Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 20-24: Cryoglobulinemia + Key Features Download Section PDF Listen +++ ++ 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 Download Section PDF Listen +++ ++ 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 + Diagnosis Download Section PDF Listen +++ ++ Compatible clinical picture and a positive serum test for cryoglobulins Presence of a disproportionately low C4 level and/or rheumatoid factor can be a diagnostic clues to the presence of cryoglobulinemia + Treatment Download Section PDF Listen +++ ++ Antiviral regimens 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