What are the diagnostic criteria for Hereditary Hemorrhagic Telangiectasia (HHT)?

Diagnostic Criteria for Hereditary Hemorrhagic Telangiectasia (HHT)

The diagnosis of HHT is established using the Curaçao criteria, which requires the presence of at least 3 out of 4 clinical features: spontaneous and recurrent epistaxis, multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose), visceral arteriovenous malformations (pulmonary, hepatic, cerebral, spinal, or gastrointestinal), and a first-degree relative with HHT. 1, 2

The Four Curaçao Criteria

1. Epistaxis

• Must be spontaneous and recurrent nosebleeds 1, 2
• This is the most common manifestation, occurring in over 90% of adults with HHT 2
• Typically begins around age 11 years on average 2

2. Telangiectasias

• Must be multiple lesions present at characteristic sites 1, 2
• Specific locations include: lips, oral cavity, fingers, nose, face, ears, fingertips, tongue 1, 2, 3
• These are age-dependent and may not be present in younger patients 2

3. Visceral Lesions

• Arteriovenous malformations in specific organs 1, 2:
  • Pulmonary AVMs
  • Hepatic AVMs
  • Cerebral or spinal AVMs
  • Gastrointestinal telangiectasias
• These can be asymptomatic but carry risk of life-threatening complications 2

4. Family History

• A first-degree relative (parent, sibling, or child) with HHT diagnosed according to these same criteria 1, 2, 4
• Given the autosomal dominant inheritance, each child has a 50% chance of inheriting the condition 2

Diagnostic Classification Based on Criteria Met

Definite HHT diagnosis: 3 or 4 criteria present 1, 2, 4

Possible/Suspected HHT: Exactly 2 criteria present 1, 2, 4

Unlikely HHT: Fewer than 2 criteria present 1, 2, 4

Critical Caveat for Children

Children of affected individuals should be considered at risk even with fewer than 2 criteria, because HHT has age-related penetrance and clinical features develop over time 2, 4

Genetic Testing to Confirm Diagnosis

While clinical diagnosis using Curaçao criteria is primary, genetic testing identifies causative mutations in 97% of patients with definite clinical diagnosis 2:

• ENG gene (endoglin) - causes HHT type 1, found in 54% of HHT families 2, 5
• ACVRL1 gene (ALK-1) - causes HHT type 2, found in 43% of HHT families 2, 6
• SMAD4 gene - causes juvenile polyposis-HHT overlap syndrome, found in 1-2% of cases 2

Genetic testing is particularly recommended for asymptomatic individuals from families with known HHT, allowing for early screening and preventive treatment before complications develop 2

Mandatory Screening After Diagnosis

Once HHT is diagnosed (3+ criteria), comprehensive organ screening must be performed regardless of symptoms 2:

Pulmonary Screening

• All HHT patients require screening for pulmonary AVMs using contrast echocardiography or chest CT 2
• These can be treated presymptomatically to prevent stroke, cerebral abscess, and hemorrhage 2

Liver Screening

• Doppler ultrasonography is first-line imaging for all HHT patients 1, 2
• Liver involvement is graded 0-4 based on hepatic artery diameter (>6mm abnormal), peak flow velocity (>80 cm/sec abnormal), resistivity index (<0.55 abnormal), and peripheral hypervascularization 1

Cerebral Screening

• MRI of the brain to detect cerebral vascular malformations 2

Gastrointestinal Evaluation

• Upper endoscopy for patients with unexplained anemia disproportionate to epistaxis severity 2

Critical Management Pitfall to Avoid

Never perform liver biopsy in any patient with proven or suspected HHT due to extremely high risk of life-threatening hemorrhage from the vascular malformations 1, 2, 5