Epistaxis Severity Research Articles

Epistaxis in a Pediatric Outpatient Clinic: Could It be an Alarming Sign?

Introduction Epistaxis is a common presentation among children. Objective To investigate the suitability of a simple tool of assessment for patients with epistaxis that could guide in subgrouping those with possible bleeding tendencies who may need further assessment. Methods Children who presented to a tertiary outpatient clinic with epistaxis of an unknown cause were recruited. They underwent thorough clinical assessment and answered the pediatric bleeding questionnaire and the epistaxis severity score. All patients underwent complete blood count as well as coagulation profile, and confirmatory diagnostic tests were performed as needed. Results Among the 30,043 patients who presented to the outpatient clinic over a year, 100 children had epistaxis, with an estimated annual frequency of 1 in 300. A total of 84% of the patients were younger than 12, and nearly half of these were younger than 6 years. Seventy-six patients had recurrent epistaxis, and 12 had systemic comorbidities. A significant higher percentage of patients presented with epistaxis in the hot months of the year. A total of 90% of the patients presented anterior bleeding, and the majority were treated with nasal compression only. Forty-three patients presented with epistaxis only; 37 of them were diagnosed as idiopathic epistaxis, and 6 had local causes. Fifty-seven patients presented with other bleeding manifestations, 47 of whom had a definite bleeding disorder and the other 10 had undiagnosed bleeding tendency. Those with other bleeding manifestations showed a higher frequency of positive family history of epistaxis; of being referred from a primary care physician; of having alarming low platelet count, and of presenting less seasonal variability. A bleeding score ≥ 2 showed significant value in suspecting an underlying systemic pathology as a cause of epistaxis. Conclusion The pediatric bleeding questionnaire is a useful and simple tool in the identification of pediatric patients who need further diagnostic testing to detect any underlying bleeding tendency.

Beneficial Effects of Remote Medical Care for Patients with Hereditary Hemorrhagic Telangiectasia during the COVID-19 Pandemic.

Background: Hereditary hemorrhagic telangiectasia (HHT) needs high-quality care and multidisciplinary management. During the COVID-19 pandemic, most non-urgent clinical activities for HHT outpatients were suspended. We conducted an analytical observational cohort study to evaluate whether medical and psychological support, provided through remote consultation during the COVID-19 pandemic, could reduce the complications of HHT. Methods: A structured regimen of remote consultations, conducted by either video-calls, telephone calls, or e-mails, was provided by a multidisciplinary group of physicians to a set of patients of our HHT center. The outcomes considered were: number of emergency room visits/hospitalizations, need of blood transfusions, need of iron supplementation, worsening of epistaxis, and psychological status. Results: The study included 45 patients who received remote assistance for a total of eight months. During this period, 9 patients required emergency room visits, 6 needed blood transfusions, and 24 needed iron supplementation. This was not different from what was registered among the same 45 patients in the same period of the previous year. Remote care also resulted in better management of epistaxis and improved quality of life, with the mean epistaxis severity score and the Euro-Quality of Life-Visual Analogue Scale that were significantly better at the end than at the beginning of the study. Discussion: Remote medical care might be a valid support for HHT subjects during periods of suspended outpatient surveillance, like the COVID-19 pandemic.

Evaluating the efficacy of Achillea Millefolium ointment in the treatment of recurrent idiopathic epistaxis; a randomized double-blind clinical trial

Epistaxis is one of the most common reasons for patient referral to ear, nose and throat (ENT) clinics and reported to involve 60 % of the total population. This study aimed to evaluate the efficacy of Achillea Millefolium ointment in the treatment of recurrent idiopathic epistaxis. In this randomized, double-blind, placebo-controlled, trial, fifty patients with idiopathic recurrent epistaxis completed the study. Full initial assessments and coagulation tests were performed prior to the study. The patients were randomly divided into two groups of case and control and received "Vitamin A and Achillea Ointment" or "Vitamin A and Placebo ointment" on alternate days respectively (Vitamin A ointment on day 1 and Achillea or Placebo ointment on the next day) for 10 days. Nasal examinations and coagulation tests were carried out on day 10 and patients were visited at the end of first and third month following treatment initiation. The amount of bleeding was recorded by Epistaxis Severity Score (ESS) before and after the intervention (10th Day, 1st and 3rd Month). There was no significant difference in frequency and duration of bleeding between two groups on day 10 (p = 0.105). However, a significant reduction in frequency and duration of bleeding was seen in the case group in the first and third month follow-up (p < 0.001). No complications were reported during the treatment in the case group. This study indicated that Achillea ointment 1% was effective in decreasing ESS and duration of bleeding in patients with recurrent idiopathic epistaxis with no detectable side effects.

Effects of bevacizumab on familial epistaxis caused by hereditary hemorrhagic telangiectasia

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

Classification of endonasal HHT lesions using digital microscopy

BackgroundRecurrent spontaneous epistaxis is the most common clinical manifestation and the most debilitating symptom in hereditary haemorrhagic telangiectasia (HHT) patients. To this date, there exist only a classification of HHT patients by different genetic mutations. There is no standard classification for the mucocutaneous endonasal manifestations of HHT. The aim of the present study was to document the variety of endonasal HHT lesions using digital microscopy and to propose a clinical classification.MethodsWe recorded the endonasal HHT lesions of 28 patients using a digital microscope. We reconstructed the 3D images und videos recorded by digital microscope afterwards and classified the endonasal lesions of HHT in two classes: Grade A, presence of only flat telangiectasias in the mucosa level and Grade B, (additional) presence of raised berry or wart-like telangiectasia spots. We investigated also Haemoglobin level by routine laboratory procedures, plasma VEGF level by ELISA, Severity of epistaxis by epistaxis severity score (ESS) and quality of life by a linear visual analogue scale (VAS).ResultsWe found a higher quality of life and a lower severity of epistaxis in Grade A patients in comparison to Grade B patients. No difference in plasma VEGF level and in Haemoglobin between Grad A patients and Grade B patients could be detected. Plasma VEGF levels showed no gender specific differences. It could also not be correlated to the extranasal manifestation.ConclusionThe classification for endonasal manifestation of HHT proposed in this study indicates severity of epistaxis und quality of life. Digital microscopy with the ability of 3D reconstruction of images presents a useful tool for such classifications. The classification of endonasal HHT lesions using digital microscopy allows to evaluate the dynamic of HHT lesions in the course of time independent of examiner. This allows also to evaluate the efficacy of the different treatment modalities by dynamic of HHT lesions. Moreover digital microscopy is very beneficial in academic teaching of rare diseases.

Weekly epistaxis duration as an indicator of epistaxis severity in hereditary hemorrhagic telangiectasia-Preliminary results from a randomized controlled trial.

ObjectivesThere is great interest in developing and studying novel therapies for epistaxis in hereditary hemorrhagic telangiectasia (HHT) given its associated morbidity and impact on patients' quality of life. Several recent randomized controlled trials (RCTs) have been negative, likely attributed to poorly characterized outcome measures. This study reported on and evaluated an epistaxis outcome measure, weekly epistaxis duration (WED) in an ongoing RCT, with the aim of better characterizing the measurement of epistaxis for clinical trials.Materials and methodsPatients were recruited to an ongoing phase II, double‐blind, cross‐over RCTs of oral doxycycline for HHT‐associated epistaxis. Patients were included for the epistaxis measures analysis if they had already completed the initial 3‐month run‐in period, and had received treatment of either study drug doxycycline or placebo for a minimum of 6 months. The primary measure of interest was patient‐reported outcome (PRO)‐WED, captured from prospective daily diaries. Epistaxis severity score (ESS) was collected as a secondary outcome.ResultsSeven patients were included for analysis, with 98% completion of the daily diary. The average PRO‐WED across all patients was 85.0 minutes, SD 93.2 at baseline, and 65.6 minutes, SD 59.5 during treatment/placebo. Coefficient of variance for PRO‐WED at baseline and during treatment/placebo was 0.49, SD 0.1 and 0.58, SD 0.2, respectively. Statistically significant changes in the mean PRO‐WED from baseline to treatment/placebo was noted in six patients (86%). Only two patients (29%) had a significant change in ESS, with both reporting decreased (improved) scores after treatment/placebo as compared to baseline.ConclusionsPRO‐WED was a feasible clinical trials measure, was reasonably stable during baseline measurement, and appeared to be variable with treatment state, suggesting it may provide a sensitive clinical trials PRO in HHT.

A comparative study of two grading systems for epistaxis in hereditary haemorrhagic telangiectasia.

Different institutions use different grading systems for hereditary haemorrhagic telangiectasia (HHT)-associated epistaxis. It is important to have a universal, standardized grading system to compare and evaluate the effectiveness of different treatment options. We introduced the "Intensity, Frequency and need for Blood Transfusion" (IFT) grading system for HHT-associated epistaxis in 2008. Hoag et al. proposed the "Epistaxis Severity Score" (ESS) for the International HHT foundation in 2010. This study aimed to evaluate the potential correlation between the ESS and IFT grading systems. The study included 354 simultaneous reports using the IFT and ESS from 106 patients. The correlation between the ESS, IFT and haemoglobin levels was measured using Pearson's correlation coefficient. The ESS and IFT were scored simultaneously by the patient and doctor in 48 cases to evaluate if there was a discrepancy in the scoring applied by either set of responders. The measured correlation between the two grading systems was good (0.75). The grade of epistaxis reported by patients and doctors respectively showed no significant difference. Both the IFT and ESS grading systems correlate significantly to the haemoglobin level. Both the IFT and ESS scores correlate to each other, and their results are comparable. Whether the IFT or ESS scoring was performed by the patient or doctor had no significant impact.

For nasotracheal intubation, which nostril results in less epistaxis: right or left?: A systematic review and meta-analysis.

Nasotracheal intubation is usually required in patients undergoing oromaxillofacial, otolaryngological or plastic surgery to prevent the airway encroaching into the operating field. Epistaxis is the most common complication, but which nostril is associated with a lower incidence and severity of epistaxis is still unclear. When both nostrils are patent, to determine the preferred nostril for nasotracheal intubation under general anaesthesia. A systematic review and meta-analysis of randomised controlled trials (RCTs). The primary outcome was the incidence of epistaxis and the secondary outcomes included the incidence of severe epistaxis, the time required to pass the tube through the nasal passage and total intubation time. PubMed, Embase and the Cochrane Register of Controlled Trials were searched from database inception to 1 March 2020. The only studies included were RCTs comparing epistaxis related to nasotracheal intubation via right or left nostril, in adult surgery patients undergoing general anaesthesia. Ten RCTs with 1658 patients were included. Compared with the left nostril, intubation via the right nostril was associated with a significantly lower incidence of epistaxis: risk ratio (RR) and 95% confidence intervals (CI) were 0.78 (0.62 to 0.99), P = 0.04: a lower incidence of severe epistaxis (five studies, n=923), RR 0.40 (0.22 to 0.75), P = 0.004: and a shorter intubation time (three studies, n=345), mean difference -7.28 (-14.40 to -0.16) seconds, P = 0.05. In two studies (n=310), no significant difference between the right and left nostril was observed in the time to pass the tube through the nasal passages, mean difference -0.59 (-1.95 to 0.77) s, P = 0.40. On the basis of the current available evidence, when both nostrils are patent, the right nostril is more appropriate for nasotracheal intubation, with a lower incidence and severity of epistaxis and faster intubation time. The study protocol has been registered in PROSPERO (CRD42020169949).

The Impact of Traditional Anticoagulants, Novel Anticoagulants, and Antiplatelets on Epistaxis.

Anticoagulant and antiplatelet medications (ACAP) are known to be associated with an increased risk for epistaxis. There are conflicting results regarding the impact of Novel Oral Anticoagulants (NOAC) on epistaxis and its severity. Retrospective chart review of patients who were admitted to the ED in our tertiary level hospital with a diagnosis of epistaxis during the years 2012 to 2018. Retrospective analysis of patients presenting to tertiary level emergency otolaryngological care during the years 2012 to 2018. The impact of various ACAP medications on epistaxis severity, hospital admission, and recurrence was analyzed. A total of 470 patients were identified. Two hundred and twenty-nine patients (49%), were not on any anticoagulant/antiplatelet (ACAP) medications (controls) and 241 patients (51%) were taking at least one ACAP medication (ACAP group). Patients in the ACAP group were at a higher risk for severe epistaxis (OR=1.8, P < .05) and were more likely to be hospitalized (OR=2.17, P < .05). Surprisingly, the risk for recurrence was similar in the ACAP and control groups (15%, P > .05). Compared to controls, Warfarin and Enoxaparin increased the overall risk for severe epistaxis (OR=4.4, P < .05) and for hospital admission (OR=2.1, P < .05). Specifically, an increased risk for posterior tamponade (OR=19, P < .001), significant blood loss (OR=4.4, P=.032), and blood transfusion (OR=4.7, P=.007) were identified as well. Interestingly, NOACs were not associated with increased risk for severe epistaxis, hospital admission, tamponade, and significant blood loss or blood transfusion compared to controls. Compared to older generation anticoagulants and antiplatelet medications, NOACs demonstrated an improved safety profile, in terms of epistaxis severity, need for hospital admission and outcomes. These results may suggest a more conservative approach and less hospitalization when treating epistaxis in patients receiving NOACs. 4 Laryngoscope, 131:1946-1951, 2021.

Role of hypertension in epistaxis

Background: The aim of the study was to study the role of hypertension in patients hospitalized for serious epistaxis. Methodology: This is a retrospective study conducted over duration of 2 years from August 2014 to July 2016 over 140 patients hospitalized for serious epistaxis. Epistaxis was classified into serious and severe type. The following parameters were recorded: age, gender, blood pressure recordings, patients in whom blood pressure is difficult to control, duration of hospital stay, history of hypertension, severity of epistaxis, including medical and/or surgical management, medications affecting clotting.Results: Mean age of our patients was 52 years, 55% of the patients had a history of hypertension. There was no statistically significant difference between patients with a history of epistaxis in the two groups (with or without a history of hypertension). There was no statistical significance between blood pressure recordings on admission between the two groups. The severity of hypertension was also not associated with severe epistaxis versus serious epistaxis.Conclusion: Hypertension does not appear to be causal factor of serious epistaxis.

Costs Associated with Recurrent Epistaxis in a Patient with a Ventricular Assist Device

Mucosal bleeding is a well-known complication of having a ventricular assist device and commonly presents with epistaxis. Although the frequency of epistaxis as a complication in patients with a ventricular assist device has been documented in the literature, to our knowledge the cost of this complication has not been reported. This case report examines the financial burden of ventricular assist device-associated epistaxis in a single patient from September 2018 to December 2019 using ICD 10 diagnostic codes. The patient was found to have accumulated $138,020 in costs over 38 encounters. This case report not only highlights the recurrent nature and potential high cost of epistaxis in this patient population, but also identifies a target to reduce healthcare spending. Further research is needed to assess whether cheap and simple preventative measures such as nasal hygiene regimen can decrease the frequency and/or severity of epistaxis in the patients with a ventricular assist device.

The clinical and genetic features of hereditary haemorrhagic telangiectasia (HHT) in central South Africa-three novel pathogenic variants.

Hereditary haemorrhagic telangiectasia (HHT) is supposedly rare in Africa, with only three pathogenic variants documented to date. We describe the clinical and genetic features of HHT patients in central South Africa, who fulfilled the Curaçao criteria. Sixteen patients (median age 38.5years, range 12-65years), from six families were included. Fifteen patients were of African descent and one was of Afrikaner descent. The mean epistaxis severity score was 3.18, and the median haemoglobin was 9.5g/dL (range 3.5-13.5g/dL). On transthoracic contrast echocardiography 69% had a shunt grade ≥ 1, but only 20% had pulmonary arteriovenous malformations (AVMs) on computed tomography of the chest. Hepatic AVMs were found in 13% of patients, while 13% had brain vascular malformations. Four patients were HIV positive, of whom two had worsening epistaxis while they had opportunistic infections and poor HIV control. We identified six pathogenic variants (four in ENG and two in ACVRL1) in the six probands, three of which had been described previously. Three variants have apparently not been reported previously: ENG c.[1336_1337dup];[ =] p.[(Asp446fs)];[( =)], ENG c.[ 690?_816+?del] p.[(?)], and ACVRL1 c.[268_274delins57];[ =] p.[(Cys90fs)];[( =)]. We confirmed the diagnosis of HHT in sixteen patients and identified pathogenic variants in ENG or ACVRL1 in all six probands in central South Africa, where HHT has been underreported. We describe three pathogenic variants: two of ENG and one of ACVRL1. We will be able to implement pre-symptomatic screening of patients in our area, and improve their management.

Development and Validation of the Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia (NOSE HHT)

Epistaxis is the greatest cause of morbidity in patients with hereditary hemorrhagic telangiectasia (HHT); because of this, a validated epistaxis-specific quality-of-life instrument for HHT should be made available. To develop and validate an epistaxis-specific quality-of-life patient-reported outcome measure for HHT. This survey study focused on the development and validation of the Nasal Outcome Score for Epistaxis (NOSE) in HTT (NOSE HHT) outcome measure with data prospectively collected from December 10, 2019, to March 15, 2020. A total of 401 patients were recruited from within the Cure Hemorrhagic Telangiectasia online patient advocacy social media network, the Washington University HHT Center of Excellence, and a randomized clinical trial investigating an intranasal timolol gel for HHT-associated epistaxis. Face and content validity, factor analysis, internal consistency as measured through Cronbach α, construct validity, responsiveness to change, and minimal clinically important difference. The NOSE HHT was developed and validated with a possible score ranging discretely from 0 to 4 for each of the 29 items and a total score ranging continuously from 0 to 4 after dividing by the total number of items answered. A total of 401 participants completed the NOSE HHT. Factor analysis identified 3 factors that matched the a priori specified subgroups of particular aspects of life affected by HHT-associated epistaxis: physical problems (mean [SD] magnitude, 1.59 [0.83]), functional limitations (mean [SD] magnitude, 1.28 [0.84]), and emotional consequences (mean [SD] magnitude, 1.95 [1.02]). The instrument had high internal consistency with an overall Cronbach α of 0.960. Convergent validity determined the total NOSE HHT score to be a strong predictor of disease severity; total NOSE HHT score can be split up into the following epistaxis severity categories: mild (0-1), moderate (1.01-2), and severe (>2). The instrument was found to be sensitive to change, and the minimal clinically important difference for the total NOSE HHT score was 0.46. Evaluation of the consistency, reliability, and responsiveness of the NOSE HHT survey found it to be a valid instrument to assess severity and change in epistaxis. Study results suggest that the NOSE HHT survey is clinically applicable and useful as an outcome measure of future HHT-associated epistaxis trials.

Topical Propranolol Improves Epistaxis Control in Hereditary Hemorrhagic Telangiectasia (HHT): A Randomized Double-Blind Placebo-Controlled Trial.

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (−2.03 ± 1.7 as compared with −0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (−1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

Efficacy of Timolol in a Novel Intranasal Thermosensitive Gel for Hereditary Hemorrhagic Telangiectasia–Associated Epistaxis

Other than nasal moisturizers, no standard-of-care medical therapy exists for epistaxis in hereditary hemorrhagic telangiectasia (HHT). With epistaxis as the greatest cause of morbidity in patients with HHT, there is a need to identify effective topical therapies. To determine the efficacy and safety of an intranasal timolol thermosensitive gel vs placebo thermosensitive gel in treating HHT-associated epistaxis. This double-blind, placebo-controlled randomized clinical trial was conducted from October 29, 2019, to May 20, 2020, at a tertiary care center. A total of 27 patients with HHT and moderate-to-severe epistaxis were recruited and included in this prespecified analysis: 14 in the timolol group and 13 in the placebo group. Inclusion criteria included (1) age 18 years or older, (2) clinical or genetic diagnosis of HHT, (3) screening Epistaxis Severity Score (ESS) of 4 or greater and 2 or more nosebleeds cumulatively lasting at least 5 minutes per week, (4) stable epistaxis pattern over the preceding 3 months, and (5) no change in epistaxis treatment or nasal hygiene regimen in the preceding month. Exclusion criteria included (1) contraindications to systemic β-blocker administration, (2) use of medications interacting with timolol, (3) use of antiangiogenic medications in the last month before recruitment, and (4) use of anticoagulants, antiplatelets, or fibrinolytic therapies within the last month. Novel thermosensitive intranasal timolol (0.1%) gel vs placebo thermosensitive gel applied twice daily to each nostril for 8 weeks. The primary outcome was the median change in ESS and percentage of participants reaching the minimal clinically important difference in ESS. Secondary outcomes were changes in Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores, Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia, and hemoglobin level. Of 27 participants randomized (median [range] age, 55 [20-76] years; 14 women [52%]; 25 White [93%]), a total of 23 patients with HHT completed the primary outcome measure. Within the timolol gel and placebo gel groups, respectively, the median change (range) in ESS was 2.32 (0.22 to 5.97) vs 1.96 (-0.91 to 5.98), and 9 of 11 (82%) vs 9 of 12 (75%) participants experienced a clinically meaningful improvement in ESS. Twenty-two of the 23 participants (96%) reported improvement via the Clinical Global Impression-Improvement score, with 81% vs 58% of participants reporting reduced severity of epistaxis in the timolol vs placebo group, respectively. Of participants completing the Nasal Outcome Score for Epistaxis in HHT at follow-up visit, 7 of 10 (70%) in the timolol group achieved a clinically important difference vs 5 of 10 (50%) in the placebo group. There was no change in hemoglobin level between or within groups. Zero participants in the placebo group and 2 of 13 (15%) in the timolol group withdrew because of adverse events. Thermosensitive gel, alone or in combination with timolol, was highly effective in reducing HHT-associated epistaxis. The timolol group had greater improvement in epistaxis and quality of life than the placebo group, but effect estimates were imprecise, and no definitive conclusions on the superiority of timolol can be drawn. Physicians treating patients with HHT-associated epistaxis should consider a thermosensitive gel (with or without timolol) for their patients. ClinicalTrials.gov Identifier: NCT04139018.

Association of Hypertension With the Risk and Severity of Epistaxis

The association between hypertension and epistaxis has long been a subject of debate. To evaluate the risk of epistaxis in patients with hypertension using a nationwide population cohort and to assess the association of hypertension with the methods of managing cases of epistaxis. In this retrospective cohort study, a hypertension cohort and comparison cohort were built using the Korean National Health Insurance Service-National Sample Cohort that represents the entire population of the Republic of Korea from January 1, 2002, to December 31, 2015. The hypertension cohort comprised 35 749 patients with a record of 3 or more prescriptions of antihypertensive medication and a diagnosis of hypertension (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code I10). Patients with other diseases associated with epistaxis, such as sinonasal tumors, facial trauma, bleeding tendency, and coagulation disorder, as well as those taking anticoagulant medications, were excluded. A comparison cohort comprised 35 749 individuals without hypertension matched sociodemographically in a 1:1 ratio. Statistical analysis was performed from January 1, 2019, to March 31, 2020. The incidence and recurrence of epistaxis were evaluated in both cohorts. The risk factors for epistaxis and management strategies were also assessed. Among the 35 749 patients in the hypertension cohort (20 579 men [57.6%]; median age, 52 years [interquartile range, 45-62 years]) the incidence rate (IR) of epistaxis was 32.97 per 10 000 persons (95% CI, 30.57-35.51 per 10 000 persons); among the 35 749 individuals in the comparison cohort (20 910 men [58.5%]; median age, 52 years [interquartile range, 45-62 years]), the IR of epistaxis was 22.76 per 10 000 persons (95% CI, 20.78-24.89 per 10 000 persons) (IR ratio, 1.45; 95% CI, 1.29-1.63; adjusted hazard ratio, 1.47; 95% CI, 1.30-1.66). The IR of recurrent epistaxis was 1.96 per 10 000 persons in the hypertension cohort and 1.59 per 10 000 persons in the nonhypertension cohort (IR ratio, 1.23; 95% CI, 0.77-2.00). Patients with hypertension who experienced epistaxis were more likely to use the emergency department (odds ratio, 2.69; 95% CI, 1.70-4.25; Cohen h effect size, 0.27; 95% CI, 0.16-0.39) and receive posterior nasal packing (odds ratio, 4.58; 95% CI, 1.03-20.38; Cohen h effect size, 0.15; 95% CI, 0.03-0.26) compared with the comparison cohort. This study suggests that patients with hypertension had an increased risk of epistaxis requiring hospital visits. In addition, epistaxis in patients with hypertension appeared to need more emergency department visits and require more posterior nasal packing procedures compared with patients without hypertension. Medical counseling about epistaxis is advisable for individuals with hypertension, and the presence of hypertension should be considered in managing nasal bleedings.

An international, multicenter study of intravenous bevacizumab for bleeding in hereditary hemorrhagic telangiectasia: the InHIBIT-Bleed study.

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.

Integration of clinical parameters, genotype and epistaxis severity score to guide treatment for hereditary hemorrhagic telangiectasia associated bleeding

BackgroundHereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited disorder characterized by development of mucocutaneous telangiectases and visceral organ arteriovenous malformations, which can lead to recurrent, spontaneous bleeding and development of iron deficiency anemia. The primary objective of this study was to ascertain the relationship between epistaxis severity scores (ESS), laboratory values, genotype, and phenotype in HHT. Our secondary objective was to assess efficacy of systemic antifibrinolytic therapy in reducing ESS in HHT.MethodologyWe conducted a retrospective review of patients seen at the UNC HHT Center from January 1, 2009 to February 28, 2015. ESS, demographics, and results of genetic testing were abstracted from the medical record. Response to antifibrinolytic therapy was evaluated by comparing pre-post ESS.ResultsOne hundred and forty nine patients were eligible with 116 having genetic testing and 33 without. Age, hemoglobin and ferritin levels were predictive of ESS. Of the 116 patients that underwent genetic testing: 63 had an ACVRL1 mutation, 40 had an ENG mutation, 2 had a SMAD4 mutation, and 11 patients had no pathologic HHT genetic variation detected. Compared to patients without a detectable HHT-associated genetic variation, patients with a HHT-associated genetic variation had higher ESS scores (p < 0.05). Neither ESS nor genotype was predictive of pulmonary or brain AVMs. Twenty-four HHT patients with ESS > 4 were started on antifibrinolytic therapy (tranexamic acid or aminocaproic acid) and had a post-treatment ESS recorded. All patients had a decrease in ESS of > 0.71 (minimal meaningful difference), but patients taking antifibrinolytics displayed larger decreases. No patients on antifibrinolytics experienced a VTE with median follow up of 13 months.ConclusionsWe demonstrate that the ESS correlates with age, hemoglobin and ferritin. Additionally, we demonstrate that HHT patients with genetic mutations have higher ESS scores. Our data demonstrate that antifibrinolytics are effective in decreasing epistaxis severity and safe with long-term use in HHT patients.

FID Score: an effective tool in Hereditary Haemorrhagic Telangiectasia - related epistaxis.

Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia and epistaxis, that is the most common cause of disability and social impairment. Patient management strictly depends on the severity of this symptom; therefore, it is of paramount importance for the clinicians to effectively grade epistaxis severity. The aim of this report was to validate the Frequency, Intensity and Duration score (FID) for grading epistaxis severity in patients with HHT; we studied repeatability and external validity comparing FID score with Epistaxis Severity Score (ESS). This is a descriptive, observational study that included 264 adult HHT patients with epistaxis. Diagnosis of HHT was established with Curacao criteria or positivity at genetic testing. Nosebleed severity was evaluated according to the FID score and the ESS. The first 30 patients were included in the validation of the FID score, which was graded on days 0, 1, 3 and 7. In the remaining 234 patients, a comparison between the ESS and FID score was performed. The statistical analysis performed in order to validate the FID score showed very good agreement between scores calculated on different days; analysis comparing the FID score with the ESS revealed a high correlation between the two grading systems. The FID score is a quick, easy and precise tool for evaluating HHT-related epistaxis and could be a possible alternative to the ESS. The FID score meets the need for an intuitive and smart grading system that is easy to manage in clinicians’ hands.

Evaluation of Nasal Mucociliary Clearance, Nasal Obstruction Symptom Evaluation, and Epistaxis Severity Score in Isotretinoin Treatment.

The study aims to investigate the possible side effects of isotretinoin use on the nasal mucosa with objective methods in the treatment of acne vulgaris. Before the treatment, nasal mucociliary clearance time (MCT) was measured in all patients. Also all patients were asked to complete the questionnaires about the nasal dryness (visual analog scale [VAS]), nasal obstruction (Nasal Obstruction Symptom Evaluation [NOSE]), and presence of epistaxis (Epistaxis Severity Score [ESS]). Both MCT and questionnaires were reevaluated in patients who completed the treatment. The results of 101 patients were evaluated. Before treatment, mean duration of nasal mucociliary clearance (NMC) was 9.55 ± 1.30 minutes, nasal dryness (VAS) value was 2.7 ± 0.7, NOSE score was 2.1 ± 1.1, and ESS score was 1.2 ± 0.7; after treatment, the duration of NMC was 13.80 ± 2.29 minutes, VAS value was 3.3 ± 1.1, NOSE score was 3.2 ± 1.3, and ESS score was 2.1 ± 1.2 (P = .018, .150, .027, .011, respectively). The nasal mucosa is adversely affected in patients due to regular use of isotretinoin in the acne treatment, anamnesis should be checked in all nasal surgeries, and routine ear nose throat control should be recommended for these patients.