Cryoglobulinemia Questions & Answers

1. Roccatello D, Saadoun D, Ramos-Casals M, Tzioufas AG, Fervenza FC, Cacoub P, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018 Aug 2. 4 (1):11. [QxMD MEDLINE Link].

2. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet. 2011 Aug 23. [QxMD MEDLINE Link].

3. Gulli F, Basile U, Gragnani L, Napodano C, Pocino K, Miele L, et al. IgG cryoglobulinemia. Eur Rev Med Pharmacol Sci. 2018 Sep. 22 (18):6057-6062. [QxMD MEDLINE Link]. [Full Text].

4. Trendelenburg M, Schifferli JA. Cryoglobulins are not essential. Ann Rheum Dis. 1998 Jan. 57(1):3-5. [QxMD MEDLINE Link].

5. Néel A, Perrin F, Decaux O, Dejoie T, Tessoulin B, Halliez M, et al. Long-term outcome of monoclonal (type 1) cryoglobulinemia. Am J Hematol. 2014 Feb. 89(2):156-61. [QxMD MEDLINE Link].

6. Terrier B, Karras A, Kahn JE, Le Guenno G, Marie I, Benarous L, et al. The spectrum of type I cryoglobulinemia vasculitis: new insights based on 64 cases. Medicine (Baltimore). 2013 Mar. 92(2):61-8. [QxMD MEDLINE Link].

7. Jablonska J, Zabek J, Pawelczyk A, Kubisa N, Fic M, Laskus T, et al. Hepatitis C virus (HCV) infection of peripheral blood mononuclear cells in patients with type II cryoglobulinemia. Hum Immunol. 2013 Dec. 74(12):1559-62. [QxMD MEDLINE Link].

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

9. Wang AC, Wells JV, Fudenberg HH. Chemical analyses of cryoglobulins. Immunochemistry. 1974 Jul. 11(7):341-5. [QxMD MEDLINE Link].

10. 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. [QxMD MEDLINE Link].

11. 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. 1975 Jan. 12(1):29-37. [QxMD MEDLINE Link].

12. 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. 2002 Oct 15. 169(8):4644-50. [QxMD MEDLINE Link].

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

14. 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. 1998 May. 185(1):86-90. [QxMD MEDLINE Link].

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

16. 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). 2006 Jun. 45(6):685-93. [QxMD MEDLINE Link].

17. 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. 1997 May. 25(5):1237-44. [QxMD MEDLINE Link].

18. 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. 1995 Feb. 21(2):305-12. [QxMD MEDLINE Link].

19. 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. 1995 Oct. 131(10):1119-23. [QxMD MEDLINE Link].

20. Pocino K, Napodano C, Gragnani L, Ciasca G, Colantuono S, Marri S, et al. Solving the mystery of HBV-related mixed cryoglobulinemia: potential biomarkers of disease progression. Rheumatology (Oxford). 2021 Feb 16. [QxMD MEDLINE Link].

21. 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. 1980 Aug. 69(2):287-308. [QxMD MEDLINE Link].

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

23. Cacoub P, Saadoun D. Extrahepatic Manifestations of Chronic HCV Infection. N Engl J Med. 2021 Mar 18. 384 (11):1038-1052. [QxMD MEDLINE Link].

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

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

26. 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. [QxMD MEDLINE Link].

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

28. 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. 2006 Oct 23. 166(19):2101-8. [QxMD MEDLINE Link].

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

30. 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. 1966 Jun. 40(6):837-56. [QxMD MEDLINE Link].

31. 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. 1995 Feb. 88(2):115-26. [QxMD MEDLINE Link].

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

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

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

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

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

37. 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. 1995 Feb. 47(2):618-23. [QxMD MEDLINE Link].

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

39. 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. 1989 Sep. 8(3):331-8. [QxMD MEDLINE Link].

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

41. 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. 2008 Jun. 31(6):1374-8. [QxMD MEDLINE Link].

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

43. Montagnino G. Reappraisal of the clinical expression of mixed cryoglobulinemia. Springer Semin Immunopathol. 1988. 10(1):1-19. [QxMD MEDLINE Link].

44. 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. 1992 Jun. 19(6):889-95. [QxMD MEDLINE Link].

45. Fallahi P, Ferrari SM, Ruffilli I, Elia G, Giuggioli D, Colaci M, et al. Incidence of thyroid disorders in mixed cryoglobulinemia: Results from a longitudinal follow-up. Autoimmun Rev. 2016 Jul. 15 (7):747-51. [QxMD MEDLINE Link].

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

47. 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. 2008 Oct. 103(10):2488-94. [QxMD MEDLINE Link].

48. 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. 2003 Jan. 119(1):114-22. [QxMD MEDLINE Link].

49. Muchtar E, Magen H, Gertz MA. How I treat cryoglobulinemia. Blood. 2017 Jan 19. 129 (3):289-298. [QxMD MEDLINE Link].

50. 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. 2011 Dec 7. [QxMD MEDLINE Link].

51. Emery JS, Kuczynski M, La D, Almarzooqi S, Kowgier M, Shah H, et al. Efficacy and Safety of Direct Acting Antivirals for the Treatment of Mixed Cryoglobulinemia. Am J Gastroenterol. 2017 Aug. 112 (8):1298-1308. [QxMD MEDLINE Link].

52. [Guideline] Jadoul M, Berenguer MC, Doss W, Fabrizi F, Izopet J, Jha V, et al. Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management. Kidney Int. 2018 Oct. 94 (4):663-673. [QxMD MEDLINE Link]. [Full Text].

53. 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. 2003 May 15. 101(10):3827-34. [QxMD MEDLINE Link].

54. 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). 2006 Jul. 45(7):842-6. [QxMD MEDLINE Link].

55. 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. 2003 May 15. 101(10):3818-26. [QxMD MEDLINE Link].

56. Sneller MC, Hu Z, Langford CA. A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis. Arthritis Rheum. 2012 Mar. 64(3):835-42. [QxMD MEDLINE Link]. [Full Text].

57. Roccatello D, Sciascia S, Baldovino S, Rossi D, Alpa M, Naretto C, et al. Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study. Am J Nephrol. 2016. 43 (4):251-60. [QxMD MEDLINE Link].

58. Colantuono S, Mitrevski M, Yang B, Tola J, Carlesimo M, De Sanctis GM, et al. Efficacy and safety of long-term treatment with low-dose rituximab for relapsing mixed cryoglobulinemia vasculitis. Clin Rheumatol. 2017 Mar. 36 (3):617-623. [QxMD MEDLINE Link].

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

60. Mazzaro C, Dal Maso L, Urraro T, Mauro E, Castelnovo L, Casarin P, et al. Hepatitis B virus related cryoglobulinemic vasculitis: A multicentre open label study from the Gruppo Italiano di Studio delle Crioglobulinemie - GISC. Dig Liver Dis. 2016 Apr 2. [QxMD MEDLINE Link].

61. Ostojic P, Jeremic IR. Managing refractory cryoglobulinemic vasculitis: challenges and solutions. J Inflamm Res. 2017. 10:49-54. [QxMD MEDLINE Link].

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

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