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Cryoglobulins are immunoglobulins that precipitate at low temperatures and redissolve upon rewarming. Cryoglobulinemia refers to the presence of circulating cryoglobulins in serum, and generally leads to a systemic inflammatory syndrome characterized by fatigue, arthralgia, purpura, neuropathy and glomerulonephritis. The disease mainly involves small to medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes. Cryoglobulinemia is classified into three types (I, II and III) on the basis of immunoglobulin composition. Predisposing conditions include lymphoproliferative disease, collagen disease and hepatitis C virus (HCV) infection. The diagnosis of cryoglobulinemic syndrome is predominantly based on the laboratory demonstration of serum cryoglobulins. Treatment is often directed towards the underlying disease state. For patients with chronic HCV infection, anti-viral therapy is indicated. Intense immunosuppressive or immunomodulatory therapy, including steroids, plasmapheresis and cytotoxic agents, is reserved for organ-threatening or recalcitrant disease. In this review, we discuss the clinical characteristics of the three types of cryoglobulinemia.