Hereditary Angioedema (HAE)
Hereditary angioedema (HAE) is a rare inherited condition that causes recurrent episodes of severe swelling (angioedema).
Overview
Hereditary angioedema (HAE) is a rare inherited condition that causes recurrent episodes of severe swelling (angioedema). The swelling can affect different parts of the body, including the hands, feet, face, abdomen and airways. Unlike common allergic swelling, HAE is not caused by allergy and does not usually cause itching or hives. Swelling episodes can be painful and, if they affect the throat, may become life-threatening. Symptoms often begin in childhood or adolescence and can vary in frequency and severity.
Causes and Genetics
Most cases of hereditary angioedema are caused by changes (mutations) in the SERPING1 gene. This gene provides instructions for making a protein called C1 inhibitor, which helps regulate inflammation and swelling in the body. When C1 inhibitor levels are low or the protein does not function properly, a substance called bradykinin increases. Bradykinin causes blood vessels to become leaky, leading to swelling. HAE is inherited in an autosomal dominant pattern, meaning a person only needs one altered copy of the gene to have the condition. An affected individual has a 50% chance of passing the condition to each child.
Symptoms and Features
Symptoms occur in episodes (attacks) that can last several hours to several days. Triggers may include stress, minor injury, infection, dental procedures or hormonal changes, although attacks can occur without a clear trigger.
Characteristic Symptoms and Features
- Skin swelling: non-itchy swelling of the hands, feet, arms, legs or face. The skin may feel tight or painful
- Abdominal attacks: severe abdominal pain, nausea, vomiting and diarrhoea due to swelling in the bowel wall. These attacks can mimic a surgical emergency
- Airway swelling: swelling of the throat or tongue can cause difficulty swallowing, voice changes or breathing difficulty. This is a medical emergency and requires urgent treatment
Other Associated Symptoms and Features
- Swelling of the genital area
- Fatigue before or after an attack
- A non-itchy skin rash (in some individuals) before swelling begins
The frequency of attacks varies widely. Some individuals have frequent episodes, while others have only occasional attacks.
Treatment
People with HAE are advised to carry emergency medication where appropriate, inform healthcare professionals before surgical or dental procedures, and avoid known triggers if possible. Patients are usually managed through specialist immunology or rare disease centres. With modern treatments, most individuals are able to lead active lives.
Research and Future Directions
Research has led to major advances in targeted therapies that block bradykinin or replace C1 inhibitor. New long-acting treatments are improving convenience and reducing attack frequency. Studies are ongoing to develop oral treatments and explore gene-based therapies. Improved awareness and earlier diagnosis continue to improve safety and quality of life for people living with hereditary angioedema.