Symptoms of Hereditary Hemorrhagic Telangiectasia (HHT)
Recurrent spontaneous nosebleeds (epistaxis) are the hallmark symptom of HHT, occurring in over 90% of patients, typically beginning around age 11 years and often increasing in frequency with age. 1, 2
Primary Clinical Manifestations
Mucocutaneous Features
- Multiple telangiectasias appear as punctate, linear, or splinter-like red spots on characteristic sites including the lips, tongue, oral cavity, fingers, nose, and nail beds 1, 2, 3
- These visible vascular lesions have enlarged vessels with thin walls that are prone to spontaneous rupture and bleeding 1
- Telangiectasias show age-related expression, becoming more apparent over time 2
Bleeding Manifestations
- Epistaxis is the universal presenting symptom, with nosebleeds being spontaneous, recurrent, and progressively worsening with age in most patients 1, 2, 4
- Gastrointestinal bleeding from telangiectasias in the stomach, small bowel, and colon causes melena (blood in stool) and can range from minor to life-threatening 3, 5
- Bleeding frequency increases with age, leading to chronic blood loss 1
Systemic Consequences of Chronic Bleeding
- Iron deficiency anemia develops in approximately 50% of HHT patients due to chronic blood loss, manifesting as fatigue, reduced exercise tolerance, weakness, dizziness, and palpitations 2, 3, 6
- Severe anemia may require regular blood transfusions 1, 3
- Hair loss can occur as a manifestation of iron deficiency 2
Visceral Arteriovenous Malformations (Often Asymptomatic)
Pulmonary AVMs
- Present in a significant proportion of HHT patients, particularly HHT type 1 (ENG mutations) 7, 4
- May be asymptomatic but create risk for stroke, cerebral abscess, or paradoxical emboli due to right-to-left shunting 2, 7
- Can cause hypoxemia and reduced exercise tolerance 2
Hepatic AVMs
- More common and symptomatic in HHT type 2 (ACVRL1 mutations), with marked female predominance 2, 7
- Generally asymptomatic, but when symptomatic can cause high-output cardiac failure, which considerably worsens fatigue 2
Cerebral AVMs
- More common in HHT type 1 7, 4
- May be asymptomatic until they cause stroke, seizures, or hemorrhage 2
- Nearly one in five HHT patients develop stroke or cerebral abscess 8
Gastrointestinal Telangiectasias
- Frequent throughout the GI tract, particularly in stomach and small bowel 4, 5
- Cause chronic or acute bleeding episodes 3, 5
Quality of Life Impact
- Significant psychosocial morbidity including social isolation, difficulties with employment, travel limitations, and impairment of routine daily activities due to unpredictable bleeding episodes 2
- Chronic fatigue from anemia affects daily functioning beyond just hemoglobin levels—complete iron depletion contributes to persistent symptoms 2
- Extensive medical expenses from repeated treatments, transfusions, and hospitalizations 1
Genotype-Specific Symptom Patterns
HHT Type 1 (ENG mutations)
- Pulmonary AVMs are more frequent and larger 7
- Cerebral AVMs occur more commonly 7
- Symptoms typically appear around age 30, with epistaxis starting at mean age 11 years 7
HHT Type 2 (ACVRL1 mutations)
- Hepatic vascular malformations are substantially more common and symptomatic, with marked female predominance 2, 7
SMAD4 mutations (Juvenile Polyposis-HHT Overlap)
- Combined syndrome features including severe gastric polyposis (73% prevalence) 8
- All HHT manifestations including life-threatening AVMs occur in up to 76% of SMAD4 carriers 8
- Cardiovascular anomalies including thoracic aortic disease and mitral valve dysfunction occur in 38% 8
Critical Clinical Pitfall
Patients may have asymptomatic but life-threatening visceral AVMs despite minimal bleeding symptoms, making systematic screening essential rather than waiting for symptoms to develop. 2, 8 This is particularly true for pulmonary and cerebral AVMs, which can cause catastrophic complications like stroke or cerebral abscess without warning 2, 7