Ann IM 2002;137:571; Nejm 1997;337:1512

Cause:98% have hepatitis C (Hepatitis C) as the cause (Ann IM 1992;117:573) if no clear other cause like SBE, HIV in 23% (Ann IM 1999;130:226), or leprosy. Both types II and III are associated w hepatitis B and C, Sjögren's, and Waldenström's (Nejm 1992;327:1490)

Pathophys:Small-vessel vasculitis due to circulating immune complexes of IgG (the antigen) and IgM (the rheumatoid factor autoantibody), hence "mixed cryoglobulinemia". Type II IgM is polyclonal; type III is monoclonal and 10% of the time can evolve to B-cell lymphoma. Chronic viral infection may stimulate, or select a genetic translocation that precipitates the lymphoma.

Sx:Arthralgias

Si:Purpura, neuropathic weakness (Ann IM 1977;87:287)

Membranoproliferative glomerulonephritis, and porphyria cutanea tarda (Ann IM 1995;123:615, 625; 1992;117:573; Nejm 1993;328:465); debatably Sjögren's/sicca syndrome, polyarteritis; B-cell lymphomas

Lab:

• Type I: monoclonal IgG, usually assoc w malignancy
• Type II: mixed, polyclonal IgG and IgM rheumatoid factor
• Type III: mixed polyclonal IgG and monoclonal IgM rheumatoid factor
• Complement: C₄ very low but normal C₃

Rx:NSAIDs, steroids, cyclophosphamide; if systemic disease, possibly interferon-2a helps, esp in hep C types (Nejm 1994;330:751)