Intranasal topical estrogen in the management of epistaxis in hereditary hemorrhagic telangiectasia

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.     

The natural history of epistaxis in hereditary hemorrhagic telangiectasia

The purpose of this retrospective study is to document the natural history of epistaxis in patients with hereditary hemorrhagic telangiectasia. A telephone questionnaire was administered to 73 patients who had been previously screened for pulmonary arteriovenous malformations (PAVMs). The incidence of epistaxis in this population was 93%, with a mean onset age of epistaxis of 12 years, a mean frequency of bleeding of 18 episodes per month, and a mean duration of bleeding of 7.5 minutes. More than 90% of patients experienced the onset of epistaxis before the age of 21 and symptoms were progressive with age. There were no differences in the age of onset, frequency of epistaxis, or duration of epistaxis between patients with PAVMs versus those without PAVMs. Although the natural history of epistaxis does not predict the presence or absence of pulmonary arteriovenous malformations, epistaxis is an early marker of the disease, hereditary hemorrhagic telangiectasia, and might guide screening for pulmonary and cerebral arteriovenous malformations in children of affected parents.     

A treatment algorithm for the management of epistaxis in hereditary hemorrhagic telangiectasia.

We examined the management options used for epistaxis of varying severity in patients with hereditary hemorrhagic telangiectasia (HHT) to develop a treatment algorithm. Fifty patients with HHT were studied from 1991 to 1997 to consider various treatment options and their relative efficacy. There were 28 females and 22 men; their ages ranged from 15 to 85. Follow-up ranged from 6 months to 6 years. A wide variety of treatments had been used (including various forms of cautery, septal surgery, topical and systemic hormones, antifibrinolytic therapy, arterial ligation, laser therapy, and closure of the nostrils). Treatments used during the follow-up period were argon laser therapy (40), systemic estrogen or progesterone (17), septodermoplasty (12), or closure of the nostrils (14). Patients were divided into those with mild to moderate disease (requiring one or no blood transfusions during the course of their illness) and those with severe disease (requiring more than one blood transfusion). Using this broad categorization, those with mild to moderate disease did well with sequential argon laser therapy with or without the adjunct of septodermoplasty or hormone therapy. Those with severe disease did not find argon laser therapy beneficial but found their epistaxis completely stopped with closure of the nasal cavities. Based on these findings, a simple treatment algorithm defines the optimum treatment options for epistaxis in this difficult-to-treat group of patients.     

Hormonal and antihormonal therapy for epistaxis in hereditary hemorrhagic telangiectasia

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.     

Validation of epistaxis severity score for hereditary hemorrhagic telangiectasia in Japan

ObjectiveThis study aimed to assess the health-related QoL (HR-QoL) of patients with hereditary hemorrhagic telangiectasia (HHT), with emphasis on the role/social aspects, and validate the Japanese version of the epistaxis severity score (ESS) in these patients.MethodsThe Japanese version of the ESS was created through forward and reverse translation, and consultation with the original author. A validation analysis was performed by comparing ESS severity with the invasiveness of previous treatments for epistaxis and assessing the correlation between the ESS and HR-QoL. Medical history forms, ESS questionnaires, and the Medical Outcomes Study Short Form 36 (SF-36) were distributed to participants with HHT in August 2020. The relation between the ESS and summary scores of SF-36 was assessed by performing analysis of variance and Spearman's correlation.ResultsIn total, 73 participants were included in this study. The average ESS was 5.02; there were mild (32.9%), moderate (45.2%), and severe (21.9%) epistaxis groups. Patients with higher ESS received a significantly more invasive treatment (Fisher's exact test, p < 0.05). The ESS was also negatively correlated with the physical component score (PCS) (r = -0.489, p < 0.001). Comorbid liver and gastrointestinal arteriovenous malformations significantly reduced the PCS (p < 0.05). Multiple regression analysis revealed that the ESS was a significant variable (p < 0.01). The role/social component score was significantly lower in the severe ESS group than in the mild or moderate group.ConclusionThe Japanese version of the ESS was considered valid and may be useful as an outcome measure of future HHT-associated epistaxis trials in Japan.     

The effect of treatment for epistaxis secondary to hereditary hemorrhagic telangiectasia

BACKGROUND: Epistaxis is the most common symptom in patients with hereditary hemorrhagic telangiectasia. Different treatment options have been described but with little reference to their effect on quality of life or disease severity. METHODS: This study prospectively investigated the effect of nasal closure, argon laser, and a combination of septodermoplasty and argon laser treatments on quality-of-life scores and disease severity ratings in a group of 29 patients with moderate to severe epistaxis referred to a tertiary referral center. RESULTS: The only group of patients who showed a significant improvement (p < 0.05) in quality of life were those who underwent nasal closure. In addition, the nasal closure patients were the only group in which there was a complete cessation of bleeding. CONCLUSION: Nasal closure should be offered to patients with moderate to severe epistaxis secondary to hereditary hemorrhagic telangiectasia that has proved unresponsive to other treatment.     

贝伐珠单抗治疗遗传性出血性毛细血管扩张症所致家族性鼻出血的疗效观察北大核心CSCD

目的： 观察贝伐珠单抗治疗遗传性出血性毛细血管扩张症（hereditary hemorrhagic telangiectasia,HHT）所致家族性鼻出血的临床效果。 方法： 回顾性分析2016年12月至2019年12月期间于北京安贞医院、解放军总医院第一医学中心和滨州医学院附属滨州市中心医院接受静脉滴注贝伐珠单抗治疗的27例HHT所致家族性鼻出血患者的相关资料,其中男性14例,女性13例,年龄（55.3±11.2）岁。按5 mg/kg体重计算贝伐珠单抗剂量,观察第一次用贝伐珠单抗治疗1个月后的疗效。用视觉模拟量表（VAS）对比治疗前后患者全身症状自我评分;用鼻出血严重程度量表（epistaxis severity score,ESS）对治疗前后患者的6个问题（鼻出血频率、持续时间、出血强度、治疗需求、是否贫血、是否输血）进行对比分析;对比治疗前后患者的血红蛋白水平变化情况。采用SPSS 20.0统计软件处理数据。 结果： 第一次贝伐珠单抗治疗1个月后,27例患者中22例自诉鼻出血严重程度明显改善,5例自诉治疗效果不显著,治疗有效率81.5%（22/27）。用药效果显著的22例患者疗效维持时间5～24个月,中位时间11.23个月。全身症状VAS评分较治疗前明显下降,差异有统计学意义［（2.41±2.55）分比（8.19±1.47）分,t=9.708,P<0.01］。ESS的6个问题的得分及ESS标准化评分较治疗前均明显下降［鼻出血频率（1.78±1.22）分比（3.44±0.80）分,t=6.814,P<0.01;出血持续时间（0.85±0.91）分比（3.00±0.73）分,t=8.845,P<0.01;出血强度（0.19±0.40）分比（1.00±0.00）分,t=10.696,P<0.01;治疗需求（0.22±0.42）分比（1.00±0.00）分,t=9.539,P<0.01;是否贫血（0.41±0.50）分比（0.89±0.32）分,t=4.914,P<0.01;是否输血（0.11±0.32）分比（0.41±0.50）分,t=3.309,P<0.01;ESS标准化评分（2.50±2.45）分比（7.60±1.30）分,t=9.344,P<0.01］。治疗后血红蛋白水平较治疗前明显提高,差异有统计学意义［（105.48±24.31） g/L比（73.07±23.71） g/L,t=6.864,P<0.01］。27例患者中HHT1型（ENG基因）8例,HHT2型（ACVRL1基因）19例;药物应用后鼻出血改善持续时间前者为（4.76±5.12）个月,后者为（7.60±10.84）个月,后者长于前者,但差异无统计学意义（P>0.05）。治疗前后ESS评分在两组基因型患者中的差异无统计学意义（P>0.05）。第一次用药治疗后2例女性患者出现停经,所有患者均未出现其他不良反应。 结论： 贝伐珠单抗静脉滴注治疗HHT所致家族性鼻出血疗效显著、安全性高。.;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.     

Treatment of epistaxis in hereditary hemorrhagic telangiectasia patients by argon plasma coagulation with local anesthesia

BACKGROUND: Recurrent epistaxis is the most common manifestation of hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to determine the role and efficacy of argon plasma coagulation (APC) in the management of epistaxis caused by HHT. METHODS: From 1997 to 2004, 43 patients with diagnosed HHT were treated for recurrent epistaxis with APC in our department. RESULTS: Thirty-six patients reported substantial reduction of bleeding after treatment. Of the 18 patients who previously needed blood transfusions, 13 reported substantial reduction of bleeding after treatment and no blood transfusions were necessary. CONCLUSION: APC allows a control of epistaxis in HHT patients and guarantees a long time free from blood transfusions. This treatment modality can be performed with local anesthesia, is not invasive, is well tolerated, is inexpensive, and can be used as a first step even in patients who need to undergo several blood transfusions for their epistaxis.