Chronic verrucous varicella zoster virus skin lesions: clinical, histological, molecular and therapeutic aspects

[en] The outbreak of HIV infection introduced a new phenomenon in varicella zoster virus (VZV) pathology, namely the long-standing wart-like skin lesions that are frequently associated with resistance to thymidine kinase (TK)-dependent antiviral agents. This paper reviews the clinical, histological, and molecular aspects and the therapeutic management of these verrucous lesions. The majority of lesions are characterized by chronically evolving, unique or multiple wart-like cutaneous lesions. The main histopathological features include hyperkeratosis, verruciform acanthosis and VZV-induced cytopathic changes with scant or absent cytolysis of infected keratinocytes. The mechanism that establishes the chronic nature of the lesions appears to be associated with a particular pattern of VZV gene expression exhibiting reduced or nondetectable gE and gB synthesis. Drug resistance to TK-dependent antiviral agents is a result of nonfunctional or deficient viral TK. This necessitates alternative therapeutic management using antiviral agents that target the viral DNA polymerase.

Disciplines :

Immunology & infectious disease
Dermatology

Author, co-author :

Nikkels, Arjen ; Université de Liège - ULiège > Dermatologie

Snoeck, Robert

Rentier, Bernard ; Université de Liège - ULiège > Services administratifs généraux > Recteur - GIGA-R : Virologie - Immunologie

Pierard, Gérald ; Université de Liège - ULiège > Dermatopathologie

Language :

English

Title :

Chronic verrucous varicella zoster virus skin lesions: clinical, histological, molecular and therapeutic aspects

Publication date :

September 1999

Journal title :

Clinical and Experimental Dermatology

ISSN :

0307-6938

eISSN :

1365-2230

Publisher :

Blackwell

Volume :

Issue :

Pages :

346-353

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

The definitive version is available at http://www.blackwell-synergy.com/doi/pdf/10.1046/j.1365-2230.1999.00498.x

Available on ORBi :

since 30 January 2009

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Bibliography

Grose C. Varicella zoster virus infections: chickenpox, shingles and varicella vaccine. In: Herpes Virus Infections Glaser R, Jones JF. eds. New York: Marcel Dekker Inc., 1994: 1117-85.
Gilden DH, Mahalingham R, Dueland AM, Cohrs R. Herpes zoster: pathogenesis and latency. Prog Med Virol 1992; 39: 19-75.
Arvin AM. Varicella-zoster virus. Clin Microbiol Rev 1996; 9: 361-81.
Perronne C, Lazanas M, Leport C et al. Varicella in patients infected with the human Immunodeficiency virus. Arch Dermatol 1990: 126: 1033-6.
Cohen PR, Beltrani VP, Grossman ME. Disseminated herpes zoster in patients with human immunodeficiency virus infection. Am J Med 1988; 84: 1076-80.
Nikkels AF, Delvenne P. Sadzot-Delvaux C et al Distribution of varicella zoster virus and herpes simplex virus in disseminated fatal infections. J Clin Pathol 1996; 49: 243-8.
Whitley RJ. Gnann JW. Editorial response: herpes zoster in patients with human immunodeficiency virus infection - an ever-expanding spectrum of disease. Clin Inf Dis 1995; 21: 989-90.
Baselga E, Drolet BA, Segura AD, Leonardi CL, Esterly NB. Dermatomal lichenoid chronic graft-vs-host disease following varicella-zoster infection despite absence of viral genome. J Cutan Pathol 1996; 23: 576-811.
Nikkels AF, Sadzot-Delvaux C, Rentier B. Pierard-Franchimont C, Pierard GE. Low-productive alpha-herpesviridac infection in chronic lichenoid dermatoses. Dermatology 1998: 196: 442-6.
Nikkels AF, Debrus S, Sadzot-Delvaux C, Piette J, Rentier B, Pierard GE. Localization of varicella-zoster virus nucleic acids and proteins in human skin. Neurology 1995; 45: 47-9.
Muraki R, Iwasaki T, Sata T, Sato Y, Kurata T. Hair follicle involvement in herpes zoster: pathway of viral spead from ganglia to skin. Virchows Arch 1996: 428: 275-80.
Weinberg JM, Mysliwiec A, Turiansky GW, Redfield R. James WD. Viral folliculitis. Arch Dermatol 1997; 133: 983-6.
Jura E, Chadwick EG, Josephs SH et al. Varicella-zoster virus infections in children infected with human immunodeficiency virus. Pediatr Inject Dis J 1989: 8: 586-90.
Tsao II, Tahan SR. Johnson RA. Chronic varicella zoster infection mimicking a basal cell carcinoma in an AIDS patient. J Am Acad Dermatol 1997; 36: 831-3.
Jacobson MA, Berger TG, Fikrig S et al. Acyclovir-resistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS). Ann Int Med 1990; 112: 187-91.
Janier M, Hillion B, Baccard M et al. Chronic varicella zoster infection in acquired immunodeficiency syndrome. J Am Acad Dermatol 1988; 18: 584-5.
Gallagher JG, Merigan TC. Prolonged herpes zoster infection associated with immunosuppressive therapy. Ann Int Med 1979; 91: 842-6.
Disler RS, Dover JS. Chronic localized herpes zoster in the acquired immunodeficiency syndrome. Arch Dermatol 1990;126: 1105-6.
Grossman MC, Grossman ME. Chronic hyperkeratotic herpes zoster and human immunodeficiency virus infection. I am Acad Dermatol 1993; 28: 306-8.
Gilson IH, Barnett JH, Conant MA, Laskin OL, Williams J. Jones PG. Disseminated ecthymatous herpes varicella zoster virus infection in patients with acquired immunodeficiency syndrome. J Am Acad Dermatol 1989; 20: 637-42.
Tronnier M, Plettenberg A, Meigel WN, Wolff HH. Recurrent verrucous herpes zoster in an HIV patient. Demonstration of the virus by immunofluorescence and electron microscopy. Eur J Dermatol 1994; 4: 604-7.
Leboit PE, Limova M, Yen TSB, Palefsky JM, White CR, Berger TG. Chronic verrucous varicella zoster virus infection in patients with the acquired immunodeficiency syndrome. Am J Dermatopathol 1992; 14: 1-7.
Hoppenjans WB, Bibler MR, Orme RL, Solinger AM. Prolonged cutaneous herpes zoster in acquired immunodeficiency syndrome. Arch Dermatol 1990; 126: 1048-50.
Colebunders R, Van Damme L, Van den Abbeele K, Fleerackers Y, Van den Enden E, Dockx P. Atypical varicella-zoster infection in persons with HIV infection. Acta Clin Belg 1994; 49: 104-7.
Bernard P. Obel N. Chronic ulcerating acyclovir-resistant varicella zoster virus in an AIDS patient. Scand J Inf Dis 1995; 27: 623-5.
Leibowitz E, Kaul A, Rigaud M, Bebenroth D, Krasinski K, Borkowsky W. Chronic varicella zoster in a child infected with human immunodeficiency virus: case report and review of the literature. Cutis 1993: 49: 27-31.
Vaughan-Jones SA, McGibbon DH, Bradbeer CS. Chronic verrucous varicella-zoster infection in a patient with AIDS. Clin Exp Dermatol 1994; 19: 327-9.
Lokke-Jensen B, Weismann K, Mathiesen J., Thomsen HK. Atypical varicella-zoster infection in AIDS. Acta Derm Venereol 1993; 73: 123-5.
Smith KJ, Skelton HG, Frissman DM, Angritt P. Verrucous lesions secondary to DNA viruses in patients infected with the human immunodeficiency virus in association with increased factor XIII - a positive dermal dendritic cells. J Am Acad Dermatol 1992; 27: 943-50.
Aronson MD, Phillips CF, Gump DW, Albertini RJ, Phillips CA. Vidararbine therapy for severe herpesvirus infections: an unusual syndrome of chronic varicella and transient immunologic deficiency. J Am Med Assoc 1976; 255: 1339-42.
Dolin R. Reichman RC, Mazur MH, Whitley RJ. Herpes zoster-varicella infections in immunosuppressed patients. Ann Int Med 1978; 89: 375-88.
Nikkels AF, Pierard GE. Recognition and treatment of shingles. Drugs 1994; 48: 528-48.
Snoeck K. Andrei G, De Clercq E. Current pharmacological approaches to the therapy of varicella-zoster virus infections: a guide to treatment. Drugs, 1999; 57: 187-206.
Snoeck R, De Clercq E. Herpesvirus infections in immunocompromised patients. Cancer Treat Res 1995; 79: 149-71.
Ljungman P. Herpes virus infections in immunocompromised patients: problems and therapeutic interventions. Ann Med 1993; 25: 329-33.
Veraldi Gnecchi L, Zorzi F. Verrucous-crusted herpes zoster in an immunocompetent patient. Acta Derm Venereol 1998: 78: 236-7.
Pahwa S, Biron KK, Lim W et al. Continuous varicella zoster infection associated with acyclovir resistance in a child with AIDS. J Am Med Assoc 1988; 260: 2879-82.
Lim W, Sadick N, Gupta A, Kaplan M, Pahwa S, Skin diseases in children with HIV infection and their association with degree of immunosuppression. Int J Dermatol 1990: 29: 24-30.
Prose NS. HIV infection in children. J Am Acad Dermatol 1990; 22: 1223-31.
Tappero JW, Perkins BA, Wenger JD, Berger TG. Cutaneous manifestations of opportunistic infections in patients infected with human immunodeficiency virus. Clin Microbiol Rev 1995: 8:440-50.
Alessi E. Cusini M. Zerboni R et al. Unusual varicella zoster virus infection in patients with the acquired immunodeficiency syndrome. Arch Dermatol 1988; 124: 1011-3.
Smith KJ, Skelton HG, Yeager J et al. Cutaneous findings in HIV-1 positive patients: a 42-month study. J Am Acad Dermatol 1994: 31: 746-54.
Manian FA, Kindred M, Fulling KH. Chronic varicella-zoster virus myelitis without cutaneous eruption in a patient with AIDS. report of a fatal case. Clin Inf Dis 1995: 21: 986-8.
Zaal MJW, Maudgal PC, Rietveld E, Suir EPE. Chronic ocular zoster. Curr Eye Res 1991, 10 (Suppl.): 125-30.
Nikkels AF, Rentier B, Pierard GE. Chronic varicella zoster virus skin lesions in patients with human immunodeficiency virus are related to decreased expression of gE and gB. J Infect Dis 1997: 176: 261-4.
Sadzot-Delvaux C. Debrus S. Nikkels AF, Piette J, Rentier B. Varicella-zoster virus latency in the adult rat is a useful model for human latent infection. Neurology 1995; 45: 18-20.
Debrus S, Sadzol-Delvaux C, Nikkels AF, Piette J, Rentier B. Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency. J Virol 1995: 69: 3240-5.
Meier JL, Holman RP, Croen KD, Smialek JE, Straus S. Varicella-zoster virus transcription in human trigeminal ganglia. Virology 1993; 193: 193-200.
Vafai A, Murray RS, Wellish M, Devlin M, Gilden D. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia. Proc Natl Acad Sci USA 1988; 85: 2362-6.
Mahalingham R, Wellish M. Cohrs R et al. Expression of protein encoded by varicella zoster virus open reading frame 63 in latently infected human ganglionic neurons. Proc Natl Acad Sci USA 1996: 93: 2122-4.
Sadzot-Delvaux C, Thonard P, Schoonbroodt S, Piette J. Rentier B. Varicella-zoster virus induces apoptosis in cell culture. J Gen Virol 1995; 76: 2875-9.
Cohen JI. Infection of cells with varicella-zoster virus down-regulates surface expression of class 1 major histo-compatibility complex antigens. J Inf Dis 1998; 177: 1390-3.
Modiano P, Salloum E, Gillet-Terver MN et al. Acyclovir-resistant chronic cutaneous herpes simplex in Wiskott-Aldrich syndrome. Br J Dermatol 1995; 133: 475-8.
Safrin S, McKinley G, McKeough M, Robinson D, Spruance SL. Treatment of acyclovir unresponsive cutaneous herpes simplex virus infection with topically applied SP-303. Antiviral Res 1994; 25: 185-92.
Abeck D, Brandt O, Weichenthal M, Kowalzick L, Mensing H. Chronische mukokutane herpes simplex infektion. Auftreten im rahmen einer hepatisch bedingten immundefizienz. Hautarzt 1993; 44: 670-3.
Beasley KL, Cooley GE, Kao GF et al. Herpes simplex vegetans: atypical genital herpes infection in a patient with common variable immunodeficiency. J Am Acad Dermatol 1997; 37: 860-3.
Yeh V, Hopp ML, Goldstein NS, Meyer RD. Herpes simplex chronic laryngitis and vocal cord lesions in a patient with acquired immunodeficiency syndrome. Ann Otol Rhinol Laryngol 1994; 103: 726-31.
Chin RH, Ross BC, Taylor KI, Yung AP, Johnson PD. Chronic meningitis due to herpes simplex virus in an immunocompetent host. Eur J Clin Microbiol Inf Dis 1996; 15: 650-3.
Andrei G, Snoeck R, Reymen D et al. Comparative activity of selcted antiviral compounds against clinical isolates of varicella-zoster virus. Eur J Clin Microbiol infect Dis 1995; 14: 318-28.
Nikkels AF, Debrus S, Sadzot-Delvaux C, Piette J, Rentier B. Pierard GE. Immunohistochemical identification of Varicella-Zoster Virus gene 63-encoded protein (IE63) and Late (gE) protein on smears and cutaneous biopsies: Implications for diagnostic use. J Med Virol 1995; 47: 342-7.
Cavicchini S, Brezzi A, Alessi E. Ultrastructural findings in mucocutaneous infections of patients seropositive to HIV. Am J Dermatopathol 1993; 15: 320-5.
Lyall EGH. Ogilvie MM, Smith NM, Burns S. Acyclovir resistant varicella zoster and HIV infection. Arch Dis Child 1994;70: 133-5.
Ljungman P. Herpesvirus infections in immunocompromised patients: problems and therapeutic interventions. Ann Med 1993; 25: 329-33.
Gulick RM, Heath-Chiozzi M, Crumpacker CS. Varicella-zoster virus disease in patients with human immunodeficiency virus infection. Arch Dermatol 1990; 126: 1086-8.
Linnemann C Jr, Biron KK, Hoppenjans W et al. Emergence of acyclovir resistant varicella zoster virus in an AIDS patient on prolonged acyclovir therapy. AIDS 1990; 4: 577-9.
Snoeck R, Gerard M, Sadzot-Delvaux C et al. Meningoradiculoneuritis due to acyclovir-resistant varicella zoster virus in an acquired immune deficiency syndrome patient. J Med Virol 1994; 42: 338-47.
Safrin S, Berger TG, Gilson I et al. Foscarnet therapy in live patients with AIDS and acyclovir-resistant varicella-zoster virus infection. Ann Intern Med 1991; 115: 1921.
Boivin G, Edelman CK, Pednault L, Talarico CL, Biron KK, Balfour HH. Phenotypic and genotypic characterization of acyclovir-resistant varicella-zoster viruses isolated from persons with AIDS. J Infect Dis 1994; 170: 68-75.
Talarico CL, Phelps WC, Biron KK. Analysis of the thymidine kinase genes from acyclovir-resistant mutants of varicella-zoster virus isolated from patients with AIDS. J Virol 1993; 67: 1024-33.
Sall RK, Kauffman L, Levy CS. Successful treatment of progressive acyclovir-resistant herpes simplex virus using intravenous foscarnet in a patient with the acquired immunodeficiency syndrome. Arch Dermatol 1989; 125: 1548-50.
Fillet A-M, Visse B, Caumes E, Dumont B, Gentilini M, Huraux J-M. Foscarnet-resistant multidermatomal zoster in a patient with AIDS. Clin Inf Dis 1995; 21: 1348-9.
Reusser P. Herpesvirus resistance to antiviral drugs: a review of the mechanisms, clinical importance and therapeutic options. J Hosp Infect 1996; 33: 235-48.
Balfour HH, Benson C, Braun J et al. Management of acyclovir-resistant herpes simplex and varicella-zoster virus infections. J Acquir Immune Defic Syndr 1994; 7: 254-60.
Rossi S, Whitfeld M, Berger TG. The treatment of acyclovir-resistant herpes zoster with trifluorothymidine and interferon alpha. Arch Dermatol 1995; 131: 24-6.
Martinez CM, Luks-Golger DB. Cidofovir use in acyclovir-resistant herpes infection. Ann Pharmacother 1997; 31: 1519-21.
Alder J. Mitten M. Norbeck D. Marsh K, Kern ER, Clement J. Efficacy of A-73209, a potent orally active agent against VZV and HSV infections. Antiviral Res 1994; 23: 93-105.