Pharmacotherapy of Raynaud's phenomenon.

Abstract

Primary Raynaud's phenomenon is common, particularly in younger women, and may be familial. Vasospasm is not confined to the digits and may involve, for example, the tongue and nose, and also visceral organs like the heart, oesophagus or lung and cerebral circulation. Symptoms tend to be milder in primary compared with secondary Raynaud's phenomenon, which is associated with other disorders such as the connective tissue diseases. Indeed, the severity of symptoms often acts as the predictor for the much later onset of the associated systemic disease. Occupational Raynaud's phenomenon is related to the use of vibrating instruments, and a significant proportion of patients may be cured by an early change in job. In those over 60 years of age, Raynaud's phenomenon is commonly a result of atherosclerotic obstructive arterial disease, and screening for and treatment of the risk factors is appropriate. The best-studied mechanisms in Raynaud's phenomenon involve the blood and vascular endothelium. Microcirculatory flow may be impeded by activated platelet clumps, rigid red and white blood cells and damaged endothelium. These platelet clumps, white blood cells and damaged endothelium also release vasoactive/vasoconstrictive compounds which may additionally trigger the clotting cascade and thrombosis. Initial management for mild disease should focus on support and advice regarding avoidance of known precipitating factors, including vasospastic drugs. Cold protection with warming agents, 'Abel' shoes and also electrically heated gloves and socks is effective, but may be too cumbersome and inconvenient for some patients. Simple vasodilators like naftidrofuryl, inositol nicotinate and possibly pentoxifylline (oxpentifylline) are useful in mild disease, with adverse effects like headache and flushing being less problematic. The 'gold standard' of Raynaud's phenomenon treatment is nifedipine, a calcium channel antagonist/blocker. Full dosage, however, can be limited by ankle swelling, headache and flushing, but adverse effects may be reduced by using the 'retard' or long-acting preparations. Adverse effects are also reduced with the newer calcium channel antagonists like diltiazem but at the expense of efficacy. Useful, enhanced benefit is also achieved by combination therapy with vasodilators. Newer treatments include the prostaglandin analogues which are effective but disadvantaged by their parenteral route of administration, and lack of licence in some countries. Oral preparations are, however, being studied and are in the pipeline. Essential fatty acid supplementation is mildly effective, while ketanserin and calcitonin gene-related peptide both look promising. Lumbar sympathectomy retains its important role in the treatment of Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic relief is now possible for many patients with Raynaud's phenomenon and this should certainly be the aim for all patients seeking medical help.