遗传性出血性毛细血管扩张症1例

遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasis,HHT)是一种常染色体显性遗传的出血性疾病,临床上主要表现为全身或局部毛细血管扩张和同一部位反复自发性出血,以鼻出血最为常见。本文对HHT伴鼻出血1例进行报道。     

遗传性出血性毛细血管扩张症1例

遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasis,HHT)是一种常染色体显性遗传的出血性疾病,临床上主要表现为全身或局部毛细血管扩张和同一部位反复自发性出血,以鼻出血最为常见。本文对HHT伴鼻出血1例进行报道。     

遗传性出血性毛细血管扩张症8例及相关文献复习

遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasia,HHT),又称为Olser-Weber-Rendu综合征,是一种常染色体显性遗传疾病,其典型临床表现为反复鼻出血、黏膜皮肤毛细血管扩张、内脏动静脉血管畸形.目前已报道的发病率为1/5000[1].鼻出血是HHT最常见...     

遗传性出血性毛细血管扩张症

遗传性出血性毛细血管扩张症(hereditary hemorrhagictelangiectasia,HHT)又称Osler Ren du Weber综合征。1865年Babington报道第1例HHT患者,Rendu1896年提出遗传为家族性出血及毛细血管扩张的原因,后被Osler(1901)及We ber(1907)证实。HHT为一常染色体显性遗传性疾病,在各个种     

遗传性出血性毛细血管扩张症1例及家系报告

患者,男,47岁。因左侧鼻腔反复出血1个月于2009年11月入院。     

遗传性出血性毛细血管扩张症一家系调查

遗传性出血性毛细血管扩张症是一种少见的遗传性毛细血管发育异常所致的出血性疾病.我院收治的一家系16例成员中罹患本病者6例,现报告如下.     

遗传性出血性毛细血管扩张症致严重鼻出血的早期基因诊断

目的:探讨遗传性出血性毛细血管扩张症(HHT)致严重鼻出血的早期基因诊断。方法:对2个HHT家系共23例成员进行详细的临床检查及评估,提取外周静脉血DNA,聚合酶链反应扩增目的基因ENG和ACVRL-1,测序并进行序列分析,判断突变的致病性。结果:NMG-1家系采集到静脉血标本的11例中有6例携带ACVRL-1基因的错义突变c.263A>G。GD-2家系采集到静脉血标本的12例中有5例携带ACVRL-1基因的错义突变c.199C>G。有鼻出血病史者突变基因检出率为100%,无鼻出血者史突变基因检出率为25%。结论:基因诊断极高的灵敏度和特异性在HHT早期诊断中具有重要的应用价值,可成为临床常规检测项目。     

遗传性出血性毛细血管扩张症的诊断

目的总结遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasis,HHT)病例,提高临床诊断水平。方法回顾本组5例HHT患者,通过症状、体征以及腹部B彩超发现HHT的典型特征,结合家族史信息,参照国际诊断标准确诊HHT。结果 5例患者中男性3例,女性2例,年龄31～73岁,中位数年龄72岁,3例有家族史,2例为散发病例,符合典型症状体征,腹部彩超发现肝脏和脾脏异常血管改变。结论 HHT的诊断应该综合症状、体征以及腹部彩超等辅助检查。     

遗传性出血性毛细血管扩张症病例表型和基因型分析[论著]

目的　分析遗传性出血性毛细血管扩张症（hereditary hemorrhagic telangiectasia,HHT）患者的临床症状和基因突变,探讨基因检测和遗传咨询对疾病诊断和预防中的应用。方法　收集2例HHT患者的病例资料及外周血样本,应用PCR扩增-测序方法对该病相关的 ENG、ACVRL1、SMAD4和BMP9 基因全部编码区进行序列分析。结果　2例HHT病例均具有反复的鼻出血、皮肤黏膜毛细血管扩张。F1病例具有家族史,F2病例具有肺动脉高压,鼻出血严重程度分析发现年龄大的F2病例较F1病例鼻出血严重程度量表epistaxis severity score,ESS）评分高。基因检测发现,2例患者均携带ACVRL1 基因的c.1135G>A（p.Glu379Lys）突变。F1病例的家系成员基因检测发现Ⅲ：2携带c.1135G>A突变,该个体具有反复鼻出血和皮肤黏膜毛细血管扩张明确诊断;无症状的Ⅳ：1和Ⅳ：2为野生型,排除诊断。结论　来源于不同家系的具有相同突变的2例HHT表型具有相似性,为HHT的临床分型奠定基础;F1病例家系成员的病史调查和基因检测结果肯定了基因筛查和遗传咨询在HHT早期诊断中的作用,为HHT基因检测和遗传咨询的应用提供了理论依据和实践基础。     

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.     

Outcome of septal dermoplasty in patients with hereditary hemorrhagic telangiectasia

OBJECTIVES/HYPOTHESIS: Septal dermoplasty has been recommended as the treatment of choice for life-threatening epistaxis in patients with hereditary hemorrhagic telangiectasia. The purpose of the study was to evaluate the effectiveness and outcomes of septal dermoplasty for management of transfusion-dependent epistaxis. STUDY DESIGN: Retrospective study. METHODS: Between 1994 and 2004, septal dermoplasty was performed on 67 consecutive patients with severe epistaxis attributable to hereditary hemorrhagic telangiectasia. The numbers of units of blood received 1 year before and 1 year after septal dermoplasty were obtained. A subjective appraisal of the results of the surgery as well as second procedures after septal dermoplasty was determined. Patients were screened for pulmonary and cerebral arteriovenous malformations, gastrointestinal tract bleeding, and symptomatic liver disease. RESULTS: Data were obtained in 66 of 67 (98%) patients with a mean age of 61.5 years (mean follow-up, 3.9 y). Accurate transfusion requirements 1 year before and 1 year after septal dermoplasty were available in 32 of 66 (48%) patients. In these 32 patients, the mean units of blood received decreased from 21 units (range, 2-100 units) 1 year before septal dermoplasty to 1 unit (range, 0-10 units) in the year after septal dermoplasty (P < .001). Improved quality of life was claimed in 57 patients. Second therapies, ranging from cautery to repeat partial septal dermoplasty, were required in 15 patients during follow-up. Among the 67 patients, 31 (46%) had pulmonary arteriovenous malformation, 14 (21%) had gastrointestinal tract bleeding, 7 (10%) had symptomatic liver disease, and 5 (7%) had cerebral arteriovenous malformation. During the follow-up, 14 patients died of other complications of hereditary hemorrhagic telangiectasia (11 patients) and unrelated causes (3 patients). CONCLUSION: Septal dermoplasty remains an effective way of reducing transfusion requirements in patients with hereditary hemorrhagic telangiectasia and subjectively improves their quality of life. The otolaryngologist caring for patients with hereditary hemorrhagic telangiectasia should be familiar with other organ involvement by hereditary hemorrhagic telangiectasia to prevent complications during surgery.     

The value of screening for multiple arterio-venous malformations in hereditary hemorrhagic telangiectasia: a diagnostic study

Occult visceral arterio-venous malformations (AVMs) may be a constant threat to patients suffering from hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome (M. ROW). HHT patients predominantly become symptomatic through chronic, recurrent epistaxis, a symptom that can alert physicians at an early stage of the disease. The purpose of this study was to investigate whether occult, visceral arterio-venous malformations could be detected by screening imaging studies in patients suffering from HHT. In a comprehensive diagnostic study, Rendu-Osler-Weber patients were examined for potential visceral arterio-venous malformations by physical examination and non-invasive imaging techniques. The Department of Otolaryngology of the Philipps University of Marburg is a major referral center and coordinated the screening procedures. Thirty-five individuals with the presumed diagnosis of HHT gave informed consent to the screening investigations. Eighteen of 35 individuals were found to suffer from visceral vascular malformations; most of the AVMs were diagnosed in the lung, but also the liver, spleen, brain and eyes were affected. Six patients could be treated preventively by arterial embolization for AVMs of the lung, liver and brain. Comprehensive screening for occult AVMs in HHT patients seems to be justified to avert potential complications in this group of patients.     

Nasal dermoplasty for Japanese hereditary hemorrhagic telangiectasia

OBJECTIVE: While generally considered an effective treatment for moderate to severe epistaxis in hereditary hemorrhagic telangiectasia (HHT), nasal dermoplasty (ND) has not been well established in Japan. This prompted the present Japanese assessment of clinical efficacy and patient satisfaction following this procedure. METHODS: Retrospective analysis of clinical records of 15 patients with HHT undergoing ND between August 1991 and May 2004 and survey of these patients as to postsurgical conditions. Main outcome measures were skin graft "take" frequency after surgery (all patients), reported patient satisfaction (eight recent patients), and reported volume and frequency of epistaxis after versus before surgery (eight recent patients). RESULTS: Graft take rate was 100%. Most patients experienced reduced frequency and volume of bleeding. One patient required an additional operation, total closure of the external nares, 2 years later. Overall patients felt satisfied with ND, experiencing less nasal obstruction than expected. CONCLUSIONS: ND is effective in Japanese patients with moderate and severe nasal bleeding from HHT, reducing their risk of bleeding.