Gender differences in hereditary hemorrhagic telangiectasia severity

Abstract

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.

Sequence variations of ACVRL1 play a critical role in hepatic vascular malformations in hereditary hemorrhagic telangiectasia

“…In the present study we investigated the role of different genetic factors in the occurrence of HAVM in HHT patients. We confirmed the more severe hepatic involvement in females than in males, already observed in previous studies, with a growing proportion of women with the severity of hepatic disease (Table 1 ) [ 15 , 16 , 25 ]. One striking characteristic of HHT is the wide interfamilial and intrafamilial variability in the clinical expression of visceral AVMs.…”

Topical Propranolol Improves Epistaxis Control in Hereditary Hemorrhagic Telangiectasia (HHT): A Randomized Double-Blind Placebo-Controlled Trial

“…Moreover, important parameters that may affect bleeding such as clinical variants of HHT, type of mutations, as was previously shown by Lesca et al [ 35 ], family relations of the participants, age, and gender were not evaluated. Notably, we had female predominance and, although recent publication did not find a difference in epistaxis frequency between genders [ 36 ], a match for gender should be considered in a larger study.…”

Integration of clinical parameters, genotype and epistaxis severity score to guide treatment for hereditary hemorrhagic telangiectasia associated bleeding

“…Larger studies comparing HHT patients with and without underlying pathogenic variants in HHT-associated genes are needed to further explore this finding. Overall, these data suggest that The data regarding genotype and prevalence of pulmonary and cerebral AVMs varies between studies, with some studies demonstrating an association while others do not [6,13,14,29,31,32,34]. This discrepancy between studies may be related to racial/ethnic differences in the study populations, study methodologies, and the impact of co-existing gene variants that modify HHT biology [35,36].…”

“…Our data do not demonstrate an association between gender or genotype and prevalence of pulmonary or brain AVMs; however, this may be due to lack of sufficient numbers, especially within the brain AVM cohort. Recent data from Mora-Lujan et al has demonstrated an association between female gender and increased risk of hepatic AVMs [31]. Unfortunately, our data set did not include information regarding hepatic AVM.…”

“…The association between genotype, epistaxis, and visceral AVMs has been previously evaluated [6,13,14,[29][30][31][32]. Epistaxis is the most common (> 90%) manifestation in patients with both ENG and ACVRL1 mutations, although patients with ENG mutations are believed to have onset of epistaxis at a younger age [6,[13][14][15]33].…”