Search Results (13)

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Rendu–Osler–Weber syndrome, is a disorder of angiogenesis characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations. This rare autosomal dominant disorder is caused by pathogenic variants in the ENG and ACVRL1 genes, and only 1–3% of case variants occur in SMAD4. HHT clinical manifestations include telangiectasias, epistaxis, and arteriovenous malformations in multiple organ systems. Clinical diagnosis is based on Curaçao Criteria. Here, we describe a pauci-symptomatic 10-year-old girl with an orbital and sinus infectious disease. Her clinical history was unremarkable, except for sporadic, self-limiting epistaxis episodes. She showed finger clubbing and low oxygen saturation levels on pulse oximetry, suggesting a chronic lung disease, and a large lung arteriovenous malformation. She also developed acute neurological symptoms, with evidence of multiple cerebral abscess lesions on MRI. HHT was therefore suspected and confirmed by genetic analysis, which revealed a de novo pathogenic variant in the ENG gene [c.1183G>T p.(Glu395Ter)] found in only 15% of the reads from NGS analysis, performed on peripheral blood lymphocytes, indicating a possible mutational mosaicism. This case outlines that HHT could present with unusual clinical symptoms highlighting the importance of diagnosis using both clinical criteria and genetic test. Full article

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease, is an autosomal dominant vascular disorder caused most commonly by pathogenic variants in the ENG and ACVRL1/ALK1 genes. It is characterized by mucocutaneous telangiectasias and arteriovenous malformations (AVMs) in various organs, leading to recurrent epistaxis, gastrointestinal bleeding, and iron deficiency anemia. Diagnosis relies on the Curaçao Criteria, which include recurrent nosebleeds, characteristic telangiectasias, visceral AVMs, and family history. This review aims to present current therapeutic approaches and emerging treatment strategies for HHT. Traditional surgical and laser-based methods are increasingly complemented or replaced by targeted pharmacological interventions. Antiangiogenic agents such as bevacizumab and thalidomide have demonstrated efficacy in reducing bleeding frequency and transfusion requirements, although adverse effects may limit long-term use. Novel therapies under investigation target molecular pathways involved in vascular remodeling, including tyrosine kinase inhibitors (sorafenib, nintedanib), anti-ANGPT2 antibodies, and modulators of BMP9/ALK1 signaling (tacrolimus, sirolimus). Preclinical and early clinical studies suggest that these agents may provide disease-modifying benefits. Continued research should focus on optimizing treatment efficacy, reducing toxicity, and developing individualized therapeutic regimens based on genetic and clinical characteristics. Full article

Vascular liver diseases (VLDs) include different pathological conditions that affect the liver vasculature at the level of the portal venous system, hepatic artery, or venous outflow system. Although serological investigations and sometimes histology might be required to clarify the underlying diagnosis, imaging has a crucial role in highlighting liver inflow or outflow obstructions and their potential causes. Cross-sectional imaging provides a panoramic view of liver vascular anatomy and parenchymal patterns of enhancement, making it extremely useful for the diagnosis and follow-up of VLDs. Nevertheless, multiparametric ultrasound analysis provides information useful for differentiating acute from chronic portal vein thrombosis, distinguishing neoplastic invasion of the portal vein from bland thrombus, and clarifying the causes of venous outflow obstruction. Color Doppler analysis measures blood flow velocity and direction, which are very important in the assessment of VLDs. Finally, liver and spleen elastography complete the assessment by providing intrahepatic and intrasplenic stiffness measurements, offering further diagnostic information. Full article

Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu–Osler–Weber Syndrome (ROW) is an autosomal dominant vascular disease, with an estimated prevalence of 1:5000. Genes associated with HHT are ACVRL1, ENG, SMAD4, and GDF2, all encoding for proteins involved in the TGFβ/BMPs signaling pathway. The clinical diagnosis of HHT is made according to the “Curaçao Criteria,” based on the main features of the disease: recurrent and spontaneous epistaxis, muco-cutaneous telangiectases, arteriovenous malformations in the lungs, liver, and brain, and familiarity. Since the clinical signs of HHT can be misinterpreted, and the primary symptom of HHT, epistaxis, is common in the general population, the disease is underdiagnosed. Although HHT exhibits a complete penetrance after the age of 40, young subjects may also present symptoms of the disease and are at risk of severe complications. Here we review the literature reporting data from clinical, diagnostic, and molecular studies on the HHT pediatric population. Full article

Objectives: To evaluate short- and long-term safety and efficacy of embolization with Onyx^® for recurrent pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia (HHT). Methods: In total, 45 consecutive patients (51% women, mean (SD) age 53 (18) years) with HHT referred to a reference center for treatment of recurrent PAVM were retrospectively included from April 2014 to July 2021. Inclusion criteria included evidence of PAVM recurrence on CT or angiography, embolization using Onyx^® and a minimal 1-year-follow-up CT or angiography. Success was defined based on the standard of reference criteria on unenhanced CT or pulmonary angiography if a recurrence was suspected. PAVMs were analyzed in consensus by two radiologists. The absence of safety distance, as defined by a too-short distance for coil/plug deployment, i.e., between 0.5 and 1 cm, between the proximal extremity of the primary embolic material used and a healthy upstream artery branch, was reported. Results: In total, 70 PAVM were analyzed. Mean (SD) follow-up was 3 (1.3) years. Safety distance criteria were missing in 33 (47%) PAVMs. All procedures were technically successful, with a short-term occlusion rate of 100% using a mean (SD) of 0.6 (0.5) mL of Onyx^®. The long-term occlusion rate was 60%. No immediate complication directly related to embolization was reported, nor was any severe long-term complication such as strokes or cerebral abscesses. Conclusions: In HHT, treatment of recurrent PAVM with Onyx^® showed satisfactory safety and efficacy, with an immediate occlusion rate of 100% and a long-term rate of 60%. Full article

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disorder of vascular development. Common manifestations include epistaxis, telangiectasias and arteriovenous malformations in multiple organs. Different deletions or nonsense mutations have been described in the ENG (HHT1) or ACVRL1/ALK1 (HHT2) genes, all affecting endothelial homeostasis. A novel mutation in ACVRL1/ALK1 has been identified in a Peruvian family with a clinical history compatible to HHT. Subsequently, 23 DNA samples from oral exchanges (buccal swaps) of the immediate family members were analyzed together with their clinical histories. A routine cDNA PCR followed by comparative DNA sequencing between the founder and another healthy family member showed the presence of the aforementioned specific mutation. The single mutation detected (c.525 + 1G > T) affects the consensus splice junction immediately after exon 4, provokes anomalous splicing and leads to the inclusion of intron IV between exons 4 and 5 in the ACVRL1/ALK1 mRNA and, therefore, to ALK1 haploinsufficiency. Complete sequencing determined that 10 of the 25 family members analyzed were affected by the same mutation. Notably, the approach described in this report could be used as a diagnostic technique, easily incorporated in clinical practice in developing countries and easily extrapolated to other patients carrying such a mutation. Full article

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant vascular disease defined by the presence of mucosal and cutaneous telangiectasia and visceral arterio-venous malformations. The latter are abnormal capillary-free direct communications between the pulmonary and systemic circulations with the following consequences: arterial hypoxemia caused by right-to-left shunts; paradoxical embolism with transient ischemic attack or stroke and brain abscess caused by the absence of the normally filtering capillary bed; and hemoptysis or hemothorax due to the rupture of the thin-walled arterio-venous malformations (particularly during pregnancy). It is frequently underdiagnosed, commonly presenting as complications from shunting through arterio-venous malformations: dyspnea, chronic bleeding, or embolism. Arterio-venous malformations are present not only in the lungs, but can also be found in the liver, central nervous system (mainly in the brain), nasal mucosa, or the gastrointestinal tract. The first choice of therapy is embolization of the afferent arteries of the arterio-venous malformations, a minimally invasive procedure with a high efficacy, a low morbidity, and low mortality. Other therapeutic modalities are surgery (resection) or stereotactic radiosurgery (using radiation). Routine screening for arterio-venous malformations is indicated in patients diagnosed with this condition and can prevent severe complications such as acute hemorrhages, brain abscesses, or strokes. Clinicians should provide a long-term follow-up for patients with arterio-venous malformations, in an effort to detect their growth or reperfusion in case of previously treated malformations. In spite of two experts’ consensuses, it still possesses multiple therapeutic challenges for physicians, as several aspects regarding the screening and management of arterio-venous malformations still remain controversial. Multidisciplinary teams are especially useful in complex cases. Full article

Appropriate management of hereditary hemorrhagic telangiectasia (HHT) is of particular importance in females, as HHT-mediated modifications of the vascular bed and circulation are known to increase the risk of complications during pregnancy and delivery. This study was undertaken to evaluate female HHT patients’ awareness of and experience with HHT during pregnancy and delivery, with a focus on epistaxis. In this retrospective study, 46 females (median age: 60 years) with confirmed HHT completed a 17-item questionnaire assessing knowledge of HHT and its pregnancy-associated complications, the severity of epistaxis during past pregnancies and deliveries, and the desire for better education and counselling regarding HHT and pregnancy. Results revealed that 85% of participants were unaware of their disease status prior to the completion of all pregnancies. Further, 91% reported no knowledge of increased pregnancy-related risk due to HHT. In regard to epistaxis, 61% of respondents reported experiencing nosebleeds during pregnancy. Finally, approximately a third of respondents suggested that receiving counseling on the risks of HHT in pregnancy could have been helpful. Findings suggest that awareness of HHT and its potential for increasing pregnancy-related risk is poor. Best practices in HHT management should be followed to minimize negative effects of the disorder. Full article

Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia (HHT), is a rare, autosomal dominant condition that affects approximately 1 in 5000 patients causing abnormal blood vessel formation. HHT patients have mucocutaneous telangiectasias and arteriovenous malformations in various organs. The most prominent symptom of HHT is epistaxis, which, together with gastrointestinal bleeding, may cause iron deficiency anemia. This study is a case report of a 62-year-old patient who was admitted to the Department of Gastroenterology due to acute upper gastrointestinal bleeding and a history of recurrent epistaxis and melena for 4 days, which was confirmed in digital rectal examination. Urgent upper gastrointestinal endoscopy revealed active bleeding from multiple angioectatic spots with bright-looking salmon-colored patches in the antrum and the body suggestive of HHT. The bleeding from two angioectatic spots was stopped by argon plasma coagulation, and four clips were placed to provide good hemostasis. The patient was treated with a proton pomp inhibitor infusion and iron infusion. She was discharged with no signs of GI bleeding, normalized iron levels and a diagnosis of HHT. She was referred to further genetic testing, including evaluation of first-degree relatives. She also had performed unenhanced thin-cut computed tomography (CT) with angiography to exclude the presence of pulmonary arteriovenous malformations (PAVMs). Due to the fact that the patient did not manifest any other HHT-related symptoms and that the instrumental screening discloses no silent AVMs in other organs, the “watch-and-wait strategy” was applied. Although, Osler-Weber-Rendu syndrome is widely described in the medical literature, effective treatment of gastrointestinal telangiectasias is not always available and still lacks standardization to date, which makes the management of gastroenterological involvement still a challenging issue. Full article

Hereditary hemorrhagic telangiectasia (HHT; Rendu-Osler-Weber syndrome) affects the capillary and larger vessels, leading to arteriovenous shunts. Epistaxis is the main symptom impairing quality of life. The aim of the Osler Calendar is to offer information about the extent of the systemic disease and the current state of treatment. A care plan with information on the rare disease and self-treatment of epistaxis was created. Organ examinations and ongoing treatments were recorded. A questionnaire documents the treatment success, including patient satisfaction, frequency of hemorrhage and hemoglobin levels. The patients using the Osler Calendar for at least one year (n = 54) were surveyed. Eighty-five percent of patients (n = 46) used the calendar to gain information about HHT. Seventy-two percent (n = 39) used the Osler Calendar for instructions on the self-treatment of nosebleeds. The calendar increased patients’ understanding for the need for organ screenings from 48% (n = 26) to 81% (n = 44). Seventy-nine percent (n = 43) of patients confirmed that the Osler Calendar documented their therapeutic process either well or very well. Fifty-two percent (n = 28) saw an improvement in the therapeutic process due to the documentation. The Osler Calendar records the individual intensity of the disease and facilitates the communication between attending physicians. It is a tool for specialists to review treatment strategies. Furthermore, the calendar enhances patients’ comprehension of their condition. Full article

In this review, we discuss the role of transforming growth factor-beta (TGF-β) in the development of pulmonary vascular disease (PVD), both pulmonary arteriovenous malformations (AVM) and pulmonary hypertension (PH), in hereditary hemorrhagic telangiectasia (HHT). HHT or Rendu-Osler-Weber disease is an autosomal dominant genetic disorder with an estimated prevalence of 1 in 5000 persons and characterized by epistaxis, telangiectasia and AVMs in more than 80% of cases, HHT is caused by a mutation in the ENG gene on chromosome 9 encoding for the protein endoglin or activin receptor-like kinase 1 (ACVRL1) gene on chromosome 12 encoding for the protein ALK-1, resulting in HHT type 1 or HHT type 2, respectively. A third disease-causing mutation has been found in the SMAD-4 gene, causing a combination of HHT and juvenile polyposis coli. All three genes play a role in the TGF-β signaling pathway that is essential in angiogenesis where it plays a pivotal role in neoangiogenesis, vessel maturation and stabilization. PH is characterized by elevated mean pulmonary arterial pressure caused by a variety of different underlying pathologies. HHT carries an additional increased risk of PH because of high cardiac output as a result of anemia and shunting through hepatic AVMs, or development of pulmonary arterial hypertension due to interference of the TGF-β pathway. HHT in combination with PH is associated with a worse prognosis due to right-sided cardiac failure. The treatment of PVD in HHT includes medical or interventional therapy. Full article

Hemorrhagic telangiectasia (HHT) is a disease of initially mild course - manifesting with recurrent nosebleeds and increased fatigue. Nevertheless, its progression can deteriorate patient’s health. Solid organ transplantation becomes the only therapeutic option to save a life. The case report describes a 19-year-old female patient who was diagnosed with HHT and qualified for lung transplantation. She met the Curacao criteria for HHT (¾). Her health deteriorated significantly to the point of the referral to Department of Cardiac, Vascular and Endovascular Surgery and Transplantology in Silesian Center for Heart Diseases. Due to her condition, she was qualified for lung transplantation as one diagnosed with pulmonary arteriovenous malformations and then transplanted at the age of 17. A direct postoperative period was complicated by HSV2 infection of the wound. 18 months after the procedure, the patient underwent acute cholangitis. The presence of portal and systemic fistulas was noted and the final diagnosis of HHT was made. Despite the fact that proper diagnosis was made posttransplant, it was a good treatment. The patient is currently 2 years after the lung transplantation and feels good. Lung transplantation is a viable therapeutic option for patients with HHT as there are reports of other patients who have benefited from lung transplantation after other therapeutic options were exhausted. Full article