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Intralesional Cidofovir for Treating Extensive Genital Verrucous Herpes Simplex Virus Infection FREE

Karolyn A. Wanat, MD1; Rachel H. Gormley, MD1; Misha Rosenbach, MD1; Carrie L Kovarik, MD1
[+] Author Affiliations
1Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia
JAMA Dermatol. 2013;149(7):881-883. doi:10.1001/jamadermatol.2013.4014.
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Published online

Verrucous herpes simplex viral infections in immunocompromised patients can be a therapeutic challenge, and we present a case of successful treatment with intralesional cidofovir.

REPORT OF A CASE

A 55-year-old man with human immunodeficiency virus (HIV) and hepatitis C virus coinfection presented with new lesions on his scrotum and perianal area. He noted mild tingling and slow growth over the prior 2 months. His medications included darunavir, ritonavir, emtricitabine/tenofovir, and trimethoprim-sulfamethoxazole. His CD4 count was stable at 350 cells/µL, and he had an undetectable HIV viral load. Findings of a comprehensive metabolic panel and complete blood cell count were normal, and rapid plasma reagin was nonreactive. Physical examination was notable for exophytic, verrucous, and ulcerated plaques on his right inferior scrotum and perianal area (Figure 1A and B). Biopsy and tissue culture were performed. Histopathologic analysis demonstrated full-thickness epidermal ulceration with adjacent pseudoepitheliomatous hyperplasia (Figure 2A and B). Multinucleated keratinocytes with peripheral rimming of nuclear chromatin were present at the edge of the ulceration (Figure 2B and C), and immunostaining for herpes simplex virus (HSV) was positive, confirming HSV infection (Figure 2D). Gram and periodic acid-Schiff stainings and Treponema pallidum immunostaining were negative. Tissue culture had no growth, and viral resistance testing could not be performed.

Place holder to copy figure label and caption
Figure 1.
Verrucous Herpes Simplex Virus Before (A and B) and After (C and D) Treatment

Exophytic, verrucous, and ulcerated plaques were found on his right inferior scrotum (A) and perianal area (B). After 6 treatments with intralesional cidofovir, there was resolution of the plaques on the scrotum (C) and near complete resolution in the perianal area (D).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Histopathologic Images

A, Acanthotic epidermis at the edge of an ulceration with acute inflammation (hematoxylin-eosin, original magnification ×100) with prominent multinucleated giant cells (B and C, hematoxylin-eosin, original magnification ×200 and ×400, respectively). D, Herpes viral infection was confirmed with positive immunoperoxidase staining of multinucleated giant cells (herpes simplex virus immunohistochemical staining, original magnification ×200).

Graphic Jump Location

The patient began treatment for HSV, and despite successive 1-month courses of high-dose oral acyclovir, valacyclovir, and famciclovir, his lesions progressed. A repeated tissue culture for viral resistance testing was not successful in growing virus. A repeated biopsy confirmed the original diagnosis of verrucous HSV. Given concern for acyclovir-resistant HSV, oral therapy was discontinued, and intravenous (IV) cidofovir treatment was initiated, with improvement noted after 3 doses. This treatment was complicated by elevations in serum creatinine levels and discontinued. Intralesional cidofovir was then initiated every other week, as previously reported,1 with resolution of his scrotal lesion and dramatic improvement in his perianal lesion after 6 treatments (Figure 1C and D).

DISCUSSION

Herpes simplex virus infections cause significant morbidity in immunocompromised patients, and active HSV infection increases HIV transmission.2 Infection with acyclovir-resistant HSV strains is about 10-fold higher in patients with HIV than in immunocompetent individuals and appears related to the degree of immunosuppression and duration of antiretroviral therapy.2 Treatment options for acyclovir-resistant HSV are limited and include foscarnet, cidofovir, imiquimod, and immunomodulating dipeptides.3,4 Foscarnet and cidofovir are not dependent on phosphorylation of viral thymidine kinase for activation and can therefore be used in acyclovir-resistant cases; however, both have limited formulations, and drug-induced nephrotoxic effects are potentially serious complications. Topical and intralesional administrations of cidofovir have also been used for acyclovir-resistant disease.1,5

In this case, acyclovir resistance was not confirmed with viral resistance testing but inferred from lack of treatment response. Given the disease extent, treatment with IV cidofovir was first attempted than discontinued owing to nephrotoxic effects. Topical cidofovir was considered but not pursued, to avoid the significant potential for local irritation and burning in the setting of ulcerated plaques. Intralesional cidofovir was ultimately used because of previously reported success in the treatment of facial acyclovir-resistant HSV.1 Since increased sensation is known to occur in the genital area, a ring block with lidocaine and epinephrine followed by a 1:4 dilution of cidofovir (75 mg/mL) was used, with 5 mL infiltrated into the scrotal lesion and 5 mL into the perianal lesion. The patient tolerated the injections well, requiring no additional pain medication, and had remarkable improvement without laboratory abnormalities (Figure 1C and D).

This report highlights the successful use of intralesional cidofovir in a patient with verrucous HSV infection of the scrotum and perianal area. Given its low risk of adverse effects and ease of use in the outpatient setting, it should be considered in this patient population.

ARTICLE INFORMATION

Corresponding Author: Carrie L. Kovarik, MD; Department of Dermatology, University of Pennsylvania, 3600 Spruce St, Philadelphia, PA 19104 (carrie.kovarik@uphs.upenn.edu).

Conflict of Interest Disclosure: None reported.

REFERENCES

Castelo-Soccio  L, Bernardin  R, Stern  J, Goldstein  SA, Kovarik  C.  Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146(2):124-126.
PubMed   |  Link to Article
Lolis  MS, González  L, Cohen  PJ, Schwartz  RA.  Drug-resistant herpes simplex virus in HIV infected patients. Acta Dermatovenerol Croat. 2008;16(4):204-208.
PubMed
Lascaux  AS, Caumes  E, Deback  C,  et al.  Successful treatment of aciclovir and foscarnet resistant Herpes simplex virus lesions with topical imiquimod in patients infected with human immunodeficiency virus type 1. J Med Virol. 2012;84(2):194-197.
PubMed   |  Link to Article
Rose  WA  II, Tuthill  C, Pyles  RB.  An immunomodulating dipeptide, SCV-07, is a potential therapeutic for recurrent genital herpes simplex virus type 2 (HSV-2). Int J Antimicrob Agents. 2008;32(3):262-266.
PubMed   |  Link to Article
Toro  JR, Sanchez  S, Turiansky  G, Blauvelt  A.  Topical cidofovir for the treatment of dermatologic conditions: verruca, condyloma, intraepithelial neoplasia, herpes simplex and its potential use in smallpox. Dermatol Clin. 2003;21(2):301-309.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Verrucous Herpes Simplex Virus Before (A and B) and After (C and D) Treatment

Exophytic, verrucous, and ulcerated plaques were found on his right inferior scrotum (A) and perianal area (B). After 6 treatments with intralesional cidofovir, there was resolution of the plaques on the scrotum (C) and near complete resolution in the perianal area (D).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Histopathologic Images

A, Acanthotic epidermis at the edge of an ulceration with acute inflammation (hematoxylin-eosin, original magnification ×100) with prominent multinucleated giant cells (B and C, hematoxylin-eosin, original magnification ×200 and ×400, respectively). D, Herpes viral infection was confirmed with positive immunoperoxidase staining of multinucleated giant cells (herpes simplex virus immunohistochemical staining, original magnification ×200).

Graphic Jump Location

Tables

References

Castelo-Soccio  L, Bernardin  R, Stern  J, Goldstein  SA, Kovarik  C.  Successful treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir. Arch Dermatol. 2010;146(2):124-126.
PubMed   |  Link to Article
Lolis  MS, González  L, Cohen  PJ, Schwartz  RA.  Drug-resistant herpes simplex virus in HIV infected patients. Acta Dermatovenerol Croat. 2008;16(4):204-208.
PubMed
Lascaux  AS, Caumes  E, Deback  C,  et al.  Successful treatment of aciclovir and foscarnet resistant Herpes simplex virus lesions with topical imiquimod in patients infected with human immunodeficiency virus type 1. J Med Virol. 2012;84(2):194-197.
PubMed   |  Link to Article
Rose  WA  II, Tuthill  C, Pyles  RB.  An immunomodulating dipeptide, SCV-07, is a potential therapeutic for recurrent genital herpes simplex virus type 2 (HSV-2). Int J Antimicrob Agents. 2008;32(3):262-266.
PubMed   |  Link to Article
Toro  JR, Sanchez  S, Turiansky  G, Blauvelt  A.  Topical cidofovir for the treatment of dermatologic conditions: verruca, condyloma, intraepithelial neoplasia, herpes simplex and its potential use in smallpox. Dermatol Clin. 2003;21(2):301-309.
PubMed   |  Link to Article

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