Hereditary Angioedema (HAE) is a rare, chronic, potentially life-threatening genetic condition resulting from a deficiency in C1 Inhibitor protein. This form of angioedema is not accompanied by hives and does not respond to antihistamines, corticosteroids or adrenaline. Most patients affected by this genetic disorder experience their first attack during childhood or adolescence. HAE symptoms include episodes of swelling, usually lasting between 2-5 days, in various body parts including the hands, feet, face, genitalia, abdomen and airway. Patients often have bouts of severe abdominal pain, nausea and vomiting that is caused by swelling in the intestinal wall. Airway swelling is particularly dangerous and can lead to death by asphyxiation. Medical help should always be sought immediately in the event of any airway swelling.
What Causes HAE?
HAE patients have a defect in the gene that controls a blood protein called C1 Inhibitor. The genetic defect results in production of either inadequate or non-functioning C1-Inhibitor protein. The defective C1-Inhibitor does not perform its regulatory function of dampening the immune response, which then continues to make the blood vessels release fluids into surrounding tissue, causing oedema or swelling.
HAE is called “hereditary” because the genetic defect is passed on in families. A child has a 50% chance of inheriting this disease if one of his or her parents has it. The absence of family history does not rule out the HAE diagnosis. Many HAE cases result from a spontaneous mutation of the C1-Inhibitor gene.
HAE is a rare condition and can be difficult to diagnose because of a lack of recognition of the condition particularly in patients where there is no family history or when the patient has abdominal attacks only and no obvious outward swellings. If you have a family history of HAE or suspect these are your symptoms, the first step would be to see your family doctor and then be referred on to a specialist who deals with HAE. Once the diagnosis is considered then it can be confirmed simply with a blood test : a screening test for C4 (complement protein in the blood) is usually done initially and if abnormal, more specific tests measuring C1-inhibitor quantitative (antigenic) and C1- inhibitor functional levels (not available in South africa) are performed.
The most common form of the disease–Type I–is characterised by low quantitative levels of C1-inhibitor and affects about 85% of patients with HAE.
Type II HAE patients have normal or elevated levels of C1-inhibitor, but the protein does not function properly so will have abnormal functional levels.
Type III (HAE with normal C1 inhibitor levels) is a very rare form not due to deficiency of C1 INH. It mainly affects females and is worsened by high oestrogen levels. It is becoming clear that there are rare families who have a variety of genetic defects in the complement, contact and coagulation pathways that lead to a similar presentation to classical HAE.
All patients with a diagnosis of HAE should have a HAE card with their personal information, diagnosis and their treating doctor’s contact details.
The management of HAE consists of avoiding attack triggers, and treatment of acute attacks as well as long and short term prevention therapy as suitable for individual patients. Options are best discussed with your treating physician.
The aim of acute treatment is to halt the progression of the oedema and alleviate the symptoms. This applies particularly to episodes affecting the airways, which can cause death by suffocation.
Icatibant is an injection given under the skin(subcutaneous) and is usually self -administered, after training; is the commonest and most convenient medication used for ‘on demand’ treatment of acute attacks from 2 years and older.
C1 INH concentrate (Berinert®) administered intravenously by a health professional in a hospital/clinic or by an individual after adequate training. This is used for acute treatment in pregnant and breast feeding women and in those who do not respond to icatibant.
Recombinant C1 esterase inhibitor concentrate (Ruconest/ Konestat alpha) is administered intravenously by a health professional in a hospital or clinic.
Fresh frozen or freeze-dried plasma is a plasma-derived source of C1 sterase inhibitor. It is given intravenously by a health professional in a hospital or clinic for acute attacks if other medications are not available.
Preventive (prophylactic) Treatments
Short-term preventative therapy with recombinant C1 esterase inhibitor concentrate is recommended for patients undergoing surgery or dental procedures which have been known to trigger an attack.
Oral prophylaxis options include:
Tranexamic acid -an antifibrinolytic drug. It is not commonly used but may be used in paediatric practice for children who have frequent attacks when no other treatment is available to them. It may be useful for some adult patients.
Danazol is an androgen. It can reduce the number of attacks. It does have a number of potential side effects, necessitating monitoring.