Hereditary Hemorrhagic Telangiectasia With Multiple Ear, Nose, and Throat (ENT) Manifestations: A Case Report.

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare autosomal dominant multisystem disorder. It is a mucocutaneous and fibrovascular dysplasia, the diagnosis of which is based on the fulfillment of the four Curaçao criteria: 1) recurrent epistaxis; 2) dermatovascular mucosal telangiectasias at characteristic sites: skin of the face, ears, fingertips, lips, tongue, and oral and nasal cavity; 3) arteriovenous malformations (AVMs) of visceral organs and central nervous system; and 4) family history: diagnosis of HHT in a first-degree relative. We describe a case of a 76-year-old patient who presented to our department with clinical manifestations of HHT in the skin (face, fingertips), lips, hard palate, tongue, ears, and nasal cavities. Individual and family history was obtained, as well as clinical laboratory examination, pan-endoscopy of the ear, nose, and throat (ENT) systems, and treatment of active foci of bleeding from the above areas. The otolaryngologist may be the first doctor to suspect Rendu-Osler-Weber syndrome and the one responsible for treating patients with HHT since recurrent epistaxis is the most frequent (90-96% of patients) and the earlier manifestation of the disease and the main reason for the arrival of these patients in the Emergency Department. The purpose of this study is to present a clinical case of Rendu-Osler-Weber syndrome with multiple ENT manifestations, as well as a review of the literature on their management and treatment.

Current guidelines for diagnosis and management of hepatic involvement in hereditary hemorrhagic teleangiectasia.

Hereditary hemorrhagic teleangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is the most common cause of hepatic vascular malformations in adults. Different vascular shunts (arteriovenous, arterioportal or portovenous) lead to different clinical manifestations. Even though no hepatic-related symptoms are reported in the majority of cases, the severity of liver disease could lead to refractory medical conditions, in some cases requiring liver transplantation. The aim of this manuscript is to provide an updated overview of the current evidence regarding the diagnosis and treatment of HHT liver involvement and liver-related complications.

Cirugía de Young para el tratamiento quirúrgico de la epistaxis en telangiectasia hemorrágica hereditaria: reporte de un caso y revisión de la literatura / Young's procedure for surgical treatment of epistaxis in hereditary hemorrhagic telangiectasia: A case report and literature review

La telangiectasia hemorrágica hereditaria (THH) es una displasia vascular multisistémica, de herencia autosómica dominante, caracterizada por el desarrollo de telangiectasias mucocutáneas y malformaciones arteriovenosas viscerales. El diagnóstico se realiza mediante los criterios de Curasao publicados en el año 2000 y su manejo requiere de un equipo multidisciplinario donde el rol del otorrinolaringólogo(a) es fundamental, puesto que la epistaxis se presenta en un 90%-95% de los pacientes siendo una de las primeras manifestaciones clínicas de la enfermedad y pudiendo amenazar la vida del paciente. En la literatura se describen múltiples alternativas de tratamiento médico y quirúrgico para la epistaxis, sin existir un tratamiento definitivo para la enfermedad. A continuación, presentaremos el caso de una paciente de 56 años con THH y epistaxis recurrentes severas que, tras no responder al tratamiento médico conservador y múltiples procedimientos quirúrgicos, se realizó el cierre nasal mediante el procedimiento de Young, constituyendo el primer caso reportado en nuestro país.

Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia, of autosomal dominant inheritance, characterized by the development of mucocutaneous telangiectasias and visceral arteriovenous malformations. The diagnosis is made using the Curafao criteria published in 2000 and its management requires a multidisciplinary team where the role of the ENTs is fundamental, since epistaxis occurs in 90%-95% of patients, being one of the first clinical manifestations of the disease and may threaten the life of the patient. Multiple medical and surgical treatment alternatives for epistaxis are described in the literature without a definitive treatment for the disease. Here, we present the case of a 56-year-old patient with severe recurrent HHT and epistaxis who, after not responding to the initial conservative and surgical treatments, a nasal closure was performed, using the Young's procedure, constituting the first case reported in our country.

Hereditary Hemorrhagic Telangiectasia Associating Neuropsychiatric Manifestations with a Significant Impact on Disease Management-Case Report and Literature Review.

(1) Background: Genetic hereditary hemorrhagic telangiectasia (HHT) is clinically diagnosed. The clinical manifestations and lack of curative therapeutic interventions may lead to mental illnesses, mainly from the depression-anxiety spectrum. (2) Methods: We report the case of a 69-year-old patient diagnosed with HHT and associated psychiatric disorders; a comprehensive literature review was performed based on relevant keywords. (3) Results: Curaçao diagnostic criteria based the HHT diagnosis in our patient case at 63 years old around the surgical interventions for a basal cell carcinoma, after multiple episodes of epistaxis beginning in childhood, but with a long symptom-free period between 20 and 45 years of age. The anxiety-depressive disorder associated with nosocomephobia resulted in a delayed diagnosis and low adherence to medical monitoring. A comprehensive literature review revealed the scarcity of publications analyzing the impact of psychiatric disorders linked to this rare condition, frequently associating behavioral disengagement as a coping strategy, psychological distress, anxiety, depression, and hopelessness. (4) Conclusions: As patients with HHT face traumatic experiences from disease-related causes as well as recurring emergency hospital visits, active monitoring for mental illnesses and psychological support should be considered as part of the initial medical approach and throughout the continuum of care.

Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder, affecting 1:5000 individuals worldwide. All the genes associated to the disease (ENG, ACVRL1, SMAD4, GDF2) belong to the TGF-ß/BMPs signaling pathway. We found 19 HHT unrelated families, coming from a Northern Italy region and sharing the ACVRL1 in-frame deletion c.289_294del (p.H97_N98). METHODS: To test the hypothesis of a founder effect, we analyzed 88 subjects from 19 families (66 variant carriers, showing clinical signs of HHT, and 22 non-carriers, unaffected) using eight microsatellite markers within 3.7 Mb around the ACVRL1 locus. After the haplotype reconstruction, age estimation of the variant was carried out. RESULTS: We observed a common disease haplotype in 16/19 families, while three families showed evidence of recombination around the ACVRL1 locus. The subsequent age estimation analyses suggested that the mutation occurred about 8 generations ago, corresponding to about 200 years ago. We also present novel in silico and modeling data supporting the variant pathogenicity: the deletion alters the protein stability and removes the unique extracellular glycosylation site. CONCLUSION: We have demonstrated, for the first time, a "founder effect" for a HHT pathogenic variant in Italy.

HHT-Related Epistaxis and Pregnancy-A Retrospective Survey and Recommendations for Management from an Otorhinolaryngology Perspective.

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.

An update on the ophthalmic features in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber syndrome is a rare autosomal dominant disease, characterised by systemic angiodysplasia. Dysfunction of the signalling pathway of ß transforming growth factor is the main cause of HHT principally owing to mutations of the genes encoding for endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1). Clinical manifestations can range from mucocutaneous telangiectasia to organ arterio-venous malformations and recurrent epistaxis. The early clinical manifestations may sometimes be subtle, and diagnosis may be delayed. The main ophthalmic manifestations historically reported in HHT are haemorrhagic epiphora, and conjunctival telangiectasia present in 45-65% of cases, however, imaging with wide-field fluorescein angiography has recently shown peripheral retinal telangiectasia in 83% of patients. Optimal management of HHT requires both understanding of the clinical presentations and detection of early signs of disease. Advances in imaging methods in ophthalmology such as wide-field fluorescein angiography, spectral domain optical coherence tomography, and near infrared reflectance promise further insight into the ophthalmic signs of HHT towards improved diagnosis and early management of possible severe complications.

Hereditary Hemorrhagic Telangiectasia: Success of the Osler Calendar for Documentation of Treatment and Course of Disease.

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.

Left Atrial Appendage Occlusion: A Therapeutic Option in a Patient With Atrial Fibrillation and Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a predominantly inherited disorder of blood vessel structure, characterized by mucocutaneous telangiectasias, multiple arteriovenous malformations, and frequent epistaxis. A 67-year-old female with atrial fibrillation and high thromboembolic risk (CHADs2Vasc2: 4) with renal arterial thrombosis started oral anticoagulation (OAC). The patient had multiple episodes of heavy nasal and gastrointestinal bleeding (requiring multiple blood transfusions) such that OAC had to be interrupted, and a complementary investigation led to the diagnosis of HHT. Due to concomitant high thromboembolic and hemorrhagic risks, the patient was proposed left atrial appendage occlusion as an alternative to OAC intolerance. After the procedure, there were no new episodes of bleeding or thrombotic events.

Anesthetic considerations for cesarean delivery in a parturient with hereditary hemorrhagic telangiectasia: a case report.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare autosomal dominant disorder characterized by mucocutaneous telangiectasia and arteriovenous malformations (AVMs). There are some anesthetic considerations for cesarean delivery in a parturient with HHT. CASE PRESENTATION: A 27-year-old parturient with pulmonary hemorrhage was admitted to our tertiary perinatal center. She was first diagnosed with HHT and a cesarean delivery using spinal anesthesia at 37 weeks of gestation was initially planned. However, magnetic resonance imaging (MRI) at 32 weeks of gestation revealed spinal AVM ranging from the thoracic to the lumbar levels. Thus, elective cesarean delivery under general anesthesia was planned. The parturient had an uneventful perioperative course. CONCLUSIONS: HHT should be considered as a differential diagnosis when parturients develop pulmonary hemorrhage. In a cesarean delivery of parturients with HHT, spinal MRI during pregnancy can help in deciding the anesthetic procedure to be used.

Rupture of suppurated liver hematoma into the anterior abdominal wall in a patient with Rendu-Osler-Weber syndrome.

We report a case of ruptured liver hematoma as a result of suppurated arteriovenous malformation (AVM) in a patient with Rendu-Osler-Weber (ROW) syndrome. The patient presented with unexplained fever and upper right abdominal pain associated with microcytic anemia. A computed tomography scan revealed increasing subcapsular liver hematoma and features of liver abscess. Intraoperatively, a left liver hematoma mixed with pus was found that was attached to the anterior abdominal wall. Surgery included left lateral bisegmentectomy, while pathohistological analysis showed AVM and genetic tests confirmed ROW. This is the first such life-threatening surgical case of ROW complication reported in the scientific literature.

Reportamos el caso de una paciente con síndrome de Rendu-Osler-Weber y rotura de un hematoma hepático supurado como resultado de una malformación arteriovenosa. La paciente presentó fiebre inexplicable y dolor abdominal superior derecho asociado con anemia microcítica. La tomografía computarizada reveló un aumento del hematoma hepático subcapsular y las características del absceso hepático. Durante la cirugía se encontró un hematoma hepático izquierdo mezclado con pus que estaba unido a la pared abdominal anterior. La intervención incluyó bisegmentectomía lateral izquierda. El análisis histopatológico mostró malformación arteriovenosa y las pruebas genéticas confirmaron el síndrome de Rendu-Osler-Weber. Este es el primer caso quirúrgico potencialmente mortal de complicación de síndrome de Rendu-Osler-Weber reportado en la literatura científica.

Osler-Weber-Rendu Syndrome with Severe Hepatic Manifestations: A Rare Clinical Case.

Rendu-Osler-Weber syndrome is a rare inherited syndrome with autosomal dominant transmission characterized by systemic arteriovenous malformations (AVMs) with multi-organ involvement. Its incidence is 1-2/100,000 and it is predominant in females (the male/female ratio varies from 1:2 to 1:4.5). Clinical manifestations and complications are related to recurrent bleeding and, in some cases, the development of end-organ failure. Management is mostly supportive care and it is essential to promote control of the disease as much as possible and screen eventual complications. We describe the case of a 67-year-old male patient with Rendu-Osler-Weber syndrome admitted to the emergency department with decompensated heart failure due to acute anaemia because of severe epistaxis. During hospitalization, the patient progressed to acute-on-chronic liver failure with hepatic encephalopathy and an abdominal computed tomography scan showed multiple hepatic AVMs considered to be the cause of the chronic liver disease. LEARNING POINTS: Rendu-Osler-Weber syndrome is a rare autosomal dominant syndrome characterized by systemic arteriovenous malformations (AVMs) with multi-organ involvement, in which the most common manifestation is recurrent epistaxis.In more severe cases the prognosis is determined by organ dysfunction caused by AVMs, including hepatic involvement, which happens in 74-79% of cases, leading to poor outcomes.The treatment is mainly supportive care so early recognition of major organ involvement is fundamental to prevent severe complications.

Life-threatening Anaemia in Patient with Hereditary Haemorrhagic Telangiectasia (Rendu-Osler-Weber Syndrome).

Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare autosomal dominant vascular disorder. Patients with HHT may present with a wide spectrum of clinical manifestations from epistaxis to clinically significant arteriovenous malformations (AVM) in the lungs, liver, brain and spine. The diagnosis of HHT is based on clinical criteria. There is a long diagnostic delay of nearly 3 decades since disease onset. The treatment is based on various types of haemostasis. There is ongoing research with potential therapies which may prevent and decrease the severity of epistaxis. Thalidomide may be an effective treatment to decrease the bleeding symptoms of patients with HHT.

Intranasal Efudix reduces epistaxis in hereditary hemorrhagic telangiectasia.

BACKGROUND: Local application of fluorouracil (Efudix, 5-FU) induces sclerosis in patients with sinonasal tumors and superficial basocellular skin carcinoma. As a 'back against the wall' treatment, we investigated the local effect of nasally applied 5-FU and whether this could decrease the burden of severe epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: HHT patients with severe and frequent epistaxis, subsequent anemia and a necessity for blood and/or iron infusions were treated with a nasal tampon with 5-FU. This tampon was placed unilaterally in the nasal cavity on the side of the most severe epistaxis and replaced once weekly during 4 weeks. Outcome measures were safety and side effects, the aspect of the nasal mucosa measured with the mucosal HHT score, the epistaxis severity score (ESS), hemoglobin and ferritin plasma levels, and quality of life assessment pre-treatment, one and three months post-treatment. RESULTS: Six HHT patients participated. During treatment and follow-up, the nasal mucosa turned more pale and sclerotic and the number of telangiectases diminished. The mucosal HHT score improved and the ESS declined (p = 0.01). The decline of ESS persisted up to 3 months post-5-FU treatment. Moreover, mean hemoglobin levels increased from 6.0 pre-5-FU to 6.8 after one month post-5-FU. CONCLUSION: Unilateral application of 5-FU on a nasal tampon diminished the severity and frequency of epistaxis in all HHT patients. This effect sustained up to three months post-treatment, despite the fact that the contralateral side remained untreated. Subsequently, hemoglobin levels increased. Intranasal 5-FU is a promising entity for further research on epistaxis treatment in HHT patients.

Intra and extra oral clinical manifestations of Rendu-Osler-Weber syndrome: case report and literature review.

Hereditary Hemorrhagic Telangiectasia or Rendu-Osler-Weber syndrome is an incomplete penetrance dominant autosomal transmission disease which determines microcirculatory beds alterations (capillary and venules), caused by the loss of the support tissues that usually enclose blood vessels, and hemorrhage potentially in every organ. The syndrome clinical manifestations are multiple telangiectasia of small proportions on the skin or on the mucous membranes (e.g. of the gastrointestinal tract or other organs), in association with recurring bleedings of the affected areas and external and internal melena. The treatment is a supportive one so to prevent complications. This study reports a case of a patient affected by this syndrome in need of a dental implant following the fracture of a tooth. Furthermore, a bibliographical review of etiopathogenesis, clinical manifestations and therapy options has been made.

Rendu-Osler-Weber disease: a gastroenterologist's perspective.

Hereditary hemorrhagic teleangectasia (HHT, or Rendu-Osler-Weber disease) is a rare inherited syndrome, characterized by arterio-venous malformations (AVMs or Telangiectasia). The most important and common manifestation is nose bleeds (epistaxis). The telangiectasias (small AVMs) are most evident on the lips, tongue, buccal mucosa, face, chest, and fingers, however; large arterio-venous malformations can also occur in the lungs, liver, pancreas, or brain. Telangiectasias in the upper gastrointestinal tract are known to occur, however data regarding possible small-bowel involvement is limited due to technical difficulties in visualizing the entire gastrointestinal tract. The occurrence of AVMs in the stomach and small bowel can result in chronic bleeding and anaemia. Less frequently, this may occur due to bleeding from oesophageal varices, as patients with HHT can develop hepatic parenchymal AVMs or vascular shunts which cause hepatic cirrhosis and portal hypertension. Gastroenterologists have a crucial role in the management of these patients, however difficulties remain in the detection and management of complications of HHT in the gastrointestinal tract.

[Rendu-Osler disease and recurrent thromboembolic venous disease]. / Maladie de Rendu-Osler et maladie veineuse thromboembolique récidivante.

Rendu-Osler-Weber syndrome is a rare systemic fibrovascular dysplasia, recognized by mucocutaneous telangiectasias, arteriovenous malformations, epistaxis and family history. Venous thromboembolic disease is a poor prognostic factor in this disease given the risk of increased bleeding caused by anticoagulant therapy. We report a new case of a 56-year-old patient with Osler disease who developed recurrent thromboembolic venous disease when anticoagulants were discontinued. According to a review of the literature, this association does not appear to be fortuitous and is a factor of disease severity.

Liver transplantation in a patient with hereditary haemorrhagic telangiectasia and pulmonary hypertension.

Hereditary haemorrhagic telangiectasia or Rendu-Osler-Weber syndrome is a systemic vascular disease with autosomal dominant inheritance, mucocutaneous telangiectasia, and repeated nasal bleeding due to vascular abnormalities. Hereditary haemorrhagic telangiectasia may occasionally lead to complications, including arteriovenous malformations and pulmonary hypertension. We present a case of a 52-year-old female patient with hereditary haemorrhagic telangiectasia who was referred to our hospital for treatment of pulmonary hypertension. She had been diagnosed with hereditary haemorrhagic telangiectasia during adolescence and was being followed up. Six months prior to presentation, she had undergone coil embolization for pulmonary haemorrhage due to pulmonary arteriovenous malformations. She was in World Health Organization functional class IV, with a mean of pulmonary arterial pressure of 38 mmHg, a pulmonary capillary wedge pressure of 10 mmHg, and a right atrial pressure of 22 mmHg. A contrast-enhanced computed tomography angiography showed large arteriovenous malformations in the liver. Right heart catheterization revealed an increase in oxygen saturation in the inferior vena cava between the supra- and infra-hepatic veins, low pulmonary vascular resistance, and high right atrial pressure. Hence, she was diagnosed with hereditary haemorrhagic telangiectasia with pulmonary hypertension due to major arteriovenous shunt resulting from arteriovenous malformations in the liver. Therefore, we considered liver transplantation as an essential treatment option. She underwent cadaveric liver transplantation after a year resulting in dramatic haemodynamic improvement to World Health Organization functional class I. Liver transplantation is a promising treatment in patients with hereditary haemorrhagic telangiectasia and pulmonary hypertension resulting from arteriovenous shunt caused by arteriovenous malformations in the liver.

Severe Hepatic and Pulmonary Involvement in Rendu-Osler-Weber Syndrome.

We report the case of a young woman with hereditary hemorrhagic telangiectasia (HHT) with severe liver involvement and pulmonary shunting. The medical imaging in this patient illustrates the severe shunting that can occur in these patients who often are asymptomatic. By showing this case, we want to highlight the role of liver transplantation in HHT with hepatic involvement.

Telangiectasia hemorrágica hereditaria: a propósito de un caso clínico / Hereditary hemorrhagic telangiectasia: on the subject of a clinical case

La epistaxis, es un síntoma frecuente en la consulta de otorrinolaringología. Dentro de las causas posibles encontramos la telangiectasia hemorrágica hereditaria (síndrome de Rendu Osler Weber), que corresponde a un desorden autosómico dominante caracterizado por sangrados nasales y gastrointestinales asociados a malformaciones arteriovenosas sistémicas. Su manifestación más frecuente es la epistaxis, presentándose más frecuentemente en personas mayores de 40 años, sin predilección por género. Se presenta el caso de un paciente de sexo masculino de 46 años quien consulta por epistaxis a repetición y severa. Durante la hospitalización se efectúa el tratamiento convencional de la epistaxis, diagnóstico retroactivo del síndrome de Rendu Osler Weber y manejo multidisciplinario de la patología. Se realiza revisión de la literatura y discusión del manejo del paciente que cursa con esta enfermedad.

Epistaxis is a common symptom in the otorhinolaryngology consultation. Among the possible causes are hereditary hemorrhagic telangiectasia (Rendu Osler Weber syndrome), which corresponds to an autosomal dominant disorder characterized by nasal and gastrointestinal bleeding associated with systemic arteriovenous malformations. Its most frequent manifestation is epistaxis, presenting more frequently in people over 40 years of age, without gender preference. We present the case of a male patient of 46 years old who consults for recurrence and severe epistaxis. During hospitalization, conventional treatment of epistaxis, retroactive diagnosis of Rendu Osler Weber syndrome and multidisciplinary management of pathology are performed. We review the literature and discuss the management of patients with this disease.