Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia

In medicine, hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome,^[1] is an autosomal dominant genetic disorder that leads to vascular malformations.

 Signs and symptoms

HHT is characterised by telangiectasia (small vascular malformations) on the skin and mucosal linings, epistaxis (nosebleeds), and arteriovenous malformations (AVMs) in various internal organs. Skin and mucosa telangiectasias are most remarkable on the tongue, hands/fingers, nose, lips, mouth/throat and conjunctiva.

The internal organs that can harbor AVMs often include the brain and lungs. In both, bleeding can seriously endanger life. Anemia may occur due to bleeding from digestive tract AVMs. Congestive cardiac failure (high-output heart failure) may develop in the presence of marked shunting arterial blood to the venous circulation, e.g. when AVMs are present in the liver.

Diagnosis

There are four diagnostic criteria.^[2] If three or four are met, a patient has definite HHT, while two gives a possible diagnosis:

1. Spontaneous recurrent epistaxis
2. Multiple teleangiectasias on typical locations (see above)
3. Proven visceral AVM (lung, liver, brain, spine)
4. First-degree family member with HHT

When HHT is suspected, physical examination focuses on inspecting the whole skin for teleangiectasias, auscultation of the lungs and liver, and neurological examination.

Pulmonary AVMs can be anticipated by measuring oxygen levels and performing arterial blood gas (ABG) sampling. An X-ray of the chest can show susceptible lesions; in addition, low oxygen tension (<96% or a 2% decrease upon standing) or low blood oxygen levels on ABG are required for a diagnosis.

Pathophysiology

The mechanism underlying the formation of vascular malformations is not completely understood, but signalling of transforming growth factor-β1 is most likely to be involved. Possibly, connective tissue is required to support and guide proliferating blood vessels during angiogenesis, and defects in TGF-β signalling adversely affect connective tissue and matrix production.

Treatment

There is no specific treatment for the condition. Anemia due to bleeding from digestive tract AVMs often necessitates repeated blood transfusions. AVMs in critical organs often necessitates surgery. If major AVMs are all the patient has in terms of long-term problems, the surgery performed will block the malformed arteries, ruling out the risk for stroke and blood-clots. This surgery will hopefully lead to a normal life for the patient, and also help doctors diagnose patients with HHT more easily around the globe.

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