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Cryoglobulinemia is characterized by the presence of cryoglobulins in the serum. This may result in a clinical syndrome of systemic inflammation caused by cryoglobulin-containing immune complexes.

Cryoglobulins are single or mixed immunoglobulins that undergo reversible precipitation at low temperatures. Several types of cryoglobulins have been identified, and the potential clinical manifestations vary by cryoglobulin type.

This disease may be classified based on cryoglobulin composition with the Brouet classification, which is as follows:

    Type I, is the result of a monoclonal immunoglobulin, usually immunoglobulin M or, less frequently, immunoglobulin G, immunoglobulin A, or light chains.
    Types II and III contain rheumatoid factors, which are usually IgM and, rarely, IgG or IgA. These RFs form complexes with the fragment, crystallizable portion of polyclonal IgG. The actual RF may be monoclonal or polyclonal immunoglobulin. Types II and III represent 80% of all cryoglobulins.

This disease is a syndrome with many possible symptoms. Most common are weakness, aching joints, and purple bruises, most commonly of the lower extremities. Besides the skin and joints, organs commonly involved include nerves, kidneys and liver. Symptoms and signs may include:
  • Weakness
  • Joint aches
  • Purple/red spots on the extremities
  • Raynaud's phenomenon
  • Fever
  • Weight loss
  • High blood pressure
  • Swelling of ankles and legs
  • Numbness, tingling, or weakness in the hands or feet
  • Skin ulcers and gangrene
  • Enlarged liver or spleen
  • Abdominal pain
  • Kidney damage

  • Causes:
    Cryoglobulinemia can be present alone or can be associated with other diseases such as:
  • Infection, particularly hepatitis C infection
  • Blood cancers such as lymphoma and multiple myeloma
  • Connective tissue disease

  • Treatment:
    Treatment depends on the underlying cause. Treating the cause will often treat the disease.

    Mild cases can be treated by avoiding cold temperatures.

    For patients with Hepatitis C and mild or moderate cryoglobulinemia, the standard Hepatitis C treatment (interferon-alpha, with or without ribavirin) is often sufficient. However, the condition can return when treatment stops.

    A severe case that involves vital organs or large areas of skin, is treated with corticosteroids and medications that suppresses the immune system. Treatment may also involve plasma cleaning.

    Treatment with the medication rituximab (Rituxan) is currently under investigation.

    Possible Complications:
    Bleeding in the digestive tract (rare)
    Heart disease (rare)
    Infections of ulcers
    Kidney failure
    Liver failure
    Skin death


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