From the Guidelines
Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disease characterized by clinically significant vascular malformations (VMs) of skin and mucous membranes, particularly in the nose and gastrointestinal (GI) tract, as well as the brain, lung, and liver 1.
Key Characteristics
- Estimated prevalence of approximately 1 in 5000 individuals 1
- Clinically significant VMs in various organs, leading to complications such as epistaxis, gastrointestinal bleeding, and anemia 1
- Often underdiagnosed, with a long diagnostic delay 1
Diagnosis and Management
- Diagnosis allows for appropriate screening and management of HHT-related symptoms and complications 1
- The Second International HHT Guidelines provide evidence-based recommendations for the management and prevention of HHT-related symptoms and complications, including epistaxis, gastrointestinal bleeding, and anemia 1
- Systemic therapies, such as tranexamic acid, are now recommended as an option for managing epistaxis that does not respond to moisturizing topical therapies alone 1
From the Research
Definition and Characteristics of Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare autosomal dominant disorder characterized by vascular malformations 2, 3, 4, 5, 6. The disorder leads to abnormal blood vessel formation in the skin, mucous membranes, and organs such as the lung, liver, and brain.
Clinical Manifestations
The most common symptom of HHT is recurring nosebleed (epistaxis), which begins in childhood and affects about 90-95% of people with HHT 3. Other common signs and symptoms include:
- Punctate, linear, or splinter-like telangiectasias on the upper body, oral mucosa, or nail beds
- Gastrointestinal bleeding
- Iron deficiency anemia
- Visceral arteriovenous malformations (AVMs) in the lungs, liver, and brain, which can lead to severe complications such as ischemic stroke, brain abscess, and hepatic failure 4, 5
Diagnosis and Diagnostic Criteria
The diagnosis of HHT is made by clinical screening, baseline investigations, genetic testing, and detailed medical imaging to detect visceral AVMs 3. The Curaçao criteria are currently used for diagnosis. The diagnosis is often delayed due to the rarity of the disease and the variety of clinical manifestations.
Management and Treatment
The management of HHT includes:
- Systematic screening for visceral AVMs at regular intervals
- Preventive interventions to reduce the risk of complications
- Symptomatic measures such as intravenous iron therapy, antifibrinolytics, ablation therapies, and systemic anti-angiogenic agents 3, 5, 6
- A multidisciplinary standardized program in specialized centers may improve the management of patients with HHT 6
Genetic Basis
HHT is caused by mutations in one of the genes involved in the transforming growth factor-β signaling pathway, including ACVRL1, ENG, and SMAD4 2, 3, 4. The two known genes that are implicated in HHT are endoglin (ENG) and activin-receptor-like kinase (ALK1), which distinguish HHT type 1 and type 2 4.