Cryoglobulinemia - Cryoglobulin

Cryoglobulinemia - Cryoglobulin

 

The majority of cryoglobulinemias are secondary manifestations of other diseases and not “essential” as previously reported.

Classification

  • Type I (25%) – monoclonal immunoglobulins, consisting of IgM, occasionally IgG and, rarely, IgA or Bence Jones protein
    • Associated diseases – plasma cell dyscrasia, MGUS, lymphoproliferative diseases
  • Type II (25%) – mixed cryoglobulins, where a monoclonal immunoglobulin is directed against a polyclonal immunoglobulin
    • Includes monoclonal IgM or, occasionally, IgG or IgA, complexed with autologous normal IgG
    • Associated diseases – hepatitis C virus (HCV), autoimmune disorders, other infections
  • Type III (50%) – polyclonal proteins made of 2 or more immunoglobulins, none of which are homogeneous
    • Includes polyclonal IgM and IgG
    • Associated disorders – autoimmune, HCV, lymphoproliferative, other infections

 Pathophysiology

  • Cryoglobulins, proteins that reversibly precipitate at 0-4° C, are usually associated with plasma cell and lymphoproliferative disorders, but may also occur in:
    • Connective tissue diseases       
    • Hepatitis C infection
    • Other infections such as infectious mononucleosis and cytomegalovirus disease
  • Low levels of cryoglobulins may also occur in apparently healthy individuals

Click here for a chart of Clinical Conditions that May Be Associated with Cryoglobulinemia.

Clinical Presentation

  • Target organs – skin, nerves, kidney, liver
  • Symptoms related to cryoglobulinemia Types II and III result from the tendency of cryoglobulins to precipitate at low temperatures, which occlude blood vessels, resulting in vasculitic symptoms
    • Vascular purpura (palpable purpura)
    • Bleeding tendencies
    • Cold-induced urticaria
    • Raynaud phenomenon
    • Digital pain and cyanosis
  • All cryoglobulins can lead to renal disease such as glomerulonephritis
  • Essential mixed cryoglobulinemia, a vasculitic syndrome, results in purpura, arthralgia and weakness
    • Often associated with lymphadenopathy, hepatosplenomegaly and renal failure

Diagnosis

  • Indications for testing
    • Appropriate clinical signs and symptoms are present
  • Laboratory testing
    • Cryoglobulin testing – positive circulating cryoglobulins
    • Serum protein electrophoresis should be preformed in patients with cryoglobulinemia to identify the specific immunoglobulins present and determine if there is a monoclonal protein present
  • Histology studies
    • Skin biopsy demonstrating immune complex deposition to secure diagnosis in vasculitis

See Also