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Rituximab in cryoglobulinaemic vasculitis, evidence for its effectivity: a case report and review of literature

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Abstract

Cryoglobulinaemia associated with systemic vasculitis mediated by immune complexes is a rare combination. These immune complexes are composed of immunoglobulins and precipitate when exposed to cold temperature. Cryoglobulinaemic vasculitis, treated or untreated, may lead to substantial morbidity and even mortality. Novel targeted therapies may well provide new therapeutic options following or perhaps even prior to the classical cytotoxic therapies. Systemic B cell depletion with rituximab, a chimeric monoclonal antibody against CD20 antigen, is commonly applied in patients with non-Hodgkin’s lymphoma or in refractory rheumatoid factor-positive rheumatoid arthritis. Since B cell clones are the source of cryoglobulins, therapeutic effectiveness of rituximab in cryoglobulinaemic vasculitis may be expected. We describe a 72-year-old woman with mixed cryoglobulinaemia type 2, who has successfully been treated with rituximab infusions after failing on prednisone and azathioprine. We reviewed the literature and found 142 cases of cryoglobulinaemic vasculitis, 138 mixed (type 2 or 3) and four, type 1. Rituximab was applied mostly after failure on other treatments. Significant reduction in levels of rheumatoid factor, cryoglobulins and IgM were reported after rituximab therapy. Of the total 142, cases 119 could be evaluated for the response on rituximab therapy, the other 23 cases only regarding side effects. Of the 119 evaluated patients, 71 (60%) had complete response; 28 (23%), partial response and 20 patients (17%), no response. Data were not blinded or placebo-controlled. Side effects were seen in 27 of the 142 patients. Occurrence of the side effects was associated with high baseline levels of cryoglobulins, with a high dose of rituximab infusion of 1,000 mg and with a high level of complement activation. Death was reported four times and was related with the disease.

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References

  1. Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M (1974) Biological and clinical significance of cryoglobulins: a report of 86 cases. Am J Med 57:775–788

    Article  CAS  PubMed  Google Scholar 

  2. Meltzer M, Franklin EC, Elias K, McCluskey RT, Cooper N (1966) Cryoglobulinemia: a clinical and laboratory study. Am J Med 40(6):837–856

    Article  CAS  PubMed  Google Scholar 

  3. Lamprecht P, Gause A, Gross WL (1999) Cryoglobulinemic vasculitis. Arthritis Rheum 42(12):2507–2516

    Article  CAS  PubMed  Google Scholar 

  4. Plosker GL, Figgitt DP (2003) Rituximab: a review of its use in non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 63(8):803–843

    Article  CAS  PubMed  Google Scholar 

  5. Leandro MJ, Edwards JC, Cambridge G (2002) Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion. Ann Rheum Dis 61:883–888

    Article  CAS  PubMed  Google Scholar 

  6. Higashida J, Wun T, Schmidt S, Naguwa SM, Tuscano JM (2005) Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment. J Rheumatol 32(11):2109–2115

    CAS  PubMed  Google Scholar 

  7. Nehme-Schuster H, Korganow AS, Pasquali JL, Martin T (2005) Rituximab inefficiency during type I cryolobulinaemia. Rheumatology (Oxford) 44(3):410–411

    Article  CAS  Google Scholar 

  8. Cohen H, Green S, Jones S, Amos N, William BD (2007) Lack of efficacy of rituximab in a patient with essential mixed cryoglobulinaemia. Rheumatology 46:366–367

    Article  CAS  PubMed  Google Scholar 

  9. Roccatello D, Baldovino S, Rossi D, Giachino O, Mansouri M (2008) Rituximab as a therapeutic tool in severe mixed cryoglobulinemia. Clin Rev Allergy Immunol 34:111–117

    Article  CAS  PubMed  Google Scholar 

  10. Zaja F, De Vita S, Mazzaro C, Sacco S, Damiani D (2003) Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 101:3827–3834

    Article  CAS  PubMed  Google Scholar 

  11. Sansonno D, De Re V, Lauletta G, Tucci FA, Boiocchi M, Dammacco F (2003) Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon α with an anti-CD20. Blood 101:3818–3826

    Article  CAS  PubMed  Google Scholar 

  12. Sène D, Ghillani-Dalbin P, Amoura Z, Musset L, Cacoub P (2009) Rituximab may form a complex with IgMκ mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis C virus-induced vasculitis. Arthritis Rheum 60(12):3848–3855

    Article  PubMed  Google Scholar 

  13. Bryce AH, Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV (2006) Response to rituximab in patients with type II cryoglobulinemia. Clin Lymphoma Meyloma 7(2):140–144

    Article  CAS  Google Scholar 

  14. Arzoo K, Sadeghi S, Liebman HA (2006) Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis 61:922–924

    Article  Google Scholar 

  15. Koukoulaki M, Abeygunasekara SM, Smith KGC, Jayne DRW (2005) Remission of refractory hepatitis C-negative cryoglobulinaemic vasculitis after rituximab and infliximab. Nephrol Dial Transplant 20:213–216

    Article  CAS  PubMed  Google Scholar 

  16. Rego TCG, Massumoto CM, Batista RS, De Moura LH, Soares LMC, Gomes AP (2007) The use of monoclonal antibody (rituximab) in the treatment of type II mixed cryoglobulinemia. Braz J Infect Dis 11(1):174–175

    Article  PubMed  Google Scholar 

  17. Lamprecht P, Lerin-Lozano C, Merz H, Dennin RH, Gause A, Voswinkel J, Peters SA, Gutzeit O, Arlt AC, Solbach W, Gross WL (2003) Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis. Ann Rheum Dis 62:1230–1233

    Article  CAS  PubMed  Google Scholar 

  18. Ruch J, McMahon B, Ramsey G, Kwaan HC (2009) Catastrophic multiple organ ischemia due to an anti-Pr cold agglutinin developing in a patient with mixed cryoglobulinemia after treatment with rituximab. Am J Hematol 84:120–122

    Article  CAS  PubMed  Google Scholar 

  19. Pekow J, Chung RT (2006) Treatment of type II cryoglobulinemia associated with hepatitis C with rituximab. J Clin Gastroenterol 40(5):450

    Article  PubMed  Google Scholar 

  20. Ghijsels E, Lerut E, Vanrenterghem Y, Kuypers D (2004) Anti-CD20 monoclonal antibody (rituximab) treatment for hepatitis C-negative therapy-resistant essential mixed cryoglobulinemia with renal and cardiac failure. Am J Kidney Dis 43(5):e34–e38

    Article  PubMed  Google Scholar 

  21. Braun A, Neumann T, Oelzner P, Hein G, Gröne HJ, Ziemer M, Wolf G (2008) Cryoglobulinaemia type III with severe neuropathy and immune complex glomerulonephritis: remission after plasmapheresis and rituximab. Rheumatol Int 28:503–506

    Article  PubMed  Google Scholar 

  22. Cai FZJ, Ahern M, Smith M (2006) Treatment of cryoglobulinemia associated peripheral neuropathy with rituximab. J Rheumatol 33(6):1197–1198

    PubMed  Google Scholar 

  23. Massari M, Catania A, Magnani G (2007) Efficacy and risk of rituximab in type II mixed cryoglobulinemia: a significant case report. Dig Liver Dis 39(suppl 1):S134–S135

    Article  PubMed  Google Scholar 

  24. Pandrangi S, Singh A, Wheeler DE, Rossi NF (2008) Rituximab treatment for a patient with type I cryoglobulinemic glomerulonephritis. Nat Clin Pract Nephrol 4(7):393–397

    Article  PubMed  Google Scholar 

  25. Evans JT, Shepard MM, Oates JC, Self SE, Reuben A (2008) Rituximab-responsive cryoglobulinemic glomerulonephritis in a patient with autoimmune hepatitis. J Clin Gastroenterol 42(7):862–863

    Article  PubMed  Google Scholar 

  26. Pasa S, Altintas A, Cil T, Danis R, Ayyildiz O, Muftuoglu E (2009) A case of essential mixed cryoglobulinemia and associated acquired von-Willebrand disease treated with rituximab. J Thromb Thrombolysis 27:220–222

    Article  PubMed  Google Scholar 

  27. Basse G, Ribes D, Kamar N, Mehrenberger M, Esposito L, Guitard J (2005) Rituximab therapy for de novo mixed cryoglobulinemia in renal transplant patients. Transplantation 80:1560–1564

    Article  CAS  PubMed  Google Scholar 

  28. Visenti M, Granata M, Veneziano ML, Borghese F, Carlesimo M, Pimpinelli F, Fiorilli M, Casato M (2007) Efficacy of low-dose rituximab for mixed cryoglobulinemia. Clin Immunol 125:30–33

    Article  Google Scholar 

  29. Cavallo R, Roccatello D, Menegatti E, Naretto C, Napoli F, Baldovino S (2009) Rituximab in cryoglobulinemic peripheral neuropathy. J Neurol 256:1076–1082

    Article  CAS  PubMed  Google Scholar 

  30. Saadoun D, Resche-Rigon M, Sene D, Perard L, Piette JC, Cacoub P (2008) Rituximab combined with peg-interferon-ribavirin in refractory HCV-associated cryoglobulinemia vasculitis. Ann Rheum Dis 67(10):1431–1436

    Article  CAS  PubMed  Google Scholar 

  31. Catuogno M, Rezai S, Priori S, Magrini L, Valesini G (2005) Serum sickness associated with rituximab in a patient with hepatitis C virus-related mixed cryoglobulinemia. Rheumatology 44:406

    Article  CAS  PubMed  Google Scholar 

  32. Quartuccio L, Soardo G, Romano G, Zaja F, Scott CA, De Marchi G, Fabris M, Ferraccioli G, De Vita S (2006) Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroid. Rheumatology 45:842–846

    Article  CAS  PubMed  Google Scholar 

  33. Korte MR, van Heerde MJ, de Man RA, Betjes MHG (2008) Rituximab for the treatment of glomerulonephritis in hepatitis C associated cryoglobulinaemia. Neth J Med 66(1):27–30

    CAS  PubMed  Google Scholar 

  34. Uppal R, Charles E, Lake-Bakaar G (2009) Acute wrist and foot drop associated with hepatitis C virus related mixed cryoglobulinemia: rapid response to treatment with rituximab. J Clin Virol 47(1):69–71

    Article  PubMed  Google Scholar 

  35. Zaja F, De Vita S, Russo D, Michelutti A, Fanin R, Ferraccioli G, Baccarani M (2002) Rituximab for the treatment of type II mixed cryoglobulinemia. Arthritis Rheum 46(8):2252–2254

    Article  PubMed  Google Scholar 

  36. Zaja F, Russo D, Patriarca F, Ermacora A, Baccarani M (1999) Rituximab for the treatment of type II mixed cryoglobulinemia. Haematologica 84(12):1157–1158

    CAS  PubMed  Google Scholar 

  37. Silverman GJ, Weisman S (2003) Rituximab therapy and autoimmune disorders: prospects for anti-B cell therapy. Arthritis Rheum 48(6):1484–1492

    Article  CAS  PubMed  Google Scholar 

  38. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, Watier H (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 99(3):754–758

    Article  CAS  PubMed  Google Scholar 

  39. Cacoub P, Delluc A, Saadoun D, Landau DA, Sene D (2008) Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemia vasculitis: where do we stand? Ann Rheum Dis 67(3):283–287

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Rheumatology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands

    Freke Wink & Pieternella M. Houtman

  2. Department of Rheumatology, University Medical Centre Nijmegen St. Radboud, Nijmegen, The Netherlands

    Tim L. Th. A. Jansen

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  1. Freke Wink
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  2. Pieternella M. Houtman
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  3. Tim L. Th. A. Jansen
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Correspondence to Tim L. Th. A. Jansen.

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Wink, F., Houtman, P.M. & Jansen, T.L.T.A. Rituximab in cryoglobulinaemic vasculitis, evidence for its effectivity: a case report and review of literature. Clin Rheumatol 30, 293–300 (2011). https://doi.org/10.1007/s10067-010-1612-2

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  • DOI: https://doi.org/10.1007/s10067-010-1612-2

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