Hereditary angioedema
| Hereditary angioedema (HAE) | |
|---|---|
| Other names | Hereditary angioneurotic edema (HANE),[1] familial angioneurotic edema[2] |
| Swollen right hand during a hereditary angioedema attack. | |
| Specialty | Hematology |
| Symptoms | Recurrent attacks of severe swelling[3] |
| Usual onset | Childhood[3] |
| Duration | Attacks last a few days (without treatment)[3] |
| Types | Type I, II, III[3] |
| Causes | Genetic disorder (autosomal dominant)[3] |
| Diagnostic method | Measuring C4 and C1-inhibitor levels.[2] |
| Differential diagnosis | Intestinal obstruction, other types of angioedema[2] |
| Prevention | plasma kallikrein inhibitors, C1 inhibitor concentrates[1] |
| Treatment | Supportive care, medications[1] |
| Medication | C1 inhibitor, ecallantide, icatibant, sebetralstat[1] |
| Prognosis | 25% risk of death if airway involved (without treatment)[2] |
| Frequency | ~1 in 50,000[3] |
Hereditary angioedema (HAE) is a rare disease that results in recurrent attacks of severe swelling.[3] HAE affects approximately 1 in 50,000 people.[3] The condition is typically first noticed in childhood.[3]
The swelling most commonly affects the arms, legs, face, intestinal tract, and airway.[3] If the intestinal tract is affected, abdominal pain and vomiting may occur.[1] Swelling of the airway can result in its obstruction and can cause trouble breathing.[1] Without treatment, this can cause a risk of death in about 25% of people.[2] With treatment, outcomes are generally good.[2] Without preventive treatment, attacks typically occur every two weeks and last for a few days.[3]
There are three main types of HAE.[3] 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).[4] Types I and II affect females and males equally,[5] while HAE with normal C1 inhibitor affects females more often than males.[2]
Six known mutations are described in the literature under HAE with normal C1 inhibitor.[4] The result is increased levels of kallikrein activity and bradykinin, which promotes swelling.[3] The condition may be inherited in an autosomal dominant manner or occur as a spontaneous mutation.[3]
Known common HAE triggers are[6]:
- 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.[7] Attacks can often occur without any obvious preceding events or a known trigger.[3]
Diagnosis of HAE types I and II is based on measurement of C4 and C1-inhibitor levels or genetic testing.[8]
Management of HAE involves efforts to prevent attacks and the treatment of attacks if they occur.[1] During an attack, supportive care such as intravenous fluids and airway support may be required.[1] Preventative treatments include C1-inhibitor concentrates and plasma kallikrein inhibitors.[1] Acute treatment options include C1-inhibitor concentrates, bradykinin receptor antagonists like icatibant, and plasma kallikrein inhibitors such as ecallantide and sebetralstat.[9]
The condition was first described in 1888 by Canadian physician William Osler.[10]
- ^ a b c d e f g h i "Hereditary angioedema". GARD. 2017. Archived from the original on 4 July 2017. Retrieved 10 July 2017.
- ^ a b c d e f g "Orphanet: Hereditary angioedema". www.orpha.net. August 2011. Archived from the original on 9 October 2015. Retrieved 10 July 2017.
- ^ a b c d e f g h i j k l m n o Reference GH (5 July 2017). "hereditary angioedema". Genetics Home Reference. Archived from the original on 10 July 2017. Retrieved 10 July 2017.
- ^ a b Smith TD, Riedl MA (October 2024). "The future of therapeutic options for hereditary angioedema". Annals of Allergy, Asthma & Immunology. 133 (4): 380–390. doi:10.1016/j.anai.2024.04.029. PMID 38679158.
- ^ "Hereditary Angioedema - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). 2008. Archived from the original on 14 July 2017. Retrieved 10 July 2017.
- ^ "US Hereditary Angioedema Association". www.haea.org. Retrieved 24 July 2025.
- ^ "Attack Triggers". HAE International (HAEi). 4 July 2022. Retrieved 24 July 2025.
- ^ "Diagnosis". HAE International (HAEi). 16 April 2015. Retrieved 24 July 2025.
- ^ "How can HAE be treated?". HAE International (HAEi). 4 March 2022. Retrieved 24 July 2025.
- ^ Levin AV, Enzenauer RW (2017). The Eye in Pediatric Systemic Disease. Springer. p. 71. ISBN 9783319183893. Archived from the original on 10 September 2017.