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Angioedema: Causes, Symptoms and Treatment

Angioedema is a sudden, deep swelling of the skin and mucous membranes, often affecting the face, lips, or throat. It can be allergic, hereditary, or medication-induced.

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Things worth knowing about "Angioedema"

Angioedema is a sudden, deep swelling of the skin and mucous membranes, often affecting the face, lips, or throat. It can be allergic, hereditary, or medication-induced.

What is Angioedema?

Angioedema (also known as Quincke edema or angioneurotic edema) is a rapid, deep-tissue swelling occurring in the subcutaneous tissue and mucous membranes. Unlike urticaria (hives), which affects the surface layers of the skin, angioedema develops in deeper tissues. While it can be mild and self-limiting, it may also be life-threatening, especially when the larynx or airways are involved.

Causes and Types

Angioedema is classified into several types based on its underlying cause:

Allergic angioedema: Triggered by an allergic reaction to foods, medications, insect stings, or other allergens. It often occurs alongside urticaria.
Hereditary angioedema (HAE): A rare genetic condition caused by a deficiency or dysfunction of the C1-inhibitor protein, leading to recurrent swelling episodes.
Drug-induced angioedema: Most commonly associated with ACE inhibitors used to treat high blood pressure. Non-steroidal anti-inflammatory drugs (NSAIDs) may also be triggers.
Idiopathic angioedema: In some patients, no identifiable cause can be found.

Symptoms

Typical signs and symptoms of angioedema include:

Sudden, doughy swellings, most commonly affecting the face (lips, eyelids, tongue, cheeks)
Swelling of the throat and neck, which can cause difficulty swallowing or breathing
Swelling of the hands, feet, or genitalia
Abdominal pain, nausea, and vomiting (when the intestinal mucosa is involved, particularly in hereditary angioedema)
Itching or burning of affected areas (more typical in the allergic form)

In severe allergic cases, angioedema can be accompanied by anaphylactic shock, a life-threatening emergency requiring immediate medical attention.

Diagnosis

Diagnosis is based on a thorough medical history and physical examination. Depending on the suspected cause, the following investigations may be performed:

Blood tests: Measurement of C1-inhibitor levels and activity, C3 and C4 complement levels (if hereditary angioedema is suspected)
Allergy testing: Skin prick tests and specific IgE antibody levels (if an allergic cause is suspected)
Medication review: Assessment of current medications, particularly ACE inhibitors
Imaging studies (ultrasound, CT scan) in cases of unexplained abdominal pain

Treatment

Acute Management

In acute cases, securing the airway is the immediate priority. Treatment depends on the underlying type:

Allergic angioedema: Antihistamines, corticosteroids, and epinephrine (adrenaline) as emergency medication. Patients with a known severe allergy should carry an epinephrine auto-injector at all times.
Hereditary angioedema: Specific treatments include C1-inhibitor concentrate, icatibant (a bradykinin receptor antagonist), or ecallantid (a kallikrein inhibitor).
ACE inhibitor-induced angioedema: Immediate discontinuation of the causative drug; supportive care in severe cases.

Long-term Therapy and Prophylaxis

For hereditary angioedema, long-term prophylaxis options include lanadelumab (a monoclonal antibody) and berotralstat. For allergic angioedema, strict allergen avoidance is essential.

When to Seek Medical Help

If sudden swelling occurs in the face, mouth, or throat area, or if breathing or swallowing difficulties develop, emergency services (911 or 112) should be contacted immediately. These symptoms may indicate a life-threatening situation.

References

Magerl M. et al. - Guideline on Angioedema, AWMF Register No. 013-028, German Dermatological Society (2021).
Cicardi M. et al. - Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency. Allergy, 67(2), 147-157 (2012).
Zuraw B.L. - Clinical practice: Hereditary angioedema. New England Journal of Medicine, 359(10), 1027-1036 (2008).

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