Angioedema

Symptoms

The main symptom of the pathology is the appearance of painless swelling of the skin of various sizes. Patients note a feeling of fullness and tension, there are no other subjective complaints. Unlike inflammatory edema, the affected area is characterized by a paler color than the surrounding areas of the skin and the absence of a local increase in tissue temperature. Most often, edematous manifestations are found on the upper and lower extremities, face (lips, cheeks, eyelids, auricles), neck, in the genital area. Skin itching is uncharacteristic, but can be determined by the combination of angioedema with urticaria.

In some patients, edema is detected in the area of the mucous membranes, sometimes the pathological process also affects the submucosal plate. The organs of the oral cavity (tongue, soft palate), respiratory tract, and gastrointestinal tract are most often affected. With the development of angioedema of the organs of the respiratory system, there is a feeling of lack of air , hoarseness or complete loss of voice, barking cough . Involvement of the gastrointestinal tract is manifested by a pronounced abdominal syndrome - pain, nausea, vomiting. There is tension in the muscles of the abdominal wall, creating a false picture of peritonitis or acute intestinal obstruction .

Extremely rare symptoms of the disease are signs of pleural effusion (cough, chest pain, shortness of breath). Other rare pathology options include local cerebral edema (depression of consciousness, hemiparesis is recorded), bladder angioedema (accompanied by acute urinary retention ), muscle and joint damage. Isolated forms of the disease develop slowly over 12-48 hours. After that, in the absence of complications, a slow resolution of swelling occurs within 5-8 days. Some combined variants of angioedema (especially allergic genesis) can progress much faster - within minutes or hours.

Causes

There are a huge number of external and internal factors that contribute to the development of angioedema. The direct cause of the pathology is changes in the complement system and a violation of some other physiological processes (blood coagulation, fibrinolytic and kinin reactions). In the vast majority of cases, the anomaly is caused by a deficiency or insufficient activity of the c1 inhibitor, a blood protease that slows down and stops a number of biochemical reactions in the blood and tissues. This phenomenon occurs under the influence of the following factors:

•    Genetic features. A significant part of the episodes of congenital angioedema is caused by a mutation of the sepring1 gene located on the 11th chromosome. It encodes the protein sequence of the c1 inhibitor, therefore, when this gene is changed, there is a deficiency of the protease or loss of its function.

•    Lymphoproliferative pathologies. Some conditions with accelerated multiplication of lymphocytes or their precursor cells (for example, lymphomas ) may be accompanied by angioedema. The reason for this lies in the increase in the rate of destruction of the c1 inhibitor.

•    Autoimmune reactions. Under certain conditions, antibodies to c1-esterase are formed that bind this enzyme and contribute to its destruction. The process can occur both in isolation and in systemic allergic reactions or other disorders.

A rare variant of the pathology is angioedema, which develops at an optimal level of c1 inhibitor - basically, it includes the so-called estrogen-dependent edema. It is believed that they are caused by genetic factors and are transmitted by an x-linked mechanism, the course of the disease is aggravated by taking estrogen preparations. There is also a type of disease provoked by the use of angiotensin-converting enzyme inhibitors, which are part of numerous antihypertensive drugs.

Treatment

Therapeutic measures for angioedema are divided into two groups - methods for stopping an acute attack and techniques for preventing its subsequent development. In both cases, similar medicinal substances are used - only the dosage regimen and dosage change depending on the purpose of their appointment. Most often, the following drugs are used to treat angioedema in modern immunology:

•    Androgens. Some analogues of male sex hormones (danazol, methyltestosterone) are able to enhance the synthesis of c1-esterase in liver cells. They reduce the severity of the symptoms of pathology and reduce the likelihood of an attack of the disease in the future.

•    Fibrinolysis inhibitors. Drugs that interfere with fibrinolytic processes also slow down the reactions of the kallikrein pathway. Due to this, the rate of plasma diffusion in the tissue decreases, and the likelihood of angioedema decreases. The use of drugs of this group (e-aminocaproic or tranexamic acid) is carried out under the control of the state of the blood coagulation system.

•    Fresh frozen plasma. Transfusion of donor plasma containing c1-inhibitor is an effective method for the relief of acute edema, especially of a hereditary nature.

In the presence of autoantibodies against complement components, their removal from the bloodstream using plasmapheresis is indicated. This is a temporary measure that can significantly reduce the severity of edematous manifestations. If the life of the patient is threatened (for example, due to obturation of the respiratory tract), the introduction of adrenaline is recommended, and if it is ineffective, a conico- or tracheotomy is recommended. If the cause of angioedema was the presence of another disease (allergic, autoimmune or other), a treatment regimen is developed according to the indications. There are also promising inhibitor drugs being used in some countries to treat this condition.
 

Tests Required for Diagnosis

In most cases, the diagnosis of angioedema is made by an immunologist . Less commonly, this pathology is encountered by specialists in other areas - dermatologists, pediatricians, gastroenterologists, therapists . The definition of the disease is often difficult due to its diverse etiology and very wide range of clinical manifestations. The main attention is paid to anamnestic information and the results of specific laboratory studies. Diagnosis of angioedema includes the following methods:

•    Questioning and inspection. During external examination, the prevalence and localization of the edematous area are specified, and the absence of pain is confirmed. By the method of questioning, they find out what preceded the development of pathological manifestations (stress, the use of any products, taking medications), whether similar reactions occurred in relatives.

•    Lab tests. A specific method for diagnosing angioedema is to determine the level of c1-inhibitor in blood plasma - its absence or decrease in the amount indicates in favor of the presence of the disease. It is possible to determine the titer of antibodies to the c1 inhibitor - this technique allows you to find out whether the disease has an acquired autoimmune character.

•    Additional research. When the respiratory system is affected, bronchoscopy , chest x-ray are performed. Usually, swelling of the tissues of the larynx, bronchospasm is detected, occasionally a pleural effusion is detected. Ultrasound of the abdominal organs makes it possible to differentiate abdominal forms of angioedema from peritonitis and other pathologies of the gastrointestinal tract.

In addition to the above methods, a huge number of various factors are taken into account in the diagnosis of this condition. For example, the age of the patient: hereditary varieties are more often found in people under 20 years old, acquired forms - in people over 40 years old with a burdened history. Take into account the presence or absence of concomitant symptoms - urticaria, respiratory disorders. Differential diagnosis is carried out with edema of a different origin - as a result of renal pathology, poisonous insect bites, local allergic and inflammatory reactions.