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.

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.


Diagnosis of cryoglobulinemia involves a blood test. The blood is kept at body temperature, 98.6 F (37 C), for a time. Then it's cooled before being tested. The sample must be handled this way to get correct results.

Other blood and urine tests also might be used to find the underlying cause.


Treatment depends on the cause of cryoglobulinemia and how bad it is. Watchful waiting might be a choice if you have no symptoms. Treatment may include medicines that calm the immune system or fight viral infections. For severe symptoms, a treatment that swaps blood plasma for donor plasma or another fluid might be used.

Even with treatment, cryoglobulinemia often returns. You might need regular follow-up visits with your health care professional to watch for its return.

Lifestyle and home remedies

If you have cryoglobulinemia, it's important to stay out of cold temperatures. Protect your fingers and toes. You may want to wear gloves when using the freezer or refrigerator. Check your feet daily for sores. Cryoglobulinemia can make it harder for foot damage to heal.

Preparing for an appointment

You may start by seeing your primary health care professional. Or you may be sent right away to a specialist in blood disorders, called a hematologist.

Here are some tips to help you get ready for your appointment.

What you can do

When you make the appointment, ask if there's anything you need to do in advance, such as fasting before having tests. Make a list of:

  • Your symptoms, including any that seem not linked to the reason for your appointment, and when they began.
  • Key personal information, including major stresses, recent life changes and family medical history.
  • All medicines, vitamins or other supplements you take, including the doses.
  • Questions to ask your care team.

Take a family member or friend along, if possible, to help you remember what your care team tells you.

For cryoglobulinemia, some basic questions to ask include:

  • What's likely causing my symptoms?
  • Other than the most likely cause, what are other possible causes for my symptoms?
  • What tests do I need?
  • Is my condition likely to go away or be long-lasting?
  • What's the best course of action?
  • I have these other health conditions. How can I best manage them together?
  • Should I see a specialist?
  • Are there brochures or other printed pages I can have? What websites do you suggest?

Be sure to ask all the questions you have about your condition.

What to expect from your doctor

Your care professional is likely to ask you questions, such as:

  • Have your symptoms been constant, or do they come and go?
  • How bad are your symptoms?
  • What, if anything, seems to make your symptoms better?
  • What, if anything, seems to make your symptoms worse?

What you can do in the meantime

Do not do anything that seems to make your symptoms worse.

Content From Mayo Clinic Updated: 12/27/2023
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