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Hereditary hemorrhagic telangiectasia: an update on clinical manifestations and diagnostic measures

Hereditäre hämorrhagische Teleangiektasie: aktuelle Übersicht zu klinischen Krankheitsmerkmalen und diagnostischen Verfahren

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Zusammenfassung

Die hereditäre hämorrhagische Teleangiektasie (HHT), auch als Morbus Rendu-Osler-Weber bekannt, ist eine autosomal-dominant vererbte Erkrankung des Gefäßbindegewebes. Die Erkrankung wird charakterisiert durch die klassische Trias bestehend aus (muko-)kutanen Teleangiektasien, arteriovenösen Malformationen mit rezidivierender Epistaxis und Hämorrhagien sowie der Heredität. Eine Vielzahl unterschiedlicher klinischer Manifestationsformen der HHT sind beschrieben worden. In mehr als 90% der Fälle stellt die Epistaxis das klinische Erstsymptom dar, wodurch Hals-Nasen-Ohrenärzten eine wichtige Schlüsselrolle in der Diagnosestellung und der Behandlung der HHT zukommt. Trotz neuester diagnostischer und therapeutischer Entwicklungen ist eine Heilung dieser, den Betreffenden in seiner Lebensqualität oft einschränkenden Erkrankung nicht möglich. Außer der Nase sind vor allem die Haut, die Lunge, das Hirn, die Leber und der Gastrointestinaltrakt von arterio-venösen Malformationen (AVM) befallen. Die Entstehung der HHT wird im wesentlichen Mutationen zweier Gene zugeschrieben. Zum einen handelt es sich hierbei um Endoglin (ENG) auf Chromosom 9q33-q34 und activin-receptor like kinase (ALK1) auf Chromosom 12q13. Mutationen von Endoglin werden dem HHT Typ 1 zugeschrieben mit einer Inzidenz von bis zu 40% für pulmonale arteriovenöse Malformationen (AVM). Mutationen von ALK1 entsprechen dem HHT Typ 2 mit einer Inzidenz von bis zu 14% für pulmonale AVM. Diese Arbeit dient zum besseren Verständnis der Komplexität der HHT-Erkrankung, wobei anhand einer Übersicht zur aktuellen Literatur vor allem ein Schwerpunkt auf die klinischen Manifestationsformen, die Molekulargenetik und die Diagnosemöglichkeiten gelegt werden soll. Therapeutische Optionen in der Behandlung der HHT sind hier bewusst nicht erwähnt worden, da sie Gegenstand einer weiteren Arbeit sind. Dadurch, dass die HHT häufiger vorkommt als vermutet und eine weite Bandbreite klinischer Manifestationen aufweisen kann, stellt sie für viele Subspezialisierungen eine enorme Herausforderung dar, die ein eingehendes interdisziplinäres diagnostisches Screening in der Behandlung verlangt.

Summary

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal dominant disorder of the fibrovascular tissue. It is characterized by the classic triad of (muco-)cutaneous telangiectases, arteriovenous malformations with recurrent epistaxis and hemorrhages, and inheritance. A wide variety of clinical manifestations in HHT have been described. In more than 90% of the patients, nosebleeds are the first predominant symptom, therefore ENT physicians often play a key role as far as diagnosis and management of the disease are concerned. In spite of recent diagnostic and therapeutic progress, a cure for this often burdening and handicapping disease is still not available. Apart from affecting the nose, arteriovenous malformations (AVMs) may also affect the skin, lungs, brain, liver and gastrointestinal tract. The two known genes that are implicated in HHT are endoglin (ENG) located on chromosome 9q33-q34 and activin-receptor-like kinase (ALK1) located on chromosome 12q13. Mutations of ENG are observed in HHT type 1 with an incidence up to 40% for pulmonary AVMs, whereas mutations of ALK1 are observed in HHT type 2 with an incidence of only 14% for pulmonary AVMs, which clinically distinguishes these two types of mutation. The emphasis of this paper is mainly on the clinical manifestation, molecular genetics and diagnosis of HHT, taking account of current literature on HHT in order to better understand the complexity of the disease. Recent therapeutic options in the treatment of HHT have been omitted from this paper as they are subject of a following paper. HHT is more common than previously thought and shows a broad range of different clinical organ manifestations that can be sources of substantial morbidity and mortality, making HHT a continuing challenge for many sub-specialties where interdisciplinary diagnostic screening is mandatory in the management of the disease.

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany

    Haneen Sadick, Karl Götte, Ramin Naim, Frank Riedel, Gregor Bran & Karl Hörmann

  2. Institute of Clinical Radiology, University Hospital Mannheim, Mannheim, Germany

    Maliha Sadick

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  1. Haneen Sadick
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  2. Maliha Sadick
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  3. Karl Götte
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Correspondence to Haneen Sadick.

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Sadick, H., Sadick, M., Götte, K. et al. Hereditary hemorrhagic telangiectasia: an update on clinical manifestations and diagnostic measures. Wien Klin Wochenschr 118, 72–80 (2006). https://doi.org/10.1007/s00508-006-0561-x

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