During cryoglobulinemia, abnormal proteins in the blood called cryoglobulins clump together at low temperatures, causing inflammation and damage to the blood vessels and various organs, including the skin, joints, nerves, kidneys, and liver.
Cryoglobulinemia can be classified into three types, depending on the type of cryoglobulins involved:
Type I cryoglobulinemia is usually associated with an underlying blood or immune system cancer, such as multiple myeloma, Waldenstrom macroglobulinemia, or chronic lymphocytic leukemia.
Type II and III cryoglobulinemia, also known as mixed cryoglobulinemia, are often seen in people with chronic inflammatory conditions, such as autoimmune diseases, infections, or liver diseases. The most common infection associated with mixed cryoglobulinemia is hepatitis C virus (HCV).
The exact cause of cryoglobulinemia is not fully understood, but it is believed to be related to an abnormal immune response that produces cryoglobulins.
Some people with cryoglobulinemia may not have any symptoms, while others may experience symptoms that come and go. The most common symptom of cryoglobulinemia is a purplish rash on the lower legs, caused by bleeding under the skin. Other symptoms may include:
Joint pain and swelling, resembling rheumatoid arthritis.
Numbness, tingling, or weakness in the hands or feet, due to nerve damage.
Skin ulcers and gangrene, due to poor blood circulation.
Raynaud’s phenomenon, which is a change in the color of the fingers or toes in response to cold temperatures.
Fatigue and weight loss.
Swelling of the ankles and legs, due to fluid retention.
Enlargement of the liver or spleen.
Kidney damage, which can lead to proteinuria (protein in the urine), hematuria (blood in the urine), or kidney failure.
Blood tests can detect cryoglobulins in the blood to determine the diagnosis of cryoglobulinemia. This test, however, may not be conclusive, since some people may have low levels of cryoglobulins without symptoms, while others may have symptoms without detectable cryoglobulin levels. To confirm the diagnosis, other tests may be necessary, including:
A complete blood count (CBC), which measures the number and types of blood cells.
A blood chemistry panel, which checks the levels of various substances in the blood, such as electrolytes, glucose, and liver enzymes.
A urinalysis, which examines the physical and chemical properties of the urine.
A kidney biopsy, which involves taking a small sample of kidney tissue for microscopic examination.
A skin biopsy, which involves taking a small sample of skin tissue for microscopic examination.
An immunofixation test, which identifies the type and subtype of cryoglobulins in the blood.
A viral test, which checks for the presence of viral infections, such as hepatitis C, hepatitis B, HIV, or Epstein-Barr virus.
The treatment of cryoglobulinemia depends on the type, severity, and underlying cause of the condition. The main goals of treatment are to:
Reduce the production of cryoglobulins, by treating the underlying disease or infection, such as cancer, autoimmune disease, or hepatitis C.
Prevent the clumping of cryoglobulins, by keeping the body warm and avoiding exposure to cold temperatures.
Relieve the symptoms and complications, by using medications, such as corticosteroids, immunosuppressants, antivirals, or blood thinners, depending on the specific problem.
Support the kidney function, by using dialysis or kidney transplantation, in case of kidney failure.
There is no known way to prevent cryoglobulinemia, but some measures may help reduce the risk or severity of the condition, such as:
Getting tested and treated for hepatitis C, if you have risk factors, such as injection drug use, blood transfusion, or organ transplant.
Following your doctor’s advice on managing your chronic condition, such as cancer, autoimmune disease, or liver disease.
Avoiding or limiting the use of alcohol and tobacco, which can worsen the inflammation and damage to the blood vessels and organs.
Keeping your body warm and avoiding exposure to cold temperatures, which can trigger the clumping of cryoglobulins.
Seeking medical attention promptly, if you develop any signs or symptoms of cryoglobulinemia, such as rash, joint pain, or kidney problems.
