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Disease associations of human herpesvirus 8 infection

INTRODUCTION

The epidemiology of Kaposi sarcoma (KS), a rare malignancy prior to the advent of the AIDS epidemic, suggested a link between the development of disease and a transmissible agent. In 1994, a novel gamma herpesvirus was subsequently identified in KS biopsies. After sequence analysis of the genome and characterization of the viral life cycle, this virus was subsequently named human herpesvirus 8 (HHV-8), or Kaposi sarcoma associated herpesvirus (KSHV).

The first disease associated with HHV-8 infection was KS. However, it soon became appreciated that several other conditions, especially body cavity based lymphoma (also known as primary effusion lymphoma or PEL) and Castleman's disease, were also linked to this virus. Host factors influence disease expression, since HHV-8 seroprevalence is relatively common. The onset of disease typically occurs several years after acquisition of infection.

The diseases that are or may be associated with HHV-8 infection will be reviewed here. The epidemiology, mode of transmission, diagnosis, and treatment of HHV-8 infection are discussed separately. (See "Virology, epidemiology, and transmission of human herpesvirus 8 infection" and "Diagnosis and antiviral therapy of human herpesvirus 8 infection".)

PRIMARY INFECTION

The symptoms and signs of primary infection with subsequent HHV-8 seroconversion have been described in children, men who have sex with men (MSM), and immunocompromised hosts.

Children — Primary HHV-8 infection may be associated with fever and a maculopapular rash in immunocompetent children. Evidence of HHV-8 infection was determined by serology and polymerase chain reaction (PCR) of blood and saliva in a prospective study of 86 children who presented to an emergency department with a febrile syndrome of uncertain origin [1]. Thirty-six (42 percent) were seropositive; 14 of these patients had PCR evidence of HHV-8 DNA (mostly in saliva), but only six had evidence supporting primary HHV-8 infection.

                    

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Literature review current through: Nov 2014. | This topic last updated: Oct 10, 2013.
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References
Top
  1. Andreoni M, Sarmati L, Nicastri E, et al. Primary human herpesvirus 8 infection in immunocompetent children. JAMA 2002; 287:1295.
  2. Wang QJ, Jenkins FJ, Jacobson LP, et al. Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins. Blood 2001; 97:2366.
  3. Casper C, Wald A, Pauk J, et al. Correlates of prevalent and incident Kaposi's sarcoma-associated herpesvirus infection in men who have sex with men. J Infect Dis 2002; 185:990.
  4. Luppi M, Barozzi P, Santagostino G, et al. Molecular evidence of organ-related transmission of Kaposi sarcoma-associated herpesvirus or human herpesvirus-8 in transplant patients. Blood 2000; 96:3279.
  5. Oksenhendler E, Cazals-Hatem D, Schulz TF, et al. Transient angiolymphoid hyperplasia and Kaposi's sarcoma after primary infection with human herpesvirus 8 in a patient with human immunodeficiency virus infection. N Engl J Med 1998; 338:1585.
  6. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994; 266:1865.
  7. Moore PS, Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med 1995; 332:1181.
  8. Chuck S, Grant RM, Katongole-Mbidde E, et al. Frequent presence of a novel herpesvirus genome in lesions of human immunodeficiency virus-negative Kaposi's sarcoma. J Infect Dis 1996; 173:248.
  9. Buonaguro FM, Tornesello ML, Beth-Giraldo E, et al. Herpesvirus-like DNA sequences detected in endemic, classic, iatrogenic and epidemic Kaposi's sarcoma (KS) biopsies. Int J Cancer 1996; 65:25.
  10. Sitas F, Carrara H, Beral V, et al. Antibodies against human herpesvirus 8 in black South African patients with cancer. N Engl J Med 1999; 340:1863.
  11. Purvis SF, Katongole-Mbidde E, Johnson JL, et al. High incidence of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in tumor lesions and peripheral blood mononuclear cells from patients with Kaposi's sarcoma in Uganda. J Infect Dis 1997; 175:947.
  12. Dupin N, Grandadam M, Calvez V, et al. Herpesvirus-like DNA sequences in patients with Mediterranean Kaposi's sarcoma. Lancet 1995; 345:761.
  13. Gao SJ, Kingsley L, Hoover DR, et al. Seroconversion to antibodies against Kaposi's sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi's sarcoma. N Engl J Med 1996; 335:233.
  14. Iscovich J, Boffetta P, Winkelmann R, et al. Classic Kaposi's sarcoma in Jews living in Israel, 1961-1989: a population-based incidence study. AIDS 1998; 12:2067.
  15. Cook-Mozaffari P, Newton R, Beral V, Burkitt DP. The geographical distribution of Kaposi's sarcoma and of lymphomas in Africa before the AIDS epidemic. Br J Cancer 1998; 78:1521.
  16. Taylor JF, Templeton AC, Vogel CL, et al. Kaposi's sarcoma in Uganda: a clinico-pathological study. Int J Cancer 1971; 8:122.
  17. Penn I. Kaposi's sarcoma in transplant recipients. Transplantation 1997; 64:669.
  18. Gallant JE, Moore RD, Richman DD, et al. Risk factors for Kaposi's sarcoma in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group. Arch Intern Med 1994; 154:566.
  19. Qunibi W, Al-Furayh O, Almeshari K, et al. Serologic association of human herpesvirus eight with posttransplant Kaposi's sarcoma in Saudi Arabia. Transplantation 1998; 65:583.
  20. Grossman Z, Iscovich J, Schwartz F, et al. Absence of Kaposi sarcoma among Ethiopian immigrants to Israel despite high seroprevalence of human herpesvirus 8. Mayo Clin Proc 2002; 77:905.
  21. Chen N, Nelson KE, Jenkins FJ, et al. Seroprevalence of human herpesvirus 8 infection in Northern Thailand. Clin Infect Dis 2004; 39:1052.
  22. Chariyalertsak S, Sirisanthana T, Saengwonloey O, Nelson KE. Clinical presentation and risk behaviors of patients with acquired immunodeficiency syndrome in Thailand, 1994--1998: regional variation and temporal trends. Clin Infect Dis 2001; 32:955.
  23. Vitale F, Briffa DV, Whitby D, et al. Kaposi's sarcoma herpes virus and Kaposi's sarcoma in the elderly populations of 3 Mediterranean islands. Int J Cancer 2001; 91:588.
  24. Penn I. Sarcomas in organ allograft recipients. Transplantation 1995; 60:1485.
  25. Farge D. Kaposi's sarcoma in organ transplant recipients. The Collaborative Transplantation Research Group of Ile de France. Eur J Med 1993; 2:339.
  26. Francès C, Mouquet C, Marcelin AG, et al. Outcome of kidney transplant recipients with previous human herpesvirus-8 infection. Transplantation 2000; 69:1776.
  27. Diociaiuti A, Nanni G, Cattani P, et al. HHV8 in renal transplant recipients. Transpl Int 2000; 13 Suppl 1:S410.
  28. Cattani P, Capuano M, Graffeo R, et al. Kaposi's sarcoma associated with previous human herpesvirus 8 infection in kidney transplant recipients. J Clin Microbiol 2001; 39:506.
  29. Regamey N, Tamm M, Wernli M, et al. Transmission of human herpesvirus 8 infection from renal-transplant donors to recipients. N Engl J Med 1998; 339:1358.
  30. Barozzi P, Luppi M, Facchetti F, et al. Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors. Nat Med 2003; 9:554.
  31. Mendez JC, Paya CV. Kaposi's Sarcoma and Transplantation. Herpes 2000; 7:18.
  32. Sin SH, Roy D, Wang L, et al. Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Blood 2007; 109:2165.
  33. Bhatt AP, Bhende PM, Sin SH, et al. Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas. Blood 2010; 115:4455.
  34. Guba M, von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002; 8:128.
  35. Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005; 352:1317.
  36. Cesarman E, Chang Y, Moore PS, et al. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995; 332:1186.
  37. Nador RG, Cesarman E, Chadburn A, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 1996; 88:645.
  38. Strauchen JA, Hauser AD, Burstein D, et al. Body cavity-based malignant lymphoma containing Kaposi sarcoma-associated herpesvirus in an HIV-negative man with previous Kaposi sarcoma. Ann Intern Med 1996; 125:822.
  39. Carbone A, Gloghini A, Vaccher E, et al. Kaposi's sarcoma-associated herpesvirus DNA sequences in AIDS-related and AIDS-unrelated lymphomatous effusions. Br J Haematol 1996; 94:533.
  40. Casper C. The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol 2005; 129:3.
  41. Uldrick TS, Wang V, O'Mahony D, et al. An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease. Clin Infect Dis 2010; 51:350.
  42. Gyulai R, Kemény L, Kiss M, et al. Human herpesvirus 8 DNA sequences in angiosarcoma of the face. Br J Dermatol 1997; 137:467.
  43. McDonagh DP, Liu J, Gaffey MJ, et al. Detection of Kaposi's sarcoma-associated herpesvirus-like DNA sequence in angiosarcoma. Am J Pathol 1996; 149:1363.
  44. Remick SC, Patnaik M, Ziran NM, et al. Human herpesvirus-8-associated disseminated angiosarcoma in an HIV-seronegative woman: report of a case and limited case-control virologic study in vascular tumors. Am J Med 2000; 108:660.
  45. Steiner MC, Smith ME, Spittle MF. A patient with classical Kaposi's sarcoma and angiosarcoma: bad luck or a common aetiology? Clin Oncol (R Coll Radiol) 1997; 9:186.
  46. Lasota J, Miettinen M. Absence of Kaposi's sarcoma-associated virus (human herpesvirus-8) sequences in angiosarcoma. Virchows Arch 1999; 434:51.
  47. Lin BT, Chen YY, Battifora H, Weiss LM. Absence of Kaposi's sarcoma-associated herpesvirus-like DNA sequences in malignant vascular tumors of the serous membranes. Mod Pathol 1996; 9:1143.
  48. Lebbé C, Tatoud R, Morel P, et al. Human herpesvirus 8 sequences are not detected in epithelial tumors from patients receiving transplants. Arch Dermatol 1997; 133:111.
  49. Murakami M, Sugita Y, Ishii N, et al. Detection and sequence diversity of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) DNA. Eur J Dermatol 1999; 9:13.
  50. Takata M, Hatta N, Takehara K, Fujiwara H. Absence of human herpesvirus-8 DNA in angiosarcomas and other skin tumours in immunocompetent patients, and in graft-versus-host disease in the immunosuppressed recipients of bone marrow transplants. Br J Dermatol 1997; 137:156.
  51. Tomita Y, Naka N, Aozasa K, et al. Absence of Kaposi's-sarcoma-associated herpesvirus-like DNA sequences (KSHV) in angiosarcomas developing in body-cavity and other sites. Int J Cancer 1996; 66:141.
  52. Memar OM, Rady PL, Goldblum RM, et al. Human herpesvirus 8 DNA sequences in blistering skin from patients with pemphigus. Arch Dermatol 1997; 133:1247.
  53. Jang HS, Oh CK, Lim JY, et al. Detection of human herpesvirus 8 DNA in pemphigus and chronic blistering skin diseases. J Korean Med Sci 2000; 15:442.
  54. Bezold G, Sander CA, Flaig MJ, et al. Lack of detection of human herpesvirus (HHV)-8 DNA in lesional skin of German pemphigus vulgaris and pemphigus foliaceus patients. J Invest Dermatol 2000; 114:739.
  55. Dupin N, Marcelin AG, Calvez V, Andr C. Absence of a link between human herpesvirus 8 and pemphigus. Br J Dermatol 1999; 141:159.
  56. Cathomas G, Stalder A, Regamey N, et al. No evidence of HHV-8 infection in patients with pemphigus vulgaris/foliaceus. Arch Dermatol 1998; 134:1162.
  57. Cohen SS, Weinstein MD, Herndier BG, et al. No evidence of human herpesvirus 8 infection in patients with paraneoplastic pemphigus, pemphigus vulgaris, or pemphigus foliaceus. J Invest Dermatol 1998; 111:781.
  58. Avalos-Peralta P, Herrera A, Ríos-Martín JJ, et al. Localized Kaposi's sarcoma in a patient with pemphigus vulgaris. J Eur Acad Dermatol Venereol 2006; 20:79.
  59. Pantanowitz L, Dezube BJ. Kaposi's sarcoma and pemphigus. J Eur Acad Dermatol Venereol 2007; 21:571.
  60. Trento E, Castilletti C, Ferraro C, et al. Human herpesvirus 8 infection in patients with cutaneous lymphoproliferative diseases. Arch Dermatol 2005; 141:1235.
  61. Henghold WB 2nd, Purvis SF, Schaffer J, et al. No evidence of KSHV/HHV-8 in mycosis fungoides or associated disorders. J Invest Dermatol 1997; 108:920.
  62. Nagore E, Ledesma E, Collado C, et al. Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T- and B-cell lymphomas. Br J Dermatol 2000; 143:320.
  63. Kreuter A, Bischoff S, Skrygan M, et al. High association of human herpesvirus 8 in large-plaque parapsoriasis and mycosis fungoides. Arch Dermatol 2008; 144:1011.
  64. Rettig MB, Ma HJ, Vescio RA, et al. Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science 1997; 276:1851.
  65. Said JW, Rettig MR, Heppner K, et al. Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. Blood 1997; 90:4278.
  66. Hoffman LJ, Bunker CH, Pellett PE, et al. Elevated seroprevalence of human herpesvirus 8 among men with prostate cancer. J Infect Dis 2004; 189:15.
  67. Cool CD, Rai PR, Yeager ME, et al. Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med 2003; 349:1113.
  68. Laney AS, De Marco T, Peters JS, et al. Kaposi sarcoma-associated herpesvirus and primary and secondary pulmonary hypertension. Chest 2005; 127:762.
  69. Montani D, Marcelin AG, Sitbon O, et al. Human herpes virus 8 in HIV and non-HIV infected patients with pulmonary arterial hypertension in France. AIDS 2005; 19:1239.
  70. Di Alberti L, Piattelli A, Artese L, et al. Human herpesvirus 8 variants in sarcoid tissues. Lancet 1997; 350:1655.
  71. Bélec L, Mohamed AS, Lechapt-Zalcman E, et al. Lack of HHV-8 DNA sequences in sarcoid tissues of French patients. Chest 1998; 114:948.
  72. Maeda H, Niimi T, Sato S, et al. Human herpesvirus 8 is not associated with sarcoidosis in Japanese patients. Chest 2000; 118:923.
  73. Sobngwi E, Choukem SP, Agbalika F, et al. Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-saharan africans. JAMA 2008; 299:2770.
  74. Caselli E, Rizzo R, Ingianni A, et al. High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus. J Med Virol 2013.