Living with hereditary hemorrhagic telangiectasia: optimizing diagnostics, treatment, and capturing patient impact

The aim of this thesis was to contribute to improving diagnostic strategies, evaluating novel treatment approaches and exploring the broader impact of the disease of patients’ lives. In part I, the use of TTCE in PAVM-screening and follow-up was assessed. Reported key insights include prolonging the rescreening interval is safe in patients with initial negative screening, in children a conservative screening method is sufficient to prevent complications and chest CT can be withheld in patients with only a minimal shunt after PAVM embolization. In the future, these insights contribute to a more tailored approach with a decrease in the number of required diagnostics (TTCE and chest CT). For the treatment of HHT-related bleeding, there is a shift towards systemic treatments, of which two agents are described in part II of this thesis. Preliminary results of tacrolimus are positive; a randomized clinical trial is needed for further evaluation. The safety of engasertib is very promising in the phase 1b RCT and the efficacy will be further studied in the coming years. Lastly, part III describes the attempt to capture the impact of HHT on family planning and sexual activity with an unneglectable amount experiencing impact on sexual activity, emphasizing the need for improvement awareness and epistaxis management. Concluding, this thesis has examined three key aspects of the path towards cultivating tailored HHT-care and contributed to improved PAVM-screening strategies, the development of novel systemic treatment options and more knowledge about the impact of the disease with the ultimate goal of improving living with HHT.