Hereditary angioedema: what is it, symptoms, treatment, prognosis

What is hereditary angioedema?

Hereditary angioedema (NAO) Is a rare hereditary disorder characterized by repeated episodes of fluid buildup outside the blood vessels that blocks normal blood flow or lymphatic fluid, causing rapid tissue swelling in the hands, feet, limbs, face, intestines, or respiratory tract ways. Usually this edema not accompanied by itching, as can be the case with allergic reaction. Swelling of the gastrointestinal tract leads to seizures. Airway edema can lead to obstruction, a potentially very serious complication.

These symptoms develop as a result of a deficiency or malfunctioning of certain proteins, which help maintain normal fluid flow through very small blood vessels (capillaries). In some cases, fluid can build up in other internal organs. The severity of the disease varies greatly among affected individuals.

The most common form of HAE is type I hereditary angioedema, which is the result of abnormally low levels of certain complex proteins in the blood (C1 esterase inhibitors) known as complements. They help regulate various bodily functions (for example, the flow of body fluids into and out of cells). Hereditary angioedema type II, a more rare form of the disorder, results from the production of abnormal complement proteins.

Signs and symptoms

A characteristic symptom of hereditary angioedema is repeated episodes of edema of the affected area due to the accumulation of excess fluid in the body. The most commonly affected areas of the body include the arms, legs, eyelids, lips, and / or genitals. Edema may also occur in the mucous membranes that line the respiratory and digestive tracts, which is more common in people with HAO than in those with other forms angioedema (i.e. acquired or traumatic). People with this disorder usually have hard and painful swelling rather than red and itchy swelling. Dermal urticarial rash (hives) is rarely present.

Symptoms of hereditary angioedema may recur and may become more severe. Trauma, severe pain, surgery, dental procedures, viral illnesses, and / or stress can cause or worsen recurrent HAE symptoms.

Symptoms associated with swelling of the digestive system (gastrointestinal tract) include nausea, vomiting, severe abdominal pain, and / or other signs of obstruction. Swelling of the throat (pharynx) or voice box (larynx) can lead to pain, difficulty swallowing (dysphagia), difficulty speaking (dysphonia), noisy breathing (stridor) and potentially life-threatening asphyxia.

Causes

Hereditary angioedema is inherited as an autosomal dominant trait. Genetic diseases are determined by two genes, one of which is passed on from the father and the other from the mother.

Dominant genetic disorders occur when only one copy of an abnormal gene is needed for a disease to appear. The abnormal gene can be inherited from either parent, or it can be the result of a spontaneous new mutation (gene change) in the affected person. The risk of passing the abnormal gene from the affected parent to the offspring is 50% with every pregnancy, regardless of the sex of the child.

Symptoms of type I hereditary angioedema develop due to a deficiency of a protein known as C1 esterase inhibitor (C1-INH), which is part of the complement system. Type II hereditary angioedema is a rarer form of the disorder and can result from abnormal C1 esterase proteins that do not function properly.

The gene that causes hereditary angioedema is located on the long arm of chromosome 11 (11q12-q13.1). Chromosomes, which are present in the nucleus of human cells, carry the genetic information of each person. Pairs of human chromosomes are numbered 1 through 22, and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm, labeled "p", and a long arm, labeled "q". Chromosomes are further subdivided into multiple bands, which are numbered. For example, "chromosome 11q12-q13.1" refers to bands 12-13.1 on the long arm of chromosome 11. The numbered stripes indicate the location of the thousands of genes present on each chromosome.

Affected populations

Hereditary angioedema is a rare condition that affects men and women in equal proportions. Symptoms usually begin in early childhood. Approximately one in 50,000 to 150,000 people suffer from this disease worldwide.

Symptomatic disorders

Symptoms of the following disorders may be similar to those of hereditary angioedema. Comparisons can be useful for differential diagnosis:

• Acute non-hereditary angioedema affects the skin and mucous membranes. It usually goes away on its own in 1-2 days. Any number of allergens can be responsible for it, including medications, insect bites, and certain foods (such as eggs, shellfish, nuts, and fruits). Some people have very severe allergic reactions (anaphylaxis), which can lead to respiratory angioedema. Acquired angioedema can also occur due to immune disorders (eg, B-cell lymphoproliferative disease), chronic lymphocytic leukemia, multiple myeloma, systemic lupus erythematosus (SLE), chronic sinusitis, a dental infection, or certain blood diseases (major cryoglobulinemia). Other acquired edema may result from surgery (i.e. mastectomy), malignant neoplasms, and / or autoimmune diseases. Acquired angioedema can occur at any age.
• Elastolysis Is a rare congenital or acquired connective tissue disorder characterized by sagging skin. The affected areas of the skin can be thickened and dark. This disorder is usually diagnosed at birth or early childhood. The initial symptom is usually facial swelling and can be confused with hereditary angioedema. Elastolysis progresses, causing skin changes and blood vessel damage.

Diagnostics

The diagnosis of HAE is made by careful clinical evaluation, a detailed history of the patient, and blood tests that detect a decrease in complement protein levels. In cases of high clinical suspicion and recurrent episodic angioedema of undetermined etiology, genetic testing is indicated.

Standard treatments

Treatment for NAO includes:

• Medicines such as ecallantide or a purified C1 inhibitor.
• Fresh frozen plasma.
• Drugs to prevent future seizures.

Sometimes the swelling can be reduced with certain medications, such as ecallantide or a purified C1 inhibitor (which is made from human blood). However, these drugs are not readily available. In such cases, fresh frozen plasma or, in the European Union, tranexamic acid may be prescribed. Antihistamines and corticosteroids are ineffective.

Pain relievers, medications to relieve nausea (antiemetic drugs), and fluids can help relieve symptoms.

- Emergency treatment.

Sometimes, when there is sudden airway swelling and difficulty breathing, doctors must restore airway patency. To do this, they can inject adrenaline subcutaneously or intramuscularly (to reduce swelling). However, epinephrine may not result in rapid or long-term reduction in edema. Doctors can then insert a breathing tube into the windpipe through the person's mouth or nose (intubation).

Sometimes doctors have to make a small incision in the skin above the windpipe (trachea) to insert the breathing tube.

- Drugs to prevent seizures.

Stanozolol and danazol (synthetic male hormones) can help prevent subsequent seizures. These medications can be taken several days before and after a dental or surgical procedure that may trigger an attack. Or they may be prescribed to prevent seizures in the long term.

These drugs, when taken by mouth, can stimulate the body to produce more C1 inhibitor.

Because these drugs can have virilizing side effects, when taken by women over a long period of time, the dose should be reduced as soon as possible and as much as possible.

A C1 inhibitor, if available, may be prescribed 1 hour before dental or surgical procedures in place of stanozolol or danazol.

Forecast

Despite its rarity, HAO is a potentially catastrophic disease. Laryngeal edema can lead to asphyxiation. Abdominal seizures can lead to unnecessary surgery and delayed diagnosis, as well as drug dependence due to an addiction to strong pain relievers. Skin seizures are both disfiguring and disabling, resulting in a reduced quality of life.

Patients with early-onset hereditary angioedema have a poorer prognosis than patients with late-onset seizures.

Before the development of effective therapy, mortality was 20-30%. With appropriate preventive therapy, the prognosis for HAE patients is now excellent. The judicious use of androgens reduces both short-term and long-term negative effects. The advent of C1 inhibitor concentrate has also significantly improved patient care.