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Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4. Am J Med Genet A 2015; 167A:1758. 31. Joyce KE, Onabanjo E, Brownlow S, et al. Whole genome sequences discriminate hereditary hemorrhagic telangiectasia phenotypes by non-HHT deleterious DNA variation. Blood Adv 2022; 6:3956. 32. Guilhem A, Portal s P, Dupuis-Girod S, et al. Altered expressions of CXCR4 and CD26 on T- helper lymphocytes in hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis 2021; 16:511. 33. Finnamore H, Le Couteur J, Hickson M, et al. Hemorrhage-adjusted iron requirements, hematinics and hepcidin define hereditary hemorrhagic telangiectasia as a model of https://www.uptodate.com/contents/hereditary-hemorrhagic-telangiectasia-hht-routine-care-including-screening-for-asymptomatic-avms/print 24/32 7/5/23, 12:21 PM Hereditary hemorrhagic telangiectasia (HHT): Routine care including screening for asymptomatic AVMs - UpToDate hemorrhagic iron deficiency. PLoS One 2013; 8:e76516. 34. Shovlin CL, Simeoni I, Downes K, et al. Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. Blood 2020; 136:1907. 35. Santhirapala V, Williams LC, Tighe HC, et al. Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations. PLoS One 2014; 9:e90777. 36. 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Catecholamine-induced opening of intrapulmonary arteriovenous anastomoses in healthy humans at rest. J Appl Physiol (1985) 2012; 113:1213. https://www.uptodate.com/contents/hereditary-hemorrhagic-telangiectasia-hht-routine-care-including-screening-for-asymptomatic-avms/print 25/32 7/5/23, 12:21 PM Hereditary hemorrhagic telangiectasia (HHT): Routine care including screening for asymptomatic AVMs - UpToDate 45. Duke JW, Davis JT, Ryan BJ, et al. Decreased arterial PO2, not O2 content, increases blood flow through intrapulmonary arteriovenous anastomoses at rest. J Physiol 2016; 594:4981. 46. Yang W, Liu A, Hung AL, et al. Lower risk of intracranial arteriovenous malformation hemorrhage in patients with hereditary hemorrhagic telangiectasia. Neurosurgery 2016; 78:684. 47. Shovlin CL, Letarte M. Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax 1999; 54:714. 48. 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Topic 123017 Version 20.0 https://www.uptodate.com/contents/hereditary-hemorrhagic-telangiectasia-hht-routine-care-including-screening-for-asymptomatic-avms/print 28/32 7/5/23, 12:21 PM Hereditary hemorrhagic telangiectasia (HHT): Routine care including screening for asymptomatic AVMs - UpToDate GRAPHICS Overview of the incidence, presenting findings, evaluation, and management of the major clinical features of hereditary hemorrhagic telangiectasia (HHT) Presentation patterns Site Incidence Evaluation Treatment Nasal telangiectasia >90% Nose bleeds are usually the first History, inspection Routine therapy includes nasal lubrication and manifestation of treatment of iron deficiency when needed. HHT, frequently commencing in Laser treatment is generally preferred over childhood. 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 telangiectasia 50 to 80% Increase in size and number Inspection (oral, mucosa, Generally not indicated, but laser therapy can be with age. Main concerns are conjunctivae, face, trunk, used. cosmetic. May extremities, nail hemorrhage. beds) Gastrointestinal 11 to 40% Onset generally Flexible Iron supplementation telangiectasia over 30 years: endoscopy, and transfusion are the mainstays of treatment. Iron deficiency anemia, endoscopy angiogram, Medical (systemic) treatments are available occasionally acute capsule endoscopy and may be highly beneficial, but they carry gastrointestinal hemorrhage. https://www.uptodate.com/contents/hereditary-hemorrhagic-telangiectasia-hht-routine-care-including-screening-for-asymptomatic-avms/print 29/32 7/5/23, 12:21 PM Hereditary hemorrhagic telangiectasia (HHT): Routine care including screening for asymptomatic AVMs - UpToDate risks of prothrombotic side effects. Pulmonary AVMs >50% Usually silent. Cyanosis, Chest radiography, Therapeutic embolization. clubbing, bruit, dyspnea, blood gas measurement, Antibiotic prophylaxis for dental and surgical paradoxical helical CT, procedures. embolism, cerebral angiography, chest Surgical resection may be indicated in highly selected cases. abscess. echocardiography Cerebral AVMs 10 to 15% Usually silent. Headache, CT, MRI, Doppler sonography, Most do not require treatment. epilepsy, angiography Therapeutic embolization, ischemia, intracerebral neurovascular surgery, or stereotactic radiosurgery hemorrhage. in highly selected cases. Hepatic AVMs 30 to 70% Usually silent. Hepatic artery- Doppler sonography, CT, Most do not require treatment. hepatic vein AVMs: MRI For the small proportion of patients who develop Hyperdynamic symptoms, standard hepatic medical care is circulation. Portasystemic often sufficient to resolve symptoms. shunts: Ascites and Liver transplantation in selected cases. encephalopathy. 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; https://www.uptodate.com/contents/hereditary-hemorrhagic-telangiectasia-hht-routine-care-including-screening-for-asymptomatic-avms/print 30/32 7/5/23, 12:21 PM Hereditary hemorrhagic telangiectasia (HHT): Routine care including screening for asymptomatic AVMs - UpToDate 54:714. Graphic 74593 Version 3.0 https://www.uptodate.com/contents/hereditary-hemorrhagic-telangiectasia-hht-routine-care-including-screening-for-asymptomatic-avms/print 31/32 7/5/23, 12:21 PM Hereditary hemorrhagic telangiectasia (HHT): Routine care including screening for asymptomatic AVMs - 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/hereditary-hemorrhagic-telangiectasia-hht-routine-care-including-screening-for-asymptomatic-avms/print 32/32