Cryoglobulin Syndromes

Cryoglobulin Syndromes is a topic covered in the Washington Manual of Medical Therapeutics.

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General Principles

Cryoglobulins are serum immunoglobulins that reversibly precipitate in the cold. Cryoglobulins are categorized as type 1 (monoclonal, no RF activity) or as those with RF activity, the “mixed” types 2 (monoclonal) and 3 (polyclonal).


  • Patients with type 1 usually have an underlying hematologic disorder such as myeloma, lymphoma, or Waldenström macroglobulinemia.
  • Types 2 and 3 are associated with small-vessel vasculitis and can be present in patients with chronic inflammatory diseases such as hepatitis B and C virus infection, endocarditis, SLE, and RA. The majority of patients with mixed cryoglobulinemia have hepatitis C, although only 5% of patients with hepatitis C and cryoglobulins develop vasculitis.
  • “Essential” cryoglobulinemia (cryoglobulinemia without an etiology) has become exceedingly rare since the discovery of hepatitis C.

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