Hereditary Angioedema (HAE) is a rare, potentially life-threatening autosomal dominant genetic condition affecting approximately 1: 30 000 people.

Many doctors are not familiar with the symptoms, which often mimic those of allergies. Because HAE is extremely rare, patients may go undiagnosed or misdiagnosed for many years. Left untreated, the disorder places strain on patients, often restricting their ability to lead normal lives.

What causes HAE?

Approximately 85% of patients have a lack of C1-inhibitor protein or dysfunctional C1-inhibitor protein. It is less commonly seen in people who have normal and functional levels of C1-INH.

There are three types of HAE:

• Type I is the most common form of the disease, characterised by low levels of C1-inhibitor and affects about 85% of patients.
• Type II HAE patients have normal or elevated levels of C1-INH, but abnormal functional levels.
• Type III (or HAE with normal C1 INH) is a very rare form not due to deficiency of C1-INH. They represent a small subset of patients and mainly affects females and is exacerbated by high oestrogen levels.

Swelling from HAE is caused by an over-production of the enzyme bradykinin, which causes the blood vessels to leak fluid into the surrounding tissues.  This leads to the fluid build-up (oedema) and the swelling that people with HAE experience. This is an important differentiating feature of HAE when compared with allergic reactions, which are primarily mediated by histamine.

Symptoms

Patients experience recurrent episodes of swelling, progressing over 12 to 36 hours and lasting between 2-5 days, with some patients experiencing attacks that last over a week.

Symptoms such as unusual fatigue, mood changes and muscle aches are commonly reported before attacks. Approximately 25% of HAE patients experience a non-itching red rash or tingling feeling before an attack. The frequency and severity of attacks varies between patients and development of oedema does not follow a typical pattern.
Patients with HAE may suffer excruciating abdominal pain, nausea, and vomiting caused by swelling in the intestinal wall. Swelling of the airway or throat can cause death by asphyxiation.

Swelling can occur almost anywhere on the body, including:

1. Hands
2. Abdomen
3. Feet
4. Genitalia
5. Face
6. Airway

Diagnosing HAE

Most cases of angioedema or swelling are not HAE.

HAE can be difficult to diagnose particularly in patients where there is no family history or who only experience abdominal attacks.

There are three specific blood tests used to confirm HAE Type I or II:

• C1-Inhibitor quantitative (antigenic)
• C1-Inhibitor functional
• C4

Genetic testing may be used to confirm diagnosis, particularly in patients with no family or those patients with normal C1-INH.

Treating HAE

Swelling from HAE is not the same as swelling due to allergies and cannot be treated as an allergic reaction. Medications such as epinephrine, antihistamines, or corticosteroids are not effective in treating HAE symptoms.
Attacks can be managed through a combination of avoiding triggers, taking long-term prophylaxis as well as the treatment of acute attacks. The aim of acute treatment is to halt the progression and alleviate the symptoms of swelling, particularly for attacks affecting the airway. Short-term preventative therapy is recommended for patients undergoing surgery or dental procedures.

Preventative treatments include Danogen, an attenuated androgen which can reduce the number of attacks, and tranexamic acid, an antifibrinolytic drug which may be used as alternative to androgens.

Acute treatments currently available include Firazyr (Icatibant) a bradykinin B2 receptor antagonist indicated for treatment of acute attacks in patients from two years and older. Firazyr is delivered by subcutaneous injection and may be self-administered. Fresh-Frozen Plasma (FFP) may be given as an intravenous infusion in hospital.

Finding support

HAE S.A is a non-profit advocacy group for patients with HAE and their families, dedicated to establishing a strong, knowledgeable physician network across the country and empowering patients as well as the medical community through education about the condition, as well as providing emotional and personal support for patients and caregivers.
The Sinovuyo Virtual Angioedema Centre is a virtual and online cloud-based platform. The specialist team at the virtual centre offers advice and support for patients with hereditary and other forms of angioedema; their families and carers; medical practitioners; as well as nurses caring for angioedema patients.

The South African Angioedema Hotline – 082 091 5684 allows doctors and patients around South Africa direct access to angioedema specialists when they are managing angioedema cases.