Hereditary Haemorrhagic Telangiectasia (HHT)

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🧬 Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler–Weber–Rendu disease, is a rare autosomal dominant vascular disorder. It causes fragile blood vessels (telangiectasias and AVMs) prone to bleeding, affecting the skin, mucous membranes, lungs, liver, and brain. Early diagnosis and treatment are essential to prevent serious complications such as GI bleeding, haemorrhagic stroke, and paradoxical emboli.

📖 About

• Definition: Genetic disorder causing abnormal blood vessel formation (telangiectasia, AVMs).
• Inheritance: Autosomal dominant - only one abnormal gene needed to manifest 👪.
• Sites involved: Skin, mucous membranes, lungs, liver, brain 🧠.
• Family history: Common; many affected individuals have a first-degree relative.
• Prevalence: ~1 in 5,000–8,000 worldwide 🌍.

🔎 Brain AVMs occur in ~10% of HHT patients, while pulmonary AVMs (PAVMs) are present in the majority. Screening for AVMs is critical to prevent life-threatening complications.

🧬 Aetiology

• Disorder of angiogenesis → malformed, fragile vessels.
• Genes: ENG (HHT1), ACVRL1 (HHT2), SMAD4 (HHT/Juvenile Polyposis overlap).
• Genotype–phenotype correlation:
  • HHT1: ENG mutation, ↑ risk of brain AVMs (13%).
  • HHT2: ACVRL1 mutation, lower brain AVM risk (2%).
  • SMAD4: Associated with GI polyposis + HHT.

🧠 Stroke Mechanisms in HHT

• 💥 Haemorrhage from ruptured cerebral AVMs.
• 🫀 Paradoxical emboli via pulmonary AVMs → ischaemic stroke.
• 🩸 Fragility of GI vessels → severe GI bleeds & anaemia.

⚡ Clinical Features

• 👃 Epistaxis: Recurrent nosebleeds (most common).
• 🩸 GI bleeding: Haematemesis, melaena, iron deficiency anaemia (esp. >50 yrs).
• 🧠 Neurological: Haemorrhagic stroke (cerebral AVMs), embolic stroke (PAVMs).
• 🩺 Mucocutaneous telangiectasia: Lips, oral cavity, nose, fingertips.
• 🫁 Pulmonary AVMs: Can rupture → haemoptysis, hypoxaemia.

📸 Clinical Signs

📊 Diagnostic Criteria (Curaçao Criteria)

✅ Definite HHT: ≥3 criteria ⚠️ Possible: 2 criteria ❌ Unlikely: <2 criteria

🔬 Investigations

• Bloods: FBC, ferritin, iron studies, B12/folate.
• Brain: MRI/MRA for AVMs.
• Lungs: Bubble echocardiogram (screening), CT pulmonary angiogram if positive 🫁.
• GI tract: Endoscopy/colonoscopy ± capsule endoscopy.
• Genetic testing: Confirms subtype, guides family screening 👪.

🩺 Management

• Emergency: ABC resuscitation, transfusions, urgent intervention for GI bleed or haemorrhagic stroke 🚑.
• Epistaxis: ENT laser ablation, cautery, nasal packing 👃.
• GI Bleeds: Iron replacement, endoscopic therapy 🍽️.
• Pulmonary AVMs: Embolization via interventional radiology 🫁.
• Medical: Antifibrinolytics (tranexamic acid), avoid antithrombotics 🚫.
• Genetics: Genetic counselling for families 🧬.

📈 Prognosis

• Chronic but variable disease course.
• Many lead normal lives with treatment ✅.
• Complications: GI bleeding, haemorrhagic stroke, embolic stroke.
• Early screening & treatment of AVMs improves long-term outcomes 🌱.

📚 References

• Prevalence of Brain AVMs in HHT – Systematic Review
• MR of HHT – Cerebrovascular Malformations
• Surgical vs Nonsurgical Treatment of AVMs
• NCBI Bookshelf – HHT

Cases - Hereditary Haemorrhagic Telangiectasia (HHT)

• Case 1 - Recurrent Epistaxis: A 28-year-old woman presents with recurrent nosebleeds since childhood, requiring frequent cautery. On exam, she has multiple red vascular lesions on her lips and tongue. FBC shows iron-deficiency anaemia. Her mother and grandfather had similar symptoms. Diagnosis: HHT with recurrent epistaxis and mucocutaneous telangiectasia.
• Case 2 - Pulmonary AV Malformation: A 40-year-old man presents with exertional dyspnoea and digital clubbing. CXR and CT chest show a large pulmonary arteriovenous malformation (PAVM). Contrast echo demonstrates right-to-left shunt. Past history of nosebleeds. Diagnosis: HHT with pulmonary AVM causing hypoxaemia.
• Case 3 - GI Bleeding and AVMs: A 65-year-old woman presents with melaena and iron-deficiency anaemia. Endoscopy reveals multiple telangiectatic lesions in the stomach and duodenum. She also reports a family history of “bleeding problems.” Diagnosis: HHT with gastrointestinal telangiectasia leading to chronic blood loss.

Teaching Commentary 🩸

Hereditary Haemorrhagic Telangiectasia is an autosomal dominant vascular disorder caused by mutations in TGF-β signalling genes (ENG, ACVRL1, SMAD4). Clinical diagnosis uses the Curaçao criteria: 1. Recurrent epistaxis, 2. Telangiectasia at characteristic sites (lips, oral cavity, nose, fingers), 3. Visceral AVMs (pulmonary, hepatic, cerebral, GI), 4. First-degree relative with HHT. Presence of 3–4 = definite HHT. Complications include chronic iron-deficiency anaemia, paradoxical emboli (via pulmonary AVMs), and cerebral haemorrhage. Management is supportive (iron, tranexamic acid, endoscopic therapy) and preventive (embolisation of AVMs, genetic counselling, antibiotic prophylaxis before procedures in those with PAVMs).