Clinical characteristics of hereditary hemorrhagic telangiectasia - case series and review of the literature

Introduction. Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder with estimated prevalence of one in 5,000 to 10,000. The disease has age-related penetrance and the HHT signs and symptoms occur and worsen with age. A diagnosis of HHT is based on the Curacao`s criteria. Case report. We report a case series of 6 patients diagnosed with HHT, 5 with definite and one with probable diagnosis according to the Curacao criteria. In 5 patients, the recurrent epistaxis occurred in adolescence as the first presentation while one patient presented with melena. The diagnosis was delayed in 5 patients and the presence of HHT was diagnosed during or after the fifth decade. In 4 patients, the overt gastrointestinal bleeding occurred in the later course of the disease. The asymptomatic pulmonary circulation arteriovenous malformations were detected in 2 patients. The cerebral arteriovenous malformations were not detected. Conclusion. Hereditary hemorrhagic telangiectasia is a rare disorder affecting multiple organs. It should be considered in the adolescents with recurrent epistaxis and in the differential diagnosis of anemia with signs of the gastrointestinal bleeding in order to shorten the delay in the diagnosis and subsequently improve the outcome of the disease.

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Hereditary haemorrhagic telangiectasia and pregnancy: a review of the literature

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1286-z ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Olivier Dupuis ◽

Laura Delagrange ◽

Sophie Dupuis-Girod

Keyword(s):

Heart Failure ◽

Literature Review ◽

Arteriovenous Malformations ◽

Case Reports ◽

Case Series ◽

Main Body ◽

Hereditary Haemorrhagic Telangiectasia ◽

Review Of The Literature ◽

Management Decisions ◽

Recurrent Epistaxis

Abstract Background Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder that has prevalence of 1:5000 to 1:8000, and which is characterised by recurrent epistaxis, cutaneous telangiectasia, and arteriovenous malformations (AVMs) that affect many organs including the lungs, gastrointestinal tract, liver, and central nervous system. The aim here was to carry out a review of the literature on HHT complications during pregnancy in order to guide management decisions. Main body A literature review was carried out to analyse all publications on complications that occurred during pregnancy in women with HHT. The PubMed/Medline and Scopus databases were searched. The complications observed in HHT women during pregnancy were then described. The authors identified 5 case series and 31 case reports that describe the evolution of 1577 pregnancies in 630 women with HHT. The overall maternal death rate described in the case series was estimated at 1.0% of pregnancies in the case series and 2 maternal deaths occurred in 31 pregnancy case reports. Severe maternal complications occurred in 2.7 to 6.8% of pregnancies in the case series. Severe complications occurred mostly in the second and third trimester in non-diagnosed and non-screened HHT patients. Severe complications were related to visceral involvement. The most frequent complications were related to pulmonary arteriovenous malformations (PAVMs) (haemothorax (n = 10), haemoptysis (n = 4), and severe hypoxaemia (n = 3)). Neurological complications were related to PAVMs in one case (right to left shunt) and to cerebral arteriovenous malformations (CAVM) and intracranial haemorrhage in 2 cases. Complications were related to hepatic arteriovenous malformations (HAVMs) in 8 cases (acutely decompensated heart failure due to hepatic involvement (n = 1), dyspnoea related to heart failure (n = 5), and hepatobiliary necrosis (n = 2)). Conclusion Based on the literature review, most pregnancies in HHT women occur normally. However, these pregnancies should be considered high-risk, given the potential life-threatening events related to AVM rupture. Furthermore, there is currently no international consensus regarding the medical follow-up of pregnancy in women with HHT and the aim here was to carry out a review of the literature in order to guide screening and management decisions for this rare disease.

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Hereditary Hemorrhagic Telangiectasia in a Sudanese Patient

Case Reports in Medicine ◽

10.1155/2020/6395629 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Omer Ali Mohamed Ahmed Elawad ◽

Ahmed Abdalazim Dafallah Albashir ◽

Mohammed Mahgoub Mirghani Ahmed ◽

Ahmed Ali Mohamed Ahmed Elawad ◽

Osman Eltieb Elbasheer Mohamed

Keyword(s):

Heart Failure ◽

Mitral Regurgitation ◽

Hereditary Hemorrhagic Telangiectasia ◽

Hepatic Veins ◽

Autosomal Dominant Disorder ◽

Liver Size ◽

Abdominal Ultrasonography ◽

Lower Lip ◽

Her Family ◽

Recurrent Epistaxis

Background. Hereditary hemorrhagic telangiectasia (HHT) also known as Osler–Weber–Rendu syndrome is a rare autosomal dominant disorder, which results in vascular dysplasia affecting mainly visceral and mucocutaneous organs. Case Presentation. A 65-year-old woman with a 12-year history of recurrent spontaneous epistaxis presented with shortness of breath, easy fatigability, and bilateral lower limb edema. Her family history was significant for definite hereditary hemorrhagic telangiectasia in first-degree relatives. During the previous 15 days, she has experienced three episodes of recurrent nasal bleeding. She has a background of chronic mitral regurgitation. Physical examination revealed telangiectases in her tongue, lower lip, and hand in addition to signs of congestive heart failure. The patient met 3\4 Curacao criteria and had a definite HHT. Her laboratory workup revealed a hemoglobin count of 5.4 g/dl. Echocardiography revealed a left systolic ejection fraction of 51% with left atrial dilatation and severe mitral regurgitation. Chest X-ray showed features of cardiomegaly and pulmonary edema. The abdominal ultrasonography showed enlarged liver size with homogenous texture and congested hepatic veins without features of hepatic AVMs. She was treated with intravenous frusemide, iron supplement, tranexamic acid, blood transfusion, and nasal packing. Conclusions. HTT usually passes unnoticed in Sudan. The rarity of HHT, difficulties in affording diagnostic imaging studies, and low clinical suspicion among doctors are important contributing factors. Anemia resulting from recurrent epistaxis might have an influential role in precipitating acute heart failure in those with chronic rheumatic valvular disease.

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High output cardiac failure in 3 patients with hereditary hemorrhagic telangiectasia and hepatic vascular malformations, evaluation of treatment

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01583-6 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Lilian B. Olsen ◽

Anette D. Kjeldsen ◽

Mikael K. Poulsen ◽

Jens Kjeldsen ◽

Annette D. Fialla

Keyword(s):

Liver Transplantation ◽

Orthotopic Liver Transplantation ◽

Cardiac Failure ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Vascular Malformations ◽

Symptom Relief ◽

Case Series ◽

Hospital Treatment ◽

High Output

Abstract Background This report addresses how patients with hereditary hemorrhagic telangiectasia (HHT) and high output cardiac failure (HOCF) due to hepatic vascular malformations, should be evaluated and could be treated. HHT is a genetic disorder, leading to vascular abnormalities with potentially serious clinical implications. In the liver, arteriovenous malformations occur in more than 70% of patients, but only about 8% present clinical symptoms such as HOCF with pulmonary hypertension and less commonly portal hypertension, biliary ischemia and hepatic encephalopathy. Results Three female patients with HHT type 2 and HOCF caused by severe arteriovenous malformations in the liver are presented in this case series. The patients were seen at the HHT-Centre at Odense University Hospital. Treatment with either orthotopic liver transplantation (one patient) or bevacizumab (two patients) was initiated. All patients experienced marked symptom relief and objective improvement. New York Heart Association—class were improved, ascites, peripheral edema and hence diuretic treatment was markedly reduced or discontinued in all three patients. Bevacizumab also resulted in notable effects on epistaxis and anemia. Conclusion Our findings substantiate the importance of identification of symptomatic arteriovenous malformations in the liver in patients with HHT. Bevacizumab may possibly, as suggested in this case series and supported by previous case studies, postpone the time to orthotopic liver transplantation or even make it unnecessary. Bevacizumab represents a promising new treatment option, which should be investigated further in clinical trials.

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Hereditary Hemorrhagic Telangiectasia: A Primer for Critical Care Nurses

Critical Care Nurse ◽

10.4037/ccn2016270 ◽

2016 ◽

Vol 36 (3) ◽

pp. 36-48 ◽

Cited By ~ 1

Author(s):

Kathleen M. Sacco ◽

Thomas W. Barkley

Keyword(s):

Critical Care ◽

Health Care Providers ◽

Genetic Disease ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Early Death ◽

Signs And Symptoms ◽

Critical Care Nurses ◽

Care Providers ◽

Abnormal Growth

Hereditary hemorrhagic telangiectasia is a rare, autosomal dominant genetic disease that causes abnormal growth of blood vessels and, subsequently, life-threatening arteriovenous malformations in vital organs. Epistaxis may be one of the initial clues that a patient has more serious, generalized arteriovenous malformations. Recommended treatment involves careful evaluation to determine the severity and risk of spontaneous rupture of the malformations and the management of various signs and symptoms. The disease remains undiagnosed in many patients, and health care providers may miss the diagnosis until catastrophic events happen in multiple family members. Prompt recognition of hereditary hemorrhagic telangiectasia and early intervention can halt the dangerous course of the disease. Critical care nurses can assist with early diagnosis within families with this genetic disease, thus preventing early death and disability.

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A novel treatment for patients with hereditary haemorrhagic telangiectasia

The Journal of Laryngology & Otology ◽

10.1258/00222150260293709 ◽

2002 ◽

Vol 116 (10) ◽

pp. 849-850 ◽

Cited By ~ 3

Author(s):

T. B. Farnan ◽

G. Gallagher ◽

C. M. Scally

Keyword(s):

Fibrin Glue ◽

Arteriovenous Malformations ◽

Autosomal Dominant ◽

Hereditary Haemorrhagic Telangiectasia ◽

Cerebral Arteriovenous Malformations ◽

Autosomal Dominant Disorder ◽

Novel Treatment ◽

Recurrent Epistaxis ◽

Thin Walled ◽

Intractable Epistaxis

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by dermal, mucosal, and visceral telangiectases as well as pulmonary and cerebral arteriovenous malformations. Recurrent epistaxis occurs in the majority of patients, and by the very nature of the thin walled vessels involved it is often refractory to conventional forms of treatment. We present the case of an 82-year-old lady with intractable epistaxis secondary to HHT, that was successfully controlled by the application of fibrin glue.

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Resveratrol As a Novel Treatment for Recurrent Epistaxis in SMAD4+ Hereditary Hemorrhagic Telangiectasia

Blood ◽

10.1182/blood-2021-149800 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1048-1048

Author(s):

Shahbegh Gill ◽

Shadi Swaidani ◽

Joseph Parambil ◽

Keith R. McCrae

Keyword(s):

Quality Of Life ◽

Hereditary Hemorrhagic Telangiectasia ◽

Autosomal Dominant ◽

Deficiency Anemia ◽

Severe Bleeding ◽

Autosomal Dominant Disorder ◽

Severity Scores ◽

Recurrent Epistaxis ◽

History Of

Abstract Introduction Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by the development of arteriovenous malformations or telangiectasias that may affect any organ system, but are most prevalent in the nose and gastrointestinal tract. Nasal telangiectasia account for epistaxis, the most frequent manifestation of HHT, which may be frequent, debilitating and lead to decreased quality of life. Epistaxis is quantified by the Epistaxis Severity Scores (ESS), which ranges from 1-10 with higher scores associated with more severe bleeding. The diagnosis of HHT is based on clinical criteria and requires three or more of the following features: epistaxis, mucocutaneous telangiectasis, visceral AVMs, and/or a family history of HHT. HHT is associated with several mutations that may involve ENG, ACVRL1, or SMAD4; the latter occurs in only ~2% of HHT patients, which is also associated with the Juvenile Polyposis Syndrome (JPS), another autosomal dominant disorder associated with an increased risk for colorectal, stomach, small intestine, and pancreatic cancers. Methods Case report with serial ESS scores, hemoglobin and hematocrit monitoring. Results A 25-year-old male was diagnosed with JPS/HHT and a c.1081C>T mutation in SMAD4 leading to an R361C missense mutation was diagnosed in 2013. The patient had a longstanding history of frequent epistaxis leading to severe iron deficiency anemia and requiring at least two 750 mg iron infusions annually (total of 14), and did not improve with oral iron supplements. In December 2020, the patient initiated a 1 g daily dose of resveratrol for general anti-aging and health benefits. His epistaxis improved immediately, and his ESS decreased from 6 (consistent with severe bleeding) to 1 (no bleeding) over a two week period. The frequency, severity and duration of epistaxis all improved dramatically (Figure). No additional iron therapy has been required since initiation of resveratrol. Recent serum iron and ferritin values (6/2021) were both within normal limits. Of interest, in parallel with the resolution of epistaxis, the patient also had a dramatic reduction in colonic polyposis after starting resveratrol. Conclusions There are no approved therapies for the treatment of HHT, and patients with this disorder may suffer from a markedly reduced quality of life due to unpredictable epistaxis and other manifestations. While a responses to bevacizumab have been reported in 60-70% of patients, treatment is expensive and may be associated with thromboembolic events, and patients may become refractory over time. Invasive approaches such as sclerotherapy may be initially, but only temporarily effective. Thus, there is an urgent need for better HHT therapies. Figure 1 Figure 1. Disclosures McCrae: Sanofi, Novartis, Alexion, and Johnson & Johnson: Consultancy, Honoraria; Dova, Novartis, Rigel, and Sanofi Genzyme: Consultancy.

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Significant Hematochezia and Intracranial Bleeding in Neonatal Hereditary Hemorrhagic Telangiectasia

American Journal of Perinatology Reports ◽

10.1055/s-0039-1677735 ◽

2019 ◽

Vol 09 (01) ◽

pp. e10-e14 ◽

Cited By ~ 1

Author(s):

Matthew Merves ◽

Kimberly Parsons ◽

Adina Alazraki ◽

Jonathan Meisel ◽

Cary Sauer ◽

...

Keyword(s):

High Risk ◽

Gastrointestinal Bleeding ◽

Intracranial Hemorrhage ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Autosomal Dominant ◽

Clinical Course ◽

Vascular Dysplasia ◽

Prenatal Imaging ◽

Delivery Options

AbstractHereditary hemorrhagic telangiectasia (HHT) is an underreported autosomal dominant vascular dysplasia. Neonatal presentations of HHT are rare, as this disorder typically presents in adolescence or beyond with epistaxis. We report a female neonate with hematochezia on the 1st day of life secondary to multiple gastrointestinal arteriovenous malformations (AVMs) along with intracranial hemorrhage. We describe her clinical course and management, as well as her novel family mutation in ENG. This is the first reported HHT case with significant gastrointestinal bleeding in the newborn. We review neonatal HHT and raise the consideration for more directed prenatal imaging and delivery options for fetuses at high risk of HHT.

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High-Output Heart Failure Contributing to Recurrent Epistaxis Kiesselbach Area Syndrome in a Patient With Hereditary Hemorrhagic Telangiectasia

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709617692833 ◽

2017 ◽

Vol 5 (1) ◽

pp. 232470961769283

Author(s):

Venugopal Brijmohan Bhattad ◽

Jennifer N. Bowman ◽

Hemang B. Panchal ◽

Timir K. Paul

Keyword(s):

Heart Failure ◽

Blood Vessels ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Hemoglobin Level ◽

Blood Disorder ◽

Recurrent Epistaxis ◽

High Output Heart Failure ◽

Abnormal Bleeding ◽

High Output

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare genetic blood disorder that leads to abnormal bleeding due to absent capillaries and multiple abnormal blood vessels known as arteriovenous malformations. A feature of HHT is high-output heart failure due to multiple arteriovenous malformations. High-output heart failure can lead to recurrent epistaxis Kiesselbach area syndrome (REKAS), further exacerbating heart failure through increased blood loss and resultant anemia. We report a patient with HHT who presented with high-output heart failure contributing to REKAS. In patients with REKAS, we propose if anemia is present, REKAS can be avoided by correcting the anemia by increasing the hemoglobin level to greater than 9 to 10 g/dL. This decreases hyperdynamic circulation and reduces pressure in the blood vessels of the nose.

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An International Multicenter Study of Intravenous Bevacizumab for the Treatment of Chronic Bleeding and Anemia in Hereditary Hemorrhagic Telangiectasia: The Inhibit-Bleed Study

Blood ◽

10.1182/blood-2019-129418 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1060-1060

Author(s):

Hanny Al-Samkari ◽

Raj S. Kasthuri ◽

Hasan A. Albitar ◽

Yahya Almodallal ◽

Marcelo M. Serra ◽

...

Keyword(s):

Hereditary Hemorrhagic Telangiectasia ◽

Research Funding ◽

Case Series ◽

Dramatic Reduction ◽

Off Label ◽

Bevacizumab Treatment ◽

Transfusion Requirements ◽

Platelet Disorder ◽

Recurrent Epistaxis ◽

Rbc Transfusion

Introduction : Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare hereditary multisystem vascular disease of disordered angiogenesis. Pathologic elevations in vascular endothelial growth factor (VEGF) result in fragile, abnormal vessels in nasal and gastrointestinal (GI) mucosa causing recurrent epistaxis, chronic GI bleeding, and anemia that is often transfusion-dependent. Bevacizumab is a monoclonal IgG1 antibody that neutralizes circulating VEGF and is a potential targeted anti-angiogenic treatment in HHT, which has no FDA-approved therapy. Data for use of intravenous (IV) bevacizumab in HHT is currently limited to case reports and small single-center retrospective case series. The International HHT Intravenous Bevacizumab Investigative Team study of Bleeding (InHIBIT-Bleed) is an international collaboration of HHT Centers seeking to more definitively describe the safety and effectiveness of systemic bevacizumab to treat chronic bleeding and anemia in HHT. Methods : The following data was retrospectively collected at each participating center for all HHT patients treated for at least 3 months with off-label systemic bevacizumab for chronic bleeding: demographics, baseline HHT characteristics, epistaxis severity score (ESS, a validated 10-point scale to evaluate epistaxis in HHT), bevacizumab dosing, treatment-emergent adverse events (TEAEs), hemoglobin (Hgb), red blood cell (RBC) transfusions, and IV iron infusions. Hgb and ESS at baseline were compared with post-bevacizumab values at 3, 6, 9, and 12 months with the paired t-test. RBC transfusion and iron infusion requirements before and after bevacizumab treatment were compared with the Wilcoxon signed rank test. Results : 140 HHT patients were treated with IV bevacizumab for chronic bleeding for a median of 23 (range, 3-96) months with a median of 12 (range, 2-74) total infusions. Bevacizumab was dosed at 5 mg/kg every 2 weeks for the first 2 months, then monthly for 4 months; following this, maintenance dosing practices varied depending on center. Baseline patient characteristics are given in Table 1. After bevacizumab initiation, patients with baseline anemia (Hgb<11, N=104) had an increase in mean Hgb from 8.6 g/dL to 11.9 g/dL at 3 months (P<0.0001) up to 12.5 g/dL at 12 months (P<0.0001) (Table 2, Figure 1). For patients with epistaxis as an indication for treatment (N=119), mean ESS dropped from 6.8 at baseline to ≤3.5 on treatment (P<0.0001) (Table 2, Figure 2). In patients requiring RBC transfusion prior to bevacizumab (N=81), transfusion requirements decreased from a median of 8 units in the 6 months before treatment to a median of 0 units in the first 6 months after treatment (P<0.0001); similarly, in patients requiring iron infusion prior to bevacizumab (N=99), requirements decreased from a median of 4 infusions to 2 infusions (P<0.0001) (Table 2). RBC transfusion and iron infusion requirements continued to improve with ongoing bevacizumab treatment (Table 2) and improvement occurred regardless of baseline bleeding severity; Figure 3 illustrates the dramatic reduction in RBC transfusion and iron infusion requirements in a severe patient sub-cohort. Overall, compared with pretreatment, RBC transfusion and iron infusion requirements decreased by 86% and 66%, respectively, on bevacizumab. On subgroup analysis by underlying mutation (ENG vs. ACVRL1), there were no significant differences in baseline parameters or bevacizumab response. Bevacizumab was well-tolerated; TEAEs felt to be likely or possibly related to bevacizumab occurred in 36% of patients (Table 3), with new or worsened hypertension (16%) and fatigue (9%) most common. No patient developed venous thromboembolism on bevacizumab. Only 5 patients (4%) discontinued bevacizumab for TEAEs and only 3 patients (2%) discontinued bevacizumab for lack of effectiveness. Conclusions : We present results of IV bevacizumab treatment of chronic bleeding and anemia in a large cohort of 140 HHT patients, demonstrating that bevacizumab was highly effective, with an improvement in mean Hgb of 3.9 g/dL, dramatic reduction in ESS, and decrease in RBC transfusion and iron infusion requirements by 86% and 66%, respectively. Effectiveness was maintained over time. Safety analysis included a total of 194 patient-years of IV bevacizumab administration to HHT patients and had low TEAE rates with only 4% discontinuing treatment due to TEAEs. Disclosures Al-Samkari: Agios: Consultancy, Research Funding; Moderna: Consultancy; Dova: Consultancy, Research Funding. Kuter:Caremark: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Dova: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Zafgen: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria; Shinogi: Consultancy, Honoraria; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Agios: Consultancy, Honoraria, Research Funding; Platelet Disorder Support Association: Consultancy, Honoraria; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Caremark: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Merck Sharp Dohme: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Argenx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Kezar: Research Funding; Shire: Consultancy, Honoraria; Kezar: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Principia: Consultancy, Honoraria, Research Funding; Zafgen: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Principia: Consultancy, Honoraria, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Protalix: Consultancy, Honoraria; Protalix: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Rigel: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; UCB: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Protalex: Consultancy, Honoraria, Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Shinogi: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Dova: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Momenta: Consultancy, Honoraria. OffLabel Disclosure: The presentation will discuss off-label use of systemic bevacizumab for the treatment of chronic bleeding and anemia in hereditary hemorrhagic telangiectasia.

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Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations

BMJ Case Reports ◽

10.1136/bcr-2020-238385 ◽

2021 ◽

Vol 14 (1) ◽

pp. e238385

Author(s):

Louise Dunphy ◽

Ambika Talwar ◽

Neil Patel ◽

Alex Evans

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Arteriovenous Malformations ◽

Transforming Growth Factor ◽

Plasma Concentrations ◽

Delayed Diagnosis ◽

Hereditary Haemorrhagic Telangiectasia ◽

Pulmonary Arteriovenous Malformations ◽

Autosomal Dominant Disorder ◽

Recurrent Epistaxis

Hereditary haemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu syndrome is an autosomal dominant disorder affecting 1 in 8000 individuals. The eponym recognises the 19th-century physicians William Osler, Henri Jules Louis Marie Rendu and Frederick Parkes Weber who each independently described the disease. It is characterised by epistaxis, telangiectasia and visceral arteriovenous malformations. Individuals with HHT have been found to have abnormal plasma concentrations of transforming growth factor beta and vascular endothelial growth factor secondary to mutations in ENG, ACVRL1 and MADH4. Pulmonary artery malformations (PAVMs) are abnormal communications between pulmonary arteries and veins and are found in up to 50% of individuals with HHT. The clinical features suggestive of PAVMs are stigmata of right to left shunting such as dyspnoea, hypoxaemia, cyanosis, cerebral embolism and unexplained haemoptysis or haemothorax. The authors present the case of a 33-year-old woman presenting with progressive dyspnoea during the COVID-19 pandemic. She had a typical presentation of HHT with recurrent epistaxis, telangiectasia and pulmonary arteriovenous malformations. Although rare, PAVM should be considered in individuals presenting to the emergency department with dyspnoea and hypoxaemia. Delayed diagnosis can result in fatal embolic and haemorrhagic complications.

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