Osler–Weber–Rendu disease

Overview

Osler–Weber–Rendu disease, also known as Hereditary Hemorrhagic Telangiectasia (HHT), is a rare autosomal dominant genetic disorder that affects blood vessel formation. It is characterized by the development of telangiectasias (small, dilated blood vessels) and arteriovenous malformations (AVMs), direct connections between arteries and veins that bypass the capillary system. These abnormalities lead to a lifelong tendency for bleeding, particularly from the nose, skin, gastrointestinal tract, and internal organs such as the lungs, brain, and liver.

HHT affects approximately 1 in 5,000 to 8,000 individuals worldwide and varies widely in severity. Early recognition and multidisciplinary management are essential to reduce the risk of life-threatening complications, such as stroke, brain abscess, or high-output heart failure.

Causes

Osler–Weber–Rendu disease is caused by mutations in genes involved in blood vessel development and repair. These mutations disrupt normal angiogenesis and vessel integrity, leading to fragile and improperly connected blood vessels.

Common Genetic Mutations

• ENG gene: Causes HHT type 1 (more commonly associated with pulmonary and cerebral AVMs)

• ACVRL1 (ALK1) gene: Causes HHT type 2 (more commonly associated with hepatic AVMs)

• SMAD4 gene: Rare; causes combined syndrome of HHT and juvenile polyposis

Inheritance Pattern

• Autosomal dominant: A single copy of the mutated gene from an affected parent is enough to cause the disorder

• Each child of an affected individual has a 50% chance of inheriting the mutation

Symptoms

Symptoms of HHT often appear gradually and can vary significantly in severity, even among family members. The disease primarily affects mucocutaneous and visceral blood vessels.

Common Clinical Features

• Recurrent epistaxis (nosebleeds): The most common and often earliest symptom; typically begins in childhood or adolescence

• Telangiectasias: Small, red spots found on the lips, tongue, face, hands, and inside the nose and mouth

• Gastrointestinal bleeding: Often begins in adulthood; may lead to iron-deficiency anemia

Visceral Arteriovenous Malformations (AVMs)

• Pulmonary AVMs: Can cause shortness of breath, low oxygen levels, paradoxical embolism, or brain abscess

• Cerebral AVMs: May lead to seizures, stroke, or hemorrhage

• Hepatic AVMs: May cause high-output heart failure, portal hypertension, or liver dysfunction

Other Possible Features

• Fatigue and exertional dyspnea due to chronic blood loss

• Headaches or neurologic symptoms from cerebral AVMs

• Palpitations or signs of heart failure from liver AVMs

Diagnosis

Diagnosis of Osler–Weber–Rendu disease is based on clinical criteria (Curacao criteria), imaging studies, and genetic testing. A combination of symptoms and family history is used to establish a definitive or probable diagnosis.

Curacao Diagnostic Criteria

• Spontaneous, recurrent nosebleeds

• Multiple telangiectasias at characteristic sites

• Visceral AVMs (lungs, liver, brain, GI tract)

• First-degree relative with confirmed HHT

Diagnosis interpretation:

• 3 or more criteria: Definite HHT

• 2 criteria: Possible or suspected HHT

• 1 or fewer: Unlikely HHT

Imaging and Diagnostic Tests

• Contrast echocardiography (bubble study): To screen for pulmonary AVMs

• CT or MRI of the chest and brain: For detailed evaluation of AVMs

• Endoscopy: To identify GI bleeding sources

• Liver ultrasound or CT: For hepatic AVMs

Genetic Testing

• Can confirm the diagnosis in individuals with known mutations

• Useful for family screening and early intervention

Treatment

There is no cure for Osler–Weber–Rendu disease, but treatment focuses on managing symptoms, preventing complications, and monitoring for AVMs. A multidisciplinary approach is essential, involving ENT specialists, pulmonologists, gastroenterologists, geneticists, and interventional radiologists.

Nosebleeds

• Humidification and nasal lubricants: First-line management

• Topical therapies: Estrogen creams or antifibrinolytics (e.g., tranexamic acid)

• Laser therapy or cauterization: For recurrent bleeding

• Septodermoplasty or Young’s procedure: In severe, refractory cases

Gastrointestinal Bleeding

• Iron supplementation: Oral or intravenous for anemia

• Endoscopic treatment: Argon plasma coagulation of bleeding lesions

• Antifibrinolytic agents: In select patients with chronic bleeding

Pulmonary and Cerebral AVMs

• Embolization: Minimally invasive treatment for pulmonary AVMs to prevent stroke or brain abscess

• Surgical resection: Rarely needed unless AVMs are large or complex

• Neurologic AVMs: Managed based on size, location, and risk of hemorrhage

Hepatic AVMs

• Usually managed conservatively

• Heart failure symptoms may require cardiac medications

• Liver transplantation in severe, symptomatic cases

Prognosis

The prognosis for individuals with Osler–Weber–Rendu disease depends on the severity of AVMs and the degree of organ involvement. With proper screening, regular follow-up, and management, many people with HHT can live a normal lifespan and maintain good quality of life.

Complications such as stroke, severe anemia, or high-output cardiac failure can be life-threatening if not detected early. Genetic counseling and early intervention are critical for affected families. Advances in interventional radiology and targeted therapies continue to improve outcomes for individuals with this complex vascular disorder.