Living with Hereditary Angioedema

Ann Price recalls her family's experience of hereditary angioedema over four generations:

The story of hereditary angioedema in our family is a very positive one. Although it started with much ignorance, fear, pain and mismanagement, we now understand the disorder and have confidence and enough control over the situation to live full and active lives. We hope that in the future, with the advances in gene therapy, the prospects will be still brighter. I have told our story to encourage those who have had to struggle - and perhaps continue to struggle - with many years of misdiagnosis and inadequate treatment.

Let me start by introducing our family as we are today. I am a 52-year-old part-time nurse. My husband John, also 52, is a health and safety specialist. We have three children: Helen, who is 24 and has just qualified as a doctor, David who is 23 and studying medicine, and Edward, aged 13.

My own symptoms first occurred when I started taking the contraceptive pill at the age of 23. I immediately experienced severe bouts of gross oedema about once a week, involving arms, legs, face and gut. It was very frightening. Only at this stage was I told the family history of this weird condition. My grandfather had HAE severely over many years and he died at the age of 39. My father suffered severely until he was 30, when his symptoms suddenly ceased, never to return. Several aunts and uncles were affected. My mother regarded the condition as "all down to nerves" and "peculiar and all in the mind". My doctor prescribed massive doses of antihistamines, to no effect.

My symptoms continued, but gradually decreased over the next few years. Doctors were emphatic that there was no connection with the pill, but when I discontinued it the oedema stopped completely.

When I became pregnant with my first child, Helen, I had regular oedema from four months, but all symptoms ceased after her birth. The same pattern occurred during my second and third pregnancies, although the symptoms were more severe. However, between the pregnancies I was free of symptoms.

Our third son, Andrew, appeared to be a very bonny, healthy baby, but our lives were devastated when he tragically died in infancy.

It was at this time that my GP spent an afternoon researching into HAE at the postgraduate medical library on our behalf. Subsequent blood tests revealed that Helen and David were, like me, deficient in a susbtance in our blood called C1-inhibitor (C1INH). However, they were symptom-free at the time. Because of these diagnoses I was determined to find some answers. As a nurse I had access to medical literature and our GPs were supremely helpful. We found a specialist consultant in London. Gradually over the next few years more information and treatment became available.

Two years after Andrew, we had Edward, who also has HAE.

In l983 C1INH was being produced in Holland and towards the end of my pregnancy with Edward I was the first patient in this country to have C1INH injections. It was like a miracle. What had been a three-day session of very acute abdominal pain, vomiting and diarrhoea was relieved within an hour of the injection.

The availability of C1INH has been the central factor in transforming the lives of our family.

Without treatment, for instance, Helen would not have been able to manage a career and she would have experienced a lot of severe pain and distress. Her symptoms had increased in severity since the age of 14. She suffered severe incapacitating abdominal symptoms for three days out of every seven to ten days. At first she was given high doses of Danazol, but the androgenic properties of this were prohibitive. Her periods became very erratic, her appetite and weight increased, she developed facial hair and her voice deepened considerably.

She is now controlled by self-injecting two vials of ClINH intravenously as soon as abdominal or throat symptoms develop. Thanks to this replacement therapy Helen has been able to qualify as a doctor. She now lives a normal and happy life and has travelled all over the world.

David developed problems in adolescence, but his condition appears to be less marked and he is maintained relatively symptom-free on small daily doses of Danazol. He always keeps C1INH available in case of severe symptoms or laryngeal emergencies.

Edward has the deficiency but is at present without symptoms. However, we always have our safety net, in the form of C1INH, at the ready.

The main points of our management at present are:

Because of the small risk attached to blood products we still look forward to the day when gene therapy will provide an actual cure for our condition.

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Hereditary Angioedema and Acquired C1-Inhibitor Deficiency:
The Medical Background

Our Medical Advisory Panel explains the causes and treatment of these two conditions.

Hereditary Angioedema
HAE occurs in approximately one in every 50,000 to 100,000 of the population. Although it is an inherited disorder, and therefore present at birth, many people do not experience symptoms until they are in their late teens or, occasionally, much later in life.

HAE has an autosomal dominant pattern of inheritance. This means that if one parent is affected, half of the children will inherit the abnormal gene. However, in a significant number of cases, the deficiency occurs spontaneously in individuals without a family history. In these cases, it is thought to be due to a new mutation in the C1-inhibitor gene in one of the parents.

Acquired C1-Inhibitor Deficiency
Acquired C1-inhibitor deficiency is a recently described form of the deficiency, and is also very rare. It is not inherited but is caused when the body produces an antibody to its own C1-inhibitor, which prevents C1-inhibitor from performing its normal function (hence the alternative name for this condition: autoimmune C1-inhibitor deficiency).

C1-Inhibitor, and the Effects of Its Deficiency
In healthy people C1-inhibitor acts as a brake on the activity of the complement and kallikrein systems, which are responsible for the swelling occurring at the site of an injury to the body. In people who are deficient in C1-inhibitor, the triggering of these systems is uncontrolled and leads to leakage of fluid into tissues, causing excessive swelling. This swelling can be quite gross and may affect any part of the body. Swelling in the bowel can cause severe abdominal pain; a swelling in the throat can interfere with breathing, and therefore can have fatal consequences. A deficiency in C1-inhibitor is, therefore, a potentially lethal condition.

Untreated, an attack of angioedema will usually last for 48 hours before abating.

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The Treatment of These Conditions

As with other primary immunodeficiencies, there is currently no known cure for either hereditary angioedema and acquired Cl-inhibitor deficiency. Fortunately, modern treatment has greatly improved the prospects and quality of life for people with hereditary angioedema. Five main strategies are adopted:

Avoidance of precipitating factors
Attacks may be caused by a number of different events, including mild trauma (such as dental treatment) and infections. Oral contraceptives can worsen the disease in some women.

Prevention of acute attacks
If a person with HAE or acquired C1-inhibitor deficiency requires surgical procedures (including dental manipulations), action should be taken to prevent a possible attack. The person should be admitted overnight prior to surgery and should receive an infusion of concentrate. In addition, they should be monitored carefully for 24 hours after surgery.

Treatment of acute attacks
Acute attacks are treated by general supportive measures and also by infusion with the missing protein. Although this blood product (C1-inhibitor concentrate) is commercially available, it is not yet licensed, so it is not straightforward to obtain. Usually, an infusion of 25 units per kilogram of body weight will terminate an attack. Following infusion of the concentrate, an attack should begin to remit within an hour. This can be life-saving in the case of an attack which involves the head or neck area.

If C1-inhibitor concentrate is unavailable, an acute attack may be treated with fresh frozen plasma, which is more readily available. However, the plasma contains complement components which could theoretically make the condition worse, although in practice this does not lead to problems.

If an attack of angioedema affects the throat, lips or mouth, the person should go to hospital immediately. It is also unwise to assume that all attacks of abdominal pain in patients with C1-inhibitor deficiency are necessarily due to angioedema. However, if symptoms are atypical and/or do not respond to therapy, the person should go to hospital immediately.

In order to save time and to help the casualty officer, a person with C1-inhibitor deficiency should carry a card or a letter from their immunologist stating the nature of the disease, the recommended treatment and the telephone number at which the immunologist can be contacted.

Maintenance therapy using drugs
The frequency and severity of the long-term attacks of angioedema can be reduced by androgenic steroids, such as Danazol or Stanozolol, and by tranexamic acid. Both types of drug may produce side effects, but in most patients these can be kept to a minimum if advice is available from an experienced physician, and if the drug is given at the lowest effective dose.

Maintenance therapy using inhibitor concentrate
It is possible to use inhibitor concentrate in maintenance therapy. Although this would seem to be preferable to drug therapy, the concentrate has the disadvantage of lasting only for a short time in the body. It is therefore inappropriate, except for the management of particular procedures such as dental extractions. Every effort must be made to manage the condition using the drugs mentioned above. Only when this approach fails, or if the drugs are contraindicated, should reliance on the inhibitor be considered. This is unusual so experience so far with the inhibitor is scant.

The importance of support
The value of a support group like the PiA for people with hereditary angioedema and acquired C1-inhibitor deficiency is enormous. Because the conditions are rare and treatment is expensive, people feel themselves to be in a very vulnerable situation, especially in the current climate of change in the health service. The PiA aims to keep people informed, to enable contact with others and to give advice on specific non-medical issues when appropriate. In particular, we strongly recommend that each person is looked after by a physician experienced in the management of these rare conditions.

Medical information published by the PiA is approved by our Medical Advisory Panel. However, it is intended for general guidance only, and should not be used in place of the personal consultation needed with your physician.

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