A 21-year-old Caucasian woman with no past medical history presents with 9 months of painful color changes of her fingers upon cold exposure. She has no other complaints, and a thorough review of systems is negative. Her family history is significant for her mother having rheumatoid arthritis. She is a nonsmoker. Physical examination is normal other than dilated capillary loops and capillary dropout on nailfold capillary microscopy. Laboratory values reveal a positive antinuclear antibody (ANA) of 1:160 but are otherwise unremarkable. She is diagnosed with Raynaud phenomenon (RP).

RP is an exaggerated, reversible, vasospastic response of acral blood vessels upon exposure to cold or emotional stress. Clinically, it is characterized by sharply demarcated color changes of the digits often accompanied by pain or paresthesias (Figure 74-1).

The true prevalence of RP is difficult to establish because there is no gold standard diagnostic test.

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  Estimated prevalence between 2% and 20% of the population.^{1,2,3, and 4}

  
  
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  Female-to-male ratio between 3:1 and 9:1.^{1,2,3, and 4}

  
  
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  More common in younger age groups; mean age of onset in second to third decades.

  
  
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  Equal occurrence across races.

Primary RP (PRP) is the term used when there is no identifiable underlying disorder contributing to the vasospasm and there is no history of tissue damage from ischemia.

Secondary RP (SRP) occurs in the setting of an underlying disorder, most often a rheumatologic disease, and is often complicated by significant morbidity from digital ischemia (Table 74-1 and Figures 74-2,Figures 74-3, and 74-4). In severe disease with prolonged ischemic attacks, destruction of the distal phalanges may occur—a phenomenon known as acro-osteolysis (Figure 74-5).

The regulation of cutaneous blood flow involves complex interactions between structural components of blood vessels, neuronal signaling, and vasoactive chemical mediators. The precise ways in which this complicated system is disordered in RP have yet to be defined. Abnormalities in endothelial function, vascular reactivity, the secretion of vasoactive chemical mediators, and neurologic control of vasomotor tone have all been implicated in RP.⁵ Several experiments have pointed to a central role of alpha-2 adrenergic receptors in RP,^{6,7, and 8} possibly associated with increased protein tyrosine kinase activity.^9,10 Increased platelet activation via upregulation of the glycoprotein (GpIIb or IIIa) receptor was recently shown in patients with PRP.¹¹ While it appears that there is overlap in some of the functional impairments underlying PRP and SRP, the latter also involves intrinsic structural blood vessel abnormalities absent in PRP. Gross histologic examinations of digital arteries from patients with SRP have revealed intimal hypertrophy and fibrosis, vessel narrowing, and microthrombi, which are largely absent in PRP.

The diagnosis of RP usually is made on the basis of a compelling history, as there are no gold standard diagnostic tests. Attempts to reproduce Raynaud attacks for purposes of confirming a diagnosis are met with inconsistent responses and are rarely helpful. While a number of techniques are available in the research setting to help diagnose RP (thermography, angiography, laser Doppler imaging, and direct measures of skin temperature and local blood flow), they are rarely practical in everyday clinical practice. The following criteria have been suggested as helpful for diagnosing RP¹²: