What is Osler-Weber-Rendu Syndrome?
Osler Weber Rendu Syndrome, otherwise known as hereditary hemorrhagic telangiectasia refers to an autosomal dominant hereditary condition that is characterized by the development of atypical blood vessels of the skin, mucous membranes and visceral affectations including the lungs, liver and brain leading to excessive bleeding. The chromosomal abnormality can already be manifested and be passed on to generations just by having one defective gene.
The abnormality is described as a problem in the small capillaries which direct the arterial blood into the veins towards the heart. In this condition, the involved arteries join directly with the veins. Due to the difference in the blood pressure in the veins and arteries, the junction where the two blood vessels directly connect is likely to rupture, leading to hemorrhage in certain areas of the body.
In 10,000 people, around 1 person is affected with the disease or roughly 1.2 million worldwide. Most commonly affected are individuals from Africa, Asia and Arabia. Men and women are equally affected and usually the disease affects those who are 30 to 40 years of age. This is a separate condition from a blood clotting disease related to hemophilia. This disorder was named after William Osler (described a family with characteristic symptoms which include nosebleeds and multiple telangiectasia of the skin and mucous membranes) Henri Jules Louis Marie Rendu (stated the difference of the condition from hemophilia) and Frederick Parkes Weber (described angiomas) who explained the disease in medical literature separately.
HHT or OWR syndrome is a lifetime condition. With prompt and proper medical therapies, generally, this disease is controllable and affected individuals will only be subjected to episodic periods of disability associated with the bleeding.
Signs and Symptoms
The following are the clinical manifestations of OWR syndrome:
- The patient may complain of epistaxis which occurs frequently, hemoptysis, melena and other indications of acute gastrointestinal hemorrhage. Roughly about 20% have symptomatic gastrointestinal lesions which can, sooner or later lead to iron depletion due to chronic slow bleeding. In addition, the patient may report of repeated and spontaneous bleeding after suffering from a minor injury.
- In approximately 80% of the cases, patients exhibit skin and oral lesions which bleed less frequently however, are likely to become cosmetically disturbing. These red to violet small lesions measuring less than 5 millimeters in size may emerge more commonly in the lips, nose, hands and other areas which are frequently exposed to the sun.
In OWR syndrome, larger organs including the lungs, liver, brain and rarely the spinal cord are affected by arteriovenous malformations.
- Approximately 50% of affected individuals have vascular malformations in the lungs. Although these abnormalities in the vessels can cause coughing up of blood and hemothorax, still, hemorrhage is comparatively uncommon. The real problem is when the bacteria in the lungs migrate to the brain. Naturally, these organs have a filtering mechanism against microorganism and blood clots in the circulation. In the case of arteriovenous malformation, the capillary networks of the respiratory system are bypassed, permitting them to move to the brain. Once the microorganisms reach the brain, they initiate brain abscess and clots which predisposes an individual to brain stroke. Another problem these bring is that the deoxygenated blood coming from the right ventricle may detour the alveoli. The patient then experiences breathlessness as the already oxygen-depleted blood does not have an occasion to take in fresh oxygen from the lungs. When malformations involve the very large vessels, there is a significant incapacity of the body to receive adequate oxygen. Patient exhibits platypnea, cyanosis and clubbing of fingernails.
- Patient may report of headaches as arteriovenous malformations in the brain intermittently exert pressure to the surrounding tissues and organs. The frequency of seizure attacks may also be increased. The rupture of these abnormal vessels can result in subarachnoid or intracerebral hemorrhage. Patient then suffers severe headache, decreasing level of consciousness, body weakness and speaking difficulties.
- Clinically, arteriovenous malformations in the liver depend notably on the nature of the connections created between blood vessels. When arteries and veins are directly joined, there is a considerable volume of blood bypassing the organs, thus, the heart pumps more blood as a compensatory mechanism. In time, the patient develops congestive heart failure. When AVMs form a junction linking the portal vein and blood vessels in the liver, the result is portal hypertension, leading to the formation of collateral blood vessels in the esophagus which could hemorrhage aggressively.
Genetics plays an important role in the development of this disorder. Few genes are identified which are believed to cause the condition. There are about five different genetic types of hereditary hemorrhagic telangiectasia or OWR syndrome. Among these types, 3 of them are related to a specific gene abnormality while the other two are linked to a particular locus.
- HHT1 is due to mutation in gene endoglin. Patients with this type of disease are likely to have lung problems.
- HHT2 is due to gene transmutation in activin receptor-like kinase 1 and is mapped to the 12th chromosome. Affected individuals with this type of syndrome are likely to develop lung problems such as pulmonary arterial hypertension.
- HHT3 and HHT4 are associated with a particular locus.
- JPHT is related to MADH4 mutation. In addition to OWR syndrome, the patient may also have colonic polyposis and colorectal cancer. The defect can be located in the 18th chromosome.
The precise pathophysiology by which gene mutations that result to Osler Weber Rendu syndrome induce telangiectasias and arteriovenous malformations is still not transparent. However, its presence may disturb the stability among the pro- and antiangiogenic signals in the arteries, veins and capillaries.
As a preventive measure, couples who wish to have a child but have a family history of the genetic condition, then genetic counseling must be advised.
Rather than dealing with the disease itself, the treatment is directed towards blood loss reduction, minimization of sequelae of arteriovenous malformations which may occur in various body systems and prevention of common complications as there is no way AVMs can be stopped directly. The management for OWR syndrome lies primarily on how severe the condition has become, so it is important for a person to get early screening and be properly diagnosed. If the disease is still graded as mild, then, it may only require minor to no treatment at all. For a much more serious case;
There are many measures to be used to address acute nosebleeds which include the application of atraumatic packing in the nasal cavity with absorbent gels. When a patient experiences frequent heavy epistaxis, electrocautery and laser surgery are recommended. Initially, the occurrence of nosebleeds can be lowered when the nostrils are kept moist which can be achieved by utilizing a humidifier and lubricating the nasal lining with saline solution. If this becomes unsuccessful, generally a laser coagulation therapy can present satisfactory outcome with lesser risk of injury to the nasal lining compared to electric and chemical cauterization. For severe situations, septal dermoplasty is performed by a surgeon, wherein the nasal lining is surgically restored using a skin graft.
For digestive system
- Iron supplements in tablet form can be given if anemia is present. If the patient cannot tolerate taking the drugs orally, intravenous iron sucrose is administered.
- Generally, hemorrhage in gastrointestinal tract is not addressed with any specific treatment except when it is profuse enough to cause anemia. When the bleeding in the gastrointestinal tract becomes persistent, the patient may need to undergo an endoscopic argon plasma coagulation, laser therapy, segmental bowel resection and cautery of AVMs.
For Lung AVMs
For pulmonary AVMs, the treatment of choice is embolization with detachable metal coils. In this procedure, the patient is placed under general anesthesia and then, a catheter is inserted through a large vein in the groin towards the lungs to impede the bleeding artery. Once it has reached the pulmonary artery, the doctor will inject the contrast medium to visualize the area. After the lesions are detected, the metal coils are installed then.
For Liver AVMs
Treatment consists of antiarrhytmic drugs, diuretics to lessen the volume of blood in the circulation and salt and fluid intake restriction. If these therapies fail to be effective, the last selection is liver transplant.
For Brain AVMs
When there are arteriovenous malformations in the brain, it is necessary for the patient to immediately undergo craniotomy and open brain surgery for lesions grade I-V, endovascular embolization for small lesions with a single feeding vessel and stereotactic radiosurgery for tiny lesions yet adjacent to vital organs.
- To close up the telangiectasias, laser therapy, particularly the long pulsed Nd:YAG laser is an option.
- To improve clotting and decrease episodes of bleeding, the physician may consider adding hormonal therapy with combined estrogen and progesterone medications and an aminocaprioic acid. However, it is important for a patient that prior to treatment; he must undergo screening examinations to rule out pulmonary arteriovenous malformations. Current studies have revealed that the use of estrogen-related hormones raises a person’s risk of thrombotic events in affected patients who already have pulmonary AVMs.
- To restore blood volume, periodic blood transfusions must be given when blood loss becomes severe.
- Patients are restricted from taking drugs which diminish the ability of blood to clot such as aspirin.
- When there is a visible bleeding, locally apply pressure and administer vasoconstricting medications in topical form.
- Instruct the patient to protect himself from injury and from unwarranted bleeding, as well as interventions for minor episodes of hemorrhage and abrupt medical management for major bleeding.