Heat insoluble cryoglobulin associated with gangrene in multiple myeloma

Cryoglobulins are immunoglobulins that have tendency to precipitate in temperatures below 37 degrees C and dissolve with rewarming. Monoclonal cryoglobulins are usually associated with a distinct hematological disorder and often are asymptomatic. Heat insoluble cryoglobulin has been described with Sjogren's syndrome and glomerulonephritis but, not with multiple myeloma. Severe sensitivity to cold occurs with high thermal insolubility of the cryoprotein, with dramatic symptoms when exposed to minimal lowering of the temperature. We report a case of a 49 year old man with multiple myeloma and an unusual type I cryoglobulin that caused occlusive gangrene. The cryoglobulin appeared as a milky white precipitate that was resistant to re-suspension and did not dissolve at 37 degrees C. Immunoelectrophoresis of the cryoglobulin, which dissolved at 56 degrees C, showed it to be composed of a monoclonal IgG kappa protein (3.5 g/dl). Unlike most high thermal insoluble cryoglobulin, cold associated symptoms were not seen. In addition to steroids, plasmapheresis was initiated thrice a week with albumin fluid replacement. Plasmapheresis caused a marked decline in cryocrit levels from 21% to less than 0.5% in 9 days after 4 procedures with resolution of the gangrene of the feet and after 6 treatments, vasculitic symptoms improved dramatically. The cryoglobulin test was negative 2 weeks after initiation of treatment. The patient was treated for the myeloma and there was no recurrence of occlusive symptoms. Proper laboratory procedure and careful examination and handling of cryoglobulinemic samples facilitate detection of unusual cryoglobulins. This is a unique report of multiple myeloma with gangrene of lower extremities that has a heat insoluble cryoglobulin.