Summary
A six-year history of repeated attacks of fatigue, fever, arthralgias, skin changes, Raynaud's phenomenon, and neuropathy is reported in a patient with chronic liver disease. The following diagnoses were made: (1) leukocytoclastic vasculitis; (2) acute urticaria; (3) cryoglobulinemia type II with Raynaud's phenomenon and low serum level of C4; (4) peripheral polyneuropathy; (5) sicca syndrome; and (6) chronic hepatitis C virus infection. Despite therapy with corticosteroids symptoms increased gradually over years. In the first PCR of the nested PCR analysis, HCV-RNA was exclusively detected in the cryoglobulin fraction but not in the serum supernatant, suggesting that antibodies bind HCV particles, forming circulating immune complexes. As diagnoses 1-5 are well-known organ manifestations of cryoglobulinemia, we speculated whether treatment of hepatitis C with IFN-μ (3 million IU IFN-μ2b three times a week) would inhibit HCV replication, decrease the cryocrit level and thereby ameliorate organ manifestations such as neuropathy and vasculities. During treatment with IFN-μ only a very weak or no signal could be detected for HCV-RNA in the cryoglobulin fraction as well as in the serum supernatant. This held true also for the serum supernatant in the second PCR. In parallel, cryoglobulin level, immunoglobulins, and liver enzymes decreased substantially to normal or near normal levels. Clinical symptoms—leukocytoclastic vasculitis and neuropathy—disappeared. We conclude that chronic HCV infection is involved in the pathogenesis of cryoglobulinemia and that IFN-μ might be an effective treatment in these patients.
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Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Gerber MA, Sampliner RE, Meeks EL, Beach MJ, for the Sentinel Counties Chronic Non-A, Non-B Hepatitis Study Team: The natural history of community-acquired hepatitis C in the United States. N Engl J Med 327:1899–1905, 1992
Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, Hollinger FB, Gitnick G, Knodell RG, Perrillo RP, Stevens CE, Hollingsworth CG, National Heart Lung, and Blood Institute Study Group: Long-term mortality after transfusion-associated non-A, non-B hepatitis. N Engl J Med 327:1906–1911, 1992
Agnello V, Chung R, Kaplan LM: A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 327:1490–1495, 1992
Casato M, Taliani G, Pucillo LP, Goffredo F, Lagana B, Bonomo L: Cryoglobulinemia and hepatitis C virus. Lancet 337:1047–1048, 1991
Ferri C, Greco F, Longombardo G, Palla P, Moretti A, Marzo E, Fosella PV, Pasero G, Bombardieri S: Antibodies against hepatitis C virus in mixed cryoglobulinemia patients. Infection 19:417–420, 1991
Misiani R, Bellavita P, Borelli G, Marchesi D, Massazza M, Vendramin G, Comotti B, Tanzi E, Scudeller G, Zanetti A: Hepatitis C virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med 117:573–577, 1992
Marcellin P, Descamps V, Martinot-Peignoux M, Larzul D, Xu L, Boyer N, Pham B-M, Crickx B, Guillevin L, Belaich S, Erlinger S, Benhamou J-P: Cryoglobulinemia with vasculitis associated with hepatitis C virus infection. Gastroenterology 104:272–277, 1993
Cohen SJ, Pittelkow MR, Su WPD: Cutaneous manifestations of cryoglobulinemia: Clinical and histopathologic study or seventy-two patients. J Am Acad Dermatol 25:21–27, 1991
Durand JM, Lefevre P, Harle JR, Boucrat J, Vitvitski L, Soubeyrand J: Cutaneous vasculitis and cryoglobulinemia type II associated with hepatitis C virus infection. Lancet 337:499–500, 1991
Hearth-Holmes M, Zahranka SL, Beathge BA, Wolf RE: Leukoklastic vasculitis associated with hepatitis C. Am J Med 90:765–766, 1991
Herrero C, Vicente A, Bruguera M, Ercilla MG, Barrera JM, Vidal J, Teres J, Mascaro JM, Rodes J: Is hepatitis C virus infection a trigger of porphyria cutanea tarda? Lancet 341:788–789, 1993
Johnson RJ, Gretch DR, Yamabe H, Hart J, Bacchi CE, Hartwell P, Couser WG, Wener MH, Alpers CE, Willson R: Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med 328:465–470, 1993
Pakula AS, Garden JM, Roth SI: Cryoglobulinemia and cutaneous leukocytoclastic vasculitis associated with hepatitis C virus infection. J Am Acad Dermatol 28:850–853, 1993
Brouet J-C, Clauvel J-P, Danon F, Klein M, Seligmann M: Biologic and clinical significance of cryoglobulins. Am J Med 57:775–788, 1974
Gorevic PD, Kassab HJ, Yoram L, Kohn R, Meltzer M, Prose P, Franklin EC: Mixed cryoglobulinemia: Clinical aspects and long-term follow-up of 40 patients. Am J Med 69:287–308, 1980
Levo Y, Gorevic PD, Kassab HJ, Zucker-Franklin D, Franklin EC: Association between hepatitis B virus and essential cryoglobulinemia. N Engl J Med 296:1501–1504, 1977
Popp J-W Jr, Dienstag JL, Wands JR, Bloch KJ: Essential mixed cryoglobulinemia without evidence for hepatitis B virus infection. Ann Intern Med 92:379–383, 1980
Garson JA, Tedder RS, Briggs M, Tuke P, Glazebrook JA, Trute A, Parker D, Barbara JAJ, Contreras M, Aloysius S: Detection of hepatitis C viral sequences in blood donations by “nested” polymerase chain reaction and prediction of infectivity. Lancet 335:1419–1422, 1990
Durand JM, Kaplanski G, Lefevre P, Richard MA, Andrac L, Trepo C, Soubeyrand J: Effect of interferon-alpha 2b on cryoglobulinemia related to hepatitis C virus infection. J Infect Dis 165:779–780, 1992
Ferri C, Zignego L, Longombardo G, Monti M, La Civita L, Lombardini F, Greco F, Mazzoni A, Pasero G, Gentilini P, Bombardieri S, Manns M: Effect of alpha-interferon on hepatitis C virus chronic infection in mixed cryoglobulinemia patients. Infection 21:93–97, 1993
Bonomo L, Casato M, Afeltra A, Caccavo D: Treatment of idiopathic mixed cryoglobulinemia with alpha interferon. Am J Med 83:726–730, 1987
Casato M, Laganá B, Antonelli G, Diazani F, Bonomo L: Long-term results of therapy with interferon-alpha for type II essential mixed cryoglobulinemia. Blood 78:3142–3147, 1991
Margin S, Craxi A, Di Marco V, Lolacono O, Fabiano C, Diquattro O, Fiorentino G, Marino L, Simonetti R, Almasio P, Wilber J, Urdea M, Neuwald P, Pagliaro L: Hepatitis C viremia in chronic liver disease: Response to corticosteroids and alpha-interferon. J Hepatol 18(suppl 1):S51, 1993 (abstract)
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Dedicated to Gustav Paumgartner on his 60th birthday.
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Schirren, C.A., Zachoval, R., Schirren, C.G. et al. A role for chronic hepatitis C virus infection in a patient with cutaneous vasculitis, cryoglobulinemia, and chronic liver disease. Digest Dis Sci 40, 1221–1225 (1995). https://doi.org/10.1007/BF02065527
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DOI: https://doi.org/10.1007/BF02065527