What are the diagnostic steps for hereditary hemorrhagic telangiectasia (HHT)?

Diagnostic Steps for Hereditary Hemorrhagic Telangiectasia (HHT)

The diagnosis of HHT should be established using the Curaçao criteria and genetic testing, with screening for visceral vascular malformations in confirmed cases to prevent life-threatening complications. 1

Curaçao Diagnostic Criteria

The cornerstone of HHT diagnosis is the Curaçao criteria, which includes:

1. Epistaxis: Spontaneous, recurrent nosebleeds
2. Telangiectases: Multiple at characteristic sites (lips, oral cavity, fingers, nose)
3. Visceral lesions: Including pulmonary, hepatic, cerebral, spinal vascular malformations, or gastrointestinal telangiectases
4. Family history: First-degree relative with HHT according to these criteria 1

HHT diagnosis is:

• Definite: If three or more criteria are present
• Possible/Suspected: If two criteria are present
• Unlikely: If fewer than two criteria are present 1

Diagnostic Algorithm

1. Initial Assessment:

   • Detailed history focusing on recurrent epistaxis and family history of HHT
   • Thorough examination for telangiectases in nasal and oral mucosa, lips, fingers, and face 2
   • Assessment for symptoms suggesting visceral involvement (dyspnea, hemoptysis, neurological symptoms)

2. Laboratory Testing:

   • Complete blood count to assess for anemia
   • Coagulation studies to rule out other bleeding disorders
   • Liver function tests to evaluate hepatic involvement 2

3. Genetic Testing:

   • Recommended for:
     • Patients with suspected HHT (2 Curaçao criteria)
     • Asymptomatic relatives of patients with confirmed HHT
     • Children of affected individuals before manifestations develop 1
   • Tests for mutations in:
     • ENG (HHT type 1)
     • ACVRL1/ALK1 (HHT type 2)
     • SMAD4 (juvenile polyposis-HHT overlap) 1, 3
   • A causative mutation is identified in 97% of patients with definite clinical diagnosis 1

4. Screening for Visceral Involvement:

   • Pulmonary AVMs:

     • Contrast echocardiography (first-line)
     • Chest CT if echocardiography is positive 2, 4

   • Cerebral AVMs:

     • Brain MRI with and without contrast 2

   • Hepatic VMs:

     • Doppler ultrasound is recommended as first-line imaging 1
     • Avoid liver biopsy in patients with suspected HHT due to bleeding risk 1

   • Gastrointestinal Telangiectases:

     • Endoscopy if anemia is disproportionate to epistaxis or if there's evidence of GI bleeding 4

Important Considerations

• Age-dependent expression: The manifestations of HHT, particularly epistaxis and telangiectases, have age-related expression, making diagnosis challenging in younger patients 1, 4

• Diagnostic delay: HHT is frequently underdiagnosed with significant diagnostic delays, emphasizing the importance of early recognition 1, 2

• Avoid invasive procedures: Liver biopsy should be avoided in any patient with proven or suspected HHT due to high risk of bleeding 1

• Multidisciplinary approach: Once diagnosed, patients should be referred to an HHT specialist center for comprehensive management 2, 5

• Family screening: First-degree relatives of affected individuals should be offered screening and genetic testing 1, 3

• Genetic subtype implications: The specific gene mutation affects the frequency of arteriovenous malformations in particular organs and the occurrence of certain rare symptoms 3

By following this structured approach to diagnosis, clinicians can identify HHT early, implement appropriate screening for visceral involvement, and initiate preventive measures to reduce morbidity and mortality associated with this condition.