EDN1 and systemic sclerosis: The pathogenesis of pruritus in SSc is still not completely understood and is not specifically associated with a particular immunological profile.[15] Various pruritogens, including histamine, lysophosphatidic acid, prostaglandin E2, endothelin-1, and neuropeptides from unmyelinated nerve endings, have all been linked to pruritus in SSc.[16] Furthermore, opioid receptors have been implicated in the pathogenesis of itch.