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Anogenital pseudotumoral herpes and HIV infection: a new challenge for diagnosis and treatment

Di Lucca-Christment, Juliea,*; Jacobelli, Simona; Gressier, Ludiviena; Plantier, Françoiseb; Laude, Hélènec,d; Rosenberg, Florec,d; Morini, Jean-Pierrea; Dallot, Alexianee; Avril, Marie-Françoisea; Dupin, Nicolasa,d

doi: 10.1097/QAD.0b013e32835049be
Research Letter

HIV-infected patients may develop rare anogenital pseudotumoral herpes potentially mimicking epidermoid carcinoma. We assessed treatment in five new cases with a median follow-up of 3.3 years. Recurrence and clinical nucleoside analog resistance were observed in all patients. All drug treatments were only temporarily curative and clinical responses varied between patients and recurrences. Foscavir seemed to be the most appropriate second-line treatment and cidofovir or thalidomide should be considered as alternative treatments.

aDermatology Department

bPathology Department

cVirology Department of Cochin Hospital, APHP

dUPRES EA 1833, René Descartes University Faculty of Medicine, Paris

eRobert Ballanger Hospital, Aulnay sous Bois, Paris, France.

*Present address: Dermatology Unit, Hospital Bichat, APHP, Paris, France.

Correspondence to Nicolas Dupin, Service de Dermatologie, Hôpital Cochin, APHP, Pavillon Tarnier, 89 rue d’Assas, 75006 Paris, France. Tel: +33 158 411 813; fax: +33 158 411 765; e-mail:

Received 29 August, 2011

Revised 9 November, 2011

Accepted 12 December, 2011

Genital herpes simplex virus (HSV) may be deceptive in HIV-infected patients [1]. Chronic HSV infection masquerading as carcinoma vegetans was first described in 1983 by Leming et al. [2]. Thirty-three cases in HIV-infected patients [3–22] and seven in immunocompromised patients without HIV infection [2,23–28] have since been published. We report five new HIV-related cases, focusing in treatment options and long-term follow-up.

Between 2007 and 2009, we identified five cases of pseudotumoral herpes in a cohort of more than 500 HIV-infected patients. Tumoral lesions with HSV infection documented by PCR and immunochemistry on a proper excisional biopsy specimen, with histological features excluding invasive carcinoma, were considered to be pseudotumoral herpes. Clinical data were extracted retrospectively.

The patients studied were four women and one man, aged from 39 to 48 years, all originally from Congo. Highly-active antiretroviral therapy had increased their CD4 cell counts to 154–616 cells/μl, and the virus had been undetectable for the last 6 months. All patients reported previous recurrent genital herpes.

The four women had vulval tumors, with three bifocal perineal localizations. The man had a tumor at the base of the penis that recurred in the perianal area and the groin. The location often changed between recurrences in a given patient. The lesions ranged from 1.5 to 7 cm in diameter.

During the median follow-up period of 3.3 years, all patients presented recurrences, despite surgical excision and/or drug treatment. No event was correlated with CD4 cell count. Recurrences and initial lesions often occurred at different sites. Clinical responses differed considerably between patients and recurrences. The size of the lesion was not predictive of the effect of drug treatment.

Recurrences were observed in all four cases treated by complete local excision, with a disease-free period of 1 month to 4 years.

Oral nucleoside analogs (2–3 g/day valacyclovir) were initially administered to all patients, with no improvement. Case 1 received high doses of intravenous acyclovir (15 mg/kg/8 h for 15 days), but two courses of this treatment did not result in complete remission.

Intravenous foscavir treatment was successful in four patients, who received 80 mg/kg/day until complete remission, with a maximum of 4 weeks of treatment. Complete remission was observed after 15 days (cases 2, 3 and 5), 1 (case 3) and 2 months (case 1; Fig. 1a and b). The disease-free period lasted from 0 to 2 years.

Fig. 1

Fig. 1

Three cases received topical treatment with 1% cidofovir, which was applied to lesions, 5 days per week, until complete remission. This drug was used alone (cases 1 and 2) or in combination with valacyclovir (cases 1 and 4). Complete remission was achieved in three patients, after 1–3 months of treatment. A recurrence occurred in one patient after 7 months (case 1), but the reinitiation of topical cidofovir treatment led to secondary cure.

Thalidomide (100 mg/day for 1.5 months) cured recurrences in two cases (Fig. 1c,d), but with one dissociated response in a bifocal tumor. Imiquimod was used in combination with valacyclovir in one case, with the complete resolution of two of the three lesions.

Foscavir was not given in case 4 because renal failure had occurred during previous treatment with foscavir for chronic genital herpes. No adverse effects of any of the treatments used were reported during this study.

It is difficult to compare the results of different studies because diverse treatments are administered and follow-up times are short [9]. Whatever the treatment, lesions often recur in the longer term.

Surgery provides immediate resolution of the lesion but does not protect against short-term recurrence, with possible problems of surgical closure in cases of large and/or periorificial lesions [11]. In our opinion, drugs should, therefore, be preferred for first-line treatment.

Nucleoside analogs are the approved first-line treatment for HSV infection. Unfortunately, such treatments decrease the size of most pseudotumoral lesions but do not eliminate them completely. This persistence of tumors may be accounted for by the presence of mixed resistant and wild populations of HSV [15], and may explain why acyclovir continues to be efficient at preventing other forms of herpes.

For patients displaying either resistance or an inadequate response to nucleoside analogs, intravenous foscarnet is recommended. We report the largest ever series of cases of pseudotumoral herpes treated with foscavir. Our experience and published findings suggest that this drug should be offered as a first-line intravenous treatment.

Topical treatments have been developed because relapses are frequent and systemic treatments have potential side effects. Topical applications of 1–2% cidofovir and 2.4% foscarnet have been reported to be effective. We consider such treatments to be of potential value when used in combination and/or in relay with systemic antiviral treatment. Immunomodulation treatments have also recently been tested. Interferon-α is produced principally by plasmacytoid dendritic cells, which are lacking in patients with AIDS; this cytokine plays a critical role in the control of viral infection. Imiquimod has been successfully used in three published cases [16,18] and in case four reported here.

Thalidomide is known to downregulate proinflammatory cytokines and to be antiangiogenic, antiproliferative and proapoptotic. Following the successful treatment of recurrent aphthous ulceration in HIV-infected patients [29] with thalidomide, this drug was successfully used to treat five HIV-infected individuals with genital hypertrophic herpes [14], and two further cases treated by us. As thalidomide may exacerbate the immunodeficiency associated with HIV and/or the secondary effects of some antiviral drugs, we restrict its use to cases of resistance to systemic antiviral drugs and multiple recurrences.

Finally, if the lesion does not regress rapidly despite the use of these various drug treatments, surgery should be carried out to prevent the misdiagnosis of carcinoma.

In HIV-infected patients with a good immune status and recurrent genital herpes, pseudotumoral herpes should be considered on the basis of a proper excisional biopsy, in the differential diagnosis of anogenital carcinoma, to prevent unnecessary major surgery. The disparity of the results obtained for treatments that were only temporarily curative and the short follow-up period for this series made it impossible to draw firm conclusions about treatment. However, we suggest that drugs should be favored as a first-line treatment, with surgery limited to small or resistant lesions.

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Clinical investigators: D.L.C.J., J.S., G.L., M.J.P., D.A., A.M.F., D.N.

Referent pathologist: P.F.

Referent for viral analysis: L.H., R.F.

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Conflict of interest

There are no conflicts of interest.

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1. Bagdades EK, Pillay D, Squire SB, O’Neil C, Johnson MA, Griffiths PD. Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection. AIDS 1992; 6:1317–1320.
2. Leming PD, Martin SE, Zwelling LA. Atypical herpes simplex (HSV) infection in a patient with Hodgkin's disease. Cancer 1984; 54:3043–3047.
3. 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 XIIIa-positive dermal dendritic cells. The Military Medical Consortium of Applied Retroviral Research Washington, D. C. J Am Acad Dermatol 1992; 27:943–950.
4. Vogel P, Smith KJ, Skeleton HG, Cuozzo D, Wagner KF. Vegetans lesions of herpes simplex in HIV-1+ patients. Military Medical Consortium for the Advancement of Retroviral Research. Int J Dermatol 1993; 32:680–682.
5. Tong P, Mutasim DF. Herpes simplex virus infection masquerading as condyloma acuminata in a patient with HIV disease. Br J Dermatol 1996; 134:797–800.
6. Husak R, Tebbe B, Goerdt S, et al. Pseudotumour of the tongue caused by herpes simplex virus type 2 in an HIV-1 infected immunosuppressed patient. Br J Dermatol 1998; 139:118–121.
7. Samaratunga H, Weedon D, Musgrave N, McCallum N. Atypical presentation of herpes simplex (chronic hypertrophic herpes) in a patient with HIV infection. Pathology 2001; 33:532–535.
8. Gubinelli E, Cocuroccia B, Lazzarotto T, Girolomoni G. Nodular perianal herpes simplex with prominent plasma cell infiltration. Sex Transm Dis 2003; 30:157–159.
9. Carrasco DA, Trizna Z, Colome-Grimmer M, Tyring SK. Vegetans herpes of the scrotum in a human immunodeficiency virus-positive man: case report and review of the literature. J Eur Acad Dermatol Venereol 2002; 16:511–515.
10. Lanzafame M, Mazzi R, Di Pace C, Trevenzoli M, Concia E, Vento S. Unusual, rapidly growing ulcerative genital mass due to herpes simplex virus in a human immunodeficiency virus-infected woman. Br J Dermatol 2003; 149:216–217.
11. 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; 48:2289–2293.
12. Dehen L, Vilmer C. [Tumoral presentation of genital herpes in a female HIV-positive patient]. Ann DermatolVenereol 2006; 133:393–394.
13. Ghislanzoni M, Cusini M, Zerboni R, Alessi E. Chronic hypertrophic acyclovir-resistant genital herpes treated with topical cidofovir and with topical foscarnet at recurrence in an HIV-positive man. J Eur Acad Dermatol Venereol 2006; 20:887–889.
14. Holmes A, McMenamin M, Mulcahy F, Bergin C. Thalidomide therapy for the treatment of hypertrophic herpes simplex virus-related genitalis in HIV-infected individuals. Clin Infect Dis 2007; 44:96–99.
15. Boothby M, Radcliffe K. An unusual vulval lesion in an HIV-infected woman. Int J STD AIDS 2007; 18:218–219.
16. Abbo L, Vincek V, Dickinson G, Shrestha N, Doblecki S, Haslett PA. Selective defect in plasmacyoid dendritic cell function in a patient with AIDS-associated atypical genital herpes simplex vegetans treated with imiquimod. Clin Infect Dis 2007; 44:25–27.
17. Lautenschlager S, Schwarzkopf S, Keller B. Exophytic ulcerated tumors in HIV patients: diagnostic and therapeutic problems. Dermatology 2008; 216:60–63.
18. Patel AB, Rosen T. Herpes vegetans as a sign of HIV infection. Dermatol Online J 2008; 14:6.
19. Simonsen M, Nahas SC, Silva Filho EV, Araújo SE, Kiss DR, Nahas CS. Atypical perianal herpes simplex infection in HIV-positive patients. Clinics (Sao Paulo) 2008; 63:143–146.
20. Yudin MH, Kaul R. Progressive hypertrophic genital herpes in an HIV-infected woman despite immune recovery on antiretroviral therapy. Infect Dis Obstet Gynecol 2008; 2008:592532.
21. Mosunjac M, Park J, Wang W, et al. Genital and perianal herpes simplex simulating neoplasia in patients with AIDS. AIDS Patient Care STDS 2009; 23:153–158.
22. Barde C, Piguet V, Pechère M, Masouye I, Saurat JH, Wunderli W, et al. L. Management of resistant mucocutaneous herpes simplex infections in AIDS patients: a clinical and virological challenge. HIV Med 2011; 12:367–373.
23. Meunier L, Guillot B, Lavabre-Bertrand T, Barnéon G, Izarn P, Meynadier J. [Chronic herpes of the pyodermatitis vegetans type in chronic cutaneous lymphoid leukemia]. Ann Dermatol Venereol 1986; 113:1199–1204.
24. Burke EM, Karp DL, Wu TC, Corio RL. Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation. Eur Arch Otorhinolaryngol 1994; 251:301–303.
25. 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; 37:860–863.
26. Hershko K, Hershko AY, Leibovici V, Meir K, Ingber A. Herpes simplex virus infection in a hyper-IgE patient: appearance of unusual mass lesions. Acta Derm Venereol 2002; 82:204–205.
27. Tabaee A, Saltman B, Shutter J, Hibshoosh H, Markowitz A. Recurrent oral herpes simplex virus infection presenting as a tongue mass. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 97:376–380.
28. Hickman G, Berville S, Clerici T, Saiag P, Mahé E. [Acute perianal tumors]. Ann Dermatol Venereol 2008; 135:700–703.
29. Jacobson JM, Greenspan JS, Spritzler J, et al. N Engl J Med Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997; 336:1487–1493.
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