Hereditary Hemorrhagic Telangiectasia and Arterio-Venous Malformations—From Diagnosis to Therapeutic Challenges

Abstract

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant vascular disease defined by the presence of mucosal and cutaneous telangiectasia and visceral arterio-venous malformations. The latter are abnormal capillary-free direct communications between the pulmonary and systemic circulations with the following consequences: arterial hypoxemia caused by right-to-left shunts; paradoxical embolism with transient ischemic attack or stroke and brain abscess caused by the absence of the normally filtering capillary bed; and hemoptysis or hemothorax due to the rupture of the thin-walled arterio-venous malformations (particularly during pregnancy). It is frequently underdiagnosed, commonly presenting as complications from shunting through arterio-venous malformations: dyspnea, chronic bleeding, or embolism. Arterio-venous malformations are present not only in the lungs, but can also be found in the liver, central nervous system (mainly in the brain), nasal mucosa, or the gastrointestinal tract. The first choice of therapy is embolization of the afferent arteries of the arterio-venous malformations, a minimally invasive procedure with a high efficacy, a low morbidity, and low mortality. Other therapeutic modalities are surgery (resection) or stereotactic radiosurgery (using radiation). Routine screening for arterio-venous malformations is indicated in patients diagnosed with this condition and can prevent severe complications such as acute hemorrhages, brain abscesses, or strokes. Clinicians should provide a long-term follow-up for patients with arterio-venous malformations, in an effort to detect their growth or reperfusion in case of previously treated malformations. In spite of two experts’ consensuses, it still possesses multiple therapeutic challenges for physicians, as several aspects regarding the screening and management of arterio-venous malformations still remain controversial. Multidisciplinary teams are especially useful in complex cases.

A Rare Association: Hereditary Hemorrhagic Telangiectasia with Liver Cirrhosis Causing Portal Hypertension

“…In cases of arterioportal fistulas, the primary clinical manifestation is the late development of portal hypertension, which becomes evident in the sixth or seventh decade of life, accompanied by ascites and variceal upper gastrointestinal bleeding [ 6 ]. In HHT, the liver can exhibit partial or diffuse regenerative activity, leading to nodular regenerative hyperplasia [ 6 , 7 ]. The combination of fibrosis, nodular regenerative hyperplasia, and portal hypertension makes the diagnosis of cirrhosis challenging [ 7 ].…”

Hereditary Hemorrhagic Telangiectasia Associating Neuropsychiatric Manifestations with a Significant Impact on Disease Management—Case Report and Literature Review

“…Mental illness associated with hereditary hemorrhagic telangiectasia is not frequently reported in the literature, but patients often present with a significant impact on their health-related quality of life [ 1 , 6 , 7 , 40 , 41 ]. There are many possible reasons for a high prevalence of depression (88.7%), post-traumatic stress disorder (28.1%), and anxiety (43.9%) in individuals living with HHT [ 40 , 41 , 42 ].…”

“…Generally, the mortality of HHT is generated by complications of AVMs, particularly in the brain, lungs, and gastrointestinal area. In our case, each bleeding episode and even the chronic anemia associated with recurrent hemorrhaging added to the anxiety and fear of hospital care [ 6 , 7 , 40 , 41 , 42 ].…”

“…A positive diagnosis of HHT is almost always clinical, based on the Curaçao diagnostic criteria established in 1999 [ 3 , 7 , 8 ], requiring at least three out of these four criteria to be met: spontaneous recurrent epistaxis, multiple telangiectasias, visceral involvement, and a relevant family history. If only two characteristics are present, the diagnosis is probable, and further tests or follow-up are necessary.…”

“…Concerning the alarming manifestations and scarce therapy options, and in relation to intrinsic pathophysiology, these patients may develop mental illnesses like anxiety, post-traumatic stress disorder, and depression [ 8 , 9 ]. Moreover, the presence of cerebral AVMs—although less frequent, identified in 10–20% of HHT cases [ 8 , 10 , 11 ]—could induce psychiatric manifestations depending on their localization, although these are very rarely mentioned in the available publications [ 6 , 7 , 11 ].…”