Cryoglobulinemia in Hematology

Cryoglobulinemia is classified into three types: type one with monoclonal immunoglobulin in plasma cell or lymphoplasmacytic disease, type two mixed with monoclonal IgM rheumatoid factor against polyclonal IgG often hepatitis C related, and type three polyclonal often in autoimmune disease. Cryoglobulins precipitate below thirty seven degrees and dissolve on warming causing immune complex deposition vasculitis.

Manifestations include lower limb palpable purpura, arthralgias of small joints, peripheral sensory motor neuropathy, membranoproliferative glomerulonephritis with hematuria and proteinuria, hepatic involvement, and rare central nervous system or pulmonary disease. Diagnostic workup needs warm transport and centrifugation of serum sample to detect cryoglobulin precipitate at four degrees and characterize subtype by immunofixation.

Treatment addresses the underlying cause with direct acting antivirals for hepatitis C achieving sustained virologic response and frequent vasculitis remission, rituximab for refractory mixed cryoglobulinemia, plasmapheresis for severe organ threatening disease, and corticosteroids for acute flares. Type one cryoglobulinemia may need plasma cell directed therapy with bortezomib daratumumab or transplant when associated with multiple myeloma.