HCV-Associated Cryoglobulinemia

HCV-Associated Cryoglobulinemia - HCVAssociated...

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HCV‐Associated Cryoglobulinemia Nicola Sumorok September 13, 2011
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Background Cryoglobulinemia is characterized by the clonal expansion of rheumatoid factor expressing B cells in the liver, lymph nodes, and peripheral blood Cryoglobulins are cold insoluble immune complexes In HCV associated cryoglobulinemia, containing rheumatoid factor, polyclonal IgG, and HCV RNA Precipitate and deposit on vascular endothelium vasculitis in organs such as the kidneys, skin, and peripheral nerves Subset of patients develop low grade lymphoma Comprised of B cells that are immunophenotypically similar to the expanded B cell seen in CG Unclear how the B cells become dysregulated
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Classification: Brouet et al Type I: Monoclonal Ig only; usually found in hematologic disorders (multiple myeloma, Waldenstroms, MGUS) Type II: Polyclonal IgG with monoclonal RF activity Type III: Polyclonal IgG and polyclonal RF HCV primarily associated with Type II and to a lesser extent, Type III Also seen in other infections (HIV, HBV) and immune disorders (SLE, sjogren syndrome, systemic sclerosis) All states of chronic inflammation in the setting of high antigenic load Suggests antigen driven B cell dysregulation is a prerequisite for the development of MC
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Prevalence Clinically significant: 1:100,000 Circulating mixed cryoglobulins found in 40 60% of HCV infected patients Cryoglobulinemia vasculitis in 5 10% of cases All HCV genotypes have been found in HCV MC, with no clear association with a particular genotype Detectable levels of circulating CG in significant portion of pts with chronic infections and/or inflammation: HIV 15 20% Connective tissue disease 15 25% HCV/HIV coninfection 65%
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Clinical Manifestations “Meltzer’s Triad”: palpable purpura, arthralgia, and myalgia Palpable purpura 70 90% usually transient, lower extremities Renal involvement–20 35% Type I membranoproliferative glomerulonephritis (>70 80%) Arthralgia 40 80% Neuropathy – 55% Variable: sensimotor neuropathy, painful paresthesias, mononeuritis (foot or wrist drop)
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Renal Manifestations: Type I MPGN Endocapillary mesangial cell proliferation (A) Glomerular infitration by activated macrophages Splitting of the GBM resulting in double contours, “tram tracking” Immunofluroescence exhibits subendothelial deposits of IgM, IgG, and complement (B, C) EM shows subendothelial immune deposits (D)
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HCV‐related Lymphoproliferation Association of HCV with other B cell lymphoproliferative
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HCV-Associated Cryoglobulinemia - HCVAssociated...

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