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Cryoglobulinemic Vasculitis

What is cryoglobulinemic vasculitis?

Cryoglobulins are immune complexes - collections of antibodies bound to other proteins during the course of a response to infection or in some autoimmune diseases – that are particularly large and that fall out of solution from the blood and become solid when stored in the cold in the laboratory. In the body, immune complexes can stick to the cells that line small blood vessels, attracting white blood cells that damage blood vessel walls. The most common organs involved are the skin, nerves, and kidneys, with a wide range of other organs involved much less commonly. Most patients also feel ill, with fatigue and pain in the muscles and joints. Only a small percentage of patients have damage specifically to parts of the body that are exposed to the cold. These patients have “type I” cryoglobulins that can block blood flow without necessarily causing vasculitis, as opposed to the “type II” or “type III” cryoglobulins that typically destroy blood vessels through inflammation.

Who gets cryoglobulinemic vasculitis?

About 70-80% of patients have chronic infection with the hepatitis C virus. Many other patients have either lupus or Sjogren’s syndrome, and some others have lymphoma. In a small percentage of patients, the cause is completely unknown, and the term “essential cryoglobulinemia” is sometimes used.

What causes cryoglobulinemic vasculitis?

Deposition of immune complexes in the walls of small blood vessels causes white blood cells to stick to them and then act as they would if they were fighting a serious infection. “Activation” of white blood cells, particularly neutrophils, within blood vessels is destructive, and the organs supplied by those blood vessels are at risk of not receiving enough oxygen and nutrients. In patients with hepatitis C virus infection, the virus is contained in the immune complex and is clearly the cause. In patients with lupus, Sjogren’s syndrome, or lymphoma, the disease is thought to be autoimmune, meaning the immune system is mistakenly attacking one of its own components. Essential cryoglobulinemia is suspected to be autoimmune also, but chronic infection is also a possibility, and causes may differ among patients.

How cryoglobulinemic vasculitis diagnosed?

A biopsy showing vasculitis plus a blood test for cryoglobulins is the typical way to diagnose cryoglobulinemic vasculitis. Skin is by far the most common site for biopsy, but muscle or nerve are other common sites. Damage to the kidney by cryoglobulins looks different than in other diseases and thus is diagnostic also. In some cases, a biopsy may not be necessary; for example, a patient with purpura (the typical skin damage in vasculitis) and new neuropathy and infection with hepatitis C may not need a biopsy. In addition to the blood test for cryoglobulins, several other blood tests that are abnormal in 80% of patients are often sent, because the cryoglobulin test requires different processing than other blood tests and is often performed improperly.

What is the treatment for cryoglobulinemic vasculitis?

For patients with hepatitis C, eradication of the virus cures vasculitis in most patients. Patients who have severe disease may need immune-suppressive treatment to control vasculitis before or during anti-viral treatment. Rituximab is probably the most effective treatment in such patients, but other medications such as prednisone, cyclophosphamide, and azathioprine have often been used. Sometimes plasma exchange, which directly removes cryoglobulins directly from the blood temporarily, is used in the small number of patients who have life-threatening disease. For patients without hepatitis C, there is no known cure, so immune-suppressive drugs are required in most patients. The effectiveness of different drugs has not been studied as extensively as it has in the setting of hepatitis C.