Hereditary hemorrhagic telangiectasia

Osler's disease or Osler 's disease (after William Osler ), and Osler -Weber- Rendu, Osler -Weber-Rendu or hereditary hemorrhagic telangiectasia (HHT ) is an autosomal dominant inherited disorder in which there is an abnormal dilation of blood vessels comes. These so-called telangiectasias can occur anywhere (hence the symptom epistaxis ) can be found, however, particularly in the nose, mouth, face and the mucous membranes of the gastrointestinal tract. Since the vasodilation are very vulnerable, it can easily lead to cracks and thus to bleeding.

Among other things, the smallest vessels widen of skin and mucous membranes and are then seen as a pinhead to rice-sized red spots. Special significance of these telangiectasias in the gastrointestinal tract, because they can be the cause of recurring (recurrent ) bleeding there. However, it can also significantly greater vasodilation occur. These are formed, especially in the lungs, the brain and the liver. The changes often make for a long time not noticeable, but can also be caused bleeding suddenly very threatening will (see below). But usually the first signs of the disease appear in puberty with epistaxis, in a few patients even without nose bleeds and sometimes much later.

In Germany, about 35,000 people suffer from Osler.

Causes

The disease is inherited as an autosomal dominant trait. This means that one set of parents, in which a partner Osler's disease patient is, half of the children are affected regardless of gender on average.

There are at least three genes that may lead in an altered state ( mutation) to the clinical picture of the Osler. Two of these genes are now known and can be studied in patients and their family members ( endoglin, a TGFβ1 receptor on chromosome 9q and ALK -1 = activin receptor like kinase 1 on chromosome 12q ) *. There may also be patients who are genetically disease - Osler - patients, but never show signs of the disease.

Diagnostics

The diagnosis is mainly clinical, but genetic studies can play a crucial role.

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

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

The Osler is regarded as confirmed if at least three of these four criteria are met. Two criteria were met, one starts from a suspected case. Even if only a fulfilled criterion Osler's disease is unlikely that nevertheless such as children affected, which often only the fourth point has been met, while the other can only be set in the course of life is possible. Here is often genetic diagnosis helpful.

Symptoms and Treatment

Nosebleed

90% of people with Osler's disease have a nosebleed, which is usually already occurs in puberty and can have dimensions that can lead to impaired quality of life up to the inability to work. In many patients it comes to anemia (anemia). It may be necessary to supply iron or blood. To prevent nasal ointments are used in the case of a bleeding nasal packing. Surgical therapies are the treatment of the laser light vasodilation or transplantation wherein the diseased mucous membrane is replaced by the skin from other areas of the face ( for example, behind the ear ). A cure in the long term is not yet possible.

Lung

Approximately 5 to 30 % of all disease - Osler - patients have large vasodilatation in the lungs, called pulmonary arteriovenous malformations ( PAVM ). Due to this large vessel shorts also clot and bacteria can happen and lead to strokes and Hirneiterungen ( abscesses ). For medical treatment, in particular dental treatments, it can come to Einschwemmung of bacteria in the blood. It is therefore recommended that all patients in whom a PAVM could exist previously received antibiotics. Especially during pregnancy, the abnormal vessels of the lungs can significantly increase in size. If the short circuit is too large, it may lead to overloading of the circuit. Pulmonary hemorrhage rarely occurs, but may be life-threatening. In cases of suspected PAVM a computed tomography ( CT) or magnetic resonance imaging of the chest, a blood gas analysis or suitable ultrasound is performed.

If necessary, the dilated vessels can be through the introduction of metal spirals or small balloons close ( embolization ). Rarely, however, major surgery with opening of the thorax are displayed.

Brain

As discussed above, can pass through the lungs and lead to strokes or brain abscesses in lung vascular dilations ( PAVM ) clots and bacteria. In addition, can also cerebral vascular malformations (CVM, cerebral "belonging to brain " stands for vascular vessel) occur. Even with the CVM bleeding may occur, but it must not be treated any CVM. It must be weighed, how big is the risk of bleeding compared to the risk of treatment. The vascular malformations can be surgically removed by introducing material via a catheter closed ( embolization ) or by opening the skull. It is estimated the frequency of CVM to 5 to 20%, therefore, recommends the American self-help organization the Crohn's patients Osler, that in all patients after the age of 12, a special MRI scan of the head should be performed. When suspicions (eg headache or paralysis ) but this can already be used to make sense.

Gastrointestinal tract

Especially from the age of 40 may cause stomach and intestinal bleeding. This bleeding can geringgradig, but also be very severe. The chair can look at heavy bleeding teerähnlich dark and " rotten " smell or durchmengt with red chair. In mild bleeding but these signs can go unnoticed. Sometimes only brings the investigation of anemia, which is felt by the patient usually as general weakness and fatigue, the doctor on the right track. A gastrointestinal mirroring To clarify then performed frequently. Find there a few extensions and suitable vessel, then a treatment with lasers, injections or electrical desolation are often performed in the same procedure. If there are many sources of bleeding and it comes to repeated bleeding, so treatment with female hormones can be attempted. Because of the potential side effects (including on the cardiovascular system and breast formation in men) must be a careful consideration of the advantages and disadvantages.

Liver

Also in the liver vascular shorts can (shunts ) may occur. This can lead to an overload of the heart, which is often perceived by stakeholders to fatigue and lack of physical strength, similar to the anemia. Drug improvement of cardiac function is often attempted as a first step of treatment. There are a number of engaging treatment, in particular the embolization (see above), and liver transplantation. Since the side effects can be serious, careful balancing of the pros and cons here is similar as required in the CVM.