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Topic 1345 Version 43.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 31/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate GRAPHICS Mucosal telangiectasias in hereditary hemorrhagic telangectasia (Osler Weber Rendu syndrome) Superficial telangectasias are seen on the lips of a man with hereditary hemorrhagic telangectasia syndrome who had a solitary pulmonary arteriovenous malformation. Reproduced with permission from Gossage JR, Kanj G, Am J Respir Crit Care Med 1998; 158:643 Graphic 77416 Version 4.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 32/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate MRI showing pulmonary AVM-induced cerebral abscess Contrast-enhanced magnetic resonance image (MRI) from a patient with HHT and pulmonary AVM. Note enhancing vascular capsule and central area of necrosis in the temporoparietal abscess. PAVM: Pulmonary arteriovenous malformation. Reproduced by permission from: Macmillan Publishers Ltd: Shovlin C, Bamford K, Wray D. Post-NICE 2008: Antibiotic prophylaxis prior to dental procedures for patients with pulmonary arteriovenous malformations (PAVMs) and hereditary haemorrhagic telangiectasia. Br J Dent 2008; 205:531. Copyright 2008. Graphic 63662 Version 7.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 33/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Overview of the incidence, presenting findings, evaluation, and management of the major clinical features of hereditary hemorrhagic telangiectasia (HHT) Presentation Site Incidence Evaluation Treatment patterns Nasal >90% Nose bleeds are History, Routine therapy includes telangiectasia usually the first inspection nasal lubrication and treatment of iron manifestation of HHT, frequently deficiency when needed. commencing in childhood. Laser treatment is generally preferred over cauterization. Surgery in expert hands offers good results for selected patients. Medical (systemic) treatments are an alternative and may be highly beneficial, but carry risks of prothrombotic side effects. Emergency treatments such as packing may be required. Mucocutaneous 50 to 80% Increase in size Inspection (oral, Generally not indicated, telangiectasia and number with age. Main mucosa, conjunctivae, but laser therapy can be used. concerns are face, trunk, cosmetic. May hemorrhage. extremities, nail beds) Gastrointestinal 11 to 40% Onset generally Flexible Iron supplementation and transfusion are the telangiectasia over 30 years: Iron deficiency endoscopy, endoscopy mainstays of treatment. anemia, occasionally angiogram, capsule Medical (systemic) treatments are available and may be highly acute gastrointestinal endoscopy beneficial, but they carry hemorrhage. risks of prothrombotic side effects. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 34/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Pulmonary >50% Usually silent. Chest Therapeutic AVMs Cyanosis, clubbing, bruit, radiography, blood gas embolization. Antibiotic prophylaxis for dyspnea, measurement, dental and surgical procedures. paradoxical embolism, helical CT, angiography, Surgical resection may be indicated in highly cerebral abscess. chest echocardiography selected cases. Cerebral AVMs 10 to 15% Usually silent. CT, MRI, Doppler Most do not require Headache, sonography, treatment. epilepsy, ischemia, angiography Therapeutic embolization, neurovascular surgery, or intracerebral hemorrhage. stereotactic radiosurgery in highly selected cases. Hepatic AVMs 30 to 70% Usually silent. Doppler Most do not require Hepatic artery- hepatic vein sonography, CT, MRI treatment. For the small proportion AVMs: of patients who develop symptoms, standard Hyperdynamic circulation. hepatic medical care is often sufficient to resolve Portasystemic shunts: Ascites symptoms. and Liver transplantation in encephalopathy. selected cases. Embolization is a higher- risk procedure; some centers do not perform embolization unless the patient is accepted into a liver transplantation program. Less-common clinical manifestations include AVMs in other sites, high cardiac output states, and pulmonary hypertension. Refer to UpToDate for additional details of our approach. AVM: arteriovenous malformation; CT: computed tomography; MRI: magnetic resonance imaging. Adapted and updated from the original table in: Shovlin CL, Letarte M. Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax 1999; 54:714. Graphic 74593 Version 3.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 35/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Endoscopic image of colonic angiodysplasia Angiodysplasia appears endoscopically as peripherally expanding dilated capillaries with a central origin measuring between 0.1 to 1.0 cm in diameter. Courtesy of Rome Jutabha, MD. Graphic 50137 Version 4.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 36/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Endoscopic image of colonic angiodysplasia Courtesy of T Edward Bynum, MD. Graphic 73541 Version 2.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 37/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Angiography of colonic angiodysplasia A superior mesenteric arteriogram demonstrates puddling of contrast material in tortuous distended vessels in the cecal wall (arrows). Courtesy of Jonathan Kruskal, MD. Graphic 52754 Version 4.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 38/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Oral telangiectasia in hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) Osler-Weber-Rendu syndrome (also known as hereditary hemorrhagic telangiectasia). Note the multiple 1 to 2 mm, discrete, red macular and papular telangiectases on the lower lip and tongue. Reproduced with permission from: Fitzpatrick TB, Johnson RA, Wol K, Suurmond D. Color Atlas & Synopsis of Clinical Dermatology, 4th ed, McGraw Hill Medical Publishing, New York 2001. Copyright 2001 McGraw-Hill. Graphic 52483 Version 6.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 39/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate CT of a pulmonary arteriovenous malformation (AVM) Pulmonary arteriovenous malformation presenting as a solitary pulmonary nodule. Chest CT shows a nodule in the periphery of the right middle lobe (arrow) with a proximal tail-like extension corresponding to the supplying artery and the draining vein. CT: computed tomography; AVM: arteriovenous malformation. Courtesy of Paul Stark, MD. Graphic 56072 Version 5.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 40/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Angiogram showing pulmonary arteriovenous malformation (AVM) Magnified view of the left lower lung field from a digital subtraction angiogram in a patient with PAVM and HHT. The angiography catheter (c) is seen entering the feeding artery at the upper left corner. The angiogram shows a single feeding artery (a), which bifurcates to supply the two sacs of the bilobed PAVM. The draining vein (v) is seen as a faint vessel inferior to the feeding artery. PAVM: pulmonary arteriovenous malformation; HHT: hereditary hemorrhagic telangiectasia. Courtesy of James R Gossage, MD. Graphic 54651 Version 4.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 41/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Complications of pulmonary AVMs in all published series 1948-1999 Mean, percent Range, percent Respiratory Asymptomatic 50 25 to 58 Dyspnea 48 27 to 71 Chest pain 14 6 to 18 Haemoptysis 11 4 to 18 Haemothorax <1 0 to 2 Cyanosis 30 9 to 73 Clubbing 32 6 to 68 Bruit 49 25 to 58 Embolic phenomenon Cerebral abscess 10 0 to 25 CVA or TIA 27 11 to 55 Shovlin CL, Letarte M. Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax 1999; 54:714. Graphic 54074 Version 2.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 42/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Brain arteriovenous malformation pretreatment angiography Characteristic angiographic appearance of a brain arteriovenous malformation (AVM) before therapy. Courtesy of Guy Rordorf, MD. Graphic 75190 Version 2.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 43/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate MRI of brain arteriovenous malformation T2-weighted MRI of the brain demonstrates multiple flow voids in the right hemisphere, suggestive of a large arteriovenous malformation. MRI: magnetic resonance imaging. From: Flemming KD, Lanzino G. Management of Unruptured Intracranial Aneurysms and Cerebrovascular Malformations. Continuum (Minneap Minn) 2017; 23:181. DOI: 10.1212/CON.0000000000000418. Copyright 2017 American Academy of Neurology. Reproduced with permission from Wolters Kluwer Health. Unauthorized reproduction of this material is prohibited. Graphic 53992 Version 6.0 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 44/45 7/5/23, 12:20 PM Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - UpToDate Contributor Disclosures Claire L Shovlin, PhD, FRCP Patent Holder: Imperial College London [The use of trametinib for treatment of HHT bleeding is the subject of a patent application by my employer]. Grant/Research/Clinical Trial Support: National Institute for Health Research [Imaging angiogenesis by PET CT - A pilot study in patients with arteriovenous malformations and hereditary haemorrhagic telangiectasia]. Consultant/Advisory Boards: European Reference Network for Rare Multisystemic Vascular Diseases [HHT]; Genomics England Respiratory GeCIP [Genomic medicine]; International Guidelines Committee [Cure HHT]; NHS Genomic Medicine Service Alliance [Genomic medicine]; NIH ClinGen Expert Panel for hereditary haemorrhagic telangiectasia GRAMB [HHT]. All of the relevant financial relationships listed have been mitigated. Lawrence LK Leung, MD No relevant financial relationship(s) with ineligible companies to disclose. Jennifer S Tirnauer, MD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemorrhagic-telangiectasia-osler-weber-rendu-syndrome/print 45/45