Type 1 Cryoglobulinemia Response to Thalidomide and Lenalidomide

Among the varying etiologies of cryoglobulinemia (Cg), type I Cg represents the rarest form and is most often associated with lymphoproliferative disorders such as non-Hodgkin lymphoma, Waldenstrom macroglobulinemia, or multiple myeloma. Clinical manifestations are generally those of small-vessel vasculitis and/or hyperviscosity. The treatment of patients with type 1 disease generally consists of chemotherapy directed at the lymphoproliferative disorder or varying levels of empiric immunosuppression including apheresis, glucocorticoids, and cytotoxic agents. In recent years, anecdotes of biologic and/or immunomodulatory therapy with rituximab and thalidomide have been reported.(1-4) Occasionally. patients present with severe type 1 cryoglobulinemic disease in the absence of a defined malignancy but with monoclonal gammopathy of otherwise undetermined significance (MGUS); the treatment of such patients is controversial.(5,6) We recently treated such a patient with traditional immunosuppressives and rituximab but found him ultimately to respond only to thalidomide and its congener, lenalidomide.