Mucosal Telangiectasia Research Articles

Genetic analysis of a family with hereditary hemorrhagic telangiectasia caused by endoglin gene mutation

Objective: To explore the genetic characteristics of a family with hereditary hemorrhagic telangiectasia (HHT) caused by endoglin (ENG) gene mutations. Methods: A total of 17 individuals from a 3-generation HHT family attending the First Affiliated Hospital of Dali University were selected as the research subjects. Clinical data and familial disease status of the HHT family proband were collected. Whole exome sequencing technology was used to screen for suspected pathogenic genes in the proband, and Sanger sequencing was used for family validation. Results: The proband and her mother had recurrent epistaxis and skin mucosal telangiectasia, and enhanced CT scans of the chest of the proband and her mother, daughter, and cousin indicated the presence of varying degrees of pulmonary arteriovenous malformations. The results of the full exon sequencing results showed that the proband carried the ENG gene c.579_599del non-shift deletion mutation, and Sanger sequencing showed that the mother, daughter, and cousin carried the same mutation. Conclusion: ENG gene c.579_ 599del mutation may be the genetic basis of HHT in this family.

Identifying racial disparities in hereditary hemorrhagic telangiectasia

BackgroundHereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis (nose bleeds), mucosal telangiectasias (spider veins), and arteriovenous malformations. Although HHT affects all racial groups, few...

Management of epistaxis in hereditary haemorrhagic telangiectasia (HHT) patients using pulsed dye laser and the effect of withholding treatment during the COVID pandemic.

Using a patient survey, pulsed dye laser (PDL) treatment of epistaxis for hereditary haemorrhagic telangiectasia (HHT) patients was evaluated after initial referral. Subsequently, due to the COVID pandemic, a natural experimental set-up allowed assessment of an enforced withdrawal of treatment. A total of 34 subjects were identified as undergoing PDL for HHT-related epistaxis. They were surveyed to look at the effectiveness of PDL treatment after initial referral and at the effect of delay to treatment during COVID on epistaxis and the associated quality of life. The survey also examined the comparison to other available treatments. Retrospective pre-COVID Epistaxis Severity Scores (ESS) were compared to post-COVID data to assess the effect of treatment withdrawal. The patients were then followed up after resumption of their treatment to assess the ensuing change in ESS. After initial referral, frequency and severity of epistaxis decreased. Fifty-six percent of patients experienced several bleeds per day before treatment, compared to 12% after. 88% of patients had episodes of epistaxis longer than 5min, which was halved to 44% after treatment. Average ESS pre-COVID was 4.42 compared to 5.43 post-COVID delay, with a significant statistical difference (p = 0.02). On resumption of treatment, average ESS reduced to below pre-COVID levels at 4.39 after only 2 sessions. Seventy-six percent of patients found that withdrawal of PDL during COVID diminished their quality of life. PDL treatment of nasal mucosal telangiectasia reduces the frequency and duration of epistaxis. The ESS is reduced following treatment with PDL and quality of life subjectively improved.

Sclerotherapy for Hereditary Hemorrhagic Telangiectasia-Related Epistaxis: A Systematic Review.

Hereditary hemorrhagic telangiectasia (HHT) is a common inherited condition characterized by mucosal telangiectasias, recurrent epistaxis, and arteriovenous malformations. HHT results in detriment to quality of life. Morbidity and mortality result from severe anemia. Conventional interventions for HHT-related epistaxis include nasal packing, diathermy, lasers, coblation, microdebridement, bevacizumab (topical and systemic), as well as septodermoplasty and nasal closure. Sclerotherapy has been recently described in the literature as a novel approach to HHT-related epistaxis. We hypothesize that sclerotherapy is an effective treatment for HHT-related epistaxis and improves upon the current standard of care for this disease. A systematic review was conducted to study sclerotherapy for treating HHT-related epistaxis. Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science were searched. Articles were evaluated and excluded according to PRISMA guidelines and reviewed by 2 authors. Reported variables included number of injections, months of follow up, changes in Epistaxis Severity Score, previous treatments used to control epistaxis, and post-injection side effects. Seven studies with a total of 196 patients met inclusion criteria. Three studies reported significant improvement as measured by the Epistaxis Severity Score scale. One reported improvement through subjective patient surveys and others used the Bergler-Sadick scale to measure frequency and intensity of epistaxis. All studies reported improvement in HHT-related epistaxis. The lack of uniform reporting measures however precluded formal meta-analysis. Based on limited data, sclerotherapy appears to be effective for treating HHT-related epistaxis and offers promise for treating this recalcitrant condition. However, larger, prospective, multi-centered studies using universally validated instruments for epistaxis are needed to definitively evaluate outcomes from sclerotherapy.

Ischemic cholangitis during Osler-Weber-Rendu disease: a case report

BackgroundOsler-Weber-Rendu disease (OWRD) is a rare autosomal dominant genetic disease that causes skin and mucosal telangiectasias and visceral arteriovenous malformations. These shunts can lead to high-output heart failure, portal hypertension, biliary or mesenteric ischemia. We report the case of a patient with OWRD complicated by ischemic cholangitis and biloma.Case presentationA 50-year-old female patient with personal history of spontaneous epistaxis and gingival bleeding, family history of Osler-Weber-Rendu disease (OWRD) in mother, and epistaxis in siblings. She consulted for intermittent and minimal biliary colic. Physical exam found mucocutaneous telangiectasia. Abdominal Doppler ultrasound/CT angiography showed arteriovenous shunts in the liver between hepatic artery and hepatic vein, hepatic artery and portal vein. Other sites of arteriovenous malformations were found in the nostril and jejunum. The diagnosis of OWRD was made. The evolution after 1 year was marked by the appearance of a slight anicteric cholestasis. MRCP found intrahepatic bilomas with associated ischemic cholangitis of segment VII. We decided to continue monitoring only.ConclusionThe management of OWRD is based on screening for visceral arteriovenous malformations and on symptomatic measures that are often disappointing. Ischemic cholangitis is a rare complication, the diagnosis is based on imaging, liver transplantation is the only therapeutic alternative in this cases.

Clinical Practice Guideline: Nosebleed (Epistaxis).

ObjectiveNosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the majority of nosebleeds are limited in severity a...

Clinical Practice Guideline: Nosebleed (Epistaxis) Executive Summary.

ObjectiveNosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the great majority of nosebleeds are limited in seve...

Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Bi-allelic Loss of ENG or ACVRL1

Hereditary hemorrhagic telangiectasia (HHT) is a Mendelian disease characterized by vascular malformations (VMs) including visceral arteriovenous malformations and mucosal telangiectasia. HHT is caused by loss-of-function (LoF) mutations in one of three genes, ENG, ACVRL1, or SMAD4, and is inherited as an autosomal-dominant condition. Intriguingly, the constitutional mutation causing HHT is present throughout the body, yet the multiple VMs in individuals with HHT occur focally, rather than manifesting as a systemic vascular defect. This disconnect between genotype and phenotype suggests that a local event is necessary for the development of VMs. We investigated the hypothesis that local somatic mutations seed the formation HHT-related telangiectasia in a genetic two-hit mechanism. We identified low-frequency somatic mutations in 9/19 telangiectasia through the use of next-generation sequencing. We established phase for seven of nine samples, which confirms that the germline and somatic mutations in all seven samples exist in trans configuration; this is consistent with a genetic two-hit mechanism. These combined data suggest that bi-allelic loss of ENG or ACVRL1 may be a required event in the development of telangiectasia, and that rather than haploinsufficiency, VMs in HHT are caused by a Knudsonian two-hit mechanism.

Overview of Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia

Pulmonary arteriovenous malformations (PAVMs) are rare and commonly caused by an autosomal dominant disorder known as hereditary hemorrhagic telangiectasia (HHT). HHT is an often-missed vascular disorder causing symptoms of epistaxis, mucosal telangiectasia, AVMs, hemoptysis, dyspnea, and iron deficiency anemia. Large AVMs in the lungs, liver, and brain can be life-threatening. Early diagnosis and intervention are imperative to prevent serious complications of massive hemoptysis, stroke, cerebral abscess, and gastrointestinal bleeding. This case study of an incidental finding of a PAVM on routine chest-ray proves to be a life-saving event for a young African American woman with undiagnosed HHT.

Possibilities of using dendritic cell vaccine in treatment of radiation injury of the bladder

Background . Radiation therapy for patients with cervical and endometrial cancer is often associated with the development of radiation cystitis which is treated mainly symptomatically. Objective was the rationale for dendritic cell vaccines in the treatment of the bladder damage after radiation therapy. Materials and methods . The treatment effectiveness of late radiation damage to the bladder in 26 oncogynecologic patients after chemoradiotherapy was analyzed in the article. Results . The effectiveness of 25.000.000 autologous dendritic cells vaccine introduced into all the tops of the rhombus of Michaelis for 5 cycles with 2-week intervals was proved. Mucosal erosions, ulcerous defects and telangiectasia during dendritic cell therapy were managed in 100, 81.8 and 78.6 % of cases, respectively, while in control — in 66.7, 50 and 30 % of cases, respectively (p <0.05). One of the mechanisms of action of dendritic cell vaccines in the treatment of radiation injuries may comprise a high phenotypic plasticity of dendritic cells and macrophages and their ability to regulate inflammatory and anti-inflammatory functions and regenerate and repair damaged tissues. Conclusion . The results of treatment for radiation cystitis resistant to the standard anti-inflammatory therapies demonstrate the obvious benefits of immunotherapy.

Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia, embolization, and Young’s procedure: oral surgical management

Hereditary hemorrhagic telangiectasia (HHT) case with history of embolization and Young’s procedure: surgical management. Introduction: Osler–Weber–Rendu disease hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular dysplasia. It causes hemorrhagic manifestations, cutaneous and mucosal telangiectasia and visceral vascular shunts, which sometimes lead to brain abscesses after dental avulsion. Acute epistaxis can be managed by vascular ligature or selective embolization. In rare cases, management can even go as far as nasal closure. Observation: A case of five dental avulsions is described, in a patient affected by HHT who previously underwent a bilateral embolization in the area of the facial artery as well as Young’s procedure for frequent epistaxis. Comments-Conclusion: The management of patients affected by HHT needs rigorous hemostatic methods and outpatient postoperative monitoring. Additionally, the remarkable imaging from panoramic radiography used in this case was instrumental in keeping track of embolization, by clearly highlighting the arterial pathways.

Hereditary hemorrhagic telangiectasia with severe anemia and recurrent CNS infections

Hereditary hemorrhagic telangiectasia also known as Osler–Rendu–Weber disease is a rare autosomal dominant disorder affecting small vessels of multiple systems whose main pathological change is the presence of abnormal arteriovenous communications. It usually presents as skin and mucosal telangiectasia, epistaxis, gastrointestinal bleeding, and visceral arteriovenous malformations. Although epistaxis and gastrointestinal blood loss can result in anemia, patients with hereditary hemorrhagic telangiectasia rarely present with severe anemia and central nervous system (CNS) infections. Here, we report the case of a 57-year-old man who presented with severe anemia resulting in congestive cardiac failure with a history of recurrent blood transfusions and recurrent CNS infections who was ultimately diagnosed as hereditary hemorrhagic telangiectasia with recurrent epistaxis as a cause of his severe anemia.

A rare case of pulmonary arterio-venous malformation with recurrent anemia: Hereditary hemorrhagic telangiectasia.

Arteriovenous malformation (AVM) is a rare vascular anomaly of the lung, which manifests predominantly as dyspnea (due to right to left shunting) and paradoxical embolism. Hereditary Hemorrhagic Telangiectasia (HHT) being a rare genetic disorder is one of the most common causes of pulmonary arteriovenous malformation (PAVM). Here we report an interesting case of recurrent anemia in an elderly female, who was subsequently found to have multiple cutaneous and mucosal telangiectasias and a large pulmonary AVM.

Radiofrequency ablation using BarRx for the endoscopic treatment of radiation proctopathy: a series of three cases.

Radiation proctopathy is a complication of pelvic radiotherapy, which occurs in patients treated for carcinoma of the prostate, rectum, urinary bladder, cervix, uterus, and testes. If it presents within 6 weeks to 9 months after therapy, it is called acute radiation proctitis/proctopathy (ARP), and if it occurs 9 months to a year after treatment, it is classified as chronic radiation proctitis/proctopathy (CRP). CRP occurs in 5%–20% of patients receiving pelvic radiation, depending on the radiation dose and the presence or absence of chemotherapy. In many cases, CRP resolves spontaneously, but in some, it can lead to persistent rectal bleeding. Other symptoms of CRP include diarrhea, mucoid discharge, urgency, tenesmus, rectal pain, and fecal incontinence. Despite the availability of several therapies, many patients fail to respond, and continue to suffer in their quality of life. Radiofrequency ablation (RFA) is a newer endoscopic technique that uses radiofrequency energy to ablate tissue. This is an emerging way to treat radiation proctopathy and other mucosal telangiectasia. We present three cases of radiation proctopathy treated with RFA at our institute and review the literature on treatment modalities for CRP. We were also able to find 16 other cases of CRP that used RFA, and review their literature as well as literature on other treatment modalities.

High prevalence of arterial aneurysms in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder, characterized by recurrent epistaxis, cutaneous and mucosal telangiectasias as well as arteriovenous malformations (AVM) in the lung, liver, brain and gastrointestinal tract [1]. Mutations in the ENG and ACVRL1 genes encoding for TGF-β signaling proteins (respectively endogline and ALK1) in endothelial cells respectively characterize the two main HHT phenotypes, namely HHT1 and HHT2. Mutations in BMP9 or SMAD4 genes, which are also involved in TGF-β signaling, have been reported in HHT [1].

Hyperbaric oxygen therapy for bleeding due to gastritis induced by chemoradiotherapy for regional recurrence of esophageal cancer post-radical esophagectomy

Chemoradiotherapy is effective for locoregional recurrence of esophageal cancer after esophagectomy, although it is important to watch out for adverse events, especially following the late phase. We encountered a patient with bleeding from the gastric conduit caused by chemoradiation-induced gastritis after chemoradiotherapy for mediastinal lymph node recurrence post-radical esophagectomy for esophageal cancer. A 58-year-old male was undergoing chemoradiotherapy for mediastinal lymph node recurrence. About 3 months after the start of the therapy, the patient presented with anemia and bleeding from the gastric conduit caused by chemoradiation-induced gastritis as assessed by fiber optic upper gastrointestinal endoscopy and blood examination. Multiple sessions of argon plasma coagulation for ablation of the gastric mucosal telangiectasia proved ineffective. However, hyperbaric oxygen therapy was effective and the symptom has not recurred until date after this therapy.

Development of a New Minipig Model to Study Radiation-Induced Gastrointestinal Syndrome and its Application in Clinical Research.

Because of insufficient clinical data regarding acute radiation damage after single high-dose radiation exposure, acute radiation-induced gastrointestinal (GI) syndrome remains difficult to treat. The goal of this study was to establish an appropriate and efficient minipig model to study high-dose radiation-induced GI syndrome after radiation exposure. For endoscopic access to the ileum, ileocutaneous anastomosis was performed 3 weeks before irradiation in six male Göttingen minipigs. Minipigs were locally irradiated at the abdominal area using a gamma source as follows: 1,000 cGy (n = 3) and 1,500 cGy (n = 3). Endoscopic evaluation for the terminal ileum was periodically performed via the ileocutaneous anastomosis tract. Pieces of tissue were serially taken for histological examination. The irradiated intestine presented characteristic morphological changes over time. The most obvious changes in the ileum were mucosal atrophy and telangiectasia from day 1 to day 17 after abdominal irradiation. Microscopic findings were characterized as architectural disorganization, loss of villi and chronic active inflammation. Increase in cyclooxygenase-2 (COX-2) expression was closely correlated with severity of tissue damage and inflammation. Particularly, the plasma citrulline level (PCL), a potential marker for radiation-induced intestinal damage, was significantly decreased the day after irradiation and recovered when irradiated mucosa was normalized. Our results also showed that PCL changes were positively correlated with microscopic changes and the endoscopic score in radiation-induced mucosal damage. In conclusion, the ileocutaneous anastomosis model using the minipig mimics human GI syndrome and allows the study of sequential changes in the ileum, the main target tissue of abdominal irradiation. In addition, PCL could be a simple biomarker for radiation-induced intestinal damage.

Rendu-Osler-Weber syndrome: what radiologists should know. Literature review and three cases report

Rendu-Osler-Weber syndrome or hereditary hemorrhagic telangiectasia is an autosomal dominant vascular disease involving multiple systems whose main pathological change is the presence of abnormal arteriovenous communications. Most common symptoms include skin and mucosal telangiectasias, epistaxis, gastrointestinal, pulmonary and intracerebral bleeding. The key imaging finding is the presence of visceral arteriovenous malformations. The diagnosis is based on clinical criteria and can be confirmed by molecular biology techniques. Treatment includes measures for management of epistaxis, as well as surgical excision, radiotherapy and embolization of arteriovenous malformations, with emphasis on endovascular treatment. The present pictorial essay includes a report of three typical cases of this entity and a literature review.

A Case of Hereditary Hemorrhagic Telangiectasia Diagnosed through Spontaneous Hemothorax

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare autosomal dominant disease characterized by heterogenous multisystemic dysplasia of the vascular tissue. Prevalence of HHT is 1 in 5,000∼8,000. HHT commonly presents with recurrent epistaxis, but may have more serious consequences if visceral vascular beds are involved. Approximately 30∼50% of HHT cases also present with pulmonary arteriovenous malformation (PAVM). Spontaneous hemothorax is less common, and PAVM is one of the causes leading to hemothorax. Our case involved an 18-year-old female who had suddenly developed right chest pain. The reason for chest pain was due to right spontaneous hemothorax accompanied by PAVM in the right middle lobe. The patient was additionally diagnosed with HHT upon examination of her family history, specifically through her mother`s symptom that included recurrent epistaxis and mucosal telangiectasia.