Hereditary Hemorrhagic Telangiectasia

(Osler-Weber-Rendu syndrome)

Genetics

1 in 5,000-8,000 individuals Autosomal dominant Can have incomplete penetrance Genetic heterogeneity Endoglin (ENG) on chromosome 9 = HHT1 Activan receptor-like kinase 1 (ALK1 or ACVRL1) on

chromosome 12 = HHT2 At least one other unknown gene

Both ENG and ALK1 involved in transforming growth factor beta pathway

Clinical Features of HHT

Epistaxis >90% Skin, lips, mouth telangiectasias 80% Pulmonary AVMs 30% Hepatic AVMs <30% GI bleeds 15% Cerebral AVMs 10% Spinal AVMs 1%

Diagnosis

Criteria Recurrent spontaneous epistaxis Mucocutaneous telangiectasias Visceral involvement Affected first degree relative

3+ criteria = definite HHT 2 criteria = suspected HHT 1 criteria = unlikely HHT

Onset of HHT symptoms

Begbie, et al. Postgrad Med J 2003;79:18-24

Epistaxis

90+% of HHT patients Treatment options Treat anemia: iron replacement, transfusion Topical therapy: nasal sprays, creams, hemostatics Systemic therapy:

Estrogen +/- progesterone or androgens Antiestrogens Antifibrinolytics

Local ablation: lasers (Nd:YAG, Argon, KTP, PDL) Surgery: e.g., septodermatoplasty Embolization?

Visceral involvement

GI bleeding 15% of HHT individuals Telangiectasias can occur anywhere in GI tract Usually stomach and duodenum Treatment Iron, transfusions Systemic estrogens Repeated endoscopic laser ablation

Visceral involvement

Pulmonary arteriovenous malformations 30% of HHT individuals Thin walled vessels in place of capillaries Right to left shunting of deoxygenated blood Lack of pulmonary filtering of emboli Risk of bleeding into lower airway

HHT patients should be screened for PAVMs Treat with embolization

Visceral involvement

Cerebral AVMs 10% of HHT individuals Neurologic symptoms Intracranial hemorrhage Treat with embolization

Hepatic AVMs <30% of HHT individuals Usually asymptomatic Can result in left to right shunt and high output cardiac

failure, portal hypertension, and/or biliary disease Treat with liver transplantation in cases of liver failure

Take Home Points

HHT is not that rare Consider in patients with epistaxis and family hx

and/or telangiectasias Morbidity/mortality from visceral involvement Major blood loss from aerodigestive tract AVMs Screening important

Treatments (but no cure) Local ablation with vascular lasers Systemic estrogens +/- progesterone or androgens Embolism for AVMs