Cryoglobulinemia Medication

  • Author: Adam M Tritsch, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 18, 2012
 

Medication Summary

The overall aim of therapy is treatment of any underlying condition and general suppression of the immune response. Mild anti-inflammatory medications (eg, NSAIDs) are effective in mild cases, and corticosteroid therapy is reserved for the more severe or refractory cases. Patients who require potent immunosuppression or other more aggressive therapies for severe disease should be treated by a specialist. Cyclophosphamide may be used as a steroid-sparing agent or administered concomitantly in severe cases of vasculitis, particularly in patients with renal disease. Azathioprine is commonly used as a steroid-sparing agent, and chlorambucil has also been used for severe vasculitis.

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Nonsteroidal anti-inflammatory drugs

Class Summary

NSAIDs such as ibuprofen, naproxen, and indomethacin have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. NSAIDs may have additional mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions. NSAIDs are used to reduce the resultant inflammatory response of cryoglobulin precipitation.

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Ibuprofen (Advil, Motrin, Excedrin IB, Ibuprin)

 

NSAIDs are the DOC in patients with mild symptoms of arthralgia or fatigue. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

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Corticosteroids

Class Summary

These medications are used to reduce the resultant immune response from cryoglobulin precipitation, particularly in patients with more severe symptoms or some evidence of organ damage.

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Prednisone (Sterapred)

 

DOC in patients with evidence of acute vasculitis.

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Immunosuppressive agents

Class Summary

These are commonly used as steroid-sparing agents.

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Cyclophosphamide (Cytoxan, Neosar)

 

Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, interfering with growth of normal and neoplastic cells.

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Azathioprine (Imuran)

 

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

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Chlorambucil (Leukeran)

 

Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.

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Interferons

Class Summary

These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. IFN-alfa is generally administered subcutaneously.

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Interferon alfa-2b (Intron A)

 

Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles. Has antiviral activity in HCV infection.

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Peginterferon alfa-2a (Pegasys)

 

Used in combination with ribavirin to treat patient with chronic HCV infection who have compensated liver disease and have not received IFN-alfa previously. Consists of interferon alfa-2a attached to a 40-kD branched PEG molecule. Predominantly metabolized by the liver.

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Peginterferon alfa 2b (PEG-Intron)

 

Escherichia coli recombinant product. Used to treat chronic HCV infection in patients not previously treated with INF-alfa who have compensated liver disease. Exerts cellular activities by binding to specific membrane receptors on cell surface, which, in turn, may suppress cell proliferation and may enhance phagocytic activity of macrophages. May also increase cytotoxicity of lymphocytes for target cells and inhibit virus replication in virus-infected cells.

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Antiviral agents

Class Summary

Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit herpes simplex virus (HSV) polymerase with 30-50 times the potency of human alpha-DNA polymerase.

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Ribavirin (Virazole)

 

Antiviral nucleoside analogs. Chemical name is 1-beta-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. Given alone, has little effect on the course of HCV infection. When used with IFN, significantly augments rate of sustained virologic response.

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Antiviral Agent, Oral

Class Summary

This agent inhibits the viral reverse transcriptase enzyme, which limits viral replication.

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Entecavir (Baraclude)

 

Guanosine nucleoside analogue with activity against HBV polymerase. Competes with natural substrate deoxyguanosine triphosphate to inhibit HBV polymerase activity (ie, reverse transcriptase). Less effective for lamivudine-refractory HBV infection. Indicated for treatment of chronic hepatitis B infection. Available as tab and oral solution (0.05 mg/mL; 0.5 mg = 10 mL).

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Antineoplastic agents

Class Summary

These agents inhibit cell growth and proliferation.

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Rituximab (Rituxan)

 

Genetically engineered human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.

Immunomodulates response against malignant cells.

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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: Amgen Stocks None

Coauthor(s)

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.

Colin C Edgerton, MD  Clinical Assistant Professor, Department of Medicine, Medical College of Georgia; Chief of Rheumatology Service, Eisenhower Army Medical Center

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

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.

Specialty Editor Board

Kristine M Lohr, MD, MS  Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and 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 and American College of Rheumatology

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor Timothy M Straight, MD, to the development and writing of this article.

References

  1. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet. Aug 23 2011;[Medline].

  2. Trendelenburg M, Schifferli JA. Cryoglobulins are not essential. Ann Rheum Dis. Jan 1998;57(1):3-5. [Medline].

  3. Uki J, Young CA, Suzuki T. A 22S cryomacroglobulin with antibody-like activity. I. Physico-chemical characterization and modification of its cryoproperties. Immunochemistry. Nov 1974;11(11):729-40. [Medline].

  4. Wang AC, Wells JV, Fudenberg HH. Chemical analyses of cryoglobulins. Immunochemistry. Jul 1974;11(7):341-5. [Medline].

  5. Pastore Y, Lajaunias F, Kuroki A, Moll T, Kikuchi S, Izui S. An experimental model of cryoglobulin-associated vasculitis in mice. Springer Semin Immunopathol. 2001;23(3):315-29. [Medline].

  6. Saulk PH, Clem W. Studies on the cryoprecipitation of a human IGG3 cryoglobulin: the effects of temperature-induced comformational changes on the primary interaction. Immunochemistry. Jan 1975;12(1):29-37. [Medline].

  7. Kikuchi S, Pastore Y, Fossati-Jimack L, Kuroki A, Yoshida H, Fulpius T, et al. A transgenic mouse model of autoimmune glomerulonephritis and necrotizing arteritis associated with cryoglobulinemia. J Immunol. Oct 15 2002;169(8):4644-50. [Medline].

  8. Abel G, Zhang QX, Agnello V. Hepatitis C virus infection in type II mixed cryoglobulinemia. Arthritis Rheum. Oct 1993;36(10):1341-9. [Medline].

  9. Magalini AR, Facchetti F, Salvi L, Fontana L, Puoti M, Scarpa A. Clonality of B-cells in portal lymphoid infiltrates of HCV-infected livers. J Pathol. May 1998;185(1):86-90. [Medline].

  10. Sansonno D, Dammacco F. Hepatitis C virus, cryoglobulinaemia, and vasculitis: immune complex relations. Lancet Infect Dis. Apr 2005;5(4):227-36. [Medline].

  11. De Re V, De Vita S, Sansonno D, Gasparotto D, Simula MP, Tucci FA. Type II mixed cryoglobulinaemia as an oligo rather than a mono B-cell disorder: evidence from GeneScan and MALDI-TOF analyses. Rheumatology (Oxford). Jun 2006;45(6):685-93. [Medline].

  12. Sansonno D, Gesualdo L, Manno C, Schena FP, Dammacco F. Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus-infected patients with cryoglobulinemic membranoproliferative glomerulonephritis. Hepatology. May 1997;25(5):1237-44. [Medline].

  13. Sansonno D, Cornacchiulo V, Iacobelli AR, Di Stefano R, Lospalluti M, Dammacco F. Localization of hepatitis C virus antigens in liver and skin tissues of chronic hepatitis C virus-infected patients with mixed cryoglobulinemia. Hepatology. Feb 1995;21(2):305-12. [Medline].

  14. Karlsberg PL, Lee WM, Casey DL, Cockerell CJ, Cruz PD Jr. Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of hepatitis C virus-induced mixed cryoglobulinemia. Arch Dermatol. Oct 1995;131(10):1119-23. [Medline].

  15. Gorevic PD, Kassab HJ, Levo Y, Kohn R, Meltzer M, Prose P, et al. Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients. Am J Med. Aug 1980;69(2):287-308. [Medline].

  16. Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M. Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med. Nov 1974;57(5):775-88. [Medline].

  17. Beddhu S, Bastacky S, Johnson JP. The clinical and morphologic spectrum of renal cryoglobulinemia. Medicine (Baltimore). Sep 2002;81(5):398-409. [Medline].

  18. Bryce AH, Kyle RA, Dispenzieri A, Gertz MA. Natural history and therapy of 66 patients with mixed cryoglobulinemia. Am J Hematol. Jul 2006;81(7):511-8. [Medline].

  19. Invernizzi F, Pioltelli P, Cattaneo R, Gavazzeni V, Borzini P, Monti G, et al. A long-term follow-up study in essential cryoglobulinemia. Acta Haematol. 1979;61(2):93-9. [Medline].

  20. La Civita L, Zignego AL, Monti M, Longombardo G, Pasero G, Ferri C. Mixed cryoglobulinemia as a possible preneoplastic disorder. Arthritis Rheum. Dec 1995;38(12):1859-60. [Medline].

  21. Saadoun D, Sellam J, Ghillani-Dalbin P, Crecel R, Piette JC, Cacoub P. Increased risks of lymphoma and death among patients with non-hepatitis C virus-related mixed cryoglobulinemia. Arch Intern Med. Oct 23 2006;166(19):2101-8. [Medline].

  22. Monti G, Galli M, Invernizzi F, Pioltelli P, Saccardo F, Monteverde A, et al. Cryoglobulinaemias: a multi-centre study of the early clinical and laboratory manifestations of primary and secondary disease. GISC. Italian Group for the Study of Cryoglobulinaemias. QJM. Feb 1995;88(2):115-26. [Medline].

  23. Cohen SJ, Pittelkow MR, Su WP. Cutaneous manifestations of cryoglobulinemia: clinical and histopathologic study of seventy-two patients. J Am Acad Dermatol. Jul 1991;25(1 Pt 1):21-7. [Medline].

  24. Rossi D, Mansouri M, Baldovino S, Gennaro M, Naretto C, Alpa M, et al. Nail fold videocapillaroscopy in mixed cryoglobulinaemia. Nephrol Dial Transplant. Sep 2004;19(9):2245-9. [Medline].

  25. Ramos-Casals M, Trejo O, García-Carrasco M, Cervera R, Font J. Mixed cryoglobulinemia: new concepts. Lupus. 2000;9(2):83-91. [Medline].

  26. Weinberger A, Berliner S, Pinkhas J. Articular manifestations of essential cryoglobulinemia. Semin Arthritis Rheum. Feb 1981;10(3):224-9. [Medline].

  27. Levo Y, Gorevic PD, Kassab HJ, Zucker-Franklin D, Franklin EC. Association between hepatitis B virus and essential mixed cryoglobulinemia. N Engl J Med. Jun 30 1977;296(26):1501-4. [Medline].

  28. Tarantino A, Campise M, Banfi G, Confalonieri R, Bucci A, Montoli A, et al. Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis. Kidney Int. Feb 1995;47(2):618-23. [Medline].

  29. Bombardieri S, Paoletti P, Ferri C, Di Munno O, Fornal E, Giuntini C. Lung involvement in essential mixed cryoglobulinemia. Am J Med. May 1979;66(5):748-56. [Medline].

  30. Viegi G, Fornai E, Ferri C, Di Munno O, Begliomini E, Vitali C, et al. Lung function in essential mixed cryoglobulinemia: a short-term follow-up. Clin Rheumatol. Sep 1989;8(3):331-8. [Medline].

  31. Bertorelli G, Pesci A, Manganelli P, Schettino G, Olivieri D. Subclinical pulmonary involvement in essential mixed cryoglobulinemia assessed by bronchoalveolar lavage. Chest. Nov 1991;100(5):1478-9. [Medline].

  32. Girard N, Vasiljevic A, Cottin V, Falchero L, Meyronet D, Thivolet-Bejui F, et al. Respiratory failure with diffuse bronchiectases and cryoglobulinaemia. Eur Respir J. Jun 2008;31(6):1374-8. [Medline].

  33. Della Rossa A, Tavoni A, Bombardieri S. Cryoglobulinemia. In: Hochberg M, ed. Rheumatology. 3rd ed. Philadelphia: Pa: Mosby; 2003:1697-1703.

  34. Montagnino G. Reappraisal of the clinical expression of mixed cryoglobulinemia. Springer Semin Immunopathol. 1988;10(1):1-19. [Medline].

  35. Ferri C, La Civita L, Cirafisi C, Siciliano G, Longombardo G, Bombardieri S, et al. Peripheral neuropathy in mixed cryoglobulinemia: clinical and electrophysiologic investigations. J Rheumatol. Jun 1992;19(6):889-95. [Medline].

  36. Meltzer M, Franklin EC, Elias K, McCluskey RT, Cooper N. Cryoglobulinemia--a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med. Jun 1966;40(6):837-56. [Medline].

  37. Antonelli A, Ferri C, Fallahi P, Ferrari SM, Sebastiani M, Ferrari D, et al. High values of CXCL10 serum levels in mixed cryoglobulinemia associated with hepatitis C infection. Am J Gastroenterol. Oct 2008;103(10):2488-94. [Medline].

  38. Nash JW, Ross P Jr, Neil Crowson A, Taylor J, Morales JE, Yunger TM, et al. The histopathologic spectrum of cryofibrinogenemia in four anatomic sites. Skin, lung, muscle, and kidney. Am J Clin Pathol. Jan 2003;119(1):114-22. [Medline].

  39. Iannuzzella F, Vaglio A, Garini G. Management of hepatitis C virus-related mixed cryoglobulinemia. Am J Med. May 2010;123(5):400-8. [Medline].

  40. Mazzaro C, Monti G, Saccardo F, Zignego AL, Ferri C, De Vita S, et al. Efficacy and safety of peginterferon alfa-2b plus ribavirin for HCV-positive mixed cryoglobulinemia: a multicentre open-label study. Clin Exp Rheumatol. Dec 7 2011;[Medline].

  41. Enomoto M, Nakanishi T, Ishii M, Tamori A, Kawada N. Entecavir to treat hepatitis B-associated cryoglobulinemic vasculitis. Ann Intern Med. Dec 16 2008;149(12):912-3. [Medline].

  42. Zaja F, De Vita S, Mazzaro C, Sacco S, Damiani D, De Marchi G, et al. Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood. May 15 2003;101(10):3827-34. [Medline].

  43. Quartuccio L, Soardo G, Romano G, Zaja F, Scott CA, De Marchi G, et al. Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids. Rheumatology (Oxford). Jul 2006;45(7):842-6. [Medline].

  44. Boyer O, Saadoun D, Abriol J, Dodille M, Piette JC, Cacoub P, et al. CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood. May 1 2004;103(9):3428-30. [Medline].

  45. Ferri C, Moriconi L, Gremignai G, Migliorini P, Paleologo G, Fosella PV, et al. Treatment of the renal involvement in mixed cryoglobulinemia with prolonged plasma exchange. Nephron. 1986;43(4):246-53. [Medline].

  46. Ferri C, Pietrogrande M, Cecchetti R, Tavoni A, Cefalo A, Buzzetti G, et al. Low-antigen-content diet in the treatment of patients with mixed cryoglobulinemia. Am J Med. Nov 1989;87(5):519-24. [Medline].

  47. Gemignani F, Pavesi G, Fiocchi A, Manganelli P, Ferraccioli G, Marbini A. Peripheral neuropathy in essential mixed cryoglobulinaemia. J Neurol Neurosurg Psychiatry. Feb 1992;55(2):116-20. [Medline].

  48. Gorevic PD. Connective Tissue Disease Associated with Other Immunologic Disorders. Cryoglobulinemia. In: Koopman WJ, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology. 13th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1997:1572-8.

  49. Gorevic PD. Cryopathies: Cryoglobulins and Cryofibrinogenemia. In: Samter's Immunologic Disease. 5th ed. Boston, Mass: Little, Brown, and Co; 1995:951-974.

  50. Guillevin L, Pagnoux C. Indications of plasma exchanges for systemic vasculitides. Ther Apher Dial. Apr 2003;7(2):155-60. [Medline].

  51. Koukoulaki M, Abeygunasekara SC, Smith KG, Jayne DR. Remission of refractory hepatitis C-negative cryoglobulinaemic vasculitis after rituximab and infliximab. Nephrol Dial Transplant. Jan 2005;20(1):213-6. [Medline].

  52. Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, et al. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology. May 1994;106(5):1291-300. [Medline].

  53. Madore F, Lazarus JM, Brady HR. Therapeutic plasma exchange in renal diseases. J Am Soc Nephrol. Mar 1996;7(3):367-86. [Medline].

  54. Meltzer M, Franklin EC. Cryoglobulinemia--a study of twenty-nine patients. I. IgG and IgM cryoglobulins and factors affecting cryoprecipitability. Am J Med. Jun 1966;40(6):828-36. [Medline].

  55. Miescher PA, Huang YP, Izui S. Type II cryoglobulinemia. Semin Hematol. Jan 1995;32(1):80-5. [Medline].

  56. Sansonno D, De Re V, Lauletta G, Tucci FA, Boiocchi M, Dammacco F. Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood. May 15 2003;101(10):3818-26. [Medline].

 
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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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