An update on the ophthalmic features in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber syndrome is a rare autosomal dominant disease, characterised by systemic angiodysplasia. Dysfunction of the signalling pathway of β transforming growth factor is the main cause of HHT principally owing to mutations of the genes encoding for endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1). Clinical manifestations can range from mucocutaneous telangiectasia to organ arterio-venous malformations and recurrent epistaxis. The early clinical manifestations may sometimes be subtle, and diagnosis may be delayed. The main ophthalmic manifestations historically reported in HHT are haemorrhagic epiphora, and conjunctival telangiectasia present in 45–65% of cases, however, imaging with wide-field fluorescein angiography has recently shown peripheral retinal telangiectasia in 83% of patients. Optimal management of HHT requires both understanding of the clinical presentations and detection of early signs of disease. Advances in imaging methods in ophthalmology such as wide-field fluorescein angiography, spectral domain optical coherence tomography, and near infrared reflectance promise further insight into the ophthalmic signs of HHT towards improved diagnosis and early management of possible severe complications.

Hereditary hemorrhagic telangiectasia (HHT): a practical guide to management

Hereditary hemorrhagic telangiectasia (HHT), the second most common inherited bleeding disorder, is associated with the development of malformed blood vessels. Abnormal blood vessels may be small and cutaneous or mucosal (telangiectasia), with frequent complications of bleeding, or large and visceral (arteriovenous malformations [AVMs]), with additional risks that can lead to significant morbidity and even mortality. HHT can present in many different ways and can be difficult to recognize, particularly in younger patients in the absence of a known family history of disease or epistaxis, its most common manifestation. HHT is commonly diagnosed using the established Curaçao clinical criteria, which include (1) family history, (2) recurrent epistaxis, (3) telangiectasia, and (4) visceral AVMs. Fulfillment of 3 or more criteria provides a definite diagnosis of HHT, whereas 2 criteria constitute a possible diagnosis of HHT. However, these criteria are insufficient in children to rule out disease due to the age-dependent development of some of these criteria. Genetic testing, when positive, can provide definitive diagnosis of HHT in all age groups. Clinical course is often complicated by significant epistaxis and/or gastrointestinal bleeding, leading to anemia in half of adult patients with HHT. The management paradigm has recently shifted from surgical approaches to medical treatments aimed at control of chronic bleeding, such as antifibrinolytic and antiangiogenic agents, combined with aggressive iron replacement with intravenous iron. Guidelines for management of HHT, including screening and treatment, were determined by expert consensus and originally published in 2009 with updates and new guidelines in 2020.

Experimental study of the possibility of topical application of polyvinylpyrrolidone for epistaxis

Nasal packing is widely used in patients with epistaxis, especially in cases where it is impossible to electrocoagulate the bleeding vessel. The disadvantages of gauze packing are well known. First of all, this is the risk of recurrent bleeding after removing the tampons from the nose. The cause of recurrent epistaxis is the activation of local fibrinolysis during prolonged stay of the tampon in the nasal cavity. To overcome this drawback, we have proposed the topical application of polyvinylpyrrolidone (PVP). In an experiment on animals, the absence of a damaging effect of PVP on mucociliary transport was proved.

Skull base low-grade non-intestinal adenocarcinoma in a paediatric patient

Background: Non-intestinal adenocarcinomas of the sinonasal tract are uncommon neoplasms in adults, and particularly rare in the paediatric population. Case presentation: A 10-year-old male presented to the Paediatric Otolaryngology clinic with symptoms of recurrent epistaxis, persistent clear nasal discharge, and a left-sided polypoidal swelling causing nasal obstruction. An endoscopic biopsy of the polyp under general anaesthesia found a mass arising from the anterior olfactory cleft, and the histology report described the mass as a low-grade non-intestinal adenocarcinoma. CT and MRI of the sinuses post-biopsy demonstrated no bony structure infiltration. The patient underwent a further endoscopic operation for definitive excision of the nasal mass, and the histology findings confirmed a complete resection of the tumour. Conclusion: This case demonstrates the first case of a primary low-grade non-intestinal adenocarcinoma originating from the olfactory cleft.

Epistaxis as a marker of the unfavorable course of hypertension

The aim of this research was to study changes in the nasal mucosa vessels in hypertensive patients suffering from recurrent epistaxis. Patients and methods. 78 hypertensive patients aged between 50 and 70, admitted due to epistaxis, were studied. Diabetic, coagulopathic patients and those taking anticoagulants were excluded from the research. All the patients were divided into 2 groups: group 1 (46 people) with a single epistaxis, group 2 (32 people) with a recurrent epistaxis. At the admission, all the patients showed elevated blood pressure, yet the differences between the patients of group 1 and group 2 were not significant. 14 patients of group 2 did not reveal any source of hemorrhage due to a severely deviated septum. These patients underwent septoplasty followed by mucoperichondrium biopsy. Histological study of the samples showed multiple erosions within the epithelial layer, as well as necrotic patches spreading to the deeper mucous coat layers. The microvasculature showed dystrophic changes in the endothelium, its focal desquamation with basal membrane exposure and thrombocytes and erythrocytes adhesion at such places, erythrocyte aggregation, plasma separation, erythrocyte and fibrinous thrombi formation. Thus, the cause of epistaxis is not high blood pressure, but those changes in the nasal mucosa vessels promoted by long-term arterial hypertension.

Mutational and clinical spectrum of Japanese patients with hereditary hemorrhagic telangiectasia

Background Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited vascular disorder characterized by recurrent epistaxis, skin/mucocutaneous telangiectasia, and organ/visceral arteriovenous malformations (AVM). HHT is mostly caused by mutations either in the ENG or ACVRL1 genes, and there are regional differences in the breakdown of causative genes. The clinical presentation is also variable between populations suggesting the influence of environmental or genetic backgrounds. In this study, we report the largest series of mutational and clinical analyses for East Asians. Methods Using DNAs derived from peripheral blood leukocytes of 281 Japanese HHT patients from 150 families, all exons and exon–intron boundaries of the ENG, ACVRL1, and SMAD4 genes were sequenced either by Sanger sequencing or by the next-generation sequencing. Deletions/amplifications were analyzed by the multiplex ligation-dependent probe amplification analyses. Clinical information was obtained by chart review. Results In total, 80 and 59 pathogenic/likely pathogenic variants were identified in the ENG and ACVRL1 genes, respectively. No pathogenic variants were identified in the SMAD4 gene. In the ENG gene, the majority (60/80) of the pathogenic variants were private mutations unique to a single family, and the variants were widely distributed without any distinct hot spots. In the ACVRL1 gene, the variants were more commonly found in exons 5–10 which encompasses the serine/threonine kinase domain. Of these, 25/59 variants were unique to a single family while those in exons 8–10 tended to be shared by multiple (2–7) families. Pulmonary and cerebral AVMs were more commonly found in ENG-HHT (69.1 vs. 14.4%, 34.0 vs. 5.2%) while hepatic AVM was more common in ACVRL1-HHT (31.5 vs. 73.2%). Notable differences include an increased incidence of cerebral (34.0% in ENG-HHT and 5.2% in ACVRL1-HHT), spinal (2.5% in ENG-HHT and 1.0% in ACVL1-HHT), and gastric AVM (13.0% in ENG-HHT, 26.8% in ACVRL1-HHT) in our cohort. Intrafamilial phenotypic heterogeneity not related to the age of examination was observed in 71.4% and 24.1% of ENG- and ACVRL1-HHT, respectively. Conclusions In a large Japanese cohort, ENG-HHT was 1.35 times more common than ACVRL1-HHT. The phenotypic presentations were similar to the previous reports although the cerebral, spinal, and gastric AVMs were more common.

Mean platellet volume and red cell distribution width values in children with recurrent epistaxis

Objective: This study aimed to evaluate the relationship between mean platelet volume and red blood cell distribution width, recurrent epistaxis in children. Material and Method:This study was conducted with 60 pediatric patients who applied to our clinic between complaint of epistaxis. The control group consisted of 60 pediatric patients with similar number of age and gender characteristics as the study group. mean platelet volume (MPV) and red cell distribution width (RDW) values measured routinely in the complete blood count (CBC) were investigated Results: Mean RDW value was founded 11.98±0.75% in patients with epistaxis and 12.44±0.78% in the control group. Since the p-value calculated according to these data was found to be 0.02, the difference was found to be statistically significant. The MPV value was 6.65±1.31 femtoliter in patients with epistaxis and 6.41±1.22 femtoliter in the control group. The difference was not statistically significant since the p-value was higher than 0.05. Conclusion: It is thought that the high values of RDW and MPV, which are among the parameters measured in complete blood count, may be associated with the increase in thrombotic activity. It is also observed that MPV and RDW values are high in cerebrovascular cases and coronary artery diseases. The low RDW value in patients who with recurrent epistaxis gives rise to thought that this value may not be a result of bleeding, but a cause.

Efficacy of Trans-nasal Endoscopic Sphenopalatine Artery Ligation in the Management of Recurrent Posterior Epistaxis

Background: Recurrent posterior epistaxis is a challenging problem for most otolaryngologists. Of the several proposed treatment modalities, endoscopic ligation of SPA (Sphenopalatine artery) provides a simple and effective solution with relatively minor complications. Objectives: Aim of this study was to find out the success rate and complications of endoscopic ligation of SPA in the management of recurrent posterior epistaxis. Materials and Methods: This was an observational study conducted from Jan 2019 to Jan 2021. Total 60 patients were included in this study. Inclusion criteria were - recurrent epistaxis (at least 4 episodes in last 2 months) with bleeding point not seen in anterior rhinoscopy, Failure of previous conservative management with medications and nasal packing, age between 18–60 years of both sexes. All the patients underwent trans-nasal endoscopic Sphenopalatine artery ligation, and patients were followed up for 12 weeks to identify repeated bleeding and to evaluate complications. Results: In this study male to female ratio was 1.5:1. Mean age of study group was 44.66 (±8.62) years. No recurrent bleeding occurred in 51 (85%) and in 9 (15%) nasal bleeding occurred in the 2 months postoperative period. Anesthesia of incisor teeth occurred in 18 patients (30%), 22 patients (37%) complained about increased nasal crusting. Conclusion: Endoscopic ligation of Sphenopalatine artery shows good outcome in prevention of further episodes of epistaxis in most patients. Although some minor complications can occur, these are manageable. KYAMC Journal. 2021;12(3): 133-137

Geriatric epistaxis: Management of epistaxis in the geriatric patient group

OBJECTIVE: In this study, given the recent increases in the geriatric population and the consequent impacts on healthcare services, we examined the characteristics of geriatric patients admitted to the emergency department due to epistaxis. METHODS: This retrospective study included 55 patients (33 males, 22 females; mean age: 72±6.8 years; range, 65 to 93 years) with epistaxis admitted to the Cukurova University Emergency Medicine Department and University of Health Sciences Adana City Training and Research Hospital Otolaryngology Emergency Polyclinic between 01.05.2019-01.04.2020. The patients were divided into two groups according to age: Group 1 consisted of patients aged 65 to 75 years; Group 2 consisted of patients over 75. Postoperative bleeding and trauma history were excluded in all patients in the study. RESULTS: There were no significant differences between the two groups regarding the rate of hospital discharge (p=1.00). Patients with posterior hemorrhage and posterior nasal tampons required significantly more hospitalizations (p<0.001). CONCLUSION: The presence of comorbidities and drug use may cause persistent and recurrent epistaxis. It is necessary for physicians to be more cautious about the use of off-label antiaggregants and anticoagulants.

Resveratrol As a Novel Treatment for Recurrent Epistaxis in SMAD4+ Hereditary Hemorrhagic Telangiectasia

Introduction Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by the development of arteriovenous malformations or telangiectasias that may affect any organ system, but are most prevalent in the nose and gastrointestinal tract. Nasal telangiectasia account for epistaxis, the most frequent manifestation of HHT, which may be frequent, debilitating and lead to decreased quality of life. Epistaxis is quantified by the Epistaxis Severity Scores (ESS), which ranges from 1-10 with higher scores associated with more severe bleeding. The diagnosis of HHT is based on clinical criteria and requires three or more of the following features: epistaxis, mucocutaneous telangiectasis, visceral AVMs, and/or a family history of HHT. HHT is associated with several mutations that may involve ENG, ACVRL1, or SMAD4; the latter occurs in only ~2% of HHT patients, which is also associated with the Juvenile Polyposis Syndrome (JPS), another autosomal dominant disorder associated with an increased risk for colorectal, stomach, small intestine, and pancreatic cancers. Methods Case report with serial ESS scores, hemoglobin and hematocrit monitoring. Results A 25-year-old male was diagnosed with JPS/HHT and a c.1081C&gt;T mutation in SMAD4 leading to an R361C missense mutation was diagnosed in 2013. The patient had a longstanding history of frequent epistaxis leading to severe iron deficiency anemia and requiring at least two 750 mg iron infusions annually (total of 14), and did not improve with oral iron supplements. In December 2020, the patient initiated a 1 g daily dose of resveratrol for general anti-aging and health benefits. His epistaxis improved immediately, and his ESS decreased from 6 (consistent with severe bleeding) to 1 (no bleeding) over a two week period. The frequency, severity and duration of epistaxis all improved dramatically (Figure). No additional iron therapy has been required since initiation of resveratrol. Recent serum iron and ferritin values (6/2021) were both within normal limits. Of interest, in parallel with the resolution of epistaxis, the patient also had a dramatic reduction in colonic polyposis after starting resveratrol. Conclusions There are no approved therapies for the treatment of HHT, and patients with this disorder may suffer from a markedly reduced quality of life due to unpredictable epistaxis and other manifestations. While a responses to bevacizumab have been reported in 60-70% of patients, treatment is expensive and may be associated with thromboembolic events, and patients may become refractory over time. Invasive approaches such as sclerotherapy may be initially, but only temporarily effective. Thus, there is an urgent need for better HHT therapies. Figure 1 Figure 1. Disclosures McCrae: Sanofi, Novartis, Alexion, and Johnson & Johnson: Consultancy, Honoraria; Dova, Novartis, Rigel, and Sanofi Genzyme: Consultancy.