What is hht

Overview

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a rare genetic bleeding disorder affecting approximately 1 in 5,000 to 1 in 8,000 people worldwide. The condition causes abnormal formation of blood vessels, resulting in chronic bleeding, potentially life-threatening hemorrhages, and vascular malformations. Early diagnosis and management are critical for preventing serious complications.

Genetic Basis

HHT is inherited as an autosomal dominant condition, meaning only one mutated gene copy inherited from either parent causes the disease. Mutations typically occur in genes responsible for blood vessel formation, most commonly:

• ALK1 (TLR1) gene - accounts for approximately 60% of HHT cases
• ENG (endoglin) gene - accounts for approximately 40% of cases
• SMAD4 gene - causes a combined HHT and juvenile polyposis syndrome

These genes produce proteins essential for proper blood vessel wall structure. Mutations compromise vessel integrity, leading to characteristic symptoms and complications.

Symptoms and Clinical Features

HHT manifests through several characteristic features:

• Recurrent nosebleeds (epistaxis) - often the first symptom, occurring in 50-90% of patients, ranging from minor to severe
• Telangiectasia - small dilated blood vessel clusters appearing as red or purple spots on skin and lips, typically developing in adulthood
• Anemia - resulting from chronic blood loss through nosebleeds and gastrointestinal hemorrhage
• Fatigue and weakness - secondary to anemia and bleeding

Symptoms vary significantly between affected individuals, even within the same family.

Arteriovenous Malformations (AVMs)

Beyond superficial telangiectasia, HHT causes arteriovenous malformations (AVMs) - direct abnormal connections between arteries and veins - in internal organs. These are particularly dangerous in:

• Pulmonary AVMs - can cause stroke, brain abscess, and bleeding into lungs
• Cerebral AVMs - risk of hemorrhagic stroke and bleeding into the brain
• Hepatic AVMs - can cause heart failure and cirrhosis
• Gastrointestinal bleeding - chronic blood loss requiring transfusions

Diagnosis and Screening

Diagnosis typically combines clinical features with genetic testing. The Curaçao criteria help identify HHT based on:

• Family history of HHT
• Presence of telangiectasia
• Recurrent nosebleeds
• Documented AVMs

Patients should undergo screening for complications through chest imaging (for pulmonary AVMs), brain imaging (for cerebral AVMs), echocardiography, and gastrointestinal evaluation.

Management and Treatment

While no cure exists, management focuses on preventing bleeding and detecting complications early:

• Epistaxis management - topical treatments, cauterization, or tranexamic acid
• Antibiotic prophylaxis - for patients with pulmonary AVMs to prevent stroke
• Transfusions - when anemia becomes severe
• Surgical or radiologic intervention - for particularly dangerous AVMs
• Genetic counseling - for affected families