric patients. Pediatrics, 120(3), e713-e722. https://doi.org/10.1542/peds.2007-0127

  3. Kaplan, A. P. (2017). Angioedema. World Allergy Organization Journal, 10(1), 29. https://doi.org/10.1186/s40413-017-0161-6

  4. Longhurst, H. J., & Bork, K. (2019). Hereditary angioedema: Causes, manifestations and treatment. British Journal of Hospital Medicine, 80(7), 391-398. https://doi.org/10.12968/hmed.2019.80.7.391

  5. Zuraw, B. L., & Christiansen, S. C. (2016). Pathophysiology of hereditary angioedema. American Journal of Rhinology & Allergy, 30(1), 9-13. https://doi.org/10.2500/ajra.2016.30.4264