Assessment of Intestinal Vascular Malformations in Patients with Hereditary Hemorrhagic Teleangiectasia and Anaemia

Abstract

Introduction: Hereditary hemorrhagic teleangiectasia (HHT), or Rendu Osler Weber's disease, is an autosomal dominant disorder with mucocutaneous teleangiectasia and visceral arteriovenous malformations. Mutations of endoglin and Activin A receptor like kinase 1 lead to different phenotypes, HHT1 and HHT2 respectively. The gastrointestinal tract is frequently affected which can result in iron deficiency anaemia. There is limited information on the relationship between gastrointestinal/small intestinal teleangiectasia and the genotype. Aim: To determine whether different genotypes HHT have different phenotypes with respect to the presence of small intestinal teleangiectasia as assessed by videocapsule endoscopy. Methods: HHT patients, referred for anaemia, were analysed by videocapsule endoscopy (Given Imaging, Yoqneam, Israel). A chart review was performed to obtain information on the genotype and the presence of HHT manifestations in nose, brain, lungs, liver, upper and lower gastrointestinal tract. Results: Twenty five patients were analysed (M/F 13/9, mean age 49 +/− 15 yrs., range 18-72 yrs.). Fourteen patients had HHT1 and 8 patients had HHT2. In three patients no known mutation was found. The mean haemoglobin level was 7.2 +/− 1.7 mmol/l. Epistaxis occurred in 24/25 (96%) of patients. Gastroduodenoscopy revealed the presence of teleangiectasia in 7/12 (56%) HHT1 patients and in 3/8 (38%) of HHT2 patients. VCE found small intestinal teleangiectasia in all HHT1 patients and in 9/14 patients they were classified as large. In HHT2 patients 5/8 (63%) had small intestinal teleangiectasia, in all but one patient these were small. Vascular abnormalities in the colon occurred in 6/11 (55%) of the HHT1 patients. No abnormalities of the colon were observed in the HHT2 patients. Hepatic arteriovenous malformations were present in 1/7 HHT1 patients and in 5/6 HHT2 patients. Arteriovenous malformations outside the digestive tract were present in the lungs of 9 HHT1 patients and 2 patients with an unknown mutation, and in the cerebrum of 2 HHT1 patients and 1 patient without identified mutation. Conclusion: Teleangiectasia are common in the gastrointestinal tract of HHT patients. The presence of large teleangiectasia in the small intestine and the colon is restricted to HHT1 patients in this study. HAVM predominantly occurs in HHT2 patients. VCE should be performed in HHT patients with anaemia to determine the extent of teleangiectasia.