Multifactorial pathways contributing to the development and impact of foot problems in systemic sclerosis (scleroderma)

Systemic sclerosis (SSc) is a heterogeneous connective tissue disease characterised by vasculopathy, immune activation and fibrosis [1-3]. The multisystem nature of the disease has a wide-ranging impact on the patient’s overall health on physical, psychological and psychosocial levels [4] [5-7]. While foot problems in patients with SSc have been previously described and that their presence is associated with disability [8-10], the impact of such problems and its major contributors has yet to be determined. The underpinning hypothesis of this thesis was that the development and impact of foot problems on the Quality of Life (QoL) of patients with SSc is multifactorial; involving a complex inter-relationship between disease, functional impairment, personal factors, environmental factors and psychosocial factors. In order to explore this hypothesis, a multiple methodological approach was employed. First, a literature review and a consultation with clinical experts was undertaken to identify the potential candidate factors that may contribute to foot problems. Second, a case-control, cross-sectional study of 121 patients with SSc and 51 healthy participants was undertaken in order to investigate the impact of factors that contribute to foot problems. Finally, the pathway by which the candidate factors that were identified as contributing to foot pathology impacted on the overall quality of life in people with SSc was explored. Using data from the same 121 patients with SSc, structural equation modelling (SEM) was used to explore the inter-relationships between multifactorial pathways associated with foot pathology and its impact on patients with SSc. The results from this thesis can be summarised as follows: i) patients with SSc have significant foot problems; ii) SSc has both a physical and psychological impact; iii) foot problems are affected by complex interrelations between multiple factors; and iv) foot problems are a significant contributor to the impact on the quality of life of patients with SSc.