Pathogenesis and treatment of Raynaud's phenomenon

Abstract

The pathogenetic theories and treatment of Raynaud's phenomenon are reviewed. In primary Raynaud's disease, most evidence supports a local defect at the digital artery level, with vasoconstriction or vasospasm of the digital arteries inducing the color changes. Normal sympathetic activity, low transmural arterial distending forces, and serotonin may be associated factors in the production of vasospastic attacks. In Raynaud's phenomenon, persistent vasoconstriction, thickened vessel walls, increased blood viscosity, and low digital artery blood pressure distal to obstructions may lead to vasospastic attacks with normal sympathetic nerve stimuli. Since the underlying cause of primary Raynaud's disease is unknown, treatment involves the use of agents to reduce sympathetic nerve activity or to prevent vascular smooth muscle contraction. Most patients will respond to conservative measures, but if they fail nifedipine is the drug of choice and alleviates the syndrome in about two thirds of patients. Reserpine and guanethidine may be as effective, but well-controlled studies have not been performed. The beneficial response to prazosin is moderate and dissipates with time. Side effects with these drugs prevent their use in many patients. Diltiazem and nitroglycerin ointments are of questionable value. Ketanserin, a serotonergic S2-receptor antagonist, which has been shown to decrease the frequency of vasospastic attacks, and parenteral prostacyclin are among the new promising therapies.

Partial agonist activity of α1-adrenergic receptor antagonists for chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3

“…α 1 -Adrenergic receptor (AR) antagonists are widely used as antihypertensive drugs, for the treatment of benign prostate hyperplasia, and off-label for the treatment of Raynaud’s syndrome[ 1 – 3 ]. Moreover, the α 1 -AR antagonist prazosin has recently been evaluated in clinical trials in patients with post-traumatic stress disorders and nightmares[ 4 ].…”

Guillain-Barré syndrome presenting with Raynaud's phenomenon: a case report

“…Two subtypes are described, primary Raynaud’s which is not associated with any other illness and secondary Raynaud’s phenomenon, where vasospasms are associated with another disease, commonly autoimmune diseases, mixed connective tissue disease and scleroderma. Pathogenesis of primary Raynaud’s phenomenon is not fully understood but vascular, intravascular and neural mechanisms are proposed [ 6 ],[ 11 ]. Of the neural mechanisms, central impairment of the autonomic function resulting in Raynaud’s phenomenon is suggested by the research done by Koszewicz et al [ 12 ].…”

“…Mallipeddi et al concluded that primary Raynaud’s phenomenon is associated with sympathetic denervation in chronic autonomic failure [ 10 ]. Sympathetic over-activity provoking vasospasm by exaggerated vascular response is also suggested as one of the mechanisms causing Raynaud’s phenomenon [ 11 ],[ 13 ]. Hyperactivity of the α2c adrenorecepters is also postulated as one of the mechanisms [ 6 ].…”

Raynaud’s phenomenon and related vasospastic disorders

“…• There is predominance of α 2 -adrenoceptors in digital arteries and dermal arterioles 119,120 • Patients with RP are hypersensitive to the vasoconstrictor effects of α 2 -adrenoceptor agonist clonidine, but not to α 1 -adrenoceptor agonist phenylephrine 18,121,122 • α 2 -adrenoceptor antagonist yohimbine increases finger blood flow and decreases vascular resistance during reflex sympathetic vasoconstriction caused by body cooling 123 Beta-adrenergic blockade…”