Maurizio Memeo

Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers

Summary.  Background: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs), particularly in the brain (CAVMs), lungs (PAVMs), liver (HAVMs) and gastrointestinal tract (GI). The identification of a mutated ENG (HHT1) or ALK‐1 (HHT2) gene now enables a genotype–phenotype correlation. Objective: To determine the incidence of visceral localizations and evaluate phenotypic differences between ENG and ALK1 mutation carriers. Methods: A total of 135 consecutive adult patients were subjected to mutational screening in ENG and ALK1 genes and instrumental tests to detect AVMs, such as chest–abdomen multislice computed tomography (MDCT), brain magnetic resonance imaging and magnetic resonance angiography (MRI/MRA), upper endoscopy, were offered to all patients, independent of presence of clinical symptoms. The 122 patients with identified mutations were enrolled in the study and genotype–phenotype correlations were established. Results: PAVMs and CAVMs were significantly more frequent in HHT1 (75% vs. 44%, P < 0.0005; 20% vs. 0%, P < 0.002, respectively) and HAVMs in HHT2 (60% vs. 84%, P < 0.01). No age difference was found for PAVMs whereas HAVMs were significantly higher in older patients in both HHT1 and HHT2. Neurological manifestations secondary to CAVMs/PAVMs were found only in HHT1 patients, whereas severe liver involvement was detected only in HHT2. Respiratory symptoms were mainly detected in HHT1. Conclusions: Our study evidences a higher visceral involvement in HHT1 and HHT2 compared with previous reports. HHT1 is more frequently associated with congenital AVM malformations, such as CAVMs and PAVMs whereas HHT2 predominantly involves the liver. The ENG gene should be first targeted for mutational screening in the presence of large PAVM in patients < 45 years.

Hepatic involvement in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterized by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations) that may be widely distributed throughout the cardiovascular system. The recognition of mucocutaneous telangiectases, the occurrence of spontaneous and recurrent episodes of epistaxis, the presence of visceral involvement, and a family history of this disease are the clinical criteria that allow diagnosis. In comparison with skin, lungs, gastrointestinal tract, and brain involvement, hepatic involvement defined by clinical criteria alone has long been considered uncommon. Our experience with a large group of HHT patients, even those asymptomatic for liver involvement, demonstrates that it is more frequent than reported and is characterized by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases, and other vascular lesions. Congestive cardiac failure, portal hypertension, portosystemic encephalopathy, cholangitis, and atypical cirrhosis have been reported as possible serious complications related to this condition. Thus, a correct diagnosis is important, and diagnostic imaging has a fundamental role in detecting alterations involving the liver. The possibilities to perform a multiphasic study and to provide high-quality multiplanar and angiographic reconstructions, gives multidetector row helical computed tomography the ability to detect and characterize the complex anatomopathologic alterations typical of this disease.

Diagnostic imaging in the study of visceral involvement of hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterised by mucocutaneous or visceral angiodysplastic lesions. Its diagnosis is exclusively based on clinical criteria. The brain, lungs and liver, in growing order of prevalence, are the most frequently involved organs. Diagnostic imaging based on ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) has a fundamental role in detecting visceral involvement in HHT patients and is therefore crucial for the prognostic assessment and therapeutic approach. Arteriovenous shunts are the most common cerebrovascular malformations (CVMs). MRI and CT angiography are the methods of choice for diagnosing cerebral involvement, and it is debated whether MRI could be considered as a screening examination on account of its noninvasiveness. Pulmonary arteriovenous malformations, diffuse telangiectases or high-flow, low-pressure shunts between pulmonary arteries and veins can be studied with contrast-enhanced US, but multidetector CT seems to provide the most comprehensive evaluation of their angioarchitecture, whereas angiography has a predominant role in treatment. Liver involvement is frequent and characterised by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases and other vascular lesions. US is useful for detecting hepatic lesions but should be completed by more accurate imaging methods such as multidetector CT and MRI.RiassuntoLa telangiectasia emorragica ereditaria (HHT), o malattia di Rendu-Osler-Weber, è un disordine vascolare ereditario, caratterizzato dalla comparsa di lesioni angiodisplasiche mucocutanee e viscerali, la cui diagnosi si basa esclusivamente su criteri clinici. L’encefalo, i polmoni ed il fegato sono, in ordine crescente di prevalenza, le sedi viscerali più frequentemente coinvolte. La diagnostica per immagini, mediante gli ultrasuoni (US), la tomografia computerizzata (TC), la risonanza magnetica (RM) e la angiografia (DSA), ha un ruolo cruciale nella diagnosi del coinvolgimento viscerale nei pazienti affetti da HHT ed è, pertanto, fondamentale nella valutazione prognostica e nella impostazione terapeutica. Tra le malformazioni vascolari cerebrali gli shunt arterovenosi costituiscono l’alterazione più frequente. La RM e la angio-TC sono le metodiche di scelta nella diagnosi dell’interessamento cerebrale, ed è dibattuto se, per la scarsa invasività, la RM sia da proporre come metodica di screening. Le malformazioni arterovenose polmonari, telangiectasie diffuse o fistole tra arterie e vene polmonari, possono essere ricercate con US con MdC, ma la TC multidetettore appare l’indagine più completa per la valutazione della loro angioarchitettura mentre l’angiografia mantiene un ruolo prevalentemente terapeutico. L’interessamento epatico è frequente e caratterizzato dalla comparsa di fistole arterovenose, telangiectasie intraparenchimali ed altre alterazioni vascolari. Gli US sono utili nella ricerca delle lesioni epatiche, ma devono essere integrati da indagini più accurate quali la TC multidetettore e la RM.

Lipoma gastrico sanguinante

1. Neoformazione vegetante peduncolata della parete anteriore dell’antro, a partenza sottomucosa. La lesione appare disomogenea per la presenza di una componente adiposa nel cui contesto sono evidenti alcune aree iperdense. 2. Lipoma ulcerato con recenti emorragie intralesionali. 3. Le scansioni senza mdc consentono gia una diagnosi, ma l’introduzione del mdc potrebbe evidenziare un eventuale stravaso dello stesso, indice di sanguinamento in atto. 4. Tutte le lesioni gastriche a partenza sottomucosa, generalmente di origine mesenchimale (GISTs, leiomiomi e leiomioblastomi, schwannomi e neurofibromi).

Diverticolo del colon sanguinante trattato per via endovascolare

1. La presenza di mdc iperdenso nel contesto del lume del tratto distale del colon discendente (freccia e asterisco) in un paziente con multipli diverticoli del colon (teste di freccia). 2. Emorragia acuta gastrointestinale bassa ad origine diverticolare. 3. No, non e sufficiente. 4. Emorragia da lesione angiodisplasica o da coagulopatia.

Hereditary Haemorrhagic Teleangiectasia: Diagnostic Imaging of Visceral Involvement

Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterised by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations), which may be widely distributed throughout the cardiovascular system. Its diagnosis is based on clinical criteria. Liver, lungs and brain, in order of prevalence, are the most frequently involved visceral districts of the body other than skin and nasal mucosa. Liver involvement is frequent and characterised by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases and other vascular lesions. Although it is usually asymptomatic, congestive cardiac failure, portal hypertension, portosystemic encephalopathy, cholangitis or atypical cirrhosis are possible complications. Pulmonary arteriovenous malformations involve more than one third of HHT patients and can consist of diffuse telangiectases or high-flow low-pressure shunts between pulmonary arteries and veins. Pulmonary involvement can cause serious complications: hypoxaemia, pulmonary or pleural hemorrhage, paradoxical embolism into cerebral circulation. Various types of cerebrovascular malformations can affect HHT patients and the most common are arteriovenous malformations, consisting of one or more feeding arteries connected to one or more draining veins. Diagnostic imaging has a fundamental role in detecting the alterations involving these various districts in the body. The possibility to perform fast and complete studies and to provide high quality multiplanar and angiographic reconstructions, gives multi-detector row helical computed tomography and magnetic resonance the ability to detect and characterise the complex anatomo-pathological alterations typical of HHT. Ultrasonography seems to be the best screening modality for hepatic and pulmonary involvement.