Optimal management of hereditary hemorrhagic telangiectasia

Abstract

Neetika Garg,1 Monica Khunger,2 Arjun Gupta,3 Nilay Kumar4 1Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 2Department of Medicine, All India Institute of Medical Sciences, New Delhi, India; 3Department of Medicine, UT Southwestern Medical Center, Dallas, TX, USA; 4Department of Medicine, Cambridge Health Alliance/Harvard Medical School, Cambridge, MA, USA Abstract: Hereditary hemorrhagic telangiectasia (HHT), also known by the eponym Osler–Weber–Rendu syndrome, is a group of related disorders inherited in an autosomal dominant fashion and characterized by the development of arteriovenous malformations (AVM) in the skin, mucous membranes, and/or internal organs such as brain, lungs, and liver. Its prevalence is currently estimated at one in 5,000 to 8,000. Most cases are due to mutations in the endoglin (HHT1) or ACVRLK1 (HHT2) genes. Telangiectasias in nasal and gastrointestinal mucosa generally present with recurrent/chronic bleeding and iron deficiency anemia. Larger AVMs occur in lungs (~40%–60% of affected individuals), liver (~40%–70%), brain (~10%), and spine (~1%). Due to the devastating and potentially fatal complications of some of these lesions (for example, strokes and brain abscesses with pulmonary AVMs), presymptomatic screening and treatment are of utmost importance. However, due to the rarity of this condition, many providers lack an appreciation for the whole gamut of its manifestations and complications, age-dependent penetrance, and marked intrafamilial variation. As a result, HHT remains frequently underdiagnosed and many families do not receive the appropriate screening and treatments. This article provides an overview of the clinical features of HHT, discusses the clinical and genetic diagnostic strategies, and presents an up-to-date review of literature and detailed considerations regarding screening for visceral AVMs, preventive modalities, and treatment options. Keywords: arteriovenous malformations, epistaxis, bevacizumab, embolization, guidelines, screening, review