Cryofibrinogenemia triggered by a monoclonal paraprotein successfully treated with cyclophosphamide

Cryofibrinogenemia is a rare clinical finding with a yet unknown physiopathogenic mechanism. We describe the case of a woman with cold-induced extensive necrotic lesions that responded poorly to initial corticosteroid and anticoagulant therapies. Serum cryoglobulin determinations were persistently negative. After several years of evolution, she developed severe cold-related skin lesions that required left-leg amputation. Further analysis disclosed the presence of cryofibrinogen and an apparently insignificant serum monoclonal immunoglobulin Gκ peak. We additionally demonstrate that the cold precipitation of fibrinogen was directly related to the monoclonal paraprotein presence. The lesions responded dramatically to a B cell-targeted therapy with intravenous cyclophosphamide and dexamethasone.