Raynaud Phenomenon at a Glance
- Affects 10% of the population; 4:1 female–male ratio.
- Chronic episodic attacks of digital ischemia provoked by exposure to cold or emotional stress.
- Classified into primary (idiopathic) and secondary (underlying disease or cause present) forms; severity ranges from mild/benign to severe with loss of digital tissues.
- Connective tissue diseases—particularly systemic sclerosis—are the most common forms of secondary Raynaud.
- Both nonpharmacologic and drug therapies are used to reduce the frequency and severity of attacks.
Studies of the epidemiology of Raynaud phenomenon are biased by underreporting (most patients with primary Raynaud never seek medical attention) and studies done by investigators interested in the secondary forms of the disorder. Surveys indicate that Raynaud phenomenon affects up to 10% of the general population.1,2 Primary Raynaud phenomenon is estimated to be approximately twice as common as secondary Raynaud.3 Symptoms most often first develop in the teenage years, and most series show a female predominance of the disorder (female–male = 4:1). Increases in the frequency and severity of attacks during menses suggest that female sex hormones may be involved in the pathogenesis.4 Differences in seasonal skin temperatures, marital status, alcohol use, age, and smoking between women and men have also been suggested to contribute to the sex differences.5,6 Familial aggregation has been identified in a number of studies and suggests the contribution of genetic factors.7 Other associations reported in epidemiologic studies include living in a cold climate, occupation, cardiovascular disease, low body–mass index, and use of vibratory tools.
The pathophysiology of the vasospasm is complex and only partially understood. Studies show significant reductions of peripheral blood flow throughout all phases of central body cooling and rewarming, suggesting impairments of central thermoregulatory control mechanisms.8 Additional features which likely contribute to the development of Raynaud phenomenon include local defects of digital blood vessels causing abnormal vascular reactivity or reduced blood flow; an imbalance of locally produced vasoconstrictors or vasodilators; hyperreactivity of the sympathetic nervous system; and abnormal properties of the blood that compromise distal perfusion.
The gross histology of digital arteries in patients with primary Raynaud phenomenon is normal. Structural abnormalities of the digital microvasculature are frequently seen in patients with secondary forms of Raynaud phenomenon, particularly in the connective tissue diseases. Studies show a range of pathology, including intimal hyperplasia, narrowing or total occlusion of arteries, or thrombi. In most patients with systemic sclerosis, there exists evidence of activation and damage of the endothelium, fibrinolysis, and platelet activation.9 Autoantibodies and microvascular damage appear to be independent predictive factors for the progression of Raynaud phenomenon to systemic sclerosis.10
Microcirculatory flow studies with laser Doppler in patients with scleroderma have shown marked reductions in blood flow and hand temperature during an attack, with prominent abnormalities during rewarming—findings that suggest a failure of the arteriovenous anastomoses to open.11
Serotonin is also incriminated ...