ABSTRACT
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterised by small telangiectasias and larger multisystem arteriovenous malformations (AVMs). Common sites of AVMs include in the nose, lungs, brain and liver. These lesions are prone to rupture, leading to complications including recurrent epistaxis and significant haemorrhage. Pulmonary hypertension (PH) can also occur. This review presents an update on the genetics, clinical manifestations, management options, and screening recommendations for children with HHT.
ABSTRACT
Hereditary haemorrhagic telangiectasia is a genetic condition of abnormal blood vessel formation resulting from an imbalance of pro- and anti-angiogenic products of the transforming growth factor ß/bone morphogenetic protein signalling pathway which contributes to vascular remodelling and maintenance. Hepatic vascular malformations are common although less frequently symptomatic, but may result in high-output cardiac failure, portal hypertension and biliary ischaemia. Whilst the understanding of the genetic and cell signalling pathways that are the hallmark of hereditary haemorrhagic telangiectasia have been clarified, there remain challenges in therapy for these patients. Only patients with symptomatic hepatic vascular malformations require treatment, with most (63%) responding to first-line medical therapy. For non-responders, bevacizumab is effective in reducing cardiac output in those with heart failure secondary to hepatic vascular malformations as well as other manifestations of the disease. Although liver transplantation is the only curative option, optimal timing is critical. Novel anti-angiogenetic drugs and those that target aberrant cell signalling pathway are being explored.
Subject(s)
Liver Transplantation , Telangiectasia, Hereditary Hemorrhagic , Humans , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasia, Hereditary Hemorrhagic/genetics , Angiogenesis Inhibitors/therapeutic use , Liver/blood supply , Signal Transduction , Hypertension, Portal/etiology , Hypertension, Portal/physiopathology , Bevacizumab/therapeutic useABSTRACT
We report our experience of managing a massive haemothorax caused by a ruptured, previously unknown, pulmonary arteriovenous malformation (pAVM) at 34 + 5 weeks of gestation, which proved to be a manifestation of hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome. The patient underwent an emergency caesarean section under general anaesthesia after placement of a chest tube and gave birth to a healthy infant. A postoperative thoracic computed tomography angiography highlighted the presence of the large pAVM. Transcatheter embolization was performed right after the delivery. Subsequent patient's anamnesis, family history and genetic analysis finally revealed the presence of the syndrome. The aim of our report is to create awareness of this serious condition with potential life-threatening complications, especially in pregnancy. Simple criteria have been published and allow to easily consider HHT and the presence of potential AVM during anamnesis, ideally even before pregnancy.
ABSTRACT
Osler-Weber-Rendu syndrome or Hereditary Haemorrhagic Telangiectasia (HHT) is a rare condition, with very few reported cases, especially in Pakistan. As healthcare workers, we encounter multiple cases of recurrent epistaxis in the emergency as well as outpatient departments. However, patients are usually treated symptomatically without a thorough workup. HHT should be considered among the differentials for recurrent epistaxis, as a clinical diagnosis can be made with detailed family history and physical examination. Here is the case of a 58-year-old male who presented to the Gastroenterology OPD, Combined Military Hospital, Lahore, in November 2021, with complaints of generalised weakness and blood in stools. He had a history of recurrent epistaxis and telangiectasias, and further inquiry revealed a strong family history of similar symptoms. He was diagnosed as a case of Osler-Weber- Rendu Syndrome. Informed consent was taken from the patient prior to the writing of the manuscript.
Subject(s)
Epistaxis , Recurrence , Telangiectasia, Hereditary Hemorrhagic , Humans , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/genetics , Telangiectasia, Hereditary Hemorrhagic/complications , Male , Epistaxis/etiology , Epistaxis/diagnosis , Middle Aged , PakistanABSTRACT
Background: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. Objective: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. Methods A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. Results: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 24; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 23; mean 2.61) vs 2 (IQR 23; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. Conclusions DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments. (AU)
Antecedentes: La telangiectasia hemorrágica hereditaria (THH) se caracteriza por la presencia de telangiectasias y malformaciones arteriovenosas de mayor tamaño en diferentes órganos. Las telangiectasias a nivel mucocutáneo pueden sangrar y convertirse en un problema estético, afectando la calidad de vida (CdV). Sin embargo, aún no se ha definido su mejor enfoque terapéutico. Objetivo: Evaluar la eficacia y la seguridad del láser dual secuencial de longitud de onda de 595/1064nm (DWSL) en comparación con el láser de 1064nm (Nd:YAG) solo. Por otro lado, evaluar el deterioro de la calidad de vida en los pacientes con THH y su mejora tras la terapia con láser. Métodos: Estudio prospectivo, doble ciego, aleatorizado, comparativo, de cuerpo dividido (DWSL vs. Nd:YAG). Se registraron las características demográficas, clínicas y del tratamiento. La gravedad y el grado de mejora fueron evaluados por tres examinadores ciegos que calificaron las imágenes previas al tratamiento y posteriores al tratamiento en una escala de 5 puntos. Los pacientes cumplimentaron las pruebas Skindex-29 y FACE-Q® y se evaluó el dolor asociado al procedimiento y la satisfacción del paciente. Resultados: Se analizaron 111 áreas de tratamiento (55 tratadas con DWSL y 56 con Nd:YAG) de 26 pacientes. La mediana del número de sesiones de láser fue de 2 (rango intercuartílico [RIC] 2-4; media 2,90 vs. 2,88, respectivamente). La mediana de la puntuación de mejora, independientemente de la ubicación, fue significativamente mayor para Nd:YAG en comparación con DWSL: 3 (IQR 2-3; media 2,61) frente a 2 (IQR 2-3; media 2,32), p=0,031. Tanto el índice FACE-Q como los resultados de la prueba Skindex-29 mejoraron significativamente (p<0,001), y el 92,4% de los pacientes informaron un alto grado de satisfacción (≥8). No se informaron eventos adversos graves... (AU)
Subject(s)
Humans , Telangiectasia, Hereditary Hemorrhagic , Lasers, Solid-State , Quality of Life , Arteriovenous Malformations , Laser Therapy , Retinal Telangiectasis , Prospective Studies , Randomized Controlled Trials as TopicABSTRACT
Antecedentes: La telangiectasia hemorrágica hereditaria (THH) se caracteriza por la presencia de telangiectasias y malformaciones arteriovenosas de mayor tamaño en diferentes órganos. Las telangiectasias a nivel mucocutáneo pueden sangrar y convertirse en un problema estético, afectando la calidad de vida (CdV). Sin embargo, aún no se ha definido su mejor enfoque terapéutico. Objetivo: Evaluar la eficacia y la seguridad del láser dual secuencial de longitud de onda de 595/1064nm (DWSL) en comparación con el láser de 1064nm (Nd:YAG) solo. Por otro lado, evaluar el deterioro de la calidad de vida en los pacientes con THH y su mejora tras la terapia con láser. Métodos: Estudio prospectivo, doble ciego, aleatorizado, comparativo, de cuerpo dividido (DWSL vs. Nd:YAG). Se registraron las características demográficas, clínicas y del tratamiento. La gravedad y el grado de mejora fueron evaluados por tres examinadores ciegos que calificaron las imágenes previas al tratamiento y posteriores al tratamiento en una escala de 5 puntos. Los pacientes cumplimentaron las pruebas Skindex-29 y FACE-Q® y se evaluó el dolor asociado al procedimiento y la satisfacción del paciente. Resultados: Se analizaron 111 áreas de tratamiento (55 tratadas con DWSL y 56 con Nd:YAG) de 26 pacientes. La mediana del número de sesiones de láser fue de 2 (rango intercuartílico [RIC] 2-4; media 2,90 vs. 2,88, respectivamente). La mediana de la puntuación de mejora, independientemente de la ubicación, fue significativamente mayor para Nd:YAG en comparación con DWSL: 3 (IQR 2-3; media 2,61) frente a 2 (IQR 2-3; media 2,32), p=0,031. Tanto el índice FACE-Q como los resultados de la prueba Skindex-29 mejoraron significativamente (p<0,001), y el 92,4% de los pacientes informaron un alto grado de satisfacción (≥8). No se informaron eventos adversos graves... (AU)
Background: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. Objective: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. Methods: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. Results: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 24; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 23; mean 2.61) vs 2 (IQR 23; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. Conclusions: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments. (AU)
Subject(s)
Humans , Telangiectasia, Hereditary Hemorrhagic , Lasers, Solid-State , Quality of Life , Arteriovenous Malformations , Laser Therapy , Retinal Telangiectasis , Prospective Studies , Randomized Controlled Trials as TopicABSTRACT
Hereditary haemorrhagic telangiectasia is an inherited disorder characterised by vascular dysplasia that leads to the development of arteriovenous malformations. Pulmonary arteriovenous malformations occur in approximately 30% of patients with haemorrhagic telangiectasia. Given the complex characteristics of haemorrhagic telangiectasia lesions, the application of three-dimensional fusion imaging holds significant promise for procedural guidance and decrease in contrast and radiation dosing. We reviewed all patients who underwent transcatheter approach for pulmonary arteriovenous malformation occlusion with fusion image guidance from June 2018 to September 2023 from a single centre. A total of nine cases with haemorrhagic telangiectasia and transcatheter occlusion of pulmonary arteriovenous malformations using fusion imaging were identified. Five (56%) were male, mean age at procedure was 15.7 years (10-28 years) and mean number of pulmonary arteriovenous malformations intervened was three per patient (1-7). Two of the cases were complex repeat embolisations. The mean fluoroscopy time was 40.6 min (10.7-68.8 min), with mean contrast dose of 28.8 mL (11-60 mL; mean of 0.51 mL/kg) and mean radiation dose of 66.3 mGy (25.6-140 mGy; mean of 40.5 mGy/m2). There were no complications reported during the procedures, with no additional interventions necessary. Fusion imaging in pulmonary arteriovenous malformations embolisation for patients with haemorrhagic telangiectasia is feasible and has the potential to reduce contrast and radiation doses. To our knowledge, we describe the lowest radiation and contrast doses per patient using fusion imaging technology reported in the literature to date.
ABSTRACT
Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.
Subject(s)
Afibrinogenemia , Antifibrinolytic Agents , Blood Coagulation Disorders , Pregnancy , Female , Humans , Blood Coagulation Disorders/drug therapy , Hemorrhage/etiology , Hemorrhage/prevention & control , Fibrinogen/therapeutic use , Blood Coagulation Factors/therapeutic use , Afibrinogenemia/diagnosis , Antifibrinolytic Agents/therapeutic useABSTRACT
Introduction: Hereditary haemorrhagic telangiectasia (HHT) is a rare multi-organ vascular disease. It is characterised by mucocutaneous telangiectasia, epistaxis, and arteriovenous malformations. Some 70% of patients with HHT are thought to have issues with gastrointestinal (GI) bleeding. Traditional management of GI bleeding in HHT includes monitoring for iron deficiency anaemia, iron replacement, antifibrinolytic therapy and control of identifiable bleeding sites with argon photocoagulation during gastrointestinal endoscopy. Blood transfusion may also be required. Case description: Our case describes a man in his 40s with confirmed HHT, with transfusion-dependent anaemia secondary to GI bleeding. He was commenced on fortnightly bevacizumab (5 mg/kg) for 12 weeks in an attempt to reduce his blood transfusion requirement and manage his anaemia. In the months prior to starting bevacizumab, our patient's transfusion requirement ranged from 3-5 units of packed red cells per month to maintain an Hb >8 g/dl. He had a marked improvement in his symptoms within the first month of treatment and did not require any further blood transfusion during the three months of treatment. He was given one further IV iron infusion in the final month of his 3-month bevacizumab treatment and did not experience any adverse side effects from bevacizumab. Discussion: HHT results from alterations to genes which encode proteins involved in blood vessel formation. This provides the rationale for using anti VEGF drugs such as bevacizumab. Current evidence for this treatment approach is limited. Conclusion: Bevacizumab can be an effective treatment option in patients with HHT refractory to traditional management. LEARNING POINTS: Gastrointestinal bleeding in hereditary haemorrhagic telangiectasia can be difficult to treat.Bevacizumab, an anti-vascular endothelial growth factor, can be used to treat refractory anaemia secondary to gastrointestinal bleeding in hereditary haemorrhagic telangiectasia.
ABSTRACT
BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.
Subject(s)
Aluminum , Lasers, Dye , Lasers, Solid-State , Telangiectasia, Hereditary Hemorrhagic , Telangiectasis , Yttrium , Humans , Lasers, Dye/adverse effects , Lasers, Solid-State/adverse effects , Neodymium , Prospective Studies , Quality of Life , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasis/etiology , Telangiectasis/radiotherapy , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: Hereditary haemorrhagic telangiectasia (HHT) is a genetic disease with fragile blood vessels and vascular malformations, potentially causing neurological manifestations, including stroke and cerebral abscesses. The study aimed to investigate neurological manifestations in the Danish HHT database, focusing on pulmonary arteriovenous malformations (PAVMs) as a risk factor for cerebral events. METHODS: Retrospective analysis of the Danish HHT database was conducted, cross-referencing neurological outcomes with the Danish Apoplexy Register for accuracy. Patients were stratified by HHT type. Primary outcomes included ischaemic stroke, transient ischaemic attack and cerebral haemorrhage. Secondary outcomes comprised age, age at HHT diagnosis, age at cerebral ischaemic event, and PAVM and cerebral arteriovenous malformation status. RESULTS: Six hundred and sixty-four HHT patients were included. PAVM was diagnosed in 54% of patients, with higher prevalence in HHT type 1 (70%) compared to HHT type 2 (34%) and juvenile polyposis HHT (66%). Ischaemic stroke or transient ischaemic attack occurred in 12.5%, with a higher risk associated with macroscopic PAVM. Logistic regression showed a nearly 10 times increased risk of ischaemic stroke with macroscopic PAVM. Cerebral abscesses occurred in 3.2% of patients, all with macroscopic PAVM. Incomplete PAVM closure increased cerebral abscess risk. CONCLUSION: This study provides valuable insights into the prevalence of neurological manifestations and vascular events in HHT patients. The presence of PAVM was associated with an increased risk of ischaemic stroke, highlighting the importance of early screening and intervention. The findings emphasize the need for comprehensive management strategies targeting both vascular and neurological complications in HHT patients, especially regarding secondary stroke prevention.
Subject(s)
Brain Abscess , Brain Ischemia , Ischemic Attack, Transient , Ischemic Stroke , Stroke , Telangiectasia, Hereditary Hemorrhagic , Humans , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasia, Hereditary Hemorrhagic/epidemiology , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Retrospective Studies , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/epidemiology , Brain Ischemia/complications , Brain Ischemia/epidemiology , Stroke/complications , Stroke/epidemiology , Ischemic Stroke/complications , Brain Abscess/complications , Brain Abscess/epidemiologyABSTRACT
BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.
Subject(s)
Aluminum , Lasers, Dye , Lasers, Solid-State , Telangiectasia, Hereditary Hemorrhagic , Telangiectasis , Yttrium , Humans , Lasers, Dye/adverse effects , Lasers, Solid-State/adverse effects , Neodymium , Prospective Studies , Quality of Life , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasis/etiology , Telangiectasis/radiotherapy , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right-to-left shunts was also assessed post hoc. METHODS: This was a cross-sectional population-based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble-echocardiography to detect vascular right-to-left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). RESULTS: Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble-echocardiography. The median age of participants was 54 years (IQR 45-62) and 19/57 (33%) were females compared with 59 years (IQR 48-68, p = 0.05) and 41/85 females (48%, p = 0.22) in non-participants. Bubble-echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06-11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. CONCLUSIONS: Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right-to-left shunts amongst brain abscess patients corresponds to the prevalence in the general population.
Subject(s)
Arteriovenous Fistula , Arteriovenous Malformations , Brain Abscess , Pulmonary Artery/abnormalities , Pulmonary Veins/abnormalities , Telangiectasia, Hereditary Hemorrhagic , Adult , Female , Humans , Middle Aged , Male , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/epidemiology , Cross-Sectional Studies , Arteriovenous Malformations/diagnosis , Arteriovenous Malformations/etiology , Brain Abscess/complications , Brain Abscess/epidemiologyABSTRACT
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by vascular dysplasia. Hepatic vascular malformations (VMs) range from small telangiectases to significant vascular shunting. Here we report two cases of HHT. Case 1 had diffuse ectasia of the hepatic artery along its intrahepatic and extrahepatic course with a hepatic arterial aneurysm. Case 2 presented with ileal and hepatic telangiectases. Knowledge of these vascular variants is indispensable for clinicians and radiologists in aiding diagnosis and surgical and interventional management.
Subject(s)
Telangiectasia, Hereditary Hemorrhagic , Humans , Telangiectasia, Hereditary Hemorrhagic/diagnostic imaging , Hepatic Artery/diagnostic imagingABSTRACT
Introduction: Hepatic hereditary haemorrhagic telangiectasia (HHHT) is a rare autosomal dominant genetic disease. Some patients may develop cardiac failure, portal hypertension, and biliary ischaemia. To date, there is no standard surgical treatment for HHHT. The present authors propose a move from open to laparoscopic surgery; however, laparoscopic surgery has not been reported previously as a surgical treatment for HHHT. Report: Two women were admitted with histories of exertional dyspnoea and upper abdominal pain, respectively. Combined with recurrent epistaxis and their positive family history, a diagnosis of clinical HHHT was made based on Curacao criteria after comprehensive evaluation of imaging features. Next generation sequencing (NGS) results also confirmed typical gene mutations responsible for HHT. Both patients underwent laparoscopic double hepatic artery banding and or ligation successfully and were discharged four to six days after operation without severe complications. The symptoms of cardiac insufficiency including exertional dyspnoea and shortness of breath of the first patient improved six months after the operation. The second patient, with epigastric pain, remained pain free without medication three months after the operation. Discussion: Laparoscopic surgery for HHHT is technically challenging. Clinical data and follow up information showed that laparoscopic double hepatic artery banding and or ligation was a technically feasible surgical approach for HHHT patients with simple hepatic artery dilation.
ABSTRACT
BACKGROUND: Patients with the rare disease; Hereditary haemorrhagic telangiectasia (HHT) often bleed from telangiectatic lesions in mucosal surfaces. Studies suggest that impaired platelet function may also play a role in their bleeding tendency. The aim of the present study was to investigate whether HHT-patients with epistaxis have impaired platelet function. METHOD: We conducted a case-control study based on a sample size calculation and included 22 HHT-patients (inclusion criteria: epistaxis severity score ≥ 4, no intake of medicine affecting platelet function the last 5 days, HHT-type 1 or 2, age ≥ 18 years) and 20 controls. We assessed the platelet function with standard haemostasis parameters, flow cytometry (platelet function and micro aggregation), rotational thromboelastometry and Platelet Function Analyzer 200. RESULTS: We found no significant difference in mean platelet volume and immature platelet fraction and no difference in platelet activation as measured by exposure of CD62P, CD63P and PAC1 binding. Nor did we find a significant difference in platelet aggregation response in HHT-patients compared with the control group for all agonists (thrombin receptor activating peptide, adenosine diphosphate and collagen-related peptide). The PFA-200 analysis was without difference between the two groups and thromboelastometry showed no impairment of global haemostasis. CONCLUSION: Reduced platelet function is unlikely to contribute to the frequent and long bleeding episodes that HHT-patients suffer from. We propose that further studies should focus on whether patients with HHT have hypercoagulability.
Subject(s)
Telangiectasia, Hereditary Hemorrhagic , Humans , Adolescent , Epistaxis , Case-Control Studies , Disease SusceptibilityABSTRACT
OBJECTIVE: The Hereditary Haemorrhagic Telangiectasia (HHT) is a low prevalence disease which presents heterogeneous signs and symptoms and just few population-based epidemiological studies are available. The aims of this paper were to describe the sociodemographic characteristics of people affected by HHT in the Valencian Region (VR), to determine its prevalence and mortality rate, and to analyse the sources of recruitment and verification tests used by the Rare Diseases Information System of the VR (SIER-CV). METHODS: Cross-sectional observational epidemiological study of HHT prevalent cases between 2010-2019 in SIER-CV was performed. The distribution of sociodemographic and clinical characteristics were determined, the prevalence and mortality rates, and the sources of recruitment and verification tests used by SIER-CV were analysed. Statistical analysis was performed using Stata (version 16.1) and Microsoft Excel Office. RESULTS: During 2010-2019, two hundred cases were identified, 55.5% were female. The mean ages were: 56.8 years at recruitment and 50.9 years at diagnosis. 48.4% of cases were diagnosed between thirty-six/sixty-four years of age. 25.5% died, with a mean age of 76.6 years, identifying statistically significant differences above the age of 64. The prevalence was 39.6/1,000,000 inhabitants and the crude mortality rate was 10.1/1,000,000 inhabitants. 95.5% of cases were recruited from the Hospital discharges database and the most frequent verification test was the clinical basis (45.7%). CONCLUSIONS: The increasing trend in prevalence coincides with a better knowledge of HHT, which favours its detection, and also with dying at older ages. To describe the situation of HHT in the VR facilitates its health management and contributes to the establishment of the relevant health policies for the HHT. The need to promote genetic diagnosis and to incorporate the Primary Care Clinical History as a source of recruitment in the population-based registries has been shown.
OBJECTIVE: La Telangiectasia Hemorrágica Hereditaria (THH) es una enfermedad de baja prevalencia, que se presenta con signos y síntomas muy heterogéneos y de la que apenas se dispone de estudios epidemiológicos de base poblacional. Los objetivos de este estudio fueron describir las características sociodemográficas de las personas afectadas por THH en la Comunitat Valenciana (CV), determinar su prevalencia y mortalidad, y analizar las fuentes de captación y pruebas de verificación utilizadas por el Sistema de Información de Enfermedades Raras de la CV (SIER-CV). METHODS: Se realizó un estudio epidemiológico observacional transversal de casos prevalentes de THH durante 2010-2019 en el SIER-CV. Se determinó la distribución de las características sociodemográficas y clínicas, la prevalencia y mortalidad, y se analizaron las fuentes de captación y pruebas de verificación utilizadas por SIER-CV. El análisis estadístico de los datos se realizó mediante el programa Stata (versión 16.1) y Microsoft Excel Office. RESULTS: Durante 2010-2019 se identificaron doscientos casos, de los que el 55,5% eran mujeres. Las edades medias fueron: de captación 56,8 años, y de diagnóstico 50,9 años. El 48,4% fueron diagnosticados entre los treinta y seis, y los sesenta y cuatro años. Fallecieron el 25,5%, con 76,6 años de edad media, identificándose diferencias estadísticamente significativas en mayores de sesenta y cuatro años. La prevalencia fue 39,6 por cada millón de habitantes y la tasa cruda de mortalidad de 10,1 por cada millón de habitantes. El 95,5% se captaron por el Conjunto Mínimo Básico de Datos y la prueba de verificación más frecuente fue la base clínica (45,7%). CONCLUSIONS: La tendencia ascendente de la prevalencia coincide con un mejor conocimiento de la THH, que facilita la detección de casos, y también con fallecimientos en edades avanzadas. Describir la situación de la THH en la CV facilita su manejo sanitario y contribuye al establecimiento de las políticas sanitarias correspondientes. Se muestra la necesidad de favorecer el diagnóstico genético e incorporar la Historia de Atención Primaria como fuente de captación en los registros poblacionales.
Subject(s)
Telangiectasia, Hereditary Hemorrhagic , Humans , Female , Aged , Middle Aged , Male , Cross-Sectional Studies , Spain , Telangiectasia, Hereditary Hemorrhagic/epidemiology , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/genetics , Death , PrevalenceABSTRACT
Fundamentos: La Telangiectasia Hemorrágica Hereditaria (THH) es una enfermedad de baja prevalencia, que se presenta con signos y síntomas muy heterogéneos y de la que apenas se dispone de estudios epidemiológicos de base poblacional. Los objetivos de este estudio fueron describir las características sociodemográficas de las personas afectadas por THH en la Comunitat Valenciana (CV), determinar su prevalencia y mortalidad, y analizar las fuentes de captación y pruebas de verificación utilizadas por el Sistema de Información de Enfermedades Raras de la CV (SIER-CV). Métodos: Se realizó un estudio epidemiológico observacional transversal de casos prevalentes de THH durante 2010-2019 en el SIER-CV. Se determinó la distribución de las características sociodemográficas y clínicas, la prevalencia y mortalidad, y se analizaron las fuentes de captación y pruebas de verificación utilizadas por SIER-CV. El análisis estadístico de los datos se realizó mediante el programa Stata (versión 16.1) y Microsoft Excel Office. Resultados: Durante 2010-2019 se identificaron doscientos casos, de los que el 55,5% eran mujeres. Las edades medias fueron: de captación 56,8 años, y de diagnóstico 50,9 años. El 48,4% fueron diagnosticados entre los treinta y seis, y los sesenta y cuatro años. Fallecieron el 25,5%, con 76,6 años de edad media, identificándose diferencias estadísticamente significativas en mayores de sesenta y cuatro años. La prevalencia fue 39,6 por cada millón de habitantes y la tasa cruda de mortalidad de 10,1 por cada millón de habitantes. El 95,5% se captaron por el Conjunto Mínimo Básico de Datos y la prueba de verificación más frecuente fue la base clínica (45,7%). Conclusiones: La tendencia ascendente de la prevalencia coincide con un mejor conocimiento de la THH, que facilita la detección de casos, y también con fallecimientos en edades avanzadas...(AU)
Background: The Hereditary Haemorrhagic Telangiectasia (HHT) is a low prevalence disease which presents heterogeneous signs and symptoms and just few population-based epidemiological studies are available. The aims of this paper were to describe the sociodemographic characteristics of people affected by HHT in the Valencian Region (VR), to determine its prevalence and mortality rate, and to analyse the sources of recruitment and verification tests used by the Rare Diseases Information System of the VR (SIER-CV).Methods: Cross-sectional observational epidemiological study of HHT prevalent cases between 2010-2019 in SIER-CV was performed. The distribution of sociodemographic and clinical characteristics were determined, the prevalence and mortality rates, and the sources of recruitment and verification tests used by SIER-CV were analysed. Statistical analysis was performed usingStata (version 16.1) and Microsoft Excel Office. Results: During 2010-2019, two hundred cases were identified, 55.5% were female. The mean ages were: 56.8 years at recruitment and 50.9 years at diagnosis. 48.4% of cases were diagnosed between thirty-six/sixty-four years of age. 25.5% died, with a mean age of 76.6 years, identifying statistically significant differences above the age of 64. The prevalence was 39.6/1,000,000 inhabitants and the crude mortality rate was 10.1/1,000,000 inhabitants. 95.5% of cases were recruited from the Hospital discharges database and the most frequent verification test was the clinical basis (45.7%). Conclusions: The increasing trend in prevalence coincides with a better knowledge of HHT, which favours its detection, and also with dying at older ages. To describe the situation of HHT in the VR facilitates its health management and contributes to the establishment of the relevant health policies for the HHT...(AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Telangiectasia, Hereditary Hemorrhagic , Prevalence , Rare Diseases/epidemiology , Information Systems , Ataxia Telangiectasia , Spain , Cross-Sectional Studies , Epidemiologic Studies , Public Health , Rare Diseases/mortalityABSTRACT
We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient's staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.
Subject(s)
Heart Diseases , Telangiectasia, Hereditary Hemorrhagic , Univentricular Heart , Humans , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/genetics , Univentricular Heart/complications , Mutation , Heart Diseases/complications , Smad4 Protein/geneticsABSTRACT
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger visceral arteriovenous malformations (AVMs), which directly connect the feeding arteries with the draining veins. These lesions are fragile, prone to rupture, and lead to recurrent epistaxis and/or internal hemorrhage among other complications. Germline heterozygous loss-of-function (LOF) mutations in Bone Morphogenic Protein 9 (BMP9) and BMP10 signaling pathway genes (endoglin-ENG, activin like kinase 1 ACVRL1 aka ALK1, and SMAD4) cause different subtypes of HHT (HHT1, HHT2 and HHT-juvenile polyposis (JP)) and have a worldwide combined incidence of about 1:5000. Expert clinicians and international scientists gathered in Cascais, Portugal from September 29th to October 2nd, 2022 to present the latest scientific research in the HHT field and novel treatment strategies for people living with HHT. During the largest HHT scientific conference yet, participants included 293 in person and 46 virtually. An impressive 209 abstracts were accepted to the meeting and 59 were selected for oral presentations. The remaining 150 abstracts were presented during judged poster sessions. This review article summarizes the basic and clinical abstracts selected as oral presentations with their new observations and discoveries as well as surrounding discussion and debate. Two discussion-based workshops were also held during the conference, each focusing on mechanisms and clinical perspectives in either AVM formation and progression or current and future therapies for HHT. Our hope is that this paper will represent the current progress and the remaining unanswered questions surrounding HHT, in order to serve as an update for those within the field and an invitation to those scientists and clinicians as yet outside of the field of HHT.