Treatment of essential mixed cryoglobulinemia

INTRODUCTION

Essential mixed cryoglobulinemia, also called type II cryoglobulinemia, is most often induced by hepatitis C virus (HCV) infection and follows a chronic, smoldering course. (See "Overview of cryoglobulins and cryoglobulinemia" and "Clinical manifestations and diagnosis of essential mixed cryoglobulinemia".)

The main indication for active therapy is progressive systemic disease affecting the small blood vessels, kidneys, liver, or peripheral nerves. The prognosis of the renal disease, for example, is variable. Approximately one-third of patients undergo partial or complete remission, while most of the remaining patients have a slowly progressive course that may be complicated by periodic acute exacerbations [1-4].

GENERAL APPROACH TO THERAPY

Prior to the recent discovery of the association with HCV, both prednisone and cytotoxic drugs (such as cyclophosphamide and chlorambucil) were often used as maintenance therapy in patients with slowly progressive disease, although there was no clear evidence that these modalities were beneficial [2,3,5]. An exception to this general rule occurs in patients with a treatable underlying disease. As an example, chemotherapy (usually with chlorambucil) may lead to improvement in renal function and at least partial resolution of proteinuria in patients with cryoglobulinemia due to chronic lymphocytic leukemia [5].

Plasmapheresis and immunosuppression — Aggressive therapy in idiopathic mixed cryoglobulinemia is primarily reserved for patients with acute severe disease, as manifested by progressive renal failure, distal necroses requiring amputation, or advanced neuropathy.

In this setting, plasmapheresis (to remove the circulation cryoglobulins) has been used in conjunction with glucocorticoids (1000 mg of intravenous methylprednisolone daily times three, followed by conventional oral prednisone) and cyclophosphamide to prevent new antibody formation (graph 1) [2,3,6,7]. The height of the cryocrit does not correlate with clinical severity, nor with response to therapy, thus the decision to initiate this aggressive therapy is typically based on the severity of the disease manifestations [8].