Cold Agglutinin Disease – Physical Exam

Acrocyanosis

• Symmetric painless discoloration of distal parts of the body (usually hands and feet), aggravated by cold or dependency.
• Pathophysiology has not been well-established, but may be related to autonomic function abnormality.
• Classified as:
  • Primary:
    • No underlying disease
    • A generally benign condition requiring no specific treatment
    • More commonly affecting women in the second and third decades.
  • Secondary – manifestation of other diseases
• Typically presents with persistent, symmetric, painless purple or cyanotic discoloration of hands and feet that worsens with dependency and improves with elevation. May be associated with hyperhidrosis of the affected areas.

Raynaud syndrome

• Episodic attacks of well-demarcated blanching or cyanosis of the digits on exposure to cold.
• Classified as:
  • Primary:
    • No identifiable underlying cause
    • Benign clinical course
  • Secondary – manifestation of an underlying condition including hematological conditions such as:
    • Cryoglobulinemia
    • Primary or secondary cold agglutinin disease (up to 91% of the patients with primary cold agglutinin disease have Raynaud syndrome).
• The classic description of Raynaud syndrome includes acute attacks of triphasic color changes of the digits brought on by exposure to cold or emotion, presenting with:
  • Skin pallor owing to vasoconstriction, followed by:
  • Cyanosis owing to deoxygenation, and finally:
  • Rubor owing to hyperemia with release of vasoconstriction
  • Notes:
    • Most patients with Raynaud syndrome report biphasic color changes with pallor and cyanosis alone.
    • The color changes start at the tip of the finger with a clear demarcation. Pallor may involve the distal phalanx or can extend to the web space.
• May be associated with numbness and/or pain.
• Raynaud syndrome is a clinical diagnosis based on color changes of the fingers. It is rare to observe directly. Patients will often bring photos of episodes.

Livedo reticulitis

• A violaceous reticular discoloration of the skin involving more commonly the extremities, but can affect other sites.
• The peripheral venous plexuses of the skin become visible when there is venodilation or deoxygenation of the blood.
• Livedo reticularis can be primary or secondary.
• The discoloration of livedo reticularis can be transient or fixed. It is usually asymptomatic and does not require therapy.