Everything you always wanted to know about systemic sclerosis but were afraid to ask: Part 2. Intermediate pathophenotypes the best pathogenetic background in systemic sclerosis

Abstract

Systemic sclerosis (SSc, scleroderma) is a chronic systemic connective tissue disease with a complex pathogenesis that is still not fully understood, in the course of which attention is increasingly drawn to the dynamic, sequential pathogenetic mechanisms according to disease stage. An increasing understanding of the diversity of mechanisms underlying this disease, as well as the prevalence of certain pathogenetic elements that depend i.a. on disease stage, will enable more effective therapeutic interventions in the future. Systemic sclerosis can thus be seen as a complex process, where the main players are immune cells, endothelial cells and fibroblasts, and the focal point is probably impaired function and subsequent damage to endothelial cells. Systemic sclerosis is also the final stage of a certain continuum of events, starting with a state of susceptibility to the development of the disease (dependent on genetic conditions and environmental influences), followed by disruption of homeostasis and initiation of pathological processes (e.g. as a result of viral infections), progression of pathological responses (inflammation, endothelial damage, fibrosis) and consequently organ damage. According to most authors, the key event and focal point of the cascade of phenomena is endothelial cell damage, and the mechanisms that lead to this damage are related to the activation of the immune system. There is growing acceptance of the thesis of an autoimmune origin of the disease involving mechanisms of innate and acquired immunity, both cellular and humoral.