June/July 2007

Fig.2

Fig.3

HISTOPATHOLOGY: HSV infection in the keratinocytes of the hair follicles and CMV cytopathic effect in the keratinocytes and endothelial cells of the vasculature. In the first slide there are intranuclear inclusion bodies that are typical of CMV infection. In the second slide, there are multinucleated keratinocytes with intranuclear inclusion bodies characteristic of HSV infection.

TISSUE BIOPSY VIRAL CULTURE: + HSV

PATIENT COURSE:
The patient was started on valganciclovir for cytomegalovirus viremia, bactrim for pneumocystis prophylaxis and a combination of ethambutol and clarithromycin for disseminated mycobacterial disease. The patient will follow-up in infectious disease clinic for further consideration of restarting HAART therapy.

DISCUSSION:

Patients who are immunocompromised either secondary to HIV infection, hematologic malignancy or organ transplantation may present with atypical presentations of common viral infections such as herpes simplex virus (HSV), cytomegalovirus (CMV), varicella-zoster virus (VZV), molluscum contagiosum and oral hairy leukoplakia (1-3 ). Although verrucous forms of both HSV and CMV have been described in HIV infected patients (2,4 ), cutaneous CMV lesions are relatively rare and have been reported less frequently than either verrucous HSV or VZV. These verrucous lesions will often appear as generalized, papillomatous, hyperkeratotic or ulcerated vegetating plaques resembling verrucous carcinoma. Such a presentation has most commonly been reported in association with advanced HIV-1 disease (1,5,6 ). Lesions can be painful depending on the underlying etiology and can increase in number and size with increasing immunosuppression and impairment of the cell-mediated immune response.

Although the exact cause of verrucous lesions remains uncertain, it has been suggested that the epidermal hyperplasia may be mediated by overproduction of tumor necrosis factor-alpha (TNF-alpha) by hyperproliferating dermal factor XIIIa-positive dendritic cells. Increased numbers of factor XIIIa-positive dendritic cells have been demonstrated in hyperkeratotic eruptions in HIV infected patients and their production of TNF-alpha may stimulate proliferation of keratinocytes resulting in hyperkeratotic, verrucous lesions (5).

Treatment of verrucous lesions depends on the underlying etiology. Therapeutic possibilities for verrucous HSV and CMV infections include the antiviral agents such as acyclovir, valciclovir, famciclovir and foscarnet and surgical treatment (7 ). Recurrences are common and typically occur in patients with lower CD4 lymphocyte counts (8 ). In HIV patients with recurrent HSV outbreaks, survival benefits with acyclovir use remains a controversial issue. Two clinical trials noted improved survival in patients treated with both acyclovir and zidovudine in comparison to patients treated with zidovudine alone (9,10). However, Gallant et al could not find a significant association between acyclovir treatment and improved survival in HIV-patients (11).

REFERENCES:
1. Beasley KL, Cooley GE, Kao GF, Lowitt MH, Burnett JW, Aurelian L. Herpes simplex vegetans: atypical genital herpes infection in a patient with common variable immunodeficiency. J Am Acad Dermatol. 1997 Nov;37(5 Pt 2):860-3.
2. Bournerias I, Boisnec S, Patey O, et al. Unusual cutaneous cytomegalovirus involvement in patients with acquired immunodeficiency syndrome. Arch Dermatol. 1989 Sep;125(9):1243-6.
3. Alessi E, berti E, Cusini M, eta l. Oral hairy leukoplakia. J Am Acad dermatol 1990; 2: 79-86.
4. Smith KJ, Skelton HG 3rd, James WD et al. Concurrent epidermal involvement of cytomegalovirus and herpes simplex virus in two HIV-infected patients. Military Medical Consortium for Applied Retroviral Research (MMCARR). J Am Acad Dermatol. 1991 Sep;25(3):500-6.
5. Smith KJ, Skelton HG 3rd, Frissman DM, Angritt P. Verrucous lesions secondary to DNA viruses in patients infected with the human immunodeficiency virus in association with increased factor XIIa-positive dermal dendritic cells. The Military Medical Consortium of Applied Retroviral Research Washington, D.C. Am Acad Dermatol. 1992 Dec;27(6 Pt 1):943-50.
6. Vogel MP, Smith KJ, Skelton HG, Cuozzo MD, Wagner KF. Verrucous lesions of herpes simplex in HIV-1+ patients. Military Medical Consortium for the Advancement of Retroviral Research. Int J Dermatol. 1993 Sep;32(9):680-2.
7. Carrasco DA, Trizna Z, Colome-Grimmer M, Tyring SK. Verrucous herpes of the scrotum in a human immunodeficiency virus-positive man: case report and review of the literature. J Eur Acad Dermatol Venereol. 2002 Sep;16(5):511-5.
8. Nadal SR, Calore EE, Manzione CR, Horta SC, Ferreira AF, Almeida LV. Hypertrophic herpes simplex simulating anal neoplasia in AIDS patients: report of five cases.
Dis Colon Rectum. 2005 Dec;48(12):2289-93.
9. Stein DS, Graham NM, Park LP et al. The effect of the interaction of acyclovir with zidovudine on progression to AIDS and survival. Analysis of data in the Multicenter AIDS Cohort Study. Ann Intern Med. 1994 Jul 15;121(2):100-8.
10. Englund JA, Zimmerman ME, Swierkosz EM, Goodman JL, Scholl DR, Balfour HH Jr. Herpes simplex virus resistant to acyclovir. A study in a tertiary care center. Ann Intern Med. 1990 Mar 15;112(6):416-22.
11. Gallant JE, Moore RD, Keruly J, Chaisson RE. Lack of association between acyclovir use and survival in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group. J Infect Dis. 1995 Aug;172(2):346-52.

This case was presented by Arta Farshidi and Drs. Chynna Steele and Maria Canizares. Histology photographs courtesy of Drs. Kimberly Crone and Anne Lind.