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For further information, see CMDT Part 22-15: Nephritic Spectrum Glomerular Diseases

Key Features

  • Essential (mixed) cryoglobulinemia is a vasculitis caused by cold-precipitable immunoglobulins (cryoglobulins)

  • Causes

    • Hepatitis C infection (usual)

      • Clonal expansion of B lymphocytes produces IgM rheumatoid factor

      • Immune complexes form from rheumatoid factor, hepatitis C viral antigen, and polyclonal anti-hepatitis C viral IgG

    • Other overt or occult infections

    • Viral, bacterial, and fungal infections

    • Some autoimmune diseases and lymphoproliferative disorders

Clinical Findings

  • Purpuric and necrotizing skin lesions in dependent areas

  • Arthralgias

  • Fever

  • Hepatosplenomegaly


  • Serum complement levels are low

  • Rheumatoid factor often elevated

  • Kidney biopsy: crescent formation, glomerular capillary thrombi, membranoproliferative glomerulonephritis (MPGN)


  • Aggressive targeting of the causative infection

  • Pulse corticosteroids, plasma exchange, rituximab, and cytotoxic agents have been used when

    • There is little risk of exacerbating the underlying infection

    • No infection is present

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