INTRODUCTIONRendu-Osler-Weber (ROW) disease is a hereditary blood vessel disease with an estimated prevalence of 1 in 10,000 people in the Netherlands. This description provides some brief information about ROW, as knowledge about this rare disease is often limited. ROW is also known as hereditary hemorrhagic telangiectasia.GENETICSROW is dominantly inherited and not sex-linked, meaning that either the father or mother can pass on the faulty (mutated) gene, and there is a 50% chance that a child of a parent with the disease will develop the disease. The genetic basis lies in mutations on either chromosome 9 or 12. A mutation on chromosome 9 leads to a form (ROW-1) with frequent abnormalities of the lungs and brain. A mutation on chromosome 12 leads to a form (ROW-2), in which primarily the skin and mucous membranes are affected.DISEASE PICTUREROW is characterized by the development of direct connections between arteries and veins, with the absence of capillaries. Small connections (telangiectasias) occur on the skin (face and fingers) and mucous membranes (lips, mouth, nose). Nosebleeds are therefore frequent (90%) and can usually begin at a young age. The skin lesions usually develop after puberty and increase in severity. Telangiectasias of the gastrointestinal tract occur in approximately 30% of ROW patients and lead to blood loss and anemia, especially in middle age.
Larger connections between arteries and veins (arteriovenous malformations, AVMs) occur in the lung (PAVM) in 35% of ROW-1 patients and in 10% of ROW-2 patients, in the brain (CAVM) in 10-15%, and in the liver (HAVM) in 3-5%.
The most threatening location is the PAVM, which increases in size especially after puberty and during pregnancy. On the one hand, PAVM leads to "shunting," resulting in oxygen deficiency and reduced exercise tolerance (tiredness). On the other hand, clots—infected or otherwise—can pass through the filter of the pulmonary capillaries and lead, for example, to occlusion of leg or brain vessels (emboli) or to inflammation (abscess), with a brain abscess being particularly dangerous.
Such emboli occur in up to 50% of untreated PAVMs. Finally, PAVM can lead to bleeding (in the trachea or chest cavity).
Usually, there are no symptoms until a complication occurs.
CAVM has an estimated risk of bleeding of 0.5% per year. Beforehand, there are usually no symptoms, sometimes seizures. Migraines are common in ROW, but are generally not indicative of CAVM.
HAVM can lead to increased pressure in the pulmonary artery and cardiac weakness due to "shunting." A vascular murmur is then heard over the liver.DIAGNOSISAlthough ROW is a congenital condition, the first symptoms (usually nosebleeds) usually appear in childhood between the ages of 10 and 15. However, nosebleeds are not a prerequisite for diagnosis. Conversely, nosebleeds and ROW in one parent are insufficient grounds for diagnosis (in a child).
The clinical diagnosis is made based on a combination of relationship and nosebleeds, and the presence of typical telangiectasias in the usual locations or the presence of an AVM. Knowledge of the telangiectasias is essential. In adults, the diagnosis can sometimes be uncertain or rejected. In children, uncertainty is more common. Fortunately, in the vast majority of the more than 100 Dutch families with ROW, the gene mutation is known. In these families, the genetic (hereditary) diagnosis can therefore be confirmed or rejected through DNA testing of the blood.SCREENINGPatients with the disease, as well as their family members, are advised to be screened for the presence of the disease and/or for dangerous locations elsewhere in the body. DNA testing is also an option. For understandable reasons, a distinction is made in the screening program for adults and children.
Children:
Screening should be performed in childhood to prevent complications of a PAVM. Significant PAVMs can reasonably be ruled out with a standard lung X-ray and oxygen measurement with a cap over the finger (oximetry). This test is not unpleasant or painful for children. It is sometimes possible to diagnose ROW at a young age. The typical telangiectasias are usually absent, even though the disease is present. Therefore, renewed testing is necessary after several years, after puberty, unless DNA testing (this does involve a blood test) has ruled out the disease. Because lung abnormalities can increase significantly during pregnancy, a repeat test is important before a potential pregnancy.
Adults:
The examination in adults is more comprehensive and consists of a general physical examination, possibly supplemented with microscopic examination of the nail fold and examination by an ENT specialist. Blood samples are also taken and a chest X-ray is performed. If the diagnosis of ROW is plausible, PAVM and CAVM can be ruled out with reasonable reliability using certain examination techniques (PAVM: blood oxygen measurement, cardiac ultrasound with contrast, chest X-ray, lung scan; CAVM: CT scan, MRI, intravenous angiography).TREATMENTTreatment of nosebleeds with cauterization or laser therapy unfortunately usually has only a temporary effect, so repeated treatments are often necessary. In severe cases, surgery, embolization, or hormone therapy can be considered. Closure of the nasal passages, for example, with a silicone prosthesis or patch, also reduces bleeding. In severe acute bleeding, tamponade for several days using Merocel tampons may be necessary.
Bleeding telangiectasias of the gastrointestinal tract are suitable for treatment with laser therapy and possibly hormone therapy.
PAVM with a supplying vessel greater than 3 mm should always be treated with embolization. Embolization involves occlusion of the supplying artery using IUDs. This is performed through a catheter in the groin under local anesthesia. The results of embolization are very good, but knowledge and experience with the procedure are necessary. Embolization should only be performed in specialized centers. One of the most important recommendations for PAVM is that patients with embolized or non-embolized PAVM should use antibiotics as a precaution during non-sterile procedures (such as dental extractions). In these situations, it is conceivable that bacteria can enter the bloodstream and spread via the bloodstream, potentially causing abscesses elsewhere in the body. Antibiotic use is also recommended for patients in whom PAVM cannot be definitively ruled out.
CAVMs can usually be treated with a special form of radiation therapy with an 80% chance of success. The location of embolization or surgery is still under discussion.
HAVMs are difficult to treat. The options are liver transplantation or embolization.OUTPUT CHECK-UPPatients with or without treated PAVM are advised to have annual checkups.
Patients without PAVM should have regular checkups every 3 to 5 years, unless there are additional problems, such as severe nosebleeds, intestinal bleeding, CAVM, or HAVM.SUMMARYROW is a hereditary vascular disease, meaning that 50% of a patient's children will have the disease. Patients with ROW can have symptoms in virtually any organ, but can also be symptom-free and still have, for example, the dangerous location in the lungs.
Screening family members before pregnancy is useful because the dangerous locations in the lungs and brain can be treated effectively and potential complications can be prevented.
St. Antonius Hospital in Nieuwegein and Martini Hospital in Groningen have multidisciplinary ROW working groups. Both collaborate on screening, registration, protocol development, and treatment of ROW. |
