Most common among women younger than 30 years, Raynaud's disease is an idiopathic, vasospastic disorder that affects an estimated 10% of the US adult population. Many patients with the condition also suffer from migraine headaches and chronic stress.1 This clinical review differentiates primary Raynaud's (or Raynaud's disease) from secondary Raynaud's (or Raynaud's phenomenon), highlights key clinical features that distinguish Raynaud's disease from other peripheral vascular diseases, and presents some emerging treatment options.
Although there is no mortality associated with it, Raynaud's disease is uncomfortable and can be embarrassing for many patients. Moreover, the possibility that the signs and symptoms represent a more serious underlying condition (such as lupus erythematosus or scleroderma) is cause for concern. Therefore, clinicians must distinguish carefully between primary and secondary Raynaud's and be prepared to offer both reassurance and current treatment options when the condition truly proves to be primary and idiopathic.
Primary versus secondary Raynaud's
Patients with primary Raynaud's present with the well-known, classic signs of “red, white, and blue” fingers or toes, indicative of reactive hyperemia followed by pallor and cyanosis. This triphasic color response occurs in up to 65% of patients,2 many of whom also experience pain and/or paresthesia in the affected digits. Attacks of primary Raynaud's are set off abruptly and predictably by exposure to cold environments, including air-conditioned spaces, and by emotion
al stress3 (see Figure 1). Bilateral involvement usually occurs in the fingers; but the toes, nose, ears, lips, and nipples may also be affected. Primary Raynaud's is considered benign; however, 10% to 15% of patients actually have early connective tissue disease, or secondary Raynaud's.4 Table 1 lists some factors that are key to distinguishing between primary and secondary Raynaud's.
Secondary Raynaud's, which produces similar vasospastic signs and symptoms, results from trauma, toxicity, or an underlying vascular or connective tissue disorder (see Table 2).1 The signs that an underlying disease is the cause include skin changes, nail pitting, ulcers on the fingertips, or an abnormal result on the Allen test. The diagnoses that should be considered include connective tissue disease, arterial occlusive disease, drug or heavy metal toxicity, hematologic abnormalities, neurologic disorders, renal failure, and neoplasm.
Secondary Raynaud's is one of the five components of the CREST (calcinosis, Raynaud's, esophageal dysfunction, sclerodactyly, telangiectasia) syndrome, which is associated with scleroderma. But a more common cause of secondary Raynaud's is repeated trauma, especially among people who work with vibratory tools such as pneumatic hammers, chain saws, sanders, or grinders. It also has been seen in typists, pianists, meat cutters, and sewing machine operators.
Patients who are not experiencing an acute attack of Raynaud's will have normal findings on physical examination. Although trauma may be detected through the patient history, a differential diagnosis of systemic illness requires a thorough serologic evaluation—including, but not limited to, urinalysis, CBC, ESR, C-reactive protein, complement, cryoglobulins, and autoantibodies (antinuclear antibodies [ANA], anti-DNA, SCL-70 [scleroderma], and anticentromere antibodies).5
Other mimicking conditions
In addition to scleroderma and other connective tissue diseases, three other syndromes that should be ruled out when evaluating a patient with cold hands are peripheral arterial disease (PAD), chronic idiopathic acrocyanosis (CIA), and thromboangiitis obliterans (Buerger's disease). Signs and symptoms of each of these conditions can mimic those of Raynaud's. 
PAD, a vaso-occlusive disorder that results from atherosclerosis, is a strong possibility in diabetic patients and in patients older than 40 years who smoke. Hyperlipidemia, hypertension, and hyperhomocysteinemia are other risk factors for PAD. The prompt and accurate diagnosis of PAD is critical, as patients with PAD have almost the same relative risk for death as patients with coronary or cerebrovascular disease.6
CIA is an uncommon condition characterized by symmetric coolness and violet discoloration of the hands and feet. As with secondary Raynaud's, the toes, nose, ears, lips, and nipples may be affected; the condition generally worsens with cold temperatures; and it may be secondary to a variety of underlying conditions (see Table 3). Unlike Raynaud's, CIA persists in both warm and cool environments, even though the lesions may change in appearance during the course of the day. CIA does not produce sclerodactyly, digital ulceration, or oral telangiectasias, all of which may occur in secondary Raynaud's.6,7
Buerger's disease is both an inflammatory and a thrombotic process of the peripheral vessels. The cause is unknown, but 80% of patients with Buerger's disease are men, usually younger than 40 years, who smoke. A classic symptom is digital pain at rest caused by intermittent claudication, which can lead to tissue necrosis. By definition, Buerger's disease affects more than one limb, in which proximal pulses are intact but distal pulses are diminished. Patients have pale, cyanotic, or erythematous digits, resembling those of patients with primary Raynaud's. In fact, patients with Buerger's disease often have a history of primary Raynaud's or cold sensitivity.1
