Pathophysiology
Clinical meaning
Cryoglobulins are immunoglobulins that precipitate at temperatures below 37°C and dissolve upon rewarming. Classification: Type I (monoclonal IgM or IgG, associated with lymphoproliferative disorders like Waldenström macroglobulinemia or multiple myeloma -- causes hyperviscosity). Type II (mixed, monoclonal IgM with rheumatoid factor activity against polyclonal IgG -- most common, strongly associated with hepatitis C virus, ~90%). Type III (mixed, polyclonal IgG and IgM -- associated with autoimmune diseases and chronic infections). Types II and III cause small-vessel vasculitis through immune complex deposition, complement activation, and endothelial injury, manifesting as palpable purpura, arthralgias, glomerulonephritis (membranoproliferative pattern), and peripheral neuropathy. The classic Meltzer triad of mixed cryoglobulinemia: purpura, weakness, and arthralgias.