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Cryoglobulinemia is the presence of abnormal proteins in the blood. These proteins thicken in cold temperatures.

Causes of Cryoglobulinemia

Cryoglobulins are antibodies. It is not yet known why they become solid or gel-like at low temperatures. When this occurs, these antibodies can cause inflammation and block blood vessels. This may lead to problems ranging from skin rashes to kidney failure.

Cryoglobulinemia is part of a group of diseases that cause damage and inflammation of the blood vessels throughout the body (vasculitis). There are three main types of cryoglobulinemia. They are grouped based on the type of antibody that is produced:

  • Type I
  • Type II
  • Type III

Types II and III are also referred to as mixed cryoglobulinemia.

Type I cryoglobulinemia is most often related to cancer of the blood or immune systems.

Types II and III are most often found in people who have a chronic (long-lasting) inflammatory condition, such as an autoimmune disease or hepatitis C. Most people with this form of the disease have a chronic hepatitis C infection.

Other conditions that may be related to cryoglobulinemia include:

Cryoglobulinemia Symptoms

Symptoms will vary depending on the type of disorder you have and the organs that are involved. Symptoms may include:

Tests and Exams

The health care provider will do a physical exam. You will be checked for signs of liver and spleen swelling.

Tests for cryoglobulinemia include:

Other tests may include:

  • Angiogram
  • Chest x-ray
  • ESR
  • Hepatitis C test
  • Nerve conduction tests, if the person has weakness in the arms or legs

Treatment of Cryoglobulinemia

Mixed cryoglobulinemia (Types II and III)

Mild or moderate forms of cryoglobulinemia can often be treated by taking steps to deal with the underlying cause.

  • Mild cases can be treated by avoiding cold temperatures.
  • Standard hepatitis treatments work for most people who have hepatitis C and mild or moderate disease. The condition can come back when treatment stops.

Severe cryoglobulinemia involves vital organs or large areas of skin. It is treated with corticosteroids and other medicines that suppress the immune system.

  • Rituximab is an effective drug and has fewer risks than other medicines.
  • Cyclophosphamide is used in life-threatening conditions where rituximab is not working or available. This medicine was used often in the past.
  • A treatment called plasmaphereis is also used. In this his procedure, blood plasma is taken out of blood circulation and abnormal cryoglobulin antibody proteins are removed. The plasma is replaced by fluid, protein, or donated plasma.

Type I cryoglobulinemia:

This disorder is due to a cancer of the blood or immune system such as multiple myeloma. Treatment is directed against the abnormal cancer cells that produce the cryoglobulin.

Prognosis (Outlook)

Most of the time, mixed cryoglobulinemia does not lead to death. Outlook can be poor if the kidneys are affected.

Potential Complications

Complications include:

  • Bleeding in the digestive tract (rare)
  • Heart disease (rare)
  • Infections of ulcers
  • Kidney failure
  • Liver failure
  • Skin death
  • Death

When to Contact a Health Professional

Call your health care provider if:

  • You develop symptoms of cryoglobulinemia.
  • You have hepatitis C and develop symptoms of cryoglobulinemia.
  • You have cryoglobulinemia and develop new or worsening symptoms.

Prevention of Cryoglobulinemia

There is no known prevention for the condition.

  • Staying away from cold temperatures may prevent some symptoms.
  • Testing and treatment for hepatitis C infection may reduce your risk.


Dammacco F, Sansonno D. Therapy for hepatitis C virus-related cryoglobulinemic vasculitis. N Engl J Med 2013; 369:1035. PMID: 24024840. Available at:

De Vita S, Quartuccio L, Isola M, et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis Rheum 2012; 64:843. PMID: 22147661. Available at:

Rajkumar VS. Plasma cell disorders. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 24th ed. hiladelphia, PA: Elsevier Saunders; 2011:chap 193.

Stone JH. Immune complex-mediated small vessel vasculitis. In: Firestein GS, Budd RC, Gabriel SE, et al, eds. Kelley's Textbook of Rheumatology. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 91.

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Review Date: 1/20/2015
Reviewed By: Gordon A. Starkebaum, MD, Professor of Medicine, Division of Rheumatology, University of Washington School of Medicine, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.
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