Introduction

Cryoglobulins are abnormal immunoglobulins that characteristically precipitate at temperatures below 37 C (98.6 F) and dissolve on rewarming.  The presence of these immunoglobulins in the serum is referred to as cryoglobulinemia.  Cryoglobulins can form immune complexes (ICs) that deposit within small- to medium-sized blood vessels, triggering inflammation and tissue damage (ie, cryoglobulinemic vasculitis).  In addition, cryoglobulins can increase serum viscosity, leading to mechanical occlusion of the microcirculation.

Classification

Cryoglobulinemia is classified into 3 types based on immunoglobulin composition:

  • Type I:  Single monoclonal immunoglobulin (IgM or IgG), usually associated with lymphoproliferative disorders (eg, multiple myeloma, Waldenström macroglobulinemia).
  • Type II:  Mixed cryoglobulins comprising monoclonal IgM with rheumatoid factor (RF) activity and polyclonal IgG; strongly linked to chronic hepatitis C virus (HCV) infection.
  • Type III

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