Hereditary Angioedema: Causes, Symptoms & Treatment

Hereditary angioedema is the name given to a rare hereditary disease. In it, affected individuals suffer from repeated episodes of edema.

What is hereditary angioedema?

Hereditary angioedema is an autosomal dominant hereditary disease in the course of which angioedema (Quincke’s edema) forms repeatedly. The disease is a special form of Quincke’s edema. Hereditary angioedema is characterized by swelling of the skin, mucous membranes and internal organs. It is estimated that one in 10,000 to 50,000 people suffer from the hereditary disease. However, it is considered likely that the number of unreported cases is significantly higher. Women and men are equally affected. The disease was first described in 1882 by the German internist Heinrich Irenaeus Quincke (1842-1922). In earlier years, the disease was called hereditary angioneurotic edema. However, in the absence of a neurologic influence on the development of the disease, the term hereditary angioedema became accepted over time.

Causes

The originator of hereditary angioedema is a genetic defect. This causes a deficiency in the C1 esterase inhibitor (C1-INH). This fulfills the task of activating the complement system. In total, there are more than 200 mutations. Either too little of the C1-esterase inhibitor is produced or malfunctions occur. The lack of the C1-esterase inhibitor causes the development of edema within the complement system and the contact system of blood clotting. It is believed that the peptide bradykinin has a crucial role in the contact system. The release of bradykinin occurs at the end of a reaction sequence that is a response of the body to injury. Bradykinin causes increased leakage of fluid from the vessels into the tissues. This can cause edema (water retention) to form. In addition, the vessels are dilated by the bradykinin as well as causing muscle contractions that lead to pain and cramps. In normal cases, the C1 esterase inhibitor ensures that bradykinin release is limited. However, deficiency can cause significantly more of the peptide to be released than is needed. In some cases, autoimmune diseases are responsible for a deficiency of the C1-esterase inhibitor. However, this is not a hereditary but an acquired angioedema. Sometimes, drugs such as ACE inhibitors also trigger severe edema attacks. The reason for this is their influence on bradykinin metabolism. In some patients, no specific cause for the disease can be found. Doctors then speak of idiopathic angioedema.

Symptoms, complaints, and signs

In principle, hereditary angioedema can occur at any age. However, it most commonly manifests in the first two decades of life. Thus, 75 percent of all patients suffer symptoms before the age of 20. The attacks are particularly frequent during puberty and in young adults. The use of the contraceptive pill is considered to be a trigger in young women who have previously been inconspicuous. However, attacks can also be provoked by triggers that cannot be identified. These include in particular anxiety, stress as well as minor injuries. A typical symptom of hereditary angioedema is the development of extensive edema on the skin. Water retention can also occur in the respiratory tract or in the gastrointestinal tract. If hereditary angioedema forms in the larynx, there is even a danger to life. The frequency of edema attacks varies greatly from patient to patient. For example, in some patients they occur once a week, while in others they occur only once a year. A typical sign of hereditary angioedema is the absence of itching. As a rule, the edema attacks last three to five days. It is not possible to predict when the next edema will appear.

Diagnosis and course

The symptoms of hereditary angioedema resemble those of intestinal colic or allergies, which are more common. For this reason, the rare condition is often discovered late. If the edema does not respond to the administration of cortisone or antihistamines, this is considered a significant indication of the disease. This makes it possible to distinguish it from allergies. If edema attacks occur only within the gastrointestinal tract, diagnosis is particularly difficult. The patient’s medical history also provides important information.Otherwise, he needs a laboratory analysis for an exact diagnosis. In this context, it is not the C1-INH deficiency that is detected, but low levels of complement factor C4. Its consumption takes place in the complement system reaction chain of the body’s defense system. Because the regulation of the C1-esterase inhibitor is absent, the C1-INH is permanently overactive. Hereditary angioedema can take a dangerous course if attacks occur within the respiratory tract. Thus, mucosal swelling of the trachea is one of the most common causes of death in patients.

Complications

In most cases, this disease affects only young adults or people in puberty. Women who take birth control pills are particularly likely to be affected. They experience anxiety, panic attacks and excessive stress. These complaints generally have a very negative effect on the patient’s body and can lead to psychological discomfort. Furthermore, there is the formation of edema, which can cover the entire body. It is not uncommon for life-threatening situations to arise if the water retention forms in the stomach or in the respiratory tract. In the worst case, the affected person can die without treatment. As a rule, this also reduces life expectancy if the symptoms are not treated by a doctor. In most cases, relatively simple treatment of the disease is possible, with no particular complications. The treatment is mainly carried out with the help of medication and can greatly limit the symptoms. However, the affected person is usually dependent on lifelong therapy, since the disease cannot be treated causally.

When should one go to the doctor?

If changes in the mucous membranes of the mouth and throat are noticed, a doctor should be consulted. This is especially true if symptoms persist and do not seem to subside. If there is a concrete suspicion of hereditary angioedema, a doctor must be consulted immediately. In particular, symptoms such as difficulty swallowing, shortness of breath and palpitations should be clarified. Persistent heart rhythm disturbances indicate a serious disease that must be examined and treated immediately. Medical advice is required at the latest if severe pain, gastrointestinal complaints or fever symptoms are also present. In case of doubt, the patient should visit a hospital. If hereditary angioedema is not treated, respiratory distress, bleeding and other serious complications may occur that require emergency medical treatment. Quincke’s edema occurs predominantly after taking ACE inhibitors and generally in allergic reactions. Patients who regularly take medication, allergy sufferers and chronically ill patients should immediately go to the responsible physician with the symptoms mentioned. In addition to the family doctor, the dermatologist or an internist is also a good option.

Treatment and therapy

Treatment of hereditary angioedema is divided into therapy of acute symptoms and long-term prophylaxis. In the acute phase, the development of edema should be stopped as quickly as possible. For this purpose, the patient in Germany usually receives a C1-INH concentrate. This consists of donor blood and is administered intravenously. If necessary, freshly frozen blood plasma containing C1-INH can also be administered. In the meantime, a recombinant C1-INH preparation is also available in Germany that does not require donor plasma. If the edema attacks occur at least once a month, long-term prophylaxis is required. For this purpose, male sex hormones are usually used, which increase the production of C1-INH.

Outlook and prognosis

Without treatment, hereditary angioedema leads to a decrease in life expectancy. Edema of the skin and mucous membranes recurs and may be acutely life-threatening. This is particularly the case if the swelling occurs in the upper respiratory tract. There is then a risk of suffocation. Where and when the edema appears can never be predicted. Edema in the gastrointestinal tract produces severe colic. The attacks come unprepared. They may occur once a year or once a week. Each attack can be potentially fatal. As the name implies, it is a congenital disorder that is genetic.Due to a genetic defect, minor events such as minor injuries, irritations, infections or medical interventions lead to a sudden increase in the permeability of the affected vessels, so that fluid can leak into the surrounding tissue, forming a swelling. Due to the rarity of the condition, it is often undiagnosed or diagnosed too late. In diagnosed cases, long-term therapy with androgen derivatives (danazol) or the bradykinin receptor antagonist Icatibant can be started. This effectively prevents sudden edema formation. Danazol was taken off the market in Germany in 2005 because it produces benign liver tumors. Before surgery or dental treatment, a C1-INH concentrate must be administered shortly before the procedure as prophylaxis. However, the patient should also always be prepared for acute therapy in case of a sudden attack.

Prevention

Hereditary angioedema is one of the hereditary diseases. Therefore, there are no preventive measures.

Follow-up

In most cases, the affected person has very few or no special measures and options for aftercare available for this disease. In this case, the affected person must contact a doctor at an early stage to prevent further complications or a further worsening of the symptoms. Since it is a hereditary disease, it cannot be treated completely. However, if the patient wishes to have children, genetic testing and counseling can be performed to prevent the recurrence of the disease in the children. Self-cure cannot occur in this case. In most cases, the treatment of this disease is done by blood transfusions, which must be performed monthly. It is necessary to pay attention to a regular application, so that it does not come to further complications. Further measures of a treatment cannot be carried out thereby. Furthermore, those affected by this disease often need the support of the whole family and friends. This can also prevent psychological upsets or depression, and intensive and loving conversations can also have a positive effect on the course of the disease. No general prediction can be made about the life expectancy of the affected person.

What you can do yourself

In any case, hereditary angioedema must be clarified and treated by a doctor. Accompanying medical measures, self-treatment is also possible in some cases. The most important step is to eliminate the triggering circumstances. For example, if the edema was triggered by a certain medication, this must be discontinued and replaced by another preparation. A typical trigger is the contraceptive pill, which should be discontinued if the symptoms are present, preferably in consultation with the gynecologist to avoid any complications. Alternatively, you can try to avoid so-called triggers – possible triggers of an attack. These include, for example, stress, anxiety and minor injuries. However, if any of the above-mentioned symptoms occur, the family doctor or a dermatologist must be consulted immediately. If the hereditary angioedema is treated with medication at an early stage, it disappears again on its own in many cases and does not require independent treatment. Since such edema can occur again and again, preventive measures should be taken. These include avoiding mentioned triggers as well as regular visits to the doctor and a healthy lifestyle with a balanced diet and sufficient exercise.