Mixed Cryoglobulinemia

...less medical jargon in a 'Quick Glance' format!

Mixed Cryoglobulinemia (MC) is a chronic autoimmune disorder that is almost always associated with chronic liver inflammation due to hepatitis C virus (HCV) infection. It is a combination of an immune complex disorder and a lymphoproliferative disorder, with distinct symptoms caused by each aspect of the disease. MC is believed to develop when chronic liver inflammation causes B cells to grow out of control and produce excessive amounts of antibodies, especially anti-IgG antibodies known as rheumatoid factors. The B-1 (CD5+) cells are believed to be important in the production of rheumatoid factors found in MC patients. MC is a relatively rare disorder, affecting only 13-54% of HCV infected individuals.


  • purple spotted rash caused by internal bleeding.
  • joint pain (experienced by 83% of patients)
  • weakness (experienced by 89% of patients)

  • Cause:
    The exact mechanism by which mixed cryoglobulinemia arises from HCV infection is unknown. MC symptoms fall into two distinct categories: those due to the accumulation of immune complexes and those due to liver damage, lymphomas, etc. Immune complexes accumulate because of the excessive amounts of IgG antibodies and rheumatoid factors in the blood due to chronic inflammation. The IgG and rheumatoid factors form immune complexes capable of activating complement. Lymphoproliferation may be caused by a variety of factors, including surface proteins on HCV that stimulate B cell activation, molecular mimicry, and natural genetic mutations that become more likely with increasing cell division. In many ways the immune complex disorder is a result of the excessive lymphoproliferation, but the two aspects of the disease can become self-sustaining.

    The most primary goal of any treatment regimen for MC is elimination of the HCV infection. When the level of virus in the serum decreases, patients usually experience a decrease in symptoms as well. For this reason, Interferon is the current drug of choice. Interferon is a general antiviral treatment that prevents viral replication within cells, increases antigen presentation, and activates NK cells to clear out infection. Unfortunately, interferon treatment sometimes only produces transient results and has been shown to increase the likelihood of peripheral sensory neuropathy. These effects can be reduced by a combination the interferon treatment with ribavirin, although the efficacy of this combination has not yet been proven. Studies into HCV vaccines have demonstrated the feasibility of creating antibodies that block HCV binding sites. This treatment would prevent them from infecting new cells.

    The secondary goal of mixed cryoglobulinemia treatment is alleviation of the symptoms, which requires immunosuppression. Non-steroidal anti-inflammatory drugs are used to treat minor symptoms such as purpura, weakness, and joint pain. Steroids are prescribed for more serious symptoms such as sensory neuropathy and glomerulonephritis. A low-antigen content diet has also shown promise for treatment of liver disease. It is thought that the diet works by decreasing the amounts of large ingested substances that compete with immune complexes for clearance by the mononuclear phagocytic system. If the diet reduces the concentration of these substances, the immune complexes may be more efficiently cleared. The most seriously life threatening conditions, such as acute progressive glomerulonephritis, motor neuropathy, and hyperviscosity syndrome, are treated with plasma exchange therapy accompanied by immunosuppressive drugs. This treatment rapidly decreases the number of circulating immune complexes.


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    ...less medical jargon in a 'Quick Glance' format!