|
1
|
Benaim EH, Kallenberger EM, Mirmozaffari Y, Klatt-Cromwell C, Ebert CS, Kimple AJ, Senior BA, Kasthuri RS, Thorp BD. Surgical Management of Moderate to Severe Epistaxis in Hereditary Hemorrhagic Telangiectasia: Systematic Review and Meta-Analysis. Am J Rhinol Allergy 2025; 39:159-168. [PMID: 39906953 DOI: 10.1177/19458924241308952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
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.
Collapse
Affiliation(s)
- Ezer H Benaim
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Ethan M Kallenberger
- Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - Yasine Mirmozaffari
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Cristine Klatt-Cromwell
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Charles S Ebert
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Adam J Kimple
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Brent A Senior
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Raj S Kasthuri
- Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Brian D Thorp
- Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| |
Collapse
|
|
2
|
Geisthoff UW, Mahnken AH, Denzer UW, Kemmling A, Nimsky C, Stuck BA. Hereditary Hemorrhagic Telangiectasia (Osler's Disease): Systemic, Interdisciplinary, Relatively Common—and Often Missed. DEUTSCHES ARZTEBLATT INTERNATIONAL 2024; 121:601-607. [PMID: 39158362 PMCID: PMC11661474 DOI: 10.3238/arztebl.m2024.0111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 05/16/2024] [Accepted: 05/16/2024] [Indexed: 08/20/2024]
Abstract
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..
Collapse
Affiliation(s)
- Urban W. Geisthoff
- VASCERN HHT Reference Centre, Giessen and Marburg University Hospital
- Department of Otorhinolaryngology, Head and Neck Surgery, Marburg University Hospital, Philipps University of Marburg
- German Osler’s Disease Self-Help Association, Berlin
| | - Andreas H. Mahnken
- VASCERN HHT Reference Centre, Giessen and Marburg University Hospital
- Diagnostic and Interventional Radiology, Marburg University Hospital, Philipps University of Marburg
| | - Ulrike W. Denzer
- VASCERN HHT Reference Centre, Giessen and Marburg University Hospital
- Department of Gastroenterology, Endocrinology, Metabolism, and Clinical Infectiology, Marburg University Hospital, Philipps University of Marburg
| | - André Kemmling
- VASCERN HHT Reference Centre, Giessen and Marburg University Hospital
- Department of Neuroradiology, Marburg University Hospital, Philipps University of Marburg
| | - Christopher Nimsky
- VASCERN HHT Reference Centre, Giessen and Marburg University Hospital
- Department of Neurosurgery, Marburg University Hospital, Philipps University of Marburg
| | - Boris A. Stuck
- VASCERN HHT Reference Centre, Giessen and Marburg University Hospital
- Department of Otorhinolaryngology, Head and Neck Surgery, Marburg University Hospital, Philipps University of Marburg
| |
Collapse
|
|
3
|
Al-Samkari H. How I treat bleeding in hereditary hemorrhagic telangiectasia. Blood 2024; 144:940-954. [PMID: 38864625 PMCID: PMC11830975 DOI: 10.1182/blood.2023021765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/07/2024] [Accepted: 06/08/2024] [Indexed: 06/13/2024] Open
Abstract
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.
Collapse
Affiliation(s)
- Hanny Al-Samkari
- Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| |
Collapse
|
|
4
|
Wang D, Ito S, Waldron C, Butt A, Zhang E, Krumholz HM, Al-Samkari H, Goshua G. Cost-effectiveness of bevacizumab therapy in the care of patients with hereditary hemorrhagic telangiectasia. Blood Adv 2024; 8:2835-2845. [PMID: 38537061 PMCID: PMC11176968 DOI: 10.1182/bloodadvances.2024012589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 03/15/2024] [Accepted: 03/15/2024] [Indexed: 04/30/2024] Open
Abstract
ABSTRACT No US Food and Drug Administration- or European Medicines Agency-approved therapies exist for bleeding due to hereditary hemorrhagic telangiectasia (HHT), the second-most common inherited bleeding disorder worldwide. The current standard of care (SOC) includes iron and red cell supplementation, alongside the necessary hemostatic procedures, none of which target underlying disease pathogenesis. Recent evidence has demonstrated that bleeding pathophysiology is amenable to systemic antiangiogenic therapy with the anti-vascular endothelial growth factor bevacizumab. Despite its high cost, the addition of longitudinal bevacizumab to the current SOC may reduce overall health care resource use and improve patient quality of life. We conducted, to our knowledge, the first cost-effectiveness analysis of IV bevacizumab in patients with HHT with the moderate-to-severe phenotype, comparing bevacizumab added to SOC vs SOC alone. The primary outcome was the incremental net monetary benefit (iNMB) reported over a lifetime time horizon and across accepted willingness-to-pay thresholds, in US dollar per quality-adjusted life year (QALY). Bevacizumab therapy accrued 9.3 QALYs while generating $428 000 in costs, compared with 8.3 QALYs and $699 000 in costs accrued in the SOC strategy. The iNMB of bevacizumab therapy vs the SOC was $433 000. No parameter variation and no scenario analysis, including choice of iron supplementation product, changed the outcome of bevacizumab being a cost-saving strategy. Bevacizumab therapy also saved patients an average of 133 hours spent receiving HHT-specific care per year of life. In probabilistic sensitivity analysis, bevacizumab was favored in 100% of all 10 000 Monte Carlo iterations across base-case and all scenario analyses. Bevacizumab should be considered for more favorable formulary placement in the care of patients with moderate-to-severe HHT.
Collapse
Affiliation(s)
| | - Satoko Ito
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | | | - Ayesha Butt
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
| | - Ellen Zhang
- Department of Medicine, Stanford University Medical Center, Palo Alto, CA
| | - Harlan M. Krumholz
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT
| | - Hanny Al-Samkari
- Division of Hematology Oncology, Massachusetts General Hospital, Cambridge, MA
| | - George Goshua
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT
| |
Collapse
|
|
5
|
Hayama M, Maeda Y, Obata S, Tsuda T, Takeda K, Nishida T, Inohara H. Understanding hereditary hemorrhagic telangiectasia: From genetic anomalies to systemic manifestations, quality of life, and epistaxis management-Exploring the otolaryngologist's integral role. Auris Nasus Larynx 2024; 51:305-312. [PMID: 38008660 DOI: 10.1016/j.anl.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 10/19/2023] [Accepted: 11/07/2023] [Indexed: 11/28/2023]
Abstract
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.
Collapse
Affiliation(s)
- Masaki Hayama
- Department of Otorhinolaryngology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya City, Hyogo, Japan; Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.
| | - Yohei Maeda
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan; Department of Otorhinolaryngology, Japan Community Healthcare Organization Osaka Hospital, Osaka City, Osaka, Japan
| | - Sho Obata
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
| | - Takeshi Tsuda
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
| | - Kazuya Takeda
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
| | - Takeo Nishida
- Department of Neurosurgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya City, Hyogo, Japan; Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
| | - Hidenori Inohara
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
| |
Collapse
|
|
6
|
Chitsuthipakorn W, Hoang MP, Kanjanawasee D, Seresirikachorn K, Snidvongs K. Treatments of Epistaxis in Hereditary Hemorrhagic Telangiectasia: Systematic Review and Network Meta-Analysis. Curr Allergy Asthma Rep 2023; 23:689-701. [PMID: 37995018 DOI: 10.1007/s11882-023-01116-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2023] [Indexed: 11/24/2023]
Abstract
PURPOSE OF REVIEW To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. RECENT FINDINGS Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.
Collapse
Affiliation(s)
- Wirach Chitsuthipakorn
- Center of Excellence in Otolaryngology, Head & Neck Surgery, Rajavithi Hospital, Bangkok, Thailand
- College of Medicine, Rangsit University, Bangkok, Thailand
| | - Minh P Hoang
- Department of Otolaryngology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Dichapong Kanjanawasee
- Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Center of Research Excellence in Allergy & Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Kachorn Seresirikachorn
- Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand
- Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kornkiat Snidvongs
- Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand.
- Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
| |
Collapse
|
|
7
|
Al-Samkari H, Kasthuri RS, Parambil JG, Albitar HA, Almodallal YA, Vázquez C, Serra MM, Dupuis-Girod S, Wilsen CB, McWilliams JP, Fountain EH, Gossage JR, Weiss CR, Latif MA, Issachar A, Mei-Zahav M, Meek ME, Conrad M, Rodriguez-Lopez J, Kuter DJ, Iyer VN. An international, multicenter study of intravenous bevacizumab for bleeding in hereditary hemorrhagic telangiectasia: the InHIBIT-Bleed study. Haematologica 2021; 106:2161-2169. [PMID: 32675221 PMCID: PMC8327711 DOI: 10.3324/haematol.2020.261859] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Indexed: 12/13/2022] Open
Abstract
Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder that causes chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHTassociated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, Epistaxis Severity Score (ESS), red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. Bevacizumab was given to 238 HHT patients for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% confidence interval: 2.9-3.5 g/dL); i.e., from a mean hemoglobin of 8.6 (8.5-8.8) g/dL to 11.8 (11.5-12.1) g/dL; P<0.0001) and decreased the ESS by 3.4 (3.2-3.7) points (mean ESS 6.8 [6.6-7.1] versus 3.4 [3.2-3.7]; P<0.0001) during the first year of treatment. Compared with 6 months before treatment, the number of red blood cell units transfused decreased by 82% (median of 6.0 [interquartile range, 0.0-13.0] units versus 0 [0.0-1.0] units; P<0.0001) and iron infusions decreased by 70% (median of 6.0 [1.0-18.0] infusions versus 1.0 [0.0-4.0] infusions, P<0.0001) during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of the underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as-needed maintenance but with more drug exposure. Bevacizumab was well tolerated: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective for managing chronic bleeding and anemia in HHT.
Collapse
Affiliation(s)
- Hanny Al-Samkari
- Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Raj S Kasthuri
- Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | | | - Hasan A Albitar
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - Carolina Vázquez
- Department of Internal Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Marcelo M Serra
- Department of Internal Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Sophie Dupuis-Girod
- Centre de Reference pour la maladie de Rendu-Osler, Hospices Civils de Lyon, Lyon, France
| | - Craig B Wilsen
- Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Justin P McWilliams
- Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Evan H Fountain
- Division of Pulmonary, Critical Care, and Sleep Medicine, Augusta University, Augusta, GA, USA
| | - James R Gossage
- Division of Pulmonary, Critical Care, and Sleep Medicine, Augusta University, Augusta, GA, USA
| | - Clifford R Weiss
- Div. of Interventional Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Muhammad A Latif
- Div. of Interventional Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Assaf Issachar
- Schneider Children's Medical Center of Israel, Tel Aviv University, Israel
| | - Meir Mei-Zahav
- Schneider Children's Medical Center of Israel, Tel Aviv University, Israel
| | - Mary E Meek
- Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Miles Conrad
- Dept. of Radiology, University of California San Francisco Medical Center, San Francisco, CA, USA
| | - Josanna Rodriguez-Lopez
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - David J Kuter
- Division of Hematology, Massachusetts General Hospital, Boston, MA, USA
| | - Vivek N Iyer
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
8
|
Long-term efficacy assessment of current treatment options for epistaxis in HHT. Eur Arch Otorhinolaryngol 2021; 278:4321-4328. [PMID: 33661356 PMCID: PMC8486717 DOI: 10.1007/s00405-021-06701-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 02/09/2021] [Indexed: 12/27/2022]
Abstract
Purpose Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder that presents with recurrent, intractable epistaxis. The aim of this study was to retrospectively analyze the efficacy of various treatment options for epistaxis in patients with HHT, over a period of 18 years, and to correlate these findings with available evidence in the literature.
Methods Records of patients with HHT, treated for epistaxis between 2000 and 2018 were analyzed. Treatment procedures carried out and their efficacy were extracted and analyzed.
Results Forty-three records were evaluated. All patients were given nasal humidifying ointments, 93% required acute treatment with bipolar electrocautery, and 60% underwent atraumatic nasal packing. Recurrent cases were treated medically with tranexamic acid (26%), oestrogen (19%), and bevacizumab (2%). Laser photocoagulation was done in selected cases (40%) and if unsuccessful, septal dermoplasty was performed (2.3%). Endovascular embolization was reserved for life-threatening emergencies (7%). Conclusion Epistaxis in HHT is not curable, but can be managed by employing a comprehensive stepwise approach. An algorithm for effective and comprehensive management has been presented.
Collapse
|
|
9
|
Hsu YP, Hsu CW, Bai CH, Cheng SW, Chen C. Medical Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia: A Meta-analysis. Otolaryngol Head Neck Surg 2018; 160:22-35. [DOI: 10.1177/0194599818797316] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Objectives The aim of this study (PROSPERO ID: CRD42017081952) was to evaluate medical treatment for epistaxis from hereditary hemorrhagic telangiectasia (HHT). Data Sources PubMed, Embase, Scopus, and Cochrane Library databases were interrogated from their inceptions to November 2017. Review Methods Randomized clinical trials comparing medical treatment with placebo for epistaxis of HHT were included. We used a random-effects model to synthesize overall effects. Heterogeneity was evaluated with the I2 statistic. Results Eight studies were identified after systematic searching. The use of bevacizumab (BV), tranexamic acid, and estrogen, regardless of the route of administration, had no significant influence on frequency of episodes. Tamoxifen was superior to placebo in both frequency and severity of epistaxis. For duration of epistaxis, nasal spray BV, oral or nasal spray tranexamic acid, and nasal spray estrogen had no significant differences versus placebo, but patients receiving submucosal BV showed lower duration of epistaxis (mean difference: −219.00 min/mo, 95% CI: −271.90 to −166.10). Medical treatment for HHT had no significant changes of mean hemoglobin concentration (pooled mean difference: −0.23 mg/dL, 95% CI: −0.65 to 0.20, I2 = 0%) or quality of life (pooled standardized mean difference: 0.07, 95% CI: −0.16 to 0.30, I2 = 0%). Conclusions Only limited evidence provides a benefit on frequency of epistaxis by treatment with tamoxifen and duration of epistaxis by treatment with submucosal BV among patients with HHT. Mean hemoglobin concentration and quality of life were not influenced by medical treatment.
Collapse
Affiliation(s)
- Yuan-Pin Hsu
- Emergency Department, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chin-Wang Hsu
- Emergency Department, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chyi-Huey Bai
- Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sheng-Wei Cheng
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chiehfeng Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan
- Division of Plastic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| |
Collapse
|
|
10
|
Nardone G, Compare D, Martino A, Rocco A. Pharmacological treatment of gastrointestinal bleeding due to angiodysplasias: A position paper of the Italian Society of Gastroenterology (SIGE). Dig Liver Dis 2018; 50:542-548. [PMID: 29610020 DOI: 10.1016/j.dld.2018.02.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 01/11/2018] [Accepted: 02/08/2018] [Indexed: 02/08/2023]
Abstract
Angioectasias (AD) belong to benign vascular malformations of the gastrointestinal tract and are responsible for about 4-7% of upper non variceal bleeding, 30-40% of small bowel occult bleeding and 3-40% of colonic bleeding episodes. Gastrointestinal haemorrhage secondary to AD represents an important diagnostic and therapeutic problem that negatively impacts on the quality of life of patients and heath care costs. Endoscopic interventions are the mainstay in both diagnosis and treatment of vascular malformations. However, in a substantial percentage of the cases, age of the patients, comorbidities, clinical severity of anaemia and blood loss as well as size, site and number of lesions prevent this therapeutic approach. Hormonal therapy, thalidomide and somatostatin analogues have been investigated for their potential role as rescue therapies in controlling AD bleeding although, thus far, no recommendations have been provided on their use in this clinical setting. In order to implement appropriate prescription of pharmacological agents to manage gastrointestinal bleeding due to ADs, the Italian Society of Gastroenterology (SIGE) nominated a panel of experts who reviewed the available clinical literature and produced practical clinical recommendations.
Collapse
Affiliation(s)
- Gerardo Nardone
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy.
| | - Debora Compare
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
| | - Alberto Martino
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
| | - Alba Rocco
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
| |
Collapse
|
|
11
|
Chetcuti Zammit S, Koulaouzidis A, Sanders DS, McAlindon ME, Rondonotti E, Yung DE, Sidhu R. Overview of small bowel angioectasias: clinical presentation and treatment options. Expert Rev Gastroenterol Hepatol 2018; 12:125-139. [PMID: 28994309 DOI: 10.1080/17474124.2018.1390429] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Elderly patients with multiple co-morbidities are at an increased risk of developing small bowel angioectasias. Treating these lesions can be both challenging and costly with patients requiring extensive investigations and recurrent admissions for iron infusions and blood transfusions as well as invasive procedures. This review presents treatment options and describes in detail drugs that should be considered whilst taking into account their effectiveness and their safety profile. Areas covered: A PubMed search was carried out using the following keywords: small bowel angiodysplasias, small bowel angioectasias, small bowel bleeding and obscure gastrointestinal bleeding to assess existing evidence. The pathophysiology and risk factors are covered in this review together with appropriate methods of investigation and management. Treatment options discussed are endoscopic measures, surgical options and pharmacotherapy. The role of serum biomarkers is also discussed. Expert commentary: Future work should be directed at alternative drugs with a good safety profile that target biomarkers. Novel pharmacotherapy directed at biomarkers could potentially provide a non-invasive treatment option for angioectasias particularly in the elderly where management can be challenging.
Collapse
Affiliation(s)
| | | | - David S Sanders
- a Gastroenterology Department , Royal Hallamshire Hospital , Sheffield , UK
| | - Mark E McAlindon
- a Gastroenterology Department , Royal Hallamshire Hospital , Sheffield , UK
| | | | - Diana E Yung
- b Endoscopy Unit , the Royal Infirmary of Edinburgh , Edinburgh , UK
| | - Reena Sidhu
- a Gastroenterology Department , Royal Hallamshire Hospital , Sheffield , UK
| |
Collapse
|
|
12
|
Dar T, Yarlagadda B, Vacek J, Dawn B, Lakkireddy D. Management of Stroke risk in atrial fibrillation patients with bleeding on Oral Anticoagulation Therapy-Role of Left Atrial Appendage Closure, Octreotide and more. J Atr Fibrillation 2017; 10:1729. [PMID: 29487685 DOI: 10.4022/jafib.1729] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 11/19/2017] [Accepted: 12/14/2017] [Indexed: 12/18/2022]
Abstract
Background Bleeding complications especially gastrointestinal bleeding remains a major challenge associated with oral anticoagulation therapy (OAT) and often leads clinicians to withdraw oral anticoagulation therapy (OAT) . This exposes patients to risk of stroke and systemic thromboembolism (STE). Novel oral anticoagulants (NOACs) have proved no better when it comes to bleeding events and in fact studies have shown that overall NOACs are associated with higher incidence of gastrointestinal (GI) bleeding compared to warfarin . Objectives In this review, we describe the difficulties encountered in managing OAT in patients with bleeding and strategies to maneuver around these bleeding complications particularly gastrointestinal bleeding secondary to arteriovenous malformations (AVM) and other vascular abnormalities. Findings Left atrial appendage closure (LAAC) has emerged as a very elegant and promising tool for stroke prevention in non-valvular atrial fibrillation (AF) patients who are intolerant to OAT. But the need for OAT post procedure for a brief period is becoming a major hurdle for clinicians to pursue in this direction in patients with recurrent gastrointestinal bleeds. And in majority of cases, recurrent or refractory gastrointestinal bleeds are usually secondary to arteriovenous malformations/angiodysplasias (AVM/AD). We suggest that the problem has to be approached by decreasing or eliminating the acute bleeding risk and closing the LAA in the long term, to enable the patients to come off of OAT and minimize the risk of recurrent bleeding.
Collapse
Affiliation(s)
- Tawseef Dar
- Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Hospital & Medical Center, Kansas City, KS
| | - Bharat Yarlagadda
- Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Hospital & Medical Center, Kansas City, KS
| | - James Vacek
- Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Hospital & Medical Center, Kansas City, KS
| | - Buddhadeb Dawn
- Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Hospital & Medical Center, Kansas City, KS
| | - Dhanunjaya Lakkireddy
- Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Hospital & Medical Center, Kansas City, KS
| |
Collapse
|
|
13
|
Chetcuti Zammit S, Sanders DS, Sidhu R. Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre. Scand J Gastroenterol 2017; 52:962-968. [PMID: 28506132 DOI: 10.1080/00365521.2017.1325929] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs. METHOD Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes. RESULTS Twelve patients (67% males, mean age 74 SD ± 15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD ± 14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis. There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131-166 g/L, p = .012). The mean number of bleeding episodes (4.18 versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received improved. Patients required less DBEs ± APCs after starting lanreotide (19 versus 11 p = .048). CONCLUSION Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.
Collapse
Affiliation(s)
- S Chetcuti Zammit
- a Department of Gastroenterology , Royal Hallamshire Hospital , Sheffield, UK
| | - D S Sanders
- a Department of Gastroenterology , Royal Hallamshire Hospital , Sheffield, UK
| | - R Sidhu
- a Department of Gastroenterology , Royal Hallamshire Hospital , Sheffield, UK
| |
Collapse
|
|
14
|
Combined therapy for epistaxis by hereditary hemorrhagic teleangiectasia: A 3-year follow up study on 45 patients. J Craniomaxillofac Surg 2017; 45:1179-1182. [DOI: 10.1016/j.jcms.2017.05.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Revised: 04/27/2017] [Accepted: 05/18/2017] [Indexed: 11/20/2022] Open
|
|
15
|
Patel A, Patel S, Wickremesinghe PC, Vadada D. Radiofrequency ablation using Barrx ® for the endoscopic treatment of gastric antral vascular ectasia: a series of three cases and a review of the literature on treatment options. Clin Exp Gastroenterol 2017; 10:113-120. [PMID: 28744150 PMCID: PMC5513699 DOI: 10.2147/ceg.s80241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Gastric antral vascular ectasia (GAVE), also known as "watermelon stomach", is an uncommon condition, which can cause gastrointestinal bleeding due to rupture of blood vessels that line the stomach. The pathogenesis of GAVE remains unclear; however it is thought that hemodynamic changes, mechanical stress, and autoimmune factors all have a part to play. A range of conditions are also commonly associated with the syndrome, such as portal hypertensive gastropathy, liver cirrhosis, and autoimmune disorders. Less commonly, chronic renal failure, cardiac diseases, and bone marrow transplantation have coexisted with GAVE. The diagnosis is usually based on visualization of the tissue upon endoscopy; however, histology plays a role in uncertain cases. The typical "watermelon" appearance relates to the tissue having a striped appearance radiating out from the pylorus. Medical treatment has failed to show satisfactory results and surgery is usually considered as a last resort, due to its increased risk for complications and mortality. Lasers and argon plasma coagulation have been used recently, and been shown to be as effective as surgery and a safer option. We present three cases of gastric antral vascular ectasia treated at our institution with radiofrequency ablation and review the literature on treatment modalities for GAVE.
Collapse
Affiliation(s)
- Anish Patel
- Department of Gastrointestinal Medicine, Richmond University Medical Center, Staten Island, NY, USA
| | - Sunil Patel
- Department of Gastrointestinal Medicine, Richmond University Medical Center, Staten Island, NY, USA
| | | | - Deepak Vadada
- Department of Gastrointestinal Medicine, Richmond University Medical Center, Staten Island, NY, USA
| |
Collapse
|
|
16
|
Arthur H, Geisthoff U, Gossage JR, Hughes CCW, Lacombe P, Meek ME, Oh P, Roman BL, Trerotola SO, Velthuis S, Wooderchak-Donahue W. Executive summary of the 11th HHT international scientific conference. Angiogenesis 2016; 18:511-24. [PMID: 26391603 DOI: 10.1007/s10456-015-9482-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is a hereditary condition that results in vascular malformations throughout the body, which have a proclivity to rupture and bleed. HHT has a worldwide incidence of about 1:5000 and approximately 80 % of cases are due to mutations in ENG, ALK1 (aka activin receptor-like kinase 1 or ACVRL1) and SMAD4. Over 200 international clinicians and scientists met at Captiva Island, Florida from June 11-June 14, 2015 to present and discuss the latest research on HHT. 156 abstracts were accepted to the meeting and 60 were selected for oral presentations. The first two sections of this article present summaries of the basic science and clinical talks. Here we have summarized talks covering key themes, focusing on areas of agreement, disagreement, and unanswered questions. The final four sections summarize discussions in the Workshops, which were theme-based topical discussions led by two moderators. We hope this overview will educate as well as inspire those within the field and from outside, who have an interest in the science and treatment of HHT.
Collapse
MESH Headings
- Activin Receptors, Type II/genetics
- Activin Receptors, Type II/metabolism
- Antigens, CD/genetics
- Antigens, CD/metabolism
- Congresses as Topic
- Endoglin
- Humans
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/metabolism
- Smad4 Protein/genetics
- Smad4 Protein/metabolism
- Telangiectasia, Hereditary Hemorrhagic/genetics
- Telangiectasia, Hereditary Hemorrhagic/metabolism
- Telangiectasia, Hereditary Hemorrhagic/pathology
- Telangiectasia, Hereditary Hemorrhagic/therapy
Collapse
Affiliation(s)
- Helen Arthur
- Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, UK
| | - Urban Geisthoff
- Department of Otorhinolaryngology, Essen University Hospital, Essen, Germany
| | - James R Gossage
- Department of Medicine, Georgia Regents University, Augusta, GA, USA.
| | - Christopher C W Hughes
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Pascal Lacombe
- Department of Diagnostic and Interventional Radiology, Hôpital Ambroise Paré, Université de Versailles, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France
| | - Mary E Meek
- Department of Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Paul Oh
- Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL, USA
| | - Beth L Roman
- Department of Human Genetics and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Scott O Trerotola
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sebastiaan Velthuis
- Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Whitney Wooderchak-Donahue
- ARUP Institute for Clinical and Experimental Pathology, Department of Pathology, University of Utah, Salt Lake City, UT, USA
| |
Collapse
|
|
17
|
Sautter NB, Smith TL. Treatment of Hereditary Hemorrhagic Telangiectasia–Related Epistaxis. Otolaryngol Clin North Am 2016; 49:639-54. [DOI: 10.1016/j.otc.2016.02.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
18
|
Minami K, Haji T. Intranasal topical estrogen in the management of epistaxis in hereditary hemorrhagic telangiectasia. Acta Otolaryngol 2016; 136:528-31. [PMID: 26808464 DOI: 10.3109/00016489.2015.1129070] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONCLUSION Application of topical estriol ointment is an effective treatment for hereditary hemorrhagic telangiectasia (HHT) epistaxis. OBJECTIVE HHT is an autosomal-dominant disease characterized by epistaxis in more than 96% of patients. Management of this major symptom, epistaxis, has not been standardized. This study reports experience with topical application of estriol in patients with HHT. METHODS Five patients with a confirmed diagnosis of HHT who first visited the hospital between 2012 and 2013 received 0.1% estriol ointment and were guided to apply the ointment twice daily to the anterior part of both nasal cavities. Severity of epistaxis was valued using epistaxis severity score (ESS) before and 3 months after initiating therapy. RESULTS Five patients (three males, two females) received treatment. After the initiation of treatment, intensity and frequency of epistaxis became moderate in all patients. ESS decreased significantly from pre- to post-treatment (p = 0.043). No adverse events were recorded during follow-up.
Collapse
Affiliation(s)
- Kazuhiko Minami
- a Department of Head and Neck Surgery , Saitama Medical University International Medical Center , Hidaka , Saitama , Japan
| | - Tomoyuki Haji
- b Department of Communication Science and Disorders, Faculty of Health and Welfare , Prefectural University of Hiroshima , Mihara , Hiroshima , Japan
| |
Collapse
|
|
19
|
Chin CJ, Rotenberg BW, Witterick IJ. Epistaxis in hereditary hemorrhagic telangiectasia: an evidence based review of surgical management. J Otolaryngol Head Neck Surg 2016; 45:3. [PMID: 26754744 PMCID: PMC4709944 DOI: 10.1186/s40463-016-0116-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 01/05/2016] [Indexed: 12/21/2022] Open
Abstract
Patients with Hereditary Hemorrhagic Telangiectasia (HHT) frequently present with epistaxis. Up to 98 % of these patients will have epistaxis at some point in their life. There are multiple ways to deal with this problem, including conservative, medical and surgical options. We present a case and an update on the treatment options for HHT, with a focus on the newer and experimental techniques.
Collapse
Affiliation(s)
- Christopher J Chin
- Department of Otolaryngology-Head & Neck Surgery, University of Toronto, Room 413, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
| | - Brian W Rotenberg
- Department of Otolaryngology-Head and Neck Surgery, Western University, Toronto, Canada.
| | - Ian J Witterick
- Department of Otolaryngology-Head & Neck Surgery, University of Toronto, Room 413, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
| |
Collapse
|
|
20
|
Invernizzi R, Quaglia F, Klersy C, Pagella F, Ornati F, Chu F, Matti E, Spinozzi G, Plumitallo S, Grignani P, Olivieri C, Bastia R, Bellistri F, Danesino C, Benazzo M, Balduini CL. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study. LANCET HAEMATOLOGY 2015; 2:e465-73. [PMID: 26686256 DOI: 10.1016/s2352-3026(15)00195-7] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 08/27/2015] [Accepted: 09/03/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hereditary 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. METHODS We 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. FINDINGS Between 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. INTERPRETATION Low-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. FUNDING Telethon Foundation.
Collapse
Affiliation(s)
- Rosangela Invernizzi
- Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
| | - Federica Quaglia
- Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Catherine Klersy
- Service of Biometry and Clinical Epidemiology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Fabio Pagella
- Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Federica Ornati
- Department of Cardiology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy; Department of Molecular Medicine, General Biology, and Medical Genetics Unit, University of Pavia, Pavia, Italy
| | - Francesco Chu
- Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Elina Matti
- Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Giuseppe Spinozzi
- Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Sara Plumitallo
- Department of Molecular Medicine, General Biology, and Medical Genetics Unit, University of Pavia, Pavia, Italy
| | - Pierangela Grignani
- Department of Legal Medicine and Public Health, University of Pavia, Pavia, Italy
| | - Carla Olivieri
- Department of Molecular Medicine, General Biology, and Medical Genetics Unit, University of Pavia, Pavia, Italy
| | - Raffaella Bastia
- Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Francesca Bellistri
- Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Cesare Danesino
- Department of Molecular Medicine, General Biology, and Medical Genetics Unit, University of Pavia, Pavia, Italy
| | - Marco Benazzo
- Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Carlo L Balduini
- Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| |
Collapse
|
|
21
|
Geisthoff UW, Nguyen HL, Röth A, Seyfert U. How to manage patients with hereditary haemorrhagic telangiectasia. Br J Haematol 2015. [PMID: 26205234 DOI: 10.1111/bjh.13606] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Hereditary haemorrhagic telangiectasia is a rare systemic autosomal dominantly inherited disorder of the fibrovascular tissue with a wide variety of clinical manifestations. Diagnosis is based on the clinical Curaçao criteria or molecular genetic testing. Dilated vessels can develop into telangiectases or larger vascular malformations in various organs, calling for an interdisciplinary approach. Epistaxis and gastrointestinal bleeding can result from these vascular defects. Various conservative and interventional treatments have been described for these conditions. However, no optimal therapy exists. Treatment can become especially difficult due to progressive anaemia or when anticoagulant or anti-thrombotic therapy becomes necessary. Screening for pulmonary arteriovenous malformations (PAVM) should be performed in all confirmed and suspected patients. Treatment by percutaneous transcatheter embolotherapy and antibiotic prophylaxis is normally effective for PAVM. Cerebral or hepatic vascular malformations and rare manifestations need to be evaluated on a case-by-case basis to determine the best course of action for treatment.
Collapse
Affiliation(s)
- Urban W Geisthoff
- Department of Otorhinolaryngology, Essen University Hospital, Essen, Germany
| | - Ha-Long Nguyen
- Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium
| | - Alexander Röth
- Department of Haematology and Haemostaseology, Essen University Hospital, Essen, Germany
| | - Ulrich Seyfert
- Medical Practice for Haemostaseology and Transfusion Medicine, Saarbrücken, Germany
| |
Collapse
|
|
22
|
Evidence-based management of epistaxis in hereditary haemorrhagic telangiectasia. The Journal of Laryngology & Otology 2015; 129:410-5. [PMID: 25736077 DOI: 10.1017/s0022215115000365] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND There are currently no guidelines in the UK for the specific management of hereditary haemorrhagic telangiectasia related epistaxis. The authors aimed to review the literature and provide an algorithm for the management of hereditary haemorrhagic telangiectasia related epistaxis. METHOD The Medline and Embase databases were interrogated on 15 November 2013 using the search items 'hereditary haemorrhagic telangiectasia' (title), 'epistaxis' (title) and 'treatment' (title and abstract), and limiting the search to articles published in English. RESULTS A total of 46 publications were identified, comprising 1 systematic review, 2 randomised, controlled trials, 27 case series, 9 case reports, 4 questionnaire studies and 3 in vitro studies. CONCLUSION There is a lack of high-level evidence for the use of many of the available treatments for the specific management of epistaxis in hereditary haemorrhagic telangiectasia. Current management should be based on a multidisciplinary team approach involving both a hereditary haemorrhagic telangiectasia physician and an ENT surgeon, especially when systemic therapy is being considered. The suggested treatment algorithm considers that the severity of epistaxis merits intervention at different levels of the treatment ladder. The patient should be assessed using a reproducible validated assessment tool, for example an epistaxis severity score, to guide treatment. More research is required, particularly in the investigation of topical agents targeting the development and fragility of telangiectasiae in hereditary haemorrhagic telangiectasia.
Collapse
|
|
23
|
Geisthoff UW, Seyfert UT, Kübler M, Bieg B, Plinkert PK, König J. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study. Thromb Res 2014; 134:565-71. [DOI: 10.1016/j.thromres.2014.06.012] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Revised: 06/03/2014] [Accepted: 06/07/2014] [Indexed: 10/25/2022]
|
|
24
|
First experiences with an individual nasal olive in patients with hereditary haemorrhagic telangiectasia (HHT). Eur Arch Otorhinolaryngol 2014; 272:117-22. [PMID: 24854232 DOI: 10.1007/s00405-014-3086-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Accepted: 05/03/2014] [Indexed: 10/25/2022]
Abstract
Hereditary haemorrhagic teleangiectasia (HHT) is most notably characterized by vulnerable vascular formations of the nasal superficial mucosa. Epistaxis is one of the most common symptoms of the afflicted patients, with an incidence of more than 90 %. A variable series of treatments have been described, ranging from nasal ointments to the complete surgical occlusion of the nose. The objective of this pilot study is the presentation of first experiences in treating patients suffering from HHT and chronically recurrent epistaxis with an individual nasal olive made from silicone. Eleven patients (six men, five women) aging from 44 to 80 years with known HHT were treated at the ENT department of Homburg/Saar between October 2008 and July 2012 because of nasal bleeding by Nd:YAG laser or argon plasma coagulation. After the surgical treatment, an imprint of the nasal aditus was taken to manufacture an individual custom-made silicone nasal olive. Patients were wearing the nasal olive for 3-8 h a day. Check-ups were made every 6 months. Epistaxis severity score (ESS) was used pre- and post-nasal olive application. The observation period was 12-48 months. The utilization of the silicone nasal olive led to a distinct reduction of epistaxis events. Apart from the nasal olive, our patients needed no further treatment of the nose during the observation period except for a nasal ointment. Insertion and removal of the nasal olive were handled by the patients themselves. The local manipulation in handling the nasal olive caused no epistaxis itself. A significant improvement of the ESS and satisfaction was reported in all patients. Use of an individually manufactured silicone nasal olive is a promising extension to the established treatments of epistaxis in HHT patients. Tolerance towards this treatment by the patients was high due to the low personal burden and encumbrance. The extended use of the presented method in HHT patients may be beneficial. However, a more prolonged observation period is necessary in the future to judge the long-term efficiency of individual nasal olives.
Collapse
|
|
25
|
Sautter NB, Smith TL. Hereditary hemorrhagic telangiectasia-related epistaxis: innovations in understanding and management. Int Forum Allergy Rhinol 2012; 2:422-31. [PMID: 22566463 DOI: 10.1002/alr.21046] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2012] [Revised: 03/15/2012] [Accepted: 03/20/2012] [Indexed: 12/26/2022]
Abstract
BACKGROUND Epistaxis is the most common manifestation of hereditary hemorrhagic telangiectasia (HHT), affecting approximately 90% of patients at some point during their lifetime. Bleeding is chronic and varies from mild, self-limited episodes to severe, transfusion-dependent or life-threatening epistaxis. Treatment options vary from conservative, nonsurgical management to more aggressive surgical approaches. A number of treatment options have been introduced in recent years. There is little consensus in the literature regarding treatment algorithms. The objective of this investigation was to provide a contemporary review of HHT-related epistaxis, including pathophysiology, disease manifestations, and state-of-the-art treatment modalities. METHODS A systematic review of the literature for HHT-related epistaxis was performed using the search terms "hereditary hemorrhagic telangiectasia" and "epistaxis." Additional literature search regarding current recommendations for HHT evaluation and recent developments in genetic mechanisms, pathophysiology, and treatment of HHT was also performed. RESULTS A total of 308 articles were identified and reviewed for appropriateness of inclusion whereas 64 articles met inclusion criteria. Treatment options range from topical and hormonal therapy to more aggressive surgical modalities. Most treatment descriptions are case series, with few randomized controlled trials. A number of new and novel therapies have been introduced in recent years. CONCLUSION HHT is a heterogeneous disease requiring multidisciplinary evaluation and treatment. Therapeutic options for HHT-related epistaxis vary from conservative, nonsurgical measures to more aggressive surgical treatments. A graduated treatment plan is recommended. Patients present with a wide degree in variation of severity of epistaxis, and treatment is best tailored to the individual patient.
Collapse
Affiliation(s)
- Nathan B Sautter
- Oregon Sinus Center, Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, OR 97239, USA.
| | | |
Collapse
|
|
26
|
Alam MA, Sami S, Babu S. Successful treatment of bleeding gastro-intestinal angiodysplasia in hereditary haemorrhagic telangiectasia with thalidomide. BMJ Case Rep 2011; 2011:bcr.08.2011.4585. [PMID: 22674103 DOI: 10.1136/bcr.08.2011.4585] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by epistaxis, cutaneous telangiectasia and visceral arterio-venous malformations (AVMs). It affects approximately one in 5000 people. Control of sustained and repeated haemorrhages from telangiectasias in the nose and gut in patients who may be transfusion dependent is clinically challenging. After repeated endoscopic coagulations, multiple lesions often recur at other sites of gastro-intestinal tract, where endoscopic therapy or surgical resection is not possible. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Thalidomide, with its antiangiogenic mechanism of action, seems to be promising drug as a treatment option where other modalities have been unsuccessful. In this article, the authors discuss a novel treatment of bleeding gastro-intestinal angiodysplasia.
Collapse
Affiliation(s)
- Mohamed Aftab Alam
- Department of Gastroenterology/General Medicine, Scarborough General Hospital, Scarborough, North Yorkshire, UK.
| | | | | |
Collapse
|
|
27
|
Treatment of gastrointestinal angiodysplasia and unmet needs. Dig Liver Dis 2011; 43:515-22. [PMID: 21239239 DOI: 10.1016/j.dld.2010.12.007] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2010] [Revised: 11/23/2010] [Accepted: 12/08/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gastrointestinal angiodysplasia (GIAD) may either be asymptomatic or induce overt or obscure bleeding with a high risk of recurrence. Numerous therapeutic options are available but evidence bases are lacking. AIM We conducted a comprehensive review of pharmacological and endoscopic treatments for previous or active bleeding GIAD and established the unmet needs of the clinicians. METHODS Clinical trials, series, and reports, having been selected through PubMed inquiry, manual searching, and reference list reviewing, were classified by levels of evidence. RESULTS Controlled studies focusing on GIAD treatment, excluding other GI vascular malformations, are rare. Endoscopic destruction, preferably using non-contact endoscopic techniques, is most often proposed as a first-line treatment for GIAD (expert level). In addition, APC is preferred over Nd:Yag laser due to the lower risk of perforation (expert level). Pharmacological treatments for GIAD are considered either when endoscopy fails to access the AD or in order to prevent rebleeding for "chronic bleeding patients." Octreotide and oestroprogestative treatments are the best evaluated drugs; however, no appropriate comparison on cost-effectiveness and tolerance has been performed. CONCLUSIONS The most effective therapeutic strategy for bleeding GIAD is currently inconclusive, and new trials should be performed to address unmet needs.
Collapse
|
|
28
|
ROSS CS, PRUTHI RK, SCHMIDT KA, ECKERMAN AL, RODRIGUEZ V. Intranasal oestrogen cream for the prevention of epistaxis in patients with bleeding disorders. Haemophilia 2010; 17:164. [DOI: 10.1111/j.1365-2516.2010.02356.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
29
|
Yaniv E, Preis M, Hadar T, Shvero J, Haddad M. Antiestrogen therapy for hereditary hemorrhagic telangiectasia: A double-blind placebo-controlled clinical trial. Laryngoscope 2009; 119:284-8. [DOI: 10.1002/lary.20065] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
|
|
30
|
Battista MJ, Eichbaum MHR, Hosch WP, Fersis N, Sohn C. Extensive Osler-Rendu disease in a breast cancer patient: increasing hepatic arteriovenous malformations under endocrine therapy mimicking liver metastases. ACTA ACUST UNITED AC 2008; 31:328-31. [PMID: 18547975 DOI: 10.1159/000121434] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Undefined, increasing hepatic lesions are a common issue in the follow-up care of breast cancer patients and frequently result in invasive diagnostic procedures. CASE REPORT This case report describes the diagnostic approach in the case of a 58-year-old breast cancer patient with a previously unknown visceral involvement of Osler-Rendu disease. The patient was admitted to our institution because of newly diagnosed, increasing hepatic lesions occurring during endocrine treatment with aromatase inhibitors. On the basis of ultrasound findings, secondary liver metastases were suspected. After a thorough clinical and imaging examination, we reviewed the literature on typical radiological findings of visceral involvement of Osler-Rendu disease, and the impact of endocrine treatment on arteriovenous malformations. Multislice computed tomography scan identified the hepatic lesions as arteriovenous malformations. In the current literature, there are no reports available on the interaction between aromatase inhibitors and arteriovenous malformations. However, some data do show an effect of endocrine therapy with estrogen/progesterone, or tamoxifen on arteriovenous malformations, although some of the results are partially contradictory. CONCLUSION This case report demonstrates that for undefined hepatic lesions in breast cancer patients, extensive Osler-Rendu disease should be considered as a potential differential diagnosis. Furthermore, we discuss the possible influence of aromatase inhibitors on arteriovenous malformations.
Collapse
Affiliation(s)
- Marco J Battista
- University of Heidelberg, Medical School, Department of Gynecology and Obstetrics, Heidelberg, Germany
| | | | | | | | | |
Collapse
|
|
31
|
Bauditz J, Lochs H. Angiogenesis and vascular malformations: antiangiogenic drugs for treatment of gastrointestinal bleeding. World J Gastroenterol 2008. [PMID: 18023086 DOI: 10.3748/wjg.13.5979] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Treatment of gastrointestinal bleeding in patients with angiodysplasias and Osler's disease (hereditary hemorrhagic teleangiectasia) is clinically challenging. Frequently, vascular malformations occur as multiple disseminated lesions, making local treatment an unfavorable choice or impossible. After local therapy, lesions often recur at other sites of the intestine. However, as there are few therapeutic alternatives, repeated endoscopic coagulations or surgical resections are still performed to prevent recurrent bleeding. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Therefore, new therapeutic strategies are required. Understanding of the pathophysiology of angiogenesis and vascular malformations has recently substantially increased. Currently, multiple inhibitors of angiogenesis are under development for treatment of malignant diseases. Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specific drugs for the treatment of vascular malformations. However, antiangiogenics display significantly different actions and side-effects. Although antiangiogenics like thalidomide seem to inhibit gastrointestinal bleeding, other substances like bevacizumab can cause mucosal bleeding. Therefore differential and cautious evaluation of this therapeutic strategy is necessary.
Collapse
Affiliation(s)
- Juergen Bauditz
- Universitatsklinikum Charite, IV. Medizinische Klinik und Poliklinik, Chariteplatz 1, Berlin 10117, Germany.
| | | |
Collapse
|
|
32
|
Bauditz J, Lochs H. Angiogenesis and vascular malformations: antiangiogenic drugs for treatment of gastrointestinal bleeding. World J Gastroenterol 2008; 13:5979-84. [PMID: 18023086 PMCID: PMC4250877 DOI: 10.3748/wjg.v13.45.5979] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Treatment of gastrointestinal bleeding in patients with angiodysplasias and Osler's disease (hereditary hemorrhagic teleangiectasia) is clinically challenging. Frequently, vascular malformations occur as multiple disseminated lesions, making local treatment an unfavorable choice or impossible. After local therapy, lesions often recur at other sites of the intestine. However, as there are few therapeutic alternatives, repeated endoscopic coagulations or surgical resections are still performed to prevent recurrent bleeding. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Therefore, new therapeutic strategies are required. Understanding of the pathophysiology of angiogenesis and vascular malformations has recently substantially increased. Currently, multiple inhibitors of angiogenesis are under development for treatment of malignant diseases. Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specific drugs for the treatment of vascular malformations. However, antiangiogenics display significantly different actions and side-effects. Although antiangiogenics like thalidomide seem to inhibit gastrointestinal bleeding, other substances like bevacizumab can cause mucosal bleeding. Therefore differential and cautious evaluation of this therapeutic strategy is necessary.
Collapse
Affiliation(s)
- Juergen Bauditz
- Universitatsklinikum Charite, IV. Medizinische Klinik und Poliklinik, Chariteplatz 1, Berlin 10117, Germany.
| | | |
Collapse
|
|
33
|
Angiogenesis and vascular malformations: Antiangiogenic drugs for treatment of gastrointestinal bleeding. World J Gastroenterol 2007; 13:5979-5984. [DOI: 10.3748/wjg.v13.i45.5979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2024] Open
Abstract
Treatment of gastrointestinal bleeding in patients with angiodysplasias and Osler’s disease (hereditary hemorrhagic telangiectasia) is clinically challenging. Frequently, vascular malformations occur as multiple disseminated lesions, making local treatment an unfavorable choice or impossible. After local therapy, lesions often recur at other sites of the intestine. However, as there are few therapeutic alternatives, repeated endoscopic coagulations or surgical resections are still performed to prevent recurrent bleeding. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Therefore, new therapeutic strategies are required. Understanding of the pathophysiology of angiogenesis and vascular malformations has recently substantially increased. Currently, multiple inhibitors of angiogenesis are under development for treatment of malignant diseases. Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specific drugs for the treatment of vascular malformations. However, antiangiogenics display significantly different actions and side-effects. Although antiangiogenics like thalidomide seem to inhibit gastrointestinal bleeding, other substances like bevacizumab can cause mucosal bleeding. Therefore differential and cautious evaluation of this therapeutic strategy is necessary.
Collapse
|
|
34
|
Szilagyi A, Ghali MP. Pharmacological therapy of vascular malformations of the gastrointestinal tract. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2006; 20:171-8. [PMID: 16550261 PMCID: PMC2582970 DOI: 10.1155/2006/859435] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Vascular malformation (AVM) in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone) and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.
Collapse
Affiliation(s)
- Andrew Szilagyi
- Division of Gastroenterology, Department of Medicine, Sir Mortimer B Davis Jewish General Hospital, McGill University School of Medicine, Montreal, Quebec.
| | | |
Collapse
|
|
35
|
Sadick H, Bergler WF, Oulmi-Kagermann J, Naim R, Sadick M, Hörmann K, Riedel F. Estriol induced squamous metaplasia on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia. Arch Med Res 2005; 36:468-73. [PMID: 16099323 DOI: 10.1016/j.arcmed.2005.03.037] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2004] [Accepted: 03/03/2005] [Indexed: 11/23/2022]
Abstract
BACKGROUND The aim of this study was to evaluate by light and electron microscopy the effect of topical estriol on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS Twelve patients were instructed to apply twice daily 0.1% estriol as a nose ointment over a period of 12 months. Written consent was obtained from each patient, allowing biopsy specimens of the nasal mucosa to be taken prior to and 3, 6 and 12 months after estriol application. RESULTS Metaplastic change of the nasal mucosa was observed 6 months after topical estriol application. The former ciliated columnar epithelium changed into a keratinizing squamous epithelium. The effect was reversible after discontinuation of estriol application. CONCLUSIONS For the first time, we could outline the effect of topical estriol on the nasal mucosa. These histomorphological findings, and the fact that estriol is a low-potency metabolite of estradiol, make estriol a valuable agent in the treatment of HHT patients.
Collapse
Affiliation(s)
- Haneen Sadick
- Department of Otolaryngology, Head and Neck Surgery, University Hospital Manheim, Germany.
| | | | | | | | | | | | | |
Collapse
|
|
36
|
Massoud OI, Youssef WI, Mullen KD. Resolution of hereditary hemorrhagic telangiectasia and anemia with prolonged alpha-interferon therapy for chronic hepatitis C. J Clin Gastroenterol 2004; 38:377-9. [PMID: 15087700 DOI: 10.1097/00004836-200404000-00015] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Hereditary hemorrhagic telangiectasia is a group of autosomal dominant disorders, characterized by telangiectases that develop in the skin, mucous membranes, and visceral organs. Currently, there is no satisfactory treatment of hereditary hemorrhagic telangiectasia. Interferon has never been used for the treatment of hereditary hemorrhagic telangiectasia. In this case, we report disappearance of hereditary hemorrhagic telangiectasia lesions after 12 months of treatment with interferon-alpha for chronic hepatitis C. Further studies are warranted to evaluate its role and potential use in the treatment of hereditary hemorrhagic telangiectasia.
Collapse
Affiliation(s)
- Omar I Massoud
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | | | | |
Collapse
|
|
37
|
Jameson JJ, Cave DR. Hormonal and Antihormonal Therapy for Epistaxis in Hereditary Hemorrhagic Telangiectasia. Laryngoscope 2004; 114:705-9. [PMID: 15064628 DOI: 10.1097/00005537-200404000-00021] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES/HYPOTHESIS Objectives were to assess available information on hormonal therapy for bleeding in hereditary hemorrhagic telangiectasia (HHT), to determine whether there is a role for hormonal therapy as an initial therapeutic option, and to report the second known case of response in HHT to antihormonal therapy. STUDY DESIGN Literature review and case report. METHODS The literature on hormonal and antihormonal therapy for HHT was reviewed. Medical records for the case reported in the present study were evaluated to confirm the diagnosis and assess responses to surgical and nonsurgical treatments. RESULTS All reports of success using hormonal therapy for HHT-related bleeding were either retrospective or uncontrolled with the exception of two. Anecdotal evidence with high-dose estrogen appeared to show success, but serious side effects have discouraged use. One controlled trial found no benefit for intermediate dose, single-agent estrogen. The other controlled trial appeared to show benefit with low-dose estrogen-progesterone in HHT with gastrointestinal tract bleeding and was supported by an uncontrolled study showing efficacy in epistaxis. The case reported in the present study demonstrated long-term cessation of epistaxis with tamoxifen in a postmenopausal woman. CONCLUSIONS Systemic estrogen-progesterone at doses used for oral contraception may eliminate bleeding in symptomatic HHT and is a reasonable initial option in fertile women. There is no information on possible effects of lower-dose estrogen-progesterone used in postmenopausal women for hormone replacement therapy. Tamoxifen has dramatically eliminated HHT-related bleeding in two cases. It is well tolerated in postmenopausal women and should be considered for randomized clinical trials.
Collapse
Affiliation(s)
- John J Jameson
- Department of Surgery, Caritas St. Elizabeth's Medical Center of Boston and Tufts University School of Medicine, Boston, Massachusetts, USA.
| | | |
Collapse
|
|
38
|
Sadick H, Naim R, Ramin N, Oulmi J, Hörmann K, Karl H, Bergler W. Plasma surgery and topical estriol: effects on the nasal mucosa and long-term results in patients with Osler's disease. Otolaryngol Head Neck Surg 2003; 129:233-8. [PMID: 12958572 DOI: 10.1016/s0194-5998(03)00361-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
OBJECTIVE The study goal was to report on the long-term results and effect of argon plasma coagulation (APC) surgery and topical estriol in patients with Osler's disease who had recurrent epistaxis. Study design In a prospective clinical study, 52 patients underwent APC and estriol application and were followed for 18 months regarding their bleeding frequency and intensity. Patient blood samples were obtained to determine the serum estriol levels. Scanning electron microscopy of the nasal mucosa enabled a better understanding concerning the effect of estriol on the nasal mucosa. RESULTS Eighteen months after treatment, 96% of the patients stated a significantly reduced bleeding frequency and intensity. Under estriol influence, former berry-like telangiectasia of the nasal mucosa was flatter. The serum estriol levels did not increase significantly in any of the patients. No side effects from the use of topical estriol were observed. CONCLUSION The combined treatment approach with APC and topical estriol significantly reduces epistaxis in Osler's disease. SIGNIFICANCE APC and topical estriol have proved to be a promising alternative in the treatment of Osler's disease.
Collapse
Affiliation(s)
- Haneen Sadick
- Department of Otolaryngology, Head and Neck Surgery, University, Hospital Mannheim, Mannheim, Germany.
| | | | | | | | | | | | | |
Collapse
|
|
39
|
Cheng MW, Madanick RD, Barkin JS. Pharmacologic management of obscure gastrointestinal bleeding. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2003. [DOI: 10.1053/j.tgie.2003.10.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
|
|
40
|
Eroglu Y, Emerick KM, Chou PM, Reynolds M. Gastrointestinal bleeding in Turner's syndrome: a case report and literature review. J Pediatr Gastroenterol Nutr 2002; 35:84-7. [PMID: 12142816 DOI: 10.1097/00005176-200207000-00018] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- Yasemen Eroglu
- Departments of Gastroenterology, Hepatology and Nutrition, Pathology and Surgery, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60614, USA
| | | | | | | |
Collapse
|
|
41
|
Affiliation(s)
- Humphrey Hodgson
- Department of Medicine, Royal Free and University College School of Medicine, London, UK.
| |
Collapse
|
|
42
|
Bergler W, Sadick H, Gotte K, Riedel F, Hörmann K. Topical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia. Ann Otol Rhinol Laryngol 2002; 111:222-8. [PMID: 11913682 DOI: 10.1177/000348940211100306] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The aim of this study was to assess the value of topically applied estrogens in patients with hereditary hemorrhagic telangiectasia. Twenty-six patients with this disorder were treated with argon plasma coagulation and randomized into 2 groups: group A, which had postoperative application of estriol ointment (n = 14), and group B, which had postoperative application of dexpanthenol ointment (n = 12). Over a period of 12 months, the frequency and intensity of bleeding, the patient's satisfaction, and the success of the treatment were evaluated with a questionnaire. Before the operation, more than 90% of the patients in both groups complained of daily episodes of epistaxis. Twelve months after treatment, the frequency and intensity of bleeding had significantly decreased in group A as compared to group B. Of the patients in group A, 93% were satisfied with the treatment. Of the patients in group B, only 42% were satisfied with the treatment. In both groups, more than 90% of the patients were willing to undergo the same treatment again. The combined treatment approach with argon plasma coagulation and topical estriol enables us to significantly prolong the hemorrhage-free interval.
Collapse
Affiliation(s)
- Wolfgang Bergler
- From the Department of Otolaryngology-Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany
| | | | | | | | | |
Collapse
|
|
43
|
Pau H, Carney AS, Murty GE. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): otorhinolaryngological manifestations. CLINICAL OTOLARYNGOLOGY AND ALLIED SCIENCES 2001; 26:93-8. [PMID: 11309047 DOI: 10.1046/j.1365-2273.2001.00442.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder affecting blood vessels of the skin, mucous membrane and viscera. The otorhinolaryngologist is the commonest clinician involved in management as epistaxis occurs in 93% of the patients. As marked advances have recently been made regarding the pathogenesis and management of the condition, the otorhinolaryngological perspective is reviewed.
Collapse
MESH Headings
- Administration, Intranasal
- Administration, Topical
- Chromosome Aberrations/genetics
- Chromosome Disorders
- Chromosomes, Human, Pair 12/genetics
- Chromosomes, Human, Pair 9/genetics
- Embolization, Therapeutic
- Estrogens/administration & dosage
- Estrogens/therapeutic use
- Female
- Gene Expression
- Humans
- Laser Therapy
- Male
- Molecular Biology/methods
- Nasal Mucosa/pathology
- Otorhinolaryngologic Surgical Procedures/methods
- Progesterone/administration & dosage
- Progesterone/therapeutic use
- Telangiectasia, Hereditary Hemorrhagic/genetics
- Telangiectasia, Hereditary Hemorrhagic/pathology
- Telangiectasia, Hereditary Hemorrhagic/therapy
Collapse
Affiliation(s)
- H Pau
- Department of Otorhinolarynogology, Leicester Royal Infirmary, Leicester, UK.
| | | | | |
Collapse
|
|
44
|
Pau H, Carney AS, Walker R, Murty GE. Is oestrogen therapy justified in the treatment of hereditary haemorrhagic telangiectasia: a biochemical evaluation. CLINICAL OTOLARYNGOLOGY AND ALLIED SCIENCES 2000; 25:547-50. [PMID: 11122297 DOI: 10.1046/j.1365-2273.2000.00415.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Systemic and topical oestrogen can provoke squamous metaplasia of epithelium. In Hereditary Haemorrhagic Telangiectasia (HHT) the underlying telangiectasia may be protected from trauma and epistaxis reduced. Oestrogens have been advocated but their efficacy is unclear. Recent advances have now identified two oestrogen and one progesterone receptors. The aim of this study is to analyse the sex receptor status of HHT nasal mucosa to determine if oestrogen therapy is biochemically justified. Five HHT patients (three men, two women) and eight controls (four men, four women) underwent nasal mucosa biopsy. Samples were fixed in formalin and paraffin embedded. Alpha oestrogen (ERalpha) and beta oestrogen (ERss) and progesterone (PgR) receptors were identified using mouse monoclonal antibodies by the Streptavidin-biotin peroxidase method. ERss was detected in two HHT subjects (1 M: 1F) and two control subjects. ERalpha and PgR was absent in HHT subjects. This pilot study demonstrated that a subgroup of HHT patients were ERss positive. Oestrogen therapy therefore has a potential therapeutic role on a biochemical basis in these patients. ERss status should be determined before considering oestrogen therapy.
Collapse
Affiliation(s)
- H Pau
- Department of Otorhinolaryngology, Leicester Royal Infirmary and The Breast Cancer Research Unit, Glenfield General Hospital, Leicester, UK.
| | | | | | | |
Collapse
|
|
45
|
Leach M, Makris M, Hampton KK, Preston FE. Norethisterone therapy for bleeding due to gastrointestinal telangiectases in Glanzmann's thrombasthenia. Br J Haematol 1998; 100:594-6. [PMID: 9504647 DOI: 10.1046/j.1365-2141.1998.00601.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
We report a case of a patient with Glanzmann's thrombasthenia and anti-GPIIb/IIIa alloantibodies who developed life-threatening and intractable bleeding from gastrointestinal telangiectatic lesions. After a period of transfusion-dependent gastrointestinal bleeding despite tranexamic acid, oral iron, omeprazole and platelet transfusions, the use of oral norethisterone produced a significant improvement with a marked reduction in her transfusion requirements.
Collapse
Affiliation(s)
- M Leach
- Department of Haematology, Royal Hallamshire Hospital, Sheffield
| | | | | | | |
Collapse
|
|
46
|
Siple JF, Joseph CL, Pagel KJ, Leigh S. Use of estrogen therapy in a patient with gastrointestinal bleeding secondary to arteriovenous malformations. Ann Pharmacother 1997; 31:1311-4. [PMID: 9391685 DOI: 10.1177/106002809703101107] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE To describe a patient with gastrointestinal (GI) bleeding caused by arteriovenous malformations (AVMs) that was treated with estrogen therapy. CASE SUMMARY A 70-year-old white man was diagnosed with multiple AVMs in the cecum, duodenum, and stomach. Pharmacologic management included the use of ferrous sulfate; however, the patient continued to have recurrent bleeding that required multiple transfusions and endoscopic cauterization. Therapy was initiated with ethinyl estradiol 0.05 mg po qd; no further transfusions have been required for 10 months. DISCUSSION It is estimated that AVMs of the GI tract account for 1-8% of upper GI bleeding episodes and up to 6% of lower GI bleeding episodes. Hormonal agents have been reported to decrease bleeding in patients with both hereditary and acquired AVMs. CONCLUSIONS The role of estrogen therapy in treating AVMs of the GI tract is unclear and supported by only one clinical study.
Collapse
Affiliation(s)
- J F Siple
- Pharmacy Service, Veterans Affairs Medical Center (119-V), Portland, OR 97207, USA
| | | | | | | |
Collapse
|
|
47
|
Affiliation(s)
- A E Guttmacher
- Department of Pediatrics, University of Vermont College of Medicine, Burlington, USA
| | | | | |
Collapse
|
|
48
|
|
|
49
|
Abstract
Bleeding from the small intestine may be difficult to diagnose, because of the organ's length and free intraperitoneal location. Although there is a variety of causes of intestinal bleeding, angiodysplasia is the most common. Several different tests can be used to identify the bleeding site preoperatively or intraoperatively, including enteroscopy.
Collapse
Affiliation(s)
- B S Lewis
- Mount Sinai School of Medicine, New York, New York
| |
Collapse
|
|
50
|
Rebeiz EE, Parks S, Shapshay SM. Management of epistaxis in hereditary hemorrhagic telangiectasia with neodymium: Yttrium-aluminum-garnet laser photocoagulation. ACTA ACUST UNITED AC 1991. [DOI: 10.1016/s1043-1810(10)80052-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
|