National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Mixed Cryoglobulinemia is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
- Type I Cryoglobulinemia
- Type II Cryoglobulinemia
- Type III Cryoglobulinemia
- Essential Mixed Cryoglobulinemia
Mixed cryoglobulinemia is a rare disorder characterized by the presence of cryoglobulins in the blood. Cryoglobulins are abnormal proteins that thicken and clump together at cold temperatures, usually below 98.6 degrees Fahrenheit (the average human body temperature). However, the exact temperature at which this occurs may vary from one person to another. When these proteins clump together, they can restrict blood flow to joints, muscles, and organs. Eventually, damage or inflammation of affected blood vessels and surrounding tissue can develop, a condition known as vasculitis. Small blood vessels are usually affected, but occasionally larger blood vessels are involved. Common symptoms include skin lesions, joint pain (arthralgia), and weakness, but specific symptoms can vary greatly from one person to another and can potentially involve multiple organ systems. Mixed cryoglobulinemia is believed to be an immune-mediated disorder (in which the immune system response to chronic infection causes damage to various tissues) or an autoimmune disorder (in which the immune system mistakenly attacks the body's own tissue). Many cases of mixed cryoglobulinemia are associated with chronic infection with the hepatitis C virus. In rare cases, no underlying cause for the disorder can be identified (essential mixed cryoglobulinemia).
Cryoglobulinemia involves dysfunction of the immune system. The immune system is divided into several components, the combined actions of which are responsible for defending against infectious agents. The T cell system (cell-mediated immune response) contributes to fighting several viruses, some bacteria and yeast and fungi. The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g. saliva). There are five classes of immunoglobulins (Ig) known as IgA, IgD, IgE, IgG, and IgM. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells. Any substance that triggers a response by the immune system is known as an antigen.
Cryoglobulinemia is generally broken down in three subtypes. In type I cryoglobulinemia, cryoglobulins are made up of a specific immunoglobulin, usually IgM. Type I cryoglobulinemia is usually associated with an underlying disorder, specifically certain types of cancer. Type II and type III cryoglobulinemia are known as mixed cryoglobulinemia. In these disorders, cryoglobulins are abnormal immune complexes. An immune complex is formed when an antibody attaches to an antigen. Unlike type I cryoglobulinemia, the cryoglobulins in type II and type III contain rheumatoid factor, which is an autoantibody (i.e. an antibody that attacks the body own tissue). The distinction between type II and type III cryoglobulinemia is mostly technical and deals with whether the rheumatoid factor is monoclonal or polyclonal. The clinical pictures of type II and III cryoglobulinemia are similar. This report primarily deals with mixed cryoglobulinemia.
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Last Updated: 7/18/2013
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