Perineal Herpes Simplex Infection in Bedridden Geriatric Patients

Background: Herpes simplex virus (HSV) lesions are prone to reactivation and recurrence in response to various local or systemic triggering factors. Objective: To study the characteristics of five bedridden geriatric patients who presented with herpetic recurrences on the buttocks, gluteal cleft, and perianal region during hospitalization. Methods: Data were gathered regarding age, gender, reason for hospitalization, localization of lesions, clinical presentation, previous clinical diagnosis and topical treatments, immune status and immunosuppressant drugs intake, as well as prior history of labial or genital herpes. A skin biopsy was taken for histologic examination and immunohistochemical viral identification. Viral culture and viral serology were performed and data regarding antiviral therapy were recorded. Results: The five patients (three women, two men) were aged <80 years and hospitalized for either severe druginduced renal insufficiency (one case), severe pneumonia (two cases), or stroke causing restricted mobility (two cases). Numerous well demarcated, painful ulcerations developed in the perianal region of these patients, and one patient also presented with some vesicular lesions. The lesions had been confused with mycotic and/or bacterial infections for 10–14 days. No inguinal lymphadenopathies were present and there was no fever. None of the patients had a previous history of recurrent labial or genital HSV infections or HIV infection. Histology was suggestive of HSV infection in two of five patients. Immunohistochemistry identified HSV type I (three patients) and HSV type II (two patients) infections. Viral culture with immunofluorescence viral identification revealed HSV type I in one of the four patients in whom a swab for viral culture was taken. Serology revealed past HSV infection. All lesions cured gradually after 10–14 days of intravenous acyclovir (aciclovir) treatment. Conclusion: Herpetic lesions of the perineal region represent a rare complication in bedridden geriatric patients in the absence of a previous history of HSV infections at the same site. Common traits of patients with this condition were the presence of numerous ulcerated lesions, prolonged time course, and confinement to bed. The latter probably modifies the skin condition, which triggers viral reactivation and favors cutaneous extension of the infection. Complementary diagnostic methods for viral detection and identification are mandatory.     

Suppression of recurrent non-genital herpes simplex infection by prophylactic oral acyclovir

Following a primary infection with herpes simplex virus (HSV) some patients proceed to suffer repeated recurrences of the HSV infection. Whilst it has recently been shown that oral acyclovir taken prophylactically decreases the frequency of recurrent genital HSV infection (Douglas et al. , 1984; Mindel et al. , 1984; Straus et al. , 1984), to date there have been no reports of any form of effective prophylaxis against recurrent HSV infection on non-genital skin in immunocompetent patients. In order to determine if oral acyclovir could afford protection in such patients we have performed a double-blind, placebo-controlled, crossover trial of oral acyclovir in patients experiencing eight or more episodes of recurrent non-genital HSV infection per year.
Fourteen patients entered the trial and 11 completed the protocol. Only two patients experienced a recurrence during the 12-week treatment period with acyclovir (200 mg four times daily), compared with nine during placebo treatment ( P = 0016, sign test). Although lesion development was effectively suppressed in nine of the patients whilst taking acyclovir, the development of prodromal symptoms and occasionally erythema was reported by five. There was no difference between acyclovir and placebo in the time to first recurrence following completion of treatment. No patient reported any side-effects of either placebo or acyclovir therapy.
It is believed that this is the first report of any form of therapy which is effective in the suppression of the frequently recurring non-genital HSV infection in immunocompetent patients.     

Detection of herpes simplex virus DNA in a cutaneous squamous cell carcinoma by in situ hybridization

Summary A case of a cutaneous squamous cell carcinoma (SCC) occurring at the site of a long-standing recurrent HSV infection is described. No deficit of the cell-mediated immunity was recorded. HSV2 was isolated in several viral cultures. HSV DNA was visualized in the SCC by in situ hybridization with biotinylated probes in paraffin-embedded tissue. The samples were negative for HPV2, 5, 16, and 18 probes. A causal relationship between HSV infection and cutaneous SCC is hypothesized.     

Congenital Herpes Simplex Virus Type 1 Infection Mimicking Congenital Erosive and Vesicular Dermatosis: Possible Pathogenic Insights

Congenital erosive and vesicular dermatosis (CEVD) is a rare entity of unknown etiology. We report a case of congenital herpes simplex virus (HSV) type 1 infection that healed with reticulated and supple scarring, similar to that seen in CEVD. Twenty percent of previously reported cases of CEVD had recurrent HSV infection throughout the first year of life. We postulate that at least some previous cases of CEVD may have been due to undiagnosed congenital HSV infection.     

Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts

Sixty-six source contacts of index patients with first-episode genital infection caused by herpes simplex virus (HSV) were evaluated for evidence of current or past HSV infections. Forty-three source contacts (65%) reported a history consistent with previous recurrent HSV infection or were experiencing a first episode of genital herpes when initially examined. However, 60% of these 43 contacts were not aware that they had transmissible HSV infection. Twenty-nine (67%) of the 43 individuals had had recent sexual contact with an index patient when lesions were present. All of the remaining 23 source contacts, who were without a history of symptoms consistent with HSV infection, had detectable neutralizing antibody to HSV; HSV type 2 was isolated from the cervix of two of these asymptomatic source contacts. Efforts to identify individuals with undiagnosed genital herpes and to instruct these individuals concerning the risk of disease transmission in the presence of lesions are needed if the rate of transmission is to be decreased; however, methods designed to decrease the rate of transmission by asymptomatic individuals must also be evaluated.     

The herpes-specific immune response of individuals with herpes-associated erythema multiforme compared with that of individuals with recurrent herpes labialis

Infection with herpes simplex virus (HSV) is the most common precipitating factor in the development of erythema multiforme (EM). It is not known why only a few of the many individuals who experience recurrent HSV infection also develop herpes-associated EM (HAEM), although a difference in the HSV-specific immune response has been postulated. The purpose of this study was to compare the HSV-specific immune response of individuals with HSV infection alone with that of individuals with HAEM. There were 21 patients in each of the two groups. Four parameters of the HSV-specific immune response were examined: (1) anti-HSV IgG titers were measured by ELISA; (2) antibody neutralization was assessed using a plaque assay; and (3) antibody-dependent complement-mediated cytotoxicity, and (4) antibody-dependent cellular cytotoxicity were investigated using a previously described in vitro HSV-specific cytotoxicity assay. No statistically significant differences were detected between the two patient groups. Thus, a difference in these HSV-specific immune mechanisms does not explain the development of HAEM in some individuals with recurrent HSV infection.Grant support: AI 16637 from the National Institutes of Allergy and Infectious Disease     

Incidence of serum antibody titers against herpes simplex virus in Japanese patients

Herpes simplex virus (HSV) establishes latency in the sensory neuronal ganglia after primary infection, and occasionally causes recurrent infection, mainly on the lips or genitalia. Previous reports revealed an age‐related increase in HSV‐immunoglobulin G seropositive subjects in a hospital‐based study and the general population in Japan. In this report, we retrospectively analyzed the results of serological tests against HSV, in which subjects were diagnosed with or suspected as having HSV infection. A total of 1216 subjects with at least one complement fixation (CF) result were included. Of these, 771 subjects (63.4%) were positive at first visit. When stratified by age, incidence of positive patients linearly increased with age from teenagers (44.9%) to those in their 80s (88.9%). Positivity in women was higher than in men overall; significantly higher incidence was observed in women aged in their 30s, 40s and 60s. When observing changing HSV‐CF titers over time in 81 initially negative patients, 18 (22%) seroconverted during the 2121‐day observation period. In this study, we clearly show that distribution of HSV‐CF titers is similar to previous HSV‐immunoglobulin G results. This correlation is probably caused by the continual subclinical proliferation of HSV, thus maintaining CF titers. Our observations provide current data on the incidence of HSV, reconfirming that serological examination is unreliable in diagnosing recurrent herpes, and the majority of infected subjects are asymptomatic.     

Detection of herpes simplex virus DNA in the peripheral blood during acute recurrent herpes labialis.

BACKGROUND: Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which this virus may be present in the blood during a localized infection in otherwise healthy adults is unknown. OBJECTIVE: The purpose of this study was to determine whether HSV may be detected in the peripheral blood during acute recurrent herpes labialis. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from otherwise healthy adults with recurrent herpes labialis, both during an acute episode and several weeks after the lesions had healed. The PBMCs were examined for the presence of HSV with the polymerase chain reaction (PCR) and viral culture. RESULTS: By PCR, HSV DNA was detected in 7 of 34 specimens from an acute episode but in none of 24 specimens in the convalescent stage (p less than 0.004). PBMCs from seven donors, who were seronegative for HSV, were also negative for HSV by PCR. Viral cultures of 22 PBMC specimens were negative (including four specimens that were positive by PCR). CONCLUSION: The presence of HSV DNA in the blood is a transient phenomenon limited to the period of active infection in a minority of patients with herpes labialis, although it may be important in the development of disseminated disease as well as in the pathogenesis of herpes-associated cutaneous processes such as erythema multiforme.     

Relapsing herpes simplex-2 folliculitis in the beard area

We describe the case of a 52-year-old immunocompetent man with recurrent folliculitis on the left cheek, associated with intense pain. Bacteriological, mycological and Tzanck tests from the lesions were negative. Histopathological study showed an aspecific flogosis pattern. Virological tests carried out on swabs and paraffin-embedded tissue sections from the facial lesions by nested PCR technique (nPCR) demonstrated the presence of herpes simplex virus type 2 (HSV\2) in both samples. Skin swabs from other healthy areas of the face resulted negative for herpetic infection. A diagnosis of recurrent herpetic folliculitis by HSV\2 was made. This case report underlines that even in immunocompetent patients HSV\2 lesions can feature atypical clinical aspects. In dermatological assessment the benefits of routine PCR techniques for differential diagnosis of herpetic infection should be considered above all for the prompt initiation of antiviral therapy and appropriate patient management.     

Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis

A double-blind, placebo-controlled, multicenter trial of oral L-lysine monohydrochloride for the prevention and treatment of recurrent herpes simplex (HSV) infection was conducted. The treatment group was given L-Lysine monohydrochloride tablets (1,000 mg L-lysine per dose) 3 times a day for 6 months. A total of 27 (6 male and 21 female) subjects on L-lysine and 25 (6 male and 19 female) subjects on placebo completed the trial. The L-lysine treatment group had an average of 2.4 (p less than 0.05) less HSV infections, symptoms were significantly (p less than 0.05) diminished in severity and healing time was significantly reduced (p less than 0.05). L-Lysine appears to be an effective agent for reduction of occurrence, severity and healing time for recurrent HSV infection.     

Immunological Studies of herpes simplex virus infection in children with atopic eczema

Summary This study examines the role of immune defence mechanisms in herpes simplex virus (HSV) infections in atopic eczema and whether impairment of these mechanisms explains the susceptibility of some children with atopic eczema to cutaneous HSV infections. Ten children with eczema herpeticum and 13 with atopic eczema and recurrent HSV infection affecting multiple skin sites were studied, together with relevant control groups. In all children with atopic eczema, in vitro lymphoproliferation in response to stimulation with concanavalin A (Con A) was significantly decreased and natural killer (NK) cells (CD16 + 56) were reduced compared with non-atopic controls. IL-2 receptors, a marker for lymphocyte activation, were decreased during the acute phase of eczema herpeticum, and for 1 month thereafter. A positive stimulation index (>3) to HSV antigen, and high HSV lgG antibody titres measured by ELISA. Western blotting and neutralization assay, were seen in children with eczema herpeticum by 6 weeks, and also in children with atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Impairment of cell-mediated immunity in atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Imairment of cell-mediated immunity in atopic eczema was suggested by the reduced response to Con A. It is likely that reduced numbers of circulating NK cells and a decrease in IL-2 receptors during early eczema herpeticum contribute to the susceptibility of children with atopic eczema to cutaneous HSV infections.     

Update on antiviral therapy for herpes simplex virus infection

ABSTRACT: The prevalence of infection with herpes simplex virus (HSV) continues to increase largely due to the inability of current antiviral agents to eradicate latent infection. This article reviews strategies to slow the transmission of HSV infection, most importantly through the development of vaccines, as well as established and emerging choices for treatment of primary and recurrent genital herpes, herpes labialis, infections in immunocompromised hosts, and acyclovir-resistant infections. The role of chronic suppressive therapy in the management of genital herpes as well as its potential impact on transmission rates will also be discussed.
Herpes simplex virus (HSV) is a widespread pathogen in the United States, with more than 100 million U.S. citizens having serologic evidence of HSV-1 infection and 40–60 million, nearly one-fifth of the adolescent and adult population, infected with HSV-2 (1,2) . The prevalence of HSV-2, the major cause of genital herpes, has increased 30% since the late 1970s (2) . The fact that most of those infected with HSV are asymptomatic and yet may still be subclinically shedding virus further complicates efforts to slow the spread of transmission (3) . Therefore proper management of herpetic infections requires that the clinician be able to effectively diagnose those with HSV infection, to educate them regarding means of spread and symptoms indicative of infection, and to adequately treat infections which are identified in order to alleviate patient symptoms and slow the transmission of the virus. We review options for preventing infection, treating primary infections, and treating recurrent infections in order to accomplish these goals.     

Detection of herpes simplex virus genomic DNA in various subsets of Erythema multiforme by polymerase chain reaction

BACKGROUND: The wide variation in the detection of herpes simplex virus (HSV) DNA (36-75%) by polymerase chain reaction (PCR) in erythema multiforme (EM) may be partly attributed to differences in case selection in terms of subsets of EM studied. OBJECTIVE: To determine the frequencies of detection of HSV DNA in specific subsets of EM. METHODS: Nested PCR was used to detect HSV DNA in skin biopsies with histologically proven EM. RESULTS: PCR was performed on skin biopsies from 63 patients with EM. HSV DNA was detected in 3/11 (27.2%) of single-episode HSV-associated EM (HAEM), 6/10 (60%) of recurrent HAEM, 1/4 (25%) of single-episode idiopathic EM and 6/12 (50%) of recurrent idiopathic EM. HSV DNA was not detected in atypical EM (0/11), suspected drug-induced EM (0/9) or Stevens-Johnson syndrome (0/6). CONCLUSION: The overall PCR positive rates of HAEM (42.9%) and idiopathic EM (43.8%) were comparable suggesting that idiopathic EM is likely to be related to a subclinical HSV infection.     

Differential virulence of herpes simplex virus intratypic strains

Many events determine the severity, duration, and predisposition to recurrent herpes simplex virus (HSV) disease. In addition to the various host immune responses, such as local, humoral, and cellular immunity, which influence the outcome of infection and subsequent development of disease, evidence is also accumulating to suggest that intratypic strains of HSV may also play an important role in the outcome, depending on the degree of virulence each strain exhibits. Since it has been suggested that each individual is initially infected and colonized with a strain of virus whose characteristic virulence or avirulence will determine the type of HSV disease that individual will experience, it is suggested that intratypic strains should be considered an important variable in recurrent HSV disease.     

Oral acyclovir in the suppression of recurrent non-genital herpes simplex virus infection

In a double-blind, placebo-controlled, cross-over trial in 11 patients suffering eight or more episodes of recurrent non-genital herpes simplex virus (HSV) infection per annum, only two patients experienced a recurrence during treatment with oral acyclovir (200 mg 4 times daily) for up to 12 weeks, compared with nine during placebo treatment (P = 0.016). Although lesion development was effectively suppressed in nine of the patients whilst taking acyclovir, the development of prodromal symptoms, and occasionally erythema, was reported by five. There was no difference between acyclovir and placebo in the time to the next recurrence following completion of treatment. No patient reported any side effects of either placebo or acyclovir therapy. It is believed that this is the first report of any form of oral therapy which is effective in suppressing recurrent non-genital HSV infection in immunocompetent patients.     

Herpes immunization—on the threshold

Objectives To review the history, public health importance and current status of vaccines intended for the prevention and treatment of genital herpes simplex virus infection.
Background Primary and recurrent genital herpes remains a significant public health problem. Prophylactic and therapeutic vaccines offer an important strategy for control of genital herpes.
Methods Literature review.
Results For more than half a century the development of a safe and effective herpes simplex virus (HSV) has remained an elusive goal. Factors complicating vaccine development have included the complex natural history of HSV infection, an intricate viral genome which has made production of simple tissue culture attenuated live viral vaccines impossible, a general lack of understanding regarding what constitutes protective immunity and an excess of poorly conceived and seriously flawed clinical research. Over the past decade prospects for developing an effective vaccine have brightened as advances in basic immunology and molecular biology have increased our understanding of HSV, and as clinical investigators have taken lessons from the mistakes of earlier research. Investigative teams both in academic centers and in industry are now making excellent progress toward the development of HSV vaccines.
Conclusions The combination of increased understanding and focused application is expected to result in the development of safe and effective HSV vaccines which should be available to physicians within this decade. The goal of the prophylactic vaccine will be to prevent symptomatic primary genital infection and reduce the likelihood the patient will establish latent infection and experience recurrent disease. The therapeutic vaccines are designed for patients who experience recurrent infections with the intended benefit of reduced symptomatic and subclincial recurrences.     

Screening to detect asymptomatic shedding of herpes simplex virus (HSV) in women with recurrent genital HSV infection.

To investigate the asymptomatic shedding of herpes simplex virus (HSV) from women with recurrent genital herpes infection, and to assess whether inapparent shedding could occur, eight such women were examined thrice weekly for one month. At each visit colposcopy was performed and multiple sites sampled for HSV. During the study four women had no recurrence of HSV infection, but four had at least one positive viral culture. One of these patients was asymptomatically shedding HSV on nine of her 11 clinic visits. Two episodes of urethral shedding were detected. In this group of patients the presence of inguinal lymphadenopathy was appreciably associated with the isolation of HSV from the urogenital tract.     

Adjustment to the psychological and social sequelae of recurrent genital herpes simplex infection.

OBJECTIVE--To investigate whether adverse psychological consequences and impaired sexual and interpersonal functioning are present in individuals suffering from recurrent genital herpes simplex infection (HSV). DESIGN--A questionnaire-based study completed by subjects defined as having more than one episode of HSV infection. SUBJECTS--Completed questionnaires were returned from 90 subjects; 40 from the department of genitourinary medicine at our hospital and 50 from members of the Herpes Association. RESULTS--Stress and being physically run-down were identified as provoking factors by the majority of individuals (78% and 56% respectively). The frequency of sexual activity was not different when comparing rates before and after infection (p < 0.001) and the majority of subjects had told partners of their infection. Women reported significantly greater disturbances in several psychological variables and reported a greater decrement in their general health. However, overall there were no differences in the psychological sequelae following herpes infection. CONCLUSIONS--The study suggests that, given time, most people are able to adjust psychologically to having recurrent herpes infection. However, for a minority of subjects this is not the case and these individuals may require psychotherapeutic intervention.     

Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group.

OBJECTIVE: To compare the efficacy and safety of twice daily valaciclovir with five times daily aciclovir in the treatment of an episode of recurrent genital herpes simplex virus (HSV) infection in immunocompetent individuals. METHODS: 739 patients with a history of recurrent genital HSV infection received either oral valaciclovir (500 mg twice daily) or aciclovir (200 mg five times daily) for 5-days for treatment of their next recurrent episode in a controlled, randomised, double blind trial. Patients self initiated therapy at the first signs and/or symptoms of the HSV recurrence, then were assessed in clinic on five occasions over 7 days, and twice weekly thereafter until lesions had healed. Safety was evaluated through adverse experience reports and haematology and biochemistry monitoring. RESULTS: No significant differences were detected between valaciclovir and aciclovir for the primary endpoint, the duration of all signs and symptoms which included lesion healing and pain/discomfort. The hazard ratio [95% confidence interval] for valaciclovir v aciclovir was 0.93 [0.79, 1.08]. Lesion healing time was similar in each treatment group (hazard ratio valaciclovir v aciclovir 0.96 [0.80, 1.14]). The odds ratio of valaciclovir v aciclovir in preventing the development of vesicular/ulcerative lesions was 1.08 [0.82, 1.42]. Percentages of patients in whom all HSV cultures were negative were similar in the valaciclovir and aciclovir groups at 59% and 54% respectively; for patients having equal to or more than one positive culture result after treatment initiation, cessation of virus shedding was similarly rapid for the two treatments (hazard ratio 0.98 [0.75, 1.27]). The safety profiles of valaciclovir and aciclovir were comparable with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that valaciclovir 500 mg twice daily is equivalent in efficacy to aciclovir 200 mg five times daily as episodic treatment of recurrent genital HSV infection. Valaciclovir maintains the established efficacy and safety of aciclovir but offers a much more convenient twice daily dosing regimen.     

Longitudinal study of a patient with herpes-simplex-virus-associated erythema multiforme: viral gene expression and T cell repertoire usage.

BACKGROUND: Erythema multiforme is a polymorphous self-limited, often recurrent eruption that can follow herpes simplex virus (HSV) infection, hereby designated HAEM. Studies of relatively large groups of patients during one recurrent episode indicated that HAEM pathogenesis is associated with HSV gene expression, Vbeta2 T cell infiltration of lesional skin and altered T cell receptor (TCR) repertoire usage by HSV-stimulated peripheral blood mononuclear cells (PBMC). However, HAEM recurrences are not always preceded by overt HSV eruptions and virus cannot be isolated from HAEM lesional skin. Therefore, it is unknown whether all HAEM recurrences experienced by a given patient are HSV related. OBJECTIVE: The studies described in this report were designed to examine whether all HAEM recurrences experienced by a given patient are HSV related. METHODS: We describe one patient who was studied longitudinally during 6 HAEM recurrences and in the intervening lesion-free periods. Lesional skin from all HAEM episodes was studied for HSV gene expression and infiltration by Vbeta2 and Vbeta3 T cells. PBMC obtained at these times were assayed for TCR repertoire usage upon HSV stimulation. RESULTS: Lesional skin from all HAEM episodes was positive for HSV gene expression (RNA and protein) as well as Vbeta2 T cell infiltration. HSV-stimulated PBMC obtained at these times had an altered TCR repertoire characterized by a predominance of Vbeta2 cells. The duration of viral gene expression, Vbeta2 cell infiltration and altered TCR repertoire usage correlated with the duration of clinical symptoms. CONCLUSION: The data suggest that HSV and a virus-specific immunopathology component are involved in the causation of all HAEM episodes experienced by the patient.