Endoscopic surgical treatment of epistaxis in hereditary haemorrhagic telangiectasia: our experience.
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ABSTRACT: Objectives
Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterised by epistaxis. Surgical procedures for epistaxis vary from diathermocoagulation to nasal closure. The aim of this paper is to report our experience in endoscopic surgical management of epistaxis in HHT patients.Methods
This is a descriptive, longitudinal study carried out at the Otorhinolaryngology Department of IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent surgery for epistaxis from 1996 to 2015, including only those treated with endoscopic surgery.Results
Among the 591 patients hospitalised and screened for HHT, 323 (54.7%) underwent endoscopic surgery for epistaxis, for a total of 679 procedures. General anaesthesia was used in 77.2% of procedures; argon plasma coagulation was the instrument of choice in the majority of patients, followed by lasers and quantum molecular resonance technology.Conclusions
We report one of the largest cohorts undergoing endoscopic treatment of epistaxis in HHT patients. This mini-invasive surgical treatment allowed us to control epistaxis without major complications and nasal packaging and can be repeated over time. For these reasons, we recommend it as first choice in case of epistaxis in HHT patients.
SUBMITTER: Pagella F
PROVIDER: S-EPMC7982753 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Endoscopic surgical treatment of epistaxis in hereditary haemorrhagic telangiectasia: our experience.
Pagella Fabio F Pusateri Alessandro A Maiorano Eugenia E Spinozzi Giuseppe G Ugolini Sara S Lizzio Roberta R Mirabella Rosolino R Tinelli Carmine C Olivieri Carla C Matti Elina E
Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale 20210201 1
<h4>Objectives</h4>Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterised by epistaxis. Surgical procedures for epistaxis vary from diathermocoagulation to nasal closure. The aim of this paper is to report our experience in endoscopic surgical management of epistaxis in HHT patients.<h4>Methods</h4>This is a descriptive, longitudinal study carried out at the Otorhinolaryngology Department of IRCCS Policlinico San Matteo in Pavia, a reference centre for th ...[more]
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Project description:BackgroundHereditary 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.MethodsWe 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).ResultsThe 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.ConclusionsAmong 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).
| S-EPMC11412318 | biostudies-literature
Project description:Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by vascular malformations in multiple organ systems, resulting in mucocutaneous telangiectases and arteriovenous malformations predominantly in the lungs (pulmonary arteriovenous malformation; PAVM), brain (cerebral arteriovenous malformation; CAVM), and liver (hepatic arteriovenous malformation; HAVM). Mutations in the ENG and ALK-1 genes lead to HHT1 and HHT2 respectively. In this study, a genotype-phenotype analysis was performed. A uniform and well classified large group of HHT patients and their family members were screened for HHT manifestations. Groups of patients with a clinically confirmed diagnosis and/or genetically established diagnosis (HHT1 or HHT2) were compared. The frequency of PAVM, CAVM, HAVM, and gastrointestinal telangiectases were determined to establish the genotype-phenotype relationship. The analysis revealed differences between HHT1 and HHT2 and within HHT1 and HHT2 between men and women. PAVMs and CAVMs occur more often in HHT1, whereas HAVMs are more frequent in HHT2. Furthermore, there is a higher prevalence of PAVM in women compared with men in HHT1. In HHT1 and HHT2, there is a higher frequency of HAVM in women. HHT1 has a distinct, more severe phenotype than HHT2. There is a difference in the presence of symptoms between men and women. With these data, genetic counselling can be given more accurately when the family mutation is known.
| S-EPMC2563220 | biostudies-literature
Project description:The autosomal-dominant trait hereditary haemorrhagic telangiectasia (HHT) affects 1 in 5-8000 people. Genes mutated in HHT (most commonly for endoglin or activin receptor-like kinase (ALK1)) encode proteins that modulate transforming growth factor (TGF)-beta superfamily signalling in vascular endothelial cells; mutations lead to the development of fragile telangiectatic vessels and arteriovenous malformations. In this article, we review the underlying molecular, cellular and circulatory pathobiology; explore HHT clinical and genetic diagnostic strategies; present detailed considerations regarding screening for asymptomatic visceral involvement; and provide overviews of management strategies.
| S-EPMC2986493 | biostudies-literature
Project description:BackgroundHereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disease associated with epistaxis, arteriovenous malformations and telangiectasias. Disease complications may result in premature death.MethodWe investigated life-expectancies of parents of HHT patients compared with their non-HHT partners using self- or telephone-administered questionnaires sent to their children. Patients were extracted from the databases of 2 participating HHT Centres: the Toronto HHT Database (Toronto, Canada) and the St. Antonius Hospital HHT Database (Nieuwegein, The Netherlands).ResultsTwo hundred twenty five/407 (55%) of respondents were included creating HHT- (n = 225) and control groups (n = 225) of equal size. Two hundred thirteen/225 (95%) of the HHT group had not been screened for organ involvement of the disease prior to death. The life expectancy in parents with HHT was slightly lower compared to parents without (median age at death 73.3 years in patients versus 76.6 years in controls, p0.018). Parents with ACVRL 1 mutations had normal life expectancies, whereas parents with Endoglin mutations died 7.1 years earlier than controls (p = 0.024). Women with Endoglin mutations lived a median of 9.3 years shorter than those without (p = 0.04). Seven/123 (5%) of deaths were HHT related with a median age at death of 61.5 years (IQ range 54.4-67.7 years).ConclusionOur study showed that the life expectancy of largely unscreened HHT patients was lower than people without HHT. Female patients with Endoglin mutations were most strikingly at risk of premature death from complications. These results emphasize the importance of referring patients with HHT for screening of organ involvement and timely intervention to prevent complications.
| S-EPMC4841052 | biostudies-literature
Project description:BackgroundHereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy.MethodsWe recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224.FindingsBetween Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15·9 months (IQR 10·1-22·3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74-98) patients had partial responses. Overall, all 31 (100%, 89-100) patients responded to therapy with a significant decrease in all epistaxis parameters (p<0·0001 for frequency, intensity, and duration). A response was achieved by 25 (81%) patients at 50 mg/day of thalidomide, five (16%) patients at 100 mg/day, and one (3%) patient at 150 mg/day. Patients had only non-serious, grade 1 adverse effects, the most common of which were constipation (21 patients), drowsiness (six patients), and peripheral oedema (eight patients). One patient died a month after the end of treatment, but this was not deemed to be related to treatment.InterpretationLow-dose thalidomide seems to be safe and effective for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia. Our findings should be validated by further studies with larger patient populations, longer follow-up, and that also assess the benefit for quality of life.FundingTelethon Foundation.
| S-EPMC4839500 | biostudies-literature
Project description:BackgroundOur previous studies have demonstrated the tolerability and low side-effect profile of office-based sclerotherapy with sodium tetradecyl sulfate (STS) for treating recurrent epistaxis due to hereditary hemorrhagic telangiectasia (HHT). The objective of this study was to use a prospective randomized trial to determine the effectiveness of sclerotherapy with STS vs standard treatment.MethodsThis prospective randomized trial (conducted from November 1, 2011, through January 31, 2014) involved 17 patients with recurrent epistaxis due to HHT. We defined standard treatment as continuation of any treatment that the patient had previously undergone, such as moisturization, packing, and cautery. We used a crossover design, so study participants were randomized to either sclerotherapy or standard treatment during the first time period, and then to the other during the second period. The primary outcome measure was frequency and severity of epistaxis, as measured by the epistaxis severity score (ESS). The ESS is a 10-point scale, with higher scores corresponding to more bleeding.ResultsAfter controlling for treatment order, bleeding was substantially better controlled after sclerotherapy; the ESS after sclerotherapy was nearly one point lower than after standard treatment (-0.95, 1-sided p = 0.027). Treatment order, baseline ESS, the number of lesions, moisturization practices, and a history of previous blood transfusions did not significantly affect the results.ConclusionThis trial demonstrated that sclerotherapy with STS (vs standard treatment) significantly reduced epistaxis due to HHT.
| S-EPMC4756906 | biostudies-literature
Project description:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in visceral organs. HHT is predominantly caused by mutations in ENG and ACVRL1, Which both belong to the TGF-β signalling pathway. Further knowledge on how a disturbance of the TGF-β signalling pathway leads to HHT manifestations is needed in order to identify potential therapeutic targets. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT. Here we used microarray analysis to profile lncRNAs to compare the expression of HHT telangiectasial and HHT non-telangiectasial nasal tissue from the same patient in a paired design. The microarray probes were re-annotated using the GENCODE v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. By comparing HHT telangiectasial tissue versus HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (q<0.001). Using GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs are enriched for genomic loci involved in key pathways concerning HHT. Our study identified lncRNAs that are aberrantly expressed in HHT telangiectasia and indicates that lncRNAs may contribute to regulate protein-coding loci in HHT. Which suggest that the lncRNA component of the transcriptome deserves more attention in HHT. A deeper understanding of lncRNAs and their role in telangiectasia formation possesses potential for discovering therapeutic targets in HHT.
2014-12-19 | GSE53515 | GEO
Project description:Patients with hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, suffer from the consequences of abnormal vessel structures. These structures can lead to haemorrhages or shunt effects in liver, lungs and brain. This inherited and rare disease is characterized by mutations affecting the transforming growth factor-β (TGF-β)/Bone Morphogenetic Protein (BMP) pathway that results in arteriovenous malformations and studies indicate an impaired immune response. The mechanism underlying this altered immune response in HHT patients is still unknown. TGF-β interacts with hypoxia inducible factors (HIF), which both orchestrate inflammatory and angiogenic processes. Therefore, we analysed the expression of HIF and related genes in whole blood samples from HHT patients. We could show significantly decreased expression of HIF-1α on the mRNA and protein level. However, commonly known upstream regulators of HIF-1α in inflammatory responses were not affected, whereas HIF-1α target genes were significantly downregulated. There was no correlation between HIF1A or HIF2A gene expression and the severity of HHT detected. Our results represent a rare case of HIF-1α downregulation in a human disease, which underlines the relevance of HIFs in HHT. The study indicates an interaction of the known mutation in HHT and the dysregulation of HIF-1α in HHT patients, which might contribute to the clinical phenotype.
| S-EPMC8988913 | biostudies-literature
Project description:Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the presence of telangiectasias and arteriovenous malformations in various organs and organ systems, including the liver. The most frequent clinical manifestation of HHT is epistaxis.In 2010 (January-December inclusive) 51 patients with HHT were admitted to the ENT ward of our hospital for epistaxis, and in accordance with routine protocols, all 51 underwent abdominal ultrasonography in our department to detect hepatovascular lesions. They included 27 males (53%) and 24 (47%) females ranging in age from 11 to 86 years (mean 48.5 years). The sample was selected in an arbitrary manner to take maximum advantage of the hospital stay and monitor patients from regions other than our own.Retrospective analysis of the findings from these sonographic examinations revealed hepatic HHT in 27 (53%) of the 51 patients. Nineteen (70%) of these (age range 40-86 years, mean 63) had vascular malformations of various dimensions but no portal hypertension; the other eight (30%) (age range 39-81 years, mean 60) had vascular malformations plus portal hypertension.Our retrospective analysis indicates that a significant number of patients can have unrecognized hepatic involvement; that the appearance of hepatic lesions can be fairly unpredictable, even when the HHT has been diagnosed for years and the patients are already symptomatic; and that the hepatic lesions are frequently progressive. Therefore, regular sonographic follow-up is advisable for patients with HHT.The limitations of this study are related to the small number of patients examined and to the fact that all of them were symptomatic. Further study is therefore needed (especially in asymptomatic patients) to define the indications for hepatic sonography and the optimum examination schedule.Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the presence of telangiectasias and arteriovenous malformations in various organs and organ systems, including the liver. The most frequent clinical manifestation of HHT is epistaxis.In 2010 (January–December inclusive) 51 patients with HHT were admitted to the ENT ward of our hospital for epistaxis, and in accordance with routine protocols, all 51 underwent abdominal ultrasonography in our department to detect hepatovascular lesions. They included 27 males (53%) and 24 (47%) females ranging in age from 11 to 86 years (mean 48.5 years). The sample was selected in an arbitrary manner to take maximum advantage of the hospital stay and monitor patients from regions other than our own.Retrospective analysis of the findings from these sonographic examinations revealed hepatic HHT in 27 (53%) of the 51 patients. Nineteen (70%) of these (age range 40–86 years, mean 63) had vascular malformations of various dimensions but no portal hypertension; the other eight (30%) (age range 39–81 years, mean 60) had vascular malformations plus portal hypertension.Our retrospective analysis indicates that a significant number of patients can have unrecognized hepatic involvement; that the appearance of hepatic lesions can be fairly unpredictable, even when the HHT has been diagnosed for years and the patients are already symptomatic; and that the hepatic lesions are frequently progressive. Therefore, regular sonographic follow-up is advisable for patients with HHT.The limitations of this study are related to the small number of patients examined and to the fact that all of them were symptomatic. Further study is therefore needed (especially in asymptomatic patients) to define the indications for hepatic sonography and the optimum examination schedule.
| S-EPMC3558090 | biostudies-literature
Project description:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in visceral organs. HHT is predominantly caused by mutations in ENG and ACVRL1, Which both belong to the TGF-M-NM-2 signalling pathway. Further knowledge on how a disturbance of the TGF-M-NM-2 signalling pathway leads to HHT manifestations is needed in order to identify potential therapeutic targets. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT. Here we used microarray analysis to profile lncRNAs to compare the expression of HHT telangiectasial and HHT non-telangiectasial nasal tissue from the same patient in a paired design. The microarray probes were re-annotated using the GENCODE v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. By comparing HHT telangiectasial tissue versus HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (q<0.001). Using GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs are enriched for genomic loci involved in key pathways concerning HHT. Our study identified lncRNAs that are aberrantly expressed in HHT telangiectasia and indicates that lncRNAs may contribute to regulate protein-coding loci in HHT. Which suggest that the lncRNA component of the transcriptome deserves more attention in HHT. A deeper understanding of lncRNAs and their role in telangiectasia formation possesses potential for discovering therapeutic targets in HHT. Gene expression profiling of 80 paired nasal samples from patients with hereditary Haemorrhagic Telangiectasia (HHT), representing telangiectasial and non-telangiectasial (normal) tissue respectively. The patients were divided into HHT1 or HHT2 in regard to the germline mutation in ENG (HHT1) or ACVRL1 (HHT2). Additional controls were healthy siblings (not carrying the germline mutation) and external controls. The study was conducted using Agilent-028004 SurePrint G3 Human GE 8x60K Microarray platform.
2014-12-19 | E-GEOD-53515 | biostudies-arrayexpress