To determine if symptoms like sensitivity of extremities to cold is due to the presence of abnormal proteins called cryoglobulins in the blood
When a person has symptoms such as a rash, bruising, pain, weakness, joint pain, and/or paleness and coolness of the extremities that occur at cold temperatures
A blood sample taken from a vein in your arm, kept at body temperature until tested in the laboratory.
This test detects and measures the relative quantity of cryoglobulins in the blood. Cryoglobulins are circulating proteins, specifically, immunoglobulins, (i.e., IgG, IgM, IgA) that clump together (precipitate) when they are exposed to cold and dissolve when warmed. They may be present in small quantities in the blood of some healthy people but do not cause disease. In affected individuals they are most frequently associated with abnormal protein production and numerous diseases and conditions.
Precipitated cryoglobulins can slow the flow of blood and block small blood vessels. The presence of large amounts of cryoglobulins in the blood, called cryoglobulinemia can cause symptoms such as bruising, rashes, joint pain, weakness, and Raynaud's phenomenon – pain, paleness, bluing, numbness, tingling and coldness in the fingers with exposure to cold. Cryoglobulins can cause tissue damage that leads to skin ulcers and in severe cases to gangrene. They can activate the immune system, leading to the deposit of immune complexes in tissues, and cause inflammation, bleeding, and clotting that can affect circulation in organs such as the kidneys and liver.
Cryoglobulins may be seen with a variety of conditions, including infections such as Lyme disease, infectious mononucleosis (mono), hepatitis C, and HIV/AIDS, kidney disease, autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjögren syndrome, lymphoproliferative diseases such as multiple myeloma, lymphoma and lymphoid leukemia, and disorders associated with inflammation of blood vessels (vasculitis) such as Wegener's granulomatosis. Cryoglobulins are not specific for or diagnostic of any of these conditions but are one of the signs associated with them.
There are three types of cryoglobulins:
- Type I, which consists of a monoclonal immunoglobulin – a single type of protein that is produced by one abnormal cell or clone. This type is often seen in patients with myeloma or lymphoma.
- Type II, which consists of a mixture of monoclonal and polyclonal immunoglobulins. This type is often seen in patients with hepatitis C or other viral infections.
- Type III, which consists of polyclonal immunoglobulins. This type is often seen in patients with autoimmune diseases.
Initial testing does not distinguish between these three types of cryoglobulins, but the proteins involved can be determined through subsequent protein electrophoresis testing. For accurate diagnosis, it is important that the type of cryoglobulin is determined.
Cryoglobulin testing involves collecting a blood sample in a prewarmed tube and keeping the sample at or near body temperature during test preparation. The person's serum is then refrigerated for 72 hours and examined daily for precipitates. After 72 hours, if precipitates are found to be present, then the quantity is estimated and the sample is warmed to determine whether the precipitates dissolve. If they do, then cryoglobulins are present.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm. The blood must then be kept at body temperature, and not allowed to cool to room temperature before it is analysed.
Is any test preparation needed to ensure the quality of the sample?
How is it used?
A cryoglobulin test is used to help detect the presence and relative quantity of cryoglobulins in the blood. It may be requested along with other tests to help determine and rule out potential causes for cryoglobulinemia. The tests requested depend on what condition or disease is suspected. They may include tests such as rheumatoid factor (RF), antinuclear antibody (ANA), and a variety of other autoantibodies to help identify or rule out an autoimmune disorder, hepatitis C testing, etc.
If the cryoglobulin test is positive, then it will be followed with specialised protein electrophoresis and immunofixation electrophoresis (IFE) testing to determine which type(s) of protein are present as cryoglobulins and which type of cryoglobulinemia the person has.
When is it requested?
The cryoglobulin test is requested whenever a person has symptoms that may be associated with cryoglobulinemia. Some of these may include:
- Joint pain
- Raynaud's phenomenon, which is characterised by pain, paleness, bluing, numbness, tingling and coldness in the fingers and toes with exposure to cold.
Cryoglobulins may sometimes cause damage to the skin that leads to ulcers and, in severe cases of tissue damage, to gangrene.
What does the test result mean?
The cryoglobulin test is negative in most healthy people and is not routinely requested on those without symptoms.
When the test is positive, it means that cryoglobulins are present and have the potential to precipitate upon exposure to cold. The symptoms experienced when this happens will vary from person to person, may be different with each exposure, and will not necessarily correlate with the quantity of cryoglobulins present.
A positive test for cryoglobulin may be seen in numerous conditions and is not therefore not diagnostic. Some examples include:
- Infections such as Lyme disease, infectious mononucleosis (mono), hepatitis C and HIV/AIDS
- Kidney disease
- Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome
- Diseases characterized by an increase in lymphocytes such as multiple myeloma, lymphoma and lymphoid leukemia
- Disorders associated with inflammation of blood vessels (vasculitis)
Is there anything else I should know?
Cryoglobulinemias are sometimes separated into "secondary" cryoglobulinemia, associated with an underlying condition, and "essential or idiopathic" cryoglobulinemia, not associated with another disease. Many of the cases of essential cryoglobulinemia have now been shown to have a disease association, such as Hepatitis C.
Can someone prevent cryoglobulin-related symptoms?
Avoiding contact with cold objects and exposure to cold can help prevent or minimise symptoms.
Is there something I can do to get rid of my cryoglobulins?
In general, no. If they are due to a temporary condition, such as a bacterial infection, then they may go away when the infection resolves. If they are due to a chronic condition, such as an autoimmune disorder, then they may reduce as a consequence of treating the underlying condition, but many persist. In some cases, apheresis may be performed to remove cryoglobulins from the blood and to relieve symptoms, but this may help only temporarily.
What are some other tests that may be done to determine the underlying cause of cryoglobulinemia?
How is cryoglobulinemia treated?
It is primarily treated by addressing the underlying condition. Drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other immune suppressants may sometimes be needed to help relieve symptoms and minimise complications. Some patients may be suitable for B-cell depletion therapy (Rituximab).