Cryoglobulinemia

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)

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 and/or rheumatoid factor can be a diagnostic clues to the presence of cryoglobulinemia

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