Gastrointestinal Bleeding in Patients with Hereditary Hemorrhagic Telangiectasia: Risk Factors and Endoscopic Findings

Background: We aimed to describe risk factors for gastrointestinal (GI) bleeding and endoscopic findings in patients with hereditary hemorrhagic telangiectasia (HHT). Methods: This is a prospective study from a referral HHT unit. Endoscopic tests were performed when there was suspicion of GI bleeding, and patients were divided as follows: with, without, and with unsuspected GI involvement. Results: 67 (27.9%) patients with, 28 (11.7%) patients without, and 145 (60.4%) with unsuspected GI involvement were included. Age, tobacco use, endoglin (ENG) mutation, and hemoglobin were associated with GI involvement. Telangiectases were mostly in the stomach and duodenum, but 18.5% of patients with normal esophagogastroduodenoscopy (EGD) had GI involvement in video capsule endoscopy (VCE). Telangiectases ≤ 3 mm and ≤10 per location were most common. Among patients with GI disease, those with hemoglobin 3 mm). After a mean follow-up of 34.2 months, patients with GI involvement required more transfusions and more emergency department and hospital admissions, with no differences in mortality. Conclusions: Risk factors for GI involvement have been identified. Patients with GI involvement and severe anemia had larger telangiectases and higher ESS. VCE should be considered in patients with suspicion of GI bleeding, even if EGD is normal

Gender differences in Hereditary Hemorrhagic Telangiectasia severity

Background: Gender differences in organ involvement and clinical severity have been poorly described in hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to describe differences in the severity of HHT manifestations according to gender. Methods: Severity was measured according to Epistaxis Severity Score (ESS), Simple Clinical Scoring Index for hepatic involvement, a general HHT-score, needing for invasive treatment (pulmonary or brain arteriovenous malformations -AVMs- embolization, liver transplantation or Young's surgery) or the presence of adverse outcomes (severe anemia, emergency department -ED- or hospital admissions and mortality). Results: One hundred forty-two (58.7%) women and 100 (41.3%) men were included with a mean age of 48.9 ± 16.6 and 49 ± 16.5 years, respectively. Women presented hepatic manifestations (7.1% vs 0%) and hepatic involvement (59.8% vs 47%), hepatic AVMs (28.2% vs 13%) and bile duct dilatation (4.9% vs 0%) at abdominal CT, and pulmonary AVMs at thoracic CT (35.2% vs 23%) more often than men. The Simple Clinical Scoring Index was higher in women (3.38 ± 1.2 vs 2.03 ± 1.2), and more men were considered at low risk of harboring clinically significant liver disease than women (61% vs 25.3%). These differences were mantained when considering HHT1 and HHT2 patients separetely. Duodenal telangiectasia were more frequent in men than women (21% vs 9.8%). Invasive treatments were more frequently needed in women (28.2% vs 16%) but men needed attention at the ED more often than women (48% vs 28.2%), with no differences in ESS, HHT-score, anemia hospital admissions or mortality. Conclusions: HHT women showed more severe hepatic involvement than men, also among HHT1 and HHT2 patients. Women had higher prevalence of pulmonary AVMs and needed invasive procedures more frequently, while men needed attention at the ED more often. These data might help physicians to individualize HHT patients follow-up

Long-term use of somatostatin analogs for chronic gastrointestinal bleeding in hereditary hemorrhagic telangiectasia

BackgroundChronic bleeding due to gastrointestinal (GI) involvement in patients with hemorrhagic hereditary telangiectasia (HHT) can provoke severe anemia with high red blood cells (RBC) transfusion requirements. However, the evidence about how to deal with these patients is scarce. We aimed to assess the long-term efficacy and safety of somatostatin analogs (SA) for anemia management in HHT patients with GI involvement. MethodsThis is a prospective observational study including patients with HHT and GI involvement attended at a referral center. SA were considered for those patients with chronic anemia. Anemia-related variables were compared in patients receiving SA before and during treatment. Patients receiving SA were divided into responders (patients with minimal hemoglobin levels improvement >10 g/L and maintaining hemoglobin levels >= 80 g/L during treatment), and non-responders. Adverse effects during follow-up were collected. ResultsAmong 119 HHT patients with GI involvement, 67 (56.3%) received SA. These patients showed lower minimal hemoglobin levels (73 [60-87] vs. 99 [70.2-122.5], p < 0.001), and more RBC transfusion requirements (61.2% vs. 38.5%, p = 0.014) than patients without SA therapy. Median treatment period was 20.9 +/- 15.2 months. During treatment, there was a statistically significant improvement in minimum hemoglobin levels (94.7 +/- 29.8 g/L vs. 74.7 +/- 19.7, p < 0.001) and a reduction of patients with minimal hemoglobin levels <80 g/L (39 vs. 61%, p = 0.007) and RBC transfusions requirement (33.9% vs. 59.3%, p < 0.001). Sixteen (23.9%) patients showed mild adverse effects, mostly diarrhea or abdominal pain, leading to treatment discontinuation in 12 (17.9%) patients. Fifty-nine patients were eligible for efficacy assessment and 32 (54.2%) of them were considered responders. Age was associated with non-responder patients, OR 95% CI; 1.070 (1.014-1.130), p = 0.015. ConclusionSA can be considered a long-term effective and safe option for anemia management in HHT patients with GI bleeding. Older age is associated with poorer response

Adrenomedullin as a potential biomarker involved in patients with hereditary hemorrhagic telangiectasia

Background: Adrenomedullin (AM) is a vasoactive peptide mostly secreted by endothelial cells with an important role in preserving endothelial integrity. The relationship between AM and hereditary hemorrhagic telangiectasia (HHT) is unknown. We aimed to compare the serum levels and tissue expression of AM between HHT patients and controls. Methods: Serum AM levels were measured by radioimmunoassay and compared between control and HHT groups. AM levels were also compared among HHT subgroups according to clinical characteristics. The single nucleotide polymorphism (SNP) rs4910118 was assessed by restriction analysis and sequencing. AM immunohistochemistry was performed on biopsies of cutaneous telangiectasia from eight HHT patients and on the healthy skin from five patients in the control group. Results: Forty-five HHT patients and 50 healthy controls were included, mean age (SD) was 50.7 (14.9) years and 46.4 (9.9) years (p = 0.102), respectively. HHT patients were mostly female (60% vs 38%, p = 0.032). Median [Q1-Q3] serum AM levels were 68.3 [58.1-80.6] pg/mL in the HHT group and 47.7 [43.2-53.8] pg/mL in controls (p<0.001), with an optimal AM cut-off according to Youden's J statistic of 55.32 pg/mL (J:0.729). Serum AM levels were similar in the HHT subgroups. No patient with HHT had the SNP rs4910118. AM immunoreactivity was found with high intensity in the abnormal blood vessels of HHT biopsies

Mastoid obliteration and canal wall reconstruction with posterior auricular artery (PAA) fascia-periosteum flap

Objective: Unstable cavities are defined as cavities with cerumen accumulation that need frequent cavity cleaning in the out-patient clinic, cavities that are intolerant to water due to risk of infection or that are subject to frequent infection and otorrhoea. The objective of this study is to address the problem of troublesome mastoid cavities, with the performance of secondary mastoid obliteration and canal wall reconstruction, using a novel posterior auricular artery (PAA) fascia-periosteum flap. Materials and methods: A prospective study was designed, only secondary obliterations were included. Unstable mastoid cavities were defined as Merchant grade 2 or 3 and were included for surgery. Results: At 12 months of follow up, a complete external auditory canal (EAC) and a self-cleaning ear were achieved in all 23 patients. Completely dry ears were achieved in 21 patients (91.3%). An air-bone gap improvement of 5dB was achieved. Conclusion: Mastoid obliteration and EAC reconstruction are effective procedures to treat troublesome post canal wall down mastoid cavities. They improve quality of life and enable patients to overcome ear discharge. A standard EAC size enables the utilization of conventional hearing aids, it also reduces the need for constant mastoid cleaning and decreases healthcare expenses. The PAA flap seems to be an effective procedure to achieve all these features, as it is used to obliterate the mastoid and becomes a structural component of the neo-EAC