Sections

Osler-Weber-Rendu Disease (Hereditary Hemorrhagic Telangiectasia)

Sections Osler-Weber-Rendu Disease (Hereditary Hemorrhagic Telangiectasia)
Overview
Presentation
DDx
Workup
Treatment
Guidelines
Medication
Questions & Answers
Media Gallery
References

Workup

Approach Considerations

Currently, no laboratory studies are widely available to confirm the diagnosis of Osler-Weber-Rendu disease (OWRD; ie, hereditary hemorrhagic telangiectasia [HHT]). However, certain laboratory tests may be helpful in identifying specific complications.

Because of the prevalence of arteriovenous malformations (AVMs) and associated sequelae, screening with multiple (presumably complementary) imaging modalities is increasingly employed. Some investigators advocate helical computed tomography (CT); others, chest radiography with pulse oximetry. Contrast echocardiography is noninvasive and sensitive^[83]and identifies intracardiac shunts, whereas arterial blood gas evaluation and pulse oximetry do not. Magnetic resonance imaging (MRI) also appears highly effective.^[84]

Some centers screen asymptomatic children with a family history of OWRD in an effort to reduce serious complications associated with AVMs.

At specific centers and laboratories, genetic tests are available for various mutations in the endoglin gene (ENG) found on chromosome 9 and the activin receptorlike kinase type I (ALK-1) gene (ALK1) found on chromosome 12. These tests should be ordered in coordination with a physician and genetic counselor.

Currently, prenatal diagnosis is rarely used in families affected by OWRD. These families are encouraged to have DNA diagnosis of affected individuals where available. If the specific mutation within the family is revealed, cord blood from neonates may be analyzed for the presence of the disease, and multiple screening modalities for AVMs may be used.

Laboratory Studies

When a complete blood count (CBC) is done, hemoglobin may be decreased because of chronic bleeding and iron-deficiency anemia, or the patient may be polycythemic because of chronic hypoxemia from a right-to-left shunt. The platelet count may be normal or slightly increased. The white blood cell (WBC) count should be within the reference range unless an infectious complication (eg, a brain abscess) is present.

Coagulation profile findings may exclude a concurrent disorder or coagulopathy. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) values should be normal, unless severe liver involvement is present. A preliminary study also points to the usefulness of factor VIII antigen levels; elevated levels may influence thrombotic risk in OWRD.^[85]

Urinalysis should be done to assess for hematuria.^[86]Stool should be evaluated to look for the presence of blood. Liver function tests may reveal elevated enzyme levels.

Oximetry

Oximetry is performed with the patient standing and supine for 10 minutes in each position. An oxygen saturation level of less than 96% in either position is considered an indication for further testing. It is recommended that screening for pulmonary AVM using pulse oximetry in conjunction with chest radiography be performed once in childhood, once after puberty, before pregnancy, and at 10-year intervals thereafter.^[87]

Arterial Blood Gas Assessment

Arterial blood gas measurement can also be used as a screening test for pulmonary AVM. The quantification of a right-to-left shunt can be measured with the patient breathing 100% oxygen for at least 20 minutes. An arterial blood gas analysis is performed at the end of the study and shunt fraction is measured. This study can be performed in the pulmonary function laboratory.

If a right-to-left shunt is present, the arterial partial pressure of oxygen (PaO₂) will be low. If such a shunt is suspected, PaO₂ is measured while the patient is on 100% oxygen (so-called hyperoxic test). If PaO₂ shows only a minor increase in this setting, the diagnosis of a right-to-left shunt is confirmed. If no shunt is present, PaO₂ should increase to a much larger extent. Screening with a hyperoxic test has been shown to be 100% sensitive and 40% specific for the detection of pulmonary AVMs in OWRD patients suspected of having an AVM.

Technetium-99m–tagged albumin microspheres have also been used for shunt detection in the brain and kidneys.^[88]

Radiography

Posteroanterior and lateral chest radiographs may reveal a mass of enlarged arteries and veins typical of pulmonary AVM. Commonly found in the posterior lung bases, these lesions may also be hidden by the diaphragm. Chest radiography may also show a peripheral noncalcified coin lesion attached by vascular strands to the hilum.^[89]

Chest radiography followed by agitated saline solution transthoracic contrast echocardiography (TTCE) with grading has been recommended as the screening test of choice for pulmonary AVMs in patients with OWRD. Initial studies of this modality suggested that it might be more sensitive than CT; however, because long-term follow-up data are not yet available, all patients with even low-grade evidence of pulmonary pathology on TTCE require CT as a confirmatory study.^[90]

Barium enema is useful if an ulcer or neoplasm is suspected.

Computed Tomography

Helical CT has been advocated as a screening method for pulmonary AVM. However, detractors believe that the radiation exposure is unnecessary and the cost is prohibitive. CT with contrast may be used to delineate AVMs of the lung or the brain. CT of the head is indicated in the workup of stroke and brain abscess and may reveal AVM. Abdominal CT may be useful for liver, kidney, and splenic lesions.

Magnetic Resonance Imaging

Contrast-enhanced MRI is appropriate as a screening modality for pulmonary AVM. Planning for embolic treatment is possible with three-dimensional (3D) reconstructed images.^[84]MRI is also a useful screening modality for telangiectasias in the central nervpus system (CNS). When clinical suspicion is high, MRI or magnetic resonance angiography (MRA) may be useful in identifying CNS lesions not observed with CT.

One-step MRI may be useful for evaluating liver involvement in HHT, revealing vascular abnormalities, telangiectases, arteriovenous shunting, focal liver lesions, and ischemic cholangitis.^[91]

Angiography

Preoperative or preablative assessment of pulmonary AVM may warrant angiography for treatment planning. Mesenteric angiography may reveal a bleeding site or mesenteric AVM and facilitate surgical extirpation.^[92]As with other causes of gastrointestinal (GI) bleeding, a hemorrhage rate of at least 1 mL/min is necessary for detection with angiography, though GI bleeding at rates as low as 0.5 mL/min may be detected with technetium-99m–labeled autologous RBC scanning. Cerebral angiography may be indicated in the preoperative workup of CNS lesions.

Ultrasonography and Contrast Echocardiography

Doppler ultrasonography of the liver may be used for screening and first-line imaging in patients with OWRD who have hepatic AVM or other associated sequelae.

Contrast echocardiography has been shown to reveal pulmonary AVM when pulse oximetry examination or even pulmonary angiography findings were negative. Agitated saline, with its small air bubbles, creates visible contrast that can be observed in the left atrium on echocardiography. The presence of contrast in the left atrium indicates right-to-left shunt.

The ability to detect intracardiac shunts is an advantage that contrast echocardiography has over other shunt studies.^[83]Higher-grade shunts (>20-30 microbubbles/frame) have higher positive predictive value.^[93]

Genetic Testing

The sensitivity of molecular diagnosis is highest in probands with a clinically confirmed diagnosis of HHT.^[25]However, a substantial fraction of probands do not carry an identifiable mutation in the coding exons of either of the two responsible genes, ENG and ALK1. Targeted family-specific mutation analysis for ENG exon deletions could lead to misdiagnosis of some affected family members with HHT, as was illustrated by the findings of a study in which two distinct ENG deletions were found in a single family.^[94]

Endoscopy

Upper and lower GI endoscopy may reveal telangiectases or AVMs. Colonoscopy reveals GI telangiectasias as small well-defined lesions surrounded by an anemic halo.

Push enteroscopy allows visualization of the proximal small bowel distal to the ligament of Treitz, though this or further intubation of the jejunum is technically demanding. Similarly, a skilled endoscopist can use a colonoscope placed proximal to the ileocecal valve to examine the distal ileum. The entire small bowel can be visualized with push enteroscopy; however, general anesthesia and intraperitoneal access (laparotomy or laparoscopy) are needed to manipulate and thread the small bowel over the endoscope inserted per os or per rectum.

Video capsule endoscopy is useful in the evaluation of occult GI bleeding of small-bowel origin.^[95]Telangiectases from HHT can be visualized with this approach.^[96]Using the capsule for diagnosis in a series of 18 patients, investigators noted small-bowel involvement in patients with known gastric telangiectases in 56% of patients.^[97]

A study of 30 patients with HHT and overt gut bleeding or severe anemia found video capsule endoscopy to have a high diagnostic yield.^[98]This approach enables precise mapping of accessible lesions that are amenable to endoscopic treatment; innumerable diffuse lesions require a medical approach. Video capsule endoscopy may be a first-line, noninvasive digestive tract examination in selected patients with HHT.

Spiral enteroscopy has been shown to be a safe method of accessing the small bowel in patients with HHT.^[99]

Biopsy

Skin biopsy findings are often helpful in confirming the diagnosis of OWRD. Punch biopsy is usually adequate. Findings are localized in the dermal upper-horizontal plexus. The classic features are dilated capillaries and new vessel formation. In the dermis, the walls of dilated vessels may be thickened.

Histologic Findings

Telangiectases manifest as focal dilatation of the postcapillary venules. Early lesions maintain a portion of intervening capillary bed. Perivascular lymphocytic infiltrate is observed. Fully developed lesions lack an intervening capillary bed. Markedly dilated arterioles and venules connect directly in a tortuous network. The mature lesion also shows lymphocytic infiltrate, as well as multiple layers of thickened smooth-muscle cells around connecting venules.^[100]

Orthodeoxia may be detected in patients with pulmonary AVM because of increased shunting of blood through lesions in inferior areas of the lung.^[101]

Liver specimens from patients with significant liver involvement often reveal pseudocirrhosis attributable to shunting from the hepatic artery to the hepatic vein or shunting from the hepatic artery to the portal vein.

Treatment & Management

Giordano P, Lenato GM, Suppressa P, Lastella P, Dicuonzo F, Chiumarulo L, et al. Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children. J Pediatr. 2013 Jul. 163 (1):179-86.e1-3. [QxMD MEDLINE Link].
Guttmacher AE, Marchuk DA, White RI Jr. Hereditary hemorrhagic telangiectasia. N Engl J Med. 1995 Oct 5. 333 (14):918-24. [QxMD MEDLINE Link].
Nanda S, Bhatt SP. Hereditary hemorrhagic telangiectasia: epistaxis and hemoptysis. CMAJ. 2009 Apr 14. 180 (8):838. [QxMD MEDLINE Link].
Franchini M, Frattini F, Crestani S, Bonfanti C. Novel treatments for epistaxis in hereditary hemorrhagic telangiectasia: a systematic review of the clinical experience with thalidomide. J Thromb Thrombolysis. 2013 Oct. 36 (3):355-7. [QxMD MEDLINE Link].
Haitjema TJ, van Snippenburg R, Disch FJ, Overtoom TT, Westermann CJ. [Recurrent epistaxis: sometimes Rendu-Osler-Weber disease]. Ned Tijdschr Geneeskd. 1996 Nov 2. 140 (44):2157-60. [QxMD MEDLINE Link].
Plauchu H, de Chadarévian JP, Bideau A, Robert JM. Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am J Med Genet. 1989 Mar. 32 (3):291-7. [QxMD MEDLINE Link].
Porteous ME, Burn J, Proctor SJ. Hereditary haemorrhagic telangiectasia: a clinical analysis. J Med Genet. 1992 Aug. 29 (8):527-30. [QxMD MEDLINE Link]. [Full Text].
Irani F, Kasmani R. Hereditary hemorrhagic telangiectasia: fatigue and dyspnea. CMAJ. 2009 Apr 14. 180 (8):839. [QxMD MEDLINE Link].
Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6. 91 (1):66-7. [QxMD MEDLINE Link].
Shovlin CL, Hughes JM. Hereditary hemorrhagic telangiectasia. N Engl J Med. 1996 Feb 1. 334 (5):330-1; author reply 331-2. [QxMD MEDLINE Link].
Shovlin CL, Letarte M. Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax. 1999 Aug. 54 (8):714-29. [QxMD MEDLINE Link]. [Full Text].
Cole SG, Begbie ME, Wallace GM, Shovlin CL. A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5. J Med Genet. 2005 Jul. 42 (7):577-82. [QxMD MEDLINE Link]. [Full Text].
Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, et al. Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet. 2006 Sep. 43 (9):722-8. [QxMD MEDLINE Link].
Zucco L, Zhang Q, Kuliszewski MA, Kandic I, Faughnan ME, Stewart DJ, et al. Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagic telangiectasia. PLoS One. 2014. 9 (2):e89927. [QxMD MEDLINE Link]. [Full Text].
Hammill AM, Wusik K, Kasthuri RS. Hereditary hemorrhagic telangiectasia (HHT): a practical guide to management. Hematology Am Soc Hematol Educ Program. 2021 Dec 10. 2021 (1):469-477. [QxMD MEDLINE Link].
Choi EJ, Chen W, Jun K, Arthur HM, Young WL, Su H. Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia. PLoS One. 2014. 9 (2):e88511. [QxMD MEDLINE Link]. [Full Text].
Braverman IM, Keh A, Jacobson BS. Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia. J Invest Dermatol. 1990 Oct. 95 (4):422-7. [QxMD MEDLINE Link].
van Laake LW, van den Driesche S, Post S, Feijen A, Jansen MA, Driessens MH, et al. Endoglin has a crucial role in blood cell-mediated vascular repair. Circulation. 2006 Nov 21. 114 (21):2288-97. [QxMD MEDLINE Link].
Fernandez-L A, Garrido-Martin EM, Sanz-Rodriguez F, Pericacho M, Rodriguez-Barbero A, Eleno N, et al. Gene expression fingerprinting for human hereditary hemorrhagic telangiectasia. Hum Mol Genet. 2007 Jul 1. 16 (13):1515-33. [QxMD MEDLINE Link].
McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med. 2011 Jul. 13 (7):607-16. [QxMD MEDLINE Link].
David L, Mallet C, Mazebourg S, Feige J, Bailly S. Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood. 2007. 109 (5):1953-61. [QxMD MEDLINE Link].
Jerkic M, Sotov V, Letarte M. Oxidative stress contributes to endothelial dysfunction in mouse models of hereditary hemorrhagic telangiectasia. Oxid Med Cell Longev. 2012. 2012:686972. [QxMD MEDLINE Link]. [Full Text].
Shovlin CL, Hughes JM, Scott J, Seidman CE, Seidman JG. Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia. Am J Hum Genet. 1997 Jul. 61 (1):68-79. [QxMD MEDLINE Link]. [Full Text].
Grover S, Grewal RS, Verma R, Sahni H, Muralidhar R, Sinha P. Osler-Weber-Rendu syndrome: a case report with familial clustering. Indian J Dermatol Venereol Leprol. 2009 Jan-Feb. 75 (1):100-1. [QxMD MEDLINE Link].
Richards-Yutz J, Grant K, Chao EC, Walther SE, Ganguly A. Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum Genet. 2010 Jul. 128 (1):61-77. [QxMD MEDLINE Link].
Gedge F, McDonald J, Phansalkar A, Chou LS, Calderon F, Mao R, et al. Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations. J Mol Diagn. 2007 Apr. 9 (2):258-65. [QxMD MEDLINE Link]. [Full Text].
McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet. 1994 Dec. 8 (4):345-51. [QxMD MEDLINE Link].
Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996 Jun. 13 (2):189-95. [QxMD MEDLINE Link].
Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, et al. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet. 2004 Mar 13. 363 (9412):852-9. [QxMD MEDLINE Link].
Abdalla SA, Letarte M. Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease. J Med Genet. 2006 Feb. 43 (2):97-110. [QxMD MEDLINE Link]. [Full Text].
Rigelsky CM, Jennings C, Lehtonen R, Minai OA, Eng C, Aldred MA. BMPR2 mutation in a patient with pulmonary arterial hypertension and suspected hereditary hemorrhagic telangiectasia. Am J Med Genet A. 2008 Oct 1. 146A (19):2551-6. [QxMD MEDLINE Link].
Begbie ME, Wallace GM, Shovlin CL. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century. Postgrad Med J. 2003 Jan. 79 (927):18-24. [QxMD MEDLINE Link]. [Full Text].
Kjeldsen AD, Oxhøj H, Andersen PE, Elle B, Jacobsen JP, Vase P. Pulmonary arteriovenous malformations: screening procedures and pulmonary angiography in patients with hereditary hemorrhagic telangiectasia. Chest. 1999 Aug. 116 (2):432-9. [QxMD MEDLINE Link].
Dakeishi M, Shioya T, Wada Y, Shindo T, Otaka K, Manabe M, et al. Genetic epidemiology of hereditary hemorrhagic telangiectasia in a local community in the northern part of Japan. Hum Mutat. 2002 Feb. 19 (2):140-8. [QxMD MEDLINE Link].
Kjeldsen AD, Vase P, Green A. Hereditary haemorrhagic telangiectasia: a population-based study of prevalence and mortality in Danish patients. J Intern Med. 1999 Jan. 245 (1):31-9. [QxMD MEDLINE Link].
Jessurun GA, Kamphuis DJ, van der Zande FH, Nossent JC. Cerebral arteriovenous malformations in The Netherlands Antilles. High prevalence of hereditary hemorrhagic telangiectasia-related single and multiple cerebral arteriovenous malformations. Clin Neurol Neurosurg. 1993 Sep. 95 (3):193-8. [QxMD MEDLINE Link].
Westermann CJ, Rosina AF, De Vries V, de Coteau PA. The prevalence and manifestations of hereditary hemorrhagic telangiectasia in the Afro-Caribbean population of the Netherlands Antilles: a family screening. Am J Med Genet A. 2003 Feb 1. 116A (4):324-8. [QxMD MEDLINE Link].
Vase P, Grove O. Gastrointestinal lesions in hereditary hemorrhagic telangiectasia. Gastroenterology. 1986 Nov. 91 (5):1079-83. [QxMD MEDLINE Link].
Urushihara M, Furukawa S, Ota A, Iwai A, Matsumura K, Hamada Y. Hemorrhagic telangiectasia with thrombocytopenia in a newborn infant. Pediatr Int. 2000 Dec. 42 (6):693-5. [QxMD MEDLINE Link].
Mitchell RN, Halushka MK. Blood vessels. Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. 487-526.
Sabbà C, Pasculli G, Suppressa P, D'Ovidio F, Lenato GM, Resta F, et al. Life expectancy in patients with hereditary haemorrhagic telangiectasia. QJM. 2006 May. 99 (5):327-34. [QxMD MEDLINE Link].
Fulbright RK, Chaloupka JC, Putman CM, Sze GK, Merriam MM, Lee GK, et al. MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations. AJNR Am J Neuroradiol. 1998 Mar. 19 (3):477-84. [QxMD MEDLINE Link].
Rebeiz EE, Bryan DJ, Ehrlichman RJ, Shapshay SM. Surgical management of life-threatening epistaxis in Osler-Weber-Rendu disease. Ann Plast Surg. 1995 Aug. 35 (2):208-13. [QxMD MEDLINE Link].
Hoag JB, Terry P, Mitchell S, Reh D, Merlo CA. An epistaxis severity score for hereditary hemorrhagic telangiectasia. Laryngoscope. 2010 Apr. 120 (4):838-43. [QxMD MEDLINE Link].
Shovlin CL, Chamali B, Santhirapala V, Livesey JA, Angus G, Manning R, et al. Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets. PLoS One. 2014. 9 (2):e88812. [QxMD MEDLINE Link]. [Full Text].
van Gent MW, Post MC, Snijder RJ, Westermann CJ, Plokker HW, Mager JJ. Real prevalence of pulmonary right-to-left shunt according to genotype in patients with hereditary hemorrhagic telangiectasia: a transthoracic contrast echocardiography study. Chest. 2010 Oct. 138 (4):833-9. [QxMD MEDLINE Link].
Lacombe P, Lagrange C, Beauchet A, El Hajjam M, Chinet T, Pelage JP. Diffuse pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: long-term results of embolization according to the extent of lung involvement. Chest. 2009 Apr. 135 (4):1031-1037. [QxMD MEDLINE Link].
Jakobi P, Weiner Z, Best L, Itskovitz-Eldor J. Hereditary hemorrhagic telangiectasia with pulmonary arteriovenous malformations. Obstet Gynecol. 2001 May. 97 (5 Pt 2):813-4. [QxMD MEDLINE Link].
Cottin V, Dupuis-Girod S, Lesca G, Cordier JF. Pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia (rendu-osler disease). Respiration. 2007. 74 (4):361-78. [QxMD MEDLINE Link].
Berg J, Porteous M, Reinhardt D, Gallione C, Holloway S, Umasunthar T, et al. Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations. J Med Genet. 2003 Aug. 40 (8):585-90. [QxMD MEDLINE Link]. [Full Text].
McDonald MJ, Brophy BP, Kneebone C. Rendu-Osler-Weber syndrome: a current perspective on cerebral manifestations. J Clin Neurosci. 1998 Jul. 5 (3):345-50. [QxMD MEDLINE Link].
Poisson A, Vasdev A, Brunelle F, Plauchu H, Dupuis-Girod S, French Italian HHT network. Acute paraplegia due to spinal arteriovenous fistula in two patients with hereditary hemorrhagic telangiectasia. Eur J Pediatr. 2009 Feb. 168 (2):135-9. [QxMD MEDLINE Link].
Calhoun AR, Bollo RJ, Garber ST, McDonald J, Stevenson DA, Hung IH, et al. Spinal arteriovenous fistulas in children with hereditary hemorrhagic telangiectasia. J Neurosurg Pediatr. 2012 Jun. 9 (6):654-9. [QxMD MEDLINE Link].
Goodenberger DM. Visceral manifestations of hereditary hemorrhagic telangiectasia. Trans Am Clin Climatol Assoc. 2004. 115:185-99. [QxMD MEDLINE Link]. [Full Text].
Römer W, Burk M, Schneider W. [Hereditary hemorrhagic telangiectasia (Osler's disease)]. Dtsch Med Wochenschr. 1992 Apr 24. 117 (17):669-75. [QxMD MEDLINE Link].
AAssar OS, Friedman CM, White RI Jr. The natural history of epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope. 1991 Sep. 101 (9):977-80. [QxMD MEDLINE Link].
White RI Jr, Lynch-Nyhan A, Terry P, Buescher PC, Farmlett EJ, Charnas L, et al. Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy. Radiology. 1988 Dec. 169 (3):663-9. [QxMD MEDLINE Link].
Berg JN, Guttmacher AE, Marchuk DA, Porteous ME. Clinical heterogeneity in hereditary haemorrhagic telangiectasia: are pulmonary arteriovenous malformations more common in families linked to endoglin?. J Med Genet. 1996 Mar. 33 (3):256-7. [QxMD MEDLINE Link]. [Full Text].
Cottin V, Chinet T, Lavolé A, Corre R, Marchand E, Reynaud-Gaubert M, et al. Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients. Medicine (Baltimore). 2007 Jan. 86 (1):1-17. [QxMD MEDLINE Link].
Pierucci P, Murphy J, Henderson KJ, Chyun DA, White RI Jr. New definition and natural history of patients with diffuse pulmonary arteriovenous malformations: twenty-seven-year experience. Chest. 2008 Mar. 133 (3):653-61. [QxMD MEDLINE Link].
Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, et al. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2001 Aug 2. 345 (5):325-34. [QxMD MEDLINE Link].
Press OW, Ramsey PG. Central nervous system infections associated with hereditary hemorrhagic telangiectasia. Am J Med. 1984 Jul. 77 (1):86-92. [QxMD MEDLINE Link].
García-Mónaco R, Taylor W, Rodesch G, Alvarez H, Burrows P, Coubes P, et al. Pial arteriovenous fistula in children as presenting manifestation of Rendu-Osler-Weber disease. Neuroradiology. 1995 Jan. 37 (1):60-4. [QxMD MEDLINE Link].
Krings T, Chng SM, Ozanne A, Alvarez H, Rodesch G, Lasjaunias PL. Hereditary hemorrhagic telangiectasia in children: endovascular treatment of neurovascular malformations: results in 31 patients. Neuroradiology. 2005 Dec. 47 (12):946-54. [QxMD MEDLINE Link].
Easey AJ, Wallace GM, Hughes JM, Jackson JE, Taylor WJ, Shovlin CL. Should asymptomatic patients with hereditary haemorrhagic telangiectasia (HHT) be screened for cerebral vascular malformations? Data from 22,061 years of HHT patient life. J Neurol Neurosurg Psychiatry. 2003 Jun. 74 (6):743-8. [QxMD MEDLINE Link]. [Full Text].
Maher CO, Piepgras DG, Brown RD Jr, Friedman JA, Pollock BE. Cerebrovascular manifestations in 321 cases of hereditary hemorrhagic telangiectasia. Stroke. 2001 Apr. 32 (4):877-82. [QxMD MEDLINE Link].
Cloft HJ. Spontaneous regression of cerebral arteriovenous malformation in hereditary hemorrhagic telangiectasia. AJNR Am J Neuroradiol. 2002 Jun-Jul. 23 (6):1049-50. [QxMD MEDLINE Link].
Du R, Hashimoto T, Tihan T, Young WL, Perry V, Lawton MT. Growth and regression of arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia. Case report. J Neurosurg. 2007 Mar. 106 (3):470-7. [QxMD MEDLINE Link].
Leung KM, Agid R, terBrugge K. Spontaneous regression of a cerebral arteriovenous malformation in a child with hereditary hemorrhagic telangiectasia. Case report. J Neurosurg. 2006 Nov. 105 (5 Suppl):428-31. [QxMD MEDLINE Link].
Proctor DD, Henderson KJ, Dziura JD, Longacre AV, White RI Jr. Enteroscopic evaluation of the gastrointestinal tract in symptomatic patients with hereditary hemorrhagic telangiectasia. J Clin Gastroenterol. 2005 Feb. 39 (2):115-9. [QxMD MEDLINE Link].
Abdalla SA, Geisthoff UW, Bonneau D, Plauchu H, McDonald J, Kennedy S, et al. Visceral manifestations in hereditary haemorrhagic telangiectasia type 2. J Med Genet. 2003 Jul. 40 (7):494-502. [QxMD MEDLINE Link]. [Full Text].
van Cutsem E, Rutgeerts P, Vantrappen G. Treatment of bleeding gastrointestinal vascular malformations with oestrogen-progesterone. Lancet. 1990 Apr 21. 335 (8695):953-5. [QxMD MEDLINE Link].
Wu JS, Saluja S, Garcia-Tsao G, Chong A, Henderson KJ, White RI Jr. Liver involvement in hereditary hemorrhagic telangiectasia: CT and clinical findings do not correlate in symptomatic patients. AJR Am J Roentgenol. 2006 Oct. 187 (4):W399-405. [QxMD MEDLINE Link].
Garcia-Tsao G. Liver involvement in hereditary hemorrhagic telangiectasia (HHT). J Hepatol. 2007 Mar. 46 (3):499-507. [QxMD MEDLINE Link].
Garcia-Tsao G, Swanson KL. Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: in search of predictors of significant disease. Hepatology. 2008 Nov. 48 (5):1377-9. [QxMD MEDLINE Link].
Larson AM. Liver disease in hereditary hemorrhagic telangiectasia. J Clin Gastroenterol. 2003 Feb. 36 (2):149-58. [QxMD MEDLINE Link].
Garcia-Tsao G, Korzenik JR, Young L, Henderson KJ, Jain D, Byrd B, et al. Liver disease in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2000 Sep 28. 343 (13):931-6. [QxMD MEDLINE Link].
Alizad A, Seward JB. Echocardiographic features of genetic diseases: part 3. Shunts. J Am Soc Echocardiogr. 2000 Mar. 13 (3):248-53. [QxMD MEDLINE Link].
Mohler ER 3rd, Doraiswamy V, Sibley A, Bernhardt BA, Pyeritz RE. Transillumination of the fingers for vascular anomalies: a novel method for evaluating hereditary hemorrhagic telangiectasia. Genet Med. 2009 May. 11 (5):356-8. [QxMD MEDLINE Link].
Shovlin CL, Sodhi V, McCarthy A, Lasjaunias P, Jackson JE, Sheppard MN. Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services. BJOG. 2008 Aug. 115 (9):1108-15. [QxMD MEDLINE Link].
Gershon AS, Faughnan ME, Chon KS, Pugash RA, Clark JA, Bohan MJ, et al. Transcatheter embolotherapy of maternal pulmonary arteriovenous malformations during pregnancy. Chest. 2001 Feb. 119 (2):470-7. [QxMD MEDLINE Link].
Khalid SK, Pershbacher J, Makan M, Barzilai B, Goodenberger D. Worsening of nose bleeding heralds high cardiac output state in hereditary hemorrhagic telangiectasia. Am J Med. 2009 Aug. 122 (8):779.e1-9. [QxMD MEDLINE Link].
Nanthakumar K, Graham AT, Robinson TI, Grande P, Pugash RA, Clarke JA, et al. Contrast echocardiography for detection of pulmonary arteriovenous malformations. Am Heart J. 2001 Feb. 141 (2):243-6. [QxMD MEDLINE Link].
Schneider G, Uder M, Koehler M, Kirchin MA, Massmann A, Buecker A, et al. MR angiography for detection of pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia. AJR Am J Roentgenol. 2008 Apr. 190 (4):892-901. [QxMD MEDLINE Link].
Shovlin CL, Sulaiman NL, Govani FS, Jackson JE, Begbie ME. Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost. 2007 Nov. 98 (5):1031-9. [QxMD MEDLINE Link].
De Pascalis A, Napoli M, Aprile M, Antonaci A, D'Amelio A, Buongiorno E. Gross hematuria due to acquired haemophilia in hereditary hemorrhagic telangiectasia. Blood Coagul Fibrinolysis. 2008 Oct. 19 (7):731-3. [QxMD MEDLINE Link].
Faughnan ME, Hyland RH, Nanthakumar K, Redelmeier DA. Screening in hereditary hemorrhagic telangiectasia patients. Chest. 2000 Aug. 118 (2):566-7. [QxMD MEDLINE Link].
Thompson RD, Jackson J, Peters AM, Doré CJ, Hughes JM. Sensitivity and specificity of radioisotope right-left shunt measurements and pulse oximetry for the early detection of pulmonary arteriovenous malformations. Chest. 1999 Jan. 115 (1):109-13. [QxMD MEDLINE Link].
Manson D, Traubici J, Mei-Zahav M, MacLuskey I, John P, Stephens D. Pulmonary nodular opacities in children with hereditary hemorrhagic telangiectasia. Pediatr Radiol. 2007 Mar. 37 (3):264-8. [QxMD MEDLINE Link].
Al-Saleh S, Dragulescu A, Manson D, Golding F, Traubici J, Mei-Zahav M, et al. Utility of contrast echocardiography for pulmonary arteriovenous malformation screening in pediatric hereditary hemorrhagic telangiectasia. J Pediatr. 2012 Jun. 160 (6):1039-43.e1. [QxMD MEDLINE Link].
Milot L, Kamaoui I, Gautier G, Pilleul F. Hereditary-hemorrhagic telangiectasia: one-step magnetic resonance examination in evaluation of liver involvement. Gastroenterol Clin Biol. 2008 Aug-Sep. 32 (8-9):677-85. [QxMD MEDLINE Link].
Suga K, Ishikawa Y, Matsunaga N, Tanaka N, Suda H, Handa T. Liver involvement in hereditary haemorrhagic telangiectasia: assessment with 99Tcm-phytate radionuclide angiography and 123I-IMP transrectal portal scintigraphy. Br J Radiol. 2000 Oct. 73 (874):1115-9. [QxMD MEDLINE Link].
Zukotynski K, Chan RP, Chow CM, Cohen JH, Faughnan ME. Contrast echocardiography grading predicts pulmonary arteriovenous malformations on CT. Chest. 2007 Jul. 132 (1):18-23. [QxMD MEDLINE Link].
Wooderchak W, Gedge F, McDonald M, Krautscheid P, Wang X, Malkiewicz J, et al. Hereditary hemorrhagic telangiectasia: two distinct ENG deletions in one family. Clin Genet. 2010 Nov. 78 (5):484-9. [QxMD MEDLINE Link].
[Guideline] Adler DG, Leighton JA, Davila RE, Hirota WK, Jacobson BC, Qureshi WA, et al. ASGE guideline: The role of endoscopy in acute non-variceal upper-GI hemorrhage. Gastrointest Endosc. 2004 Oct. 60 (4):497-504. [QxMD MEDLINE Link].
Pennazio M, Keuchel M, Jensen DM, Dulai GS. Arteriovenous diseases. Keuchel M, Hagenmueller F, Tajiri H, eds. Video Capsule Endoscopy: A Reference Guide and Atlas. Berlin: Springer-Verlag; 2014. 193-204.
Ingrosso M, Sabbà C, Pisani A, Principi M, Gallitelli M, Cirulli A, et al. Evidence of small-bowel involvement in hereditary hemorrhagic telangiectasia: a capsule-endoscopic study. Endoscopy. 2004 Dec. 36 (12):1074-9. [QxMD MEDLINE Link].
Grève E, Moussata D, Gaudin JL, Lapalus MG, Giraud S, Dupuis-Girod S, et al. High diagnostic and clinical impact of small-bowel capsule endoscopy in patients with hereditary hemorrhagic telangiectasia with overt digestive bleeding and/or severe anemia. Gastrointest Endosc. 2010 Apr. 71 (4):760-7. [QxMD MEDLINE Link].
Ramchandani M, Reddy DN, Gupta R, Lakhtakia S, Tandan M, Darisetty S, et al. Spiral enteroscopy: a preliminary experience in Asian population. J Gastroenterol Hepatol. 2010 Nov. 25 (11):1754-7. [QxMD MEDLINE Link].
Jacobson BS. Hereditary hemorrhagic telangiectasia: A model for blood vessel growth and enlargement. Am J Pathol. 2000 Mar. 156 (3):737-42. [QxMD MEDLINE Link]. [Full Text].
Robin ED, Laman D, Horn BR, Theodore J. Platypnea related to orthodeoxia caused by true vascular lung shunts. N Engl J Med. 1976 Apr 22. 294 (17):941-3. [QxMD MEDLINE Link].
Harries PG, Brockbank MJ, Shakespeare PG, Carruth JA. Treatment of hereditary haemorrhagic telangiectasia by the pulsed dye laser. J Laryngol Otol. 1997 Nov. 111 (11):1038-41. [QxMD MEDLINE Link].
Harrison DF. Use of estrogen in treatment of familial hemorrhagic telangiectasia. Laryngoscope. 1982 Mar. 92 (3):314-20. [QxMD MEDLINE Link].
Dallas NA, Samuel S, Xia L, Fan F, Gray MJ, Lim SJ, et al. Endoglin (CD105): a marker of tumor vasculature and potential target for therapy. Clin Cancer Res. 2008 Apr 1. 14 (7):1931-7. [QxMD MEDLINE Link].
Robert F, Desroches-Castan A, Bailly S, Dupuis-Girod S, Feige JJ. Future treatments for hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2020 Jan 7. 15 (1):4. [QxMD MEDLINE Link].
[Guideline] Faughnan ME, Mager JJ, Hetts SW, Palda VA, Lang-Robertson K, Buscarini E, et al. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020 Dec 15. 173 (12):989-1001. [QxMD MEDLINE Link]. [Full Text].
Shah RK, Dhingra JK, Shapshay SM. Hereditary hemorrhagic telangiectasia: a review of 76 cases. Laryngoscope. 2002 May. 112 (5):767-73. [QxMD MEDLINE Link].
Yaniv E, Preis M, Hadar T, Shvero J, Haddad M. Antiestrogen therapy for hereditary hemorrhagic telangiectasia: a double-blind placebo-controlled clinical trial. Laryngoscope. 2009 Feb. 119 (2):284-8. [QxMD MEDLINE Link].
Isaacs E. Aminocaproic Acid. Pediatric Drug Dosage Handbook. 8th ed. Ottawa, Canada: Winnipeg Health Sciences Center and CSHP; 1998. 161.
Lebrin F, Srun S, Raymond K, Martin S, van den Brink S, Freitas C, et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med. 2010 Apr. 16 (4):420-8. [QxMD MEDLINE Link].
Harvey RJ, Kanagalingam J, Lund VJ. The impact of septodermoplasty and potassium-titanyl-phosphate (KTP) laser therapy in the treatment of hereditary hemorrhagic telangiectasia-related epistaxis. Am J Rhinol. 2008 Mar-Apr. 22 (2):182-7. [QxMD MEDLINE Link].
Lesnik GT, Ross DA, Henderson KJ, Joe JK, Leder SB, White RI Jr. Septectomy and septal dermoplasty for the treatment of severe transfusion-dependent epistaxis in patients with hereditary hemorrhagic telangiectasia and septal perforation. Am J Rhinol. 2007 May-Jun. 21 (3):312-5. [QxMD MEDLINE Link].
Layton KF, Kallmes DF, Gray LA, Cloft HJ. Endovascular treatment of epistaxis in patients with hereditary hemorrhagic telangiectasia. AJNR Am J Neuroradiol. 2007 May. 28 (5):885-8. [QxMD MEDLINE Link].
de Gussem EM, Snijder RJ, Disch FJ, Zanen P, Westermann CJ, Mager JJ. The effect of N-acetylcysteine on epistaxis and quality of life in patients with HHT: a pilot study. Rhinology. 2009 Mar. 47 (1):85-8. [QxMD MEDLINE Link].
Bose P, Holter JL, Selby GB. Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med. 2009 May 14. 360 (20):2143-4. [QxMD MEDLINE Link].
Massoud OI, Youssef WI, Mullen KD. Resolution of hereditary hemorrhagic telangiectasia and anemia with prolonged alpha-interferon therapy for chronic hepatitis C. J Clin Gastroenterol. 2004 Apr. 38 (4):377-9. [QxMD MEDLINE Link].
Wheatley-Price P, Shovlin C, Chao D. Interferon for metastatic renal cell cancer causing regression of hereditary hemorrhagic telangiectasia. J Clin Gastroenterol. 2005 Apr. 39 (4):344-5. [QxMD MEDLINE Link].
Lupu A, Stefanescu C, Treton X, Attar A, Corcos O, Bouhnik Y. Bevacizumab as rescue treatment for severe recurrent gastrointestinal bleeding in hereditary hemorrhagic telangiectasia. J Clin Gastroenterol. 2013 Mar. 47 (3):256-7. [QxMD MEDLINE Link].
Shovlin CL, Jackson JE, Bamford KB, Jenkins IH, Benjamin AR, Ramadan H, et al. Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia. Thorax. 2008 Mar. 63 (3):259-66. [QxMD MEDLINE Link].
Shovlin CL, Winstock AR, Peters AM, Jackson JE, Hughes JM. Medical complications of pregnancy in hereditary haemorrhagic telangiectasia. QJM. 1995 Dec. 88 (12):879-87. [QxMD MEDLINE Link].
Buscarini E, Plauchu H, Garcia Tsao G, White RI Jr, Sabbà C, Miller F, et al. Liver involvement in hereditary hemorrhagic telangiectasia: consensus recommendations. Liver Int. 2006 Nov. 26 (9):1040-6. [QxMD MEDLINE Link].
Lerut J, Orlando G, Adam R, Sabbà C, Pfitzmann R, Klempnauer J, et al. Liver transplantation for hereditary hemorrhagic telangiectasia: Report of the European liver transplant registry. Ann Surg. 2006 Dec. 244 (6):854-62; discussion 862-4. [QxMD MEDLINE Link]. [Full Text].
Thevenot T, Vanlemmens C, Di Martino V, Becker MC, Denue PO, Kantelip B, et al. Liver transplantation for cardiac failure in patients with hereditary hemorrhagic telangiectasia. Liver Transpl. 2005 Jul. 11 (7):834-8. [QxMD MEDLINE Link].
Mitchell A, Adams LA, MacQuillan G, Tibballs J, vanden Driesen R, Delriviere L. Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia. Liver Transpl. 2008 Feb. 14 (2):210-3. [QxMD MEDLINE Link].
Curie A, Lesca G, Cottin V, Edery P, Bellon G, Faughnan ME, et al. Long-term follow-up in 12 children with pulmonary arteriovenous malformations: confirmation of hereditary hemorrhagic telangiectasia in all cases. J Pediatr. 2007 Sep. 151 (3):299-306. [QxMD MEDLINE Link].

Media Gallery

Typical manifestations in patient with Osler-Weber-Rendu disease (ie, hereditary hemorrhagic telangiectasia) with red nodules and starry telangiectasia on cheeks.
Close-up view of typical manifestations in patient with Osler-Weber-Rendu disease (ie, hereditary hemorrhagic telangiectasia) with red nodules and starry telangiectasia on lips.
Close-up view of typical manifestations in patient with Osler-Weber-Rendu disease (ie, hereditary hemorrhagic telangiectasia) with red nodules and starry telangiectasia on cheeks.

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Author

Klaus-Dieter Lessnau, MD, FCCP Former Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Jesus Lanza, MD Fellow in Pulmonary and Critical Care Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Disclosure: Nothing to disclose.

Raghukumar D Thirumala, MD, MPH Fellow in Pulmonary Medicine, Lenox Hill Hospital, North Shore-Long Island Jewish Health System

Raghukumar D Thirumala, MD, MPH is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine, Society of Hospital Medicine

Disclosure: Nothing to disclose.

Dora E Izaguirre Anariba, MD, MPH Physician, Department of Medicine, Wyckoff Heights Medical Center

Dora E Izaguirre Anariba, MD, MPH is a member of the following medical societies: American College of Physicians, American Heart Association, American Medical Association, American Public Health Association, Colegio Medico de Honduras

Disclosure: Nothing to disclose.

Chief Editor

Vincent Lopez Rowe, MD, FACS Professor and Chief, Division of Vascular and Endovascular Surgery, Gonda (Goldschmied) Vascular Center, University of California, Los Angeles, David Geffen School of Medicine

Vincent Lopez Rowe, MD, FACS is a member of the following medical societies: American College of Surgeons, American Heart Association, American Surgical Association, Pacific Coast Surgical Association, Society for Clinical Vascular Surgery, Society for Vascular Surgery, Society of Black Academic Surgeons, Society of Black Vascular Surgeons, Southern California Vascular Surgical Society, Western Vascular Society

Disclosure: Nothing to disclose.

Acknowledgements

Geromanta Baleviciene, MD, Head and Professor, Department of Dermatology, Vilnius University, Medical Faculty, Lithuania