Hereditary haemorrhagic telangiectasia: study of hepatic vascular alterations with multi-detector row helical CT and reconstruction programs.

PURPOSE: To evaluate hepatic alterations in patients affected by Hereditary Haemorrhagic Telangiectasia (HHT) by using multidetectorrow helical CT (MDCT) and new reconstruction programs. MATERIALS AND METHODS: An MDCT multiphasic study of the liver was performed in 105 consecutive patients: 89 considered to be affected by HHT and 16 with suspicion of disease alone. The scan delay was determined by using a test bolus of contrast material. The CT examination was performed with a triphasic technique (double arterial phase and portal venous phase). Multiplanar and angiographic reconstructions were then obtained, and the images checked for the presence of shunts, hepatic perfusion disorders, vascular lesions (telangiectases and large confluent vascular masses), indirect signs of portal hypertension, and anatomical vascular variants. RESULTS: Hepatic vascular alterations were found in 78/105 cases (67/89 patients affected by HHT and 11/16 patients with clinical suspicion alone). Therefore HHT diagnosis was excluded in 5 patients. 78/100 (78%) patients with HHT had intrahepatic vascular alterations: arterioportal shunts in 40/78 (51.2%), arteriosystemic shunts in 16/78 (20.5%), and both shunt types in 22/78 (28.3%). Intraparenchymal perfusion disorders were found in 46/78 (58.9%) patients. Telangiectases were recognised in 50/78 (64.1%) patients. Large confluent vascular masses (LCVMs) were identified in 20/78 (25.6%) patients. Indirect signs of portal hypertension were found in 46/78 (58.9%) cases. Variant hepatic arterial anatomy was present in 38/100 cases (38%). CONCLUSIONS: Multiphasic MDCT and the new reconstruction programs enable the identification and characterisation of the complex vascular alterations typical of HHT.

Evidence of small-bowel involvement in hereditary hemorrhagic telangiectasia: a capsule-endoscopic study.

BACKGROUND AND STUDY AIMS: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder leading to telangiectases and arteriovenous malformations of the skin, mucosa, and viscera. Telangiectases in the upper gastrointestinal tract are known, but data regarding possible small-bowel involvement are scarce due to the technical difficulty of exploring the entire gastrointestinal tract. The aim of the present study was to use capsule endoscopy (CE) to determine the prevalence of small-bowel telangiectases in HHT patients. PATIENTS AND METHODS: From December 2001 to September 2002, 20 consecutive adult HHT patients at an interdepartmental HHT center were prospectively evaluated. All patients underwent esophagogastroduodenoscopy (EGD) followed by CE within 24 h. The telangiectases were scored according to commonly accepted criteria by two endoscopists and two observers of the video-capsule images, who were blinded to each other's findings. RESULTS: EGD revealed gastric telangiectases in 15 of the 20 patients (75 %), while CE demonstrated small-bowel involvement in 10 of 18 patients (56 %; images were not recorded for two patients due to battery failure). No preferential site for telangiectasia was found between the jejunum and the terminal ileum. All patients who were positive on CE were also found to have gastric involvement at EGD. Patients with small-bowel telangiectases were significantly older than those without (62.5 years vs. 45 years; P < 0.02). CONCLUSIONS: This study established a 56 % prevalence of small-bowel telangiectases in patients with HHT. This new endoscopic technique will probably change the etiological diagnosis of occult bleeding in HHT patients (which is too often attributed only to epistaxis) and may also be able to alter treatment strategies in HHT patients with gastrointestinal bleeding.

Endoglin gene mutations and polymorphisms in Italian patients with hereditary haemorrhagic telangiectasia.

Autosomal-dominant hereditary haemorrhagic telangiectasia (HHT) is a genetically heterogeneous disease caused by mutations in at least two different loci. We screened for mutations in four Italian families where segregation studies showed clear evidence of linkage to the endoglin (ENG) locus. In addition, one sporadic case and three patients with pulmonary arteriovenous malformations, belonging to small nuclear families unsuitable for linkage analysis, were included in the screening. The proband from each family was investigated using single-strand conformation polymorphism and heteroduplex analysis; potential variants were sequenced. Four novel and one previously reported mutation were detected, as well as three new polymorphisms. The novel mutations included deletions in exon 1 (patient 581/02), exon 5 (patient 780/01) and exon 7 (patient 700/01), and a C-->T229 substitution in exon 3 (patient 462/02). When analysing patient 700/01 and his affected daughter, we encountered a mutant ENG allele with two mutations--a deletion in exon 7 and a substitution in exon 12--which converts isoleucine 575 into threonine, in a non-conserved region. Both mutations were absent in the two healthy sons of the patient, while the polymorphic variant in exon 12 was present in his healthy father. These results and haplotype-segregation studies suggest that a de novo deletion had occurred in the gamete of paternal origin. For the first time the parental germline in which a de novo HHT mutation occurred has been identified.

Hereditary hemorrhagic teleangiectasia (Rendu-Osler-Weber disease).

Rendu-Osler-Weber disease, or hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant disorder with incomplete penetrance, characterized by vascular anomalies which may virtually develop in many organs. The prevalence varies and may range from 1/3,500 to 1/5,000 in specific regions. Two chromosal sites have been at least identified: in HHT1, mutations at chromosome 9 alter the protein endoglin and in HHT2, mutations at chromosome 12 alter the protein activine or ALK-1. Clinical manifestations include recurrent epistaxis, mucocutaneous telangiectases that bleed easily, and larger arteriovenous malformations in parenchymatous organs. Epistaxis is the first symptom, occurring in the vast majority of affected persons. The lung is the most common site for arteriovenous malformations. Brain abscess, transient ischemic attack and ischemic stroke occur exclusively in patients with pulmonary arteriovenous malformations and right-to-left shunt, which facilitates the passage of emboli into the cerebral circulation. Transcatheter embolotherapy with detachable balloons or stainless-steel coils has been used in order to occlude such malformations and to prevent such complications. At present a genetic diagnosis is possible in only a few families. The clinical diagnosis is based on 4 criteria: family history, epistaxis, mucocutaneous telangiectases and arteriovenous malformations. The diagnosis will be definite if 3 criteria are present, suspected if 2 criteria are present, unlikely if fewer than 2 criteria are present. In conclusion, the authors examine clinical features of 28 HHT patients observed in the HHT University Centre of Bari from September 2000 to May 2001.

Angiogenesis and hereditary hemorrhagic telangiectasia. Rendu-Osler-Weber disease.

To date much of the recent work on pathological angiogenesis has focused on inflammatory diseases, diabetes and cancer in particular. Hereditary hemorrhagic telangiectasia or Rendu-Osler-Weber disease provides an example of the genetic disorder of angiogenesis in which a multisystemic angiodysplasia is responsible for severe hemorrhage. The disease pathogenesis is partially explained by a defect in the TGF-beta signaling system, although in more recent works a possible role of other vascular growth factors has been proposed. This paper provides a model of an aberrant angiogenesis in which multiple vascular growth factors could be involved in a diffuse angiodysplasia.