Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by arteriovenous malformations (AVMs) ranging from telangiectases to larger AVMs. Mutations in two genes cause HHT; ENG (HHT1) and ACVRL1 (HHT2). Although the hallmark for clinical diagnosis is the presence of telangiectases, there are few publications reporting the relative distribution and frequency of these features between HHT1 and HHT2. Here, the results of such analysis of telangiectases in 268 patients with HHT1 and 130 patients with HHT2 are described. Localization of the telangiectases is reported, and patients were clustered by age to estimate the site prevalence for different age categories. We show that telangiectases of the nasal mucosa are present at a higher prevalence and start to appear earlier in life than those of the oral mucosa or dermal sites in patients with either HHT1 or HHT2. Oral and nasal mucosal telangiectases are present earlier in life in patients with HHT1 compared to patients with HHT2, whereas dermal lesions are more frequent and appear earlier in life in patients with HHT2. In patients with either HHT1 or HHT2, the number of sites affected increases with age. In patients with HHT1, more women than men had skin telangiectases, particularly on the face. These results confirm that the frequency of AVMs differ between patients with HHT1 and HHT2, and that these differences can be detected on physical examination.

Background: The inflammatory process in chronic obstructive pulmonary disease (COPD) is characterised by the presence of neutrophils in the lung that are able to synthesise de novo several inflammatory mediators. The local chronic persistent inflammatory response is accompanied by systemic effects such as cytokine induced priming of peripheral leucocytes and muscle wasting. The preactivation or priming of peripheral blood neutrophils was used to gain more insight into the mechanisms of this systemic inflammatory response. Methods: Gene arrays were performed on peripheral blood neutrophils obtained from healthy donors after stimulation in vitro with tumour necrosis factor (TNF)-a, granulocyte-macrophage colony stimulating factor (GM-CSF), or both. The expression of many inflammatory genes was regulated in these cells following stimulation. The expression of inflammatory genes in peripheral blood neutrophils in healthy subjects and those with COPD was measured by real time RT-PCR after stimulation with TNFa, GM-CSF, interleukin (IL)-8, fMLP, TNFa + GM-CSF, and lipopolysaccharide (LPS). Conclusions: These data are consistent with the hypothesis that progression of COPD is associated with the activation of neutrophils in the systemic compartment. De novo expression of inflammatory mediators by peripheral blood neutrophils suggests a pro-inflammatory role for these cells in the pathogenesis of COPD.

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Background Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT. Methods To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK. Results Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30–84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban ( n = 15), Rivaroxaban ( n = 14), and Dabigatran ( n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin. Conclusions Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban. Electronic supplementary material The online version of this article (10.1186/s13023-019-1179-1) contains supplementary material, which is available to authorized users.

Screening of HHT patients and their first-degree relatives is recommended to prevent severe complications including stroke, brain abscess and intracranial hemorrhage.