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Cutaneous Manifestations of Viral Hepatitis

  • Ahmed AkhterEmail author
  • Adnan SaidEmail author
Skin, Soft Tissue, Bone and Joint Infectious Diseases (N Safdar, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Skin, Soft Tissue, Bone and Joint Infections

Abstract

There are several extrahepatic cutaneous manifestations associated with hepatitis B and hepatitis C virus infection. Serum sickness and polyarteritis nodosa are predominantly associated with hepatitis B infection, whereas mixed cryoglobulinemia associated vasculitis and porphyria cutanea tarda are more frequently seen in hepatitis C infection. The clinico-pathogenic associations of these skin conditions are not completely defined but appear to involve activation of the host immune system including the complement system. Management of the aforementioned cutaneous manifestations of viral hepatitis is often similar to that done in cases without viral hepatitis, with control of immune activation being a key strategy. In cases associated with hepatitis B and C, control of viral replication with specific antiviral therapy is also important and associated with improvement in most of the associated clinical manifestations.

Keywords

Extrahepatic manifestations Hepatitis B Hepatitis C Serum sickness Polyarteritis nodosa Gianotti-Crosti syndrome Mixed cryoglobulinemia Porphyria cutanea tarda Lichen planus Oral lichen planus 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Ahmed Akhter and Adnan Said have no conflicts of interest.

Human and Animal Rights and Informed Consent

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

References

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

  1. 1.
    McMahon BJ, Alward WL, Hall DB, Heyward WL, Bender TR, Francis DP, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis. 1985;151(4):599–603.PubMedCrossRefGoogle Scholar
  2. 2.
    Liaw YF, Tsai SL, Sheen IS, Chao M, Yeh CT, Hsieh SY, et al. Clinical and virological course of chronic hepatitis B virus infection with hepatitis C and D virus markers. Am J Gastroenterol. 1998;93(3):354–9. doi: 10.1111/j.1572-0241.1998.00354.x.PubMedCrossRefGoogle Scholar
  3. 3.
    Dienstag JL. Hepatitis B as an immune complex disease. Semin Liver Dis. 1981;1(1):45–57. doi: 10.1055/s-2008-1063929.PubMedCrossRefGoogle Scholar
  4. 4.
    Trepo C, Guillevin L. Polyarteritis nodosa and extrahepatic manifestations of HBV infection: the case against autoimmune intervention in pathogenesis. J Autoimmun. 2001;16(3):269–74. doi: 10.1006/jaut.2000.0502.PubMedCrossRefGoogle Scholar
  5. 5.
    Hollinger FB, Lau DT. Hepatitis B: the pathway to recovery through treatment. Gastroenterol Clin North Am. 2006;35(4):895–931. doi: 10.1016/j.gtc.2006.10.002.PubMedCrossRefGoogle Scholar
  6. 6.
    McElgunn PS. Dermatologic manifestations of hepatitis B virus infection. J Am Acad Dermatol. 1983;8(4):539–48.PubMedCrossRefGoogle Scholar
  7. 7.
    Popp JW, Harrist TJ, Dienstag JL, Bhan AK, Wands JR, LaMont JT, et al. Cutaneous vasculitis associated with acute and chronic hepatitis. Arch Intern Med. 1981;141(5):623–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Liang TJ. Hepatitis B: the virus and disease. Hepatology. 2009;49(5 Suppl):S13–21. doi: 10.1002/hep.22881.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Trepo C, Thivolet J. Hepatitis associated antigen and periarteritis nodosa (PAN). Vox Sang. 1970;19(3):410–1.PubMedCrossRefGoogle Scholar
  10. 10.
    Gocke DJ, Hsu K, Morgan C, Bombardieri S, Lockshin M, Christian CL. Association between polyarteritis and Australia antigen. Lancet. 1970;2(7684):1149–53.PubMedCrossRefGoogle Scholar
  11. 11.
    Drüeke T, Barbanel C, Jungers P, Digeon M, Poisson M, Brivet F, et al. Hepatitis B antigen-associated periarteritis nodosa in patients undergoing long-term hemodialysis. Am J Med. 1980;68(1):86–90.PubMedCrossRefGoogle Scholar
  12. 12.
    Guillevin L, Lhote F, Gayraud M, Cohen P, Jarrousse B, Lortholary O, et al. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore). 1996;75(1):17–28.CrossRefGoogle Scholar
  13. 13.
    Guillevin L, Lhote F, Cohen P, Sauvaget F, Jarrousse B, Lortholary O, et al. Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients. Medicine (Baltimore). 1995;74(5):238–53.CrossRefGoogle Scholar
  14. 14.
    Han SH. Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis. 2004;8(2):403–18.PubMedCrossRefGoogle Scholar
  15. 15.
    Shusterman N, London WT. Hepatitis B and immune-complex disease. N Engl J Med. 1984;310(1):43–6. doi: 10.1056/NEJM198401053100110.PubMedCrossRefGoogle Scholar
  16. 16.
    Guillevin L, Visser H, Noel LH, Pourrat J, Vernier I, Gayraud M, et al. Antineutrophil cytoplasm antibodies in systemic polyarteritis nodosa with and without hepatitis B virus infection and Churg-Strauss syndrome—62 patients. J Rheumatol. 1993;20(8):1345–9.PubMedGoogle Scholar
  17. 17.
    McKee PH, JE JC, SR G Pathology of the skin.Google Scholar
  18. 18.
    Wartelle-Bladou C, Lafon J, Trépo C, Pichoud C, Picon M, Pellissier JF, et al. Successful combination therapy of polyarteritis nodosa associated with a pre-core promoter mutant hepatitis B virus infection. J Hepatol. 2001;34(5):774–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Willson RA. Extrahepatic manifestations of chronic viral hepatitis. Am J Gastroenterol. 1997;92(1):3–17.PubMedGoogle Scholar
  20. 20.
    Ishimaru Y, Ishimaru H, Toda G, Baba K, Mayumi M. An epidemic of infantile papular acrodermatitis (Gianotti’s disease) in Japan associated with hepatitis-B surface antigen subtype ayw. Lancet. 1976;1(7962):707–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, et al. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d’Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C. Medicine (Baltimore). 2000;79(1):47–56.CrossRefGoogle Scholar
  22. 22.
    Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette JC, et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum. 1999;42(10):2204–12. doi: 10.1002/1529-0131(199910)42:10<2204::AID-ANR24>3.0.CO;2-D.PubMedCrossRefGoogle Scholar
  23. 23.
    Ferri C, Zignego AL. Relation between infection and autoimmunity in mixed cryoglobulinemia. Curr Opin Rheumatol. 2000;12(1):53–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Vassilopoulos D, Calabrese LH. Hepatitis C virus infection and vasculitis: implications of antiviral and immunosuppressive therapies. Arthritis Rheum. 2002;46(3):585–97. doi: 10.1002/art.10107.PubMedCrossRefGoogle Scholar
  25. 25.
    Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M. Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med. 1974;57(5):775–88.PubMedCrossRefGoogle Scholar
  26. 26.
    Sene D, Ghillani-Dalbin P, Thibault V, Guis L, Musset L, Duhaut P, et al. Long-term course of mixed cryoglobulinemia in patients infected with hepatitis C virus. J Rheumatol. 2004;31(11):2199–206.PubMedGoogle Scholar
  27. 27.
    Adinolfi LE, Utili R, Attanasio V, Zampino R, Ragone E, Tripodi MF, et al. Epidemiology, clinical spectrum and prognostic value of mixed cryoglobulinaemia in hepatitis C virus patients: a prospective study. Ital J Gastroenterol. 1996;28(1):1–9.PubMedGoogle Scholar
  28. 28.
    Donada C, Crucitti A, Donadon V, Tommasi L, Zanette G, Crovatto M, et al. Systemic manifestations and liver disease in patients with chronic hepatitis C and type II or III mixed cryoglobulinaemia. J Viral Hepat. 1998;5(3):179–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Marcucci F, Mele A. Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities. Blood. 2011;117(6):1792–8. doi: 10.1182/blood-2010-06-275818.PubMedCrossRefGoogle Scholar
  30. 30.
    Darling JM, Lemon SM, Fried MW. Schiff’s diseases of the liver, 11th ed. In: Schiff ER, Maddrey WC, Sorrell MF, editorsGoogle Scholar
  31. 31.
    Sène D, Limal N, Cacoub P. Hepatitis C virus-associated extrahepatic manifestations: a review. Metab Brain Dis. 2004;19(3–4):357–81.PubMedCrossRefGoogle Scholar
  32. 32.
    Zampino R, Marrone A, Restivo L, Guerrera B, Sellitto A, Rinaldi L, et al. Chronic HCV infection and inflammation: clinical impact on hepatic and extra-hepatic manifestations. World J Hepatol. 2013;5(10):528–40. doi: 10.4254/wjh.v5.i10.528.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Degasperi E, Aghemo A. Sofosbuvir for the treatment of chronic hepatitis C: between current evidence and future perspectives. Hepat Med. 2014;6:25–33. doi: 10.2147/HMER.S44375.PubMedCentralPubMedGoogle Scholar
  34. 34.•
    Pietrogrande M, De Vita S, Zignego AL, Pioltelli P, Sansonno D, Sollima S, et al. Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients. Autoimmun Rev. 2011;10(8):444–54. doi: 10.1016/j.autrev.2011.01.008. HCV-related MC is largely based on empirical data given the limited number of randomized controlled trials. This study was unique in that it used expert opinion from multiple medical specialties, given the nature of multi-organ involvement with MC, to recommend therapy for HCV-related MC. PubMedCrossRefGoogle Scholar
  35. 35.
    Dammacco F, Tucci FA, Lauletta G, Gatti P, De Re V, Conteduca V, et al. Pegylated interferon-alpha, ribavirin, and rituximab combined therapy of hepatitis C virus-related mixed cryoglobulinemia: a long-term study. Blood. 2010;116(3):343–53. doi: 10.1182/blood-2009-10-245878.PubMedCrossRefGoogle Scholar
  36. 36.
    Ferri C, Giuggioli D, Cazzato M, Sebastiani M, Mascia MT, Zignego AL. HCV-related cryoglobulinemic vasculitis: an update on its etiopathogenesis and therapeutic strategies. Clin Exp Rheumatol. 2003;21(6 Suppl 32):S78–84.PubMedGoogle Scholar
  37. 37.
    Chuang TY, Brashear R, Lewis C. Porphyria cutanea tarda and hepatitis C virus: a case–control study and meta-analysis of the literature. J Am Acad Dermatol. 1999;41(1):31–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Hussain I, Hepburn NC, Jones A, O’Rourke K, Hayes PC. The association of hepatitis C viral infection with porphyria cutanea tarda in the Lothian region of Scotland. Clin Exp Dermatol. 1996;21(4):283–5.PubMedCrossRefGoogle Scholar
  39. 39.
    O’Reilly FM, Darby C, Fogarty J, O’Moore R, Courtney MG, O’Connor J, et al. Porphyrin metabolism in hepatitis C infection. Photodermatol Photoimmunol Photomed. 1996;12(1):31–3.PubMedCrossRefGoogle Scholar
  40. 40.
    Sinclair PR, Bement WJ, Bonkovsky HL, Sinclair JF. Inhibition of uroporphyrinogen decarboxylase by halogenated biphenyls in chick hepatocyte cultures. Essential role for induction of cytochrome P-448. Biochem J. 1984;222(3):737–48.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Smith AG, Francis JE. Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload. Biochem J. 1987;246(1):221–6.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Frank J, Poblete-Gutiérrez P. Porphyria cutanea tarda—when skin meets liver. Best Pract Res Clin Gastroenterol. 2010;24(5):735–45. doi: 10.1016/j.bpg.2010.07.002.PubMedCrossRefGoogle Scholar
  43. 43.
    Ko HM, Hernandez-Prera JC, Zhu H, Dikman SH, Sidhu HK, Ward SC, et al. Morphologic features of extrahepatic manifestations of hepatitis C virus infection. Clin Dev Immunol. 2012;2012:740138. doi: 10.1155/2012/740138.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Okano J, Horie Y, Kawasaki H, Kondo M. Interferon treatment of porphyria cutanea tarda associated with chronic hepatitis type C. Hepatogastroenterology. 1997;44(14):525–8.PubMedGoogle Scholar
  45. 45.
    Takikawa H, Yamazaki R, Shoji S, Miyake K, Yamanaka M. Normalization of urinary porphyrin level and disappearance of skin lesions after successful interferon therapy in a case of chronic hepatitis C complicated with porphyria cutanea tarda. J Hepatol. 1995;22(2):249–50.PubMedCrossRefGoogle Scholar
  46. 46.
    Pawlotsky JM, Dhumeaux D, Bagot M. Hepatitis C virus in dermatology. Rev Arch Dermatol. 1995;131(10):1185–93.CrossRefGoogle Scholar
  47. 47.
    DeRossi SS, Ciarrocca KN. Lichen planus, lichenoid drug reactions, and lichenoid mucositis. Dent Clin North Am. 2005;49(1):77–89. doi: 10.1016/j.cden.2004.08.004. viii.PubMedCrossRefGoogle Scholar
  48. 48.
    Thornhill MH. Immune mechanisms in oral lichen planus. Acta Odontol Scand. 2001;59(3):174–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Stefanova-Petrova DV, Tzvetanska AH, Naumova EJ, Mihailova AP, Hadjiev EA, Dikova RP, et al. Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients. World J Gastroenterol. 2007;13(48):6518–28.PubMedCrossRefGoogle Scholar
  50. 50.
    Carrozzo M, Gandolfo S, Carbone M, Colombatto P, Broccoletti R, Garzino-Demo P, et al. Hepatitis C virus infection in Italian patients with oral lichen planus: a prospective case–control study. J Oral Pathol Med. 1996;25(10):527–33.PubMedCrossRefGoogle Scholar
  51. 51.
    Roy K, Bagg J. Hepatitis C virus and oral disease: a critical review. Oral Dis. 1999;5(4):270–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Zhou Y, Jiang L, Liu J, Zeng X, Chen QM. The prevalence of hepatitis C virus infection in oral lichen planus in an ethnic Chinese cohort of 232 patients. Int J Oral Sci. 2010;2(2):90–7. doi: 10.4248/IJOS10028.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Carrozzo M, Gandolfo S. Oral diseases possibly associated with hepatitis C virus. Crit Rev Oral Biol Med. 2003;14(2):115–27.PubMedCrossRefGoogle Scholar
  54. 54.
    Mega H, Jiang WW, Takagi M. Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection, oral lichenoid contact sensitivity reaction and idiopathic oral lichen planus. Oral Dis. 2001;7(5):296–305.PubMedCrossRefGoogle Scholar
  55. 55.
    Nagao Y, Sata M, Kage M, Kameyama T, Ueno T. Histopathological and immunohistochemical study of oral lichen planus-associated HCV infection. Eur J Intern Med. 2000;11(5):277–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Iraji F, Faghihi G, Asilian A, Siadat AH, Larijani FT, Akbari M. Comparison of the narrow band UVB versus systemic corticosteroids in the treatment of lichen planus: a randomized clinical trial. J Res Med Sci. 2011;16(12):1578–82.PubMedCentralPubMedGoogle Scholar
  57. 57.
    Carbone M, Arduino PG, Carrozzo M, Gandolfo S, Argiolas MR, Bertolusso G, et al. Course of oral lichen planus: a retrospective study of 808 northern Italian patients. Oral Dis. 2009;15(3):235–43. doi: 10.1111/j.1601-0825.2009.01516.x.PubMedCrossRefGoogle Scholar
  58. 58.
    Pyrsopoulos NT, Reddy KR. Extrahepatic manifestations of chronic viral hepatitis. Curr Gastroenterol Rep. 2001;3(1):71–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Ismail SB, Kumar SK, Zain RB. Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci. 2007;49(2):89–106.PubMedCrossRefGoogle Scholar
  60. 60.
    Voûte AB, Schulten EA, Langendijk PN, Kostense PJ, van der Waal I. Fluocinonide in an adhesive base for treatment of oral lichen planus. A double-blind, placebo-controlled clinical study. Oral Surg Oral Med Oral Pathol. 1993;75(2):181–5.PubMedCrossRefGoogle Scholar
  61. 61.•
    Lodi G, Carrozzo M, Furness S, Thongprasom K. Interventions for treating oral lichen planus: a systematic review. Br J Dermatol. 2012;166(5):938–47. doi: 10.1111/j.1365-2133.2012.10821.x. A systematic review including 28 randomized control trials that compared common therapies for OLP. There was no significant evidence to support superiority of either topical corticosteroids or topical calcineurin inhibitors in reducing pain associated with OLP. PubMedCrossRefGoogle Scholar
  62. 62.
    Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions for treating oral lichen planus. Cochrane Database Syst Rev. 2011;7:CD001168. doi: 10.1002/14651858.CD001168.pub2.PubMedGoogle Scholar
  63. 63.
    Corrocher G, Di Lorenzo G, Martinelli N, Mansueto P, Biasi D, Nocini PF, et al. Comparative effect of tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus. J Clin Periodontol. 2008;35(3):244–9. doi: 10.1111/j.1600-051X.2007.01191.x.PubMedCrossRefGoogle Scholar
  64. 64.
    Radfar L, Wild RC, Suresh L. A comparative treatment study of topical tacrolimus and clobetasol in oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105(2):187–93. doi: 10.1016/j.tripleo.2007.07.029.PubMedCrossRefGoogle Scholar
  65. 65.
    Sonthalia S, Singal A. Comparative efficacy of tacrolimus 0.1% ointment and clobetasol propionate 0.05% ointment in oral lichen planus: a randomized double-blind trial. Int J Dermatol. 2012;51(11):1371–8. doi: 10.1111/j.1365-4632.2012.05459.x.PubMedCrossRefGoogle Scholar
  66. 66.
    Hodgson TA, Sahni N, Kaliakatsou F, Buchanan JA, Porter SR. Long-term efficacy and safety of topical tacrolimus in the management of ulcerative/erosive oral lichen planus. Eur J Dermatol. 2003;13(5):466–70.PubMedGoogle Scholar
  67. 67.
    Silverman S, Gorsky M, Lozada-Nur F, Giannotti K. A prospective study of findings and management in 214 patients with oral lichen planus. Oral Surg Oral Med Oral Pathol. 1991;72(6):665–70.PubMedCrossRefGoogle Scholar
  68. 68.
    Verma KK, Mittal R, Manchanda Y. Azathioprine for the treatment of severe erosive oral and generalized lichen planus. Acta Derm Venereol. 2001;81(5):378–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Torti DC, Jorizzo JL, McCarty MA. Oral lichen planus: a case series with emphasis on therapy. Arch Dermatol. 2007;143(4):511–5. doi: 10.1001/archderm.143.4.511.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York (outside the USA) 2015

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA

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