Randu-Osler-Weber disease is one of the most common hereditary hemorrhagic telangiectasias, the cause of which is the failure of the vascular wall of some capillaries. Symptoms of the disease are frequent nosebleeds, telangiectasia on the skin and mucous membranes, with severe forms, gastric and pulmonary hemorrhages and chronic iron deficiency anemia can occur. Diagnosis is carried out by examining the patient, endoscopic examinations, sometimes by studying the hereditary history. There is currently no specific treatment for Randu-Osler-Weber disease, various hemostatic measures and supportive therapy are used.
Randu-Osler-Weber disease (hereditary hemorrhagic telangiectasia) is a hereditary vasopathy characterized by endothelial inferiority, which leads to the development of telangiectasia and difficult to stop bleeding. The disease was described at the turn of the XIX-XX centuries by researchers Henri Randu, William Osler and Frederick Parks Weber. Further research by geneticists proved the hereditary nature of the disease, it is transmitted by an autosomal dominant type. The penetrance of the pathological gene is currently unknown (as the gene itself is unknown), Randu-Osler-Weber disease affects both men and women with equal probability, but the severity of symptoms differs in different patients. The incidence of pathology is quite high and is estimated at 1:5000. In addition to hereditary forms of the disease, cases of sporadic development of symptoms are described.
The etiology and pathogenesis of Randu-Osler-Weber disease currently remain a subject for scientific discussion. Recent genetic data indicate that the structure of the transmembrane protein of endotheliocytes – endoglin or kinase-1 – is disrupted in patients. However, this does not explain vascular dysplasia, the signs of which are the absence of muscle and elastic membranes in some vessels. This leads to the fact that the vascular wall is represented by only one endothelium and the surrounding loose connective tissue. Since the cardiovascular system is a derivative of mesenchyma, this gives rise to some researchers to consider Randu-Osler-Weber disease a variant of embryonic mesenchymal dysplasia. Vessels devoid of muscular and elastic membranes form microaneurysms, which, easily damaged, lead to hemorrhages.
The persistence of bleeding in Randu-Osler-Weber disease is also explained by the fact that spasm of blood vessels near the site of injury plays an important role in the process of hemostasis. In the absence of a muscular membrane, reflex spasm becomes impossible, thereby greatly impeding the formation of a blood clot and stopping bleeding. Presumably, defects in some endothelial receptors also complicate the process of blood clotting in Randu-Osler-Weber disease. Confirmation of the fact that hemorrhages in this pathology are not directly related to the hemostasis system is the normal level of all coagulation factors in patients. Only in severe cases of the disease, thrombocytopenia and deficiency of other factors can be observed, but they are secondary in nature and are caused by consumption coagulopathy.
The first manifestations of Randu-Osler-Weber disease become noticeable at the age of 5-10 years, they are represented by emerging telangiectasias on the skin of the nose, face, auricles, lips, as well as the mucous membranes of the oral cavity. There are three types of vascular disorders that reflect the main stages of their development – early, intermediate and nodular. Early telangiectasias have the appearance of faint reddish dots and specks. The intermediate type of vascular disorders is characterized by the formation of noticeable meshes, “spiders” and asterisks on the skin. Nodular telangiectasia are nodules of 5-8 millimeters in size, slightly protruding above the surface of the skin or mucous membranes. The rate of transformation of vascular disorders, as well as their number and age of occurrence, reflects the severity of a particular case of Randu-Osler-Weber disease.
In addition to telangiectasias, patients develop hemorrhagic disorders over time, usually persistent and causeless nosebleeds occur first. It is very difficult to identify their source even with endoscopic rhinoscopy, the use of hemostatic sponges and turundum often do not contribute to stopping bleeding and even provoke it even more. There are cases of fatal outcome due to nosebleeds in Randu-Osler-Weber disease. As a rule, with such a clinical picture, the patient is referred for examination to a hematologist, but there are no signs of coagulopathy. If hemorrhages are of a prolonged or profuse nature, then dizziness, fainting, pallor and other anemic manifestations also join the symptoms of bleeding.
In more severe cases of Randu-Osler-Weber disease, patients may have signs of gastric (melena, vomiting of coffee grounds, weakness) and pulmonary bleeding. Sometimes patients complain of shortness of breath, weakness, cyanosis – this is a sign of right-left bypass of blood in the lungs due to arteriovenous fistulas. Telangiectasia occurs not only on the surface of the skin, there are also cerebral and spinal forms of vascular disorders. This leads to epileptic seizures, subarachnoid hemorrhages, paraplegia, as well as the development of brain abscess. Some familial forms of Randu-Osler-Weber disease are manifested mainly by cerebral symptoms and disorders with moderate severity of cutaneous telangiectasia and nosebleeds.
Diagnosis of Randu-Osler-Weber disease is made on the basis of patient complaints, physical examination, endoscopic studies of the gastrointestinal and respiratory systems. If there are signs or suspicions of the development of cerebral disorders, then magnetic resonance imaging of the head is performed. Patients complain of frequent and persistent nosebleeds, bleeding gums, appetite disorders, hemoptysis. Examination reveals various types of telangiectasia on the skin of the face, trunk, neck, mucous membranes of the mouth and nasal cavity. Endoscopic examinations (laryngoscopy, bronchoscopy, EGD) also reveal vascular disorders in the larynx and trachea, gastrointestinal tract, some of them bleed.
General and biochemical blood tests, often prescribed to the patient, may not reveal any disorders, including pathologies of the hemostasis system. Only with severe bleeding, signs of chronic iron deficiency anemia first appear – a decrease in the level of hemoglobin, the number of red blood cells, a decrease in the color index. However, in the case of the development of arteriovenous shunts in the lungs, the reverse picture of polycythemia may be observed. In the case of a further increase in the frequency and volume of bleeding, signs of a violation of the hemostasis system – a decrease in the level of platelets and other clotting factors – join the anemic symptoms. This is due to the development of consumption coagulopathy, indicating a severe form of Randu-Osler-Weber disease.
In the case of drawing up a hereditary history and detecting signs of Randu-Osler-Weber disease in relatives, it is necessary to perform preventive medical examinations from childhood. This is especially necessary if there are cerebral disorders in the symptom complex – in this case, starting from adolescence, preventive magnetic resonance imaging should be performed. MRI and CT scans of the brain may reveal subarachnoid bleeding and signs of a brain abscess. Timely implementation of preventive examinations can reveal such changes at an early stage, which will allow them to be successfully eliminated without serious consequences for the patient.
Treatment and prognosis
There is no specific treatment for Randu-Osler-Weber disease, mainly supportive measures are resorted to. Nosebleeds are best stopped by laser ablation, however, it will not protect against their recurrence. A short-term effect of stopping hemorrhage can give irrigation of the nasal cavity with a cooled solution of aminocaproic acid, so experts recommend that patients constantly have it at home. In the case of the development of pulmonary and gastrointestinal bleeding, they can be stopped by endoscopic techniques, and when they are abundant, they resort to the help of surgeons. Surgical intervention is also indicated for complications of Randu-Osler-Weber disease, such as right-left bypass surgery and subarachnoid hemorrhage. In addition, supportive treatment with vitamins and iron preparations is prescribed for anemia. In severe cases, they resort to blood transfusion or erythrocyte mass.
The prognosis of Randu-Osler-Weber disease is uncertain in many cases, since everything depends on the severity of vascular disorders. A hereditary history can help clarify the picture in this regard – as a rule, the symptoms of pathology in relatives are quite similar. The prevalence of cerebral manifestations of the disease, which often lead to epilepsy, strokes, and brain abscesses, sharply worsens the prognosis. With the development of even minor nosebleeds, patients should urgently contact medical institutions, since it is often not possible to stop it at home.