Cryoglobulinemia

Definition

Cryoglobulinemia is the presence of abnormal proteins in the blood. These abnormal proteins become thick or gel-like in cold temperatures.

Causes, incidence, and risk factors

Cryoglobulins are antibodies. It is not yet known why they become solid at low temperatures. When they do thicken or become somewhat gel-like, they can block blood vessels throughout the body. This may lead to complications ranging from skin rashes to kidney failure.

Cryoglobulinemia is part of a group of diseases that cause vasculitis -- damage and inflammation of the blood vessels throughout the body. The disorder is grouped into three main types, depending on the type of antibody that is produced:

• Cryoglobulinemia type I
• Cryoglobulinemia typeII
• Cryoglobulinemia type III

Types II and III are also referred to as mixed cryoglobulinemia.

Type I cryoglobulinemia is most often related to cancer of the blood or immune systems.

Types II and III are most often found in people who have a chronic (long-lasting) inflammatory condition, such as an autoimmune disease or hepatitis C. Most patients with mixed cryoglobulinemia have a chronic hepatitis C infection.

Other conditions that may be related to cryoglobulinemia include:

• Leukemia
• Multiple myeloma
• Mycoplasma pneumonia
• Primary macroglobulinemia
• Rheumatoid arthritis
• Systemic lupus erythematosus

Symptoms

Symptoms vary depending on the type of cryoglobulinemia and the organs that are affected. In general, symptoms may include:

• Difficulty breathing
• Fatigue
• Glomerulonephritis
• Joint pain
• Muscle pain
• Purpura
• Raynaud's phenomenon
• Skin death
• Skin ulceration

Signs and tests

The doctor will perform a physical exam. There may be signs of liver and spleen swelling.

Tests for cryoglobulinemia include:

• Complete blood count (CBC)
• Complement assay -- numbers will be low
• Cryoglobulin test -- may show presence of cryoglobulins
• Liver function tests -- may be high
• Rheumatoid factor -- positive in types II and III
• Skin biopsy
• Urinalysis -- may show blood in the urine if the kidneys are affected

Other tests may include:

• Angiogram
• Chest x-ray
• ESR
• Hepatitis C test
• Nerve conduction tests, if the person has weakness in the arms or legs
• Protein electrophoresis - blood

Treatment

Treatment of mild or moderate cryoglobulinemia depends on the underlying cause. Treating the cause will often treat the cryoglobulinemia.

Mild cases can be treated by avoiding cold temperatures.

Standard hepatitis C treatments usually work for patients who have hepatitis C and mild or moderate cryoglobulinemia. However, the condition can return when treatment stops.

Severe cryoglobulinemia (involves vital organs or large areas of skin) is treated with corticosteroids and other medications that suppress the immune system.

Treatment may also involve plasmapheresis. Plasmapheresis is a procedure in which blood plasma is removed from the circulation and replaced by fluid, protein, or donated plasma.

Expectations (prognosis)

Cryoglobulinemia is not usually deadly. However, if the kidneys are affected, the outlook is poor.

Complications

Complications include:

• Bleeding in the digestive tract (rare)
• Heart disease (rare)
• Infections of ulcers
• Kidney failure
• Liver failure
• Skin death
• Death

Calling your health care provider

Call your health care provider if:

• You develop symptoms of cryoglobulinemia
• You have hepatitis C and develop symptoms of cryoglobulinemia
• You have cryoglobulinemia and develop new or worsening symptoms

Prevention

There is no known prevention. Avoiding exposure to cold temperatures may prevent some symptoms.

Because so many cases of mixed cryoglobulinemia are associated with hepatitis C, prevention of hepatitis C infection may reduce your risk of cryoglobulinemia.

References

Goldman L, Ausiello D. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa: WB Saunders; 2004:1193.

Rakel P, ed. Conn’s Current Therapy 2006. 58th ed. Philadelphia, Pa: WB Saunders; 2006:980, 1164.

Harris ED, Budd RC, Genovese MC, Firestein GS, Sargent JS, Sledge CB. Kelley's Textbook of Rheumatology. 7th ed. St. Louis, Mo: WB Saunders; 2005:1392-1393.