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

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