Rendu-Osler disease: causes, symptoms, diagnosis and treatment. Hereditary diseases. Symptoms and treatment of Osler-Weber randu disease Osler randu treatment

For this purpose bleeding surfaces irrigate with preparations containing substances that prevent the resorption of blood clots– aminocaproic acid, thromboplastin, thrombin.

In addition, oral hemostatic medications (Vikasol, Dicynon) can be used, although their use does not always give the desired result.

Rendu-Osler disease (congenital hemorrhagic telangiectasia) - an autosomal dominant disease characterized by multiple telangiectasias of the skin and mucous membranes, as well as hemorrhagic syndrome of various localizations. The disease occurs with a frequency of 1 case per 50,000 population, and according to Guttmacher, McKinnon, Upton - 1 case per 16,500 population.

A genetic defect has now been identified in this disease. McDonald et al. and Shovlm discovered the Randu-Osler disease gene in the region of chromosome 9 9q33-34 (OWR1 locus) in some families of patients. This gene has been identified as the endoglin gene (McAllister, Grogg, Johnson). Endoglin is an integral membrane glycoprotein expressed by endothelial cells of arterioles, venules and capillaries. This glycoprotein serves as a binding protein for the cytokine TGF-β (transforming growth factor). Cholvin discovered the Randu-Osler disease gene in the region of chromosome 12 12q (OWR2 locus) in other families. The latter gene has not been identified but is thought to be related to other TGF-β receptors.

The mechanism of implementation of genetic defects in Rendu-Osler disease not completely clear. The dominant idea is that congenital mesenchymal deficiency causes the occurrence of telangiectasia. The vascular wall is devoid of muscle and elastic fibers, consists almost entirely of endothelium and is surrounded by loose connective tissue. Venules and capillaries forming telangiectasia are sharply thinned, postcapillary venules are dilated and anastomose with arterioles through capillary segments (arterial-venular anastomoses are a characteristic sign of the disease). There are also degenerative changes in the mesenchyme (loosening of connective tissue), accumulation of leukocytes and histiocytes around the vessels, underdevelopment of skin papillae and poor development of sweat glands, and a decrease in the number of hair follicles.

Bleeding during Rendu-Osler disease due to the extreme fragility of small blood vessels. At the same time, some patients also have platelet dysfunction (Endo, Mamiya, Niitsu) and activation of fibrinolysis. However, these changes are rare and are not considered characteristic of Randu-Osler disease.

Clinical picture

Symptoms of the disease in the form of bleeding of various locations can appear in early childhood, even in the neonatal period, and naturally persist throughout life. However, skin manifestations of the disease usually become clearly visible much later, usually between the ages of 20 and 40.
Telangiectasia is a pathognomonic sign of Randu-Osler disease. They are small, bright red, purple spots or vascular “spiders” protruding above the surface of the skin, or bright red nodules with a diameter of 1 to 7 mm. When pressing on telangiectasia, the nodules turn pale and are distinguished by this
from other hemorrhagic manifestations. In early childhood, typical telangiectasias on the skin are very rarely visible. Similar telangiectasias appear on the mucous membrane of the mouth, nose, and gastrointestinal tract. They can also be located on the skin of the face, lips, in the nail bed area, and on the hands. By frequency, the localization of telangiectasia in the mucous membranes is distributed as follows: nose, lips, palate, throat, gums, cheeks, respiratory tract, gastrointestinal tract, genitourinary system (N. A. Alekseev).

With microtraumas, infectious diseases (viral, bacterial), especially with the development of rhinitis, with intense physical activity and even with an acute psycho-emotional stressful situation, telangiectasia can bleed, the severity of bleeding varies. Quite often spontaneous bleeding from telangiectasia develops.

Bleeding - the most characteristic sign of the disease.

90% of patients experience nosebleeds, which are often repeated.

In 5-30% of patients, arteriovenous anastomosis in the lungs is observed, more often in individuals with mutations in the region of chromosome 9q. Arteriovenous anastomoses are most often localized in the lower lobes of the lungs and are usually multiple. Such patients experience shortness of breath, general weakness, decreased performance and
exercise tolerance, cyanosis (due to mixing of arterial and venous blood in the lungs), hemoptysis (often severe pulmonary hemorrhage), hypoxemic erythrocytosis. Subsequently, pulmonary and pulmonary-heart failure may develop.

Approximately 20% of patients have bleeding from the gastrointestinal tract, but they usually appear at the age of 40-50 years. About 40% of all gastrointestinal bleeding occurs from the upper sections, about 10% from the large intestine, and in 1/2 of patients it is not possible to accurately determine from which section of the gastrointestinal tract the bleeding is developing. There is no spontaneous decrease in the frequency of gastrointestinal bleeding; on the contrary, the frequency and intensity of bleeding gradually increases.

The liver is rarely involved in the pathological process. There may be an enlargement of the liver and a violation of its functional ability. The development of arteriovenous shunts in the liver can lead to the formation of liver cirrhosis. Bernard, Mion, Henry et al. described anicteric cholestasis and atypical cirrhosis of the liver in patients with Randu-Osler disease.

In some cases, neurological symptoms may appear in the form of clinical intracerebral hemorrhages and local symptoms of cerebrovascular accident. Neurological symptoms are caused by the development of telangiectasia, arteriovenous aneurysms or cavernous hemangiomas in the brain.
It should be emphasized that often the main clinical manifestations of Randu-Osler disease can be isolated gastrointestinal bleeding or bleeding from the urinary tract, or hemoptysis in the complete absence of telangiectasia on the skin and visible mucous membranes. In such a situation, endoscopic examination methods help in making a diagnosis.

Laboratory data

General blood analysis. With frequent, recurrent bleeding, chronic posthemorrhagic hypochromic anemia develops. There are usually no other changes in the general blood test.

General urine analysis. With the development of telangiectasia in the urinary tract and bleeding, macro- or microhematuria is detected.

Blood chemistry. As a rule, no significant changes are detected. However, when the liver is involved in the pathological process, especially during the formation of liver cirrhosis, there is an increase in the content of bilirubin, alanine and aspartic aminotransferases in the blood.

Studies of the hemostasis system. In most patients, laboratory parameters reflecting the state of the hemostatic system are normal. Only in some cases minor changes in the coagulogram are observed.

Ultrasound examination of the liver and spleen reveals their increase, as a rule, with the formation of liver cirrhosis. Using Doppler ultrasonography, it is sometimes possible to detect arteriovenous aneurysms in the vascular system of the liver.

X-ray of the lungs In rare cases, it reveals small focal shadows during the formation of arteriovenous shunts in the lungs. In some cases, computed tomography of the lungs may be informative.

Determination of blood oxygen saturation. When arteriovenous shunts form in the lungs, a decrease in blood oxygen saturation can be detected.

Fibroesophagogastroduodenoscopy detects telangiectasia on the mucous membrane of the esophagus, stomach, and duodenum.

Diagnosis

Diagnosis of Randu-Osler disease is based on the following main signs:

• detection of telangiectasia on the skin and mucous membranes;
• familial nature of the disease;
• absence of pathology in the hemostatic system.

Rendu-Osler disease is a hereditary pathology that manifests itself through damage to the walls of blood vessels. Due to genetically determined lesions, many small hemorrhages are observed, called telangiectasia in the medical literature.

Rendu-Osler disease

This disease was first described by a doctor of French origin, Louis Randu. At the turn of the 19th and 20th centuries, the information was supplemented by data from doctors Osler and Weber. But the real reason for the appearance of hemorrhages in patients was determined only recently.

According to statistics, Rendu-Osler disease, also known as hemorrhagic telangiectasia, occurs approximately 1 time in 5 thousand people. The pathology is not associated with gender and manifests itself before the age of 50.

ICD-10

In the International Classification of Diseases, hemorrhagic telangiectasia has code 178.0. It is classified in the subclass “Capillary diseases”.

Classification

According to the clinical manifestations, the pathology was divided into several types. They are based on assessing the location of hemorrhages.

The following types of Rendu-Osler disease have been identified:

1. Nasal – the vessels of the nasal mucosa are damaged, which causes frequent nosebleeds.
2. Pharyngeal - rashes are detected on the mucous membrane of the pharynx.
3. Skin – hemorrhages are localized in some areas of the skin.
4. Visceral – damage to the membranes of internal organs is observed.
5. Mixed - rashes are present both on the skin and on the external and internal mucous membranes.

Causes

This disease is hereditary, that is, it is transmitted with genetic material from mother to child. The occurrence of Randu-Osler disease may be a consequence of disturbances in the structure of two genes.

The first gene is responsible for normal collagen synthesis in the body. This substance is not only responsible for the normal elasticity of the skin, but is also part of the walls of blood vessels. Due to disturbances in the structure of the substance, pinpoint hemorrhages become possible.

The second gene is responsible for the synthesis of a cellular receptor that is sensitive to tumor growth factors.

Randu-Osler syndrome is a dominant feature. If one of the parents has a defective gene, it will be passed on to the child.

There are cases where a mutation in a gene occurs spontaneously, but they are quite rare. The reason for the influence on the fetus in the womb is believed to be infectious agents or chemicals, and this is still only a theory.

Pathogenesis

A normal vascular wall consists of three layers:

1. Internal;
2. Average
3. External.

Which contain:

• Connective tissue;
• Nerve endings;
• Smooth muscles.

Due to a genetic defect, the vessels do not receive their usual structure. In patients, they have only an endothelium surrounded by loose collagen fibers.

This leads to pathological expansion of capillaries in certain areas. The phenomenon of angiomatosis also occurs - excessive growth of the vascular network.

As a result of violations, the following arise:

• Telangiectasia - “stars” on the skin and mucous membranes, which are actually dilated capillaries;
• Arteriovenous shunts are pathological connections of vessels in which arterial and;
• Aneurysms are bulges on the surface of the vascular walls.

Due to connective tissue pathology, arteries become more fragile. Cases of their damage are becoming more frequent, which leads to hemorrhages.

Clinical picture

Characteristic manifestations of the disease are “stars” of blood vessels that protrude on the mucous membranes and surface of the skin. It is telangiectasia that allows the doctor to suspect the presence of a hereditary Randu-Osler disease in a patient and confirm it.

Initially, the rash appears as simple redness in the form of spots. Gradually the defect turns into a scarlet nodule. Most often, telangiectasias appear:

• In the area of ​​the nasolabial triangle;
• On the head;
• Fingers;
• Nasal mucous membranes;
• Pharynx, trachea, esophagus.

Types of telangiectasia The most important symptoms of Randu-Osler disease:

1. Telangiectasia.
2. Bleeding from angiomas - clearly visible plexuses of blood vessels on the surface of the skin and mucous membranes.
3. Frequent nosebleeds. Sometimes hemoptysis, indicating hemorrhage from the wall of the stomach or bronchi.
4. The CBC (complete blood count) shows signs of anemia. The hemoglobin level and the number of red blood cells decrease (sometimes increase as a result of compensatory reactions), which causes corresponding clinical symptoms.

The most important syndromes for this disease are hemorrhagic and anemic. The latter is a direct consequence of the first. Due to frequent minor bleeding, the blood loses red blood cells and hemoglobin.

Signs of hemorrhage are hemoptysis, traces of blood in the urine or stool, external bleeding from the nasal cavity or pharyngeal mucosa.

Due to progressive anemia, the patient becomes lethargic, shortness of breath, fatigue, and pale or bluish skin appear.

Constant blood loss leads to slow depletion of the hematopoietic system, pulmonary heart failure and other pathologies.

Risk factors

Minor household injuries can provoke the appearance of bleeding in Rendu-Osler disease.

So are other factors:

1. Stress and nervous tension.
2. Sleep disturbances.
3. Constant use of Aspirin.
4. Rhinitis, sinusitis.
5. Alcohol.

Diagnostics

A doctor can make a diagnosis of “hemorrhagic telangiectasia” using anamnesis data, confirming his assumptions using laboratory and instrumental research methods.

The main symptom that a specialist will pay attention to is the characteristic “stars” on the skin and mucous membranes. After this, he will ask the patient how often bleeding occurs and what additional complaints there are.

The presence of malaise, shortness of breath during exercise, and dizziness will help the doctor quickly determine the expected diagnosis.

To confirm it, the following laboratory tests are carried out:

• CBC (complete blood count) - will show a decrease in hemoglobin (normally in men - 130 - 170, in women - 120 - 160);
• biochemical blood test - most often reveals iron deficiency, which is a consequence of the constant loss of the element during bleeding;
• clotting tests - sometimes intravascular coagulation is detected;
• OAM (general urinalysis) - red blood cells are often detected that enter the urine during bleeding from the mucous membranes of the urinary tract.

To detect telangiectasia on the mucous membranes of internal organs, instrumental diagnostics are performed.

The following methods are used:

1. FEGDS (fibroesophagogastroduodenoscopy) – examines the esophagus, stomach and initial parts of the small intestine.
2. Colonoscopy is an examination of the large intestine.
3. Bronchoscopy - detection of hemorrhages on the bronchial mucosa.
4. Cystoscopy is an endoscopic examination of the urinary tract.

Possible complications

The most dangerous complications of this disease are:

• massive blood loss leading to coma and neurological disorders;
• internal bleeding, which is difficult to diagnose;
• hemorrhagic strokes, the operation of which threatens even greater hemorrhages.

Pregnancy and Rendu-Osler disease

Pregnant women with this pathology are considered a high-risk group. During the supervision (examination) of pregnancy, a hematologist is involved, who advises the woman on possible complications.

Most often, problems occur during the second and third trimesters. Often at this time the woman is hospitalized in the department for observation.

Any instrumental studies using an endoscope are contraindicated in pregnant women with hemorrhagic telangiectasia. They also do not undergo MRI (magnetic resonance imaging).

This hereditary pathology rarely causes serious bleeding during childbirth. However, such women should be under close supervision of specialists.

Treatment

Since this pathology is the result of a genetic defect, all treatments are symptomatic and aimed at reducing blood loss and preventing its complications.

The treatment regimen for Randu-Osler disease consists of several points:

• Stopping and preventing bleeding.
• Restoring normal blood composition in case of large blood losses.
• Elimination of spider veins.
• Surgical interventions for major vascular disorders.

The most effective method of stopping nosebleeds is irrigation of the mucous membrane with a 5-8% solution of aminocaproic acid.

Also, after the blood has actually stopped, medications containing lanolin, dexpanthenol and vitamin E are used topically. These substances help the choroid restore its integrity.

Less effective methods of combating such blood loss are irrigation of the mucous membrane with hydrogen peroxide. It can be used at home to reduce the intensity of bleeding.

To prevent vascular damage in Rendu-Osler disease, systemic hormonal therapy with testosterone or estrogen is also used.

Prevention

Preventive measures for Randu-Osler disease include:

1. Referring to people with telangiectasia for advice from a geneticist when planning pregnancy.
2. Sufficient and comprehensive nutrition.
3. Hardening the body.
4. Maintaining a daily routine.
5. Avoiding stressful situations.
6. Quitting smoking and alcohol.

Prevention for Rendu-Osler disease is aimed at improving the quality of life. There is no way to eliminate the genetic cause of the pathology, but by adhering to these recommendations, you can avoid frequent bleeding and associated complications.

Life forecast

A patient with Randu-Osler disease has a positive prognosis for life if he sees a doctor on time for treatment and follows preventive recommendations. Most often, complications appear in people who ignore the symptoms described above and neglect to consult a doctor.

Characterized by telangiectasia - local dilation of small vessels (venules and capillaries) due to their structural inferiority; manifests itself as hemorrhages.

The disease is inherited in an autosomal dominant manner. Most patients have a heterozygous form of the disease; the homozygous form is extremely rare. Some researchers believe that local dilation of blood vessels occurs as a result of hereditary inferiority of the mesenchyme and disruption of serotonin metabolism, while others suggest that telangiectasia are microvessels newly formed from the remains of embryonic tissue.

Clinical picture. Telangiectasia begins to form at the age of 6-10 years, most clearly manifesting itself at the age of 40-50 years. They have small (1-3 mm) flat, non-pulsating, purple-violet formations that turn pale when pressed, often bleeding with minor trauma. Telangiectasia can be localized on the mucous membrane of the nose, lips, gums, tongue, cheeks, on the skin of the scalp, face (telangiectasia on the wings of the nose and earlobes are especially pathognomonic), limbs, torso, as well as on the conjunctiva and under the nails; in the generalized form and in internal organs (lungs, spleen,) and bones (usually the spine). Characterized by frequent, profuse nosebleeds not associated with external causes, which are observed in 80% of patients. Less common are bleeding from the gastrointestinal tract, pulmonary hemorrhages, hemorrhages in and around the retina. Hypochromic, iron deficiency (see Anemia) is detected, and after heavy blood loss - erythroid elements of the bone marrow, thrombocytosis. Tests reflecting the state of coagulation and platelet hemostasis were not changed.

The disease is often combined with vascular anomalies (pulmonary vascular aneurysms and angiomas in the lung tissue), leading to the formation of pulmonary arteriovenous anastomoses, which are found in 15% of patients and their family members on X-ray examination. Clinically, a combination of symptoms of blood loss and hypoxemia is observed due to the mixing of arterial and venous blood. When hypoxemia predominates, patients often develop a secondary one (see Polycythemia). In some cases of the disease, arteriovenous anastomoses can be found in the brain, retina, as well as aneurysms of the hepatic and splenic arteries and the aorta. In patients with extensive hemangiomatous lesions of the hepatic vessels, splenomegaly, Portal hypertension with signs of liver cirrhosis (Osler).

Diagnosis established on the basis of the clinical picture and anamnesis data. The search for the source of internal bleeding is carried out using endoscopic methods - esophagogastroduodenoscopy (see Gastroscopy, Esophagoscopy), colonoscopy (Colonoscopy), bronchoscopy (Bronchoscopy), cystoscopy (Cystoscopy), as well as x-ray (see Angiography) methods. Differential is carried out with a number of hereditary, mild coagulopathies, which are characterized by changes in coagulation and platelet hemostasis, for example, with von Willebrand disease (see Hemorrhagic diathesis).

Treatment symptomatic. It is carried out on an outpatient basis, in case of significant blood loss - in a therapeutic or hematological hospital. To correct iron deficiency, drugs are indicated (gemostimulin, ferroplex, ferrocal); with more severe anemia, red blood cell mass. For nosebleeds, depending on their severity, tamponade is performed in the nasal cavity, nasal mucosa, mucous membrane with affected vessels, etc. (see Nosebleeds). In the presence of bleeding telangiectasia, cryogenic destruction is performed. When bleeding worsens during menopause, hormonal therapy is prescribed.

Forecast favorable for life in most cases.

Bibliography: Kassirsky I.A. and Alekseev G.A. Clinical, M., 1970; Guide to Hematology, ed. A.I. Vorobyova, vol. 2, p. 334, M., 1985; Seldin M.A. and others. Cryotherapy for Osler's disease, Ter. ., t. 50, no. 7, p. 97, 1978, bibliogr.

1. Small medical encyclopedia. - M.: Medical encyclopedia. 1991-96 2. First aid. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic Dictionary of Medical Terms. - M.: Soviet Encyclopedia. - 1982-1984.

See what “Osler-Randu disease” is in other dictionaries:

Osler ICD 10 I ... Wikipedia

RANDUE-OSLER-WEBER DISEASE- honey Rendu Osler Weber's disease is a hereditary angiopathy manifested by multiple telangiectasias and hemorrhagic syndrome. Frequency. 1:16000 population. Genetic classification Type I (* 187300, 9q33 q34.1, defect in gene synthesis... ... Directory of diseases

- (W. Osler, 1849 1919, English doctor; N. J. L. M. Rendu, 1844 1902, French doctor; synonym: hereditary hemorrhagic angioma, Osler’s disease, Randu Weber Osler’s disease, hereditary hemorrhagic telangiectasia) hereditary disease, ... ... Large medical dictionary- (Greek haimorrhagia bleeding) a group of diseases and pathological conditions of a hereditary or acquired nature, the common manifestation of which is hemorrhagic syndrome (a tendency to recurrent intense long-term, most often ... ... Medical encyclopedia

- (erythrocytoses; erythrocyte/s/ + ōsis) increase in hemoglobin content and number of red blood cells; are not caused by diseases of the blood system. There are absolute (primary and secondary) E. caused by reactive enhancement of normal... ... Medical encyclopedia

Main article: Dr. House ... Wikipedia

I Gastritis (gastritis; Greek gaster stomach + itis) inflammatory or inflammatory-dystrophic changes in the gastric mucosa. It can be primary and considered as an independent disease and secondary, accompanying a series of... ... Medical encyclopedia