Essential mixed cryoglobulinemia


Essential mixed cryoglobulinemia is a rare immune-mediated/autoimmune condition that features cryoglobulins, which are abnormal proteins in the blood that clump together at temperatures below 98.6 degrees Fahrenheit. The clumping of these proteins can restrict blood flow to the body’s joints, muscles, and organs, which can cause vasculitis (inflammation of the blood vessels). The body’s smaller blood vessels are more typically affected, but larger blood vessels can also be involved.

Common Symptoms

Joint pain/inflammation, skin lesion, weakness, purpura/orthostatic purpura (purple-colored spots and patches that occur on the skin and in mucus membranes, including the lining of the mouth), petechiae (tiny round brown-purple spots due to bleeding under the skin), ecchymoses (a discoloration of the skin resulting from bleeding underneath, typically caused by bruising), sores, hives, necrosis of the fingers and toes (death of cells or tissues), arthralgia (joint stiffness), mild-to-severe itching, mild-to-severe pain, abdominal pain, muscle weakness, myalgia (muscle aches and pains), abnormal enlargement of the lymph nodes, abnormal enlargement of the liver and/or spleen, as well as dry mouth and dry eyes.

Coexisting Diseases and Conditions

Chronic infection with hepatitis C, peripheral neuropathy, membranoproliferative glomerulonephritis type I, lung disease, autoimmune thyroiditis, hyperthyroidism, thyroid cancer, type 2 diabetes, B-cell lymphomas, hepatocellular carcinoma, Sjogren’s syndrome, rheumatoid arthritis, autoimmune hepatitis (specifically chronic infection with Hepatitis C), systemic lupus erythematosus, Waldenstrom’s macroglobulinemia, multiple myeloma, hemolytic uremic syndrome, antiphospholipid syndrome, polyarteritis nodosa, and Raynaud’s phenomenon.

Risk Factors and Prevalence

Injection drug use, exposure to tainted blood products, and unprotected sexual intercourse are risk factors. Females tend to be affected three times more frequently than males; those who are around age 60 are also more commonly affected.


  1. Article Sources
    1. Cryoglobulinemia. (n.d.). Johns Hopkins Vasculitis Center. Retrieved July 15, 2021, from

    2. Misiani, R., Bellavita, P., Fenili, D., Borelli, G., Marchesi, D., Massazza, M., Vendramin, G., Comotti, B., Tanzi, E., Scudeller, G., & Zanetti, A. (1992). Hepatitis C Virus Infection in Patients with Essential Mixed Cryoglobulinemia. Annals of Internal Medicine, 117(7), 573–577.

    3. Mixed Cryoglobulinemia. (n.d.). NORD (National Organization for Rare Disorders). Retrieved July 15, 2021, from