Early systemic sclerosis (SSc) is a newly identified condition characterized by the association of Raynaud's phenomenon (RP) with SSc marker autoantibodies and/or with a scleroderma pattern at nailfold videocapillaroscopy (NVC), without clinical manifestations of definite SSc. Patients with early SSc do not meet the old 1980 American College of Rheumatology (ACR) nor the new 2013ACR/European League Against Rheumatism (EULAR) classification criteria for the disease. Nevertheless, they show a scleroderma-type preclinical involvement of internal organs at second level examinations in up to 42% of cases and increased serum levels of markers of endothelial, T-cell, and fibroblast activation. A number of these circulating markers, like sICAM-1, CCL2, CXCL8, and IL-13 increase their serum levels in parallel with the onset and the extent of skin sclerosis. They have been found to be elevated in patients with early SSc, but reach the highest levels in definite SSc patients with a diffuse skin disease. Other circulating markers display a peculiar behavior, being associated with distinct early SSc subsets. In fact, the carboxyterminal telopeptide of type I collagen (ICTP) has been found to be higher in early SSc patients with marker autoantibodies and impaired DLCO, while sE-selectin has been found to be higher in early SSc patients with an NVC scleroderma pattern and puffy fingers. More interestingly, IL-33, an inflammatory cytokine belonging to the IL-1β superfamily enriched in epithelial and endothelial cells, has been found to be higher in patient with early SSc than in patients with a definite, classifiable disease. Taken together, these data suggest that the cellular pathways that are implicated in the complex vascular/immune pathogenesis of SSc are active in patients with an early pre-fibrotic stage of the disease, when an increased collagen synthesis can also be suspected. In addition, they suggest that serum levels of some adhesion molecules, chemokines and cytokines may be helpful to follow the evolution of early SSc into definite SSc, while IL-33 may be investigated in large patient series as a potential biomarker of the early subset.
Disclosure of Interest None declared
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