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Background: Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for organ vascular malformations including arteriovenous malformations (AVMs) in the brain and lungs. North American HHT Centers of Excellence (CoEs) routinely screen for brain and lung AVMs, with the primary goal of detecting AVMs which can be treated before complications arise. Current international HHT guidelines provide recommendations for initial screening for brain and lung AVMs among children and adults with the disease, but rescreening recommendations are not comprehensively addressed and have not been reported. We determined current rescreening practices for brain and lung AVMs for children and adults with HHT among North American HHT CoEs., Methods: We surveyed North American HHT CoEs regarding rescreening practices for new brain and lung AVMs in children and adults with initial negative screening., Results: All thirty CoEs responded; 28 regarding pediatric (93.3%) and 30 (100%) regarding adult HHT care. The median duration of practice experience in HHT was 11.5 (range 3-30) years for providers of pediatric HHT care and 11.5 (range 3-35) years for providers of adult HHT care. The median number of patients followed at each CoE was 60 for children (range 8-500) and 375 for adults (range 30-1500). 25/28 CoEs (89.3%) reported rescreening children for brain AVMs, most commonly with enhanced MRI (21/25, 84%). 25 CoEs rescreen children for lung AVMs, most commonly every 5 years (15/25). Only 4/30 CoEs (13.3%) rescreen adults for brain AVMs. 26/30 CoEs (86.7%) reported rescreening adults for lung AVMs, most commonly every 5 years (18/26, 69.2%)., Conclusions: Most HHT CoEs routinely rescreen children for brain and lung AVMs and adults for lung AVMs when initial screening is negative, but adults are infrequently rescreened for brain AVMs. Long-term data regarding risk for new brain and lung AVMs are required to establish practice guidelines for rescreening., (© 2024. The Author(s).)

Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs) in internal organs. HHT is caused by inheritance of a loss of function mutation in one of three genes. Although individuals with HHT are haploinsufficient for one of these genes throughout their entire body, rather than exhibiting a systemic vascular phenotype, vascular malformations occur as focal lesions in discrete anatomic locations. The inconsistency between genotype and phenotype has provoked debate over whether haploinsufficiency or a different mechanism gives rise to the vascular malformations. We previously showed that HHT-associated skin telangiectases develop by a two-hit mutation mechanism in an HHT gene. However, somatic mutations were identified in only half of the telangiectases, raising the question whether a second-hit somatic mutation is a necessary (required) event in HHT pathogenesis. Here, we show that another mechanism for the second hit is loss of heterozygosity across the chromosome bearing the germline mutation. Secondly, we investigate the two-hit mutation mechanism for internal organ AVMs, the source of much of the morbidity of HHT. Here, we identified somatic molecular genetic events in eight liver telangiectases, including point mutations and a loss of heterozygosity event. We also identified somatic mutations in one pulmonary AVM and two brain AVMs, confirming that mucocutaneous and internal organ vascular malformations undergo the same molecular mechanisms. Together, these data argue that bi-allelic loss of function in an HHT gene is a required event in the pathogenesis of HHT-associated vascular malformations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population., Methods: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus., Results: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1., Conclusions: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening. We aimed to confirm whether brain VMs can form de novo in patients with HHT., Methods: The Brain Vascular Malformation Consortium HHT project is a 17-center longitudinal study enrolling patients since 2010. We analyzed the database for de novo VMs defined as those detected (1) on follow-up neuroimaging in a patient without previous brain VMs or (2) in a location distinct from previously identified brain VMs and reported those in whom a de novo VM could be confirmed on central neuroimaging review., Results: Of 1909 patients enrolled, 409 (21%) had brain VMs. Seven patients were recorded as having de novo brain VMs, and imaging was available for central review in four. We confirmed that three (0.7% of individuals with brain VMs) had de novo brain VMs (two capillary malformations, one brain arteriovenous malformation) with intervals of six, nine, and 13 years from initial imaging. Two with de novo brain VMs were <18 years. The fourth patient, a child, did not have a de novo brain VM but had a radiologically confirmed increase in size of an existing brain arteriovenous malformation., Conclusions: Brain VMs can, albeit rarely, form de novo in patients with HHT. Given the potential risk of hemorrhage from brain VMs, regular rescreening in patients with HHT may be warranted., Competing Interests: Declaration of competing interest The Brain Vascular Malformation Consortium (U54NS065705) is a part of the NCATS Rare Diseases Clinical Research Network (RDCRN) and is supported by the RDCRNData Management and Coordinating Center (DMCC) (U2CTR002818). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), NCATS, funded through a collaboration between NCATS and NINDS. L.A.B. was supported by a BVMC fellowship, as part of the funding detailed above. L.A.B. was also supported by the Children's Hospital of Philadelphia Department of Pediatrics Chair's Initiative. M.E.F. was also supported by the Li Ka Shing Knowledge Institute. None of the funding sources directly participated in the study design, data collection, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: The presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a sample of adults with hereditary hemorrhagic telangiectasia for the presence of malformations of cortical development, spatial coincidence of malformations of cortical development and AVMs, and the coincidence of brain and pulmonary AVMs., Materials and Methods: A total of 141 patients 18 years of age or older who were referred to the Augusta University hereditary hemorrhagic telangiectasia clinic and underwent brain MR imaging between January 19, 2018, and December 3, 2020, were identified. MR imaging examinations were reviewed retrospectively by 2 experienced neuroradiologists, and the presence of malformations of cortical development and AVMs was confirmed by consensus. Demographic and clinical information was collected for each case, including age, sex, hereditary hemorrhagic telangiectasia status by the Curacao Criteria, mutation type, presence of malformations of cortical development, presence of brain AVMs, presence of pulmonary AVMs, and a history of seizures or learning disabilities., Results: Five of 141 (3.5%) patients with hereditary hemorrhagic telangiectasia had malformations of cortical development. Two of the 5 patients with polymicrogyria also had closed-lip schizencephaly. One of the patients had a porencephalic cavity partially lined with heterotopic GM. The incidence of spatially coincident polymicrogyria and brain AVMs was 40% (2/5 cases). Of the patients with hereditary hemorrhagic telangiectasia and malformations of cortical development, 4/5 (80%) had pulmonary AVMs and 2/5 (40%) had brain AVMs., Conclusions: To our knowledge, we are the first group to report the presence of schizencephaly in patients with hereditary hemorrhagic telangiectasia. The presence of schizencephaly and porencephaly lends support to the hypothesis of regional in utero cerebral hypoxic events as the etiology of malformations of cortical development in hereditary hemorrhagic telangiectasia., (© 2022 by American Journal of Neuroradiology.)

Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHT-associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, epistaxis severity score, red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. 238 HHT patients received bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5, 8.8) g/dL versus 11.8 (11.5, 12.1) g/dL, p<0.0001)] and decreased the epistaxis severity score (ESS) by 3.4 (3.2-3.7) points [mean ESS 6.8 (6.6-7.1) versus 3.4 (3.2-3.7), P<0.0001] during the first year of treatment. Compared with 6 months pretreatment, RBC units transfused decreased by 82% [median of 6.0 (IQR 0.0-13.0) units versus 0 (IQR, 0.0-1.0) units, P<0.0001] and iron infusions decreased by 70% [median of 6.0 (1.0-18.0) infusions versus 1.0 (0.0-4.0) infusions, P<0.0001] during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as needed maintenance but with more drug exposure. Bevacizumab was well tolerated: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective to manage chronic bleeding and anemia in HHT.

Description: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications., Methods: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved., Recommendations: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.

Importance: Epistaxis is a major factor negatively affecting quality of life in patients with hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease). Optimal treatment for HHT-related epistaxis is uncertain., Objective: To determine whether topical therapy with any of 3 drugs with differing mechanisms of action is effective in reducing HHT-related epistaxis., Design, Setting, and Participants: The North American Study of Epistaxis in HHT was a double-blind, placebo-controlled randomized clinical trial performed at 6 HHT centers of excellence. From August 2011 through March 2014, there were 121 adult patients who met the clinical criteria for HHT and had experienced HHT-related epistaxis with an Epistaxis Severity Score of at least 3.0. Follow-up was completed in September 2014., Interventions: Patients received twice-daily nose sprays for 12 weeks with either bevacizumab 1% (4 mg/d), estriol 0.1% (0.4 mg/d), tranexamic acid 10% (40 mg/d), or placebo (0.9% saline)., Main Outcomes and Measures: The primary outcome was median weekly epistaxis frequency during weeks 5 through 12. Secondary outcomes included median duration of epistaxis during weeks 5 through 12, Epistaxis Severity Score, level of hemoglobin, level of ferritin, need for transfusion, emergency department visits, and treatment failure., Results: Among the 121 patients who were randomized (mean age, 52.8 years [SD, 12.9 years]; 44% women with a median of 7.0 weekly episodes of epistaxis [interquartile range {IQR}, 3.0-14.0]), 106 patients completed the study duration for the primary outcome measure (43 were women [41%]). Drug therapy did not significantly reduce epistaxis frequency (P = .97). After 12 weeks of treatment, the median weekly number of bleeding episodes was 7.0 (IQR, 4.5-10.5) for patients in the bevacizumab group, 8.0 (IQR, 4.0-12.0) for the estriol group, 7.5 (IQR, 3.0-11.0) for the tranexamic acid group, and 8.0 (IQR, 3.0-14.0) for the placebo group. No drug treatment was significantly different from placebo for epistaxis duration. All groups had a significant improvement in Epistaxis Severity Score at weeks 12 and 24. There were no significant differences between groups for hemoglobin level, ferritin level, treatment failure, need for transfusion, or emergency department visits., Conclusions and Relevance: Among patients with HHT, there were no significant between-group differences in the use of topical intranasal treatment with bevacizumab vs estriol vs tranexamic acid vs placebo and epistaxis frequency., Trial Registration: clinicaltrials.gov Identifier: NCT01408030.

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary condition that results in vascular malformations throughout the body, which have a proclivity to rupture and bleed. HHT has a worldwide incidence of about 1:5000 and approximately 80 % of cases are due to mutations in ENG, ALK1 (aka activin receptor-like kinase 1 or ACVRL1) and SMAD4. Over 200 international clinicians and scientists met at Captiva Island, Florida from June 11-June 14, 2015 to present and discuss the latest research on HHT. 156 abstracts were accepted to the meeting and 60 were selected for oral presentations. The first two sections of this article present summaries of the basic science and clinical talks. Here we have summarized talks covering key themes, focusing on areas of agreement, disagreement, and unanswered questions. The final four sections summarize discussions in the Workshops, which were theme-based topical discussions led by two moderators. We hope this overview will educate as well as inspire those within the field and from outside, who have an interest in the science and treatment of HHT.

Pulmonary right-to-left shunting can be encountered using transthoracic contrast echocardiography (TTCE) with agitated saline. Diseases associated with pulmonary shunting on saline TTCE include hereditary hemorrhagic telangiectasia (HHT), hepatopulmonary syndrome, and some congenital heart defects after partial or complete cavopulmonary anastomosis. Furthermore, small pulmonary shunts on saline TTCE are also documented in a proportion of healthy individuals. Pulmonary shunting carries the risk for severe neurologic complications due to paradoxical embolization. In HHT, additional chest computed tomography is recommended in case of any pulmonary shunt detected on saline TTCE, to evaluate the feasibility for transcatheter embolotherapy of pulmonary arteriovenous malformations. Furthermore, antibiotic prophylaxis is advised in case of any pulmonary shunt on saline TTCE to prevent brain abscesses after procedures with risk for bacteremia. The present review provides an overview of important aspects of pulmonary shunting and its detection using saline TTCE. Furthermore, advances in understanding the clinical implications of different pulmonary shunt grades on saline TTCE are described. It appears that small pulmonary shunts on saline TTCE (grade 1) lack any clinical implication, as these shunts cannot be used as a diagnostic criterion for HHT, are not associated with an increased risk for neurologic complications, and represent pulmonary arteriovenous malformations too small for subsequent endovascular treatment. This implies that additional chest computed tomography could be safely withheld in all persons with only small pulmonary shunts on saline TTCE and sets the stage for further discussion about the need for antibiotic prophylaxis in these subjects. Besides further optimization of the current screening algorithm for the detection of pulmonary arteriovenous malformations in HHT, these observations can be of additional clinical importance in other diseases associated with pulmonary shunting and in those healthy individuals with documented small pulmonary shunts on saline TTCE., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The purpose of this study is to present the latest advances and recommendations in the diagnosis and treatment of pulmonary vascular complications associated with hereditary haemorrhagic telangiectasia (HHT): pulmonary arteriovenous malformations (PAVMs), pulmonary arterial hypertension (PAH), pulmonary hypertension associated with high output cardiac failure or liver vascular malformations, haemoptysis, haemothorax and thromboembolic disease., Recent Findings: Transthoracic contrast echocardiography has been validated as a screening tool for PAVM in patients with suspected HHT. Advancements in genetic testing support its use in family members at risk as a cost-effective measure. Therapy with bevacizumab in patients with high output cardiac failure and severe liver AVMs showed promising results. PAH tends to be more aggressive in HHT type 2 patients., Summary: Patients suffering from this elusive disease should be referred to HHT specialized centres to ensure a standardized and timely approach to diagnosis and management.

Object: Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disorder characterized by mucocutaneous telangiectasias, frequent nosebleeds, and visceral arteriovenous malformations (AVMs). Few reports have outlined the prevalence of the various cerebral vascular malformations found in patients with HHT. The authors set out to define the prevalence of cerebral vascular malformations in a population of HHT patients who underwent imaging with 3-T imaging (MRI/MR angiography [MRA]) of the brain., Methods: A retrospective review of prospectively collected data was carried out using a database of 372 HHT patients who were seen and examined at the Georgia Regents University HHT Center and screened with 3-T MRI/MRA. Data were tabulated for numbers and types of vascular malformations in this population., Results: Arteriovenous malformations were identified in 7.7%, developmental venous anomalies in 4.3%, and cerebral aneurysms in 2.4% of HHT patients. The HHT AVMs tended to be supratentorial, small, and cortical in this series, findings consistent with other recent studies in the literature. An arteriovenous fistula, cavernous malformation, and capillary telangiectasia were identified in 0.5%, 1%, and 1.9% of HHT patients, respectively., Conclusions: Few studies have investigated the prevalence of the various vascular malformations found in HHT patients screened with 3-T MRI/MRA of the brain. Hereditary hemorrhagic telangiectasia AVMs are more likely to be multiple and have a tendency toward small size and cortical location. As such, they are often treated using a single-modality therapy.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26 ± 18 range, (0-68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26 ± 16 (range, 2-50) and 18 ± 21 (0-48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults., Objective: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease., Methods: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches., Results: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

Background and Study Aims: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by telangiectasia formation that can lead to small-bowel bleeding. In this study, video capsule endoscopy was used to compare the small-bowel findings observed in patients with HHT with those seen in patients without the condition., Patients and Methods: We performed capsule endoscopy studies in 93 consecutive patients who were being evaluated for small-bowel bleeding, 38 patients with known or suspected HHT and 55 patients without HHT. Nine patients were excluded because the capsule failed to reach the cecum. The findings in 32 patients with a final diagnosis of HHT and in 48 patients without HHT were recorded and compared., Results: Capsule endoscopy detected telangiectases evenly distributed throughout the small bowel in 26/32 (81%) patients with HHT, compared with 14/48 (29%) in patients without HHT. When active bleeding was observed in patients with HHT (n = 4), the bleeding was within reach of standard small-bowel push enteroscopy in all cases. The presence of five or more gastrointestinal telangiectases by capsule endoscopy had a sensitivity of 75% and a positive predictive value of 86% for diagnosing HHT. Unexpected findings (small-bowel polyps and mass-like lesions) were seen in both groups of patients (6.2% in patients with HHT and 2.1% in patients without HHT)., Conclusions: Small-bowel telangiectases were seen in the majority of patients with HHT and were evenly distributed throughout the small bowel. Telangiectases were observed in only a minority of patients who did not have HHT. Actively bleeding small-bowel telangiectases were located in the proximal and mid-small bowel in patients with HHT, all within reach of an enteroscope. We propose a cutoff point of at least five gastrointestinal telangiectases to support a diagnosis of HHT.