[Target organ connective tissue: the variability of systemic fibrosis].

Abstract

The group of systemic fibrosing connective tissue diseases is remarkably diverse, comprising a wide spectrum of distinct entities. Central to their pathogenesis is the fibroblast, which, when activated by exogenous or endogenous triggers, can pathologically overproduce components of the extracellular matrix or exhibit uncontrolled proliferation. Systemic sclerosis, recognized as the prototype of systemic fibrosing diseases, belongs to the connective tissue diseases. Despite considerable advancements in the understanding of its pathogenesis, diagnosis, and treatment over recent years, systemic sclerosis remains one of the most fatal conditions among inflammatory rheumatic diseases. Its hallmark features include vasculopathy, systemic fibrosis, and autoimmunity, with common organ involvement affecting the skin, lungs, heart, gastrointestinal tract, kidneys, and musculoskeletal system. Therapeutic strategies focus on improving perfusion, controlling inflammation, and implementing antifibrotic measures. Key differential diagnoses include eosinophilic fasciitis, mixed connective tissue disease, and other overlap syndromes, which often require immunomodulatory treatment. Innovative developments in the field suggest a potential paradigm shift in the treatment of inflammatory rheumatic diseases, with cell-based therapies like CD19-depleting chimeric antigen receptor (CAR) T cell therapy showing promising early outcomes. Other systemic fibrosing diseases include scleromyxedema and scleroedema adultorum Buschke, both of which belong to the mucinoses and contribute further to the complexity of this disease group.