RARE DISEASE
Hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia
Synonyms: HHT, Rendu-Osler disease, Rendu-Osler-Weber disease
Synonyms: HHT, Rendu-Osler disease, Rendu-Osler-Weber disease
Synonyms: HHT, Rendu-Osler disease, Rendu-Osler-Weber disease
Drug discovery
14
drugs
With orphan designations
Overview
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused by mutations in ENG, ACVRL1, or SMAD4 genes, leading to abnormal vasculature with telangiectases and arteriovenous malformations (AVMs). Clinical hallmarks include recurrent epistaxis (>90% of adults), mucocutaneous telangiectases, and visceral AVMs (lungs, brain, liver, GI tract). Complications range from chronic anemia to life-threatening strokes or hemorrhages. Diagnosis follows the Curaçao criteria. Management combines antiangiogenics (bevacizumab), antifibrinolytics (tranexamic acid), iron supplementation, and procedural interventions for acute bleeding [1][3][7][16].
Burden
Morbidity: 30–50% develop pulmonary, cerebral, or hepatic AVMs; 32% with HHT require iron infusions [4][9][14].
Mortality: Hazard ratio 2.03 vs. controls, driven by stroke, cerebral abscess, and hemorrhage [14][18].
Costs: 40% higher healthcare utilization vs. matched controls, driven by frequent transfusions, imaging, and hospitalizations [9][19].
Therapies
Systemic therapies: Bevacizumab (reduces transfusion needs by >80%) and tranexamic acid (17–54% epistaxis reduction) [3][10][15].
Anemia management: IV iron for severe deficiency; transfusions reserved for hemodynamic instability [10][15].
Procedural: Argon Plasma Coagulation for acute GI bleeds; anticoagulation individualized based on bleeding risk [3][5][10].
Categories: rare circulatory system diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare hepatic diseases, rare neurological diseases, rare ophthalmic disorders, rare respiratory diseases, rare skin diseases, rare systemic and rheumatological diseases
Research Papers
1,138 drug discovery papers about Hereditary hemorrhagic telangiectasia, with 2 first-in-class and 31 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,138 drug discovery papers about Hereditary hemorrhagic telangiectasia, with 2 first-in-class and 31 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2025-10-16 | Nasal RADA16 hydrogel application decreases epistaxis severity scores in adults with hereditary hemorrhagic telangiectasia.
More than 90% of adults with hereditary hemorrhagic telangiectasia (HHT) experience epistaxis, which can be recurrent and cause significant morbidity. RADA16 is a self-assembling peptide hydrogel approved by the US Food and Drug Administration for hemostasis and wound healing. In this cohort study, we assessed the effectiveness of nasal RADA16 application in controlling HHT-related epistaxis. A retrospective chart review was performed on a cohort of adult patients who received nasal RADA16 without any other changes in treatment. Pre- and post-Epistaxis Severity Scores (ESS), hemoglobin, and hematocrit were collected to assess treatment response. Of the included patients (n = 22), there were 26 applications of RADA16. The cohort was 54.5% male and 86.4% White, had a mean age of 55.5 years, and had a predominantly ACVRL1 genotype (40.9%). Baseline mean ESS was 5.0 and decreased by an average of 2.0 at an average of 46.9 days after treatment, which is 2.8 times more than the minimal clinically important difference for ESS in HHT (0.71). The mean baseline hemoglobin (n = 13) and hematocrit (n = 10), were 11.3 g/dL and 37.5%, respectively, and did not exhibit significant changes after RADA16 application. No bleeding, pain, or allergic reactions occurred due to the application. Several patients reported mild nasal congestion. Our experience demonstrates that RADA16 can be considered as a safe epistaxis treatment modality for HHT that is easy to apply and does not require the operating suite.
2025-06-24 | Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling.
Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are two distinct vascular diseases linked to impaired signaling through bone morphogenetic protein (BMP) receptor complexes in endothelial cells. Although BMP-9 plays a central role in activating this pathway by binding to ALK1 and BMPR-II, its precise function in the pulmonary microvasculature has remained unclear. In this study, we demonstrate a role for BMP-9 in regulating pulmonary vascular architecture and homeostasis. Our findings reveal that BMP-9 signaling intersects with VEGF pathways and contributes to the delicate balance between vascular growth and remodeling in the lungs. We also show that disruption of this pathway can shift vascular responses toward an HHT-like state, potentially altering disease susceptibility. These insights offer a unique perspective on how BMP-9 and ALK1 shape pulmonary vascular biology and suggest that targeting this axis could inform future strategies for treating complex vascular diseases such as PAH.
2024-10-01 | 7819 Hypoglycemia with Hereditary Hemorrhagic Telangiextsia in a Boy After Liver Transplantation
Abstract Disclosure: H. Miyagi: None. M. Igarashi: None. E. Tanimoto: None. R. Horikawa: None. Introduction: Hereditary hemorrhagic telangiectasia (HHT) causes arteriovenous malformation (AVM) in liver, lung, and brain. It is not clear whether it also causes hypoglycemia. We show a case of HHT combined with hypoglycemia after liver transplantation, improved by nutrition management and growth hormone treatment. Case: 11 months old boy born from a mother with HHT was diagnosed as having with AVM prenatally. He was once operated for the liver AVM but developed a new collateral circulation which caused severe heart failure and lead to liver transplantation. He showed severe growth retardation and malnutrition. His body weight was 4.6 kg and height were 60 cm (-5.8 SD) when he was 1 year old, and blood test showed low albumin for 3 g/dL (3.4 - 4.7 g/dL), and total protein for 4 g/dL (5.7 - 7.5 g/dL). Hypoglycemia was found while switching his nutrition from parenteral to enteral nutrition after operation. His insulin was under 0.3 µU/mL when his blood glucose was 49 mg/dL IGF1 was 17 ng/mL (ref.11 - 149 ng/mL), suggested growth hormone (GH) deficiency. GH stimulation test showed blunted response. GH treatment was started. Other pituitary hormones were within normal range. Nutritional support was added using high-calory milk. After GH treatment, IGF1 level increased to 87 ng/mL. GH and nutritional management improved not only his weight and height gain but also his glycemic control. Discussion: Hypoglycemia may be caused by both GHD and malnutrition. GHD and low IGF1 might be caused by malnutrition. Retesting GH secretion after improvement of nutrition is planned to clarify his pituitary function. Presentation: 6/2/2024
2024-03-01 | Abstract 2385 The role of the ALK1 protein in vascular disease and potential targetability in Crohn's disease
The ACVRL1 gene is highly expressed in endothelial cells and encodes the transmembrane protein activin receptor-like kinase 1 (ALK1), which is a type I cell-surface receptor serine/threonine kinase for the transforming growth factor-β (TGF-β) superfamily of ligands BMP9/GDF2 and BMP10. ALK1 comprises of an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain. Upon ligand binding, this receptor forms complexes with other TGF-β receptors, primarily BMP9 to activate intracellular downstream signaling pathways. The Smad pathway functions to regulate gene expression through transmitting nucleus signals from the TGFβ receptors. Signaling is transmitted by a cytoplasmic kinase domain of ALK1 by phosphorylating receptor-regulated Smad proteins (R-Smad proteins). Activated R-Smad proteins and the common-Smad (co-Smad) form a complex to regulate transcription of target genes together with cofactors. This pathway is essential for angiogenesis and vasculogenesis and a mutation can induce several vascular diseases. The Smad Pathway is also crucial for endothelial cell differentiation and homeostasis, which plays roles in Crohn's Disease. Differing mutations in the ACVRL1 gene can result in increased or decreased kinase activity as well as impaired ligand binding, disrupting of TGF-β signaling, and in some cases induce a rare genetic disorder known as Hereditary Hemorrhagic Telangiectasia (HHT). HHT is an inherited disorder characterized by abnormally formed blood vessels. TGF-β can act as both a tumor suppressor and a tumor promoter, and mutations or dysregulation of components in its pathway can lead to several types of cancer. In Crohn's disease patients, scientists were able to determine an increased risk of endoscopic relapse based on ALK1 levels. Additionally, activation of ALK1 has been shown to enhance colonic intestinal epithelial barrier integrity and function ex vivo in these studies. The Walton High School SMART team, with support from 3D molecular designs, has modeled ALK1 receptors to support testing of the ALK1 protein to develop potential therapies and interventions for Crohn's disease, HHT, and several cancers.
2023-03-31 | Data from ALK1-Fc Inhibits Multiple Mediators of Angiogenesis and Suppresses Tumor Growth
<div>Abstract<p>Activin receptor–like kinase-1 (ALK1) is a type I, endothelial cell–specific member of the transforming growth factor-β superfamily of receptors known to play an essential role in modulating angiogenesis and vessel maintenance. In the present study, we sought to examine the angiogenic and tumorigenic effects mediated upon the inhibition of ALK1 signaling using a soluble chimeric protein (ALK1-Fc). Of 29 transforming growth factor-β–related ligands screened by surface plasmon resonance, only bone morphogenetic protein (BMP9) and BMP10 displayed high-affinity binding to ALK1-Fc. In cell-based assays, ALK1-Fc inhibited BMP9-mediated Id-1 expression in human umbilical vein endothelial cells and inhibited cord formation by these cells on a Matrigel substrate. In a chick chorioallantoic membrane assay, ALK1-Fc reduced vascular endothelial growth factor–, fibroblast growth factor–, and BMP10-mediated vessel formation. The growth of B16 melanoma explants was also inhibited significantly by ALK1-Fc in this assay. Finally, ALK1-Fc treatment reduced tumor burden in mice receiving orthotopic grafts of MCF7 mammary adenocarcinoma cells. These data show the efficacy of chimeric ALK1-Fc proteins in mitigating vessel formation and support the view that ALK1-Fc is a powerful antiangiogenic agent capable of blocking vascularization. Mol Cancer Ther; 9(2); 379–</p></div>
small molecules
2026-08-11 | Targeting KIT prevents brain arteriovenous malformations driven by ALK1-deficient angiogenic endothelial cells.
Hereditary Hemorrhagic Telangiectasia type 2 (HHT2), caused by mutations in ACVRL1 ( also known as ALK1), is characterized by brain arteriovenous malformations (bAVMs), abnormal artery-vein connections for which treatment options remain limited. Despite evidence of endothelial cell (EC) heterogeneity, its role in bAVM pathogenesis remains poorly defined. Using endothelial-specific inducible Alk1 knockout mice (Alk1iECKO) and regionally resolved single-cell RNA sequencing, we show that loss of ALK1 signaling induces bAVMs predominantly in the perineural vascular plexus (PNVP). This process is driven by the emergence of a KIT+ angiogenic EC population with human AVM-like transcriptional features, including tip-cell markers and activation of PI3K and KRAS signaling pathways. Cross-species analyses and validation in human samples demonstrate that KIT expression is conserved in endothelial cells from both sporadic and HHT2 brain AVMs. Drug repurposing analysis identified KIT as a top actionable target, and we show that Kit is directly repressed by BMP9-ALK1-SMAD4 signaling. Pharmacological inhibition of KIT reduced angiogenic reprogramming and vascular malformations in vivo without affecting normal vasculature. These findings identify a pathogenic angiogenic EC state and position KIT signaling as a therapeutically actionable pathway in brain AVMs.
2026-08-02 | Intranasal bleomycin sclerotherapy versus local Avastin® therapy as an adjunct to laser treatment for epistaxis in hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia is a rare disease of vascular development, often accompanied by severe epistaxis. Multimodality treatment may improve epistaxis control, but the optimal combination of modalities has not yet been established. To study and compare the effects of adding intranasal bleomycin versus local Avastin ® therapy to laser treatment for epistaxis in patients with hereditary hemorrhagic telangiectasia. We present a case study of all hereditary hemorrhagic telangiectasia patients who underwent laser therapy with or without bleomycin sclerotherapy or local Avastin ® therapy for epistaxis during 8 consecutive years. We calculated the mean modified posttreatment epistaxis severity score changes, proportions of procedures after which a minimal important difference in modified epistaxis severity score was reached, and intervals between subsequent treatments. A higher mean modified epistaxis severity score change was seen after laser treatment combined with bleomycin, compared to laser treatment alone. There was a longer mean treatment interval after both laser combined with Avastin ® , and laser combined with bleomycin, compared to laser treatment alone. Adding bleomycin to laser treatment shows a higher modified epistaxis severity score improvement compared to laser treatment only or laser combined with Avastin ® in patients with hereditary hemorrhagic telangiectasia. Adding bleomycin or Avastin ® to laser may lengthen treatment intervals compared to laser therapy alone.
2026-07-21 | Living with hereditary hemorrhagic telangiectasia
The aim of this thesis was to contribute to improving diagnostic strategies, evaluating novel treatment approaches and exploring the broader impact of the disease of patients’ lives. In part I, the use of TTCE in PAVM-screening and follow-up was assessed. Reported key insights include prolonging the rescreening interval is safe in patients with initial negative screening, in children a conservative screening method is sufficient to prevent complications and chest CT can be withheld in patients with only a minimal shunt after PAVM embolization. In the future, these insights contribute to a more tailored approach with a decrease in the number of required diagnostics (TTCE and chest CT). For the treatment of HHT-related bleeding, there is a shift towards systemic treatments, of which two agents are described in part II of this thesis. Preliminary results of tacrolimus are positive; a randomized clinical trial is needed for further evaluation. The safety of engasertib is very promising in the phase 1b RCT and the efficacy will be further studied in the coming years. Lastly, part III describes the attempt to capture the impact of HHT on family planning and sexual activity with an unneglectable amount experiencing impact on sexual activity, emphasizing the need for improvement awareness and epistaxis management. Concluding, this thesis has examined three key aspects of the path towards cultivating tailored HHT-care and contributed to improved PAVM-screening strategies, the development of novel systemic treatment options and more knowledge about the impact of the disease with the ultimate goal of improving living with HHT.
2026-07-13 | Doxycycline for epistaxis in hereditary hemorrhagic telangiectasia: genotype-stratified outcomes
Hereditary Hemorrhagic Telangiectasia (HHT) patients experience recurrent epistaxis. Doxycycline has been proposed as a possible treatment, although its efficacy remains controversial. Whether the most common genotypes —ACVRL1, ENG, and SMAD4—contribute to a differential response has not been investigated. In this study, we evaluate the effectiveness of doxycycline among the different HHT genotypes. A retrospective cohort study was conducted at the University of Florida’s Hereditary Hemorrhagic Telangiectasia Center. Forty-one adult patients (age ≥18) with HHT, diagnosed by Curacao criteria and genetic testing, were classified as responders and non-responders based on the minimal clinically important change between pre- and post-treatment epistaxis severity score (ESS). Hemoglobin and hematocrit values were also collected to assess treatment response. Overall, the cohort was 61% female and 90.2% White, with a mean age of 58.1 years. 26 responders had a decrease (p<0.0001) in ESS from a baseline median of 4.6 (IQR 3.3) to post-treatment ESS of 2.4 (IQR 1.9). The total cohort ESS baseline median was 4.4 (IQR 3.3), and after a mean follow-up of 4.1 months, significantly (p<0.0001) decreased to an ESS of 3.3 (IQR 3.2). The mean hemoglobin and hematocrit values did not exhibit significant changes. The relationship between genotype and doxycycline response was not statistically significant. Patients with HHT treated with doxycycline showed an overall reduction in epistaxis severity, and it does not appear to be associated with genotype. Doxycycline may be a safe, effective and accessible treatment option for epistaxis in HHT.
2026-07-11 | ERK overstimulation leads to cell hyperproliferation in hereditary hemorrhagic telangiectasia landscape
Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder caused by pathogenic variants in members of the BMP9/ALK1 signaling hub. In the present study we show that, regardless of whether the alterations are caused by reduced BMP9/ALK1 signaling (pathogenic variants in the ENG or ALK1 genes) or by overactivation of this pathway (such as the SMAD6 pathogenic variants), all are associated with increased endothelial cell (EC) proliferation and high levels of ERK MAPK activation in patient biopsies. We reproduced this phenotype in vitro in ECs lacking SMAD6 or after SMAD1 knockdown using siRNA. Loss of SMAD6 leads to dysregulation of the Notch pathway, with downregulation of phosphatases and consequent overstimulation of ERK. In normal ECs, BMP9 and Notch signaling inhibit ERK activity by upregulating PPP1R3C, a regulatory subunit of the PP1 phosphatase. Notably, BMP9-mediated inhibition of ERK is abolished when cells are transfected with siRNA targeting PPP1R3C. ERK hyperactivation was also observed in an HHT2 mouse model (ALK1-2loxP;Cdh5-CreERT2). Loss of both ALK1 alleles in adult mice leads to vascular failure and hemorrhages in the lung and intestine; these injuries are significantly reduced by treatment with the MEK/ERK inhibitor selumetinib. Overall, our work identifies a key role for ERK activation involved in HHT pathogenesis, suggesting that ERK inhibition may represent a promising therapeutic strategy for these patients.
gene therapies
2026-08-14 | Brain Abscess as the Initial Manifestation of Hereditary Hemorrhagic Telangiectasia in a Child.
Brain abscess secondary to pulmonary arteriovenous malformation is rare in children and may be the first manifestation of hereditary hemorrhagic telangiectasia (HHT). We retrospectively reviewed the clinical presentation, laboratory findings, imaging examinations, and diagnostic process of a child with brain abscess associated with pulmonary arteriovenous malformation and HHT. A 12-year-old boy presented with fever, headache, and limb weakness. Brain abscess was diagnosed, and antimicrobial therapy was initiated. Laboratory testing revealed fungal infection and erythrocytosis. Further evaluation identified a pulmonary arteriovenous malformation. Although the family history was initially unremarkable, physical examination revealed facial telangiectasia, recurrent epistaxis, and digital clubbing in his father, fulfilling the Curaçao criteria for HHT. Right-to-left shunt should be considered in children with brain abscess of unclear origin. Early recognition of underlying HHT is critical for timely diagnosis and management.
2026-07-07 | Expected survival is decreased in hereditary hemorrhagic telangiectasia: Results from a population-based registry study.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder associated with substantial morbidity. The aim of this study was to estimate mortality in a country without centralized national care for HHT patients. Moreover, we identified causes of death and estimated the prevalence of HHT in Sweden. The Swedish National Patient Register (NPR) was used to identify individuals with HHT using the International Classification of Diseases (ICD) code I78.0. Cases included all individuals with this code between January 1, 2001 and December 31, 2003 (n = 393). Five age- and gender-matched controls from the general population were selected by Statistics Sweden (SCB) (n = 1965). Cases and controls were followed for survival until 2018 using the Swedish National Cause of Death Register (DORS). To calculate prevalence, we identified all individuals with the ICD code I78.0 in the NPR over 12 years, from January 1, 2007 to December 30, 2018. Life expectancy for cases with HHT after age 30 was estimated at 73.0 (68.0-77.2) compared to 80.5 (79.1-82.0) years for controls. Ischemic heart diseases, diseases of arteries, arterioles, capillaries, and liver diseases were significantly more common causes of death among HHT patients. The prevalence of HHT was estimated at 9.3 per 100,000 over the 12 years. HHT in Sweden is associated with markedly shorter expected survival compared to the general population, and known complications of HHT are among the most common causes of death. The estimated prevalence of HHT in Sweden was relatively low, possibly due to underdiagnosis of those with milder symptoms.
2026-06-30 | When Phenotype Outspeaks Genotype: Uncommon Vascular Anomalies in Suspected Hereditary Hemorrhagic Telangiectasia Despite Negative Genetic Testing.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder characterized by abnormal blood vessel formation involving the skin and visceral organs. Establishing the diagnosis can be challenging, particularly in the absence of classic clinical manifestations or confirmatory genetic findings. We report the case of a 42-year-old woman who presented with acute epigastric pain and was found to have extensive vascular abnormalities involving the liver, lungs, aorta, and mesenteric circulation. She had no history of recurrent epistaxis, mucocutaneous telangiectasias, or family history of vascular disease, and genetic testing for known vascular disorders was negative. Despite the absence of typical clinical and genetic features, the distribution and extent of vascular involvement raised a strong suspicion for underlying HHT. This case highlights the potential for a broader phenotypic spectrum of HHT and underscores the limitations of current diagnostic criteria and genetic testing approaches.
2026-06-29 | Atypical Presentation of Hereditary Hemorrhagic Telangiectasia Without Recurrent Epistaxis Leading to Delayed Diagnosis
Objective:Unusual clinical course Background:Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder characterized by multisystem arteriovenous malformations (AVMs).The earliest symptoms often appear in childhood and typically encompass recurrent epistaxis.Severe outcomes, including cerebral hemorrhage and thrombotic complications, can increase morbidity and mortality.HHT is estimated to have near-complete penetrance, such that 97% of patients exhibit symptoms by age 60. Case Report:A 71-year-old man presented with a 1-month history of progressive shortness of breath, fatigue, dizziness, and lower-extremity edema.Further evaluation revealed severe iron-deficiency anemia (hemoglobin 6.4 g/dL, serum iron 21 µg/dL, total iron-binding capacity 462 µg/dL, transferrin saturation ~ 5%, and ferritin 13 ng/mL).He received 4 units of packed red blood cells, resulting in symptomatic improvement.Imaging did not identify any additional visceral malformations; follow-up esophagogastroduodenoscopy and colonoscopy findings were normal.Despite negative endoscopic findings, intermittent occult gastrointestinal blood loss remained the leading consideration given his prior history of bleeding gastrointestinal AVMs and laboratory findings consistent with iron-deficiency anemia.Capsule endoscopy-recommended to screen for small-bowel telangiectasias-was deferred.His medical history was notable for a delayed diagnosis of HHT.He remained clinically asymptomatic until age 67, when he developed spontaneous bilateral subdural hematomas and gastrointestinal bleeding. Conclusions:This case highlights delayed recognition of HHT in the absence of recurrent epistaxis, followed by serious intracranial and gastrointestinal complications.Overreliance on classic mucocutaneous features may contribute to diagnostic delay.Clinicians should consider HHT in older adults with otherwise unexplained AVM-related hemorrhage or anemia to facilitate timely screening and management.
2026-06-25 | A Novel Frameshift Variant of the ACVRL1 Gene in a Korean Family with Hereditary Hemorrhagic Telangiectasia Type 2: A Case Report
Beom Joon Kim, M.D., Woo Jin Shin, M.D., Hyunji Kim, M.D., Soohyun Seo, M.D., Anna Cho, M.D., Sook-Hyang Jeong, M.D., Kyoung Un Park, M.D.. Lab Med Online 2026;16:258-63. https://doi.org/10.47429/lmo.2026.16.3.258
antibodies
2026-08-14 | Bevacizumab Reduces Epistaxis-Related Operative Burden in Hereditary Hemorrhagic Telangiectasia.
Bevacizumab reduced epistaxis-related ablation frequency by 55.6% in HHT patients. Over half of HHT patients (57.7%) required no ablation intervention after bevacizumab initiation. Maintenance bevacizumab dosing remains highly variable, underscoring the need for standardization.
2026-08-12 | Clinical characteristics of pulmonary hypertension associated with hereditary hemorrhagic telangiectasia treated with bevacizumab: a single-center case series.
Pulmonary hypertension (PH) is a severe complication of hereditary hemorrhagic telangiectasia (HHT). The experience with bevacizumab in HHT-PH is limited. Therefore, the aim was to provide our single-center experience with the use of bevacizumab in patients with HHT-PH. The clinical data of HHT-PH patients treated with bevacizumab were retrospectively reviewed between September 2021 and June 2024 at Beijing Anzhen Hospital, Capital Medical University. To describe the clinical features of these patients, we recruited pulmonary arterial hypertension (PAH) patients and PH associated with left heart diseases (PH-LHD) patients, matched for age and gender. The symptoms, underlying diseases, medication history, laboratory test results, treatments, and therapeutic responses were investigated retrospectively in all patients. In total, six cases of HHT-PH that were treated with bevacizumab, of which only five received follow-up after completing the 3-month induction therapy. Compared with PAH and PH-LHD patients, HHT-PH patients were characterized by high cardiac index (CI) [HHT-PH vs. PAH vs. PH-LHD: 6.10 (3.77, 7.60) vs. 2.37 (1.92, 3.03) vs. 2.38 (1.91, 2.63) L/min/m2, P=0.001] in conjunction with low systemic vascular resistance [740.93±333.06 vs. 1,836.07±673.64 vs. 1,667.78±453.84 dyn·s·cm-5, P=0.001] and PVR [189.94 (54.46, 289.89) vs. 886.70 (705.18, 1278.68) vs. 229.48 (179.15, 416.60) dyn·s·cm-5, P=0.002]. All the HHT-PH patients experienced significant improvements in symptoms (World Health Organization functional class), hemoglobin, brain natriuretic peptide levels and tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure after the induction therapy with bevacizumab. Of note, two of the five patients had a baseline CI <4 L/min/m2, yet still experienced clinically meaningful improvement after the bevacizumab induction therapy. Four out of five patients experienced improvements in hemodynamics and 6-minute walking distance after the induction therapy. Our study found that the hemodynamic profile of HHT-PH patients treated with bevacizumab differed significantly from that of PAH and PH-LHD. There might be patients with a CI below 4 L/min/m2 who were still in a high-output state and could benefit from bevacizumab treatment in clinical practice.
2026-06-27 | Implementation and Outcomes of a Structured Epistaxis Protocol in Hereditary Hemorrhagic Telangiectasia: An Observational Cohort Study from a Multidisciplinary Clinic.
BackgroundHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with multiorgan manifestations, necessitating a multidisciplinary approach. Epistaxis is a common manifestation leading to significant morbidity. Current treatments are variable in efficacy, and adequate control of epistaxis remains a significant challenge.ObjectiveTo describe the cohort of patients treated at a dedicated multidisciplinary HHT clinic and to evaluate the efficacy of an HHT-related epistaxis treatment protocol at a multidisciplinary HHT clinic.MethodsThis study included both retrospective and prospective cohorts of adult patients (≥ 18 years) with confirmed HHT attending a tertiary multidisciplinary clinic. The retrospective cohort comprised patients managed prior to the establishment of the treatment protocol and contributed to baseline demographic and disease characteristics only. The prospective cohort of patients, recruited from September 2022 to September 2024, was managed using a tiered protocol progressing from topical treatment to surgical intervention to systemic therapy. Epistaxis severity score (ESS) was recorded longitudinally. Treatment efficacy was assessed by comparing ESS at baseline, pre-intervention, and post-intervention time points.ResultsA total of 62 patients, including 31 retrospective and 31 prospective patients, were identified with a mean age of 52.5 ± 17.4 years and female predominance of 62.9%. Baseline ESS scores were highest in patients in the "Bevacizumab" group, followed by those in the "Surgical treatment" group, and lowest in patients in the "Topical treatment only" cohort (P = .001). Within the prospective cohort, significant improvements in ESS were observed following surgery (ΔESS = 4.31, P = .006) and bevacizumab (ΔESS = 4.74, P = .005). Nearly half (48.4%) of patients in this clinic achieved satisfactory control with conservative measures alone.ConclusionA structured, multidisciplinary protocol enables effective management of HHT-related epistaxis, matching treatment intensity to disease severity to achieve satisfactory symptom control for patients.
2026-05-04 | Bevacizumab as Rescue Therapy for GI Bleeding in Hereditary Hemorrhagic Telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by abnormal blood vessel formation, frequently involving the gastrointestinal (GI) tract. GI involvement can result in diffuse mucosal telangiectasis, chronic bleeding, iron-deficiency anemia, and transfusion dependence. Conventional treatments often provide limited benefit in patients with widespread disease. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has emerged as a potential disease-modifying agent through its anti-angiogenic properties. We report a case of a male patient with genetically confirmed HHT and comorbid pulmonary arterial hypertension who presented with recurrent GI bleeding. The patient had a long-standing history of GI bleeding requiring multiple endoscopic interventions, with findings of arteriovenous malformations throughout the GI tract. Prior management with conventional therapies provided only a transient benefit. The patient subsequently received intravenous bevacizumab induction therapy. Bevacizumab therapy resulted in marked clinical improvement, including hemoglobin stabilization, reduction in overt bleeding, and decreased transfusion requirements. Recurrence of bleeding following therapy discontinuation further supports a direct therapeutic effect. This case contributes to the growing body of evidence that VEGF inhibition is a biologically rational and clinically effective salvage strategy for refractory GI bleeding in HHT. Prospective studies are needed to define optimal dosing, maintenance strategies, and long-term outcomes.
2026-03-31 | Genotype-phenotype correlations and protein domain-level predictors of cerebrovascular malformations in hereditary hemorrhagic telangiectasia.
Hereditary Hemorrhagic Telangiectasia (HHT) exhibits marked phenotypic heterogeneity. Although gene-organ associations are well established for visceral involvement, predictors of cerebrovascular malformations (CVMs), particularly brain arteriovenous malformations (bAVMs), remain incompletely defined. This study aimed to investigate genotype-phenotype correlations and identify predictors of bAVMs in a genetically confirmed HHT cohort. We conducted a retrospective analysis of 142 Caucasian patients with genetically confirmed HHT. Clinical manifestations were systematically assessed and correlated with the mutated gene (ENG, ACVRL1, and SMAD4), variant type (truncating vs. non-truncating), and protein domain location. Multivariable logistic regression was performed to identify independent predictors of bAVMs. The cohort included 83 (58.5%) ACVRL1 and 53 (37.3%) ENG mutation carriers. Bivariate analysis demonstrated distinct phenotypic patterns. ENG mutations were strongly associated with pulmonary AVMs (p < 0.001) and bAVMs (p < 0.001), with bAVMs observed in 35.8% of ENG carriers compared with 3.6% of ACVRL1 carriers. In contrast, hepatic AVMs were more frequent among ACVRL1 carriers (44.6%), although this did not reach statistical significance (p = 0.086). In the multivariable logistic regression model (overall p < 0.001), younger age emerged as the sole independent predictor of bAVMs (OR 0.968, p = 0.040), whereas the mutated gene did not retain independent significance. ENG mutation carriers display a markedly increased cerebrovascular burden, confirming a gene-specific susceptibility to bAVMs. Younger age independently predicts bAVM presence. These findings support age- and genotype-informed risk stratification and may help refine screening strategies in HHT patients.
other
2026-01-24 | Beyond epistaxis: cascade screening and presymptomatic treatment of hereditary hemorrhagic telangiectasia.
Hereditary Hemorrhagic Telangiectasia is an autosomal dominant vascular disorder with clinical features of recurrent epistaxis, mucocutaneous telangiectasias, or visceral arteriovenous malformations, yet its early signs may be overlooked in children. We report a family in which a fifteen-year-old boy and his mother presented for genetic evaluation of recurrent epistaxis, after his previously well seven-year-old sister demised suddenly from likely spontaneous atraumatic intracranial hemorrhage (diagnosed clinically without confirmatory post-mortem imaging), following a brief history of headache and vomiting. The mother had a background of infrequent nosebleeds and a family history of recurrent epistaxis in multiple maternal relatives. Genetic testing identified heterozygosity for NM_001114753.3(ENG): c.1134G > A (p.Ala378=), a ClinVar classified pathogenic variant, confirming the diagnosis of hereditary hemorrhagic telangiectasia. Cascade testing for her two surviving children was done. Her fifteen-year-old son tested positive and was found on subsequent screening to have intracranial vascular malformations which were treated presymptomatically with gamma knife surgery. Her other son tested negative. This case emphasizes the importance of prompt recognition of hereditary hemorrhagic telangiectasia in children presenting with recurrent epistaxis and highlights the need for thorough family history. Pediatricians play a crucial role in early diagnosis and referral for genetic testing with subsequent surveillance imaging. Early identification may possibly reduce the risk of unfavorable outcomes such as intracranial hemorrhage. This case emphasizes the need for heightened awareness of hereditary hemorrhagic telangiectasia in pediatric practice and supports the value of integrating genetic cascade testing and organ-specific screening in at-risk children, even before symptoms appear.
2025-11-24 | An angiopoietin-2 vaccine improves arteriovenous malformation pathology in hereditary hemorrhagic telangiectasia mice.
Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder that causes systemic arteriovenous malformations (AVMs) associated with severe complications. Angiopoietin (ANG)-2 has been identified as a consistently upregulated secreted protein across various HHT models, and neutralizing ANG2 reduces AVMs in mice. ANG2 has thus emerged as a potential target for HHT treatment. Here, we report the development of a peptide vaccine (ANG2-P3:CRM197) that selectively targets ANG2 over ANG1 and tested its effectiveness in decreasing retinal AVMs in neonatal mice injected with BMP9/10 blocking antibodies, a model of HHT. Litter groups from female C57BL/6 mice immunized with ANG2-P3:CRM197 received injections of anti-BMP9/10 antibodies, and their retinas were examined for vascular pathology. The potential toxicity of the vaccine was evaluated in females 12 months post-immunization through echocardiography, basic metabolic panels, and lipid profiles. Circulating anti-ANG2 antibodies were detected in nursing neonates of vaccinated females, with antibody levels comparable between litters and their dams, indicating effective antibody transfer from the dams. A significant decrease in AVM number and size was observed in the retinas of pups exposed to ANG2-P3:CRM197 antibodies compared to unexposed pups. Arterial and venous diameters were normalized in the vaccinated pups' retinas. The vaccinated females showed no abnormalities in cardiac, liver, or kidney functions. A vaccine strategy targeting ANG2 appears safe and improves AVM pathology in HHT mice. These findings further support the potential of inhibiting ANG2 as a viable approach for treating AVMs in HHT.
2025-08-29 | From Epistaxis to Embolization: A Case of Hereditary Hemorrhagic Telangiectasia Presenting With Spontaneous Hemothorax.
Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a rare autosomal dominant disorder characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations (AVMs). We report a case of a 58-year-old female who presented with acute dyspnea and right-sided pleuritic chest pain. Her history included recurrent epistaxis since childhood and a positive family history of similar symptoms. Imaging revealed a right-sided hemorrhagic pleural effusion and pulmonary arteriovenous malformations (PAVMs), confirmed by CT pulmonary angiography and bubble contrast echocardiography. She underwent intercostal drainage followed by coil embolization of two large AVMs, with subsequent Amplatzer plug embolization on the contralateral side. Based on the Curacao criteria, a diagnosis of definite HHT was established. This case highlights hemothorax as a rare but potentially life-threatening initial manifestation of HHT. Early recognition, appropriate imaging, and timely embolization are essential to prevent recurrence and complications in patients with undiagnosed HHT presenting with pulmonary symptoms.
2024-10-26 | Red blood cell alloimmunization in transfused patients with hereditary hemorrhagic telangiectasia: A single centre retrospective study.
Hereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse. Retrospective chart review was conducted at St. Michael's Hospital (SMH) in Toronto, Canada. All adults with a definite clinical diagnosis of HHT AND inpatient hospital visits between January 1, 2011 and December 31, 2020 AND had undergone transfusion compatibility testing at SMH, were identified. Data were abstracted from electronic medical records. Simple descriptive statistics were used to analyze data. Institutional Research Ethics Board approval was obtained. 63 HHT patients underwent compatibility testing and were subsequently transfused at SMH. Median patient age at data abstraction was 70 years (Interquartile Range [IQR]: 18) and 35 (56 %) were female. RBC alloantibodies were found in 23 transfused patients (36.5 %) and were predominantly directed against Rh and Kell antigens: Anti-E (65 %), Anti-K (39 %) and Anti-c (22 %) were most common. Excluding an outlier who received 611 RBC units during the study period, the mean number of RBC units transfused per HHT patient at SMH was 22.1 units (Standard Deviation: 40.9, IQR: 17). Six (9.5 %) transfused patients experienced at least one transfusion reaction. RBC alloimmunization rate was 36.5 % in our cohort of transfused HHT patients; this is much higher than described in the general population and another transfused HHT cohort. The most commonly observed alloantibodies were Rh and Kell, supporting our policy of prophylactic phenotypic matching for these antigens for all transfused patients with HHT.
2024-09-17 | Catheter embolization for pulmonary arteriovenous malformations during chemotherapy for appendiceal adenocarcinoma: A case report of associated brain abscess.
Pulmonary arteriovenous malformations are rare, abnormal, low-resistance vascular structures that connect a pulmonary artery to a vein. They are common in patients with hereditary hemorrhagic telangiectasia; however, acquired malformations can occur in patients with underlying diseases such as chest trauma, hepatic cirrhosis, and mitral stenosis. Pulmonary arteriovenous malformations bypass the normal pulmonary capillary bed and result in intrapulmonary right-to-left shunts, which may cause central nervous system complications such as brain abscesses or ischemic stroke. Brain abscesses related to pulmonary arteriovenous malformations are not uncommon; however, reports of their occurrence during chemotherapy are limited. Here, we report the case of a 68-year-old woman with bilateral pulmonary arteriovenous malformations and appendiceal adenocarcinoma who developed a bacterial brain abscess during chemotherapy. The infection was treated using abscess drainage and antibiotic therapy. After the brain abscess healed, catheter embolization was performed on the pulmonary arteriovenous malformations and chemotherapy was resumed. The present case suggests that if a patient with a malignancy has a pulmonary arteriovenous malformation, clinicians should pay special attention to complications such as brain abscesses during chemotherapy. For patients who do not urgently need chemotherapy, embolization of the pulmonary arteriovenous malformation before chemotherapy may be a better treatment option.
proteins
2025-10-16 | Nasal RADA16 hydrogel application decreases epistaxis severity scores in adults with hereditary hemorrhagic telangiectasia.
More than 90% of adults with hereditary hemorrhagic telangiectasia (HHT) experience epistaxis, which can be recurrent and cause significant morbidity. RADA16 is a self-assembling peptide hydrogel approved by the US Food and Drug Administration for hemostasis and wound healing. In this cohort study, we assessed the effectiveness of nasal RADA16 application in controlling HHT-related epistaxis. A retrospective chart review was performed on a cohort of adult patients who received nasal RADA16 without any other changes in treatment. Pre- and post-Epistaxis Severity Scores (ESS), hemoglobin, and hematocrit were collected to assess treatment response. Of the included patients (n = 22), there were 26 applications of RADA16. The cohort was 54.5% male and 86.4% White, had a mean age of 55.5 years, and had a predominantly ACVRL1 genotype (40.9%). Baseline mean ESS was 5.0 and decreased by an average of 2.0 at an average of 46.9 days after treatment, which is 2.8 times more than the minimal clinically important difference for ESS in HHT (0.71). The mean baseline hemoglobin (n = 13) and hematocrit (n = 10), were 11.3 g/dL and 37.5%, respectively, and did not exhibit significant changes after RADA16 application. No bleeding, pain, or allergic reactions occurred due to the application. Several patients reported mild nasal congestion. Our experience demonstrates that RADA16 can be considered as a safe epistaxis treatment modality for HHT that is easy to apply and does not require the operating suite.
2025-06-24 | Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling.
Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are two distinct vascular diseases linked to impaired signaling through bone morphogenetic protein (BMP) receptor complexes in endothelial cells. Although BMP-9 plays a central role in activating this pathway by binding to ALK1 and BMPR-II, its precise function in the pulmonary microvasculature has remained unclear. In this study, we demonstrate a role for BMP-9 in regulating pulmonary vascular architecture and homeostasis. Our findings reveal that BMP-9 signaling intersects with VEGF pathways and contributes to the delicate balance between vascular growth and remodeling in the lungs. We also show that disruption of this pathway can shift vascular responses toward an HHT-like state, potentially altering disease susceptibility. These insights offer a unique perspective on how BMP-9 and ALK1 shape pulmonary vascular biology and suggest that targeting this axis could inform future strategies for treating complex vascular diseases such as PAH.
2024-10-01 | 7819 Hypoglycemia with Hereditary Hemorrhagic Telangiextsia in a Boy After Liver Transplantation
Abstract Disclosure: H. Miyagi: None. M. Igarashi: None. E. Tanimoto: None. R. Horikawa: None. Introduction: Hereditary hemorrhagic telangiectasia (HHT) causes arteriovenous malformation (AVM) in liver, lung, and brain. It is not clear whether it also causes hypoglycemia. We show a case of HHT combined with hypoglycemia after liver transplantation, improved by nutrition management and growth hormone treatment. Case: 11 months old boy born from a mother with HHT was diagnosed as having with AVM prenatally. He was once operated for the liver AVM but developed a new collateral circulation which caused severe heart failure and lead to liver transplantation. He showed severe growth retardation and malnutrition. His body weight was 4.6 kg and height were 60 cm (-5.8 SD) when he was 1 year old, and blood test showed low albumin for 3 g/dL (3.4 - 4.7 g/dL), and total protein for 4 g/dL (5.7 - 7.5 g/dL). Hypoglycemia was found while switching his nutrition from parenteral to enteral nutrition after operation. His insulin was under 0.3 µU/mL when his blood glucose was 49 mg/dL IGF1 was 17 ng/mL (ref.11 - 149 ng/mL), suggested growth hormone (GH) deficiency. GH stimulation test showed blunted response. GH treatment was started. Other pituitary hormones were within normal range. Nutritional support was added using high-calory milk. After GH treatment, IGF1 level increased to 87 ng/mL. GH and nutritional management improved not only his weight and height gain but also his glycemic control. Discussion: Hypoglycemia may be caused by both GHD and malnutrition. GHD and low IGF1 might be caused by malnutrition. Retesting GH secretion after improvement of nutrition is planned to clarify his pituitary function. Presentation: 6/2/2024
2024-03-01 | Abstract 2385 The role of the ALK1 protein in vascular disease and potential targetability in Crohn's disease
The ACVRL1 gene is highly expressed in endothelial cells and encodes the transmembrane protein activin receptor-like kinase 1 (ALK1), which is a type I cell-surface receptor serine/threonine kinase for the transforming growth factor-β (TGF-β) superfamily of ligands BMP9/GDF2 and BMP10. ALK1 comprises of an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain. Upon ligand binding, this receptor forms complexes with other TGF-β receptors, primarily BMP9 to activate intracellular downstream signaling pathways. The Smad pathway functions to regulate gene expression through transmitting nucleus signals from the TGFβ receptors. Signaling is transmitted by a cytoplasmic kinase domain of ALK1 by phosphorylating receptor-regulated Smad proteins (R-Smad proteins). Activated R-Smad proteins and the common-Smad (co-Smad) form a complex to regulate transcription of target genes together with cofactors. This pathway is essential for angiogenesis and vasculogenesis and a mutation can induce several vascular diseases. The Smad Pathway is also crucial for endothelial cell differentiation and homeostasis, which plays roles in Crohn's Disease. Differing mutations in the ACVRL1 gene can result in increased or decreased kinase activity as well as impaired ligand binding, disrupting of TGF-β signaling, and in some cases induce a rare genetic disorder known as Hereditary Hemorrhagic Telangiectasia (HHT). HHT is an inherited disorder characterized by abnormally formed blood vessels. TGF-β can act as both a tumor suppressor and a tumor promoter, and mutations or dysregulation of components in its pathway can lead to several types of cancer. In Crohn's disease patients, scientists were able to determine an increased risk of endoscopic relapse based on ALK1 levels. Additionally, activation of ALK1 has been shown to enhance colonic intestinal epithelial barrier integrity and function ex vivo in these studies. The Walton High School SMART team, with support from 3D molecular designs, has modeled ALK1 receptors to support testing of the ALK1 protein to develop potential therapies and interventions for Crohn's disease, HHT, and several cancers.
2023-03-31 | Data from ALK1-Fc Inhibits Multiple Mediators of Angiogenesis and Suppresses Tumor Growth
<div>Abstract<p>Activin receptor–like kinase-1 (ALK1) is a type I, endothelial cell–specific member of the transforming growth factor-β superfamily of receptors known to play an essential role in modulating angiogenesis and vessel maintenance. In the present study, we sought to examine the angiogenic and tumorigenic effects mediated upon the inhibition of ALK1 signaling using a soluble chimeric protein (ALK1-Fc). Of 29 transforming growth factor-β–related ligands screened by surface plasmon resonance, only bone morphogenetic protein (BMP9) and BMP10 displayed high-affinity binding to ALK1-Fc. In cell-based assays, ALK1-Fc inhibited BMP9-mediated Id-1 expression in human umbilical vein endothelial cells and inhibited cord formation by these cells on a Matrigel substrate. In a chick chorioallantoic membrane assay, ALK1-Fc reduced vascular endothelial growth factor–, fibroblast growth factor–, and BMP10-mediated vessel formation. The growth of B16 melanoma explants was also inhibited significantly by ALK1-Fc in this assay. Finally, ALK1-Fc treatment reduced tumor burden in mice receiving orthotopic grafts of MCF7 mammary adenocarcinoma cells. These data show the efficacy of chimeric ALK1-Fc proteins in mitigating vessel formation and support the view that ALK1-Fc is a powerful antiangiogenic agent capable of blocking vascularization. Mol Cancer Ther; 9(2); 379–</p></div>
small molecules
2026-08-11 | Targeting KIT prevents brain arteriovenous malformations driven by ALK1-deficient angiogenic endothelial cells.
Hereditary Hemorrhagic Telangiectasia type 2 (HHT2), caused by mutations in ACVRL1 ( also known as ALK1), is characterized by brain arteriovenous malformations (bAVMs), abnormal artery-vein connections for which treatment options remain limited. Despite evidence of endothelial cell (EC) heterogeneity, its role in bAVM pathogenesis remains poorly defined. Using endothelial-specific inducible Alk1 knockout mice (Alk1iECKO) and regionally resolved single-cell RNA sequencing, we show that loss of ALK1 signaling induces bAVMs predominantly in the perineural vascular plexus (PNVP). This process is driven by the emergence of a KIT+ angiogenic EC population with human AVM-like transcriptional features, including tip-cell markers and activation of PI3K and KRAS signaling pathways. Cross-species analyses and validation in human samples demonstrate that KIT expression is conserved in endothelial cells from both sporadic and HHT2 brain AVMs. Drug repurposing analysis identified KIT as a top actionable target, and we show that Kit is directly repressed by BMP9-ALK1-SMAD4 signaling. Pharmacological inhibition of KIT reduced angiogenic reprogramming and vascular malformations in vivo without affecting normal vasculature. These findings identify a pathogenic angiogenic EC state and position KIT signaling as a therapeutically actionable pathway in brain AVMs.
2026-08-02 | Intranasal bleomycin sclerotherapy versus local Avastin® therapy as an adjunct to laser treatment for epistaxis in hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia is a rare disease of vascular development, often accompanied by severe epistaxis. Multimodality treatment may improve epistaxis control, but the optimal combination of modalities has not yet been established. To study and compare the effects of adding intranasal bleomycin versus local Avastin ® therapy to laser treatment for epistaxis in patients with hereditary hemorrhagic telangiectasia. We present a case study of all hereditary hemorrhagic telangiectasia patients who underwent laser therapy with or without bleomycin sclerotherapy or local Avastin ® therapy for epistaxis during 8 consecutive years. We calculated the mean modified posttreatment epistaxis severity score changes, proportions of procedures after which a minimal important difference in modified epistaxis severity score was reached, and intervals between subsequent treatments. A higher mean modified epistaxis severity score change was seen after laser treatment combined with bleomycin, compared to laser treatment alone. There was a longer mean treatment interval after both laser combined with Avastin ® , and laser combined with bleomycin, compared to laser treatment alone. Adding bleomycin to laser treatment shows a higher modified epistaxis severity score improvement compared to laser treatment only or laser combined with Avastin ® in patients with hereditary hemorrhagic telangiectasia. Adding bleomycin or Avastin ® to laser may lengthen treatment intervals compared to laser therapy alone.
2026-07-21 | Living with hereditary hemorrhagic telangiectasia
The aim of this thesis was to contribute to improving diagnostic strategies, evaluating novel treatment approaches and exploring the broader impact of the disease of patients’ lives. In part I, the use of TTCE in PAVM-screening and follow-up was assessed. Reported key insights include prolonging the rescreening interval is safe in patients with initial negative screening, in children a conservative screening method is sufficient to prevent complications and chest CT can be withheld in patients with only a minimal shunt after PAVM embolization. In the future, these insights contribute to a more tailored approach with a decrease in the number of required diagnostics (TTCE and chest CT). For the treatment of HHT-related bleeding, there is a shift towards systemic treatments, of which two agents are described in part II of this thesis. Preliminary results of tacrolimus are positive; a randomized clinical trial is needed for further evaluation. The safety of engasertib is very promising in the phase 1b RCT and the efficacy will be further studied in the coming years. Lastly, part III describes the attempt to capture the impact of HHT on family planning and sexual activity with an unneglectable amount experiencing impact on sexual activity, emphasizing the need for improvement awareness and epistaxis management. Concluding, this thesis has examined three key aspects of the path towards cultivating tailored HHT-care and contributed to improved PAVM-screening strategies, the development of novel systemic treatment options and more knowledge about the impact of the disease with the ultimate goal of improving living with HHT.
2026-07-13 | Doxycycline for epistaxis in hereditary hemorrhagic telangiectasia: genotype-stratified outcomes
Hereditary Hemorrhagic Telangiectasia (HHT) patients experience recurrent epistaxis. Doxycycline has been proposed as a possible treatment, although its efficacy remains controversial. Whether the most common genotypes —ACVRL1, ENG, and SMAD4—contribute to a differential response has not been investigated. In this study, we evaluate the effectiveness of doxycycline among the different HHT genotypes. A retrospective cohort study was conducted at the University of Florida’s Hereditary Hemorrhagic Telangiectasia Center. Forty-one adult patients (age ≥18) with HHT, diagnosed by Curacao criteria and genetic testing, were classified as responders and non-responders based on the minimal clinically important change between pre- and post-treatment epistaxis severity score (ESS). Hemoglobin and hematocrit values were also collected to assess treatment response. Overall, the cohort was 61% female and 90.2% White, with a mean age of 58.1 years. 26 responders had a decrease (p<0.0001) in ESS from a baseline median of 4.6 (IQR 3.3) to post-treatment ESS of 2.4 (IQR 1.9). The total cohort ESS baseline median was 4.4 (IQR 3.3), and after a mean follow-up of 4.1 months, significantly (p<0.0001) decreased to an ESS of 3.3 (IQR 3.2). The mean hemoglobin and hematocrit values did not exhibit significant changes. The relationship between genotype and doxycycline response was not statistically significant. Patients with HHT treated with doxycycline showed an overall reduction in epistaxis severity, and it does not appear to be associated with genotype. Doxycycline may be a safe, effective and accessible treatment option for epistaxis in HHT.
2026-07-11 | ERK overstimulation leads to cell hyperproliferation in hereditary hemorrhagic telangiectasia landscape
Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder caused by pathogenic variants in members of the BMP9/ALK1 signaling hub. In the present study we show that, regardless of whether the alterations are caused by reduced BMP9/ALK1 signaling (pathogenic variants in the ENG or ALK1 genes) or by overactivation of this pathway (such as the SMAD6 pathogenic variants), all are associated with increased endothelial cell (EC) proliferation and high levels of ERK MAPK activation in patient biopsies. We reproduced this phenotype in vitro in ECs lacking SMAD6 or after SMAD1 knockdown using siRNA. Loss of SMAD6 leads to dysregulation of the Notch pathway, with downregulation of phosphatases and consequent overstimulation of ERK. In normal ECs, BMP9 and Notch signaling inhibit ERK activity by upregulating PPP1R3C, a regulatory subunit of the PP1 phosphatase. Notably, BMP9-mediated inhibition of ERK is abolished when cells are transfected with siRNA targeting PPP1R3C. ERK hyperactivation was also observed in an HHT2 mouse model (ALK1-2loxP;Cdh5-CreERT2). Loss of both ALK1 alleles in adult mice leads to vascular failure and hemorrhages in the lung and intestine; these injuries are significantly reduced by treatment with the MEK/ERK inhibitor selumetinib. Overall, our work identifies a key role for ERK activation involved in HHT pathogenesis, suggesting that ERK inhibition may represent a promising therapeutic strategy for these patients.
gene therapies
2026-08-14 | Brain Abscess as the Initial Manifestation of Hereditary Hemorrhagic Telangiectasia in a Child.
Brain abscess secondary to pulmonary arteriovenous malformation is rare in children and may be the first manifestation of hereditary hemorrhagic telangiectasia (HHT). We retrospectively reviewed the clinical presentation, laboratory findings, imaging examinations, and diagnostic process of a child with brain abscess associated with pulmonary arteriovenous malformation and HHT. A 12-year-old boy presented with fever, headache, and limb weakness. Brain abscess was diagnosed, and antimicrobial therapy was initiated. Laboratory testing revealed fungal infection and erythrocytosis. Further evaluation identified a pulmonary arteriovenous malformation. Although the family history was initially unremarkable, physical examination revealed facial telangiectasia, recurrent epistaxis, and digital clubbing in his father, fulfilling the Curaçao criteria for HHT. Right-to-left shunt should be considered in children with brain abscess of unclear origin. Early recognition of underlying HHT is critical for timely diagnosis and management.
2026-07-07 | Expected survival is decreased in hereditary hemorrhagic telangiectasia: Results from a population-based registry study.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder associated with substantial morbidity. The aim of this study was to estimate mortality in a country without centralized national care for HHT patients. Moreover, we identified causes of death and estimated the prevalence of HHT in Sweden. The Swedish National Patient Register (NPR) was used to identify individuals with HHT using the International Classification of Diseases (ICD) code I78.0. Cases included all individuals with this code between January 1, 2001 and December 31, 2003 (n = 393). Five age- and gender-matched controls from the general population were selected by Statistics Sweden (SCB) (n = 1965). Cases and controls were followed for survival until 2018 using the Swedish National Cause of Death Register (DORS). To calculate prevalence, we identified all individuals with the ICD code I78.0 in the NPR over 12 years, from January 1, 2007 to December 30, 2018. Life expectancy for cases with HHT after age 30 was estimated at 73.0 (68.0-77.2) compared to 80.5 (79.1-82.0) years for controls. Ischemic heart diseases, diseases of arteries, arterioles, capillaries, and liver diseases were significantly more common causes of death among HHT patients. The prevalence of HHT was estimated at 9.3 per 100,000 over the 12 years. HHT in Sweden is associated with markedly shorter expected survival compared to the general population, and known complications of HHT are among the most common causes of death. The estimated prevalence of HHT in Sweden was relatively low, possibly due to underdiagnosis of those with milder symptoms.
2026-06-30 | When Phenotype Outspeaks Genotype: Uncommon Vascular Anomalies in Suspected Hereditary Hemorrhagic Telangiectasia Despite Negative Genetic Testing.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder characterized by abnormal blood vessel formation involving the skin and visceral organs. Establishing the diagnosis can be challenging, particularly in the absence of classic clinical manifestations or confirmatory genetic findings. We report the case of a 42-year-old woman who presented with acute epigastric pain and was found to have extensive vascular abnormalities involving the liver, lungs, aorta, and mesenteric circulation. She had no history of recurrent epistaxis, mucocutaneous telangiectasias, or family history of vascular disease, and genetic testing for known vascular disorders was negative. Despite the absence of typical clinical and genetic features, the distribution and extent of vascular involvement raised a strong suspicion for underlying HHT. This case highlights the potential for a broader phenotypic spectrum of HHT and underscores the limitations of current diagnostic criteria and genetic testing approaches.
2026-06-29 | Atypical Presentation of Hereditary Hemorrhagic Telangiectasia Without Recurrent Epistaxis Leading to Delayed Diagnosis
Objective:Unusual clinical course Background:Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder characterized by multisystem arteriovenous malformations (AVMs).The earliest symptoms often appear in childhood and typically encompass recurrent epistaxis.Severe outcomes, including cerebral hemorrhage and thrombotic complications, can increase morbidity and mortality.HHT is estimated to have near-complete penetrance, such that 97% of patients exhibit symptoms by age 60. Case Report:A 71-year-old man presented with a 1-month history of progressive shortness of breath, fatigue, dizziness, and lower-extremity edema.Further evaluation revealed severe iron-deficiency anemia (hemoglobin 6.4 g/dL, serum iron 21 µg/dL, total iron-binding capacity 462 µg/dL, transferrin saturation ~ 5%, and ferritin 13 ng/mL).He received 4 units of packed red blood cells, resulting in symptomatic improvement.Imaging did not identify any additional visceral malformations; follow-up esophagogastroduodenoscopy and colonoscopy findings were normal.Despite negative endoscopic findings, intermittent occult gastrointestinal blood loss remained the leading consideration given his prior history of bleeding gastrointestinal AVMs and laboratory findings consistent with iron-deficiency anemia.Capsule endoscopy-recommended to screen for small-bowel telangiectasias-was deferred.His medical history was notable for a delayed diagnosis of HHT.He remained clinically asymptomatic until age 67, when he developed spontaneous bilateral subdural hematomas and gastrointestinal bleeding. Conclusions:This case highlights delayed recognition of HHT in the absence of recurrent epistaxis, followed by serious intracranial and gastrointestinal complications.Overreliance on classic mucocutaneous features may contribute to diagnostic delay.Clinicians should consider HHT in older adults with otherwise unexplained AVM-related hemorrhage or anemia to facilitate timely screening and management.
2026-06-25 | A Novel Frameshift Variant of the ACVRL1 Gene in a Korean Family with Hereditary Hemorrhagic Telangiectasia Type 2: A Case Report
Beom Joon Kim, M.D., Woo Jin Shin, M.D., Hyunji Kim, M.D., Soohyun Seo, M.D., Anna Cho, M.D., Sook-Hyang Jeong, M.D., Kyoung Un Park, M.D.. Lab Med Online 2026;16:258-63. https://doi.org/10.47429/lmo.2026.16.3.258
antibodies
2026-08-14 | Bevacizumab Reduces Epistaxis-Related Operative Burden in Hereditary Hemorrhagic Telangiectasia.
Bevacizumab reduced epistaxis-related ablation frequency by 55.6% in HHT patients. Over half of HHT patients (57.7%) required no ablation intervention after bevacizumab initiation. Maintenance bevacizumab dosing remains highly variable, underscoring the need for standardization.
2026-08-12 | Clinical characteristics of pulmonary hypertension associated with hereditary hemorrhagic telangiectasia treated with bevacizumab: a single-center case series.
Pulmonary hypertension (PH) is a severe complication of hereditary hemorrhagic telangiectasia (HHT). The experience with bevacizumab in HHT-PH is limited. Therefore, the aim was to provide our single-center experience with the use of bevacizumab in patients with HHT-PH. The clinical data of HHT-PH patients treated with bevacizumab were retrospectively reviewed between September 2021 and June 2024 at Beijing Anzhen Hospital, Capital Medical University. To describe the clinical features of these patients, we recruited pulmonary arterial hypertension (PAH) patients and PH associated with left heart diseases (PH-LHD) patients, matched for age and gender. The symptoms, underlying diseases, medication history, laboratory test results, treatments, and therapeutic responses were investigated retrospectively in all patients. In total, six cases of HHT-PH that were treated with bevacizumab, of which only five received follow-up after completing the 3-month induction therapy. Compared with PAH and PH-LHD patients, HHT-PH patients were characterized by high cardiac index (CI) [HHT-PH vs. PAH vs. PH-LHD: 6.10 (3.77, 7.60) vs. 2.37 (1.92, 3.03) vs. 2.38 (1.91, 2.63) L/min/m2, P=0.001] in conjunction with low systemic vascular resistance [740.93±333.06 vs. 1,836.07±673.64 vs. 1,667.78±453.84 dyn·s·cm-5, P=0.001] and PVR [189.94 (54.46, 289.89) vs. 886.70 (705.18, 1278.68) vs. 229.48 (179.15, 416.60) dyn·s·cm-5, P=0.002]. All the HHT-PH patients experienced significant improvements in symptoms (World Health Organization functional class), hemoglobin, brain natriuretic peptide levels and tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure after the induction therapy with bevacizumab. Of note, two of the five patients had a baseline CI <4 L/min/m2, yet still experienced clinically meaningful improvement after the bevacizumab induction therapy. Four out of five patients experienced improvements in hemodynamics and 6-minute walking distance after the induction therapy. Our study found that the hemodynamic profile of HHT-PH patients treated with bevacizumab differed significantly from that of PAH and PH-LHD. There might be patients with a CI below 4 L/min/m2 who were still in a high-output state and could benefit from bevacizumab treatment in clinical practice.
2026-06-27 | Implementation and Outcomes of a Structured Epistaxis Protocol in Hereditary Hemorrhagic Telangiectasia: An Observational Cohort Study from a Multidisciplinary Clinic.
BackgroundHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with multiorgan manifestations, necessitating a multidisciplinary approach. Epistaxis is a common manifestation leading to significant morbidity. Current treatments are variable in efficacy, and adequate control of epistaxis remains a significant challenge.ObjectiveTo describe the cohort of patients treated at a dedicated multidisciplinary HHT clinic and to evaluate the efficacy of an HHT-related epistaxis treatment protocol at a multidisciplinary HHT clinic.MethodsThis study included both retrospective and prospective cohorts of adult patients (≥ 18 years) with confirmed HHT attending a tertiary multidisciplinary clinic. The retrospective cohort comprised patients managed prior to the establishment of the treatment protocol and contributed to baseline demographic and disease characteristics only. The prospective cohort of patients, recruited from September 2022 to September 2024, was managed using a tiered protocol progressing from topical treatment to surgical intervention to systemic therapy. Epistaxis severity score (ESS) was recorded longitudinally. Treatment efficacy was assessed by comparing ESS at baseline, pre-intervention, and post-intervention time points.ResultsA total of 62 patients, including 31 retrospective and 31 prospective patients, were identified with a mean age of 52.5 ± 17.4 years and female predominance of 62.9%. Baseline ESS scores were highest in patients in the "Bevacizumab" group, followed by those in the "Surgical treatment" group, and lowest in patients in the "Topical treatment only" cohort (P = .001). Within the prospective cohort, significant improvements in ESS were observed following surgery (ΔESS = 4.31, P = .006) and bevacizumab (ΔESS = 4.74, P = .005). Nearly half (48.4%) of patients in this clinic achieved satisfactory control with conservative measures alone.ConclusionA structured, multidisciplinary protocol enables effective management of HHT-related epistaxis, matching treatment intensity to disease severity to achieve satisfactory symptom control for patients.
2026-05-04 | Bevacizumab as Rescue Therapy for GI Bleeding in Hereditary Hemorrhagic Telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by abnormal blood vessel formation, frequently involving the gastrointestinal (GI) tract. GI involvement can result in diffuse mucosal telangiectasis, chronic bleeding, iron-deficiency anemia, and transfusion dependence. Conventional treatments often provide limited benefit in patients with widespread disease. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has emerged as a potential disease-modifying agent through its anti-angiogenic properties. We report a case of a male patient with genetically confirmed HHT and comorbid pulmonary arterial hypertension who presented with recurrent GI bleeding. The patient had a long-standing history of GI bleeding requiring multiple endoscopic interventions, with findings of arteriovenous malformations throughout the GI tract. Prior management with conventional therapies provided only a transient benefit. The patient subsequently received intravenous bevacizumab induction therapy. Bevacizumab therapy resulted in marked clinical improvement, including hemoglobin stabilization, reduction in overt bleeding, and decreased transfusion requirements. Recurrence of bleeding following therapy discontinuation further supports a direct therapeutic effect. This case contributes to the growing body of evidence that VEGF inhibition is a biologically rational and clinically effective salvage strategy for refractory GI bleeding in HHT. Prospective studies are needed to define optimal dosing, maintenance strategies, and long-term outcomes.
2026-03-31 | Genotype-phenotype correlations and protein domain-level predictors of cerebrovascular malformations in hereditary hemorrhagic telangiectasia.
Hereditary Hemorrhagic Telangiectasia (HHT) exhibits marked phenotypic heterogeneity. Although gene-organ associations are well established for visceral involvement, predictors of cerebrovascular malformations (CVMs), particularly brain arteriovenous malformations (bAVMs), remain incompletely defined. This study aimed to investigate genotype-phenotype correlations and identify predictors of bAVMs in a genetically confirmed HHT cohort. We conducted a retrospective analysis of 142 Caucasian patients with genetically confirmed HHT. Clinical manifestations were systematically assessed and correlated with the mutated gene (ENG, ACVRL1, and SMAD4), variant type (truncating vs. non-truncating), and protein domain location. Multivariable logistic regression was performed to identify independent predictors of bAVMs. The cohort included 83 (58.5%) ACVRL1 and 53 (37.3%) ENG mutation carriers. Bivariate analysis demonstrated distinct phenotypic patterns. ENG mutations were strongly associated with pulmonary AVMs (p < 0.001) and bAVMs (p < 0.001), with bAVMs observed in 35.8% of ENG carriers compared with 3.6% of ACVRL1 carriers. In contrast, hepatic AVMs were more frequent among ACVRL1 carriers (44.6%), although this did not reach statistical significance (p = 0.086). In the multivariable logistic regression model (overall p < 0.001), younger age emerged as the sole independent predictor of bAVMs (OR 0.968, p = 0.040), whereas the mutated gene did not retain independent significance. ENG mutation carriers display a markedly increased cerebrovascular burden, confirming a gene-specific susceptibility to bAVMs. Younger age independently predicts bAVM presence. These findings support age- and genotype-informed risk stratification and may help refine screening strategies in HHT patients.
other
2026-01-24 | Beyond epistaxis: cascade screening and presymptomatic treatment of hereditary hemorrhagic telangiectasia.
Hereditary Hemorrhagic Telangiectasia is an autosomal dominant vascular disorder with clinical features of recurrent epistaxis, mucocutaneous telangiectasias, or visceral arteriovenous malformations, yet its early signs may be overlooked in children. We report a family in which a fifteen-year-old boy and his mother presented for genetic evaluation of recurrent epistaxis, after his previously well seven-year-old sister demised suddenly from likely spontaneous atraumatic intracranial hemorrhage (diagnosed clinically without confirmatory post-mortem imaging), following a brief history of headache and vomiting. The mother had a background of infrequent nosebleeds and a family history of recurrent epistaxis in multiple maternal relatives. Genetic testing identified heterozygosity for NM_001114753.3(ENG): c.1134G > A (p.Ala378=), a ClinVar classified pathogenic variant, confirming the diagnosis of hereditary hemorrhagic telangiectasia. Cascade testing for her two surviving children was done. Her fifteen-year-old son tested positive and was found on subsequent screening to have intracranial vascular malformations which were treated presymptomatically with gamma knife surgery. Her other son tested negative. This case emphasizes the importance of prompt recognition of hereditary hemorrhagic telangiectasia in children presenting with recurrent epistaxis and highlights the need for thorough family history. Pediatricians play a crucial role in early diagnosis and referral for genetic testing with subsequent surveillance imaging. Early identification may possibly reduce the risk of unfavorable outcomes such as intracranial hemorrhage. This case emphasizes the need for heightened awareness of hereditary hemorrhagic telangiectasia in pediatric practice and supports the value of integrating genetic cascade testing and organ-specific screening in at-risk children, even before symptoms appear.
2025-11-24 | An angiopoietin-2 vaccine improves arteriovenous malformation pathology in hereditary hemorrhagic telangiectasia mice.
Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder that causes systemic arteriovenous malformations (AVMs) associated with severe complications. Angiopoietin (ANG)-2 has been identified as a consistently upregulated secreted protein across various HHT models, and neutralizing ANG2 reduces AVMs in mice. ANG2 has thus emerged as a potential target for HHT treatment. Here, we report the development of a peptide vaccine (ANG2-P3:CRM197) that selectively targets ANG2 over ANG1 and tested its effectiveness in decreasing retinal AVMs in neonatal mice injected with BMP9/10 blocking antibodies, a model of HHT. Litter groups from female C57BL/6 mice immunized with ANG2-P3:CRM197 received injections of anti-BMP9/10 antibodies, and their retinas were examined for vascular pathology. The potential toxicity of the vaccine was evaluated in females 12 months post-immunization through echocardiography, basic metabolic panels, and lipid profiles. Circulating anti-ANG2 antibodies were detected in nursing neonates of vaccinated females, with antibody levels comparable between litters and their dams, indicating effective antibody transfer from the dams. A significant decrease in AVM number and size was observed in the retinas of pups exposed to ANG2-P3:CRM197 antibodies compared to unexposed pups. Arterial and venous diameters were normalized in the vaccinated pups' retinas. The vaccinated females showed no abnormalities in cardiac, liver, or kidney functions. A vaccine strategy targeting ANG2 appears safe and improves AVM pathology in HHT mice. These findings further support the potential of inhibiting ANG2 as a viable approach for treating AVMs in HHT.
2025-08-29 | From Epistaxis to Embolization: A Case of Hereditary Hemorrhagic Telangiectasia Presenting With Spontaneous Hemothorax.
Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a rare autosomal dominant disorder characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations (AVMs). We report a case of a 58-year-old female who presented with acute dyspnea and right-sided pleuritic chest pain. Her history included recurrent epistaxis since childhood and a positive family history of similar symptoms. Imaging revealed a right-sided hemorrhagic pleural effusion and pulmonary arteriovenous malformations (PAVMs), confirmed by CT pulmonary angiography and bubble contrast echocardiography. She underwent intercostal drainage followed by coil embolization of two large AVMs, with subsequent Amplatzer plug embolization on the contralateral side. Based on the Curacao criteria, a diagnosis of definite HHT was established. This case highlights hemothorax as a rare but potentially life-threatening initial manifestation of HHT. Early recognition, appropriate imaging, and timely embolization are essential to prevent recurrence and complications in patients with undiagnosed HHT presenting with pulmonary symptoms.
2024-10-26 | Red blood cell alloimmunization in transfused patients with hereditary hemorrhagic telangiectasia: A single centre retrospective study.
Hereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse. Retrospective chart review was conducted at St. Michael's Hospital (SMH) in Toronto, Canada. All adults with a definite clinical diagnosis of HHT AND inpatient hospital visits between January 1, 2011 and December 31, 2020 AND had undergone transfusion compatibility testing at SMH, were identified. Data were abstracted from electronic medical records. Simple descriptive statistics were used to analyze data. Institutional Research Ethics Board approval was obtained. 63 HHT patients underwent compatibility testing and were subsequently transfused at SMH. Median patient age at data abstraction was 70 years (Interquartile Range [IQR]: 18) and 35 (56 %) were female. RBC alloantibodies were found in 23 transfused patients (36.5 %) and were predominantly directed against Rh and Kell antigens: Anti-E (65 %), Anti-K (39 %) and Anti-c (22 %) were most common. Excluding an outlier who received 611 RBC units during the study period, the mean number of RBC units transfused per HHT patient at SMH was 22.1 units (Standard Deviation: 40.9, IQR: 17). Six (9.5 %) transfused patients experienced at least one transfusion reaction. RBC alloimmunization rate was 36.5 % in our cohort of transfused HHT patients; this is much higher than described in the general population and another transfused HHT cohort. The most commonly observed alloantibodies were Rh and Kell, supporting our policy of prophylactic phenotypic matching for these antigens for all transfused patients with HHT.
2024-09-17 | Catheter embolization for pulmonary arteriovenous malformations during chemotherapy for appendiceal adenocarcinoma: A case report of associated brain abscess.
Pulmonary arteriovenous malformations are rare, abnormal, low-resistance vascular structures that connect a pulmonary artery to a vein. They are common in patients with hereditary hemorrhagic telangiectasia; however, acquired malformations can occur in patients with underlying diseases such as chest trauma, hepatic cirrhosis, and mitral stenosis. Pulmonary arteriovenous malformations bypass the normal pulmonary capillary bed and result in intrapulmonary right-to-left shunts, which may cause central nervous system complications such as brain abscesses or ischemic stroke. Brain abscesses related to pulmonary arteriovenous malformations are not uncommon; however, reports of their occurrence during chemotherapy are limited. Here, we report the case of a 68-year-old woman with bilateral pulmonary arteriovenous malformations and appendiceal adenocarcinoma who developed a bacterial brain abscess during chemotherapy. The infection was treated using abscess drainage and antibiotic therapy. After the brain abscess healed, catheter embolization was performed on the pulmonary arteriovenous malformations and chemotherapy was resumed. The present case suggests that if a patient with a malignancy has a pulmonary arteriovenous malformation, clinicians should pay special attention to complications such as brain abscesses during chemotherapy. For patients who do not urgently need chemotherapy, embolization of the pulmonary arteriovenous malformation before chemotherapy may be a better treatment option.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
14 orphan drug designations for Hereditary hemorrhagic telangiectasia.
14 orphan drug designations for Hereditary hemorrhagic telangiectasia.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Human bispecific monoclonal antibody targeting ALK1 and BMPRII | antibodies | EMA | 2025-07-18 | — | Maxia Strategies-Europe Limited |
BMPRII: ALK1 bispecific clustering agonist antibody | antibodies | FDA | 2025-06-09 | — | Diagonal Therapeutics |
6-(4-(1-amino-3-hydroxycyclobutyl)phenyl)-1-ethyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one, L-tartrate salt | small molecules | EMA | 2023-03-20 | — | FGK Representative Service GmbH |
6-(4-((1s,3s)-1-amino-3-hydroxycyclobutyl) phenyl)-1-ethyl-7- phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one L-Tartrate salt | small molecules | FDA | 2022-12-07 | — | Vaderis Therapeutics AG |
Bevacizumab | antibodies | FDA | 2022-10-12 | — | Laboratoires Delbert SAS |
pazopanib | small molecules | FDA | 2019-10-09 | — | HHT Foundation International (d/b/a Cure HHT) |
Etamsylate | small molecules | EMA | 2018-11-19 | — | Dobecure S.L. |
thalidomide | small molecules | FDA | 2017-07-19 | — | PlumeStars s.r.l. |
Thalidomide | small molecules | EMA | 2017-02-27 | — | PlumeStars s.r.l. |
Bevacizumab | antibodies | EMA | 2014-12-16 | — | Laboratoires Delbert |
Bazedoxifene acetate | small molecules | EMA | 2014-11-19 | — | Consejo Superior de Investigaciones Cientificas (CSIC) |
bevacizumab | antibodies | FDA | 2010-10-21 | — | Terence M. Davidson, MD |
raloxifene hydrochloride | small molecules | FDA | 2010-08-20 | — | Consejo Superior de Investigaciones Cientificas |
Raloxifene hydrochloride | small molecules | EMA | 2010-06-10 | — | Consejo Superior de Investigaciones Cientificas (CSIC) |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.