Cryoglobulinemia refers to the serum presence of cryoglobulins, which are immunoglobulins that reversibly precipitate and form a gel when the temperature is <37 degree Celsius and re-dissolve if the temperature rises to >37degree Celsius. The disease mainly involves small to medium sized blood vessels and mainly causes vasculitis due to cryoglobulin containing immune complexes. The cryoglobulins maybe composed only of a monoclonal Ig (type 1), of a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains( type 2) or only of polyclonal Ig (type 3).The prevalence of cryoglobulinemia remains unknown.5.About 10-30% of the cases of mixed cryoglobulinemia are not related to HCV. The many causes include other infections, autoimmune diseases and b-cell lymphoid malignancies. The development of vasculitis with cutaneous and peripheral nervous system involvement should prompt an evaluation for lymphoma.For most patients cryoglobulinemia disease is diagnosed by the presence of typical organ involvement (mainly skin, kidney or peripheral nerve) and circulating cryoglobulins.The directed therapy for different types of cryoglobulinemia is based on expert opinion due to disease rarity.Cryoglobulinemic vasculitis unrelated to HCV: Infection should be managed with appropriate anti-infectious agents. Rituximab combined with glucocorticoid therapy is the first line treatment in the event of the autoimmune diseases.Conventional therapy is of high-dose corticosteroids, intravenous cyclophosphamide, rituximab, bortezomib, and plasma exchange. Prognosis in patients with grave manifestations is often poor. Plasma exchange therapy may deserve consideration in patients at the severe end of clinical spectrum.
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