Skip to main content

Advertisement

SpringerLink
Log in

Vasculitic complications of interferon-α treatment for chronic hepatitis C virus infection: case report and review of the literature

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Chronic infection with hepatitis C virus (HCV) may be complicated by the development of systemic vasculitis. Vasculitis is either caused by mixed cryoglobulinemia or a non-cryoglobulinemic vasculitis resembling polyarteritis nodosa (PAN). Antiviral treatment with interferon-α (IFN) and subsequent clearing of HCV mostly leads to improvement of vasculitic symptoms, but vasculitis may also be exacerbated and even cases of new onset of vasculitis may occur. Exacerbations of both cryoglobulinemic and PAN-type vasculitis in chronic HCV infection have been described under treatment with IFN. The most common symptom is vasculitic neuropathy. However, peripheral neuropathy in a HCV-infected patient treated with IFN may also be caused by direct neurotoxic or antiangiogenic effects of IFN itself, often requiring a nerve biopsy to establish the exact diagnosis. The clinical course of vasculitic complications of IFN treatment is variable and ranges from regression of symptoms despite continuation of IFN treatment to fatal exacerbations despite termination of IFN treatment and additional immunosuppressive therapy. In most cases of IFN-induced vasculitis, immunosuppressive therapy with corticosteroids has been employed, leading to improvement of symptoms. We report the case of a patient with chronic HCV infection who first developed cryoglobulinemic vasculitis after initiation of therapy with the polyethylene glycol (PEG)-conjugated form of IFN (PEG-IFN) and discuss it in the context of the relevant literature. First onset of cryoglobulinemic vasculitis after initiation of IFN therapy has not been described so far.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette J et al (1999) Extrahepatic manifestations of chronic hepatitis C. Arthritis Rheum 42:2204–2212

    Article  CAS  PubMed  Google Scholar 

  2. Boonyapisit K, Katirji B (2002) Severe exacerbation of hepatitis C associated vasculitic neuropathy following treatment with interferon alpha. A case report and literature review. Muscle Nerve 25:909–913

    Article  PubMed  Google Scholar 

  3. Cacoub P, Maisonobe T, Thibault V, Gatel A, Servan J, Musset L et al (2001) Systemic vasculitis in patients with hepatitis C. J Rheumatol 28:109–118

    Google Scholar 

  4. Agnello V, Abel G (1997) Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia. Arthritis Rheum 40:2007–2015

    Google Scholar 

  5. Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M et al (1994) Cryoglobulinemia in chronic liver disease: role of hepatitis C virus and liver damage. Gastroenterology 106:1291–1300

    CAS  PubMed  Google Scholar 

  6. Donada C, Crucitti A, Danodon V, Tommasi L, Zanette G, Crovatto M et al (1998) Systemic manifestations and liver disease in patients with chronic hepatitis C and type II or III mixed cryoglobulinemia. J Viral Hep 5:179–185

    Article  CAS  Google Scholar 

  7. Agnello V (2000) Mixed cryoglobulinemia and other extrahepatic manifestations of hepatitis C virus infection. In: Liang HJ (ed) Hepatitis C. Academic, San Diego, pp 295–313

    Google Scholar 

  8. Ferri C, La Civita L, Cirafisi C, Siciliano G, Longombardo G, Bombardieri S et al (1992) Peripheral neuropathy in mixed cryoglobulinemia: clinical and electrophysiologic investigations. J Rheumatol 19:889–895

    CAS  PubMed  Google Scholar 

  9. Cacoub P, Renou C, Kerr G, Hue S, Rosenthal E, Cohen P et al (2001) Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia. Arthritis Rheum 44:2118–2124

    Article  CAS  PubMed  Google Scholar 

  10. Naarendorp M, Kallemuchikkal U, Nuovo G, Gorevic P (2001) Longterm efficacy of interferon-alpha for extrahepatic disease associated with hepatitis C virus infection. J Rheumatol 28:2466–2473

    Google Scholar 

  11. Cacoub P, Lidove O, Maisonobe T, Duhaut P, Thibault V, Ghillani P et al (2002) Interferon-alpha and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum 46:3317–3326

    Article  CAS  PubMed  Google Scholar 

  12. Misiani R, Bellavita P, Fenili D, Vicari O, Marchesi D, Sironi P et al (1994) Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 330:751–756

    Article  CAS  PubMed  Google Scholar 

  13. Fattovich G, Giustina G, Favarato S, Ruol A (1996) A survey of adverse events in 11241 patients with chronic viral hepatitis treated with alfa interferon. J Hepatol 24:38–47

    Article  CAS  PubMed  Google Scholar 

  14. D’Amico G (1998) Renal involvement in hepatitis C infection: cryoglobulinemic glomerulonephritis. Kidney Int 54:650–671

    Article  CAS  PubMed  Google Scholar 

  15. Wilson L, Widman D, Dikman S, Gorevic P (2002) Autoimmune disease complicating antiviral therapy for hepatitis C virus infection. Semin Arthritis Rheum 32:163–173

    Google Scholar 

  16. Harle J-R, Disdier P, Pelletier J, Azulay J-P, Perreard M, Weiller J-P (1995) Dramatic worsening of hepatitis C-related cryoglobulinemia subsequent to treatment with interferon alfa. JAMA 275:126

    Article  Google Scholar 

  17. Zimmermann R, Konig V, Bauditz J, Hopf U (1993) Interferon alfa in leukocytoclastic vasculitis, mixed cryoglobulinemia, and chronic hepatitis C. Lancet 341:561–562

    Article  CAS  Google Scholar 

  18. Batisse D, Karmochkine M, Jacquot C, Kazatchkine MD, Weiss L (2004) Sustained exacerbation of cryoglobulinemia-related vasculitis following treatment of hepatitis C with peginterferon alfa. Eur J Gastroenterol Hepatol 16:701–703

    Article  CAS  PubMed  Google Scholar 

  19. Lidove O, Cacoub P, Maisonobe T, Thibault V, Piette J-C, Lèger J-M (2001) Hepatitis C virus with peripheral neuropathy is not always associated with cryoglobulinemia. Ann Rheum Dis 60:290–292

    Google Scholar 

  20. Paoletti V, Donnarumma L, De Matteis A, Mammarella A, Labbadia G, Musca A et al (2000) Peripheral neuropathy without cryoglobulinemia in patients with hepatitis C virus infection. Panminerva Med 42:175–178

    CAS  PubMed  Google Scholar 

  21. Gupta R, Singh S, Tang R, Blackwell T, Schiffman J (2002) Anterior ischemic optic neuropathy caused by interferon alpha therapy. Am J Med 112:683–684

    Article  PubMed  Google Scholar 

  22. Cid M, Hernandez-Rodriguez J, Robert J, Del Rio A, Casademont J, Coll-Vinent B et al (1999) Interferon-α may exacerbate cryoglobulinemia-related ischemic manifestations. Arthritis Rheum 42:1051–1055

    Article  CAS  PubMed  Google Scholar 

  23. Lidove O, Cacoub P, Hausfater P, Wechsler B, Frances C, Leger J-M et al (1999) Hepatitis C virus and cryoglobulinemia: worsening of peripheral neuropathy after interferon alpha treatment. Gastroenterol Clin Biol 23:403–406

    CAS  PubMed  Google Scholar 

  24. Negoro K, Fukusako T, Morimatsu M (1994) Acute axonal polyneuropathy during interferon a-2a therapy for chronic hepatitis type C. Muscle Nerve 17:1351–1352

    CAS  PubMed  Google Scholar 

  25. Zuber M, Gause A (1997) Peripheral neuropathy during interferon-a therapy in patients with cryoglobulinemia and hepatitis virus infection. J Rheumatol 24:2488–2489

    CAS  PubMed  Google Scholar 

  26. Jefferson J, Johnson R (2000) Treatment of hepatitis C-associated glomerular disease. Semin Nephrol 20:286–292

    CAS  PubMed  Google Scholar 

  27. Gorevic P, Kassab H, Levo Y, Kohn R, Meltzner M, Prose P et al (1980) Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients. Am J Med 69:287–308

    Article  CAS  PubMed  Google Scholar 

  28. Gupta G, Holmes S, Spence E, Mills P (2000) Capillaritis associated with interferon-alfa treatment of chronic hepatitis C infection. J Am Acad Dermatol 43:937–938

    Article  CAS  PubMed  Google Scholar 

  29. Friedmann G, Mehta S, Sherker A (1999) Fatal exacerbation of hepatitis C related cryoglobulinemia with interferon-α therapy. Dig Dis Sci 44:1364–1365

    Article  PubMed  Google Scholar 

  30. Kokado Y, Takahara S, Ichimaru N, Toki K, Wang J, Permpongkosol S et al (2000) Clinical outcome of HCV infection after renal transplantation. Transplant Proc 32:1940–1943

    Google Scholar 

  31. Paterton D, Fain O, Sehonnou J, Trinchet J, Beugrand M (1996) Severe necrotizing vasculitis in a patient with hepatitis C virus infection treated by interferon. Clin Exp Rheumatol 14:79–81

    PubMed  Google Scholar 

  32. La Civita L, Pasero G, Ferri C (1997) Axonal neuropathy in a patient receiving interferon-alpha therapy for chronic hepatitis C. J Rheumatol 24:1656–1657

    PubMed  Google Scholar 

  33. Ferri C, La Civita L, Fazzi P, Pasero G (1996) Polymyositis, lung fibrosis and cranial neuropathy in a patient with hepatitis C virus infection. Arthritis Rheum 39:1074–1075

    CAS  PubMed  Google Scholar 

  34. Gordon A, Edgar JD, Finch R (1998) Acute exacerbation of vasculitis during interferon-alpha therapy for hepatitis C-associated cryoglobulinaemia. J Infect 36:229–230

    Article  CAS  PubMed  Google Scholar 

  35. Scelsa S, Herskovitz S, Reichler B (1998) Treatment of mononeuropathy multiplex in hepatitis C virus and cryoglobulinemia. Muscle Nerve 21:1526–1529

    Article  CAS  PubMed  Google Scholar 

  36. Bojic I, Lilc D, Radojic C, Mijuskovic P (1994) Deterioration of mixed cryoglobulinemia during treatment with interferon-alpha-2a. J Gastroenterol 29:369–371

    CAS  PubMed  Google Scholar 

  37. Tambini R, Quattrini A, Fracasetti O, Nemni R (1997) Axonal neuropathy in a patient receiving interferon-alpha therapy for chronic hepatitis C. J Rheumatol 24:1656–1657

    PubMed  Google Scholar 

  38. Quatrini A, Comi G, Nemni R, Martinelli V, Villa A, Caimi M et al (1997) Axonal neuropathy associated with interferon-a treatment for hepatitis C: HLA-DR immunoreactivity in Schwann cells. Acta Neuropathol 94:504–508

    Article  PubMed  Google Scholar 

  39. Irioka T, Yamada M, Yamawaki M, Mizusawa H (2001) Acute autonomic and sensory neuropathy after interferon a-2b therapy for chronic hepatitis C. J Neurol Neurosurg Psychiatr 70:408–410

    Article  CAS  PubMed  Google Scholar 

  40. Marzo ME, Tintore M, Fabregues O, Montalban O, Codina A (1998) Chronic inflammatory demyelinating neuropathy during treatment with interferon-α. J Neurol Neurosurg Psychiatr 65:604

    CAS  Google Scholar 

  41. Merrigiolli M, Rowin J (2000) Chronic inflammatory demyelinating neuropathy after treatment with interferon-α. Muscle Nerve 23:433–435

    Article  PubMed  Google Scholar 

  42. Rutkove S (1997) An unusual axonal polyneuropathy induced by low-dose interferon alfa-2a. Arch Neurol 54:907–908

    CAS  PubMed  Google Scholar 

  43. Manesis E, Petrou C, Brouzas D, Hadziyannis S (1994) Optic tract neuropathy complicating low-dose interferon treatment. J Hepatol 21:474–477

    CAS  PubMed  Google Scholar 

  44. Fukumoto Y, Shigemitsu T, Omura R, Harada T, Okita K (1994) Abducent nerve paralysis during interferon alpha-2a therapy in a case of chronic active hepatitis C. Intern Med 33:637–640

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland

    Wilke Beuthien, Hans-Ullrich Mellinghoff & Johannes von Kempis

Authors
  1. Wilke Beuthien
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hans-Ullrich Mellinghoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Johannes von Kempis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Johannes von Kempis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beuthien, W., Mellinghoff, HU. & Kempis, J.v. Vasculitic complications of interferon-α treatment for chronic hepatitis C virus infection: case report and review of the literature. Clin Rheumatol 24, 507–515 (2005). https://doi.org/10.1007/s10067-005-1093-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-005-1093-x

Keywords

Search

Navigation