Hereditary hemorrhagic telangiectasia

From IDWiki

Background

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

Epidemiology

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

Risk Factors

  • Family history

Clinical Manifestations

Differential Diagnosis

Investigations

  • Labs
    • CBC and ferritin, for anemia
    • Genetic testing for ENG and ECVRL1
  • Imaging
    • Contrast echocardiography for pulmonary shunt
      • If negative, repeat every 5 years
      • If positive, proceed to CT chest every 5 years
    • Assesses location and size of AVMs
      • Risk of new lesions goes down with age
      • Head MRI for cerebral AVMs once, preferably in infancy
      • Abdominal ultrasound or CT for hepatic AVMs

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

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 abdominal 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