Information on the following diseases can be found in the Related Disorders section of this report:

• Raynaud's Disease and Phenomenon
• Purpura
• Vasculitis
• Wegener's Granulomatosis

Essential mixed cryoglobulinemia is characterized by extreme physical reactions to cold such as loss of feeling in the hands or feet. In people with this disorder, blood becomes thicker when they are is exposed to cold. Brown spots may appear under the skin. The kidneys may become inflamed and produce unusual levels of protein or even blood in the urine. There may also be arthritis type joint pain, weakness, and even central nervous system problems. Gastrointestinal symptoms usually occur and the liver and spleen may be affected. Problems in the intestines and colon may cause chronic diarrhea.

The exact cause of essential mixed cryoglobulinemia is not known. However, it is considered to be an autoimmune disorder. Autoimmune disorders are caused when the body's natural defenses against "foreign" or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. In this condition the immune system appears to be triggered by cold temperatures. Cryoglobulins are proteins in the blood that become apparent when the blood is cooled. These cryoglobulins can affect many different bodily systems causing dysfunction.

Essential mixed cryoglobulinemia is a rare autoimmune disorder that is not usually apparent until middle age and affects females more often than males.

Symptoms of the following disorders can be similar to those of essential mixed cryoglobulinemia. Comparisons may be useful for a differential diagnosis:

Raynaud's disease and phenomenon are vascular disorders. They are caused by spasms of blood vessels when a person is exposed to either hot or cold temperatures. Symptoms occur more often in cold temperatures than in hot weather, and can also be triggered by emotional upset. Patients may experience sensory changes such as aching pain, a tingling feeling or throbbing in fingers or toes when exposed to extreme temperatures. There may be the sensation of tightness or pins and needles. The feeling of coldness or numbness and a loss of color or turning blue may also occur. (For more information on this disorder, choose "Raynaud" as your search term in the Rare Disease Database.)

Purpura means a red or purple color of the skin. It results from the fusion of blood and plasma into surfaces under the skin, mucous membranes and serous membranes. Purpura is the most common symptom of a vascular bleeding disorder which is characterized by increased bruising and fragile blood vessels. It can be caused by inflammation of the blood vessels affecting the skin, joints, gastrointestinal system and kidneys. (For more information on this disorder, choose "Purpura" as your search term in the Rare Disease Database.)

Vasculitis is a common disorder characterized by an inflammation of the blood vessel walls. Arteries and veins of all sizes and in all parts of the body may be affected. Depending on the system involved there may be muscle pain, joint pain, fever, weight loss, loss of appetite, headache, or generalized weakness. The skin, eyes, stomach and kidneys may be affected. (For more information on this disorder, choose "Vasculitis" as your search term in the Rare Disease Database.)

Wegener's granulomatosis is a rare collagen vascular disorder that begins as a localized inflammation of the mucous membranes in the upper and lower respiratory tract and usually progresses into generalized inflammation of the blood vessels and kidneys. (For more information on this disorder, choose "Wegener" as your search term in the Rare Disease Database.)

Protecting the patient from cold temperatures is a necessary preventive measure for people with essential mixed cryoglobulinemia.

Treatment of essential mixed cryoglobulinemia usually consists of combinations of drugs including steroids and cyclophosphamide. These drugs can alter the immune system and alleviate symptoms in many cases.

Plasmapheresis is a procedure used for removing unwanted substances such as toxins and plasma parts from the blood. Blood is removed from the patient and blood cells are separated from plasma. The patient's plasma is then replaced with other human plasma and the blood is transfused back into the patient. Cryoglobulins can be removed from the patient's blood by cooling the blood serum during plasmapheresis.

Cryofiltration is another form of treatment that can remove the cryoglobulins from the blood without the need of plasma replacement.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Kyle RA. Plasma cell disorders. In: Bennett JC & Plum F., Cecil Textbook of Medicine. 20th ed. Phildelphia, PA: W. B. Saunders Co; 1996:966

Kyle RA. Multiple myeloma and other plasma cell disorders. In: Hoffman R, et al., eds. Hematology, Basic Principles and Practice. 2nd ed. New York, NY: Churchill Livingstone Inc; 1995:1369-70.

REVIEW ARTICLES
Cohen P., [Cryoglobulinemia related to the hepatitis B and C viruses]. Pathol Biol (Paris). 1999;47:232-36. French.

Dammacco F, et al., Hepatitis C virus infection, mixed cryoglobulinemia, and non-Hodgkin's lymphoma: an emerging picture. Leuk Lymphoma. 1998;31:463-76.

Lunel F, et al., Hepatitis C virus infection and cryoglobulinemia. Forum (Genova).
1998;8:95-103.

JOURNAL ARTICLES
Liu F, et al., Hepatitis C virus but not GB virus C/hepatitis G virus has a role in type II cryoglobulinemia. Arthritis Rheum. 1999;42:1898-901.

Gungor E, et al., Prevalence of hepatitis C virus antibodies and cryoglobulinemia inpatients with leukocystoclastic vasculitis. Dermatology. 1999;198:26-28.

Abu-Shakra M, et al., Cyclophosphamide therapy in a patient with membranoproliferative glomerulonephritis and essental mixed cryoglobulinemia. Clin Rheumatol. 1998;17:395-96.

Cacoub P, et al., Parvovirus B19 infection, hepatitis C virus infection, and mixed cryoglobulinemia. Ann Rheum Dis. 1998;57:422-24.