Cryoglobulinemia Differential Diagnoses

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

Differential Diagnoses

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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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