Hereditary Hemorrhagic Telangiectasia (Osler's Disease): Systemic, Interdisciplinary, Relatively Common—and Often Missed

Abstract

Background: Hereditary hemorrhagic telangiectasia (HHT, Rendu- Osler-Weber disease, or Osler's disease for short) is a systemic disease that can severely impair the quality of life and that requires interdisciplinary treatment. Among rare diseases, it is relatively common, with a prevalence of approximately 1/5000.

Methods: This review is based on publications retrieved by a selective literature search, including the two international guidelines on clinically relevant aspects of HHT.

Results: On average, about two decades elapse between the initial symptoms and the diagnosis of HHT. 95% of patients have nosebleeds; these usually begin before age 20 but can occur at any time, from infancy to old age. The diagnosis is usually made on clinical grounds on the basis of the characteristic telangiectases, a positive family history, and possible involvement of the gastrointestinal tract, lungs, liver, and brain. Nosebleeds can sometimes be reduced by outpatient measures including counseling on keeping the nose moist (expert consensus), self-application of a nasal packing (which improves the quality of life, according to an online survey), and the prescription of tranexamic acid (reduction of nosebleeds from 17.3% [5.5; 27.6] to 54%). In particular, screening (expert consensus) for pulmonary vascular malformations (frequency 10-50%) can prevent many adverse outcomes. If pulmonary vascular malformations cannot be ruled out, antibiotic prophylaxis is recommended before medical procedures that can cause bacteremia (expert consensus).

Conclusion: Broad awareness of the condition, early diagnosis, and interdisciplinary treatment improve the quality of life and ultimate outcome of persons with HHT. Nevertheless, there are few options supported by good evidence for the appropriate treatment of this rare, often serious disease..

Figure 1

Overview of the principle manifestations of hereditary hemorrhagic telangiectasia (HHT), also summarized in the Curaçao criteria (Box). Each criterion corresponds to one side of the rectangle, the first three sides described below to the term HHT: 1. Bottom, heredity: the disease has autosomal–dominant transmission 2. Top, hemorrhage: recurring spontaneous epistaxis 3. Left, telangiectases: multiple typical telangiectases at the favored sites, shown here on the tongue, lips, face, and hands 4. Right visceral involvement: from top to bottom, cerebral vascular malformations (here: angiogram of a cerebral arteriovenous malformation in the left cerebellum); pulmonary arteriovenous malformations (shown by computed tomography; from the case described in the eCase report); hepatic vascular malformations (computed tomography imaging of multiple dilated hepatic vessels); gastrointestinal telangiectases (endoscopic view)

Figure 2

Sequential approach for the treatment of epistaxis in hereditary hemorrhagic telangiectasia (compiled and modified from the second international guidelines [4]). Treatment options on the same level are to be understood as alternatives.

Figure 1

In the presence of pulmonary arteriovenous malformations (PAVM, see also main text, Figure 1, point 4 b) bacteria traveling via the defect in the pulmonary capillary filter have caused an occipital brain abscess, shown here on cranial magnetic resonance imaging (T1 weighting after administration of contrast medium; by kind permission of Prof. Dr. Ch. Manke, Department of Diagnostic and Interventional Radiology, Fulda Hospitals). This could have happened, for example, during professional tooth cleaning or other interventions, with the bacteria moving from the venous to the arterial branch of the vascular system along the pressure gradient.

Figures 2 and 3

One can take advantage of this shunt for diagnostic purposes by means of contrast-enhanced echocardiography. Figure 2 shows an echocardiogram before administration of contrast medium. After venous injection, contrast medium that does not pass through capillaries is normally found only in the right heart cavities, but in the presence of a shunt it reaches the left side of the heart after around five heartbeats, and Figure 3 shows complete opacification of the left cardiac cavities (by kind permission of Dr. Harald Schütt, Department of Cardiology, Angiology, and Internal Intensive Care Medicine, Giessen and Marburg University Hospital, Marburg Campus).