Raynaud phenomenon is subdivided into primary (idiopathic) and secondary forms based on whether an underlying cause or disease association can be identified.
Primary Raynaud Phenomenon
Primary Raynaud phenomenon is a disorder in which known causes of attacks of peripheral vasospasm cannot be found. Criteria for the diagnosis of primary Raynaud phenomenon have been developed by Allen and Brown19 and LeRoy and Medsger20 (Table 170-1).
Table 170-1 Criteria for Primary Raynaud Phenomenon ||Download (.pdf)
Table 170-1 Criteria for Primary Raynaud Phenomenon
- Vasospastic attacks precipitated by exposure to cold or emotional stimuli
- Bilateral involvement of extremities
- Normal vascular examination with symmetric peripheral pulses and normal nail fold capillary microscopy
- Absence of gangrene or, if present, limited to the skin of the fingertips
- No evidence of an underlying disease, drug, or occupational exposure that could be responsible for vasospastic attacks
- Negative antinuclear antibody test
- Normal erythrocyte sedimentation rate
- History of symptoms for at least 2 year
Several studies have examined the long-term outcome of patients with primary Raynaud phenomenon.3,21,22 Progression to a secondary form of Raynaud phenomenon, most commonly a connective tissue disease such as scleroderma, occurs in approximately 15% of patients during the first decade after onset. Variables predictive of a transition to a secondary form include nail fold capillary abnormalities, hand swelling, positive Allen's test, and antinuclear antibodies.
Secondary Raynaud Phenomenon
Connective Tissue Diseases
The connective tissue diseases are the most common cause of secondary Raynaud phenomenon (Table 170-2). Among patients with scleroderma, 80%–90% manifest Raynaud phenomenon and/or persistent vasospasm. It is the presenting symptom in about one-third of patients and may be the only manifestation of the disease for years. Raynaud phenomenon occurs in about one-third of patients with systemic lupus erythematosus, idiopathic inflammatory myopathies, and systemic vasculitis. Although patients with rheumatoid arthritis often complain of cold hands with mottled red and white areas, true Raynaud phenomenon appears to be no more common in persons with rheumatoid arthritis than in the general population. Arteriograms of patients with connective tissue diseases usually show digital and sometimes, ulnar or radial artery obstructions.
Table 170-2 Secondary Raynaud Phenomenon ||Download (.pdf)
Table 170-2 Secondary Raynaud Phenomenon
- Connective tissue disease
- Systemic lupus erythematosus
- Dermatomyositis and polymyositis
- Undifferentiated connective tissue disease
- Systemic vasculitis
- Sjögren syndrome
- Eosinophilic fasciitis
- Obstructive arterial disease
- Thromboangiitis obliterans (Buerger disease)
- Thoracic outlet syndrome
- Neurologic disorders
- Carpal tunnel syndrome
- Reflex sympathetic dystrophy
- Multiple sclerosis
- Drugs and toxins
- Occupation/environmental exposure
- Vibration injury (lumberjacks, pneumatic hammer operators)
- Posttraumatic injury (hypothenar hammer syndrome, crutch pressure)
- Vinyl chloride disease
- Cold injury
- Hyperviscosity disorders
- Cold agglutinins
- Infections (bacterial endocarditis, Lyme disease, viral hepatitis)
- Primary pulmonary hypertension
- Arteriovenous fistula
- Intra-arterial injections
Raynaud phenomenon may be occupational in origin. It is especially common in individuals who use vibratory tools (e.g., air hammers, chain saws, rivet guns) and in those whose occupation requires prolonged exposure of the extremities to cold temperatures (e.g., butchers, ice cream workers, fish packers). Prevalence rates correlate with the vibration level of the tool and the duration of exposure; they can be as high as 90% in high-risk occupations such as logging or mining.23
Any neurologic condition that produces permanent disuse of a limb can be associated with sympathetic nervous system disturbances to that limb. Patients often develop persistent vasospasm with coldness, paleness or cyanosis, and even ulcerations of the limb, and Raynaud phenomenon may occur. Thermoregulatory abnormalities may be a prominent feature of reflex sympathetic dystrophy syndrome.24 Nerve root pressure or nerve entrapment may produce Raynaud phenomenon. It is often present in patients with carpal tunnel syndrome and typically involves the first, index, and middle fingers, digits innervated by the median nerve. In addition, Raynaud phenomenon may occur as a result of neurovascular compression at the thoracic outlet. The compression may be caused by cervical ribs; abnormalities of the scalenus anticus muscle; bony abnormalities of the cervical vertebrae, clavicle, or first rib; or shoulder compression syndromes (the costoclavicular or hyperabduction syndrome).
Propranolol, one of the most widely used β-adrenergic blockers for cardiovascular diseases and migraine headaches, is probably the most frequently used drug responsible for Raynaud phenomenon. Ergot preparations and methysergide used to treat migraine headaches may produce vasospasm. Intra-arterial use of many medications and recreational drugs can result in toxicity to endothelial cells with irreversible structural damage to the microvasculature of the extremities and be responsible for severe Raynaud phenomenon. The chemotherapeutic agents, bleomycin and vinblastine, also may cause the phenomenon.25
Patients with hyperviscosity from cryoglobulinemia, macroglobulins, cold agglutinins, and polycythemia can exhibit Raynaud phenomenon. Cryoglobulins are most commonly present in patients with multiple myeloma, but they also occur in patients with rheumatic diseases, chronic infections, leukemia, and lymphoma, and as an idiopathic condition.
The most common endocrine disturbance associated with Raynaud phenomenon is hypothyroidism; symptoms usually remit with thyroid hormone replacement. Raynaud phenomenon may be a feature of various infectious disorders, including subacute bacterial endocarditis, Lyme disease, and viral hepatitis, presumably a reflection of systemic vasculitis. Peripheral vasospasm may also occur in association with malignant tumors, including pheochromocytoma, carcinoid, breast and ovarian carcinoma.
The major forms of vascular ischemia that must be distinguished from Raynaud phenomenon are cold digits, chilblain (pernio), livedo reticularis, and acrocyanosis (see Chapters 94 and 173). Many patients complain of cold, sometimes painful digits without color changes. This condition likely represents one extreme of the spectrum of normal sympathetic nervous system activity. Chilblain is an inflammatory condition of the skin of the extremities induced by cold. Patients develop a bluish-red discoloration and edema, typically involving the lower limb and associated with warmth, erythema, and burning. In severe cases, hemorrhagic lesions, bullae, or ulcers may develop, and secondary infections may supervene. The lesions last from 7 to 10 days, often leaving a residual pigmentation of the skin. Livedo reticularis is a bluish discoloration of the skin of the extremities with a characteristic lacy, irregular appearance. The bluish discoloration becomes more intense on exposure to cold and may disappear in a warm environment. Most patients are entirely asymptomatic, although livedo reticularis may be a feature of the antiphospholipid syndrome, in which patients are at increased risk for venous and arterial thromboses, thrombocytopenia, and pregnancy losses. In acrocyanosis, the hands, and, less commonly, the feet, develop a persistent bluish discoloration. The blue color is intensified by exposure to cold and is converted into a purplish or red color by warming; a pallor phase is absent. The skin is cold, and the palms are often wet and clammy from sweat. Trophic changes or ulcerations are rarely observed.