HCV-negative mixed cryoglobulinemia: Facts and fancies

Approximately 10% of the population with mixed cryoglobulinemia (MC) have no evidence of HCV infection. In these patients, a wide number of infectious agents have been associated with cryoglobulinemia, although only HBV and HIV have a well- documented role in causing the disorder. Several connective tissue (mainly systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis) and lymphoproliferative (in most cases B-cell non-Hodgkin lymphoma) diseases have also been shown to play an etiologic role in some cases of HCV-negative MC. Fewer than 5% of cryoglobulinemic patients show no identifiable underlying diseases and they are therefore considered as having essential MC. In HCV-negative MC, an occult HCV infection should also be taken into account. The clinical manifestations, cryoglobulin levels, and survival rates in MC patients with and without HCV seem not to differ significantly, although the data are conflicting. In symptomatic MC, therapy should aim at improvement or resolution of clinical manifestations, as elimination of the causative factor is impossible in most cases.