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Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder characterized by intractable epistaxis, mucocutaneous telangiectasias, and arteriovenous malformations (AVMs) in multiple organs, including the lungs, liver, gastrointestinal tract, brain, and spinal cord. We herein report a 50-year-old Japanese man with HHT who experienced recurrent epistaxis, telangiectasia in the cornea, apex of the tongue and fingers; hepatic AVM; and a poorly developed main arterial trunk in the right middle cerebral artery. A genetic analysis revealed a novel heterozygous mutation in the activin A receptor-like type 1 gene, with a frameshift mutation in NM_000020.3:c.826_836del (p.Ile276ProfsTer112).

Background: Hereditary hemorrhagic telangiectasia (HHT) is a bleeding disorder characterized by arteriovenous malformations, commonly presenting with epistaxis and gastrointestinal (GI) bleeding. Bleeding symptoms may be difficult to manage and may become life-threatening, with many patients developing dependence on parenteral iron and/or blood transfusion. There is a growing body of evidence that antiangiogenic therapies may be effective in management of bleeding symptoms, presumably targeting pathogenic HHT pathways such as vascular endothelial growth factor receptor., Objectives: To report single-center, retrospective real-world use of pazopanib, an orally administered tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptors, in 6 patients with HHT-associated epistaxis and/or GI bleeding., Methods: A retrospective observational analysis was performed to assess the safety/efficacy of pazopanib use in patients with confirmed HHT-associated epistaxis and/or GI bleeding between January 1, 2019, and June 14, 2023. The Indiana Hemophilia and Thrombosis institutional electronic medical record was queried for HHT patients who were treated with pazopanib for ≥3 months. Patient data were obtained from patient documentation, physician/nursing notes, and on-call documentation. Institutional review board approval was obtained for data pull as an exempt study., Results: Our observations on the real-world use of pazopanib in 6 HHT patients with moderate-to-severe bleeding showed improvement in hemoglobin levels, with reduction in iron infusions and red blood cell transfusion requirement., Conclusion: Pazopanib may be a reasonable option for patients with HHT with epistaxis or gastrointestinal bleeding that are refractory to standard treatment., Competing Interests: Declaration of Competing Interest M.L. has received consultant’s fee from Alnylam, Agios, and Genentech/Roche. She serves on the advisory board for Hema biologics. She serves as a member of the Medical and Scientific Advisory Council (MASAC) of the National Bleeding Disorder Foundation (NBDF). S.G. and A.B. have no conflict of interest to disclose. A.S. serves as the medical director at the National Hemophilia Program Coordinating Center and as a board member for the Novo Nordisk Haemophilia Foundation. She has received consultant’s fee from Novo Nordisk and Kedrion Biopharma, speakers bureau from Genentech/Roche, Kedrion Biopharma, and Sanofi-Genzyme/Bioverativ. She serves on the advisory board for Novo Nordisk, Pfizer, Genentech/Roche, Sanofi-Genzyme/Bioverativ, Hema Biologics, Be Biopharma, and BioMarin., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait and caused by loss-of-function pathogenic variants in genes encoding proteins of the BMP signalling pathway. Up to 90% of disease-causal variants are observed in ENG and ACVRL1, with SMAD4 and GDF2 less frequently responsible for HHT. In adults, the most frequent HHT manifestations relate to iron deficiency and anaemia owing to recurrent epistaxis (nosebleeds) or bleeding from gastrointestinal telangiectases. Arteriovenous malformations (AVMs) in the lungs, liver and the central nervous system cause additional major complications and often complex symptoms, primarily due to vascular shunting, which is right-to-left through pulmonary AVMs (causing ischaemic stroke or cerebral abscess) and left-to-right through systemic AVMs (causing high cardiac output). Children usually experience isolated epistaxis; in rare cases, childhood complications occur from large AVMs in the lungs or central nervous system. Management goals encompass control of epistaxis and intestinal bleeding from telangiectases, screening for and treatment of iron deficiency (with or without anaemia) and AVMs, genetic counselling and evaluation of at-risk family members. Novel therapeutics, such as systemic antiangiogenic therapies, are actively being investigated. Although HHT is associated with increased morbidity, the appropriate screening and treatment of visceral AVMs, and the effective management of bleeding and anaemia, improves quality of life and overall survival., Competing Interests: Competing interests: C.L.S. is listed as the inventor in the patent application filed by Imperial College London for the use of MEK1 inhibitors to treat telangiectasia in HHT (European Patent Application 23705641.1). O.F.E. is a consultant for Microvention, CERENOVUS and Balt, and is also a member of DSMB and on the advisory board for STREAM Study. All other authors declare no competing interests., (© 2025. Springer Nature Limited.)

Epistaxis greatly affects patients with hereditary hemorrhagic telangiectasia (HHT). Although few systemic treatment exist, nintedanib, is a good candidate thanks to its anti-angiogenic activity. Our main objective was to evaluate the efficacy of oral nintedanib on epistaxis duration in HHT patients with moderate to severe epistaxis. This multicenter phase 2 randomized, placebo-controlled, double-blind trial was conducted between June 2020 and February 2023. Inclusion criteria were being over 18 years old and having a confirmed HHT diagnosis with an epistaxis severity score greater than 4. Sixty patients were randomized to receive either nintedanib or placebo for 12 weeks with a 12 week follow-up. The primary endpoint was the proportion of patients achieving a reduction of at least 50% in mean monthly epistaxis duration comparing the 8 weeks before treatment to the last 8 weeks of treatment. Main secondary outcomes included monthly duration and frequency of epistaxis and hemoglobin levels. Of the 60 randomized patients, 56 completed the trial. Thirteen patients (43%) in the nintedanib group vs 8 (27%) in the placebo group met the primary endpoint (p = 0.28). We observed a significant decrease in median epistaxis (57% vs 27%, p = 0.013) and a significant increase in median hemoglobin levels (+ 18 vs - 1 g/L, p = 0.02) in the nintedanib vs the placebo group. Although we did not achieve our primary outcome, we observed a significant reduction in epistaxis duration and a significant increase in hemoglobin levels in patients treated with nintedanib. This supports the efficacy of nintedanib, and further studies are needed., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

A 64-year-old woman with hereditary hemorrhagic telangiectasia (HHT) characterized by a pathological variant in ACVRL1 presents to the clinic for follow-up. Manifestations of HHT include frequent epistaxis and gastrointestinal bleeding, leading to iron-deficiency anemia. Bevacizumab is initiated, with resolution of the anemia. While maintained on a regimen of bevacizumab every 6 weeks, she continues to report frequent epistaxis and has ongoing iron-deficiency requiring periodic iron infusions. She also finds the bevacizumab infusions inconvenient. She is interested in discussing other options for managing her disease., (Copyright © 2024 by The American Society of Hematology.)

Purpose of Review: Hereditary hemorrhagic telangiectasia (HHT) diagnostic and management approach for pediatrics underwent significant advances over the last couple of years., Recent Findings: In 2020, new guidelines for HHT were published that included a pediatric section thus attracting special focus into the childhood presentation., Summary: Curacao criteria are specific, but not sensitive enough in children. Genetic testing is encouraged for all family members even if asymptomatic. Standardized scoring for epistaxis is strongly encouraged, as it allows monitoring and can stratify therapeutic approaches. Early screening for pulmonary and brain visceral arteriovenous malformations (AVMs) in pediatric patients with confirmed genetic alterations of HHT should be instituted. Graded trans-esophageal echocardiogram with agitated saline contrast can be used as screening method for pulmonary AVMs. As pulmonary AVMs can develop throughout lifetime, guidelines recommend repeated screening even in asymptomatic patients at least every 5 years. Signs of stroke in childhood are more subtle than in adults. Cerebral imaging in early childhood can identify brain AVMs that may benefit from early intervention. Embolization of high-risk pulmonary and cerebral AVMs should be performed at specialized centers even at pediatric age. One or two classic HHT telangiectasia can be considered diagnostic in children. Antibiotic prophylaxis with dental procedures continues to be recommended., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Key Points: In patients with severe refractory epistaxis due to hereditary hemorrhagic telangiectasia, the most effective results are achieved by surgical closure of the nares to permanently prevent nasal airflow. Flap failure and dehiscence can occur and result in fistula formation and clinical relapse. We describe the utility of a V-Y advancement flap in repairing localized cutaneous defects in patients who have previously undergone nasal closure for severe HHT., (© 2024 ARS‐AAOA, LLC.)

Background: Epistaxis is one of the most common and debilitating symptoms of hereditary hemorrhagic telangiectasia (HHT), significantly impacting patients' quality of life. While various medical and surgical interventions exist for managing epistaxis in patients with HHT, patients with moderate to severe epistaxis are high health-care utilizers who frequently need surgical treatment., Objective: To compare the efficacy, complications, and patient-reported outcomes for common surgical interventions utilized in treating epistaxis in patients with HHT., Methods: Studies were identified in PubMed, Embase, Scopus, Redalyc, and LILACS databases and uploaded to Covidence. A systematic review following PRISMA guidelines was conducted on studies evaluating outcomes in adults with HHT with moderate to severe epistaxis who had undergone surgical interventions. We compared the respective outcomes for pre-operative and post-operative epistaxis severity/intensity, need for further interventions or transfusions, estimated blood loss, length of surgery, complications, and patient satisfaction., Results: Twenty studies with a total of 546 patients were included. The most common surgeries studied were nasal closure and laser photocoagulation. Seven studies recorded the change in epistaxis severity score and observed a significant reduction postoperatively (3.91, [95% CI 2.73-5.09]). Eleven studies found a decrease in the number of transfusions and a rise in hemoglobin levels post-operatively. Common complications reported were partial dehiscence of a nasal closure, septal perforation, and continued bleeding requiring re-operation. Most patients report improved quality of life and satisfaction with surgical intervention., Conclusion: Surgery can significantly reduce the severity of epistaxis in patients with HHT and improve quality of life. Further studies should focus on head-to-head comparisons of procedures and standardization of outcome measures., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life., Methods: We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations)., Results: The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P = 0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash., Conclusions: Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Hereditary hemorrhagic telangiectasia (HHT, Rendu- Osler-Weber disease, or Osler's disease for short) is a systemic disease that can severely impair the quality of life and that requires interdisciplinary treatment. Among rare diseases, it is relatively common, with a prevalence of approximately 1/5000., Methods: This review is based on publications retrieved by a selective literature search, including the two international guidelines on clinically relevant aspects of HHT., Results: On average, about two decades elapse between the initial symptoms and the diagnosis of HHT. 95% of patients have nosebleeds; these usually begin before age 20 but can occur at any time, from infancy to old age. The diagnosis is usually made on clinical grounds on the basis of the characteristic telangiectases, a positive family history, and possible involvement of the gastrointestinal tract, lungs, liver, and brain. Nosebleeds can sometimes be reduced by outpatient measures including counseling on keeping the nose moist (expert consensus), self-application of a nasal packing (which improves the quality of life, according to an online survey), and the prescription of tranexamic acid (reduction of nosebleeds from 17.3% [5.5; 27.6] to 54%). In particular, screening (expert consensus) for pulmonary vascular malformations (frequency 10-50%) can prevent many adverse outcomes. If pulmonary vascular malformations cannot be ruled out, antibiotic prophylaxis is recommended before medical procedures that can cause bacteremia (expert consensus)., Conclusion: Broad awareness of the condition, early diagnosis, and interdisciplinary treatment improve the quality of life and ultimate outcome of persons with HHT. Nevertheless, there are few options supported by good evidence for the appropriate treatment of this rare, often serious disease..

Abstract: Hereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu disease) affects 1 in 5000 persons, making it the second most common inherited bleeding disorder worldwide. Telangiectatic bleeding, primarily causing recurrent epistaxis and chronic gastrointestinal bleeding, is the most common and most important manifestation of this multisystem vascular disorder. HHT-associated bleeding results in substantial psychosocial morbidity and iron deficiency anemia that may be severe. Although there remain no regulatory agency-approved therapies for HHT, multiple large studies, including randomized controlled trials, have demonstrated the safety and efficacy of antifibrinolytics for mild-to-moderate bleeding manifestations and systemic antiangiogenic drugs including pomalidomide and bevacizumab for moderate-to-severe bleeding. This has led to a recent paradigm shift away from repetitive temporizing procedural management toward effective systemic medical therapeutics to treat bleeding in HHT. In this article, 4 patient cases are used to illustrate the most common and most challenging presentations of HHT-associated bleeding that hematologists are likely to encounter in daily practice. Built on a framework of published data and supported by extensive clinical experience, guidance is given for modern evidence-based approaches to antifibrinolytic therapy, antiangiogenic therapy, and iron deficiency anemia management across the HHT disease severity spectrum., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Abstract: Hereditary hemorrhagic telangiectasia (HHT) is the second-most common inherited bleeding disorder (BD) worldwide and remains without approved therapies. HHT causes serious mucosal bleeding resulting in severe iron-deficiency anemia, major psychosocial complications, and visceral arteriovenous malformations in the brain, lung, and liver, which can cause life-threatening hemorrhagic complications. No study has examined the relative morbidity of HHT and von Willebrand disease (VWD), which is the most common inherited BD in women. We performed an observational cohort study of women with HHT or VWD, comparing a representative sample of 100 randomly selected women with HHT to 100 randomly selected age-matched women with VWD. In HHT vs VWD, recurrent epistaxis and gastrointestinal bleeding were more likely (odds ratio [OR], 32.73 [95% confidence interval, 13.81-71.80]; P < .0001 and 5.69 [2.59-12.89]; P < .0001) and heavy menstrual bleeding was less likely (OR, 0.32 [0.18-0.57]; P < .0001). Iron-deficiency anemia was significantly more likely, and the lowest hemoglobin was significantly lower in HHT than in VWD. The odds of iron infusion dependence, requirement for red cell transfusion, and hemostatic surgical procedures were significantly higher-17-fold, threefold, and eightfold higher, respectively-and hospital admissions to manage disease complications were both ∼14 times more frequent in women with HHT vs those with VWD. In conclusion, much higher disease-related morbidity, mortality, and health care use were observed in women with HHT vs VWD, providing evidence that HHT may be the most clinically significant inherited BD in women. Given the vast gap in research funding for HHT compared with both hemophilia (a disease primarily of men) and VWD, these findings have significant implications for gender equity in hematology., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

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.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber syndrome, is a rare autosomal dominant disorder characterized by vascular malformations. This comprehensive review aimed to provide an overview and summarize various aspects of HHT, including the genetic abnormalities, complications associated with visceral arteriovenous malformations (AVMs), prognosis of HHT, quality of life (QOL), and treatment of epistaxis. In addition, this review highlights the challenges in diagnosing HHT and emphasizes the critical role of otolaryngologists in the early detection of HHT. Otolaryngologists can refer patients with refractory epistaxis for AVM screening to expedite intervention. Mutation of the genes involved in the transforming growth factor-β signaling pathway leads to the incidence of HHT, resulting in the formation of abnormal blood vessel formation. These vascular malformations commonly manifest as telangiectasia on the skin and mucous membranes; however, epistaxis remains the hallmark symptom of HHT. The impact of HHT goes beyond the visible symptoms and often includes the formation of life-threatening visceral AVMs in the lungs, liver, and brain. The prognosis of patients with HHT is closely related to the development of these complications, necessitating timely diagnosis and intervention. Refractory epistaxis diminishes the QOL of patients with HHT. The management of epistaxis ranges from conservative measures to advanced interventions such as prevention, conservative treatments, ablation, surgical procedures, and the administration of anti-angiogenic agents. However, effective management requires a multidisciplinary approach. The diagnosis of HHT remains challenging due to its variable presentation and lack of awareness among physicians. This review highlights the importance of reducing the duration between symptom onset and diagnosis. Otolaryngologists who are experienced in the management of refractory epistaxis can aid in identifying potential cases of HHT. They can facilitate the initiation of screening for visceral AVMs via prompt recognition of the signs and symptoms of HHT, contributing to improved patient outcomes. Early detection and intervention through screening can extend the life expectancy of patients with HHT to levels comparable with that of the general population. In conclusion, this review provides insight into various aspects of HHT and emphasizes the importance of timely diagnosis and intervention in the mitigation of the potentially life-threatening complications associated with this disorder. Otolaryngologists play a critical role in this process, serving as gatekeepers to the identification of cases of HHT and implementation of appropriate screening and management pathways, thereby improving the life expectancy and QOL of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations. Individuals with HHT often identify low humidity and temperature as detrimental to epistaxis severity. We set out to assess the relationship between humidity and temperature on epistaxis severity in patients with HHT., Methods: Retrospective cross-sectional study at an academic hospital with an HHT center between July 1, 2014 and January 1, 2022. The primary outcome of this study was ESS. Pearson correlation analyses and multiple linear regression analyses were performed to test the association between weather variables and epistaxis severity scre (ESS). Results were reported as coefficient and 95% confidence interval (CI)., Results: Four hundred twenty-nine patients were included in the analysis. Through a Pearson correlation analysis, neither humidity (regression coefficient = -0.01; 95% CI, -0.006 to 0.003; p = 0.50), daily low temperature (regression coefficient = 0.01; 95% CI, -0.011 to 0.016; p = 0.72), or daily high temperature (regression coefficient = 0.01; 95% CI, -0.004 to 0.013; p = 0.32) were significantly correlated with ESS. In a multiple linear regression analysis, adjusting for both daily low temperature and humidity, medications taken, demographics, and genotype, neither daily low temperature (regression coefficient = -0.02; 95% CI, -0.04 to 0.01; p = 0.14) nor humidity (regression coefficient = 0.01; 95% CI, -0.01 to 0.01; p = 0.64) were significantly associated with ESS., Conclusion: We have shown in a large clinical sample that neither humidity nor temperature were strongly correlated with HHT patient epistaxis severity., (© 2023 ARS-AAOA, LLC.)

Objective: To assess the utility of the Curaçao criteria by age over time in children with hereditary hemorrhagic telangiectasia (HHT)., Study Design: This was a single-center, retrospective analysis of patients attending the HHT clinic at the Hospital for Sick Children (Toronto, Canada) between 2000 and 2019. The evaluation of the Curaçao criteria was completed during initial and follow-up visits. Screening for pulmonary and brain arteriovenous malformations was completed at 5 yearly intervals., Results: A total of 116 patients with genetic confirmation of HHT were included in the analysis. At initial screening at a median (IQR) age of 8.4 (2.8, 12.9) years, 41% met criteria for a definite clinical diagnosis (≥3 criteria). In children <6 years at presentation, only 23% fulfilled at least 3 criteria initially. In longitudinal follow-up, 63% reached a definite clinical diagnosis, with a median (IQR) follow-up duration of 5.2 (3.2, 7.9) years (P = .005). Specifically, more patients met the epistaxis and telangiectasia criteria at last visit compared with initial (79% vs 60%; P = .006; 47% vs 30%; P = .02) but not for the arteriovenous malformation criterion (59% vs 57%; P = .65)., Conclusions: In the pediatric population, most patients do not meet definite clinical criteria of HHT at initial presentation. Although the number of diagnostic criteria met increased over time, mainly due to new onset of epistaxis and telangiectasia, accuracy remained low during follow-up visits. Relying solely on clinical criteria may lead to underdiagnosis of HHT in children., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

A primigravida patient, with a history of hereditary haemorrhagic telangiectasia (HHT) manifesting as nasal angiodysplasia and hepatic arteriovenous malformations (AVM), presented for delivery planning and anaesthetic evaluation at 29 weeks of gestation. She was hospitalised several times during the second and third trimester for serious recurrent epistaxis, leading to severe anaemia. In total, she required the transfusion of 20 units of packed red blood cells during her pregnancy as well as surgical nasal haemostasis under general anaesthesia (GA). The patient was referred to our tertiary centre for delivery. In the context of recurrent severe epistaxis and high cardiac output (due to hepatic AVM) in the third trimester, a multidisciplinary decision was made to plan an elective caesarean section at 35 4/7 weeks combined with nasal packing under GA. This report discusses the implications of HHT, the multidisciplinary planning of the caesarean section, intraoperative anaesthetic management and patient follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The Curaçao criteria are well-established diagnostic criteria for hereditary hemorrhagic telangiectasia (HHT), but they lack details regarding a predictive presentation of epistaxis and telangiectasias. This study collects and compares data in HHT and population cohorts to inform the application of these criteria., Methods: In-person interviews regarding epistaxis and targeted examination for telangiectases in a general population cohort (n = 204) and an HHT cohort (n = 432) were conducted., Results: Frequency of epistaxis, rather than intensity or duration, was the best discriminator of HHT. A cutoff of ≥4 nosebleeds per year alone yielded a diagnostic sensitivity of 97%, and specificity of 84%. The mean number of telangiectases at the sites investigated was 0.4 in the general population cohort and 26.5 in the HHT cohort. The most distinctive sites for telangiectases in HHT were lips and palmar fingers, whereas telangiectases of the face and dorsum of the hand were comparable in both cohorts., Conclusion: We propose that the Curaçao criteria be modified to include the following cutoffs: (1) epistaxis frequency of ≥4 nosebleeds per year and (2) telangiectasia count of at least 2 in characteristic locations (palmar aspect of fingers, lips, and oral cavity), and that cutaneous telangiectases at other sites not be considered relevant for diagnostic purposes., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile., (© 2023. The Author(s).)

Introduction: Data describing safety and tolerability of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia (HHT), the second-most-common inherited bleeding disorder, is limited., Methods: We performed a scoping review, searching MEDLINE and EMBASE from inception to March 2023 for eligible studies reporting detailed clinical data describing antithrombotic use in HHT. Data extracted included study design, patient population, and characteristics and outcomes of antithrombotic therapy., Results: Of 625 unique manuscripts identified through database search, 77 were included: 64 case reports/case series describing 65 patients and 13 cohort studies. Data were extracted on a total of 466 patients with HHT, covering 587 episodes of antithrombotic therapy. The most common reasons for antithrombotic therapy were venous thromboembolism (VTE) (44.6 %), atrial arrhythmias (17.8 %) and stroke (10.5 %). anticoagulation was used in in 356 episodes (61.9 %), antiplatelet therapy in 140 episodes (24.3 %), and both together in 50 episodes (8.7 %). Complications of therapy included worsened HHT-associated bleeding (primarily epistaxis and gastrointestinal bleeding) in 198 antithrombotic treatment episodes (38.9 %) and premature antithrombotic therapy discontinuation in 142 episodes (28.9 %). Bleeding-directed therapy (local ablative therapy and systemic therapies) were employed to address worsening bleeding in 14.6 % of episodes. No specific complications of therapy were reported in 322 total antithrombotic events (58.4 %). Rates of bleeding (8.3 % to 80 %), therapy discontinuation (14.3 % to 57.1 %), and other complications ranged considerably from study to study., Conclusion: Current publications vary widely on the outcomes and tolerability of antithrombotics in HHT, but confirm the clinical challenge of adequate antithrombotic therapy in this population. More formal studies are needed to better guide optimal antithrombotic use in HHT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Universal Disclosures (none relevant to the content of the manuscript): Zhang: No disclosures. Virk: No disclosures. Rodriguez-Lopez: No disclosures. Al-Samkari: Universal disclosures include consultancy (Agios, Dova, Rigel, Argenx, Sobi, Novartis, Moderna) and research funding to institution (Agios, Dova, Amgen, Novartis, Vaderis)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterised by recurrent epistaxis, telangiectatic lesions in the skin and mucosal membranes, and arteriovenous malformations (AVMs) in various organs. In 3%-5% of patients, HHT is caused by pathogenic germline variants (PVs) in SMAD4 , and these patients often have additional symptoms of juvenile polyposis syndrome and thoracic aneurysms. The phenotypic spectrum of SMAD4 -associated HHT is less known, including the penetrance and severity of HHT. We aimed to investigate the phenotypic spectrum of HHT manifestations in Danish patients with PVs in SMAD4 and compare the findings with current literature., Methods: The study is a retrospective nationwide study with all known Danish patients with PVs in SMAD4 . In total, 35 patients were included. The patients were identified by collecting data from genetic laboratories, various databases and clinical genetic departments across the country. Clinical information was mainly collected from the Danish HHT-Centre at Odense University Hospital., Results: Twenty-nine patients with PVs in SMAD4 (83%) were seen at the HHT-Centre. Seventy-six per cent of these fulfilled the Curaçao criteria, 86% experienced recurrent epistaxis and 83% presented with telangiectatic lesions at different anatomical localisations. Almost 60% had AVMs, mainly pulmonary and hepatic, while none was found to have cerebral AVMs. Fifteen per cent had thoracic aortic abnormalities., Conclusion: We present a nationwide study of one of the largest populations of patients with PVs in SMAD4 that has systematically been examined for HHT manifestations. The patients presented the full spectrum of HHT-related manifestations and the majority fulfilled the Curaçao criteria., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To report our experience in the use of silicone septal splint for recurrent severe epistaxis in hereditary haemorrhagic telangiectasia patients (HHT)., Methods: This is a descriptive analysis carried out at the Otorhinolaryngology Department of Fondazione IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent silicone septal splint positioning after the endoscopic surgical treatment of epistaxis from 2000 to 2022., Results: Of the 506 patients surgically treated in the period of analysis, 74 patients underwent silicone septal splint positioning and 37 were post-operatively interviewed. With a mean of 2.4 previous surgical treatments and a mean epistaxis severity of 7.38, the majority of patients presented with septal perforation (71.6%). On average, patients maintained the splint in place for 54.5 months, with a good tolerability and a significant reduction in epistaxis severity, need for blood transfusion and improvement of haemoglobin levels., Conclusions: In HHT patients with recurrent severe epistaxis and with septal perforation, the placement of septal splints offers a useful additional strategy in the management of nosebleeds., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder of the vasculature, characterized by epistaxis, telangiectasia and arteriovenous malformations in multiple organs. We herein report a 49-year-old woman with a history of early-onset myocardial infarction and intracranial aneurysms, in whom we incidentally detected multiple hepatic vascular abnormalities. We subsequently diagnosed her with HHT after discovering gastrointestinal telangiectases and a pulmonary arteriovenous fistula along with a history of recurrent epistaxis. Whole-exome sequencing revealed a novel pathogenic variant in SMAD4, a relatively rare causative gene for HHT. This case highlights the fact that HHT patients may present with asymptomatic liver lesions.

Background: Vascular malformations in hereditary hemorrhagic telangiectasia (HHT) lead to chronic recurrent bleeding, hemorrhage, stroke, heart failure, and liver disease. There is great interest in identifying novel therapies for epistaxis in HHT given its associated morbidity and impact on quality of life. We aimed to measure the effectiveness of oral doxycycline for the treatment of epistaxis and explore mechanisms of action on angiogenic, inflammatory and pathway markers in HHT using a randomized controlled trial., Methods: 13 HHT patients with epistaxis were recruited from the Toronto HHT Center at St. Michael's Hospital. Recruitment was stopped early due to COVID-19-related limitations. The study duration was 24 months. Patients were randomly assigned to the treatment-first or placebo-first study arm. We compared the change in weekly epistaxis duration and frequency, biomarkers, blood measurements, and intravenous iron infusion and blood transfusion requirements between treatment and placebo., Results: There was no significant difference in the change in weekly epistaxis duration (p = 0.136) or frequency (p = 0.261) between treatment and placebo. There was no significant difference in the levels of MMP-9, VEGF, ANG-2, IL-6 or ENG with treatment. Hemoglobin levels were significantly higher (p = 0.0499) during treatment. Ferritin levels were not significantly different between treatment and placebo. There was no significant difference in RBC transfusions between treatment periods (p = 0.299)., Conclusion: Overall, our study did not demonstrate effectiveness of doxycycline as a treatment for epistaxis in patients with HHT, though the study was underpowered. Secondary analyses provided new observations which may help guide future trials in HHT. Trial Registration ClinicalTrials.gov, NCT03397004. Registered 11 January 2018 - Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03397004., (© 2022. The Author(s).)

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease affecting 1 in 5000 individuals. Epistaxis is seen in more than 90% of patients with HHT. Severe recurrent epistaxis can significantly decrease quality of life and may be resistant to standard treatment measures. Dysregulation of angiogenesis has been shown to cause the proliferation of abnormal blood vessels. As such, antiangiogenic treatments have been investigated including beta-blockers., Objective: A systematic review of the efficacy of beta-blockers in topical treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, and severity., Methods: A systematic search was performed using the PubMed, Embase via Ovid, and Cochrane databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of beta-blocker treatment of epistaxis in patients with HHT were included for qualitative analysis., Results: Five studies (3 randomized controlled trials and 2 case series) with a total of 132 patients were included. Administration (systemically or topically via a spray or gel) of timolol and propranolol showed mixed evidence of improvement in epistaxis frequency, severity, and duration when compared with control groups. The evidence for propranolol appears more promising than timolol., Conclusion: There are significant limitations in the included studies, and further investigation with larger longitudinal or randomized prospective trials is recommended. The available evidence suggests that beta-blocker treatment may have a positive effect on HHT-related epistaxis.

Using a patient survey, pulsed dye laser (PDL) treatment of epistaxis for hereditary haemorrhagic telangiectasia (HHT) patients was evaluated after initial referral. Subsequently, due to the COVID pandemic, a natural experimental set-up allowed assessment of an enforced withdrawal of treatment. A total of 34 subjects were identified as undergoing PDL for HHT-related epistaxis. They were surveyed to look at the effectiveness of PDL treatment after initial referral and at the effect of delay to treatment during COVID on epistaxis and the associated quality of life. The survey also examined the comparison to other available treatments. Retrospective pre-COVID Epistaxis Severity Scores (ESS) were compared to post-COVID data to assess the effect of treatment withdrawal. The patients were then followed up after resumption of their treatment to assess the ensuing change in ESS. After initial referral, frequency and severity of epistaxis decreased. Fifty-six percent of patients experienced several bleeds per day before treatment, compared to 12% after. 88% of patients had episodes of epistaxis longer than 5 min, which was halved to 44% after treatment. Average ESS pre-COVID was 4.42 compared to 5.43 post-COVID delay, with a significant statistical difference (p = 0.02). On resumption of treatment, average ESS reduced to below pre-COVID levels at 4.39 after only 2 sessions. Seventy-six percent of patients found that withdrawal of PDL during COVID diminished their quality of life. PDL treatment of nasal mucosal telangiectasia reduces the frequency and duration of epistaxis. The ESS is reduced following treatment with PDL and quality of life subjectively improved., (© 2022. Crown.)

Background: Given its role in the disease pathophysiology, inhibition of vascular endothelial growth factor (VEGF)-mediated angiogenesis has received attention as a potential strategy to reduce epistaxis associated with hereditary hemorrhagic telangiectasia (HHT). In this study we evaluated the efficacy of a submucosal injection of bevacizumab, a VEGF inhibitor, in reducing the severity of epistaxis and improving quality of life when given at the time of operative electrocautery., Methods: This randomized, double-blinded, placebo-controlled trial was conducted at a single institution from 2014 to 2019. Patients scheduled to undergo operative bipolar electrocautery of nasal telangiectasias were randomized to receive a submucosal injection of saline or bevacizumab at time of surgery. Surveys to assess epistaxis severity and quality of life (QOL), including the Epistaxis Severity Score (ESS) and the 12-item Short Form (SF-12), were administered preoperatively and at 1, 2, 4, and 6 months postoperatively. The minimal clinically important difference (MCID) of the ESS instrument is reported to be 0.71., Results: Of 39 patients enrolled, 37 (94.9%) completed the study. The saline group demonstrated a reduced ESS vs baseline at 1 (-1.2; p = 0.01) and 4 (-1.2; p = 0.05) months postprocedure. The bevacizumab group demonstrated a reduced ESS score vs baseline at 1 (-2.3; p < 0.001), 2 (-2.3; p < 0.001), 4 (-2.0; p = 0.003), and 6 (-1.3; p = 0.05) months postprocedure. The additive benefit of bevacizumab over saline exceeded the MCID at 1, 2, and 4 months, but the difference was not statistically significant., Conclusion: The addition of a single treatment of submucosal bevacizumab may be associated with additional clinically meaningful benefit for up to 4 months when compared with electrocautery alone., (© 2022 ARS-AAOA, LLC.)

Management of bleeding in hereditary hemorrhagic telangiectasia (HHT), the second most common hereditary bleeding disorder in the world, is currently undergoing a paradigm shift. Disease-modifying antiangiogenic therapies capable of achieving durable hemostasis via inducing telangiectasia regression have emerged as a highly effective and safe modality to treat epistaxis and gastrointestinal bleeding in HHT. While evidence to date is incomplete and additional studies are ongoing, patients presently in need are being treated with antiangiogenic agents off-label. Intravenous bevacizumab, oral pazopanib, and oral thalidomide are the three targeted primary angiogenesis inhibitors, with multiple studies describing both reassuring safety and impressive effectiveness in the treatment of moderate-to-severe HHT-associated bleeding. However, at present there is a paucity of guidance in the literature, including the published HHT guidelines, addressing the practical aspects of antiangiogenic therapy for HHT in clinical practice. This review article and practical evidence-based guide aims to fill this unaddressed need, synthesizing published data on the use of antiangiogenic agents in HHT, relevant data for their use outside of HHT, and expert guidance where evidence is lacking. After a brief review of principles of bleeding therapy in HHT, guidance on hematologic support with iron and blood products, and alternatives to antiangiogenic therapy, this article examines each of the aforementioned antiangiogenic agents in detail, including patient selection, initiation, monitoring, toxicity management, and discontinuation. With proper, educated use of antiangiogenic therapies in HHT, patients with even the most severe bleeding manifestations can achieve durable hemostasis with minimal side-effects, dramatically improving health-related quality of life and potentially altering the disease course., Competing Interests: The author serves as consultant for Agios, Dova/Sobi, Argenx, Rigel, Novartis, and Moderna, and receives research funding from Agios, Dova/Sobi, and Amgen. He is a member of the Guidelines Working Group for the Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia; he is a recipient of the American Society of Hematology Scholar Award., (Thieme. All rights reserved.)

Introduction Osler-Weber-Rendu syndrome, or hereditary hemorrhagic telangiectasia, is a rare genetic disease that causes recurrent epistaxis and anemia. Numerous bleeding vascular malformations can be found throughout the body. Case presentation A 75-year-old woman presented to her hematologist with recurrent epistaxis, iron deficiency anemia, menorrhagia, and hypothyroidism. Her mother had similar nosebleeds, and physical examination revealed small vascular malformations on the conjunctiva, oropharynx, tongue, lip, and palate. Heavy epistaxis occurred several times per week. Multiple nasal and gastrointestinal endoscopic procedures were performed. She received over 100 iron infusions and multiple blood transfusions. Overall treatment involved integrated care with multiple medical specialties. Conclusion Hereditary hemorrhagic telangiectasia and other complex diseases are best treated with a multidisciplinary approach within an integrated health care setting.

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease leading to recurrent epistaxis, telangiectasias, and/or visceral arteriovenous malformations. Multiple treatment methods, including both pharmacologic and surgical, are described to be effective in managing symptomatic HHT. Few report the duration of symptom improvement for each of these treatment methods. This study aims to analyze the duration of effectiveness of coblation treatment for recurrent epistaxis in those with HHT., Methods: Retrospective single-center chart review was completed for patients diagnosed with HHT who underwent coblation treatment by the same otolaryngologist from December 2009 to November 2021. Demographic information was collected along with whether local Bevacizumab was used during each treatment. Months between treatment coblation sessions was used as a surrogate for duration of treatment effectiveness. Descriptive statistics were used for analysis alongside quantitative statistical analysis., Results: Over the course of 12 years, 57 patients (24 female, 42.11%) with HHT underwent a total number of 150 coblation treatments. The average age at initial coblation was 59 years (29-88) with an average follow-up time of 5 years (1-12 years). Of the 150 coblations, 30 treatments (20%) included bevacizumab injections into the nasal cavity. The average duration of treatment effectiveness across all 150 treatment sessions was 24.5 months (1-87 months). Of the 26 patients (46%) that underwent multiple coblation treatments, the overall average duration of coblation effectiveness was 16.4 months (1-72 mos). When Bevacizumab was utilized, the average duration of effectiveness was 18.3 months (3-62 mos), while the average duration of effectiveness for treatments without Bevacizumab was 15.7 months (1-87 mos, p > 0.251). Further, there was no correlation between duration of treatment effectiveness and age, sex, and race; yet,there was a significant negative correlation between the use of tobacco and duration of coblation effectiveness (p = 0.0202)., Conclusions: Coblation is an effective treatment option for the management of epistaxis in patients with HHT with duration of benefit lasting approximately 2 years. The use of Bevacizumab did not add to the duration of treatment benefit. Further, the duration of benefit was negatively impacted by smoking history., (Published by Elsevier Inc.)

Objectives/hypothesis: Surgical interventions for epistaxis management in hereditary hemorrhagic telangiectasia (HHT) demonstrate short-term success and require repeated procedures for disease control. Although electrocautery and/or laser photocoagulation (C ± L) are most frequently performed, sodium tetradecyl sclerotherapy (STS) is emerging as a promising newer treatment. We hypothesized that in a 24-month time period, STS would require fewer treatments than C ± L to maintain epistaxis severity within the mild range., Study Design: Retrospective study., Methods: We retrospectively assessed 67 patients with HHT with moderate and severe epistaxis that were treated periodically with C ± L (34 patients) versus STS (33 patients). The primary outcome was the number of procedures needed to maintain the epistaxis severity score (ESS) as mild. Secondary outcomes assessed for differences in postoperative complications, hemoglobin levels, iron stores, hematologic support, and quality-of-life (QoL) scores., Results: To maintain ESS in the mild range, 1.6 STS procedures (range, 1-4) were performed versus 3.6 C ± L procedures (range, 1-8) (P = .003). Significant postoperative differences included reduction in nasal crusting (3% vs. 32%, P = .001), foul odor (3% vs. 35%, P < .001), and septal perforation (3% vs. 29%, P = .006) after STS. There were no significant differences between the two treatments in hemoglobin levels, iron stores, hematologic support, or QoL scores., Conclusion: STS is able to attain satisfactory epistaxis control with significantly fewer procedures and lower postoperative complications than C ± L. STS should be considered as the initial surgical intervention for epistaxis in patients with HHT., Level of Evidence: 4 Laryngoscope, 132:920-925, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Hereditary haemorrhagic telangiectasia (HHT) is a rare genetic vascular disorder which is characterised by the development of arteriovenous malformations and telangiectasias. A key clinical manifestation is recurrent epistaxis. This study examined the impact of a dedicated HHT clinic in a major Australian tertiary hospital on epistaxis symptoms and subjective quality of life., Methods: A multidisciplinary HHT clinic was established in 2015. All patients satisfied either genetic diagnosis or fulfilled Curacao criteria. A protocol based clinical assessment was performed and a standardised treatment regimen was implemented. Patients completed quality of life and epistaxis severity score (ESS) questionnaires at each review., Results: Participants of the dedicated clinic included 21 females (58.3%) and 15 males (41.7%), with a mean age of 49.0 ± 24.0 years. The ACVRL1 variant was the most common (n = 20, 55.6%). A statistically significant reduction in epistaxis severity was noted between the baseline and second review (P = 0.02) and was maintained to the third visit (P = 0.015). Patients older than 50 years demonstrate a consistently higher ESS than those less than 50 years old (P = 0.03). This trend is noted throughout the follow up period with the dedicated clinic., Conclusion: The introduction of a multidisciplinary, dedicated HHT clinic to provide enhanced assessment, monitored treatment regimen and greater access to care, resulted in improvement in the management of epistaxis and quality of life in these patients., (© 2021 Royal Australasian College of Surgeons.)

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.)

A rare clinical case of recurrent nosebleeds associated with Randu-Osler disease, in which drug, hemostatic, transfusion therapy and combined nasal tamponade were ineffective, required ligation of the external carotid arteries on both sides, is presented.

Background: Hereditary hemorrhagic telangiectasia (HHT) is an inherited orphan disease, in which the absence of capillary beds between arterioles and venules lead to arteriovenous shunts. Epistaxis is the core symptom. Several case reports have described the nonselective beta-adrenergic receptor antagonist timolol as a successful treatment method of nosebleeds due in HHT patients., Objective: TIM-HHT is a single-site, prospective, randomized, placebo-controlled, double-blind, cross-over study to investigate whether the efficacy of standard laser treatment of epistaxis in HHT patients can be increased by the additional use of timolol nasal spray (1 mg/d)., Methods: Twenty patients will be randomly allocated to one of two treatment sequences. Primary outcome is the severity of epistaxis determined by the Epistaxis Severity Score (ESS). Secondary outcomes are subjective satisfaction, quality of life, as well as the hemoglobin, ferritin, and transferrin levels of the participating patients. Safety outcome is assessed by means of pulse, blood pressure, and adverse events., Conclusion: TIM-HHT will evaluate the efficacy and safety of timolol as an additional treatment of epistaxis in HHT patients in a three-month trial period. Benzalkonium chloride is used as a placebo, which has no documented positive effect on the nasal mucosa and hence on epistaxis in HHT patients (in contrast to saline)., Trial Registration: German Clinical Trials Register (DRKS), DRKS00020994. Registered on 10 March 2020.

Background: Epistaxis is the main complaint in patients with Hereditary haemorrhagic telangiectasia (HHT). Even though the role of epistaxis in affecting the quality of life (QoL) is well-known, little is known about epidemiological and clinical factors contributing to epistaxis severity and QoL., Methodology: This is a cross-sectional study, including adult patients with HHT with epistaxis. All patients underwent an otolaryngological evaluation with nasal endoscopy. Epistaxis severity was graded using the FID score, and QoL was evaluated with the Short-Form Health Survey (SF-36). Descriptive statistics were produced for demographic characteristics; the Shapiro-Wilk test was used to test the normal distribution of quantitative variables. Correlation between the quantitative variables was evaluated with Pearson's correlation coefficient. Both univariate and multivariate linear regression models were fitted to find associations between demographic or clinical factors and the FID score or SF-36., Results: A total of 234 patients with HHT were included in the study. The univariate analysis highlighted the association between high blood pressure, septal perforation, nocturnal epistaxis, surgery, blood transfusion, hormonal therapy and both FID score and QoL. Sex, allergic rhinitis and nasal polyposis were neither related to epistaxis severity nor perceived health., Conclusions: Epistaxis severity and QoL in patients with HHT are influenced by several clinical factors both dependent and independent from HHT. Some of the results are consistent with those already published, but for the first time, we extended the analysis to different clinical parameters, such as endoscopic findings, never assessed before.

From the emergency management of acute epistaxis to the surgical procedures for chronic epistaxis, this article covers the options available to control the archetypal symptom of hereditary haemorrhagic telangiectasia while exploring the psychological effect such a disease has on the patient.

Patients with hereditary haemorrhagic telangiectasia can present with a multitude of symptoms caused by telangiectasia and arteriovenous malformations in the nose, brain, gastrointestinal tract, liver and spinal cord. Clinicians should be aware of the potential diagnosis of hereditary haemorrhagic telangiectasia and how to manage these patients both in the acute and chronic setting. Identifying these patients and optimising their management can help reverse the reduced life expectancy back to that of the normal population. The management of these patients is complex and often requires a multidisciplinary approach, with difficult discussions to be had around screening for arteriovenous malformations and genetic testing. The stepwise management ladder can be used in both the medical and surgical strategies; there are multiple pharmacological and surgical options available, all with their own side effects and risks. Patient education is key to help informed decision making. This article outlines the clinical characteristics of the disease and management options available.

Nosebleeds (epistaxis) are usually minor. Medical intervention is only necessary in about 6% of cases. The source of bleeding is frequently located in the anterior region of the nose (Kiesselbach's plexus). The estimated lifetime prevalence of epistaxis is 60%. Diffuse epistaxis is often a manifestation of systemic disease. Epistaxis is the leading symptom of Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia, HHT). If intervention is required, the first-choice of treatment is bidigital compression for several minutes. Common therapeutic measures include local hemostasis using electrocoagulation or chemical agents, e.g., silver nitrate. Resorbable anterior nasal tampons or tampons with a smooth surface are also frequently employed. In case of failed surgical closure of the sphenopalatine artery, angiographic embolization is the method of choice., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: To evaluate the role of nasal endoscopy for early clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and to investigate the characteristics of epistaxis and mucocutaneous telangiectases in our pediatric population., Study Design: From May 2016 to December 2019, a cross-sectional observational study was conducted, recruiting children aged 2-18 years with a parent affected by HHT. To identify the Curaçao criteria, all children underwent collection of clinical history, mucocutaneous examination, and nasal endoscopy. The clinical data were then compared with the genetic data acquired subsequently., Results: Seventy children (median age, 10.8 years) were included. All underwent nasal endoscopy without complications. Forty-six children were positive by genetic testing; of these, 26 % had skin and oral telangiectases and 91 % had nasal telangiectases. The diagnostic sensitivity of the Curaçao criteria increased from 28 % (95 % CI, 16%-43 %) to 85 % (95 % CI, 71%-94 %; P < .0001) when the nasal telangiectases were included., Conclusions: The magnified and complete endoscopic view of the nasal cavities proved useful in increasing the diagnostic sensitivity of the Curaçao criteria. Such an examination turned out to be feasible and safe. For this reason, we believe that nasal endoscopy should be included in the diagnostic assessment of pediatric patients with suspected HHT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hereditary hemorrhagic telangiectasia is an autosomal dominant hereditary hemorrhagic disease. Its main feature is an abnormal structure of the blood vessel wall. Cirrhosis of the liver is a common chronic progressive disease with one or more causes in which diffuse liver damage occurs after long-term or repeated injury. Liver cirrhosis can cause dilation of gastrointestinal capillaries. Many patients with hereditary hemorrhagic telangiectasia accompanied by gastrointestinal vascular malformations and liver cirrhosis may be diagnosed only with liver cirrhosis if the clinician does not pay attention to physical examination findings and family history. Moreover, general treatment measures, such as blood transfusion, iron supplementation, and application of hemostatic drugs, are less effective for bleeding in patients with hereditary hemorrhagic telangiectasia than in those with liver cirrhosis alone., Case Presentation: Here, we report the rare case of a 75-year-old Chinese man who was admitted to the hospital with repeated melena and epistaxis. He was diagnosed with unexplained liver cirrhosis, which was later confirmed as hereditary hemorrhagic telangiectasia. Subsequently, we implemented the treatment intervention of oral thalidomide combined with gastrointestinal argon plasma coagulation. A follow-up of more than 8 months showed that the treatment effect was excellent., Conclusions: If patients with liver cirrhosis and gastrointestinal vascular malformations also have a family history of epistaxis, special attention should be paid to targeted physical examination results, and the possibility of hereditary hemorrhagic telangiectasia should be considered. Moreover, for patients with hereditary hemorrhagic telangiectasia and both gastrointestinal bleeding caused by gastrointestinal capillaries and repeated epistaxis, when other general treatment measures are ineffective, thalidomide combined with gastrointestinal argon plasma coagulation may be an effective intervention., (© 2021. The Author(s).)

Objective: Patients with hereditary hemorrhagic Telangiectasia (HHT) suffer from a rare and systemic disease which is characterized by vascular malformations leading to a variety of different symptoms., Material and Methods: A retrospective review of patients who were referred to our new HHT Center of Excellence (HHT COE) for evaluation and treatment between April 2014 and August 2019 was performed., Results: 235 patients were treated at the West German HHT Center. 83 % of these were diagnosed with definite HHT (235/282, 83 %) and 9 % with possible HHT (26/282). The average latency between first manifestation and definite diagnosis of HHT was 18 years. Several initial symptoms were direct or indirect signs of bleeding (224/241, 93 %). In 83 % of the patients HHT was reported having caused their degree of disability. Older, female patients and those with severe epistaxis suffered from chronic iron deficiency anemia, took iron preparations (148/261, 57 %) and received 9 blood transfusions on average (± standard deviation: 41, minimum - maximum: 0-400, number of patients: 218). 10 % of all patients tolerated anticoagulant or antiplatelet agents. 74 % of patients with HHT used nasal creams/sprays/oils (177/238) and reported fewer bleedings compared to patients without nasal care (ESS: T-Test: 3.193; p = 0.003; anemia: Chi-square: 5.173; p = 0.023)., Conclusions: The diagnostic latency of HHT was almost two decades. Patients with HHT particularly suffered from recurrent epistaxis, which was mostly treated with nasal care and coagulative therapies. Antiplatelet or anticoagulant agents can be used in patients with HHT with caution if indicated., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: To observe the clinical effects of bevacizumab in the treatment of familial epistaxis caused by hereditary hemorrhagic telangiectasia (HHT). Methods: The data of 27 patients with familial epistaxis caused by HHT who were treated with bevacizumab intravenously from Beijing Anzhen Hospital, the First Clinical Center of Chinese People's Liberation Army General Hospital and Binzhou Central Hospital between December 2016 and December 2019 were retrospectively analyzed. There were 14 males and 13 females, aged (55.3±11.2) years. The dose of bevacizumab was calculated according to the body weight of 5 mg/kg. The curative effect was observed one month after the first treatment. Visual analogue scale (VAS) was used to compare patients' self-scores of systemic symptoms before and after treatment. Epistaxis severity score (ESS) was used to compare and analyze the six problems (including the frequency, duration, intensity, treatment demand, anemia and blood transfusion) of the patients before and after treatment. The changes of hemoglobin levels before and after treatment were compared. SPSS 20.0 statistical software was used to process the data. Results: Among the 27 patients at one month after the first bevacizumab treatment, 22 cases reported that the severity of epistaxis was improved significantly, and 5 cases reported that the treatment effect was not significant. The effective rate was 81.5% (22/27). The significant effect in 22 patients lasted for 5-24 months, with a median duration of 11.23 months. The VAS score of systemic symptoms decreased significantly compared with that before treatment (2.41±2.55 vs 8.19±1.47, t =9.708, P <0.01). The scores of six aspects and standardized scores of ESS were significantly decreased after treatment (epistaxis frequency: 1.78±1.22 vs 3.44±0.80, t =6.814, P <0.01; epistaxis duration: 0.85±0.91 vs 3.00±0.73, t =8.845, P <0.01; epistaxis intensity: 0.19±0.40 vs 1.00±0.00, t =10.696, P <0.01; treatment demand: 0.22 ± 0.42 vs 1.00±0.00, t =9.539, P <0.01; anemia: 0.41±0.50 vs 0.89±0.32, t =4.914, P <0.01; blood transfusion: 0.11±0.32 vs 0.41±0.50, t =3.309, P <0.01; ESS standardized score: 2.50±2.45 vs 7.60±1.30, t =9.344, P <0.01). The hemoglobin level after treatment was significantly higher than that before treatment ((105.48±24.31) g/L vs (73.07±23.71) g/L, t =6.864, P <0.01). Among the 27 patients, there were 8 cases of HHT1 ( ENG gene) and 19 cases of HHT2 ( ACVRL1 gene). The improvement duration of epistaxis in group HHT1 and group HHT2 was (4.76±5.12) months and (7.60±10.84) months, respectively, which was in group HHT2 longer than that of group HHT1, but there was no significant difference between the two groups ( P >0.05). There was no significant difference in ESS scores between the two groups before and after treatment ( P >0.05). Two female patients had amenorrhea after the first medication. All patients had no other adverse reactions and complications. Conclusion: Intravenous bevacizumab is significantly effective and safe in the treatment of familial epistaxis caused by HHT.