Angioneurotic edema is an acute disease characterized by the appearance of a clearly limited angioedema of the skin, subcutaneous tissue, as well as the mucous membrane of various organs and systems of the body. The main causal factors are true and false allergies, infectious and autoimmune diseases. Angioedema occurs acutely and passes within 2-3 days. Therapeutic measures for angioneurotic edema include relief of complications (restoration of airway patency), infusion therapy (including C1-inhibitor and aminocaproic acid in hereditary edema), administration of glucocorticoids, antihistamines.
T78.3 Angioneurotic edema
Angioneurotic edema (angioedema) is an acutely developing local swelling of the skin, subcutaneous tissue, mucous membranes of an allergic or pseudoallergic nature, most often occurring on the face (lips, eyelids, cheek, tongue), less often – on the mucous membranes (respiratory tract, gastrointestinal tract, genitourinary organs). With the development of angioneurotic edema in the area of the tongue and larynx, the patency of the respiratory tract may be impaired, and there is a threat of asphyxia. In 25% of patients, a hereditary form is diagnosed, in 30% – acquired, in other cases it is not possible to identify the causal factor. According to statistics, during life, angioneurotic edema occurs in about 20% of the population, and in 50% of cases angioedema is combined with urticaria.
Acquired angioneurotic edema often develops in response to the penetration of an allergen into the body – a drug, a food product, as well as with insect bites and stings. The resulting acute allergic reaction with the release of inflammatory mediators increases the permeability of blood vessels located in the subcutaneous fat and submucosal layer, and leads to the appearance of local or widespread tissue edema on the face and elsewhere in the body. angioneurotic edema can also develop with pseudoallergia, when hypersensitivity to certain medications, food products and food additives develops in the absence of an immunological stage.
Another of the causal factors contributing to the occurrence of edema is taking medications such as ACE inhibitors (captopril, enalapril), as well as angiotensin II receptor antagonists (valsartan, eprosartan). In this case, angioedema is observed mainly in the elderly. The mechanism of edema when using these drugs is caused by the blockade of the angiotensin converting enzyme, as a result of which the vasoconstrictive effect of the hormone angiotensin II decreases and the destruction of the vasodilator bradykinin slows down.
Angioneurotic edema can also develop with congenital (hereditary) or acquired deficiency of a C1 inhibitor that regulates the activity of the complement system, blood clotting and fibrinolysis, and the kallikrein-kinin system. At the same time, a deficiency of the C1-inhibitor occurs both with its insufficient formation, and with increased use and insufficient activity of this component. With hereditary edema, as a result of gene mutations, the structure and function of the C1 inhibitor is disrupted, excessive activation of complement and Hageman factor occurs, and as a result, increased formation of bradykinin and C2-kinin, which increase vascular permeability and lead to the formation of angioedema. Acquired angioneurotic edema, caused by a deficiency of the C1 inhibitor, develops with its accelerated consumption or destruction (production of autoantibodies) in malignant neoplasms of the lymphatic system, autoimmune processes, and some infections.
Sometimes there is a variant of hereditary angioneurotic edema with a normal level of C1-inhibitor, for example, with a familial mutation of the Hageman factor gene, as well as in women when increased bradykinin production and its delayed destruction are caused by inhibition of ACE activity by estrogens. Often, various causal factors are combined with each other.
According to clinical manifestations, there is an acute course of angioneurotic edema lasting less than 1.5 months and a chronic course when the pathological process lasts 1.5-3 months or longer. Isolated and combined with urticaria angioedema are isolated.
Depending on the mechanism of edema development, there are diseases caused by a violation of the regulation of the complement system: hereditary (there is an absolute or relative deficiency of the C1 inhibitor, as well as its normal concentration), acquired (with a deficiency of the inhibitor), as well as angioedema developing with the use of ACE inhibitors, due to allergies or pseudoallergia, against the background of autoimmune and infectious diseases. Idiopathic angioneurotic edema is also isolated when it is not possible to identify a specific cause of the development of angioedema.
Symptoms of angioneurotic edema
Angioedema develops, as a rule, acutely within 2-5 minutes, less often angioedema can form gradually with an increase in symptoms for several hours. Typical localization sites are areas of the body where there is loose fiber: in the area of the eyelids, cheeks, lips, on the mucous membrane of the oral cavity, on the tongue, as well as on the scrotum in men.
If edema develops in the larynx, hoarseness of the voice appears, speech is disrupted, whistling stridorous breathing occurs. The development in the submucosal layer of the digestive tract leads to a picture of acute intestinal obstruction – the appearance of severe abdominal pain, nausea, vomiting, stool disorders. Significantly less common is angioneurotic edema with damage to the mucous membrane of the bladder and urethra (there is urinary retention, pain when urinating), pleura (chest pain, shortness of breath, weakness), brain (symptoms of transient cerebral circulation disorders), muscles and joints.
Disease with allergic and pseudoallergic etiology in half of cases is accompanied by urticaria with itchy skin, blisters, and can also be combined with reactions from other organs (nasal cavity, bronchopulmonary system, gastrointestinal tract), complicated by the development of anaphylactic shock.
Hereditary edema associated with a violation of the complement system, as a rule, occurs before the age of 20, manifests itself by the slow development of symptoms of the disease and their increase during the day and gradual reverse development within 3-5 days, frequent damage to the mucous membrane of internal organs (abdominal syndrome, laryngeal edema). Disease due to hereditary disorders tends to recur, recurring from several times a year to 3-4 times a week under the influence of a variety of provoking factors – mechanical damage to the skin (mucous membrane), colds, stress, alcohol intake, estrogens, ACE inhibitors, etc.
The characteristic clinical picture, typical for angioneurotic edema with localization on the face and other exposed areas of the body, allows you to quickly establish the correct diagnosis. The situation is more difficult when a picture of an “acute abdomen” or a transient ischemic attack appears, when it is necessary to differentiate the observed symptoms with a number of diseases of the internal organs and nervous system. It is even more difficult to distinguish between hereditary and acquired angioedema, to identify a specific causal factor that caused its development.
Careful collection of anamnestic information allows us to determine the hereditary predisposition in terms of allergic diseases, as well as the presence of cases of angioneurotic edema in the patient’s relatives without revealing any allergoses in them. It is worth asking about cases of death of relatives from suffocation or frequent visits to surgeons about attacks of repeated severe abdominal pain without performing any surgical interventions. It is also necessary to find out whether the patient himself was ill with any autoimmune or oncological disease, whether he takes ACE inhibitors, angiotensin II receptor blockers, estrogens.
Analysis of complaints and examination data often makes it possible to roughly distinguish between hereditary and acquired angioneurotic edema. Thus, hereditary angioedema is characterized by slowly increasing and long-lasting edema, often affecting the mucous membrane of the larynx and digestive tract. Symptoms often appear after a minor injury in young people in the absence of any connection with allergens, while antihistamines and glucocorticoids are ineffective. At the same time, there are no other manifestations of allergies (urticaria, bronchial asthma), which is typical for edema of allergic etiology.
Laboratory diagnostics in non-allergic angioedema can reveal a decrease in the level and activity of the C1 inhibitor, autoimmune pathology and lymphoproliferative diseases. With angioneurotic edema associated with allergies, blood eosinophilia, an increase in the level of total IgE, positive skin tests are detected.
In the presence of stridorous breathing with laryngeal edema, laryngoscopy may be required, with abdominal syndrome – a careful examination by a surgeon and carrying out the necessary instrumental studies, including endoscopic (laparoscopy, colonoscopy). Differential diagnosis is performed with other edema caused by hypothyroidism, compression syndrome of the superior vena cava, pathology of the liver, kidneys, dermatomyositis.
Treatment of angioneurotic edema
First of all, with angioedema of any etiology, it is necessary to eliminate the threat to life. To do this, it is important to restore the patency of the respiratory tract, including by intubation of the trachea or conicotomy. With allergic angioedema, glucocorticoids, antihistamines are administered, contact with a potential allergen is eliminated, infusion therapy, enterosorption is performed.
With angioneurotic edema of hereditary genesis in the acute period, it is recommended to introduce a C1 inhibitor (if available), freshly frozen native plasma, antifibrinolytic drugs (aminocaproic or tranexamic acid), androgens (danazole, stanozole or methyltestosterone), and with angioedema in the face and neck – glucocorticoids, furosemide. After the condition improves and remission is achieved, treatment with androgens or antifibrinolytics continues. The use of androgens is contraindicated in childhood, in women during pregnancy and lactation, as well as in men with malignant tumors of the prostate gland. In these cases, an oral solution of aminocaproic (or tranexamic) acid is used in individually selected doses.
Patients with hereditary angioneurotic edema before dental procedures or surgical interventions as a short-term prophylaxis are recommended to take tranexamic acid two days before surgery or androgens (in the absence of contraindications) six days before the surgical procedure. Immediately before the invasive intervention, it is recommended to perform an infusion of native plasma or aminocaproic acid.
Prognosis and prevention
The outcome of angioneurotic edema depends on the severity of the manifestations and the timeliness of therapeutic measures. Thus, laryngeal edema in the absence of emergency care ends in death. Recurrent urticaria, combined with angioneurotic edema and lasting for six months or more, is further observed in 40% of patients for another 10 years, and 50% may experience prolonged remission even without supportive treatment. Hereditary angioedema periodically recurs throughout life. Properly selected supportive treatment avoids complications and significantly improves the quality of life of patients with angioneurotic edema.
With an allergic genesis of the disease, it is important to observe hypoallergenic nutrition, refuse to take potentially dangerous medications. With hereditary angioedema, it is necessary to avoid damage, viral infections, stressful situations, taking ACE inhibitors, estrogen-containing drugs.
- Levy D. A., Khouader S., Leynadier F. Allergy to latex condoms // Allergy. — 1998. — Vol. 53, № 11. — Р. 1107–1108.link
- Asad H., Gohar A. Incidence of angiotensin-converting enzyme-associated angioedema among african americans compared to other races // Chest. — 2019. — Vol. 156, № 4.
- Prussin C., Metcalfe D. D. IgE, mast cells, basophils, and eosinophils // The Journal Of Allergy And Clinical Immunology. — 2003. — Vol. 111, № 2, Suppl 2. — P. 486–494.link
- Li H. H. Angioedema // Мedscape. — 2018.
- Loftus P. A., Tan M., Patel G. et al. Risk factors associated with severe and recurrent angioedema: an epidemic linked to ACE-inhibitors // Laryngoscope. 2014. — Vol. 124, № 11. — Р. 2502–2507.link
- Atalay E., Özdemir M. T., Сigsar G. et al. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death // Iran J Allergy Asthma Immunol. — 2015. — Vol. 14, № 6. — Р. 642–645.link
- Farkas H., Varga L. Ecallantide is a novel treatment for attacks of hereditary angioedema due to C1 inhibitor deficiency // Clin Cosmet Investig Dermatol. — 2011. — № 4. — Р. 61–68.link
- Evrensel A., Unsalver B. O., Ceylan M. E., Cоmert G. Sertraline induced angioedema // JNBS. — 2014. — Vol. 1, № 3. — Р. 97.