The Raynaud phenomenon, as mentioned earlier, is one of the earliest and most frequent manifestations of SSc affecting up to 95% of patients [107] It results from the altered vascular tone secondary to the imbalance between vasodilator mediators: Nitric oxide, prostaglandin I2 (PGI2), and vasoconstrictor endothelin 1. This evidence concerns the gene EDN1 and systemic sclerosis.