A 40-year-old woman presents with a complaint of painless blue discoloration of both hands and feet (Figure 76-1). The color changes are persistent, although their intensity seems to be greater with cold exposure. While the color improves in the summer, she experiences increased sweating of hands and feet. She has no significant medical history and takes no medications. Extensive medical workup has been unrevealing. The blue color resolves almost entirely when her hands or feet are elevated in a supine position for a few minutes. Pressing the blue skin elicits blanching; when released, the color refills in an irregular fashion from the periphery to the center.

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  Prevalence, incidence, geographic distribution, sex, and racial characteristics are uncertain.^1,2

  
  
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  Isolated studies more commonly describe female patients in their second and third decades of life.^3,4 However, selection bias appears to be universal, and no robust epidemiologic studies exist.

  
  
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  Familial presentations have been described.³

  
  
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  May occur more frequently in areas with a cooler climate.

  
  
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  Epidemiologic assessment may be confounded by prevalent factors underlying secondary cases. Such factors may be environmental or not easily identifiable, making it difficult to discern primary and secondary cases.^1,5

  
  
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  In secondary acrocyanosis, prevalence and incidence vary depending on the underlying condition.^1,6,7

Primary Acrocyanosis

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  Acrocyanosis is called primary when no specific underlying cause can be determined. The etiology is uncertain and, given the fact that acrocyanosis is a clinical diagnosis, it is not known whether it is a unique phenomenon or different processes with similar clinical features.³ There is a possible correlation with estrogen levels in women, and signs of acrocyanosis may resolve in some patients after menopause.

  
  
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  The defect is confined to small preterminal and terminal vessels.¹ The constriction occurs within capillaries but is marked by low capillary pressures, sluggish capillary flow, and poor pressure variability.⁸ Subpapillary vessels are dilated,⁹ and an increased number and size of arteriovenous anastomoses with blood shunting are common.¹⁰ There is no venous obstruction.⁴

Secondary Acrocyanosis

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  Associations of acrocyanosis with many other conditions have been described. When such associations are identifiable, acrocyanosis is called secondary. In cases of Ehlers-Danlos syndrome associated with acrocyanosis, hereditary vascular dysfunction of the pericytes in the subpapillary vascular plexus may produce abnormally twisted collagen fibrils.

  
  
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  Among known associations there are many conditions that are capable of producing local tissue hypoxia and vasoconstriction. Examples include exposure to many medications and chemical substances (including environmental exposures). Other associations include congenital syndromes, infections, and solid organ and blood malignancies. Cold agglutinins, cryoglobulins, cryofibrinogens, and antiphospholipid antibodies are seen in acrocyanosis with or without malignancies.¹

The diagnosis of acrocyanosis is clinical based on persistence and typical localization of the skin color changes. It requires exclusion of other conditions characterized by blue skin color changes. The diagnosis of primary acrocyanosis should be entertained only after causes of secondary acrocyanosis have been excluded.

Clinical Features

Primary acrocyanosis is a chronic, benign condition without tendency to progress, pain, or tissue loss. Skin changes tend to be painless and persistent and may be more pronounced in cold ambient temperatures and with dependency; skin color normalizes with elevation of the extremities (Figure 76-2A-D). Hyperhidrosis and clamminess of the hands and feet are often seen which worsens in warm temperature while skin color improves. Mild localized edema may be present.⁴