Cryoglobulinemia is a family of rare conditions, called vasculitis. Vasculitis causes irritation and swelling, called inflammation, of the blood vessels.

Cryoglobulins are atypical proteins in the blood. For people who have cryoglobulinemia (kry-o-glob-u-lih-NEE-me-uh), these proteins may clump together at body temperatures below 98.6 F (37 C).

These clumps can block blood flow. This can damage the skin, joints, nerves and organs, mainly the kidneys and liver.

Cryoglobulinemia care at Mayo Clinic


There are three types of cryoglobulinemia.

  • Type 1. This type has one kind of atypical protein, called monoclonal. Type 1 most often is linked to blood cancers.
  • Type 2. This has two types of atypical protein, both monoclonal and polyclonal. Type II most often is linked to hepatitis C virus.
  • Type 3. This has a mix of polyclonal proteins. Type 3 most often is linked to autoimmune diseases such as rheumatoid arthritis.


Some people have no symptoms of cryoglobulinemia. For people who have symptoms, the symptoms might come and go. They can include:

  • Skin spots. Most people with cryoglobulinemia get purple skin spots, called lesions, on their legs. On Black or brown skin, the spots might look black or brown. Some people also get open leg sores, called ulcers.
  • Joint pain. Symptoms like those of rheumatoid arthritis are common in cryoglobulinemia.
  • Peripheral neuropathy. Cryoglobulinemia can damage the nerves at the tips of the fingers and toes. This causes numbness and other problems.


It's not clear what causes cryoglobulinemia. It's been linked to:

  • Infections. Hepatitis C is the most common infection linked to cryoglobulinemia. Others include hepatitis B, HIV, Epstein-Barr, toxoplasmosis and malaria.
  • Certain cancers. Some cancers of the blood, such as multiple myeloma, Waldenstrom macroglobulinemia and chronic lymphocytic leukemia, can cause cryoglobulinemia.
  • Autoimmune diseases. Disease in which the immune system attacks healthy tissues by mistake, called autoimmune, increases the risk of getting cryoglobulinemia. Examples are lupus, rheumatoid arthritis and Sjogren syndrome.

Risk factors

Risk factors of cryoglobulinemia may include:

  • Sex. Cryoglobulinemia happens more often in women than in men.
  • Age. Symptoms of cryoglobulinemia most often begin in middle age.
  • Other diseases. Cryoglobulinemia is linked with diseases such as hepatitis C, HIV, multiple myeloma, Waldenstrom macroglobulinemia, lupus and Sjogren syndrome.


Cryoglobulinemia can affect the kidneys. The main symptoms are protein or blood in the urine. High blood pressure most often goes with the kidney symptoms. In time, kidney failure might happen.

Cryoglobulinemia care at Mayo Clinic

Dec. 28, 2023

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  1. Ferri FF. Cryoglobulinemia. In: Ferri's Clinical Advisor 2023. Elsevier; 2023. https://www.clinicalkey.com. Accessed June 27, 2023.
  2. AskMayoExpert. Cryoglobulinemia. Mayo Clinic. 2023.
  3. Desbois AC, et al. Cryoglobulinemia: An update in 2019. Joint Bone Spine. 2019; doi:10.1016/j.jbspin.2019.01.016.
  4. Cryoglobulinemia. Vasculitis Foundation. https://www.vasculitisfoundation.org/education/forms/cryoglobulinemia/#1545061420875-b116dfd5-78d9. Accessed June 27, 2023.
  5. Cryoglobulins. Testing.com. https://www.testing.com/tests/cryoglobulins/. Accessed June 27, 2023.
  6. Cacoub P. Overview of cryoglobulins and cryoglobulinemia. https://www.uptodate.com/contents/search. Accessed June 27, 2023.


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