09-15-09-Saleem_Bharmal--Hepatitis C Induced Mixed Cryoglobulinemia

09-15-09-Saleem_Bharmal--Hepatitis C Induced Mixed Cryoglobulinemia

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Hepatitis C Induced Mixed Cryoglobulinemia 7/28/09
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Hepatitis C Virus Hepatitis C virus (HCV) chronically infects over 170 million people worldwide Leading indication for liver transplantation in the United States and Europe HCV is a positive-strand RNA virus with a 9.6-kb genome that replicates predominantly in the liver HCV frequently causes extrahepatic manifestations, the most common and severe of which is mixed cryoglobulinemia (MC)
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Mixed Cryoglobulinemia Cryoglobulins are immunoglobulin complex that precipitate in the cold and dissolve on rewarming Rheumatoid Factor: Ig capable of binding to IgG (IgM kappa in HCV MC) Type II or mixed cryoglobulinemia: Cryoglobulin that contains both a polyclonal IgG and a monoclonal IgM rheumatoid factor directed against the IgG. Since the identification of HCV in 1989, it has been recognized as the cause of >90% of MC
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Mixed Cryoglobulinemia Systemic vasculitis affecting small- and medium-sized arteries and veins. Characterized by the deposition of immune complexes containing rheumatoid factor (RF), IgG, HCV RNA, and complement on endothelial surfaces In HCV MC blood tests show elevated serum RF, positive cryoglobulins and low complement (particularly C4)
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Testing for Cryoglobulins Serum preparation must be performed at 37degrees C to prevent premature immune complex precipitation Serum is stored at 4 degrees C for 7 days, inspected daily for a precipitate, and spun in a for calculation of cryocrit A cryocrit >2% is positive (Cryocrit is % of cryoglobulin in serum) The cryocrit is then typed using immunofixation
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MC Clinical Manifestations Initially described in 1966 as a clinical triad of palpable purpura, arthralgia, and weakness accompanied by organ involvement (e.g., nephropathy and neuropathy) and elevated serum RF Now known that this triad is rare, as many MC patients are asymptomatic Primarily affects the small- and medium sized vessels of the skin, kidneys, and peripheral nerves
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Skin Involvement Palpable purpura, primarily of the lower legs, occurs in more than 90% of patients with symptomatic HCV MC Frequently intermittent Often initial manifestation of HCV MC Purpuric lesions may occasionally progress to chronic ulcers and frank gangrene
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Kidney Involvement Usually presents as a type I MPGN Present in approximately 20 percent of patients at the time of diagnosis and
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09-15-09-Saleem_Bharmal--Hepatitis C Induced Mixed Cryoglobulinemia

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