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.

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.

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.

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.

• Rheumatoid factor-producing CD21low anergic clonal B-cells in essential mixed cryoglobulinaemia: a model for autoantigen-driven pathogenesis of infectious and non-infectious cryoglobulinaemias (2020)
• Risk factors for relapse in non-infectious cryoglobulinemic vasculitis, including type I cryoglobulinemia: a systematic review (2023)
• COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity (2023)
• Transforming mutations in the development of pathogenic B cell clones and autoantibodies (2022)