What diagnostic testing is recommended for a patient with multiple vascular malformations, telangiectasias, and frequent epistaxis (nose bleeds)?

Diagnostic Testing for Patients with Multiple Vascular Malformations, Telangiectasias, and Frequent Epistaxis

For patients presenting with multiple vascular malformations, telangiectasias, and frequent epistaxis, comprehensive screening for Hereditary Hemorrhagic Telangiectasia (HHT) should be performed, including Doppler ultrasonography of the liver, pulmonary screening, and cerebral imaging to detect visceral involvement. 1, 2

Initial Diagnostic Approach

• Apply the Curaçao diagnostic criteria to establish a clinical diagnosis of HHT, which includes:

  • Spontaneous and recurrent epistaxis
  • Multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose)
  • Visceral lesions (pulmonary, hepatic, cerebral, spinal arteriovenous malformations, or gastrointestinal telangiectasias)
  • First-degree relative with HHT 1

• Diagnosis is considered definite with three criteria present, possible/suspected with two criteria, and unlikely with fewer than two criteria 1

• Genetic testing should be performed, particularly for asymptomatic persons from families with known HHT, targeting mutations in:

  • Endoglin (ENG, HHT type 1)
  • Activin receptor-like kinase-1 (ACVRL1, HHT type 2)
  • SMAD4 (juvenile polyposis-HHT overlap) 1, 2

Organ-Specific Screening

Liver Screening

• Doppler ultrasonography is the recommended first-line imaging for liver involvement in all HHT patients 1
• Liver biopsy should be strictly avoided in any patient with proven or suspected HHT due to risk of hemorrhage 1
• Liver involvement grading (0-4) should be assessed based on:
  • Hepatic artery diameter
  • Peak flow velocity
  • Resistivity index
  • Presence of peripheral hepatic hypervascularization 1

Pulmonary Screening

• All HHT patients should undergo screening for pulmonary arteriovenous malformations as these can be treated presymptomatically to prevent life-threatening complications 1
• Contrast echocardiography or chest CT is recommended for detection of pulmonary VMs 1

Cerebral Screening

• MRI of the brain should be performed to detect cerebral vascular malformations 1
• This is particularly important as cerebral VMs can lead to hemorrhagic stroke if untreated 2

Gastrointestinal Evaluation

• Upper endoscopy should be considered to evaluate for gastrointestinal telangiectasias, especially in patients with unexplained anemia disproportionate to epistaxis severity 1, 3
• Small bowel evaluation may be necessary in cases of persistent anemia despite treatment of epistaxis and other visible sources of bleeding 3

Special Considerations

• Patients with HHT may develop complications beyond the typical telangiectasias:

  • Focal nodular hyperplasia in the liver occurs at higher rates in HHT patients than the general population 1
  • Portal hypertension can develop from hepatic arteriovenous malformations 4
  • Pulmonary shunts can lead to hypoxemia and paradoxical emboli 4

• Age-related expression of telangiectasias should be considered - cutaneous telangiectasias can appear as early as 6 years of age, contrary to previous beliefs that they develop later in life 5

• Bleeding outside the nasal cavity occurs in more than 25% of patients and may require specific treatment, particularly when originating from the base or body of the tongue 5

Management Implications of Diagnostic Findings

• Patients diagnosed with HHT should be referred to a multidisciplinary team with expertise in HHT management 1

• For patients with confirmed liver involvement, invasive therapies should be avoided unless they have failed to respond to intensive medical therapy 1

• Resorbable packing materials should be used for epistaxis management in HHT patients to reduce the risk of rebleeding during packing removal 1

• Newer antiangiogenic therapies (such as bevacizumab or pazopanib) may be considered for patients with severe or refractory bleeding 6, 7

• Iron replacement therapy and monitoring for anemia should be implemented for all patients with recurrent bleeding 1, 2