Pathophysiology and Clinical Consequences of Raynaud's Phenomenon Related to Systemic Sclerosis

According to the so-called vascular hypothesis, Raynaud's phenomenon (RP) is one initial event in the pathophysiological cascade leading to sclerosis in systemic sclerosis (SSc). It is characterized by recurrent, reversible spasms of small arterioles and digital arteries, usually triggered by cold and emotional stress. Clinical signs of RP are a sudden pallor of single digits of fingers followed by reactive hyperaemia and in severe cases also by cyanosis. Besides imbalances between vasoconstrictive and vasodilatory processes, structural alterations of the involved vessels are fundamental to secondary RP in SSc. The latter is the reason why secondary RP in SSc, in contrast to primary RP, often leads to ischaemia and re-perfusion injuries. New insights into the pathophysiology of RP feature a special role for alpha2c-adrenoreceptors, Rho-kinase signalling pathways and soluble mediators. They have resulted in promising therapeutic options, including antagonism of endothelin receptors, inhibition of phosphodiesterases or selective blockade of alpha2c-adrenoreceptors. They should also have a positive impact on the course of SSc in general.