Type II is associated with lymphoproliferative diseases, and both types can occur in patients with rheumatic diseases and chronic infections. Cryoglobulinemia is said to be essential when there is no identifiable underlying disease. Type II and III cryoglobulinemia frequently presents as vasculitis, most commonly with recurrentlower extremity purpura, glomerulonephritis, and peripheral neuropathy. It is now evident that most patients diagnosed with type II or type III mixed essential cryoglobulinemia have the disease as an immune response to chronic hepatitis C infection. Moreover, antviral therapy can remit the disease in some patients.
Treatment depends on the type of cryoglobulin, underlying disease, and severity of symptoms.
Cryoglobulinemia with severe hyperviscosity syndrome requires plasmapheresis and chemotherapy of the underlying malignancy. Some patients with cryoglobulinemia suffer from mild, recurrent crops of lower extremity purpura that require no specific therapy. More extensive vasculitis associated with autoimmune diseases or essential cryoglobulinemia may respond to prednisone, cyclophosphamide, or both. The most effective treatment for cryoglobulinemia associated with hepatitis C has not yet been determined. Brief use of prednisone followed by 6 months of interferon alfa has produced clinical and liver function test improvement, but relapse of liver disease and vasculitis often occurs when interferon alfa is stopped.