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Non-Infectious Cryoglobulinemia Vasculitis (CryoVas): Update on Clinical and Therapeutic Approach

  • VASCULITIS (LR ESPINOZA, SECTION EDITOR)
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Abstract

CryoVas is a small vessel vasculitis associated with the presence of circulating cryoglobulins. In the absence of HCV infection, several disorders have been identified in association of CryoVas. Although evidence is limited, a few studies have recently described the clinical presentation, prognosis, and therapeutic management of non-infectious CryoVas. Patients with type I CryoVas, especially associated with hematologic malignancies, have shown a worse clinical presentation. Recent studies have also identified prognostic factors in mixed CryoVas. Therapeutic management in non-infectious CryoVas remains to be defined. Overall, treatment options should be individualized based on severity of involvement. In this setting, new data have emerged regarding the role of biologic therapy in non-infectious CryoVas. Off-label use of rituximab should be highlighted, based on the assessment of benefits and risks, especially infections.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Terrier B, Cacoub P. Cryoglobulinemia vasculitis: an update. Curr Opin Rheumatol. 2013;25:10–8. Comprehensive report with a complete literature review on clinical and laboratory manifestations and new therapeutic approaches of cryoglobulinemia vasculitis.

    Article  PubMed  Google Scholar 

  2. Lerner AB, Watson CJ. Studies of cryoglobulins I: unusual purpura associated with the presence of a high concentration of cryoglobulin (cold precipitable serum globulin). Am J Med Sci. 1947;214:410–5.

    Article  PubMed  CAS  Google Scholar 

  3. Brouet JC, Clauvel JP, Danon F, et al. Biologic and clinical significance of cryoglobulins: a report of 86 cases. Am J Med. 1974;57:775–88.

    Article  PubMed  CAS  Google Scholar 

  4. Trejo O, Ramos-Casals M, Garcia-Carrasco M, et al. Cryoglobulinemia: study of etiologic factors and clinical and immunologic features in 443 patients from a single center. Medicine (Baltimore). 2001;80:252–62.

    Article  CAS  Google Scholar 

  5. Saadoun D, Sellam J, Ghillani-Dalbin P, et al. Increased risks of lymphoma and death among patients with nonhepatitis C virus-related mixed cryoglobulinemia. Arch Intern Med. 2006;166:2101–8.

    Article  PubMed  Google Scholar 

  6. Ramos-Casals M, Stone JH, Cid MC, et al. The cryoglobulinaemias. Lancet. 2012;379:348–60. An outstanding review with a complete description of pathophysiology, clinical manifestations, diagnosis, and treatment approaches of cryoglobulinemia vasculitis.

    Article  PubMed  CAS  Google Scholar 

  7. Della Rossa A, Tavoni A, Bombardieri S. Hyperviscosity syndrome in cryoglobulinaemia: clinical aspects and therapeutic considerations. Semin Thromb Hemost. 2003;29:473–7.

    Article  PubMed  Google Scholar 

  8. Gorevic PD, Kassab HJ, Levo Y, et al. Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients. Am J Med. 1980;69:287–308.

    Article  PubMed  CAS  Google Scholar 

  9. Tzioufas A, Boumba D, Skopouli F, et al. Mixed monoclonal cryoglobulinaemia and monoclonal rheumatoid factor cross-reactive idiotypes as predictive factors for the development of lymphoma in primary Sjogren’s syndrome. Arthritis Rheum. 1996;39:767–72.

    Article  PubMed  CAS  Google Scholar 

  10. Brito-Zerón P, Ramos-Casals M, Bove A, et al. Predicting adverse outcomes in primary Sjögren’s syndrome: identification of prognostic factors. Rheumatology (Oxford). 2007;46:1359–62.

    Article  Google Scholar 

  11. García-Carrasco M, Ramos-Casals M, Cervera R, et al. Cryoglobulinaemia in systemic lupus erythematosus: prevalence and clinical characteristics in a series of 122 patients. Semin Arthritis Rheum. 2001;30:366–73.

    Article  PubMed  Google Scholar 

  12. Morra E. Cryoglobulinemia. ASH Education Book. Hematol Am Soc Hematol Educ Program. 2005;1:368–72.

    Article  Google Scholar 

  13. Trejo O, Ramos-Casals M, López-Guillermo A, et al. Hematologic malignancies in patients with cryoglobulinaemia: association with autoimmune and chronic viral diseases. Semin Arthritis Rheum. 2003;33:19–28.

    Article  PubMed  Google Scholar 

  14. Terrier B, Krastinova E, Marie I, et al. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey. Blood. 2012;119:5996–6004. This is the largest series so far published on non-infectious mixed CryoVas analyzing the safety and efficacy of different treatment approaches. Rituximab and corticosteroids showed greater efficacy although were associated with severe infections.

    Article  PubMed  CAS  Google Scholar 

  15. Damoiseaux J and Cohen Tervaert JW. Diagnostics and treatment of cryoglobulinemia: it takes two to tango. Clin Rev Allerg Immunol 2013.

  16. Terrier B, Karras A, Kahn J, et al. The spectrum of type I cryoglobulinemia vasculitis. Medicine. 2013;92:61–8. This study describes the presentation, prognosis, and therapeutic management of the largest series of type I CryoVas patients. Severe cutaneous manifestations and high serum cryoglobulin levels characterized type I CryoVas, although the frequency of glomerulonephritis was lower than expected.

    Article  PubMed  CAS  Google Scholar 

  17. Terrier B, Carrat F, Krastinova E, et al. Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey. Ann Rheum Dis. 2013;72:374–80. This study included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years. Main prognostic factors were age older than 65 years, pulmonary and gastrointestinal involvement, and renal failure.

    Article  PubMed  Google Scholar 

  18. Terrier B, Semoun O, Saadoun D, et al. Prognostic factors in patients with hepatitis C virus infection and systemic vasculitis. Arthritis Rheum. 2011;63:1748–57.

    Article  PubMed  Google Scholar 

  19. Terrier B, Launay D, Kaplanski G, et al. Safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis: data from the French Autoimmunity and Rituximab registry. Arthritis Care Res (Hoboken). 2010;62:1787–95.

    Article  CAS  Google Scholar 

  20. Payet J, Livartowski J, Kavian N, et al. Type I cryoglobulinemia in multiple myeloma, a rare entity: analysis of clinical and biological characteristics of seven cases and review of the literature. Leuk Lymphoma. 2013;54(4):767–77.

    Article  PubMed  CAS  Google Scholar 

  21. Nehme-Schuster H, Korganow A, Pasquali J, et al. Rituximab inefficiency during type I cryoglobulinemia. Rheumatology (Oxford). 2005;44:410–1.

    Article  CAS  Google Scholar 

  22. Pandrangi S, Singh A, Wheeler D, et al. Rituximab treatment for a patient with type I cryoglobulinemic glomerulonephritis. Nat Clin Pract Nephrol. 2008;4:393–7.

    Article  PubMed  Google Scholar 

  23. Calabrese C, Faiman B, Martin D, et al. Type 1 cryoglobulinemia: response to thalidomide and lenalidomide. J Clin Rheumatol. 2011;17:145–7.

    Article  PubMed  Google Scholar 

  24. Lin R, Curran J, Zimmerman T, et al. Lenalidomide for the treatment of cryoglobulinemia and undifferentiated spondyloarthropathy in a patient with multiple myeloma. J Clin Rheumatol. 2010;16:90–1.

    Article  PubMed Central  PubMed  Google Scholar 

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Luis R. Espinoza declare that he has no conflict of interest to disclose.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Rodolfo Perez-Alamino.

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This article is part of the Topical Collection on Vasculitis

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Perez-Alamino, R., Espinoza, L.R. Non-Infectious Cryoglobulinemia Vasculitis (CryoVas): Update on Clinical and Therapeutic Approach. Curr Rheumatol Rep 16, 420 (2014). https://doi.org/10.1007/s11926-014-0420-0

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  • DOI: https://doi.org/10.1007/s11926-014-0420-0

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