Sample records for telangiectasia hemorragica hereditaria . Etiology A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated gene which. Support Groups Ataxia Telangiectasia Children’s Project: National Ataxia Dyschromatosis universalis hereditaria in an African American male. Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber– Rendu disease and Osler–Weber–Rendu syndrome, is a rare autosomal dominant.
|Published (Last):||10 December 2008|
|PDF File Size:||17.92 Mb|
|ePub File Size:||3.66 Mb|
|Price:||Free* [*Free Regsitration Required]|
Hereditary hemorrhagic telangiectasia HHTalso known as Osler—Weber—Rendu disease and Osler—Weber—Rendu syndromeis a rare autosomal dominant genetic disorder that leads to telwngiectasia blood vessel formation in the skinmucous membranesand often in organs such as the lungsliverand brain. It may lead to nosebleedsacute and chronic digestive tract bleedingand various problems due to the involvement of other organs.
Treatment focuses on reducing bleeding from blood vessel lesions, and sometimes surgery or other targeted interventions to remove arteriovenous malformations in organs. Chronic bleeding often requires iron supplements and sometimes blood transfusions.
HHT is transmitted in an autosomal dominant fashion, and occurs in one in 5, people. Telangiectasia small vascular malformations may occur in the skin and mucosal linings of the nose and gastrointestinal tract. They appear suddenly, with the number increasing over time.
These lesions may bleed intermittently, which is rarely significant enough to be noticed in the form of bloody vomiting or black stoolbut can eventually lead to depletion of iron in the body, resulting in iron-deficiency anemia. Vascular relangiectasia in the lungs may cause a number of problems. The lungs normally “filter out” bacteria and blood clots from the bloodstream; AVMs bypass the capillary telanigectasia of the lungs and allow these to migrate to the brain, where bacteria may cause a brain abscess and blood clots may lead to stroke.
This may lead to breathlessness. The symptoms produced by AVMs in the liver depend on the type of abnormal connection that they form between blood vessels. If the connection is between arteries and veinsa large amount of blood bypasses the body’s organs, for which the heart compensates by increasing the cardiac output.
Eventually congestive cardiac failure develops “high-output cardiac failure”with breathlessness and leg swelling among other problems. If the flow in the AVM is in the other direction, portal venous blood flows directly into the veins rather than running through the liver; this may lead to hepatic encephalopathy confusion due to portal waste products irritating the brain. Rarely, the bile ducts are deprived of blood, leading to severe cholangitis inflammation of the bile ducts.
In the brain, AVMs occasionally exert pressure, leading to headaches. They may telangiedtasia increase the risk of seizuresas would any abnormal tissue in the brain. Finally, hemorrhage from an AVM may lead to intracerebral hemorrhage bleeding into the brainwhich causes any of the symptoms of stroke such as weakness in part of the body or difficulty speaking.
Hereditary hemorrhagic telangiectasia
If the bleeding occurs into the subarachnoid space subarachnoid hemorrhagethere is usually a severe, sudden headache and decreased level of consciousness and often weakness in part of the body.
A very small proportion those affected by SMAD4 MADH4 mutations, see below have multiple benign polyps in the large intestinewhich may bleed telangiectassia transform into colorectal cancer. A similarly small proportion experiences pulmonary hypertensiona state in which the pressure in the lung arteries is increased, exerting pressure on the right side of the heart and causing peripheral edema swelling of the legsfainting and attacks of chest pain.
It has been observed that the risk of thrombosis particularly venous thrombosisin the form of deep vein thrombosis heerditaria pulmonary embolism may be increased. There is a suspicion that those with HHT may have a mild immunodeficiency and are therefore at a slightly increased risk from infections.
HHT is a genetic disorder with an autosomal dominant inheritance pattern. Those with HHT symptoms that have no relatives with the disease may have a new mutation. Five genetic types of HHT are recognized. Of these, three have been linked to particular geneswhile the two remaining have hereditarix only been associated with a particular locus. There is likely to be a predominance of either type in particular populations, but the data are conflicting. Telangiectasias and arteriovenous malformations in HHT are thought to arise because of changes in angiogenesisthe development of blood vessels out of existing ones.
The development of a new blood vessel requires the activation and migration of various types of cells, chiefly endotheliumsmooth muscle and pericytes. The exact mechanism by which the HHT mutations influence this process is not yet clear, and it is likely that they disrupt a balance between pro- and antiangiogenic signals in blood vessels.
The wall of telangiectasias is unusually friablewhich explains the tendency of these lesions to bleed.
The hormones do not enter the cell but link to receptors on the cell membrane; these then activate other proteins, eventually influencing cellular behavior in a number of ways such as cellular survival, proliferation increasing in number and differentiation becoming more specialized. These bind to SMAD4 and migrate to the cell nucleus where they act as transcription factors and participate in the transcription of particular genes.
Diagnostic tests may be conducted for various reasons. Firstly, some tests are needed to confirm or refute the diagnosis. Secondly, some are needed to identify any potential complications. The skin and oral cavity telangiectasias are visually identifiable on physical examinationand similarly hwreditaria lesions in the nose may be seen telanigectasia endoscopy of the nasopharynx or on laryngoscopy.
The severity of nosebleeds may be quantified objectively using a grid-like questionnaire in which the number of nosebleed episodes and their duration is recorded. Digestive tract telangiectasias may atxxia identified on esophagogastroduodenoscopy endoscopy of the esophagus, stomach and first part of the small intestine.
This procedure will typically only be undertaken if there is anemia that is more marked than expected by the severity of nosebleeds, or if there is evidence of severe bleeding vomiting blood, black stools. If the number of lesions seen on endoscopy is unexpectedly low, the remainder of the small intestine may be examined with hereditarua endoscopyin which the patient swallows a capsule-shaped device containing a miniature camera which transmits images of the digestive tract to a portable digital recorder.
Identification of AVMs requires detailed medical imaging of the organs most commonly affected by these lesions. Not all AVMs cause symptoms or are at risk of doing so, and hence there is a degree of variation between specialists as to whether such heredigaria would be performed, and by which modality; often, atsxia on this issue herexitaria reached together with the patient.
Lung AVMs may be suspected because of the abnormal appearance of the lungs on a chest X-rayor hypoxia low oxygen levels telangisctasia pulse oximetry or arterial blood gas determination. Bubble contrast echocardiography bubble echo may be used as a screening tool to identify abnormal connections between the lung arteries and veins.
This involves the injection of agitated saline into a vein, followed by ultrasound-based imaging of the heart. Normally, the lungs remove small air bubbles from the circulation, and they are therefore only seen in the right atrium and the right ventricle.
If an AVM is present, bubbles appear in the left atrium and left ventricleusually 3—10 cardiac cycles after the right side; this is slower than in heart defectsin which there are direct connections between the right and left side of the heart.
A larger number of bubbles is more likely to indicate the presence of an AVM. Liver AVMs may be suspected because of abnormal liver function tests in the blood, because the symptoms of heart failure develop, or because of jaundice or other symptoms of liver dysfunction.
The most reliable initial helangiectasia test is Doppler ultrasonography of the liver; this has a very high sensitivity for identifying vascular lesions in the ztaxia. FNH is regarded as harmless. Generally, tumor markers and additional imaging modalities are used to differentiate between FNH and malignant tumors of the liver.
This procedure carries a hereditzria risk of stroke 0.
Testing is not always needed for hereditarja, because the symptoms are sufficient to distinguish the disease from other diagnoses.
There are situations in which testing can be particularly useful. Firstly, children and young adults with a parent with staxia HHT may have limited symptoms, yet be at risk from some of the complications mentioned above; if the mutation is known in the affected parent, absence of this mutation in the child would prevent the need for screening tests. Furthermore, genetic testing may confirm the diagnosis in those with limited symptoms who otherwise would have been labeled “possible HHT” see below.
Not all mutations in these genes have been linked with disease. Mutations in the MADH4 gene is usually associated with juvenile polyposis, and detection of such a mutation would indicate a need to screen the patient and affected relatives for polyps and tumors aatxia the large intestine. Despite the designation “possible”, someone with a visceral AVM and a family history but no nosebleeds or telangiectasias is still extremely likely to have HHT, because ataxua AVMs are very uncommon in the general population.
At the same time, the same cannot be said of nosebleeds and sparse telangiectasias, both of which occur in people without HHT, in the telangiectaisa of AVMs. Treatment of HHT is symptomatic it deals with the symptoms rather than the disease itselfas there is no therapy that stops the development of telangiectasias and AVMs directly.
Spinocerebellar ataxia – Wikipedia
Furthermore, some treatments are applied to prevent the development of common complications. Those who cannot tolerate iron tablets or solutions may require administration of intravenous iron, and blood transfusion if the anemia is causing severe symptoms that warrant rapid improvement of the blood count.
Most treatments used in HHT have been described in adults, and the experience in treating children is more limited. An acute nosebleed may be managed with a variety of measures, such as packing of the nasal cavity with absorbent swabs or gels. Removal of the packs after the bleeding may lead to reopening of the fragile vessels, and therefore lubricated or atraumatic packing is recommended.
Frequent nosebleeds can be prevented in part by keeping the nostrils moist, and by applying saline solutionestrogen -containing creams or tranexamic acid ; these have few side effects and may have a small degree of benefit. Medical therapies include oral tranexamic acid and estrogen; the evidence for these is relatively limited, and estrogen is poorly tolerated by men and possibly carries risks of cancer telanigectasia heart disease in women past the menopause.
Telangiectasix, it is highly recommended to use the least heat and time to prevent hereditarria perforations and hereritaria trauma to the nasal mucosa that are already susceptible to bleeding.
This process involves injecting a small amount of an aerated irritant detergent such as sodium tetradecyl sulfate directly into the telangiectasias. The detergent causes the vessel to collapse and harden, resulting in scar tissue residue.
This is the same procedure used to treat varicose veins tellangiectasia similar disorders. It may be possible to embolize vascular lesions through interventional radiology ; this requires hereeditaria a catheter through a large artery heeditaria locating the maxillary artery under X-ray guidancefollowed by telangiectawia injection into the vessel of particles that occlude the blood vessels. The benefit from the procedure tends to be short-lived,  and it may be most appropriate in episodes of severe bleeding.
To more effectively minimize recurrence and severity of epistaxis, other options may be used in conjunction with therapies listed above. Intravenously administered anti-VEGF substances such as bevacizumab brand name Avastinpazopinab and thalidomide or its derivatives interfere tekangiectasia the production of new blood vessels that are weak and therefore prone to bleeding. Due to the past experiences with prescribing thalidomide to pregnant women to alleviate symptoms of nausea and the terrible birth defects that followed, thalidomide is a last resort therapy.
Additionally, thalidomide can cause neuropathy. Though this can be mitigated by tinkering with dosages and prescribing its derivatives such as lenolidomide and pomalidomide, many doctors prefer alternative VEGF inhibitors.
Bevacizumab has been shown to significantly reduce the severity of epistaxis without side effects. If other interventions have failed, several operations have been reported to provide benefit. One is septal dermoplasty or Saunders’ procedure,  in which skin is transplanted into the nostrils, and the other is Young’s procedure,  in which the nostrils are sealed off completely.
The skin lesions of HHT can be jereditaria, and may respond to treatment with long-pulsed Nd: Skin grafting is occasionally needed to treat this problem. With regards to digestive tract lesions, mild bleeding and mild resultant anemia is treated with iron supplementation, and no specific treatment is administered. There is limited data on hormone treatment and tranexamic acid to reduce bleeding and anemia. Severe anemia or episodes of severe bleeding are treated with endoscopic argon plasma coagulation APC or laser treatment of any lesions identified; this may reduce the need for supportive treatment.
The herreditaria benefits are not such that repeated attempts at treating lesions are advocated. Lung lesions, once identified, are usually treated to prevent episodes of bleeding and more importantly embolism to the brain.
The most effective current therapy is embolization with detachable metal coils. The procedure telsngiectasia puncture of a large vein usually under a general anestheticfollowed by telangectasia of a catheter through the right ventricle and into the pulmonary arteryafter which radiocontrast is injected to visualize the AVMs pulmonary angiography.
Once the lesion has been identified, herediharia are deployed that obstruct the blood flow and allow the lesion to regress.
In experienced hands, the procedure tends to be very effective and with limited side effects, but lesions may recur and further attempts may be required. CTA scans are repeated to monitor for recurrence.
Those with either definite pulmonary AVMs or an abnormal contrast echocardiogram with no clearly visible lesions are deemed to be at risk from brain emboli.