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Gastrointestinal Manifestations of Hereditary Hemorrhagic Telangiectasia (HHT): A Systematic Review of the Literature

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Abstract

Hereditary hemorrhagic telangiectasia (HHT), also called Osler–Weber–Rendu syndrome, is an autosomal dominant genetic disease that affects the vasculature of numerous organs. The prevalence of HHT is estimated to be between 1.5 and 2 persons per 10,000. While there is still much to learn about this condition, there is an increasing understanding its underlying pathophysiology, genetic basis, presentations, and management. Recognizing that the clinical manifestations of HHT can involve a number of organ systems will provide clinicians with a higher index of suspicion for the disease. This early diagnosis and genotyping can greatly reduce mortality for a patient with HHT through appropriate screening for complications. This review will focus on the gastrointestinal manifestations of HHT and how these can dictate treatment and prognosis.

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Abbreviations

HHT:

Hereditary hemorrhagic telangiectasia

AVM:

Arteriovenous malformation

JPHT:

Juvenile polyposis/hereditary hemorrhagic telangiectasia

GI:

Gastrointestinal

VCE:

Video capsule endoscopy

EGD:

Esophagogastroduodenoscopy

References

  1. Guttmacher AE, Marchuk DA, White RI. Hereditary hemorrhagic telangiectasia. N Engl J Med. 1995;333:918–924.

    Article  CAS  PubMed  Google Scholar 

  2. Dakeishi M, Shioya T, Wada Y, et al. Genetic epidemiology of hereditary hemorrhagic telangiectasia in a local community in the northern part of Japan. Hum Mutat. 2002;19:140–148.

    Article  CAS  PubMed  Google Scholar 

  3. Grosse SD, Boulet SL, Grant AM, Hulihan MM, Faughnan ME. The use of US health insurance data for surveillance of rare disorders: hereditary hemorrhagic telangiectasia. Genet Med. 2014;16:33–39.

    Article  PubMed  Google Scholar 

  4. 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;116A(4):324–328.

    Article  PubMed  Google Scholar 

  5. Govani FS, Shovlin CL. Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet. 2009;17:860–871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mcallister KA, Grogg KM, Johnson DW, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet. 1994;8:5–51.

    Article  Google Scholar 

  7. Johnson DW, Berg JN, Baldwin MA, et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996;13:189–195.

    Article  CAS  PubMed  Google Scholar 

  8. Gallione CJ, Repetto GM, Legius E, et al. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet. 2004;363:852–859.

    Article  CAS  PubMed  Google Scholar 

  9. Kjeldsen AD, Møller TR, Brusgaard K, Vase P, Andersen PE. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia. J Intern Med. 2005;258:349–355.

    Article  CAS  PubMed  Google Scholar 

  10. Faughnan ME, Palda VA, Garcia-tsao G, et al. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet. 2011;48:73–87.

    Article  CAS  PubMed  Google Scholar 

  11. Trembath RC, Thomson JR, Machado RD, et al. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2001;345:325–334.

    Article  CAS  PubMed  Google Scholar 

  12. Olivieri C, Lanzarini L, Pagella F, et al. Echocardiographic screening discloses increased values of pulmonary artery systolic pressure in 9 of 68 unselected patients affected with hereditary hemorrhagic telangiectasia. Genet Med. 2006;8:183–190.

    Article  PubMed  Google Scholar 

  13. Sopeña B, Pérez-Rodríguez MT, Portela D, Rivera A, Freire M, Martínez-Vázquez C. High prevalence of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. Eur J Intern Med. 2013;24:e30–e34.

    Article  PubMed  Google Scholar 

  14. Vorselaars VM, Velthuis S, Snijder RJ, Vos JA, Mager JJ, Post MC. Pulmonary hypertension in hereditary haemorrhagic telangiectasia. World J Cardiol. 2015;7:230–237.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Girerd B, Montani D, Coulet F, et al. Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am J Respir Crit Care Med. 2010;181:851–861.

    Article  CAS  PubMed  Google Scholar 

  16. Plauchu H, Dechadarévian JP, Bideau A, Robert JM. Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am J Med Genet. 1989;32:291–297.

    Article  CAS  PubMed  Google Scholar 

  17. Grigg C, Anderson D, Earnshaw J. Diagnosis and treatment of hereditary hemorrhagic telangiectasia. Ochsner J. 2017;17:157–161.

    PubMed  PubMed Central  Google Scholar 

  18. Mohler ER III, et al. Transillumination of the fingers for vascular anomalies: a novel method for evaluating hereditary hemorrhagic telangiectasia. Genet Med. 2009;11:356–358.

    Article  PubMed  Google Scholar 

  19. Latino GA, Al-saleh S, Alharbi N, Edwards C, Faughnan ME, Ratjen F. Prevalence of pulmonary arteriovenous malformations in children versus adults with hereditary hemorrhagic telangiectasia. J Pediatr. 2013;163:282–284.

    Article  PubMed  Google Scholar 

  20. Fulbright RK, Chaloupka JC, Putman CM, et al. MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations. AJNR Am J Neuroradiol. 1998;19:477–484.

    CAS  PubMed  Google Scholar 

  21. Buscarini E, Danesino C, Plauchu H, et al. High prevalence of hepatic focal nodular hyperplasia in subjects with hereditary hemorrhagic telangiectasia. Ultrasound Med Biol. 2004;30:1089–1097.

    Article  PubMed  Google Scholar 

  22. Canzonieri C, Centenara L, Ornati F, et al. Endoscopic evaluation of gastrointestinal tract in patients with hereditary hemorrhagic telangiectasia and correlation with their genotypes. Genet Med. 2014;16:3–10.

    Article  CAS  PubMed  Google Scholar 

  23. Grève E, Moussata D, Gaudin JL, 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;71:760–767.

    Article  PubMed  Google Scholar 

  24. Chamberlain SM, Patel J, Carter Balart J, Gossage JR, Sridhar S. Evaluation of patients with hereditary hemorrhagic telangiectasia with video capsule endoscopy: a single-center prospective study. Endoscopy. 2007;39:516–520.

    Article  CAS  PubMed  Google Scholar 

  25. Ingrosso M, Sabbà C, Pisani A, et al. Evidence of small-bowel involvement in hereditary hemorrhagic telangiectasia: a capsule-endoscopic study. Endoscopy. 2004;36:1074–1079.

    Article  CAS  PubMed  Google Scholar 

  26. Letteboer TG, Mager JJ, Snijder RJ, et al. Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia. J Med Genet. 2006;43:371–377.

    Article  CAS  PubMed  Google Scholar 

  27. Van Tuyl SA, Letteboer TG, Kuipers EJ, Snijder RJ, Westermann CJ, Stolk MF. Assessment of intestinal vascular malformations in patients with hereditary hemorrhagic teleangiectasia and anemia. Eur J Gastroenterol Hepatol. 2007;19:153–158.

    Article  PubMed  Google Scholar 

  28. Proctor DD, Henderson KJ, Dziura JD, Longacre AV, White RI. Enteroscopic evaluation of the gastrointestinal tract in symptomatic patients with hereditary hemorrhagic telangiectasia. J Clin Gastroenterol. 2005;39:115–119.

    PubMed  Google Scholar 

  29. Longacre AV, Gross CP, Gallitelli M, Henderson KJ, White RI, Proctor DD. Diagnosis and management of gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia. Am J Gastroenterol. 2003;98:59–65.

    Article  PubMed  Google Scholar 

  30. Chick JF, Sheehan SE, Chauhan NR. The many faces of Hereditary Hemorrhagic Telangiectasia: median arcuate ligament syndrome, arteriovenous malformations, and cerebral aneurysms. Intern Emerg Med. 2012;7:385–386.

    Article  PubMed  Google Scholar 

  31. Baba R, Hashimoto E, Yashiro K, et al. Multiple abdominal telangiectases and lymphangiectases. A limited form of Osler-Weber-Rendu disease? J Clin Gastroenterol. 1995;21:154–157.

    Article  CAS  PubMed  Google Scholar 

  32. Yakshe PN, Albert F, Ragsdale B, Travers R, Benjamin S. An unusual vascular lesion in a patient with hereditary hemorrhagic telangiectasia. Gastrointest Endosc. 1990;36:513–516.

    Article  CAS  PubMed  Google Scholar 

  33. Sivarani S, Chan YK, Liam CK, Kumar G, Abdullah BJ, Mahadeva S. Education and Imaging. Gastrointestinal: massive intraperitoneal haemorrhage in a young woman with hereditary hemorrhagic telangiectasia. J Gastroenterol Hepatol. 2010;25:1587.

    Article  CAS  PubMed  Google Scholar 

  34. Schwenter F, Faughnan ME, Gradinger AB, et al. Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation. J Gastroenterol. 2012;47:795–804.

    Article  CAS  PubMed  Google Scholar 

  35. Gamba G, Maffé GC, Mosconi E, Tibaldi A. Di domenico G, Frego R. Ultrasonographic images of spontaneous intramural hematomas of the intestinal wall in two patients with congenital bleeding tendency. Haematologica. 1995;80:388–389.

    CAS  PubMed  Google Scholar 

  36. Kjeldsen AD, Kjeldsen J. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia. Am J Gastroenterol. 2000;95:415–418.

    Article  CAS  PubMed  Google Scholar 

  37. Abdalla SA, Geisthoff UW, Bonneau D, et al. Visceral manifestations in hereditary haemorrhagic telangiectasia type 2. J Med Genet. 2003;40:494–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bayrak-toydemir P, Mcdonald J, Markewitz B, et al. Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet A. 2006;140:463–470.

    Article  PubMed  Google Scholar 

  39. Barral M, Sirol M, Placé V, et al. Hepatic and pancreatic involvement in hereditary hemorrhagic telangiectasia: quantitative and qualitative evaluation with 64-section CT in asymptomatic adult patients. Eur Radiol. 2012;22:161–170.

    Article  PubMed  Google Scholar 

  40. Ravard G, Soyer P, Boudiaf M, et al. Hepatic involvement in hereditary hemorrhagic telangiectasia: helical computed tomography features in 24 consecutive patients. J Comput Assist Tomogr. 2004;28:488–495.

    Article  PubMed  Google Scholar 

  41. Garcia-Tsao G, Korzenik JR, Young L, et al. Liver disease in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2000;343:931–936.

    Article  CAS  PubMed  Google Scholar 

  42. Brenard R, Chapaux X, Deltenre P, et al. Large spectrum of liver vascular lesions including high prevalence of focal nodular hyperplasia in patients with hereditary haemorrhagic telangiectasia: the Belgian Registry based on 30 patients. Eur J Gastroenterol Hepatol. 2010;22:1253–1259.

    Article  CAS  PubMed  Google Scholar 

  43. Costa Macedo T, Maldonado R, Valente A, et al. Hemobilia in hereditary hemorrhagic telangiectasia: an unusual complication of endoscopic retrograde cholangiopancreatography. Endoscopy. 2003;35:531–533.

    Article  CAS  PubMed  Google Scholar 

  44. Buscarini E, Buscarini L, Danesino C, et al. Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler sonographic screening in a large family. J Hepatol. 1997;26:111–118.

    Article  CAS  PubMed  Google Scholar 

  45. Mohr JP, Parides MK, Stapf C, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet. 2014;383:614–621.

    Article  CAS  PubMed  Google Scholar 

  46. Gaujoux S, Bucau M, Ronot M, Paradis V, Vilgrain V, Belghiti J. Liver resection in patients with hepatic hereditary hemorrhagic telangiectasia. Dig Surg. 2013;30:410–414.

    Article  PubMed  Google Scholar 

  47. Sabbà C, Pasculli G, Suppressa P, et al. Life expectancy in patients with hereditary haemorrhagic telangiectasia. QJM. 2006;99:327–334.

    Article  PubMed  Google Scholar 

  48. 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;116:432–439.

    Article  CAS  PubMed  Google Scholar 

  49. 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:e88511.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work received grant support from: NIH Training Grant NIDDK T32 DK07180-30 (JNB); Department of Veterans Affairs RR&D Merit Review (JRP) I01 RX000194; Human Studies CORE through CURE: Digestive Diseases Research Center supported by NIH grant P30DK41301.

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Authors and Affiliations

  1. Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Samuel B. Jackson, Nicholas P. Villano, Jihane N. Benhammou, Joseph R. Pisegna & David Padua

  2. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Samuel B. Jackson, Nicholas P. Villano, Jihane N. Benhammou, Joseph R. Pisegna & David Padua

  3. Department of Pathology and Laboratory Medicine, Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Michael Lewis

  4. Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Veterans Affairs, VA Greater Los Angeles Healthcare System (691/111C), 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA

    Samuel B. Jackson, Nicholas P. Villano, Jihane N. Benhammou, Joseph R. Pisegna & David Padua

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  1. Samuel B. Jackson
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Correspondence to David Padua.

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The authors certify that this manuscript is an original work and is not published or submitted for publication elsewhere. We have no related material submitted elsewhere and will not submit this manuscript or part of this manuscript to other publishers. We certify that each author has participated substantially in the work to create and revise this manuscript. We have no financial disclosures or conflicts of interest to declare.

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Jackson, S.B., Villano, N.P., Benhammou, J.N. et al. Gastrointestinal Manifestations of Hereditary Hemorrhagic Telangiectasia (HHT): A Systematic Review of the Literature. Dig Dis Sci 62, 2623–2630 (2017). https://doi.org/10.1007/s10620-017-4719-3

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