**1. Introduction**

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominantly inherited disorder that affects the vasculature. The predominant vascular defects range from small telangiectases within nearly all cutaneous and mucocutaneous membranes to larger AV malformations (AVM) within the lungs, liver and brain. Diagnosis of HHT is established either by genetic testing or the fulfillment of at least three of the four Curaçao criteria (recurrent epistaxis, multiple telangiectases at characteristic sites, AVM in visceral lesions, and a family history) [1,2].

About 50–80% of HHT patients form (muco-)cutaneous telangiectases, predominantly on the mucosa of the nose and mouth, tongue, lips, face and fingers [1–3]. Since the dilated vessels are compromised, they are prone to rupture. Recurrent bleedings, especially epistaxis, can lead to severe anemia that can impair patients' daily routine and quality of life [4–6]. An age-dependent penetrance of the disease [7] and highly variable clinical phenotypes are described. The age of onset, the severity and the location of the vascular lesions differ among each patient [8,9].

The mechanisms leading to new AVMs are not completely understood. In animal models for HHT mechanical stress like wounding or fluid shear stress induced new arteriovenous malformations [10,11]. However, to our knowledge, this has never been confirmed in adults with HHT. The aim of this study was to evaluate the influence of mechanical or sun-induced trauma on the number of telangiectases in patients with HHT.

#### **2. Experimental Section**

In 103 consecutive patients who fulfilled at least three out of four Curaçao criteria [1], telangiectases on both hands as well as the upper and lower lip were quantitated. Afterwards, they were surveyed about their dominant hand, level/type of regular manual labor involving strain on the hands (low, medium, high) and exposure to sunlight (low, medium, high). Examples were given to facilitate a graded assessment: medium strain by manual work would be a person from time to time but not daily having a wound on the hand due to mechanical stress from manual work. Medium sun exposure would be a person who frequently would ge<sup>t</sup> tanned but rarely had sunburns. Patients who have had laser therapy of their hands (one patient) or lips (17 patients) in the past were excluded from the analysis.

Description of the study population included number of patients (n), mean ± standard deviation (SD), t test, and 95% confidence intervals (95% CI). A Pearson correlation coefficient was performed to analyze patients' age and number of telangiectases. The Mann–Whitney U test and Kruskal–Wallis test were used for comparisons between patients, while paired tests (Wilcoxon rank sum; sign test) were used for intra-individual comparisons. A 5% significance level was determined. Statistical analyses were performed with IBM Corp. IBM SPSS Statistics for Windows, version 23.0. Armonk, NY, United States.
