Skip to main content
Erschienen in: Der Internist 3/2008

01.03.2008 | Schwerpunkt

Hepatitis-assoziierte Kryoglobulinämie

verfasst von: S. Pischke, M. Cornberg, Prof. Dr. M.P. Manns

Erschienen in: Die Innere Medizin | Ausgabe 3/2008

Einloggen, um Zugang zu erhalten

Zusammenfassung

Kryoglobuline sind Immunglobuline, die bei Temperaturen unter 37°C präzipitieren. Klinisch manifestiert sich eine Kryoglobulinämie mit sehr unterschiedlichen Symptomen an diversen Organen. Die klinisch bedeutendsten Symptome sind Fatigue, periphere Polyneuropathie und vaskulitisassoziierte Hautdefekte. Pathophysiologisch beruht eine Kryoglobulinämie auf einer gestörten Immunkaskade mit einer gesteigerten B-Zell-Aktivität. Der oftmals beobachtete Übergang einer Kryoglobulinämie in ein malignes Non-Hodgkin-Lymphom ist fließend. Die Assoziation zwischen Kryoglobulinämie und Virushepatitis ist am größten bei der Hepatitis-C-Virusinfektion. Andere Ursachen einer Kryoglobulinämie sind rheumatische und hämatologische Erkrankungen. Während früher v. a. mit Plasmapherese und Immunsuppression therapiert wurde, hat sich, durch die hohe Korrelation mit einer HCV-Infektion, die Bedeutung antiviraler Therapien im Rahmen von Kryoglobulinämien herausgestellt. Fälle von rascher Verschlechterung unter Interferon α wurden jedoch auch beobachtet. Eine vielversprechende alternative Therapieoption ist der Einsatz von Rituximab.
Literatur
1.
Zurück zum Zitat Agnello V, Chung RT, Kaplan LM (1992) A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 327: 1490–1495PubMedCrossRef Agnello V, Chung RT, Kaplan LM (1992) A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 327: 1490–1495PubMedCrossRef
2.
Zurück zum Zitat Ahmed MS, Wong CF (2007) Should rituximab be the rescue therapy for refractory mixed cryoglobulinemia associated with hepatitis C? J Nephrol 20: 350–356PubMed Ahmed MS, Wong CF (2007) Should rituximab be the rescue therapy for refractory mixed cryoglobulinemia associated with hepatitis C? J Nephrol 20: 350–356PubMed
3.
Zurück zum Zitat Alric L, Plaisier E, Thébault S et al. (2004) Influence of antiviral therapy in hepatitis C virus-associated cryoglobulinemic MPGN. Am J Kidney Dis 43: 617–623PubMedCrossRef Alric L, Plaisier E, Thébault S et al. (2004) Influence of antiviral therapy in hepatitis C virus-associated cryoglobulinemic MPGN. Am J Kidney Dis 43: 617–623PubMedCrossRef
4.
Zurück zum Zitat Basse G, Ribes D, Kamar N et al. (2006) Rituximab therapy for mixed cryoglobulinemia in seven renal transplant patients. Transplant Proc 38: 2308–2310PubMedCrossRef Basse G, Ribes D, Kamar N et al. (2006) Rituximab therapy for mixed cryoglobulinemia in seven renal transplant patients. Transplant Proc 38: 2308–2310PubMedCrossRef
5.
Zurück zum Zitat Batisse D, Karmochkine M, Jacquot C et al. (2004) Sustained exacerbation of cryoglobulinaemia-related vasculitis following treatment of hepatitis C with peg-interferon alfa. Eur J Gastroenterol Hepatol 16: 701–703PubMedCrossRef Batisse D, Karmochkine M, Jacquot C et al. (2004) Sustained exacerbation of cryoglobulinaemia-related vasculitis following treatment of hepatitis C with peg-interferon alfa. Eur J Gastroenterol Hepatol 16: 701–703PubMedCrossRef
6.
Zurück zum Zitat Blight K, Trowbridge R, Rowland R, Gowans E (1992) Detection of hepatitis C virus RNA by in situ hybridization. Liver 12: 286–289PubMed Blight K, Trowbridge R, Rowland R, Gowans E (1992) Detection of hepatitis C virus RNA by in situ hybridization. Liver 12: 286–289PubMed
7.
Zurück zum Zitat Bonomo L, Casato M, Afeltra A, Caccavo D (1987) Treatment of idiopathic mixed cryoglobulinemia with alpha interferon. Am J Med 83: 726–730PubMedCrossRef Bonomo L, Casato M, Afeltra A, Caccavo D (1987) Treatment of idiopathic mixed cryoglobulinemia with alpha interferon. Am J Med 83: 726–730PubMedCrossRef
8.
Zurück zum Zitat Bryce AH, Dispenzieri A, Kyle RA,et al. (2006) Response to rituximab in patients with type II cryoglobulinemia. Clin Lymphoma Myeloma 7: 140–144PubMedCrossRef Bryce AH, Dispenzieri A, Kyle RA,et al. (2006) Response to rituximab in patients with type II cryoglobulinemia. Clin Lymphoma Myeloma 7: 140–144PubMedCrossRef
9.
Zurück zum Zitat Cacoub P, Delluc A, Saadoun D et al. (2007) Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemia vasculitis: where do we stand? Ann Rheum Dis [Epub ahead of print] Cacoub P, Delluc A, Saadoun D et al. (2007) Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemia vasculitis: where do we stand? Ann Rheum Dis [Epub ahead of print]
10.
Zurück zum Zitat Cakir N, Pamuk ON, Umit H, Midilli K (2006) Successful treatment with adefovir of one patient whose cryoglobulinemic vasculitis relapsed under lamivudine therapy and who was diagnosed to have HBV virologic breakthrough with YMDD mutations. Intern Med 45: 1213–1215PubMedCrossRef Cakir N, Pamuk ON, Umit H, Midilli K (2006) Successful treatment with adefovir of one patient whose cryoglobulinemic vasculitis relapsed under lamivudine therapy and who was diagnosed to have HBV virologic breakthrough with YMDD mutations. Intern Med 45: 1213–1215PubMedCrossRef
11.
Zurück zum Zitat Casato M, Lilli D, Donato G et al. (2003) Occult hepatitis C virus infection in type II mixed cryoglobulinaemia. J Viral Hepat 10: 455–459PubMedCrossRef Casato M, Lilli D, Donato G et al. (2003) Occult hepatitis C virus infection in type II mixed cryoglobulinaemia. J Viral Hepat 10: 455–459PubMedCrossRef
12.
Zurück zum Zitat Choo QL, Kuo G, Weiner AJ et al. (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359–362PubMedCrossRef Choo QL, Kuo G, Weiner AJ et al. (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359–362PubMedCrossRef
13.
Zurück zum Zitat Cocquerel L, Kuo CC, Dubuisson J, Levy S (2003) CD81-dependent binding of hepatitis C virus E1E2 heterodimers. J Virol 77: 10677–10683PubMedCrossRef Cocquerel L, Kuo CC, Dubuisson J, Levy S (2003) CD81-dependent binding of hepatitis C virus E1E2 heterodimers. J Virol 77: 10677–10683PubMedCrossRef
14.
Zurück zum Zitat Colantoni A De Maria N, Idilman R, Van Thiel DH (1997) Polymerase chain reaction for the detection of HCV-RNA: cryoglobulinaemia as a cause for false negative results. Ital J Gastroenterol Hepatol 29: 273–274PubMed Colantoni A De Maria N, Idilman R, Van Thiel DH (1997) Polymerase chain reaction for the detection of HCV-RNA: cryoglobulinaemia as a cause for false negative results. Ital J Gastroenterol Hepatol 29: 273–274PubMed
15.
Zurück zum Zitat Ferri C, Giuggioli D, Cazzato M et al. (2003) HCV-related cryoglobulinemic vasculitis: an update on its etiopathogenesis and therapeutic strategies. Clin Exp Rheumatol (6 Suppl 32) 21: S78–84 Ferri C, Giuggioli D, Cazzato M et al. (2003) HCV-related cryoglobulinemic vasculitis: an update on its etiopathogenesis and therapeutic strategies. Clin Exp Rheumatol (6 Suppl 32) 21: S78–84
16.
Zurück zum Zitat Ferri C, Sebastiani M, Giuggioli D et al. (2004) Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients. Semin Arthritis Rheum 33: 355–374PubMedCrossRef Ferri C, Sebastiani M, Giuggioli D et al. (2004) Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients. Semin Arthritis Rheum 33: 355–374PubMedCrossRef
17.
Zurück zum Zitat Galossi A, Guarisco R, Bellis L, Puoti C (2007) Extrahepatic manifestations of chronic HCV infection. J Gastrointestin Liver Dis 16: 65–73PubMed Galossi A, Guarisco R, Bellis L, Puoti C (2007) Extrahepatic manifestations of chronic HCV infection. J Gastrointestin Liver Dis 16: 65–73PubMed
18.
Zurück zum Zitat Han SH (2004) Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis 8: 403–418PubMedCrossRef Han SH (2004) Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis 8: 403–418PubMedCrossRef
19.
Zurück zum Zitat Hilgard P, Treichel U, Dries V et al. (2005) Cryoglobulin-associated uptake of hepatitis C virus into human hepatocytes. Hepatogastroenterology 52: 1534–1540PubMed Hilgard P, Treichel U, Dries V et al. (2005) Cryoglobulin-associated uptake of hepatitis C virus into human hepatocytes. Hepatogastroenterology 52: 1534–1540PubMed
20.
Zurück zum Zitat Hofmann WP, Herrmann E, Kronenberger B et al. (2004) Association of HCV-related mixed cryoglobulinemia with specific mutational pattern of the HCV E2 protein and CD81 expression on peripheral B lymphocytes. Blood 104: 1228–1229PubMedCrossRef Hofmann WP, Herrmann E, Kronenberger B et al. (2004) Association of HCV-related mixed cryoglobulinemia with specific mutational pattern of the HCV E2 protein and CD81 expression on peripheral B lymphocytes. Blood 104: 1228–1229PubMedCrossRef
21.
Zurück zum Zitat Landau DA, Saadoun D, Calabrese LH, Cacoub P(2007) The pathophysiology of HCV induced B-cell clonal disorders. Autoimmun Rev 6: 581–587PubMedCrossRef Landau DA, Saadoun D, Calabrese LH, Cacoub P(2007) The pathophysiology of HCV induced B-cell clonal disorders. Autoimmun Rev 6: 581–587PubMedCrossRef
22.
Zurück zum Zitat Mazzaro C, Zorat F, Caizzi M et al. (2005) Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study. J Hepatol 42: 632–638PubMedCrossRef Mazzaro C, Zorat F, Caizzi M et al. (2005) Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study. J Hepatol 42: 632–638PubMedCrossRef
23.
Zurück zum Zitat Meltzer MFE (1966) Cryoglobulinemia – a study of twenty-nine patients. IgG and IgM cryoglobulins and factors affecting cryoprecipitability. Am J Med 40: 828–836PubMedCrossRef Meltzer MFE (1966) Cryoglobulinemia – a study of twenty-nine patients. IgG and IgM cryoglobulins and factors affecting cryoprecipitability. Am J Med 40: 828–836PubMedCrossRef
24.
Zurück zum Zitat Misiani R, Bellavita P, Fenili D et al. (1994) Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 330: 751–756PubMedCrossRef Misiani R, Bellavita P, Fenili D et al. (1994) Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 330: 751–756PubMedCrossRef
25.
Zurück zum Zitat Pawlotsky JM, Roudot-Thoraval F, Simmonds P et al. (1995) Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C virus serotypes. Ann Intern Med 122: 169–173PubMed Pawlotsky JM, Roudot-Thoraval F, Simmonds P et al. (1995) Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C virus serotypes. Ann Intern Med 122: 169–173PubMed
26.
Zurück zum Zitat Ramos-Casals M, Forns X, Brito-Zerón P et al. (2007) Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV-RNA viraemia and HIV coinfection. J Viral Hepat 14: 736–742PubMedCrossRef Ramos-Casals M, Forns X, Brito-Zerón P et al. (2007) Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV-RNA viraemia and HIV coinfection. J Viral Hepat 14: 736–742PubMedCrossRef
27.
Zurück zum Zitat Rasul I, Shepherd FA, Kamel-Reid S et al. (1999) Detection of occult low-grade b-cell non-Hodgkin’s lymphoma in patients with chronic hepatitis C infection and mixed cryoglobulinemia. Hepatology 29: 543–547PubMedCrossRef Rasul I, Shepherd FA, Kamel-Reid S et al. (1999) Detection of occult low-grade b-cell non-Hodgkin’s lymphoma in patients with chronic hepatitis C infection and mixed cryoglobulinemia. Hepatology 29: 543–547PubMedCrossRef
28.
Zurück zum Zitat Saadoun D, Asselah T, Resche-Rigon M et al. (2006) Cryoglobulinemia is associated with steatosis and fibrosis in chronic hepatitis C. Hepatology 43: 1337–1345PubMedCrossRef Saadoun D, Asselah T, Resche-Rigon M et al. (2006) Cryoglobulinemia is associated with steatosis and fibrosis in chronic hepatitis C. Hepatology 43: 1337–1345PubMedCrossRef
29.
Zurück zum Zitat Saadoun D, Sellam J, Ghillani-Dalbin P et al. (2006) Increased risks of lymphoma and death among patients with non-hepatitis C virus-related mixed cryoglobulinemia. Arch Intern Med 166: 2101–2108PubMedCrossRef Saadoun D, Sellam J, Ghillani-Dalbin P et al. (2006) Increased risks of lymphoma and death among patients with non-hepatitis C virus-related mixed cryoglobulinemia. Arch Intern Med 166: 2101–2108PubMedCrossRef
30.
Zurück zum Zitat Schiff ER (1992) Atypical clinical manifestations of hepatitis A. Vaccine (Suppl 1) 10: S18–20 Schiff ER (1992) Atypical clinical manifestations of hepatitis A. Vaccine (Suppl 1) 10: S18–20
31.
Zurück zum Zitat Schott P, Hartmann H, Ramadori G (2001) Hepatitis C virus-associated mixed cryoglobulinemia. Clinical manifestations, histopathological changes, mechanisms of cryoprecipitation and options of treatment. Histol Histopathol 16: 1275–1285PubMed Schott P, Hartmann H, Ramadori G (2001) Hepatitis C virus-associated mixed cryoglobulinemia. Clinical manifestations, histopathological changes, mechanisms of cryoprecipitation and options of treatment. Histol Histopathol 16: 1275–1285PubMed
32.
Zurück zum Zitat Sebastiani GD, Bellisai F, Caudai C et al. (2005) Association of extrahepatic manifestations with HLA class II alleles and with virus genotype in HCV infected patients. J Biol Regul Homeost Agents 19: 17–22PubMed Sebastiani GD, Bellisai F, Caudai C et al. (2005) Association of extrahepatic manifestations with HLA class II alleles and with virus genotype in HCV infected patients. J Biol Regul Homeost Agents 19: 17–22PubMed
33.
Zurück zum Zitat Stefanutti C, Di Giacomo S, Mareri M et al. (2003) Immunoadsorption apheresis (Selesorb) in the treatment of chronic hepatitis C virus-related type 2 mixed cryoglobulinemia. Transfus Apher Sci 28: 207–214PubMedCrossRef Stefanutti C, Di Giacomo S, Mareri M et al. (2003) Immunoadsorption apheresis (Selesorb) in the treatment of chronic hepatitis C virus-related type 2 mixed cryoglobulinemia. Transfus Apher Sci 28: 207–214PubMedCrossRef
34.
Zurück zum Zitat Trebst C, Wedemeyer H, Manns MP et al. (2007) Treatment of hepatitis C virus-associated inflammatory polyneuropathy with pegylated interferon-alpha and ribavirin. Eur J Gastroenterol Hepatol 19: 91–92PubMedCrossRef Trebst C, Wedemeyer H, Manns MP et al. (2007) Treatment of hepatitis C virus-associated inflammatory polyneuropathy with pegylated interferon-alpha and ribavirin. Eur J Gastroenterol Hepatol 19: 91–92PubMedCrossRef
35.
Zurück zum Zitat Vallisa D, Bernuzzi P, Arcaini L et al. (2005) Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin’s lymphoma: a multicenter Italian experience. J Clin Oncol 23: 468–473PubMedCrossRef Vallisa D, Bernuzzi P, Arcaini L et al. (2005) Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin’s lymphoma: a multicenter Italian experience. J Clin Oncol 23: 468–473PubMedCrossRef
36.
Zurück zum Zitat Vigano M, Lampertico P, Rumi MG et al. (2007) Natural history and clinical impact of cryoglobulins in chronic hepatitis C: 10-year prospective study of 343 patients. Gastroenterology 133: 835–842PubMedCrossRef Vigano M, Lampertico P, Rumi MG et al. (2007) Natural history and clinical impact of cryoglobulins in chronic hepatitis C: 10-year prospective study of 343 patients. Gastroenterology 133: 835–842PubMedCrossRef
37.
Zurück zum Zitat Visentini M, Granata M, Veneziano ML et al. (2007) Efficacy of low-dose rituximab for mixed cryoglobulinemia. Clin Immunol 125: 30–33PubMedCrossRef Visentini M, Granata M, Veneziano ML et al. (2007) Efficacy of low-dose rituximab for mixed cryoglobulinemia. Clin Immunol 125: 30–33PubMedCrossRef
38.
Zurück zum Zitat Zignego AL, Brechot C (1999) Extrahepatic manifestations of HCV infection: facts and controversies. J Hepatol 31: 369–376PubMedCrossRef Zignego AL, Brechot C (1999) Extrahepatic manifestations of HCV infection: facts and controversies. J Hepatol 31: 369–376PubMedCrossRef
39.
Zurück zum Zitat Zuckerman E, Kessel A, Slobodin G et al. (2003) Antiviral treatment down-regulates peripheral B-cell CD81 expression and CD5 expansion in chronic hepatitis C virus infection. J Virol 77: 10432–10436PubMedCrossRef Zuckerman E, Kessel A, Slobodin G et al. (2003) Antiviral treatment down-regulates peripheral B-cell CD81 expression and CD5 expansion in chronic hepatitis C virus infection. J Virol 77: 10432–10436PubMedCrossRef
Metadaten
Titel
Hepatitis-assoziierte Kryoglobulinämie
verfasst von
S. Pischke
M. Cornberg
Prof. Dr. M.P. Manns
Publikationsdatum
01.03.2008
Verlag
Springer-Verlag
Erschienen in
Die Innere Medizin / Ausgabe 3/2008
Print ISSN: 2731-7080
Elektronische ISSN: 2731-7099
DOI
https://doi.org/10.1007/s00108-007-2014-7

Weitere Artikel der Ausgabe 3/2008

Der Internist 3/2008 Zur Ausgabe

Mitteilungen der Akademie

Mitteilungen der Akademie 03/08

CME Weiterbildung • Zertifizierte Fortbildung

Differenzialdiagnose und -abklärung von Lymphknotenvergrößerungen

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.