Introduction

Essentials of Diagnosis

• Episodic bilateral digital pallor, cyanosis, and rubor.
• Precipitated by cold or emotional stress; relieved by warmth.
• Seventy to 80 percent of patients are women.

General Considerations
Raynaud’s syndrome is an episodic vasospastic disorder characterized by digital color change (white-blue-red) with exposure to cold environment or emotional stress. If idiopathic, it is called Raynaud’s disease. If associated with a possible precipitating systemic or regional disorder (autoimmune diseases, myeloproliferative disorders, multiple myeloma, cryoglobulinemia, myxedema, macroglobulinemia, or arterial occlusive disease), it is called Raynaud’s phenomenon.

The incidence of disease is estimated to be as high as 10% in the general population. Other vasospastic disorders, such as variant angina and migraine headache, are common in patients with Raynaud’s syndrome. An abnormality of the sympathetic nervous system has long been implicated in the etiology of Raynaud’s disease; recently, research has focused on the theory of up-regulation of vascular smooth muscle a2-adrenergic receptors.

Clinical Findings
Classically, Raynaud’s disease and Raynaud’s phenomenon are characterized by intermittent attacks of pallor of the hands or fingers brought on by cold or emotional stress, progressing to cyanosis and then rubor on rewarming. Mild discomfort, paresthesias, numbness, and trace edema often accompany the color changes. In Raynaud’s disease, the disease is symmetric, by rule; in Raynaud’s phenomenon, the changes may be most noticeable in one hand or even in one or two fingers only. Infrequently, the feet and toes are involved. Between attacks, the affected extremities may be entirely normal.

The distinction between Raynaud’s disease and Raynaud’s phenomenon is meant to reflect a difference in prognosis. Whereas Raynaud’s disease is benign and often controllable, Raynaud’s phenomenon may progress to atrophy of the terminal fat pads and development of fingertip gangrene. However, because many inciting diseases may not be clinically suspected at the time the diagnosis of Raynaud’s disease is made, there is a large degree of crossover between groups. The diagnosis is based on clinical criteria. Raynaud’s disease appears first between ages 15 and 45, almost always in women. A patient with suggestive symptoms that persist for over 3 years without evidence of an associated disease is given the diagnosis of Raynaud’s disease.

Differential Diagnosis
A patient with Raynaud’s syndrome must be evaluated for possible inciting systemic disorders. Directed history and physical examination and serologic testing may be helpful in excluding the collagen-vascular disorders, which include scleroderma, systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis. It is estimated that 80% of patients with scleroderma ultimately develop Raynaud’s phenomenon. Likewise, cryoglobulinemia can be excluded by appropriate testing. Raynaud’s phenomenon is also occasionally seen in patients with neurogenic thoracic outlet syndrome or carpal tunnel syndrome. Frostbite, ergotamine toxicity, and use of chemotherapeutic agents, which can also be associated with Raynaud’s phenomenon, can usually be excluded by a careful history; up to one-third of patients receiving combined bleomycin and vincristine (such as for testicular cancer) develop symptomatic vasospastic disease. An abnormal or asymmetric pulse examination, differential blood pressure cuff measurements, gangrene, or a positive Allen test are suggestive of arterial occlusive disease and should prompt upper extremity angiography to exclude stenosis or occlusion from atherosclerosis, Buerger’s disease, arterial thoracic outlet syndrome, embolic disease, or repetitive motion injury of the small vessels of the hand. Even undiseased upper extremity vessels often show intense vasospasm with contrast injection, so the arm is wrapped for warmth and prophylactic use of a vasodilator (papaverine or nitroglycerin, 30 mg, injected through the angiography catheter) is advised; both arms are imaged for side-by-side comparison.

Other vasospastic disorders that should be included in the differential but are usually easily distinguishable by physical examination are acrocyanosis and livedo reticularis.

Treatment

A. General Measures
Warmth and protection of the hands are the basic tenets of therapy. In Raynaud’s phenomenon, wounds heal slowly, and infections are consequently hard to control. Gloves should be worn in cold environments and during activities that may cause trauma to the skin, such as dishwashing, gardening, woodworking, or office filing. Moisturizing lotion should be applied frequently to avoid fissured dry skin. Smoking cessation is imperative, as nicotine is a known vasoconstrictor. Stress management should be addressed when appropriate. Oral contraceptives, ß-blockers, and ergotamines are associated with exacerbation of symptoms and ideally should be discontinued. Aspirin is prescribed to decrease the risk of thrombotic complications.

B. Vasodilators
Vasodilator drugs may be of some benefit in patients whose symptoms are not adequately controlled with simpler measures. Low-dose nifedipine (sustained release, 30 mg/d) or diltiazem (sustained release, 30 mg/d) has superseded topical or oral nitroglycerin for treatment of vasospasm. Use of prostaglandins has been disappointing, but the serotonin reuptake inhibitor and antidepressant fluoxetine (20 mg daily) shows some promise in reduction of the frequency and severity of attacks.

C. Surgery
Sympathectomy is indicated for pure vasospastic disease refractory to medical management. In the lower extremity, sympathectomy may produce complete and permanent relief of symptoms; however, for unclear reasons, the beneficial effects are often transient in the upper extremity. Limited improvement is seen in advanced ischemia, particularly if significant digital artery obstructive disease is present.

Prognosis
Raynaud’s disease is usually benign, causing mild discomfort on exposure to cold and progressing very slightly over the years. The prognosis of Raynaud’s phenomenon is that of the associated disease.

Coleiro B et al: Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001;40:1038.

Fraenkel L: Raynaud’s phenomenon: epidemiology and risk factors. Curr Rheumatol Rep 2002;4:123.

Herrick AL: Treatment of Raynaud’s phenomenon: new insights and developments. Curr Rheumatol Rep 2003;5:168.