Osler-Weber-Rendu Disease Treatment & Management
- Author: Klaus-Dieter Lessnau, MD, FCCP; Chief Editor: Vincent Lopez Rowe, MD more...
Medical therapy and surgical treatment in patients with Osler-Weber-Rendu disease (OWRD; ie, hereditary hemorrhagic telangiectasia [HHT]), are aimed at decreasing the amount of hemorrhage and minimizing the sequelae of arteriovenous malformations (AVMs), which may develop in multiple organ systems.
Indications for intervention vary according to site of involvement and presentation. One third of cases of are mild, one third are moderate, and one third are severe. In mild cases of HHT, no treatment is necessary. In other cases, pharmacologic management may be effective. When nonpharmacologic treatment is called for, it can often be accomplished via catheter-based therapies that render surgical intervention (eg, thoracotomy or craniotomy) unnecessary.
Individual skin lesions may be obliterated with cauterization, hypertonic saline sclerotherapy, or dye laser treatment.
In severe cases of HHT, recurrent epistaxis refractory to ablative treatment is treated surgically with nasal septum skin transplants by using skin taken from the lower trunk. Severe cases of HHT may respond to estrogen therapy.
Control of intermittent gastrointestinal (GI) bleeding may be achieved medically. However, brisk hemorrhage may call for endoscopic treatment or surgical resection.
Pulmonary hemorrhage may be treated surgically by using silicone balloon tamponade or other means. Embolization (embolotherapy) or surgical resection is indicated for pulmonary AVM if it is localized and accessible, with the goal of limiting the risks of embolic central nervous system (CNS) complications, hemodynamic sequelae, or hemorrhage.
Hemodynamically significant shunt from hepatic AVM may be treatable with embolization to stabilize heart failure or encephalopathy. Extensive or symptomatic liver disease may warrant evaluation for liver transplantation.
Currently available therapies, including microsurgery, embolization, and radiosurgery, are invasive and associated with considerable adverse effects. No specific medical therapy is available for brain AVM patients. For selected CNS lesions, neurosurgical resection may be indicated. Embolotherapy and radiotherapy may be alternative options, depending on lesion morphology.
Antibiotic prophylaxis should be considered before surgical or dental procedures in all patients with known pulmonary AVMs or positive contrast echocardiography findings (agitated saline solution transthoracic contrast echocardiography [TTCE] grade 1 or higher).
Studies recommend that women with HHT who conceive should be considered to have high-risk pregnancies because of rare major complications and improved survival outcome following prior recognition.
In most patients, no special diet is required. Iron can be depleted if the patient experiences chronic blood loss. Folate requirements can be high if the bone marrow is chronically activated. Most patients can continue normal activities.
Prospective trials aimed at determining ideal management of HHT have been limited by the small and varied population and by the multiorgan nature of the disease. A coordinated team approach is recommended. Preclinical work targeting endoglin (also known as CD105) has shown promising results in cancer-related research. Such studies may complement concurrent HHT-specific research in developing new therapies.
Treatment of Epistaxis
Epistaxis is often recurrent, necessitating multiple treatments. Moderate and mild epistaxis can be treated medically or with endoscopic ablation; severe epistaxis calls for surgical treatment.
Nonoperative treatment of epistaxis may include the following:
Electrocautery and argon beam ablation
Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser ablation 
In more severe cases, iron replacement may be indicated because of blood loss. Humidification of the ambient air helps decrease the amount of mucosal bleeding. Hormone therapy, including antiestrogen therapy with tamoxifen, for the treatment of epistaxis due to HHT has produced good responses, though its use remains controversial. Antifibrinolytics (eg, aminocaproic acid) may be used to enhance hemostasis when fibrinolysis contributes to bleeding.
Although estrogen-related hormones and antifibrinolytic agents are commonly used to manage bleeding, some studies suggest that this probably increases the risk of thrombotic events in OWRD patients with pulmonary AVMs. Accordingly, patients should undergo screening for the presence of pulmonary AVMs before treatment is started.
Pulsed dye laser treatment may be used to photocoagulate telangiectasias in the nasal mucosa. As many as three subsequent treatments may be necessary before any change in bleeding frequency or severity is observed.
A small prospective randomized trial (26 patients) from Germany of topical estrogen (0.5 mg of 0.1% estriol ointment twice daily) after argon beam coagulation in HHT patients with recurrent epistaxis suggested improved outcome over argon beam coagulation with application of ointment.
Although only a few cases have been reported, the published literature is concordant regarding the potential benefit of thalidomide in reducing the frequency and intensity of epistaxis in HHT patients, improving their hemoglobin levels and therefore reducing the need for transfusions.
Lebrin et al in 2010 observed in six of seven patients that treatment with thalidmide 100 mg/day resulted in lowering the frequency of epistaxis within 1 month and that none of the four transfusion-dependent patients needed further transfusion during thalidomide therapy. Thalidomide reduced the severity and frequency of epistaxis in the majority of a small group of patients with HHT, which suggests that it may hold promise as a therapeutic option.
Future research should be directed toward identifying the minimum dose of thalidomide effective in long-term control of bleeding symptoms in HHT patients without inducing thrombotic adverse events. It appears to be a potential candidate for the treatment of severe HHT-associated epistaxis unresponsive to conventional therapies.
Septal dermoplasty can reduce the severity of epistaxis by 75%. This procedure involves replacing the nasal mucosa with autologous skin grafts. Telangiectasias may also develop on the autologous skin grafts, however. Septal dermoplasty decreases the need for, but does not obviate, repeated laser ablation. Septectomy combined with septal dermoplasty may also be a viable option for patients with severe transfusion-dependent epistaxis.
Endovascular embolization for treatment of severe acute epistaxis is another treatment modality that may be considered. Patients who undergo endovascular embolization often require repeat embolization and surgical procedures.
N-acetylcysteine has been studied as an option for management of recurrent epistaxis in patients with HHT. Multiple case reports have illustrated the use of bevacizumab in the treatment of HHT, and the efficacy of this agent for the management of epistaxis in HHT is being studied. Two case reports have documented the regression of OWRD lesions with the use of interferon alfa in patients who were treated for other indications.[113, 114]
Treatment of Gastrointestinal Bleeding
Nonoperative treatment of GI bleeding may include the following:
Endoscopic photoablation or electrocautery
Aminocaproic acid blocks the conversion of plasminogen to plasmin and thus acts as a powerful inhibitor of fibrinolysis. Although coagulation is thought to be normal in HHT, some investigators believe that the cause of the bleeding tendency is multifactorial. Increased plasminogen-activator activity has been demonstrated in the telangiectatic vessel walls of some patients with HHT.
A distinction is made between the malformations of HHT and lesions of angiodysplasia, both of which tend to manifest with age. The lesions of HHT are most often diffuse, and extensive surgical resection is generally not indicated for episodic bleeding, though it may be indicated for massive hemorrhage.
A treatment regimen involving intranasal administration of diluted bevacizumab has been shown to be clinically effective in patients with HHT1 and severe GI bleeding.
Life-threatening GI bleeding can often be effectively treated by means of segmental bowel resection.
Treatment of Pulmonary Arteriovenous Malformation
Localized lesions can be effectively addressed by means of surgical resection. Diffuse multiple AVMs smaller than 1.5 cm can be observed. As with non-HHT AVMs, an enlarging or symptomatic lesion should be resected. Small solitary lesions in a patient with HHT should be considered for resection because of the tendency to enlarge over time.
Embolization has been shown to be effective in closing shunts and should be weighed with surgery as an option for addressing pulmonary AVM. It is a safe procedure that prevents brain abscess and ischemic stroke if complete occlusion of all pulmonary AVMs is achieved. Embolization is currently recommended for every pulmonary AVM with a feeding artery of 3 mm or more.
Special considerations must be applied in the management of pulmonary AVM in women planning pregnancy; progression of pulmonary shunt and fatal rupture have been described.
Treatment of Hepatic Arteriovenous Malformation
Embolization of the hepatic artery is a potential option for selected patients with liver involvement, as is liver transplantation.[118, 119]
Liver transplantation may be considered in patients with symptomatic hepatic HHT who present with life-threatening conditions such as hepatobiliary sepsis and severe cardiopulmonary changes. In a study involving 40 patients followed up for a median of 70 months, patient and graft actuarial survival was 82.5% at 10 years. Indications for transplantation included cardiac failure (n = 14), biliary necrosis with hepatic failure (n = 12), severe portal hypertension (n = 5), or a combination of two or more of these conditions (n = 9).
In a brief report of two HHT patients who underwent liver transplantation for cardiac failure, the patients had normal cardiac function 2 and 3 years after transplantation. Hepatic embolization in patients with extensive liver involvement has been discouraged because of the potential complications of liver parenchymal or biliary necrosis with ensuing sepsis.
Mitchell et al reported a case in which the use of bevacizumab reversed the need for liver transplantation in an HHT patient with heart failure from hepatic vascular malformations.
Consultation with multiple specialists can be useful in the diagnosis and treatment of OWRD (ie, HHT). Optimal management of AVMs may require a multidisciplinary approach. Similarly, management of syndromes resulting from severe hepatic disease (eg, encephalopathy, portal hypertension, and heart failure) may require cooperation between many disciplines. Certain specialists may have to be consulted only when particular complications arise.
Consultations to be considered, depending on the severity and manifestations of HHT, include the following:
Long-term, systematic follow-up is indicated. Known lesions may recur or progress and new manifestations of the syndrome may develop over time. Patients should be monitored for symptoms and signs of blood loss and anemia with yearly stool guaiac testing and complete blood count (CBC) with differential.
Patients should be screened for pulmonary, hepatic, and CNS AVMs at the time of diagnosis and at the onset of any suggestive symptoms and signs. Children who have a parent with HHT carry a 50% chance of harboring the same genetic mutation. Accordingly, pulmonary AVM screening and long-term follow-up are advocated for these children, beginning in childhood.
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