Symptoms of Hereditary Hemorrhagic Telangiectasia
Hereditary hemorrhagic telangiectasia presents with recurrent spontaneous nosebleeds (epistaxis) in over 90% of adults, visible telangiectasias on skin and mucous membranes, and potentially life-threatening arteriovenous malformations in internal organs. 1, 2
Primary Clinical Manifestations
Epistaxis (Nosebleeds)
- Recurrent spontaneous nosebleeds are the hallmark symptom, occurring in more than 90-95% of adults with HHT and typically beginning in childhood around age 11 years 1, 2, 3
- Epistaxis results from rupture of fragile nasal mucosal telangiectasias and causes significant psychosocial morbidity, social isolation, and difficulties with employment, travel, and routine daily activities 1
- The bleeding is spontaneous and recurrent, not triggered by trauma, which distinguishes it from ordinary nosebleeds 1
Mucocutaneous Telangiectasias
- Multiple telangiectasias appear at characteristic sites including lips, oral cavity (especially tongue), fingers, nose, and nail beds 1, 3
- These lesions present as punctate, linear, or splinter-like red spots on the skin and mucous membranes 3
- Telangiectasias have age-related expression, becoming more prominent over time 1
Visceral Organ Involvement
Gastrointestinal Manifestations
- Gastrointestinal telangiectasias cause chronic bleeding leading to melena (blood in stool) and severe iron deficiency anemia 3, 4
- GI bleeding may be disproportionate to the severity of epistaxis, warranting endoscopic evaluation 1
- Telangiectasias can develop throughout the GI tract including stomach, duodenum, and colon 3
Pulmonary Arteriovenous Malformations
- Pulmonary AVMs create right-to-left shunts causing hypoxemia and risk of paradoxical emboli 5, 6
- These can lead to life-threatening complications including ischemic stroke or cerebral abscess, often occurring asymptomatically before detection 5, 6
- Pulmonary AVMs are more frequent and larger in HHT type 1 (ENG mutations) compared to type 2 5, 7
Hepatic Involvement
- Hepatic vascular malformations occur in 44-74% of HHT patients, though only 5-8% become symptomatic 1
- Symptomatic liver involvement causes high-output heart failure due to left-to-right shunting 6, 4
- Hepatic AVMs are substantially more common in HHT type 2 (ACVRL1 mutations) with marked female predominance 1
Central Nervous System Manifestations
- Cerebral and spinal AVMs can cause stroke, cerebral abscess, or hemorrhage 5, 8
- Nearly one in five HHT patients develop stroke or cerebral abscess from undetected AVMs 5
- Cerebral AVMs occur more commonly in HHT type 1 1
Systemic Consequences
Anemia and Iron Deficiency
- Chronic bleeding from epistaxis and GI telangiectasias leads to severe iron deficiency anemia requiring frequent blood transfusions 3, 4
- Anemia causes fatigue, palpitations, and can progress to high-output heart failure 4
- Iron deficiency is often the primary cause of morbidity in adults with HHT 6
Important Clinical Pitfalls
- Children typically present with isolated epistaxis only, with visceral AVMs developing later, so early screening is essential even without systemic symptoms 1, 6
- Patients may have asymptomatic but life-threatening AVMs, particularly in the lungs and brain, making screening mandatory regardless of symptoms 5
- The mean age for hepatic VM presentation is 52 years, indicating symptoms evolve over time and may not be present at initial diagnosis 1
- SMAD4 mutation carriers may lack overt HHT symptoms but remain at high risk for asymptomatic AVMs and have additional risk of gastric cancer 5