Hereditary angioedema
| Hereditary angioedema (HAE) | |
|---|---|
| Other names | Hereditary angioneurotic edema (HANE), familial angioneurotic edema |
| Swollen right hand during a hereditary angioedema attack. | |
| Specialty | Hematology |
| Symptoms | Recurrent attacks of severe swelling |
| Usual onset | Childhood |
| Duration | Attacks last a few days (without treatment) |
| Types | Type I, II, III |
| Causes | Genetic disorder (autosomal dominant) |
| Diagnostic method | Measuring C4 and C1-inhibitor levels. |
| Differential diagnosis | Intestinal obstruction, other types of angioedema |
| Prevention | plasma kallikrein inhibitors, C1 inhibitor concentrates |
| Treatment | Supportive care, medications |
| Medication | C1 inhibitor, ecallantide, icatibant, sebetralstat |
| Prognosis | 25% risk of death if airway involved (without treatment) |
| Frequency | ~1 in 50,000 |
Hereditary angioedema (HAE) is a rare disease that results in recurrent attacks of severe swelling. HAE affects approximately 1 in 50,000 people. The condition is typically first noticed in childhood.
The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vomiting may occur. Swelling of the airway can result in its obstruction and can cause trouble breathing. Without treatment, this can cause a risk of death in about 25% of people. With treatment, outcomes are generally good. Without preventive treatment, attacks typically occur every two weeks and last for a few days.
There are three main types of HAE. Types I and II are caused by a mutation in the SERPING1 gene, which encodes the C1 inhibitor protein, and type III, now called HAE with normal C1 inhibitor (HAE-nl-C1INH). Types I and II affect females and males equally, while HAE with normal C1 inhibitor affects females more often than males.
Six known mutations are described in the literature under HAE with normal C1 inhibitor. The result is increased levels of kallikrein activity and bradykinin, which promotes swelling. The condition may be inherited in an autosomal dominant manner or occur as a spontaneous mutation.
Known common HAE triggers are:
- Stress
- Minor trauma
- Anxiety
- Surgery
- Ailments such as colds/flu/other viral infections
People with HAE have also reported exposure to cold and activities that cause mechanical trauma (gardening, hammering, shoveling) can also be triggers. Attacks can often occur without any obvious preceding events or a known trigger.
Diagnosis of HAE types I and II is based on measurement of C4 and C1-inhibitor levels or genetic testing.
Management of HAE involves efforts to prevent attacks and the treatment of attacks if they occur. During an attack, supportive care such as intravenous fluids and airway support may be required. Preventative treatments include C1-inhibitor concentrates and plasma kallikrein inhibitors. Acute treatment options include C1-inhibitor concentrates, bradykinin receptor antagonists like icatibant, and plasma kallikrein inhibitors such as ecallantide and sebetralstat.
The condition was first described in 1888 by Canadian physician William Osler.