Osler-Waber-Rendu Disease

Definition:

Osler-Weber-Rendu disease is a genetic disorder is a genetic disorder causing multiple abnormalities in the blood vessels. It is also well known with the name of Hereditary Hemorrhagic Telangiectasia (HHT). In this disease there are arteriovenous malformations missing of the capillaries in between, hence arterial vessels flow directly into veins rather than into the capillaries. When this occurs in the skin surface vessels, they are able to be seen as red markings known as telangiectases, hence the name HHT.

(Thomas E. Andreoli, 1997)

Etiology:

Mutations in the ENG, ACVRL1, and SMAD4 genes are the basis for hereditary hemorrhagic Telangiectasia. HHT type-1, which is caused by mutations in the gene ENG. Type-2 is caused by mutations in the gene ACVRL1. Juvenile polyposis/HHT syndrome is caused by mutations in the gene SMAD4. All these genes give commands for building proteins that are found in the lining of the blood vessels. These proteins act together with growth factors that organize blood vessel growth. The gene concerned in HHT type-3 is not known, but is supposed to be situated on chromosome 5. Mutations in these genes by and large prevent the creation of the related protein, or end result in the creation of a faulty protein that can’t accomplish its normal function. Affected person with a mutated gene will consequently have a reduced amount of the functional protein presented in the blood vessels’ lining tissue. This deficit is supposed to produce the signs and symptoms of HHT.(Wallace GM,2005)

Diagnosis:

Positive family history is a principal explanation to diagnosing HHT. If one parent has HHT, the child is supposed to be vigilantly watched and screened with pulse oximetry every 2 or 3 years to identify pulmonary arteriovenous malformations.. Genetic testing for HHT became available in late 2003. Diagnostic criteria are based on four components. The diagnosis is considered definite if three criteria are present and possible if two criteria are present and unlikely if fewer than two criteria are present. These criteria are: Nosebleeds ; Presence of Spontaneous and recurrent nosebleeds

Multiple Telangiectases; at typical sites, including the lips, oral cavity, fingers, and nose

Presence of internal visceral lesions; Gastrointestinal telangiectasia, pulmonary arteriovenous malformations, hepatic arteriovenous malformations, cerebral arteriovenous malformations, spinal arteriovenous malformations.

Family history  A first-degree relative with HHT according to these criteria. (Guttmacher AE, 200)

Who does it affect?

This disorder is inherited in an autosomal dominant pattern. In the majority of cases, an affected one has one parent with the disease. Every kid of a parent with an HHT gene has a fifty % possibility of inheriting this anomalous gene.

Symptoms:

The disease has a broad range of presentations in different patients. They may be symptom free or have several organs involvement, presenting at any age of life.

If it involves the nasal mucosa nasal bleeding or epistaxis is the most common symptom of the disease and takes place in majority of affected patients. Bleeding may occur every day or once a month.  These patients mostly present before the second decade of life. Blood transfusions are vital in ten to thirty percent of patients.

Gastrointestinal tract involvement causes recurrent painless GI bleeding in ten to forty percent of patients and usually takes place later in life typically around the fourth or fifth decades of life. Patients might report abdominal pain that could be due to thrombosis of intestinal arteriovenous malformations. (Pasculli G, 2004)

Lungs involvement is in fifteen to twenty percent of patients with the disease. Half of these patients are asymptomatic. Dyspnea and exercise intolerance is clear form the history. Cyanosis, hypoxemia, and secondary polycythemia are usually common in such patients.

Patients usually present around the third or fourth decades of life with hemoptysis which results from either telangiectasia of the trachea and bronchi or pulmonary arteriovenous fistulas. Migraine headaches are present in thirteen to fifty percent of patients with Osler-Weber-Rendu disease who have lung involvement.

CNS involvement occurs in eight to twelve percent of patients with Osler-Weber-Rendu Disease. A history of headache, seizures, and focal neurologic symptoms might be recognized on inquiring.

Fatigue has been noticed in such patients attributed to an iron deficiency anemia caused by recurrent blood loss.

Visual disturbances might be noted probably caused by intraocular bleeding. Patients might observe blood in tears, which is due to conjunctival telangiectases.

Liver involvement might present with right upper quadrant pain, jaundice, symptoms of high-output cardiac failure, and bleeding from esophageal varices. Infrequently, patients with Osler-Weber-Rendue disease may present with uncommon cirrhosis.

Pathology:

 The clinical symptoms of Osler-Weber-Rendu disease are caused by the growth of anomalous vasculature, including telangiectases, arteriovenous malformations, and aneurysms. Defects in the endothelial cell junctions leading to its degeneration, and weakness of the connective tissue around the vessels are thought to cause dilation of capillaries and postcapillary venules, which is evident as telangiectases.

Usually telangiectases involve the mucous membranes, the skin, retina, the conjunctiva, and the gastrointestinal tract. Arteriovenous malformations are found in the brain, lungs, and liver.

Treatment:

The recommended treatment for a telangiectases or arteriovenous malaformations related to this disease depends together on its size and site in body. They should be treated if they are causing a problem, such as frequent nosebleeds. Telangiectasia of the nose or skin can be treated with laser therapy and dermoplasty in which nasal mucosa is replaced with autologous skin graft.

Bleeding from the stomach or intestines is generally treated only if it causes anemia Serious GI bleeds endangering life can be efficiently treated by segmental bowel resection. Embolization, ligation, or surgical excision is recommended for expanding or symptomatic pulmonary arteriovenous fistulas or for intrahepatic fistulas.

Lungs and brain arteriovenous malformations ought to be treated prior to they cause harm in most cases. Lung AVMs can almost be treated using an outpatient procedure called embolization.

Brain AVMs are cared for in special ways depending on the size, structure and site in the brain of the anomalous blood vessel. Embolization, surgery, and radiosurgery can all be used, separately or in combination for brain involvement.

Iron and folate supplements can be required by the patient experiencing chronic blood loss.

Combination oral contraceptives have been revealed to be more useful than estrogen alone in GI bleeding. Topical preparations of estrogen and/or progesterone combinations (ethinyl estradiol 30 mcg and norethindrone 1.5 mg) can be used to help strengthen mucosa and decrease the susceptibility of the mucosa to external trauma.

Nursing Considerations:

Women using these drugs should immediately report to their physicians if signs or symptoms of any of the following occur:  abdominal pain, numbness, stiffness in legs, or buttocks, pain or heaviness in chest, shortness of breathing, severe headache, visual changes, vaginal bleeding or discharge, breast lumps, swelling of hand s or feet, yellow skin or sclera, dark urine, or light pale stools. If patient has DM advise her to report if blood glucose levels are elevated to adjust oral hypoglycemic agents. Women should discontinue taking the medication if they suspect they are pregnant or become pregnant

Antifibrinolytics agents (Aminocaproic acid) are used to improve hemostasis when bleeding is due to fibrinolysis. Aminocaproic acid might stop mucosal bleeding until bleeding stops. Before administration, check Blood Urea Nitrogen Creatinine and urine for presence of blood. Avoid fast IV injection; may cause hypotension, bradycardia, and arrhythmias. Instruct patient to report any signs of bleeding appears. It is contraindicated in patients with disseminated intravascular coagulation (DIC) due to the risk of unopposed, diffuse intravascular clotting. It is contraindicated in hematuria of upper urinary tract origin due to ureteral obstruction from clots, with ensuing renal failure. Monitor for and report any of the above undesirable effects.( Sandra M. Nettina, 2005)

Reference: 

Thomas E. Andreoli, Charles C. J.Carpenter, (1997).Cecil Essentials of Medicine, 4th edition, W. B. SaundersCompany, pg 408

Pasculli G, Resta F, Guastamacchia E, Di Gennaro L, Suppressa P, Sabba C (2004). Health-related quality of life in a rare disease: hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease. Qual Life Res. Dec;13(10):1715-23.

Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H.(2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. Mar 6;91(1):66-7.

Sandra M. Nettina,(2005). Lippincott Manual of Nursing Practice, Lippincott Williams & Wilkins, pg 1065

Cole SG, Begbie ME, Wallace GM, Shovlin CL (2005).A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5. J Med Genet. Jul;42(7):577-82.