WHAT IS HAE

Hereditary Angioedema is a rare, potentially life-threatening genetic condition that affects approximately 1 in 50 000 people. HAE is NOT an allergy or an allergic reaction. 

HAE patients often experience their first attack during childhood or adolescence.

HAE is characterised by angioedema (swelling) in various parts of the body. Swelling can occur almost anywhere in the body, including:

  • Hands
  • Feet
  • Abdomen
  • Genitalia
  • Face
  • Airway

Patients with HAE often 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.

Approximately 85% of patients with HAE have a genetic defect that causes a deficiency in the plasma protein C1-esterase Inhibitor (C1-INH). Some patients have normal or elevated levels of C1-inhibitor but the protein doesn’t function properly so has abnormal functional levels. It is less commonly seen in people who have normal and functional levels of C1-INH.

Without enough or properly functioning C1 inhibitor, a sequence of events occurs that results in an HAE attack. An enzyme in the blood called kallikrein becomes uncontrolled, triggering the overproduction of a peptide known as bradykinin. Excess bradykinin causes the blood vessels to leak fluid into the surrounding tissues, leading to fluid build-up 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. 

GENETICS

HAE is an autosomal dominant condition. When one parent has HAE, they will pass on either their normal gene or the affected gene to their child. Children of parents with HAE, therefore, have a 50% chance of inheriting the genetic defect. HAE does not skip generations, which means that children will only inherit it if they have a mother or father with the condition.

About 25% of cases have no family history and result from a spontaneous genetic mutation.

For the most reliable test result, children should be at least one year old for C1-Inhibitor testing.

Because HAE is extremely rare, patients often go undiagnosed or misdiagnosed for many years. Left untreated, the disorder places strain on patients, often restricting their ability to lead normal lives.

SYMPTOMS

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

Common indicators of attacks can be:

  • Unusual fatigue
  • Mood Changes
  • Rash
  • Muscle aches

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 the development of edema does not follow a typical pattern.

Reported frequency of attacks
Examples of HAE Swelling

Example of a swollen hand

Example of a stomach swell

Erythema marginatum on the arm of a patient with hereditary angioedema.

Example of a swollen foot

Before and After an HAE Attack

DIAGNOSIS

Not all cases of angioedema are HAE or C1-Inhibitor deficiency, and there are a number of other causes of angioedema.

HAE can be difficult to diagnose particularly in patients where there is no family history or who only experience abdominal attacks. If you have a family history of HAE or are experiencing these symptoms, please see a medical professional for testing. HAE South Africa have a network of doctors experienced in HAE whom we can refer you to.

Find a Physician

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

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

Types of Hereditary Angioedema

There are three types of HAE:

  • Type Iis the most common form of the disease, characterised by low levels of C1-inhibitor and affects about 85% of patients.
  • Type IIHAE patients have normal or elevated levels of C1-inhibitor, but the protein does not function properly so will have abnormal functional levels.
  • Type III(or HAE with normal C1 INH) is a very rare form not due to deficiency of C1 INH. There is limited data regarding the incidence of HAE with normal C1-Inhibitor, however, experts believe that the population represents a small subset of patients. It mainly affects females and is exacerbated by high oestrogen levels. Numerous rare genetic mutations have been described including mutations in factor XII, angiopoietin 1 and the plasminogen genes.

Find out more about the different Types of Angioedema

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TRIGGERS

While some attacks appear to be spontaneous, some of the more common causes of HAE attacks are:

  • Anxiety
  • Stress
  • Minor trauma
  • Surgery
  • Colds/flu/viral infections

Hormones 
Menstruation and pregnancy may affect HAE symptoms. Patients should consult with their HAE physician regarding alternative options to oestrogen birth control medications and hormone replacement therapy, as these have been associated with an increase in attacks.

ACE Inhibitors
ACE Inhibitors, used for the treatment of high blood-pressure, should be avoided as they have been known to increase the frequency and severity of HAE attacks.

Dental Procedures
Swelling can be caused by trauma to the mouth during dental procedures and can increase the risk of swelling in the throat or airway. Always consult with your treating physician before undergoing dental procedures.

TREATMENT

Most physicians have never seen a case of HAE and are not familiar with the disorder. Swelling in the abdomen is often misdiagnosed, and it is not uncommon for patients to undergo unnecessary surgical procedures.

Attacks can be managed through a combination of long-term prophylaxis, the treatment of acute attacks, as well as recognising triggers and avoiding them.

Acute treatment is crucial in order to stop attacks that may be life-threatening, such as airway swelling. Patients who are undergoing surgery or dental procedures should always use preventative therapy beforehand.

All patients with a diagnosis of HAE should have their physician assist them in completing a treatment plan. A Medic-Alert bracelet should be worn, and an emergency patient card should always be carried. HAE South Africa offer a patient card that can be filled in and printed out.

Download your Patient Information Card below.

Printable Emergency Card

Therapies currently available in South Africa includes:

Preventative Treatment

  • DANOGEN is an attenuated androgen that can reduce the number of attacks. Indicated for use in adults.
  • TRANEXAMIC ACID is an antifibrinolytic drug, that may be used as an alternative to androgens. Indicated for use in adults and children.

Acute Treatment

  • FRESH-FROZEN PLASMA (FFP) given as an intravenous infusion in hospital.
  • BERINERT® is a plasma-derived C1 Esterase Inhibitor indicated for the treatment of HAE attacks in adult and paediatric patients. Berinert is delivered intravenously.
    For more information visit: www.berinert.com.
  • FIRAZYR® (Icatibant) is a bradykinin B2 receptor antagonist indicated for treatment of acute attacks of HAE in patients from two years and older. Firazyr is delivered by subcutaneous injection and may be self-administered.
    For more information visit: www.firazyr.com.
  • RUCONEST® is a plasma free recombinant C1-Inhibitor concentrate for treating HAE attacks in adults and adolescents. Ruconest is delivered intravenously.
    For more information go to: www.ruconest.com.

Firazyr, Berinert and Ruconest are not currently registered for use in S.A. and can only be accessed via Section 21 approval, on a named patient basis. Please consult with your HAE physician for more information on accessing these treatments or contact HAE S.A. for more information.

For more information, please visit:
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