type 1 (monoclonal) cryoglobulinemia

Etiology

• multiple myeloma
• Waldenstrom's macroglobulinemia
• MGUS
• B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia
• Sjogren's syndrome
• not strongly associated with hepatitis C

Pathology

• aggregates of a single monoclonal immunoglobulin
• type-1 cryoglobulins generally do NOT activate complement
• symptoms are generally related to hyperviscosity
• ischemic ulceration from occlusion of arterioles & venules by precipitated immune complexes

Clinical manifestations

• patients generally asymptomatic
• headaches
• visual disturbances
• nosebleeds
• Raynaud's phenomenon 40%
• skin ulcerations
• vasculitis is uncommon (less common than types 2 & 3)
  • lower extremity palpable purpura
  • peripheral neuropathy, mononeuritis multiplex
  • immune complex glomerulonephritis
• acrocyanosis 15%
• digital ischemia, distal necrosis 40%
• livedo reticularis

Laboratory

• cryoglobulins in serum/plasma
  • trace amounts of cryoglobulins may be found in normal individuals
• serum protein electrophoresis & immunofixation electrophoresis
  • high concentrations of monoclonal IgM - 1-5 g/dL
  • IgG or IgA possible as well
• rheumatoid factor (RF) is negative
• serum complement C3 in serum is generally low
• serum complement C4 in serum is generally low

Management

• therapy directed at underlying disease
• hyperviscosity responds to plasmapheresis

More general terms

• cryoglobulinemia (cryoglobulinemic vasculitis)

Additional terms

• cryoglobulin