The introduction of newer technology in the past few years, especially the use of second-generation enzyme-linked immunosorbent assays, recombinant immunoblot assays, reverse transcriptase, and DNA amplification, have clearly defined the role of hepatitis C virus as the most important etiologic factor in the development of mixed cryoglobulinemia. This has led to a better understanding of the pathogenic mechanisms involved in disease expression, particularly vasculitis, and also has provided a rationale for the use of interferon alfa and other antiviral drugs in the therapy of these disorders. The clinical manifestations of the syndrome also have been well characterized, as well as some of the risk factors. There also has been an improvement in our understanding of the pathogenic mechanisms involved in multiple myeloma and related monoclonal gammopathies, as well as several attempts to improve early recognition of bone disease with magnetic resonance imaging. The susceptibility gene for familial Mediterranean fever has been better characterized, as have risk factors for colchicine toxicity. The role of cytokines has been better delineated for both monoclonal gammopathies and POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome.
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