Treatment of the mixed cryoglobulinemia syndrome
- Fernando C Fervenza, MD, PhD
Fernando C Fervenza, MD, PhD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Mayo Clinic College of Medicine
- Michael D Leise, MD
Michael D Leise, MD
- Assistant Professor of Medicine
- Mayo Clinic College of Medicine
- Dario Roccatello, MD
Dario Roccatello, MD
- Professor of Nephrology and Clinical Pathology
- University of Turin Medical School
- Robert A Kyle, MD
Robert A Kyle, MD
- Section Editor — Plasma Cell Disorders
- Professor of Medicine
- Mayo Medical School
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Mark H Wener, MD
Mark H Wener, MD
- Section Editor — Diagnostic Issues in Rheumatology
- Professor of Laboratory Medicine and Medicine/Rheumatology
- University of Washington
The mixed cryoglobulinemia syndrome is most often induced by hepatitis C virus (HCV) infection. It can also be associated with autoimmune or lymphoproliferative disorders or, rarely, can be idiopathic. Typically, it follows a chronic, smoldering course. Infrequently, mixed cryoglobulinemia may present with a rapidly progressive or even life-threatening course. (See "Overview of cryoglobulins and cryoglobulinemia" and "Clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome (essential mixed cryoglobulinemia)".)
The main indication for immunosuppressive therapy is progressive systemic disease affecting the kidneys, nervous system, gastrointestinal tract, skin, or digits. The prognosis is variable [1-6].
The treatment of patients with the mixed cryoglobulinemia syndrome will be reviewed here. An overview of cryoglobulinemia and a discussion of the clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome are provided elsewhere. (See "Overview of cryoglobulins and cryoglobulinemia" and "Clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome (essential mixed cryoglobulinemia)".)
GENERAL APPROACH TO THERAPY
Prior to the discovery of the association with hepatitis C virus (HCV), both prednisone and cytotoxic drugs (such as cyclophosphamide and chlorambucil) were often used in patients with mixed cryoglobulinemia. However, except in those patients with a rapidly progressive course, there was no clear evidence that these modalities were beneficial [3,4]. Rituximab has been gradually replacing cytotoxic drug therapy in such patients.
Rituximab is significantly more expensive than cyclophosphamide, and there are no data directly comparing rituximab with cyclophosphamide in these patients. Thus, cyclophosphamide should still be considered a therapeutic option in patients with mixed cryoglobulinemia, especially in life-threatening situations.
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- GENERAL APPROACH TO THERAPY
- IMMUNOSUPPRESSIVE THERAPY FOR SEVERE MIXED CRYOGLOBULINEMIA
- Patient selection
- Choice of immunosuppressive therapy
- - Preference for rituximab
- - Rituximab regimen
- - Preference for a rapid glucocorticoid taper
- - Glucocorticoid regimen
- Role of plasma exchange
- - Plasma exchange prescription
- Role of cyclophosphamide
- Antimicrobial prophylaxis
- TREAT THE UNDERLYING DISORDER IN ALL PATIENTS
- Therapy for HCV infection
- - General approach to HCV therapy
- - Initiation of HCV therapy
- - Drugs and dosing in HCV therapy
- Evidence for efficacy
- - Duration of therapy
- - Monitoring of patients on antiviral therapy
- Anti-HBV therapy
- Autoimmune disorders
- Idiopathic disease
- END-STAGE RENAL DISEASE
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS