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Cryoglobulinemia Treatment & Management

  • Author: Adam M Tritsch, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jun 15, 2016
 

Medical Care

The goal of therapy is to treat underlying conditions, as well as to limit the precipitant cryoglobulin and the resultant inflammatory effects.[43] Thus, hepatitis C virus (HCV) testing is required. HCV antibody or HCV RNA testing may be diagnostic. If HCV test results are negative and clinical suspicion remains high, these tests may be performed on the cryoprecipitate.

Asymptomatic cryoglobulinemia does not require treatment. Some authors recommend intervening as little as possible except when faced with severe deterioration of renal or neurologic function.

Secondary cryoglobulinemia is best managed with treatment of the underlying malignancy or associated disease. Otherwise, cryoglobulinemia is treated simply with suppression of the immune response. A paucity of controlled studies evaluating the relative efficacy of various therapies limits the use of existing data.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used in patients with arthralgia and fatigue.

Immunosuppressive medications (eg, corticosteroid therapy and/or cyclophosphamide or azathioprine) are indicated upon evidence of organ involvement such as vasculitis, renal disease, progressive neurologic findings, or disabling skin manifestations.

Plasmapheresis is indicated for severe or life-threatening complications related to in vivo cryoprecipitation or serum hyperviscosity. Concomitant use of high-dose corticosteroids and cytotoxic agents is recommended for reduction of immunoglobulin production. Some authors recommend using concomitant cytotoxic medications or corticosteroids to reduce a rebound phenomenon that may develop after plasmapheresis.

Pegylated interferon alfa (IFN-alfa) combined with ribavirin has demonstrated efficacy in patients with cryoglobulinemia associated with hepatitis C, and efficacy in patients with chronic myelogenous leukemias and low-grade lymphomas has been reported. The details of therapy and the recommended approach vary based on the clinical setting, and expert opinion should be sought.[44]

Case reports have detailed the remission of hepatitis B–related cryoglobulinemic vasculitis with entecavir therapy.[45]

Uncontrolled studies suggest the anti-CD20 chimeric monoclonal antibody rituximab is effective in controlling disease manifestations such as vasculitis, peripheral neuropathy, arthralgias, low-grade B-cell lymphomas, renal disease, and fever.[46, 47]

Rituximab therapy has been used predominantly in HCV-related mixed cryoglobulinemia refractory to or unsuitable for corticosteroids and antiviral (IFN-alfa) therapy. Rituximab therapy is reportedly well tolerated in this patient population; however, treatment has resulted in increased titers of HCV RNA of undetermined significance.[48]

Rituximab was well tolerated and effective in a randomized controlled trial that compared rituximab with immunosuppressive therapy for HCV-associated cryoglobulinemic vasculitis in 24 patients in whom antiviral therapy had failed to induce remission. These researchers observed no adverse effects of rituximab on HCV plasma viremia or on hepatic transaminase levels.[49]

In a study of long-term rituximab treatment in 31 patients with severe mixed cryoglobulinemia, complete remission of pretreatment active manifestations was observed in all cases of purpuric lesions and non-healing vasculitic ulcers, and in 80% of peripheral neuropathies. Cryoglobulinemic nephropathy improved significantly during follow-up, starting from the second month of rituximab treatment.[50]

In this study, rituximab was administered in a dose of 375 mg/m2, according to a '4 + 2' protocol (days 1, 8, 15, and 22 plus a single dose 1 and 2 months later). This protocol was also followed in nine patients who suffered relapse, after a mean of 31.1 months, again with beneficial effects. With this protocol, the probability of remaining symptom-free for 10 years without any therapy was about 60%, while the probability of living symptom-free 5 years after relapsing was 80%.[50]

In a study of 17 HBV-positive patients with cryoglobulinemic vasculitis, Mazzaro et al reported success using entecavir, adefovir, or lamivudine. After treatment, no disease progression was noted and regression of purpura and a reduction of cryocrit were observed. HBV-DNA became undetectable in all patients.[51]

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Consultations

See the list below:

  • Rheumatologist or clinical immunologist
  • Nephrologist upon evidence of renal disease (ie, hypertension, abnormal findings on urinalysis)
  • Hematologist upon evidence of underlying hematological disease or for plasmapheresis
  • Gastroenterologist or hepatologist for patients with underlying hepatitis
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Contributor Information and Disclosures
Author

Adam M Tritsch, MD Resident Physician, Department of Internal Medicine, Eisenhower Army Medical Center, Fort Gordon, Georgia

Adam M Tritsch, MD is a member of the following medical societies: American College of Physicians

Disclosure: Partner received stocks from Amgen for none.

Coauthor(s)

Colin C Edgerton, MD Clinical Assistant Professor, Department of Medicine, Medical College of Georgia; Clinical Assistant Professor, Department of Medicine, Uniformed Services University

Colin C Edgerton, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Genentech; Pfizer; Questcor.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Interim Chief, Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Acknowledgements

Craig Ainsworth, MD Chief of Medical Residents, Department of Internal Medicine, Eisenhower Army Medical Center

Craig Ainsworth, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Robert John Oglesby, MD Chief of Rheumatology Service, Department of Medicine, Walter Reed Army Medical Center; Associate Professor of Medicine, Uniformed Services University of the Health Sciences

Robert John Oglesby, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and Arthritis Foundation

Disclosure: Nothing to disclose.

Timothy M Straight, MD Instructor, Department of Medicine, Uniformed Services University of the Health Sciences

Disclosure: Nothing to disclose.

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Rash on lower extremities typical of cutaneous small-vessel vasculitis due to cryoglobulinemia secondary to hepatitis C infection.
Renal biopsy sample that shows membranoproliferative glomerulonephritis in a patient with hepatitis C–associated cryoglobulinemia (hematoxylin and eosin; magnified X 200).
 
 
 
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