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

Diagnosis

• 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

Treatment

• 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