Therapeutic measures for angioedema are divided into two groups – methods for stopping an acute attack and techniques for the prevention of its subsequent development. In both cases, similar medicinal substances are used – depending on the purpose of their administration, only the dosage regimen and dosage change.
The following drugs are most commonly used for the treatment of angioedema in modern immunology:
- Androgens. Some analogues of male sex hormones (danazol, methyltestosterone) are able to enhance the synthesis of C1-esterase in the liver cells. They reduce the severity of symptoms of the pathology and reduce the likelihood of an attack of the disease in the future.
- Fibrinolysis inhibitors. Drugs that inhibit fibrinolytic processes also slow down the reactions of the kallikrein pathway. This reduces the rate of diffusion of plasma in the tissue, decreases the likelihood of angioedema. The use of drugs in 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 a C1 inhibitor, is an effective method for the relief of acute edema, especially of hereditary nature.
In the presence of autoantibodies against the components of the complement is shown their removal from the bloodstream using plasmapheresis. This is a temporary measure that can significantly reduce the severity of edematous manifestations. If the patient’s life is threatened (for example, due to obstruction of the airways), adrenaline injection is recommended, and if it is ineffective, a koniko or tracheotomy is recommended. If the cause of angioedema is the presence of another disease (allergic, autoimmune, or other), a scheme for its treatment is developed according to the indications. There are also promising inhibitor drugs used in some countries to treat this condition.
Angioedema was first described in 1882 by the German scientist Heinrich Quincke. The researcher considered it an independent disease – angioedema. It is now established that about half of the cases of pathology arise as a result of allergic processes of the reagin type, while the rest are independent acquired or hereditary conditions.
The concept of “isolated angioedema” includes a number of diseases, which are based on impaired fluid circulation between the circulatory system and tissues. Angiotecks can be diagnosed at any age, women are detected approximately 1.5-2 times more often than men. Genetically determined variants of the pathological condition are transmitted in an autosomal dominant manner.
Causes of Angioedema
There are a huge number of external and internal factors contributing to the development of angioedema. The immediate cause of the pathology is changes in the complement system and the disruption of some other physiological processes (blood coagulation, fibrinolytic and kinin reactions). In the overwhelming majority of cases, the anomaly is caused by a deficiency or inadequate 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 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, so when changing this gene, there is a lack of protease or loss of its function.
- Lymphoproliferative pathology. Some conditions with accelerated reproduction of lymphocytes or their progenitor cells (for example, lymphoma) 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 with systemic allergic reactions or other disorders.
A rare variant of the pathology is angioedema, which develops at an optimal level of the C1 inhibitor – mainly it refers to the so-called estrogen-dependent edema. It is believed that they are due to genetic factors and are transmitted by the mechanism linked to the X chromosome, the course of the disease is aggravated when estrogen preparations are taken.
There is also a type of disease triggered by the use of angiotensin-converting enzyme inhibitors, which are part of numerous antihypertensive drugs.
Pathogenesis of angioplasty
For one reason or another, a deficiency of the C1 inhibitor leads to activation of the complement system, increases the concentration of kallikrein and bradykinin. The latter stimulate the formation of vasoactive peptide compounds that act on the vascular walls and smooth muscles. As a result, the expansion of the precapillary arterioles occurs first, then the elements of the plasma cells of the cell from the bloodstream into the extracellular space.
Thus, local angioedema is formed, which manifests itself in a characteristic clinical picture. In addition, the reactions of the bradykinin level can cause spasms of smooth muscle cells of the digestive and respiratory systems, disrupting their motility.
Classification of angioedema
Given the characteristics of the clinical course in clinical allergology, all cases of angioedema are divided into two large groups – isolated and combined. The former appear only as edema of subcutaneous fatty tissue and skin, the latter may be accompanied by urticaria, spasm of the respiratory tract and other symptoms. The separation is rather conditional, weakly reflecting the causes of the disease. On the etiological basis distinguish hereditary and acquired forms of angioedema.
Congenital species make up about 2-5% of the total number of cases of the disease, including the following types:
- Type 1. Due to the almost complete absence of a C1 inhibitor that occurs when the SEPRING1 gene mutates. It is characterized by a rather severe course – generalization and severity of edema, their appearance not only on the skin, but also on the mucous membranes of the respiratory tract or the digestive tract. It is registered in 85% of cases of hereditary angioedema.
- Type 2. Develops with a relative lack of inhibitor due to its slow formation or reduced activity due to the wrong structure of the enzyme. The clinic is less severe, edema affects mainly the tissues of the limbs, sometimes the face. This variant of the disease is diagnosed in 12-14% of patients with hereditary forms of angioedema.
- Type 3. It is extremely rare, usually – in the absence of a deficiency of C1-esterase. As a rule, estrogen-dependent edema is represented – exacerbations of pathology during pregnancy, taking combined oral contraceptives, replacement therapy during menopause.
All variants of hereditary angioedema are isolated, not accompanied by urticaria or other disorders.
Acquired species have a different classification, which includes only two main types of disease:
- Type 1. It is detected against the background of lymphoproliferative conditions – lymphomas, with some infectious lesions. The reason is the increase in consumption of the C1 inhibitor and its subsequent deficiency.
- Type 2. Occurs due to the synthesis of autoantibodies to the inhibitor, which sharply reduces its concentration in the blood. This phenomenon occurs in certain autoimmune and allergic conditions, immunodeficiencies and other pathologies.
Symptoms of angioedema
The main symptom of the disease is the appearance of painless swelling of the skin of various sizes. Patients note the feeling of pressure and tension; there are no other subjective complaints. Unlike inflammatory edema, the affected area is characterized by a paler color than the surrounding 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 area of the genital organs. Pruritus pruritus is not typical, but can be determined by the combination of angioedema and urticaria.
In some patients, edema is detected in the mucous membranes, sometimes the pathological process also affects the submucosa. 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 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 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 pathologies include localized cerebral edema (depression of consciousness, hemiparesis), 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 edema occurs within 5-8 days. Some combined variants of angioedema (especially allergic genesis) can progress much more quickly – within a few minutes or hours.
Complications of angioedema
The likelihood of complications of angioedema depends on the location of the pathological process. Most often (about half of all complicated cases), patients have difficulty breathing due to the narrowing of the lumen of the larynx or bronchi. In the absence of medical care, the violation can be fatal. Abdominal forms of pathology, which can cause peristalsis disorders with the development of obstruction and peritonitis, are relatively dangerous.
Often, edema of the digestive tract causes unnecessary surgery due to misdiagnosis. Damage to the brain can lead to coma and a number of neurological consequences (impaired coordination, speech, and perception). Acute urinary retention during edematous phenomena in the bladder causes fluid reflux, hydronephrosis and renal failure.
Diagnosis of angioedema
In most cases, the diagnosis of angioedema exposes doctor-immunologist. Less commonly, this pathology is confronted by specialists in other fields – dermatologists, pediatricians, gastroenterologists, therapists. The definition of the disease is often difficult because of its diverse etiology and a very wide range of clinical manifestations. The focus is on anamnestic information and the results of specific laboratory tests.
Diagnosis of angioedema includes the following methods:
- Survey and inspection. When external examination specify the prevalence and localization of the edematous area, confirm the absence of pain. By questioning, they find out what preceded the development of pathological manifestations (stress, use of any products, medication), whether similar reactions took place in relatives.
- Lab tests. A specific method for the diagnosis of angioedema is the determination of the level of C1-inhibitor of blood plasma – its absence or a decrease in the number is 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 if the disease has an acquired autoimmune character.
- Additional research. With the defeat of the respiratory system produce bronchoscopy, radiography of the chest. Usually revealed swelling of the larynx tissue, bronchospasm, rarely found pleural effusion. Ultrasound of the abdominal organs allows differentiation of abdominal forms of angioedema from peritonitis and other pathologies of the gastrointestinal tract.
In addition to the above methods in the diagnosis of this condition take into account a huge number of various factors. For example, the age of the patient: hereditary varieties are more often found in persons younger than 20 years, acquired forms – in people older than 40 years with a burdened history.
Take into account the presence or absence of associated symptoms – urticaria, respiratory disorders.
Differential diagnostics is performed with edemas of a different genesis – as a result of renal pathology, the bite of poisonous insects, local allergic and inflammatory reactions.
Prognosis and prevention of angioedema
The prognosis of angioedema is considered uncertain until the etiology of a particular patient is ascertained. With the hereditary nature of the pathology, there is always a risk of the development of a lethal edema of the larynx, therefore, patients should have a card with them indicating the diagnosis.
With proper prophylactic treatment, seizures are rare and do not pose a threat to the life of the patient.
The prognosis of acquired forms depends on the nature of the underlying disease. Preventive measures include the timely treatment of allergic and autoimmune conditions.