title: Pathogenesis of Raynaud's phenomenon.
abstract: The pathogenesis of Raynaud's phenomenon is not fully understood. However, the last 20 yr have witnessed enormous increases in our understanding of different mechanisms which, singly or in combination, may contribute. A key point is that Raynaud's phenomenon can be either primary (idiopathic) or secondary to a number of underlying conditions, and that the pathogenesis and pathophysiology vary between these conditions. This review concentrates upon those subtypes of Raynaud's phenomenon of most interest to rheumatologists: systemic sclerosis-related Raynaud's phenomenon, primary Raynaud's phenomenon and Raynaud's phenomenon secondary to hand-arm vibration syndrome. In this review, I shall discuss the main mechanisms thought to be important in pathophysiology under the three broad headings of 'vascular', 'neural' and 'intravascular'. While these are false distinctions because all interrelate, they facilitate discussion of the key elements: the blood vessel wall (particularly the endothelium), the neural control of vascular tone, and the many circulating factors which can impair blood flow and/or cause endothelial injury. Vascular abnormalities include those of both structure and function. Neural abnormalities include deficiency of the vasodilator calcitonin gene-related peptide (released from sensory afferents), alpha(2)-adrenoreceptor activation (possibly with up-regulation of the normally 'silent' alpha(2C)-adrenoreceptor) and a central nervous system component. Intravascular abnormalities include platelet activation, impaired fibrinolysis, increased viscosity and probably oxidant stress. As our understanding of the pathophysiology of Raynaud's phenomenon increases, so do our possibilities for identifying effective treatments.
authors.affiliation: University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK. aherrick@fs1.ho.man.ac.uk
authors.forename: A L
authors.initials: AL
authors.lastname: Herrick
mesh_terms: D006225:Hand / Q000098:blood supply; D006402:Hematologic Diseases / Q000150:complications; D006801:Humans; D008833:Microcirculation; D010523:Peripheral Nervous System Diseases / Q000150:complications; D011928:Raynaud Disease / Q000209:etiology* / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000150:complications; D014661:Vasoconstriction; D014732:Vibration / Q000009:adverse effects