Osler's disease

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Classification according to ICD-10
I78.0 Hereditary hemorrhagic telangiectasia
ICD-10 online (WHO version 2019)
Patient with Osler's disease

Osler's disease or Osler's disease , also called Osler-Weber-Rendu's disease , is a congenital disease in which there is a pathological expansion of blood vessels . These so-called telangiectasias can occur anywhere, but are particularly found in the nose (hence the main symptom nosebleed ), mouth , face and the mucous membranes of the gastrointestinal tract . Since the vasodilatation is very vulnerable, tears and bleeding can easily occur.

Synonyms are: Osler syndrome; Osler-Rendu-Weber disease; Hereditary hemorrhagic telangiectasia (HHT or angiomatosis), ORW disease in English
Not to be confused with Osler 's disease and Osler nodules .

The disease is according to a description from 1901 by the Canadian doctor William Osler , the French doctor Henri Jules Louis Marie Rendu (1844–1902), first described in 1896, and a description from 1904 by the English doctor Frederick Parkes Weber ( 1863–1962).

pathology

Among other things, the smallest vessels in the skin and mucous membrane expand and can then be seen as red spots the size of a pinhead to the size of a grain of rice. These telangiectasias are of particular importance in the gastrointestinal tract , because there they can be the cause of frequently recurring (recurrent) bleeding ( hemorrhagic diathesis ). However, significantly larger vasodilatation can also occur. These arise especially in the lungs , the brain and the liver . The changes are often not noticeable for a long time. B. suddenly become very threatening due to bleeding (see below). The first signs of the disease usually appear in puberty with nosebleeds, but in a few patients without nosebleeds and sometimes much later.

distribution

The frequency is given as between 1: 5,000 and 1: 8,000, inheritance is autosomal dominant with almost complete penetrance at the age of 50 . In Germany around 35,000 people suffer from M. Osler.

Classification and causes

Depending on the underlying mutation, a distinction is currently made between the following forms:

  • HHT1 , autosomal dominant mutations in the ENG - gene on locus 9q34.11
  • HHT2 , autosomal dominant, mutations in the ACVRL1 gene at 12q13.13
  • HHT3 , mutations at 5q31.3-q32
  • HHT4 , autosomal dominant, mutations in the ACVRL1 gene at 7p14
  • JPHT , with juvenile polyposis, autosomal dominant, mutations in the SMAD4 gene at 18q21.1

The genes ACVRL1 and ENG belong to the signal chain of transforming growth factors and lead to a disturbance of the equilibrium of the angiogenesis of the capillaries with excessive formation of new vessels. The formation of new vessels is mainly driven by the recruitment of endothelial progenitor cells with intussusceptive angiogenesis.

There may also be patients who are genetically Osler's disease patients but who never show signs of the disease.

Diagnosis

The diagnosis is mostly made clinically, but genetic testing can make a decisive contribution.

Criteria for the clinical diagnosis of Osler's disease (HHT) (so-called Curaçao criteria), created by the medical and scientific advisory committee of the American self-help group:

  • Epistaxis - nosebleeds (spontaneous and repeated)
  • Telangiectasia - typical small vascular malformations, multiple and in characteristic places (lips, oral cavity, fingers, nose)
  • Visceral manifestations - involvement of internal organs, especially of the lungs, liver, brain and gastrointestinal tract (see text)
  • Positive family history - At least one first degree relative affected by these criteria.

Osler's disease is confirmed if at least three of these four criteria are met. If two criteria are met, it is assumed that there is a suspected case. Even if Osler's disease is unlikely if only one criterion is met, this is still possible, e.g. B. Affected children, in whom often only the fourth point is fulfilled, while the others can only adjust in the course of life. Genetic diagnostics are often helpful here.

Differential diagnosis

The CREST syndrome , pulmonary artery hypertension and benign hereditary telangiectasia are to be distinguished.

Symptoms and Treatment

Epistaxis

90% of all people with Osler's disease have nosebleeds , which usually already occurs during puberty and can take on proportions that can lead to a reduction in quality of life or even incapacity for work . Many patients develop anemia ( anemia ). You may need to add iron or blood. Nasal ointments are used for prevention, and nasal tamponade in the event of bleeding . Surgical therapies include laser light treatment of vasodilation or transplantation , in which the diseased nasal mucosa is replaced with skin from other facial regions (for example from behind the ear). A permanent cure is not yet possible.

lung

Approximately 5 to 30% of all Osler disease patients have large vasodilatations in the lungs, so-called pulmonary arteriovenous malformations (PAVM). These large vascular short-circuits can also cause clots and bacteria to pass and thus lead to strokes and ulcerations ( abscesses ). During medical interventions, especially dental treatment, bacteria can enter the blood. It is therefore recommended that all patients who may have PAVM receive antibiotics beforehand . The abnormal blood vessels in the lungs can increase significantly in size, especially during pregnancy. If the short circuit becomes too large, it can overload the circuit. Lung bleeding is rare but can be life-threatening. If PAVM is suspected, computed tomography (CT) or magnetic resonance imaging of the chest, blood gas analysis, or appropriate ultrasound examinations will be done.

If necessary, the enlarged vessels can be closed by inserting metal spirals or small balloons ( embolization ). However, major operations involving opening of the thorax are also rarely indicated.

brain

As explained above, pulmonary vasculature (PAVM) can cause clots and bacteria to pass through the lungs and cause strokes or brain abscesses. In addition, cerebral vascular malformations (CVM, cerebral “belonging to the brain”, vascular stands for vessel) can occur. Bleeding can also occur with CVM, but not every CVM needs treatment. It must be weighed how great the risk of bleeding is compared to the risk of treatment. The vascular malformations can be closed by introducing material via a catheter (embolization) or surgically removed after opening the skull. The frequency of CVM is estimated at 5 to 20%, which is why the American self-help organization recommends Osler's disease patients that a special magnetic resonance tomography of the head should be carried out in all patients after the age of 12 . If there are any suspicions (e.g. headache or paralysis), however, this can be useful earlier.

Gastrointestinal tract

Gastric and intestinal bleeding can occur, especially from the age of 40. This bleeding can be minor or very severe. If the bleeding is profuse, the stool may look tar-like and smell “lazy” or be mixed with red stool. However, if the bleeding is light, these signs may go unnoticed. Sometimes only the clarification of an anemia, which is usually felt by the patient as general weakness and fatigue, puts the doctor on the right track. A gastrointestinal mirror is often performed for clarification. If there are few and suitable vasodilatations there, treatment with laser , injection or electrical sclerotherapy can often be carried out in the same procedure. If there are many sources of bleeding and repeated bleeding occurs, therapy with female hormones can be tried. Because of the possible side effects (including on the cardiovascular system and breast formation in men), the advantages and disadvantages must be carefully weighed up.

liver

Computed tomography in Osler's disease in the liver with perfusion inhomogeneities and tortuous, dilated vessels in intrahepatic shunts.

Vascular short-circuits ( shunts ) can also occur in the liver . These can lead to an overload of the heart, which is often perceived by those affected as exhaustion and a lack of physical capacity, similar to anemia. Drug improvement in heart function is often attempted as the first step in treatment. There are a number of interventional treatments, in particular embolization (see above) and liver transplantation . Since the side effects can be serious, as with CVM, careful weighing of the advantages and disadvantages is necessary.

literature

  • emedicine medscape
  • Ludwig Heilmeyer , Herbert Begemann: blood and blood diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 376–449, here: p. 445: The Osler Disease (hereditary, hemorrhagic telangiectasia or angiomatosis).

Individual evidence

  1. ↑ M. Sand, D. Sand, C. Thrandorf, V. Paech, P. Altmeyer, FG Bechara: Cutaneous lesions of the nose. In: Head & face medicine. Volume 6, 2010, p. 7, ISSN  1746-160X . doi: 10.1186 / 1746-160X-6-7 . PMID 20525327 . PMC 290354 (free full text). (Review).
  2. ↑ Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
  3. ↑ a b c d Hereditary hemorrhagic telangiectasia. In: Orphanet (Rare Disease Database).
  4. ^ WB Osler: On a family form of recurring epistaxis, associated with multiple telangiectases of the skin and mucous membranes. In: The Johns Hopkins Hospital Bulletin , 1901, Vol. 12: p. 333-337.
  5. ↑ M. Rendu: Epistaxis répétés chez un sujet porteur de petits angiomes cutanés et muqueux. In: Lancette française: gazette des hôpitaux civils et militaires , Paris, 1896, vol. 69: pp. 1322-1323.
  6. ^ FP Weber: A note on cutaneous telangiectases and their etiology. Comparison with the etiology of haemorrhoids and ordinary varicose veins. In: Edinburgh Medical Journal , 1904: pp. 346-349.
  7. ↑ Who named it
  8. ↑ Telangiectasia, hereditary hemorrhagic, type 1.  In: Online Mendelian Inheritance in Man . (English)
  9. ↑ Telangiectasia, hereditary hemorrhagic, type 2.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ Telangiectasia, hereditary hemorrhagic, type 3.  In: Online Mendelian Inheritance in Man . (English)
  11. ↑ Telangiectasia, hereditary hemorrhagic, type 4.  In: Online Mendelian Inheritance in Man . (English)
  12. ↑ Juvenile polyposis / hereditary hemorrhagic telangiectasia syndrome.  In: Online Mendelian Inheritance in Man . (English)
  13. ↑ Maximilian Ackermann, Steven J Mentzer, Wilfried Roth, Urban Geisthoff, Erich Stoelbe: Pulmonary microvascular architecture in hereditary haemorrhagic telangiectasia . In: Thorax . tape 72 , no. 9 , September 2017, ISSN  0040-6376 , p. 861–863 , doi : 10.1136 / thoraxjnl-2016-209299 ( bmj.com [accessed February 8, 2020]).

Web links

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