What is the management approach for Osler-Weber-Rendu (Hereditary Hemorrhagic Telangiectasia, HHT)?

Management of Osler-Weber-Rendu (Hereditary Hemorrhagic Telangiectasia)

Management of HHT requires a systematic approach beginning with diagnosis using Curaçao criteria, followed by comprehensive organ screening, and stepwise treatment of bleeding manifestations starting with nasal moisturization, escalating to oral tranexamic acid, then local ablative therapies, and finally systemic bevacizumab for refractory cases. 1, 2, 3

Diagnostic Confirmation

Clinical Diagnosis

• Apply the Curaçao criteria which include: (1) spontaneous/recurrent epistaxis, (2) multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose), (3) visceral arteriovenous malformations, and (4) first-degree relative with HHT 2
• Three criteria = definite diagnosis; two criteria = possible/suspected diagnosis 2
• Genetic testing for ENG, ACVRL1, and SMAD4 mutations identifies causative mutations in 97% of definite cases and is particularly important for asymptomatic family members 2, 4

Mandatory Organ Screening

Pulmonary Screening

• All HHT patients must undergo screening for pulmonary arteriovenous malformations using contrast echocardiography or chest CT, as these can be treated presymptomatically to prevent life-threatening complications including stroke and brain abscess 2

Hepatic Screening

• Perform Doppler ultrasonography as first-line imaging for liver involvement in all patients 1, 2
• Never perform liver biopsy in HHT patients due to high hemorrhage risk 1, 2
• Grade liver involvement (0-4) based on hepatic artery diameter, peak flow velocity, resistivity index, and peripheral hypervascularization 2

Cerebral Screening

• Obtain brain MRI to detect cerebral vascular malformations 2

Gastrointestinal Evaluation

• Perform upper endoscopy in patients with unexplained anemia disproportionate to epistaxis severity 2

Stepwise Treatment Algorithm for Epistaxis

First-Line: Nasal Moisturization

• Initiate air humidification and topical saline gels to prevent mucosal cracking and bleeding of fragile telangiectasias 1, 3
• This forms the foundation but is inadequate alone for most patients 1

Second-Line: Oral Tranexamic Acid

• For epistaxis inadequately controlled by moisturization, prescribe oral tranexamic acid, which reduces epistaxis duration by 17.3% and composite epistaxis endpoints (duration plus intensity) by 54% 1, 3
• Two randomized controlled trials (118 and 22 patients) demonstrated efficacy without increased thrombotic complications 1, 3

Third-Line: Local Ablative Procedures

• For moderate bleeding unresponsive to tranexamic acid, perform laser treatment or electrosurgery before advancing to systemic therapy 3
• These procedures have stronger evidence than other local ablative options 3

Fourth-Line: Systemic Bevacizumab

• For severe epistaxis failing moisturization, tranexamic acid, and/or local ablation, administer systemic bevacizumab, which produces a 50% reduction in epistaxis severity score in the InHIBIT-Bleed study (238 patients) 1, 3
• Bevacizumab substantially improves hemoglobin levels, reduces iron infusion needs, and decreases red cell transfusion requirements 3
• Safety profile is favorable with only 2% venous thromboembolism rate and no fatal adverse events 3
• This represents a paradigm shift from purely procedural to systemic targeted therapy based on understanding that VEGF excess drives telangiectasia formation 1, 3

Alternative Systemic Agent

• Thalidomide downregulates VEGF and improves vascular wall integrity, with effectiveness documented in 67 patients, but use is limited by persistent peripheral neuropathy 3

Management of Gastrointestinal Bleeding

• Apply the same stepwise approach as epistaxis: moisturization principles do not apply, but tranexamic acid, endoscopic ablation (argon plasma coagulation, laser), and systemic bevacizumab follow similar escalation 1, 5
• Endoscopic methods allow timely diagnosis and treatment of GI telangiectasias 5

Anemia Management

• Implement iron replacement therapy for all patients with recurrent bleeding 2
• Monitor hemoglobin, hematocrit, and ferritin levels regularly 5
• Blood transfusions may be necessary for severe anemia, though systemic bevacizumab can dramatically reduce transfusion requirements 5

Liver-Specific Management

• Liver involvement is generally asymptomatic, but when symptomatic can cause substantial morbidity and mortality 1
• Invasive therapies including liver transplantation should only be considered after failure of intensive medical therapy 1, 2
• The prevalence of focal nodular hyperplasia is much higher in HHT patients with liver involvement than in the general population 1

Critical Pitfalls to Avoid

• Never perform liver biopsy in suspected or confirmed HHT due to catastrophic bleeding risk 1, 2
• Do not use non-resorbable nasal packing materials; use only resorbable packing to reduce rebleeding risk during removal 2
• Do not delay pulmonary AVM screening, as presymptomatic treatment prevents stroke and brain abscess 2
• Recognize that epistaxis causes significant psychosocial morbidity, social isolation, and employment difficulties lasting hours daily—treatment decisions should prioritize quality of life, not just hemoglobin levels 1, 3

Multidisciplinary Coordination

• Refer all diagnosed patients to a multidisciplinary team with HHT expertise including hematology, otolaryngology, gastroenterology, interventional radiology, and genetics 2, 6, 7