Serum proteins, usually immunoglobulins, that precipitate from serum at cold temperatures.
Insoluble at low temperatures and dissolute after rewarming.
Most often serum cryoglobulins circulate without end-organ damage.
3 categories: Type I-represents monoclonal cryoproteins often present in the setting of lymphoproliferative disease. Type II contains a monoclonal component with rheumatoid factor activity and a polyclonal immunoglobulin component, more than 90% of this type associated with HCV. Type III contain polyclonal rheumatoid factor activity and polyclonal immunoglobulins and are associated with multiple disorders with immune complex formation.
More than 90% of patients with mixed cryoglobulinemia are infected with hepatitis C virus.
Generated by clonal expansion of B cells from either a lymphoproliferative disorder or persistent immune stimulation triggered by chronic infections or autoimmune disease.
Associated with chronic infections, especially hepatitis C and HIV infection, autoimmune disorders and hematologic cancers.
False negative laboratory results are non uncommon.
Type I and II cryogloulinemias result from from monoclonal expansion of a clone that is overtly malignant including myeloma, smoldering as Waldentrom’s macroglobulinemia, lymphoma, or indolent as with monoclonal gammopathy of unknown significance.
Type III cryoglobulinemia associated with polyclonal expansion of B cells.
Reversible precipitation on exposure to low temperatures allows detection of cryoglobulins.
Cold exposure can be a contributing factor in the clinical manifestations of cryoglobulinemia in the distal extremities