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Clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome (essential mixed cryoglobulinemia)

Fernando C Fervenza, MD, PhD
Sanjeev Sethi, MD, PhD
Robert A Kyle, MD
Steven Flamm, MD
Section Editors
Richard J Glassock, MD, MACP
Mark H Wener, MD
Deputy Editors
Albert Q Lam, MD
Monica Ramirez Curtis, MD, MPH


Essential mixed cryoglobulinemic vasculitis was the traditional term for vasculitis caused by the deposition of circulating cryoglobulins that contain both a polyclonal IgG and an IgM rheumatoid factor directed against the IgG, which are also called mixed cryoglobulins. In most patients, this disorder is associated with chronic hepatitis C virus (HCV) infection.

A more accurate term for this type of vasculitis is the mixed cryoglobulinemia syndrome, which refers to primary or idiopathic cryoglobulinemia as well as cryoglobulinemia associated with autoimmune diseases, malignancy, or infection [1]. The mixed cryoglobulinemia syndrome can be caused by either type II or type III cryoglobulins, the characteristics of which are defined in the next section. (See 'Types of cryoglobulins' below.)

The etiology, clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome will be reviewed here. The treatment of this disorder is discussed separately. (See "Treatment of the mixed cryoglobulinemia syndrome".)


Cryoglobulins are immunoglobulins that precipitate in the cold and dissolve on rewarming. The biochemical characteristics that promote cryoprecipitation are not well understood. Cryoglobulins that contain more than one immunoglobulin component are called mixed cryoglobulins.

Three different immunochemical types of cryoglobulins have been described [2,3] (see "Overview of cryoglobulins and cryoglobulinemia", section on 'Classification'):

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Literature review current through: Nov 2017. | This topic last updated: Nov 15, 2017.
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