オスラー病

OBJECTIVES: To compare the efficacy and safety of pharmacologic therapies for spontaneous epistaxis in hereditary hemorrhagic telangiectasia (HHT). DATA SOURCES: PubMed, Scopus, Embase, Web of Science, and the Cochrane Library were systematically searched up to August 2025. REVIEW METHODS: Eligible randomized controlled trials evaluating bevacizumab, doxycycline, tranexamic acid, or β-blockers versus placebo or standard care were included. Outcomes included epistaxis frequency and duration, hemoglobin (Hb), epistaxis severity score (ESS), transfusion or emergent-care requirements, quality of life (QOL), and adverse events. RESULTS: Tranexamic acid did not significantly reduce epistaxis duration or frequency or improve Hb, and it did not change transfusion or emergent-care needs, but it increased diarrhea (odds ratio 3.8, 95% confidence interval [CI] [1.7; 8.5]). Bevacizumab produced a modest reduction in epistaxis frequency (standardized mean difference -0.25, 95% CI [-0.47; -0.02]), without significant effects on duration, ESS, Hb, or QOL. Doxycycline showed no significant benefit for duration or frequency. Topical or systemic β-blockers did not significantly affect ESS, QOL, Hb, or overall adverse events. Across agents, between-study heterogeneity was generally low to moderate and CIs were wide, reflecting limited sample sizes. CONCLUSION: No pharmacologic agent demonstrated consistent, clinically robust superiority over placebo across primary endpoints. Bevacizumab may modestly reduce bleeding burden, whereas tranexamic acid increases gastrointestinal toxicity without clear efficacy. Pharmacologic control of HHT-related epistaxis remains suboptimal, underscoring the need for adequately powered trials with standardized outcome measures and optimized dosing and delivery strategies.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations (VM) focally develop in multiple organs. There are few treatment options and no cure. HHT patients inherit loss-of-function mutations affecting Alk1-Eng signaling; however, why this manifests as VMs remains poorly understood. Here we have developed a fully human cell-based microphysiological system of perfused vasculature in which inducible shRNA controls endogenous Alk1 in primary endothelial cells (EC). Resulting VMs develop over several days, recapitulate patient VM appearance, and require only a subpopulation of Alk1-deficient EC to trigger lesions. Single-cell transcriptomics suggests microvessel pruning and regression contribute to VM, while loss of PDGFB implicates mural cell recruitment. Finally, pharmacological VEGF/VEGFR inhibition blocks lesion formation. In summary, we have developed an HHT-on-a-chip model that faithfully reproduces HHT patient lesions and that can be used to better understand HHT disease biology and identify potential new HHT drugs.

Pulmonary arteriovenous malformation (PAVM) is a congenital vascular anomaly that forms a shunt between the pulmonary artery and vein. It is frequently detected incidentally in asymptomatic patients. We encountered a 69-year-old female patient with bilateral PAVMs that were incidentally detected on abdominal computed tomography( CT) performed for a detailed examination of appendicitis. Abdominal CT revealed nodular opacities with contrast enhancement in the middle lobe of the right lung and the lingular segment of the left lung. They were further examined, and a diagnosis of PAVMs measuring 14 mm and 13 mm, respectively, was made. No arteriovenous malformations were identified in other organs, and no findings suggestive of hereditary hemorrhagic telangiectasia were observed. Both lesions were located in the peripheral regions directly beneath the pleura and had a diameter of 10 mm or more. Thus, surgical resection was considered indicated, and the patient underwent thoracoscopic partial lung resection. The lesions were easily identified and resected without complications. Although percutaneous transcatheter embolization is minimally invasive, it may be difficult to perform for peripheral and large-diameter lesions. Therefore, surgery may be an effective treatment option for peripheral PAVMs, as in the case of this patient. We report a case of bilateral PAVMs that were incidentally detected and safely treated by thoracoscopic surgery.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder in which dysregulated endothelial signaling drives telangiectasias and arteriovenous malformations across multiple organs. Loss-of-function variants in ACVRL1 (ALK1), a core receptor in BMP9/10 signaling, are a major genetic cause. Here we report two patient-derived induced pluripotent stem cell (iPSC) lines generated from clinically diagnosed HHT donors carrying heterozygous ACVRL1 mutations: c.129dup (p.Pro44Alafs*125) and c.430C > T (p.Arg144*). Both lines showed expected iPSC morphology, robust expression of markers of the undifferentiated iPSC state, genomic stability by LP-WGS, and tri-lineage differentiation capacity. These resources enable human cell-based studies of ACVRL1 haploinsufficiency and provide a starting point for mechanistic and therapeutic work focused on HHT vascular pathobiology.

The circulating ligands bone morphogenetic protein (BMP)-9 and BMP-10 are emerging as dual regulators of pulmonary and systemic vascular biology. Acting through activin receptor-like kinase 1 (ALK1), BMP receptor type II (BMPRII) and endoglin receptor complexes, they maintain endothelial quiescence and vascular tone under physiological conditions. Yet, the same axis can turn pathogenic when its intensity, timing or cellular context are altered. We propose viewing BMP-9/10 not as a linear protective pathway but as a bimodal system in which both deficiency and hyperactivation disrupt vascular homeostasis, leading to distinct phenotypes such as obstructive pulmonary arterial remodeling in pulmonary arterial hypertension (PAH), intrapulmonary vasodilatation in hepatopulmonary syndrome (HPS), and arteriovenous shunting in hereditary haemorrhagic telangiectasia (HHT). The clinical success of sotatercept, an activin signaling inhibitor with partial BMP-ligand trap properties, underscores the translational potential of therapeutically "retuning" this pathway rather than globally enhancing it. Understanding when BMP-9/10 signaling protects and when it becomes pathogenic will be crucial for designing next-generation interventions that stabilize, instead of destabilize, pulmonary vascular integrity.