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Verrucous herpetic infection of the scrotum and the groin in an immuno-competent patient: Case report and review of the literature

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Verrucous herpetic infection of the scrotum and the groin in an immuno-competent patient: Case report and review of the literature
Yoon-Soo Cindy Bae-Harboe1 MD, Amor Khachemoune2 MD
Dermatology Online Journal 18 (7): 7

1. Boston University Medical Center, Boston, Massachusetts
2. SUNY Downstate, Brooklyn, New York


Abstract

Atypical presentations of genital herpes are more commonly described among immuno-compromised patients. Furthermore, verrucous lesions may be attributed to acyclovir resistant strains of herpes simplex virus as well as co-infection with fungi and other viruses in this patient population. We describe the first case of verrucous genital herpes infection in an immuno-competent patient.



Introduction

Genital herpes is most commonly caused by herpes simplex virus type 2 (HSV-2) and is one of the most prevalent sexually transmitted diseases. Herpes simplex virus (HSV) affects more than 500 million people worldwide and has an estimated incidence of 23 million infections each year [1]. Herpes simplex virus 2 (HSV-2) seroprevalence among 14- to 49-year-olds in the United States is estimated at 16 percent [2]. Infection with herpes simplex virus (HSV-2) is the leading cause of genital ulcers worldwide [3, 4] and many of those infected are unaware and transmit the virus during periods of subclinical shedding [5, 6].

To further complicate matters, the risk of human immunodeficiency virus-1 (HIV-1) acquisition is three fold higher among herpes simplex virus-2 (HSV-2) sero-positive persons [7]. Herpes simplex virus (HSV) most typically presents as grouped and confluent vesicles. However, among immunocompromised patients, atypical presentations including vegetating and keratotic plaques have been described. To date, a verrucous presentation of herpes simplex virus (HSV) has not been reported in immunocompetent patients and so we report the first case.


Case report


Figure 1Figure 2
Figures 1 and 2. Coalescing keratotic and vegetating plaques on the scrotum and inguinal folds.

A 60-year-old man with no history of human immunodeficiency virus infection (HIV), cancer, or other medical problems presented with relatively rapidly developing lesions on the scrotum, inguinal folds, and inner thighs over a period of 7 days (Figures 1 and 2). The patient denied prior episodes of similar lesions and complained of a burning sensation and mild discomfort, but no significant pain. On physical examination, multiple well-demarcated, round, pink exophytic papules and nodules coalescing into larger plaques were found on the scrotum. Some papules exhibited superficial erosions and ulcerations. Similar lesions were found on bilateral medial upper thighs, some of which had yellow overlying crust. There were no other lesions elsewhere on the body surface or the mucosae.

The differential diagnosis included pemphigus vegetans, scrotal calcinosis, deep fungal infection, perforating collagenosis, epidermal cysts, iododerma, and bromoderma.


Figure 3
Figure 3. Biopsy showing marked hyperkeratosis and acanthosis of the epidermis with dyskeratotic and necrotic keratinocytes within the epidermis as well as multinucleated keratinocytes at the base of the lesion (x20).

The patient was seen by another dermatologist and a superficial biopsy using a tangential shave technique showed only inflammation and crust. Hence, a second opinion was sought by the patient and the dermatologist. Routine blood tests ordered by the patient’s primary care physician were within normal limits or negative; HIV test was also negative. The patient was started on a course of cephalexin along with topical wound care and Vaseline ointment with once or twice daily dressing changes as needed using non-adherent pads and sterile gauze. Five days later, a subsequent biopsy of a verrucous lesion on the right inner thigh was obtained and sent for special stains for fungi and bacteria. The histopathologic examination showed ulceration, pseudoepitheliomatous hyperplasia with multinucleated giant cells and viral nuclear inclusions (Figure 3). Periodic Acid Schiff (PAS) stain for fungi, silver stain for spirochetes, and stains for acid-fast bacteria were negative. Cultures for fungi and acid-fast bacteria were negative. A diagnosis of verrucous genital herpes with a possible concomitant bacterial and viral infection was made and a course of valacyclovir (1000 mg by mouth twice daily for 10 days) was prescribed. The patient missed his follow up appointment, but he mentioned over the phone that he almost completely cleared his lesions approximately 3 weeks after the initiation of valacyclovir. Although the diagnosis of verrucous genital herpes was supported histopathologically, other diagnoses like lymphoma, immunoglobulin deficiency, and sarcoidosis have not been completely ruled out.


Discussion

After a thorough literature review using pubmed, including non-English language articles, as far as we can tell, this is the first case to describe an atypical verrucous presentation of genital herpes virus infection in an immuno-competent patient. Herpes simplex virus infected genital lesions in men typically occur on the glans penis or penile shaft [8]. The presenting lesions in our patient were keratotic and formed large vegetating plaques. These lesions did not have an obvious vesicular component as might be expected with herpetic infection. In addition, a concomitant bacterial infection (or even concomitant viral infection) could have contributed to the verrucous nature because antibacterial treatment was administered prior to the cultures. Also, secondary bacterial infection can produce a verrucous appearance in a variety of conditions.

Atypical manifestations of herpes virus infection in the genital area have been reported in the literature in immuno-compromised patient such as those with acquired immunodeficiency syndrome (AIDS) [9], human immunodeficiency virus (HIV) [10], malignancy [11], organ transplants [12], and congenital immunodeficiency disorders [13, 14]. Presentations include a papular eruption, hyperkeratotic verrucous lesions, and eroded vegetating plaques [9, 10, 15, 16, 17,18]. Many of these herpes simplex virus (HSV-2) cases have been resistant to acyclovir therapy [13, 19].

In addition, acyclovir resistant skin lesions infected with Varicella Zoster Virus (VZV) [16, 17, 20, 21, 22, 23], Cytomegalovirus (CMV) [17, 24, 25], and molluscum contagiosum [17] have also been described to appear verrucous.

Although cytomegalovirus rarely causes cutaneous lesions, when they do occur, infections typically appear papulovesicular, purpuric, nodular, and ulcerative. Unusual cases presenting as hyperkeratotic warty lesions have been reported in patients with human immunodeficiency virus (HIV) infected with varicella zoster virus (VZV), herpes simplex virus (HSV), and cytomegalovirus (CMV) [17].

Cutaneous co-infection of herpes virus and other infectious etiologies have also been reported to emerge and present unusually. Co-infection of herpes virus (typing unspecified) with fungus as well as concomitant infection with human papillomavirus (HPV), herpes simplex virus (typing unspecified), and fungus have been described as keratotic and vegetating plaques [26]. Cases of herpes simplex virus (HSV) (typing unspecified) and cytomegalovirus (CMV) co-infection [24] have also been observed and thought to contribute to the atypical presentation.

The cause of herpes simplex virus-related verrucous lesions has not been elucidated even in patients with known immuno-compromised status. In patients infected with human immunodeficiency virus (HIV), it has been proposed that proliferation of factor XIIIa positive dendritic cells that enhance growth of keratinocytes may foster a verrucous clinical presentation of HSV [17]. Some authors have postulated that the pathogenesis of verrucous HSV may be similar to that of keratoacanthomas, which can also present as verrucous, wart-like plaques and may be associated with viral infection [26]. HSV lesions that do not respond to therapy with acyclovir within 5-10 days are suspected to be caused by acyclovir-resistant strains [27]. For such cases, intravenous foscarnet is the current treatment of choice [27].


Conclusion

Often, a clinical diagnosis of herpes infection does not require biopsy; however, in unusual verrucous presentations, a diagnosis of herpes infections should be included in the differential diagnosis and biopsy considered in both immuno-compromised and immuno-competent patients. Persistent lesions should be biopsied and cultured for herpes simplex virus (HSV). Techniques like polymerase chain reaction may enhance the sensitivity of herpes simplex virus (HSV) detection. In conclusion, herpes simplex virus infection (HSV) should be considered in both immuno-competent and -compromised patients with verrucous lesions in the genitalia. Among immuno-competent patients, this presentation may herald immunodeficiency later in life. As the first published case, to our knowledge, of genital verrucous herpes simplex virus infection in an immuno-competent person, additional cases should be reported to better elucidate the subject.

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