Hereditary angioedema is a chronic genetic disease characterized by sudden but temporary swelling in the deeper layers of the skin that usually appears on its own, without hives or a rash.

In severe cases, the condition can become life-threatening and require immediate medical attention.

Symptoms of hereditary angioedema

Hereditary angioedema can occur anywhere on the body, though the lips and the skin around the eyes are the most common sites. The swelling only occurs in the skin and the mucosal linings of the throat, mouth, and intestines. Swelling episodes begin in childhood, and symptoms usually worsen at puberty.

Swelling attacks happen regularly, often without a trigger, averaging once or twice a week when untreated. They can also be triggered by injury, stress, pain, viral infections, and some medical and dental procedures including surgery.

The frequency and severity of the swelling depend on the individual and can vary significantly even among the members of an affected family. They usually disappear on their own after three to four days.

Severe attacks or events of hereditary angioedema in the mouth, throat, or intestines can cause serious health problems. When severe swelling occurs in the intestines, the individual may experience nausea, vomiting, intense and excruciating pain, and even symptoms of shock. In the mouth and throat, severe swelling can cause pain and difficulty in swallowing, speaking, and breathing.

Difficulties in breathing and the onset of shock can quickly become life-threatening emergencies and require immediate treatment.

Causes of hereditary angioedema

Hereditary angioedema is a rare genetic disease that affects approximately 1 in every 50,000 people. It is passed on from parent to child as an autosomal dominant trait, meaning only one parent has to have the disease to pass it on. There is a 50 percent risk that a parent with the condition will pass it to their children.

Types of  hereditary angioedema

There are three types of hereditary angioedema, all of which are inherited in an autosomal dominant pattern. Though they involve two different genes, all three share a common basic cause: an overproduction of bradykinin, which regulates blood pressure and inflammation by encouraging small blood vessels to dilate or widen.

Angioedema swelling occurs when bradykinin is activated in the deep layers of the skin and allows fluid to flow into the skin tissues from the bloodstream.

Types 1 and 2 of hereditary angioedema are caused by mutations in the SERPING1 gene, which carries the instructions for making a protein called C1-inhibitor (C1-I). This protein blocks the activity of two other proteins: plasma kallikrein and coagulation factor 12 involved in blood clotting and inflammation, both of which promote the production of bradykinin. When there isn’t enough C1-I available to stop them, bradykinin levels can get too high and cause an attack.

Mutations can occur anywhere in the gene and prevent the production of enough C1-I (type 1 hereditary angioedema) or can occur in a very specific region of the gene called exon 8, which causes a less-effective C1-I protein to be produced from the gene (type 2 hereditary angioedema).

Type 3 hereditary angioedema is caused by mutations in another gene called F12, which provides instructions for coagulation factor 12, which plays a crucial role in the blood clotting system and stimulates inflammation.

The mutations in type 3 hereditary angioedema cause this protein to be overactive and stimulate the inflammatory response more than usual. In response, the body produces more bradykinin causing periodic attacks of swelling.

Treatment of hereditary angioedema

In a life-threatening situation, where swelling in the throat or mouth has blocked the airway, and the individual is having trouble breathing, an EpiPen (epinephrine) or Firazyr (icatibant) can be used.

If the EpiPen is ineffective, immediate physical intervention is needed. Artificial respiration such as cardiopulmonary resuscitation (CPR) may be used to keep the patient alive until swelling subsides enough to allow the individual to breathe on his or her own, or until mechanical ventilation options become available.

In some cases, hereditary angioedema swellings do not respond effectively to allergy medications such as epinephrine, antihistamines, and corticosteroids.

More effective medications for hereditary angioedema include C1-I boosting medications such as Haegarda, Cinryze, and Kalbitor (ecallantide).

Genetic testing

Although hereditary angioedema is an autosomal dominant disease, sometimes family members who have the faulty gene causing the disease do not show obvious symptoms. Their symptoms may be mild or infrequent, attributed to some other problem, or disguised as a death of unknown cause.

It is therefore recommended that people are genetically tested if they have a family of history of chronic and recurring swelling episodes, intestinal pain and nausea, sudden and unexplained death, or diagnosed hereditary angioedema.

Genetic testing can give individuals a chance to not only treat their own symptoms, but to determine their risk of passing the disease to their children. In addition, other family members will be better aware of their own risk of having the disease.

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Angioedema News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.