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The onset of Raynaud's phenomenon at 40 years could predict whether a connective tissue disease will develop.
Researchers writing in the Oct. 5 issue of the New England Journal of Medicine say that successfully managing a case of Raynaud’s phenomenon depends on an accurate diagnosis to stave off potential serious complications and the deterioration of quality of life.
Raynaud’s consists of either a primary manifestation without concurrent disease or a condition secondary to an associated disease. The phenomenon is characterized by blanching discoloration and pain in the distal portions of the fingers and toes and affects up to 5% of the general population.
Primary Raynaud’s Phenomenon
Diagnosis of Raynaud’s phenomenon is clinical and requires the observation of two skin color changes: (white [pallor] and blue [cyanosis]) in the digits. Patients with the primary condition usually experience thumb sparing and see an onset in younger life (15-30 years) without the presence of peripheral vascular disease, digital ischemic injury or abnormal nailfold capillaries. As many as half of primary Raynaud’s patients have a close relative with the disorder suggesting a genetic component.
A normal erythrocyte sedimentation rate is no longer needed to distinguish primary Raynaud’s from the secondary forms. An international panel of experts have recommended that a negative or low-titer antinuclear antibody may also be present (≤1:40 by indirect immunofluorescence).
Secondary Raynaud’s Phenomenon
Although it is possible to have isolated primary Raynaud’s, significant portions of patients have an underlying connective tissue disorder such as systemic sclerosis (scleroderma). One study showed that 37.2 percent of 3,029 people with the primary form of the disease subsequently had a connective tissue disease. The American College of Rheumatology and the European League against Rheumatism included Raynaud’s phenomenon in the 2013 classification criteria for scleroderma.
Severity and rapid progression can predict future development of connective tissue disorders. “Recent studies have emphasized that factors such as the onset of Raynaud’s phenomenon near the age of 40 years, severe frequent events, and the presence of abnormal nail fold capillaries can help predict whether a connective tissue disease will develop and are especially helpful in identifying early scleroderma,” the authors wrote.
The pathogenesis of Raynaud’s phenomenon involves the delicate interplay between sympathetic nervous system mediated vasoconstriction of arterio-venous connections in the fingers, toes and sometimes the nose. These tissues are different than others in how they react to cold and warm conditions. Normally vasoconstriction can occur while sparing capillary nutrient flow to the skin. In Raynaud’s patients the vital nutrients are kept from reaching the skin by severe constriction in vascular beds usually spared leading to the pain and discoloration observed. Those with secondary Raynaud’s experience even more severe disruptions of blood flow due to dysfunction in the walls of the vessels as well. Vessel wall, or endothelial dysfunction keeps the normal mechanisms in place for vasodilation from working. Failure of this safety mechanism to restore adequate blood flow leads to tissue damage in patients with scleroderma and secondary Raynaud’s.
Treatment for Raynaud’s phenomenon consists of avoidance of triggers and drug therapy. Avoiding cold is very effective as is keeping warm in the cold by maintaining good core temperature as well as protecting the hands and feet with insulated gloves and socks. Active warming with warm water or radiant devices can promote recovery if an attack happens. Patients should avoid vasoconstrictors such as smoking, hyperactivity and migraine drugs. Stress and anxiety prevention are also important.
If trigger avoidance fails to bring adequate reductions in symptoms drug therapy is indicated. Although evidence is lacking there is some consensus on management strategies such as the algorithm below:
First line therapy for mild to moderate events:
Second line for severe events or digital ischemic lesions:
Third line for recurrent severe events or repeated digital ischemic lesions:
Fourth line for severe digital ischemic threatening gangrene or amputation:
While calcium-channel blockers are moderately effective for secondary Raynaud’s studies suggest that they are minimally effective for primary Raynaud’s patients. Digital sympathectomy is a last resort and is accomplished surgically.
Patients suffering from secondary Raynaud’s should be treated with vasodilators cautiously. Lowering systemic blood pressure may further decrease nutritional perfusion leading to tissue damage and necrosis. Preventing vasoconstriction is just as important in these patients. Endothelin-1 receptor antagonists do not reduce the frequency of Raynaud’s attacks but they do decrease the development of new digital ulcers in those with scleroderma. It is very important to treat the underlying disease in the case of secondary Raynaud’s.
While there are many hopeful treatments for Raynaud’s phenomenon, none have been rigorously shown to prevent the symptoms and effects of this challenging disease. The most effective strategy remains avoidance of cold and reductions in stressors that precipitate flare ups.
Start endothelin-1 inhibitor (bosentan) for scleroderma with recurrent digital ulcers.Start endothelin-1 inhibitor (bosentan) for scleroderma with recurrent digital ulcers.
Fredrick M. Wigley, M.D., and Nicholas A. Flavahan, Ph.D.
N Engl J Med 2016; 375:556-565August 11, 2016DOI: 10.1056/NEJMra1507638