What is Cryoglobulinemia?

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  • Written By: Emma Lloyd
  • Edited By: A. Joseph
  • Last Modified Date: 11 September 2019
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Cryoglobulinemia is a rare disease that develops as a result of the presence of high levels of abnormal proteins, called cryoglobulins, in the blood. In cold temperatures, these proteins clump together and block blood vessels, potentially causing a wide range of complications. There are several types of cryoglobulinemia that are classified based on the type of abnormal protein that is present in the blood.

Cryoglobulins are proteins of a specific type called immunoglobulins, or antibodies. Antibodies are molecules produced by the B cells of the immune system, and they help destroy infectious organisms that invade the blood and certain other parts of the body. At low temperatures, cryoglobulins undergo a process called precipitation, in which they clump together and form a thick, gel-like material. This process is irreversible. Not all antibodies are cryoglobulins; most antibodies function as normal and do not precipitate at cold temperatures.

The three types of cryoglobulinemia known to exist are referred to as type I, type II and type III. The main difference between these types is the nature of the cryoglobulin antibodies and the factors that caused them to develop. In most cases, type I is associated with cancers of the immune system or the blood. Type II and type III usually develop in people who have a chronic inflammatory condition such as hepatitis C or an autoimmune disease. Autoimmune diseases, which are caused by immune system dysfunction, include rheumatoid arthritis and systemic lupus erythematosus.


Cryoglobulinemia has many potential symptoms, because the presence of cryoglobulins in the blood can affect almost any organ or tissue type. This is because the precipitation of the proteins can block any of the body’s blood vessels, so the symptoms of the disease depend on the site or sites of blood vessel blockage. Even so, certain effects are more common than others.

Common symptoms of cryoglobulinemia include fatigue, muscle pain, joint pain, difficulty breathing, skin ulceration and death of large patches of skin cells. These symptoms are quite general and can develop regardless of the specific organ or organs involved. Kidney disease and liver disease are relatively common consequences. These organs are the most likely to be affected by levels of blood cryoglobulins because of their roles in filtering the blood of waste products.

People who have low levels of cryoglobulins in their blood can prevent symptoms of the disease by avoiding cold temperatures. Moderate to severe cases require immune-suppressing medications such as corticosteroids. In addition, treatment focuses on treating the underlying cause of the disease, whether this is hepatitis, an autoimmune disorder or another disease. In most cases, the presence of cryoglobulins in the blood does not progress to fatal disease, but if the kidneys become diseased, the prognosis worsens.


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