Hereditary hemorrhagic telangiectasia

Definition

• Autosomal dominant heritable disease resulting in a syndrome of artero-venous malformations in the skin (telangiectasia), lungs, brain, gut that predisposes to significant, life-threatening bleed
• Also known as Osler-Weber-Rendu syndrome

Pathophysiology

• Two most common genes are ENG and ECVRL1, followed by SMAD4

Differential Diagnosis

• Bleeding diathesis

Epidemiology

• Prevalence of 1:10,000 in North America, though likely underdetected

Risk Factors

• Family history

Diagnosis

• Nosebleeds (95%), usually starting in childhood occurring spontaneously and recurrently
• Telangiectases (95%), usually starting in young adulthood
  • Lips, hands, and oral/nasal/gastric mucosa
  • Blanchable, pink-red, and punctuate
• Ischemic stroke and brain abscesses, secondary to pulmonary shunting
• Visceral AVMs
  • Upper GI bleeds (25%), usually after age 50
  • Cerebral AVMs (10%), present at birth
  • Pulmonary AVMs causing detecable shunt in about half
  • Hepatic AVMs, often asymptomatic
  • Spinal AVMs, rarely
• First-degree relative meeting the above criteria
• Definite diagnosis when three or more of the above findings are present; possible/suspected when two findings are present

Clinical Presentation

• History, focusing on epistaxis, bleeding, anemia, polycythemia, cardio/resp/liver/neuro diseases
• Physical exam
  • Oxygen saturation, including orthodeoxia
  • Telangiectasis on fingers, ips, tongue, oropharynx, cheeks, conjunctiva
  • Liver bruits
  • High-output heart failure, from liver AVMs

Investigations

• Labs
  • CBC and ferritin, for anemia
  • Genetic testing for ENG and ECVRL1
• Imaging
  • Contrast echocardiography for pulmonary shunt
    • If negative, repeat q5yr
    • If positive, proceed to CT chest q5yr
  • Assesses location and size of PAVMs
    • Risk of new lesions goes down with age
    • Head MRI for cerebral AVMs once, preferably in infancy
    • Abdominal ultrasound or CT for hepatic AVMs

Management

Principles

• Treat telangiectases/AVMs of skin, oral, GI, and liver symptomatically
• Treat AVMs in lungs and brain prophylactically
• Screen family members

Screening

• One-time screen with MRI and contrast echo
• If contrast echo shows shunt, CT scan to assess AVMs
• Possible abdo ultrasound or CT if suspicious for liver AVMs

Follow-up

• Annual evaluation to screen for new symptoms
• Periodic CBC for anemia
• Every 5 years, reassess for PAVMs with CT (if previous AVMs) or contrast echo (it not)
• Screening for GI polyps in SMAD4-positive patients

Prophylaxis

• Always use IV with air filter
• If contrast echo positive for shunt, requires antibiotics with dental procedures
• Avoid antiplatelet medications

Treatment

Nosebleed

• Humidification and daily nasal lubricants
• Laser ablation, if mild to moderate
• Surgical treatment, if severe and refractory to above
• Avoid electric and chemical cautery
• Avoid embolization
• Oral contraceptive pill may decrease bleeding risk

GI bleeding

• Transfuse as needed
• Endoscopy or push enteroscopy
• Some small bowel sites may be amenable to surgical resection

Anemia

• Aggressive iron replacement, targetting a ferritin of greater than 50-100

Pulmonary AVMs

• Any >1-3mm should be considered for transcatheter embolization
• Follow-up CT at 6-12 months, then 5-yearly

Cerebral AVMs

• If >1cm, should be treated with neurosurgery, embolization, or stereotactic radiation

Hepatic AVMs

• No good options