Hereditary angioedema

Hereditary angioedema
Synonyms	Hereditary angioneurotic edema (HANE), familial angioneurotic edema<
Pronounce	N/A
Field	Hematology
Symptoms	Recurrent attacks of severe swelling
Complications
Onset	Childhood
Duration	Attacks last a few days
Types	Type I, II, III
Causes	Genetic disorder (autosomal dominant)
Risks
Diagnosis	Measuring C4 and C1-inhibitor levels.
Differential diagnosis	Intestinal obstruction, other types of angioedema
Prevention	C1 inhibitor
Treatment	Supportive care, medications
Medication	C1 inhibitor, ecallantide, icatibant
Prognosis	25% risk of death if airway involved (without treatment)
Frequency	~1 in 50,000
Deaths

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of severe swelling (angioedema). The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. It is caused by a deficiency or dysfunction of the C1 inhibitor protein, which is part of the complement system.

Pathophysiology

Hereditary angioedema is primarily caused by mutations in the SERPING1 gene, which encodes the C1 inhibitor protein. This protein is crucial for regulating the complement system, coagulation, and fibrinolytic system. In HAE, the deficiency or dysfunction of C1 inhibitor leads to uncontrolled activation of these systems, resulting in the overproduction of bradykinin, a peptide that increases vascular permeability and causes swelling.

Types

There are three main types of hereditary angioedema:

• Type I HAE: Characterized by low levels of C1 inhibitor. It accounts for approximately 85% of cases.
• Type II HAE: Characterized by normal levels of C1 inhibitor, but the protein is dysfunctional. This type accounts for about 15% of cases.
• Type III HAE: A rare form that is not associated with C1 inhibitor deficiency or dysfunction. It is often linked to mutations in the F12 gene and primarily affects females.

Symptoms

The symptoms of hereditary angioedema include:

• Recurrent episodes of swelling in various parts of the body, including the extremities, face, and genitals.
• Abdominal pain, nausea, and vomiting due to swelling in the intestinal tract.
• Airway swelling, which can lead to life-threatening respiratory obstruction.

Diagnosis

Diagnosis of hereditary angioedema is based on clinical evaluation, family history, and laboratory tests. Key diagnostic tests include:

• Measurement of C1 inhibitor levels and function.
• Complement component 4 (C4) levels, which are typically low during attacks.
• Genetic testing to identify mutations in the SERPING1 or F12 genes.

Treatment

Management of hereditary angioedema involves both acute treatment of attacks and long-term prophylaxis. Treatment options include:

• C1 inhibitor concentrates: Used to treat acute attacks and for prophylaxis.
• Bradykinin receptor antagonists: Such as icatibant, used to treat acute attacks.
• Kallikrein inhibitors: Such as ecallantide, used to treat acute attacks.
• Androgens: Such as danazol, used for long-term prophylaxis in some patients.

Prognosis

With appropriate treatment, individuals with hereditary angioedema can lead normal lives. However, untreated airway attacks can be life-threatening. Regular monitoring and a personalized treatment plan are essential for managing the condition.

Related pages

• Angioedema
• Complement system
• Bradykinin