Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!

For further information, see CMDT Part 20-24: Cryoglobulinemia

Key Features

  • Type I cryoglobulins (monoclonal proteins that lack rheumatoid factor activity)

    • More commonly seen in lymphoproliferative disease

    • Usually cause hyperviscosity syndromes rather than vasculitis

  • Type II (monoclonal antibody with rheumatoid factor activity) and type III (polyclonal antibody with rheumatoid factor activity) cryoglobulins

    • Cause vasculitis

    • Associated with hepatitis C and connective tissue diseases (eg, Sjögren syndrome)

Clinical Findings

  • Palpable purpura (predominantly on the lower extremities)

  • Peripheral neuropathy

  • Proliferative glomerulonephritis can develop and can manifest as rapidly progressive glomerulonephritis

  • Abnormal liver biochemical tests

  • Abdominal pain

  • Digital gangrene

  • Pulmonary disease


  • Compatible clinical picture and a positive serum test for cryoglobulins

  • Presence of a disproportionately low C4 level can be a diagnostic clue to the presence of cryoglobulinemia


  • Antiviral regimens that do not include interferon are first-line therapy for hepatitis C–associated cryoglobulinemic vasculitis that is neither life- nor organ-threatening

  • Patients with severe cryoglobulinemic vasculitis (eg, extensive digital gangrene, extensive neuropathy, and rapidly progressive glomerulonephritis) and hepatitis C should receive immunosuppressive therapy with corticosteroids and either rituximab or cyclophosphamide as well as interferon-free antiviral therapy

  • Plasma exchange may provide additional benefit in selected cases

  • Relapse of vasculitis with cryoglobulinemia following clearing of hepatitis C infection has been reported in a small number of patients

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.