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Cleveland Clinic Department of Rheumatic and Immunologic Diseases

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What You Need to Know About Cryoglobulinemia

What are cryoglobulins?
Cryoglobulins are proteins found in the blood that precipitate (clump together) in the cold and cause organ damage. These proteins can be present in the blood without any symptoms. When there are symptoms due to the cryoglobulins, the disease is called "cryoglobulinemia".

What are the symptoms of cryoglobulinemia?
Most people with cryoglobulins have no symptoms other than elevated levels on lab tests. When symptoms are present, they are most commonly fatigue, joint pain and a rash that looks like purple bruises, usually over the legs.

Other symptoms and signs may include:

  • Change of the color of hands and/or feet (from normal to white to a purplish-blue color) with cold, called ” Raynaud’s Phenomenon
  • Weight loss
  • High blood pressure
  • Swelling of ankles and legs
  • Numbness, tingling, or weakness in the hands or feet
  • Skin ulcers and gangrene
  • Enlarged liver or spleen
  • Abdominal pain
  • Kidney damage
  • Inflammation of the blood vessels (“vasculitis”)

What causes cryoglobulinemia?
Cryoglobulinemia can be present alone or can be associated with other diseases such as:

  • Infection, particularly hepatitis C infection
  • Blood cancers such as lymphoma and multiple myeloma
  • Connective tissue disease

How is cryoglobulinemia diagnosed?
Cryoglobulinemia is diagnosed by a specific blood test that will recognize the presence of cryoglobulins in the blood. Classification of the type of cryoglobulins can sometimes help in differentiating the cause of cryoglobulinemia.

How is cryoglobulinemia treated? Treatment of cryoglobulinemia depends on the organ affected and the extent of the damage as well as on the presence of other associated conditions. It is very important not only to treat the cryoglobulinemia but also to address any other associated disorders.

The mainstay of treatment is corticosteroids +/- other immunosuppressive medications depending on the affected organ and the extent of involvement.

Another form of treatment aims to diminish the amount of cryoglobulins in the blood. This can be done by plasma exchange, a treatment referred to as “plasmapheresis”.

If another associated disorder has been found, such as hepatitis C, interferon-alpha may be recommended with a referral to a hepatologist (liver specialist).

If multiple myeloma or lymphoma is identified, a referral to a hematologist is recommended.