Polidocanol sclerotherapy in Hereditary Hemorrhagic Teleangiectasia patients – outpatient and emergency visits in a retrospective view

Polidocanol sclerotherapy in Hereditary Hemorrhagic Teleangiectasia patients – outpatient and emergency visits in a retrospective view | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 22 January 2025 V1 Latest version Share on Polidocanol sclerotherapy in Hereditary Hemorrhagic Teleangiectasia patients – outpatient and emergency visits in a retrospective view Authors : ELSA-LEEA KOTOLA , Johanna Wikstén 0000-0001-9722-805X [email protected] , and EEVA CASTRÉN Authors Info & Affiliations https://doi.org/10.22541/au.173757938.86808975/v1 214 views 116 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract ABSTRACT INTRUDUCTION: Hereditary Hemorrhagic Telangiectasia (HHT) is an inherited condition causing mucosal telangiectasia and visceral arteriovenous malformations. Troublesome nosebleeds affect almost all HHT patients. Different treatments to control nosebleeds have been applied, but no clear consensus exists on the most effective one. Sclerotherapy with polidocanol is one option and previous studies have reported promising results. However, no data on the effect of sclerotherapy on epistaxis-related visits and procedures exists. The aim of our study was to investigate the impact of polidocanol sclerotherapy on epistaxis-related emergency department and outpatient visits and emergency procedures in HHT patients. MATERIAL AND METHODS: We retrospectively collected data on Helsinki University Hospital’s HHT-patients receiving polidocanol sclerotherapy. We analyzed the number of outpatient and emergency department visits in our Otorhinolaryngology unit as well as measures to control the nosebleeds, especially emergency operating room procedures. We compared the number of visits and procedures before and after initiating polidocanol sclerotherapy. RESULTS: Of the 145 HHT patients identified, 29 HHT patients received polidocanol sclerotherapy in our unit and had sufficient follow-up data. The number of emergency department visits on average per year increased from 0.21 to 0.32 and the number of outpatient visits changed from 1.30 to 1.64 after initiation of sclerotherapy. No statistically significant changes were observed. Emergency operating room procedures were not observed during the study period in this patient group. CONCLUSION: Previous studies have shown sclerotherapy to decrease the severity of nosebleeds in HHT patients. However, we did not observe changes in the numbers of epistaxis-related visits before and after initiation sclerotherapy. More studies are needed to assess the efficacy of sclerotherapy for HHT-related nosebleeds. Keywords: osler, epistaxis, nose bleed, injection, lauromacrogol ABSTRACT INTRUDUCTION: Hereditary Hemorrhagic Telangiectasia (HHT) is an inherited condition causing mucosal telangiectasia and visceral arteriovenous malformations. Troublesome nosebleeds affect almost all HHT patients. Different treatments to control nosebleeds have been applied, but no clear consensus exists on the most effective one. Sclerotherapy with polidocanol is one option and previous studies have reported promising results. However, no data on the effect of sclerotherapy on epistaxis-related visits and procedures exists. The aim of our study was to investigate the impact of polidocanol sclerotherapy on epistaxis-related emergency department and outpatient visits and emergency procedures in HHT patients. MATERIAL AND METHODS: We retrospectively collected data on Helsinki University Hospital’s HHT-patients receiving polidocanol sclerotherapy. We analyzed the number of outpatient and emergency department visits in our Otorhinolaryngology unit as well as measures to control the nosebleeds, especially emergency operating room procedures. We compared the number of visits and procedures before and after initiating polidocanol sclerotherapy. RESULTS: Of the 145 HHT patients identified, 29 HHT patients received polidocanol sclerotherapy in our unit and had sufficient follow-up data. The number of emergency department visits on average per year increased from 0.21 to 0.32 and the number of outpatient visits changed from 1.30 to 1.64 after initiation of sclerotherapy. No statistically significant changes were observed. Emergency operating room procedures were not observed during the study period in this patient group. CONCLUSION: Previous studies have shown sclerotherapy to decrease the severity of nosebleeds in HHT patients. However, we did not observe changes in the numbers of epistaxis-related visits before and after initiation sclerotherapy. More studies are needed to assess the efficacy of sclerotherapy for HHT-related nosebleeds. Keywords: osler, epistaxis, nose bleed, injection, lauromacrogol Abbreviations: Hereditary hemorrhagic telangiectasia (HHT), operating room (OR), transforming growth factor (TGF), Helsinki University Hospital (HUH) Key points • Hereditary hemorrhagic telangiectasia is rare disease • Novel treatment options for HHT exist • Regular treatment improves the quality of life of the patients but does not necessarily disminish hospital visits INTRODUCTION Hereditary hemorrhagic telangiectasia (HHT), also known as Osler’s disease is a rare inherited disease with an incidence of 1 in 5000, but it is believed to be underdiagnosed. (1) HHT is characterized by the presence of vascular malformations, such as telangiectasias in the nasal and gastric mucosa and arteriovenous malformations in the lungs, brain, and liver. (2) All known gene defects underlying the disease are related to the endothelial transforming growth factor (TGF) beta family. Mutations in several genes have been recognized to cause HHT and its different phenotypes. (3, 4) Mutations in genes of the TGF-beta family signaling pathway in HHT patients lead to unregulated vessel wall regeneration in mucous membranes and internal organs, which leads to a prolonged activation phase of angiogenesis. This results in markedly dilated and tortuous postcapillary veins that continue to enlarge and eventually join the dilated arteries via capillaries. As the size of the vascular lesion increases, the capillary segments disappear, and a direct arterial-venous connection is formed. (5, 6) The diagnosis of HHT is based on the Curaco criteria, which include recurrent epistaxis, telangiectasias of the skin and mucosa, visceral arteriovenous malformations and positive family history for HHT. (7) Troublesome nosebleeds are the most common symptom of HHT, and they impair the patients quality of life the most. (8) The nosebleeds are caused by ruptured telangiectasias of the nasal mucosa, which in severe cases lead to frequent emergency room visits, hospital stays, anemia and blood transfusions. Symptoms often become more severe with age. (8) Numerous different treatments have been applied for HHT-related epistaxis to reduce nosebleed episodes and improve the patients’ quality of life. There is still no curative treatment for HHT, and the options to control epistaxis are either topical agents, systemic medical treatment or locally invasive procedures on the nasal mucosa. (9, 10) Nosebleeds have traditionally been treated with cauterization, septodermoplasty, or even nasal closure. Also vessel embolization has been an option. These larger traditional operations require operation room (OR) with personnel, as do severe bleedings, which may unfortunately occur outside office hours. Currently, sclerotherapy has shown promising results to control epistaxis in HHT patients. (8, 11) Polidocanol, also known as lauromacgrol 400, is the most used sclerosant. (12) Polidocanol is a stable compound at room temperature with low viscosity and require only nasal local anesthesia. It results to secondary thrombosis without necrosis of the surrounding healthy tissues when injected into the intralumen, submucosa, or subperichondrium. (11) Polidocanol sclerotherapy has been shown to relieve the frequency and severity of epistaxis, reduce anemia and the need for blood transfusions, and improve the quality of life. Polidocanol treatments have not been found to cause any serious complications. (11, 13) However, the effect of sclerotherapy for HHT patients on the number of hospital visits is not known. The objection of this study was to explore, whether polidocanol sclerotherapy has an effect on the number of epistaxis-related emergency room and outpatient visits and on the need of emergency operating room procedures. METHODS We did a database search from Helsinki University Hospital (HUH)’s electronic patient registry using ICD-10 code for HHT (I78.0), and also searched for HHT patients from our hospital’s registry for rare diseases during our observation period, spanning from 2003 to 2021, to identify all HHT-patients in our area. Demographic and HHT-related data was collected. We selected those HHT-patients, who had received polidocanol sclerotherapy at HUH’s Otorhinolaryngology department and had a follow-up period of minimum three years before and one year after the year the sclerotherapy was initiated. For these patients, all emergency and outpatients visits to our department, and all procedures to control epistaxis in our unit were registered. Also, data on possible procedures requiring OR was collected. The data was analyzed using SPSS statistical package for social sciences, 28.0 version. The study protocol was accepted by the local ethics committee. RESULTS In our patient registry and in the registry of rare diseases in our hospital district, we found a total of 145 HHT patients. Out of these patients, 116 were excluded from the study according to the criteria in Figure 1. Finally, the study included 29 patients. The demographic information of HHT patients as well as the genotype and organ manifestations of the disease are presented in Table 1. The average age of the patients in the dataset was 65 years (range 28-90 years). Figure 1 Figure 1. Flow chart of the patient selection Table 1. Sex Male 11 (38 %) Female 18 (62 %) Age group (years) 20-39 3 (10 %) 40-59 6 (21 %) 60-79 17 (59 %) 80 + 3 (10 %) Gene mutation ACVRL1 10 (34 %) ENG 3 (10 %) Unknown / not tested 16 (55 %) HHT organ manifestations Epistaxis 29 (100 %) Pulmonary AVM 12 (41 %) Brain AVM 0 (0 %) Liver AVM 5 (17 %) GI tract 8 (26 %) Skin and mucosal telangectasia 20 (69 %) Table 1. Demographic and HHT-related data. Polidocanol injection treatments were initiated in our unit in 2015. Around 3-10 new patients were treated yearly. In total, there were approximately 30 injection visits per year. Patients received polidocanol injections on average 7.45 times (range 1 to 35). The total number of polidocanol treatment sessions during the observation period was 216. Outpatient Visits and Emergency Department The average annual number of outpatient visits per patient during the study period before the initiation of polidocanol sclerotherapy was 1.30, and 1.64 respectively during the post-treatment period. After the initiation of polidocanol sclerotherapy, ten patients experienced a decrease in outpatient visits, while eight patients experienced an increase. However, the overall number of visits increased when examining the changes in median averages. Statistically, the result was not significant (p = 0.192). During the period before the initiation of polidocanol sclerotherapy, the average annual number of emergency department visits per patient was 0.21. The highest average number of visits per year for a single patient was 1.33. In total, eight patients had emergency department visits before the start of injection therapy. In the post-polidocanol injection period, patients visited the emergency department on average of 0.32 times per year. The highest number of visits per patient averaged 2.67 per year. Emergency department visits decreased for four patients, while they increased for eight patients. Seventeen patients showed no change in the number of emergency department visits. Overall, emergency department visits increased when considering median averages. However, when comparing medians using the Wilcoxon-signed rank test, the result was not statistically significant (p = 0.384). Interventions to control epistaxis Procedures utilized during outpatient visits for nosebleed prevention in our unit include laser therapy, bipolar cauterization, silver nitrate cauterization, and polidocanol sclerotherapy. Among these, polidocanol sclerotherapy and laser therapy were the most used. Emergency department procedures included bipolar cauterization, laser cauterization, silver nitrate cauterization, nasal packing, and polidocanol injections. Nasal artery embolization occurred only once during the observed period and silver nitrate cauterization was used 16 times during the observed period. No procedures requiring OR were observed during the follow-up period. No statistically significant change in different intervention modalities was seen before and after initiation of polidocanol sclerotherapy (Figure 2.). Medical treatments were not examined in this study. Figure 2. Figure 2. The distribution of the number of procedures 3 years before and 1 to 3 years after the year that sclerotherapy was initiated. The number of follow-up years depends on when the sclerotherapy was initiated. The number of procedures indicates the average number of procedures per year for a given patient. DISCUSSION Treating epistaxis in HHT patients is demanding and no clear consensus exists on the best method. Here, we study for the first time the effect of polidocanol sclerotherapy on epistaxis-related visits in HHT patients. Our study did not demonstrate significant changes in the quantities of emergency department visits, outpatient visits, or different procedures before and after the initiation of polidocanol sclerotherapy. The advantage of polidocanol sclerotherapy is that it can be performed in an outpatient setting under local anesthesia and it is considered well tolerated and minimally invasive for the patient. Polidocanol sclerotherapy is considered cost-effective as it mainly does not require OR or general anesthesia. Previous studies have shown that polidocanol can reduce the frequency and severity of nosebleeds in HHT patients, as well as improve their quality of life. (11, 13) Morais et al. observed that nosebleed frequency and severity decreased in 95% of cases without significant side effects. Their study included 45 patients with a 15-year follow-up period. In Marcos et al.’s study, polidocanol sclerotherapy significantly reduced the frequency and severity of nosebleeds: the Epistaxis Severity Score decreased from 6.23 ± 2.3 to 1.64 ± 1.6. Both studies also demonstrated an improvement in quality of life. A recent systematic review on sclerotherapy for HHT showed positive yet limited data on the efficacy of sclerotherapy: only seven studies and a total of 196 patients were included (14). All studies reported improvement in epistaxis, but the lack of uniform reporting measures precluded the analysis. The studies in this review did not report effects on the number of emergency visits. The impact of polidocanol injection therapy on the quantities of emergency department visits, outpatient visits, and other procedures to control epistaxis has not been previously investigated. Especially emergency department visits and emergency OR procedures put a significant strain on our health care system, and therefore it is an important factor when assessing efficacy of a novel treatment modality. Overall, emergency department visits and outpatient visits in our study somewhat increased but neither result was statistically significant. Therefore, the reduction in nosebleed severity and frequency demonstrated in previous studies did not clearly reflect in our results. However, our clinical observation is that many HHT patients tend to struggle with nosebleeds alone without seeking medical help. After initiating sclerotherapy with a continuous care relationship to our unit, HHT patients may have sought more easily help from us also in acute epistaxis. Moreover, HHT-related epistaxis tends to aggravate with age, which may affect our results. Our study has some limitations mainly due to the retrospective study setting. First, our patient number was relatively low, mostly due to insufficient follow-up data. Second, some HHT patients started receiving polidocanol sclerotherapy late during our study period, and therefore the post-sclerotherapy follow-up period was relatively short. Third, due to technical reasons, we did not have access to epistaxis-related primary health care emergency visits of our HHT cohort. To determine the impact of polidocanol sclerotherapy on the number on epistaxis-related emergency department visits, larger studies and longer follow-up are needed. HHT-related epistaxis in emergency setting is always demanding to treat, and therefore it is crucial to find best methods to prevent emergency situations. The authors have no conflicts of interests to declare References 1. Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD, et al. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet. 2011;48(2):73-87. 2. Pierucci P, Lenato GM, Suppressa P, Lastella P, Triggiani V, Valerio R, et al. A long diagnostic delay in patients with Hereditary Haemorrhagic Telangiectasia: a questionnaire-based retrospective study. Orphanet J Rare Dis. 2012;7:33. 3. Wooderchak-Donahue WL, McDonald J, O’Fallon B, Upton PD, Li W, Roman BL, et al. BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia. Am J Hum Genet. 2013;93(3):530-7. 4. Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, et al. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet. 2004;363(9412):852-9. 5. Haubner F, Schneider A, Schinke H, Bertlich M, Weiss BG, Canis M, Kashani F. Classification of endonasal HHT lesions using digital microscopy. Orphanet J Rare Dis. 2021;16(1):182. 6. Braverman IM, Keh A, Jacobson BS. Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia. J Invest Dermatol. 1990;95(4):422-7. 7. Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000;91(1):66-7. 8. OS AA, Friedman CM, White RI, Jr. The natural history of epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope. 1991;101(9):977-80. 9. Numminen J, Taulu R. [Osler’s disease or hereditary hemorrhagic telangiectasia]. Duodecim. 2012;128(6):590-7. 10. Chin CJ, Rotenberg BW, Witterick IJ. Epistaxis in hereditary hemorrhagic telangiectasia: an evidence based review of surgical management. Journal of Otolaryngology - Head & Neck Surgery. 2016;45(1):3. 11. Morais D, Millás T, Zarrabeitia R, Botella LM, Almaraz A. Local sclerotherapy with polydocanol (Aethoxysklerol®) for the treatment of Epistaxis in Rendu-Osler-Weber or Hereditary Hemorrhagic Telangiectasia (HHT): 15 years of experience. Rhinology. 2012;50(1):80-6. 12. Doganci S, Yildirim V, Erol G, Yesildal F, Karabacak K, Kadan M, et al. Polidocanol (Lauromacrogol 400) has anti-angiogenic effects in vitro and in vivo. Eur Rev Med Pharmacol Sci. 2016;20(7):1384-9. 13. Marcos S, Botella LM, Albiñana V, Arbia A, de Rosales AM. Sclerotherapy on Demand with Polidocanol to Treat HHT Nosebleeds. J Clin Med. 2021;10(17). 14. Thiele B, Abdel-Aty Y, Marks L, Lal D, Marino M. Sclerotherapy for Hereditary Hemorrhagic Telangiectasia-Related Epistaxis: A Systematic Review. Ann Otol Rhinol Laryngol. 2023 Jan;132(1):82-90. doi: 10.1177/00034894221078075. Epub 2022 Feb 12. PMID: 35152768. Information & Authors Information Version history V1 Version 1 22 January 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations ELSA-LEEA KOTOLA Helsinki University Press View all articles by this author Johanna Wikstén 0000-0001-9722-805X [email protected] HUS-yhtyma View all articles by this author EEVA CASTRÉN HUS-yhtyma View all articles by this author Metrics & Citations Metrics Article Usage 214 views 116 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation ELSA-LEEA KOTOLA, Johanna Wikstén, EEVA CASTRÉN. 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