of asymptomatic individuals with cryoglobulinemia offers a means for finding people with serious but potentially treatable and even curable diseases. individuals who show no evidence of a disease underlying their cryoglobulinemia and who remain asymptomatic should be followed closely for any changes that may indicate development of cryoglobulinemic disease. severely symptomatic cryoglobulinemic disease people affected by the severest, often life-threatening, complications of cryoglobulinemic disease require urgent plasmapharesis and/or plasma exchange in order to rapidly reduce the circulating levels of their cryoglobulins. complications commonly requiring this intervention include: hyperviscosity disease with severe symptoms of neurological (e.g., stroke, mental impairment, and myelitis) and/or cardiovascular (e.g., congestive heart failure, myocardial infarction) disturbances; vasculitis-driven intestinal ischemia, intestinal perforation, cholecystitis, or pancreatitis, causing acute abdominal pain, general malaise, fever, and/or bloody bowel movements; vasculitis-driven pulmonary disturbances (e.g., coughing up blood, acute respiratory failure, x-ray evidence of diffuse pulmonary infiltrates caused by diffuse alveolar hemorrhage); and severe kidney dysfunction due to intravascular deposition of immunoglobulins or vasculitis. along with this urgent treatment, severely symptomatic patients are commonly started on therapy to treat any underlying disease; this treatment is often supplemented with anti-inflammatory drugs such as corticosteroids (e.g., dexamethasone) and/or immunosuppressive drugs. cases where no underlying disease is known are also often treated with the latter corticosteroid and immunosuppressive medications. type i cryoglobulinemic disease treatment of type i disease is generally directed towards treating the underlying pre-malignant or malignant disorder (see plasma cell dyscrasia, waldenström's macroglobulinemia, and chronic lymphocytic leukemia). this involves appropriate chemotherapy regimens which may include bortezomib (promotes cell death by apoptosis in cells accumulating immunoglobulins) in patients with monoclonal immunoglobulin-induced kidney failure and rituximab (antibody directed against cd20 surface antigen-bearing lymphocytes) in patients with waldenstroms macroglobulonemia). type ii and iii cryoglobulinemic disease treatment of mixed cryoglobulinemic disease is, similar to type i disease, directed toward treating any underlying disorder. this includes malignant (particularly waldenström's macroglobulinemia in type ii disease), infectious, or autoimmune diseases in type ii and iii disease. recently, evidence of hepatitis c infection has been reported in the majority of mixed disease cases with rates being 70-90% in areas with high incidences of hepatitis c. the most effective therapy for hepatitis c-associated cryoglobulinemic disease consists of a combination of anti-viral drugs, pegylated infα and ribavirin; depletion of b cells using rituximab in combination with antiviral therapy or used alone in patients refractory to antiviral therapy has also proven successful in treating the hepatitis c-associated disease. data on the treatment of infectious causes other than hepatitis c for the mixed disease are limited. a current recommendation treats the underlying disease with appropriate antiviral, anti-bacterial, or anti-fungal agents, if available; in cases refractory to an appropriate drug, the addition of immunosuppressive drugs to the therapeutic regimen may improve results. mixed cryoglobulinemic disease associated with autoimmune disorders is treated with immunosuppressive drugs: combination of a corticosteroid with either cyclophosphamide, azathioprine, or mycophenolate or combination of a corticosteroid with rituximab have been used successfully to treated mixed disease associated with autoimmune disorders.