Systemic sclerosis: from unravelling the impact of smoking to exploring new views on treatment strategies

Abstract

This thesis explores several different aspects of systemic sclerosis, including the role of sex hormones and insulin, the contribution of smoking to disease manifestations, and the applications of autologous haematopoietic stem cell transplantation. In this thesis we have analysed data from the prospective Leiden systemic sclerosis cohort, from an Italian cohort and also from patients of the multinational EUSTAR registry. The first part of this thesis is focused on hormones, in particular we revised the overall knowledge about sex hormones and we investigated the association between estrogens and development of microangiopathy. Then we analysed insulin sensitivity in systemic sclerosis patients and how it changes according to the different characteristics of the disease. In the second part, the main topic is cigarette smoking. We evaluated the effects of smoking on the risk of developing the disease, on organ progression and on autoantibody expression. We also assessed longitudinally how changes in respiratory parameters affected quality of life of SSc patients. The third part is on treatment strategies. We assessed the efficacy of HSCT in modifying the evolution of lung involvement and in improving microvascular damage. Finally, we described the changes in the prescription of SSc therapies over the last 10 years.