Hereditary hemorrhagic telangiectasia (HHT: OMIM 187300 and 600376) is an autosomal dominant vascular dysplasia that affects 1 in 5-8000. The diagnosis is clinical and based on the presence of at least three of the “Curaçao criteria”: spontaneous and recurrent epistaxis, multiple telangiectases, visceral lesions (AVMs) in lungs, liver, brain; and finally a family history. Heterozygous mutations of activine receptor-like kinase-1 (ACVRL1) gene and endoglin (ENG) gene cause HHT2 and HHT1 respectively. Recurrent severe epistaxis is the most common presentation in HHT patients (95%), frequently leading to severe anemia requiring blood transfusions. Since angiogenesis has been implicated in the pathogenesis of HHT and since thalidomide has been shown to be a potent angiogenic inhibitor in experimental models, we tried to evaluate the effectiveness of thalidomide in reducing epistaxis and in the blood transfusions requirement. By assessing parameters such as: grading of epistaxis according to the severity score by Pagella et al (Acta Otolaryngol. 2013; 133(2):174-80), transfusion requirement and hemoglobin in the blood, we report results obtained on a group of 29 HHT patients treated with thalidomide for five months. We observed differences in the response to the use of thalidomide between HHT2 and HHT1 patients; in particular the first ones showed a reduction of transfusion requirement of 45,14% compared to HHT1 patients (5,77%). These data indicate a better response in patients with mutations in ACVRL1 and then you can think of to target treatment to patients preferentially HHT2. According to data in literature, thalidomide is metabolized in small part by CYP2C19, and since it is known that specific polymorphisms in these enzymes may modulate the activity of the drug, we set out to evaluate their presence in treated patients and how they can possibly modulate the answer and the side-effects of thalidomide. The results showed that the effects in patients (5) heterozygous for the polymorphism (*1/*2) have a lower reduction of epistaxis (37%) compared to wild type (46.49%).
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