Cryofibrinogenemia

Definition

• Disease caused by cold-precipitating proteins present in the plasma but not serum (i.e. associated with the clotting factors) that is associated with skin manifestations and thrombosis

Etiology

• Primary
  • About half eventually develop lymphoma
• Secondary
  • Cancer, usually lymphoma
  • Infection
    • Bacterial
    • Viral, including HIV, herpesviruses, and viral hepatitis
  • Autoimmune
    • Systemic lupus erythematosus
    • Sjögren syndrome
    • Rheumatoid arthritis
    • Mixed connective tissue disease
    • Polymyositis
    • Dermatomyositis
    • Systemic sclerosis
    • Antiphospholipid syndrome
    • Hashimoto and Graves diseases
    • Sarcoidosis
    • Pyoderma gangrenosum
    • Psoriasis
    • Spondyloarthropathy
    • Inflammatory bowel disease
  • Vasculitis
    • ANCA-associated vasculitis
    • Giant cell arteritis
    • Behçet disease
    • Polyarteritis nodosa
    • Henoch-Schönlein purpura
  • Cryoglobulinemia

Pathophysiology

• Cryofibrinogen is composed of fibrinogen, fibronectin, and fibrin, with or without albumin and immunoglobulins

Clinical Manifestations

• Cold intolerance
• Skin findings
  • Raynaud phenomenon
  • Purpura
  • Livedo reticularis
  • Skin necrosis
  • Acral ulcers
  • Gangrene
• Arterial and venous thromboses

Investigations

• Cryofibrinogen, returns as a percentage
  • Detectable in up to 7% of healthy patients

Management

• Mild
  • Cold avoidance
• Moderate
  • Corticosteroids
  • Aspirin
  • Alternatively, stanozolol 2 to 4mg BID (an anabolic steroid)
• Severe
  • Plasmapheresis
  • Immunosuppressing medications
    • Azathrioprine
    • Chlorambucil (in addition to corticosteroids)