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Mixed Cryoglobulinemia

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.


Disorder Subdivisions

  • Type I Cryoglobulinemia
  • Type II Cryoglobulinemia
  • Type III Cryoglobulinemia
  • Essential Mixed Cryoglobulinemia

General Discussion

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.


Vasculitis Foundation
PO Box 28660
Kansas City, MO 64188
Tel: (816)436-8211
Fax: (816)436-8211
Tel: (800)277-9474

American Autoimmune Related Diseases Association, Inc.
22100 Gratiot Ave.
Eastpointe, MI 48021
Tel: (586)776-3900
Fax: (586)776-3903
Tel: (800)598-4668

NIH/National Heart, Lung and Blood Institute
P.O. Box 30105
Bethesda, MD 20892-0105
Tel: (301)592-8573
Fax: (301)251-1223

Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
Tel: (301)251-4925
Fax: (301)251-4911
Tel: (888)205-2311
TDD: (888)205-3223

Center for Peripheral Neuropathy
University of Chicago
5841 South Maryland Ave, MC 2030
Chicago, IL 60637
Tel: (773)702-5659
Fax: (773)702-5577

Autoimmune Information Network, Inc.
PO Box 4121
Brick, NJ 08723
Fax: (732)543-7285

European Society for Immunodeficiencies
1-3 rue de Chantepoulet
Geneva, CH 1211
Tel: 410229080484
Fax: 41229069140

AutoImmunity Community

For a Complete Report:

This is an abstract of a report from the National Organization for Rare Disorders (NORD). A copy of the complete report can be downloaded free from the NORD website for registered users. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational therapies (if available), and references from medical literature. For a full-text version of this topic, go to and click on Rare Disease Database under "Rare Disease Information".

The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only. NORD recommends that affected individuals seek the advice or counsel of their own personal physicians.

It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report

This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.

For additional information and assistance about rare disorders, please contact the National Organization for Rare Disorders at P.O. Box 1968, Danbury, CT 06813-1968; phone (203) 744-0100; web site or email

Last Updated: 7/18/2013
Copyright 1992, 2000, 2004, 2013 National Organization for Rare Disorders, Inc.

WebMD Medical Reference from the National Organization for Rare Disorders

Last Updated: May 28, 2015
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

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