Preliminary evidence for Herpes labialis recurrence following experimentally induced disgust.

BACKGROUND: After primary orofacial infection with the herpes simplex virus (type 1, HSV-1), up to 40% of HSV seropositive subjects suffer recurrent herpes infections which are characterized by painful erosions of the involved skin mainly around the lips (herpes labialis). Besides various other factors, there is growing evidence suggesting that psychosocial factors might trigger HSV. The present study was designed to investigate modulation of recurrent HSV infection by experimentally induced emotional distress. METHODS: Among patients with herpes labialis (n = 91), subjects who showed recurrent HSV infection (>5 acute infections/year) and who reported to suffer from HSV symptoms exclusively after confrontation with dirty dishes, i.e. dirty plates or dirty glasses were selected by standardized interview. Subjects (n = 20) were randomly assigned to two treatment groups. The experimental group (n = 10) was first exposed to 5 slides showing dirty glasses and subsequently to the glasses previously presented on the slides in vivo. The control group (n = 10) was exposed to neutral slides and neutral objects. In order to determine the proportion of leukocyte subpopulations and concentrations of tumor necrosis factor alpha (TNF-alpha), blood samples were collected 15 min before as well as 40 min and 48 h after stimulus presentation. Saliva cortisol was obtained 45, 20, 15 and 1 min before and 1, 10, 20 and 30 min after stimulus confrontation. RESULTS: Medical examination of the volunteers 48 h after the experiment indicated that four experimental subjects showed HSV-1 symptoms while not a single herpetic infection could be determined in the control subjects (p = 0.033). Moreover, significantly elevated concentrations of TNF-alpha were observed in the experimental, but not in the control group. No significant alterations of the number of leukocyte subpopulations were found 30 min or 48 h after stimulus presentation. Further, cortisol concentrations were found to be unchanged after the treatment. CONCLUSIONS: The present findings suggest that experimentally induced emotional stress such as disgust may be associated with reactivation of HSV.

Patient recognition of recrudescent herpes labialis: a clinical and virological assessment.

OBJECTIVES: The purpose of this study was to ascertain how accurate the general public was at diagnosing the condition of recrudescent herpes labialis. METHODS: An advertisement was placed in a local newspaper inviting patients to attend the Oral Medicine Clinic as soon as they thought they developed the clinically evident stage of herpes labialis. At the clinic, patients were examined to confirm the clinical presence of herpes labialis and also had a swab of the lesion(s) taken for virus culture. Virus culture was by the HEP-2 culture technique capable of detecting both herpes simplex Type 1 and herpes simplex Type 2. Patients also completed a detailed questionnaire concerning their knowledge of herpes labialis. RESULTS: In total, 41 patients attended for screening. The findings were that all patients had clinical herpes labialis, and herpes simplex virus was isolated in 96% of cases. In contrast, in only about 50% of cases were patients aware that their herpes labialis was caused by a virus. CONCLUSIONS: The general public are very good at recognizing herpes labialis lesions but need to be given more information about their infectivity.

[Clinical comparison of two topical antiviral ointments in herpes]. / Lokálisan ható két antiviralis kenöcs klinikai összehasonlítása herpesben.

Herpetic skin lesions have importance and growing frequency in the population. The authors report a double blind study involving 51 patients suffering from recurrent labial herpes to compare the effectiveness and adverse reactions of two topical antiviral preparations, the aciclovir (Zovirax) and epervudine (Hevizos). There was no significant difference between the two treatment groups in the healing tendency of herpetic lesions. The rate of relapses in a two months period was 44.4% in the group treated with aciclovir and 20.8% in the group treated with epervudine, the difference is not significant. Both preparation was well tolerated, only itching occurred as adverse reaction in the group treated with aciclovir. According to the results of the study the original Hungarian product (Hevizos), is at least as effective as the other topical preparation.

Correlation between detection of herpes simplex virus in oral secretions by PCR and susceptibility to experimental UV radiation-induced herpes labialis.

We examined the oral secretions of 25 patients for herpes simplex virus (HSV) at the time of and following experimental UV radiation (UVR). HSV was detected in one or more oral secretion specimens in 5 of 12 (42%) cases by cell culture and in 8 of 12 (67%) cases by PCR. On the day of UVR, HSV was detected in 1 of 12 (8%) patients who developed a lip lesion and 2 of 16 (13%) patients who did not (the difference is not significant). We conclude that PCR is more sensitive than culture in the detection of HSV and that HSV is not shed with increased frequency from the oral cavity before the development of UVR-induced herpes labialis.

Herpes simplex virus type 1 strain KOS-63 does not cause acute or recurrent ocular disease and does not reactivate ganglionic latency in vivo.

The virological, clinical, and histopathological manifestations of acute and experimentally reactivated infections of eyes and trigeminal ganglia have been studied following intranasal infection of rabbits with herpes simplex virus type 1 (strain KOS-63). All animals shed virus in nasal secretions, but only three shed virus in tear film during the first 12 days of infection. No animal developed clinical or histological evidence of corneal or retinal ocular disease at any time after infection. KOS-63 established trigeminal ganglionic latency; viral RNA, restricted to neuronal nuclei, was detected by in situ hybridization, and virus was recovered from co-cultivation cultures of nervous tissue, but not from cell-free homogenates. Reactivation of latent trigeminal ganglionic infection was attempted by intravenous administration of cyclophosphamide, followed by dexamethasone 24 h later. Injection of the drugs failed to reactivate KOS-63 latency; no animal shed virus in nasal or ocular secretions, and no animal developed gross or microscopic corneal lesions. In addition, viral antigens were not detected by immunofluorescence microscopy in ganglia from rabbits subjected to the drug protocol, and virus was only recovered from ganglia by in vitro co-cultivation reactivation techniques. The failure of KOS-63 to reactivate was not due to an inherent failure of populate and infect the ganglion, because the virus did not reactivate from ganglia that contained many latently infected cells. These studies demonstrate that, although KOS-63 is neuroinvasive and capable of establishing latency, it is virtually nonvirulent for the eye, and cannot be reactivated by a systemic immunosuppressive trigger known to reactivate other HSV-1 strains.

The natural history of recurrent oral-facial herpes simplex virus infection.

Oral-facial herpes simplex virus infection is a common, worldwide affliction on which neither public health procedures, vaccines, nor antiviral chemotherapy have yet to have a significant clinical impact. Careful examination of the pathogenesis and clinical features of this illness could lead to insights and a rationale for new and more effective preventive and therapeutic measures. The resistance of recurrent herpes simplex labialis to antiviral chemotherapy may be caused in part by inoculation of the skin simultaneously at multiple foci, such that only a few cycles of virus replication are needed before there is coalescence of the foci, destruction of the epidermis, and clinical lesion formation. Studies of herpes simplex labialis induced by ultraviolet radiation have suggested that there is a subpopulation of lesions that develop immediately after irradiation and that are refractory to chemotherapy. The difficulty finding a treatment for herpes simplex labialis may in part be methodological. Clinical trial protocols for antiviral drugs should target susceptible lesion subgroups and specific stages of the disease.

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.

[The virological diagnosis of recurrent labial herpes]. / Virusologicheskaia diagnostika retsidiviruiushchego gerpesa gub.

Recurrent herpes of the lips was diagnosed by virologic methods in 45 patients. Isolation of herpes simplex virus has confirmed the clinical diagnosis and helped follow up the time course of virus reproduction over 5 days of the relapse; a positive result was achieved in 80 +/- 5.9% of cases. The incidence of herpes simplex virus isolation was the highest as were its titers on day 3 of the relapse. Virologic control within this period is a reliable criterion of the antiviral effect of local therapy of recurrent herpes of the lips.

Isolation and characterization of herpes simplex virus resistant to nucleoside analogs.

Herpes simplex virus type 1 was isolated from nine patients with herpes labialis who were not previously exposed to any antiviral agent. A significant variation in the growth of these isolates in BSC1 cells in the presence of 5-iodo-2'-deoxyuridine and acyclovir was observed. One of the isolates was highly resistant to 5-iodo-2'-deoxyuridine and acyclovir and failed to induce significant activity of thymidine kinase in cultures. Herpesvirus reisolated from the same patient 3 1/2 years later did not show significant changes in its resistance to acyclovir, suggesting that the patient has a latent infection with a drug-resistant virus.

[Recurrent herpes labialis and secondary bacterial infection. A study among the employees at the Ulleval hospital]. / Residiverende herpes labialis og bakteriell sekundaerinfeksjon. En undersøkelse blant ansatte ved Ullevål sykehus.

Recurrent herpes labialis is a prevalent infection. We have investigated the annual incidence and some clinical aspects of the condition, and the frequency of probable superinfection among the staff at the largest hospital in Norway. Over a period of 12 months a total of 83 (67 females and 16 males) out of 3,565 persons with a mean age of 34.3 years experienced clinical recurrence of herpes labialis, giving an annual incidence of 23 persons with one or more eruptions per 1,000 employed. The mean recurrence rate was 4.8 episodes per year. UV-light was reported as a precipitating factor by 60% and psychological stress by 30%. Seven persons reported sick leave of one to three days' duration because of the most recent eruption. In 6/83 patients the probable pathogenic bacteriae (i.e. beta-hemolytic streptococci group A in one and Staphylococcus aureus in five cases) were isolated within the first 48 h after the skin lesions occurred. After 7-9 days S aureus was found in eight persons. The mean duration in days until all skin lesions had healed was the same in patients with or without probable superinfection. Recurrent herpes labialis does not seem to be a significant health problem among the staff of Ullevål Hospital. Probable superinfections appear to occur rarely and without significantly increasing morbidity.

Herpes labialis in parturients receiving epidural morphine following cesarean section.

A significant association exists between the use of epidural morphine (EM), reactivation of herpes labialis (HL) commonly known as coldsores, and pruritus in the obstetric population. A randomized prospective study was designed to eliminate previously identified confounding variables. Immediately following delivery, parturients having undergone cesarean section with epidural anesthesia with carbonated lidocaine (Xylocaine CO2, Astra, Mississauga, Ontario, Canada) with 1:200,000 epinephrine were sequentially randomized to receive either EM or im opioids for postoperative analgesia. One blood sample was collected for viral serology and two mouthwashes (day 0 and 2) were collected to determine oral viral shedding. The patients were observed daily for 5 days. Coldsores were cultured for herpes simplex virus (HSV). Of 187 patients, 96 received EM and 91 im opioids; herpes labialis occurred in 14 of 96 (14.6%) of the former but in 0 of 91 of the latter (P = 0.0004). All 14 experienced facial pruritus. The two groups were at equal risk for reactivation (seropositivity 64.6% and 62.6%, respectively). Analysis of data for those with positive HSV serology reveals 14 of 62 (22.5%) had EM and herpes labialis compared with 0 of 57 in the im group (P less than 0.0001). The incidence of oral viral shedding was low. Surgical stress, the local anesthetic solution, and epinephrine addition to the local anesthetic were eliminated as confounders. Stepwise logistic regression analysis revealed that EM and a history of herpes labialis in these patients were predictive for reactivating oral HSV.

Ocular shedding of herpes simplex virus.

The presence, frequency, and relationship of ocular and oral shedding of herpes simplex virus to previous herpes keratitis was investigated. This was to determine if a history of herpes keratitis predisposes to shedding of the herpes simplex virus into the tear film and/or mouth. Swabs were collected from the eyes and mouth of two groups of patients thrice weekly over a two- to four-month period. Group A comprised nine patients with a history of herpes labialis, group B 15 patients with a history of herpes keratitis. Herpes simplex virus type 1 was isolated from 1.33% of mouth specimens but was not identified in any of the ocular specimens. There was no significant difference between groups A and B in terms of ocular or oral shedding. Oral shedding appears to be independent of a previous herpes keratitis. The tear film is an unlikely source of virus in persons either with no history of herpes keratitis or between attacks in those patients with a history of previous herpes keratitis.

Immune inhibition of virus release from herpes simplex virus-infected cells by human sera.

Human sera contain antibody (IVR antibody) which will inhibit the release of herpes simplex virus type 1 from virus-infected cells. This antibody activity was removed by adsorption of sera with virus-infected cell extract. There was a positive correlation between IVR and neutralizing antibody activity, particularly when measured by augmented neutralization test; measurement of IVR antibody was equally as sensitive as measurement of neutralizing antibody by augmented neutralization test. IVR antibody levels provided indication of a history of recurrent herpes labialis, the pattern of antibody response following primary herpetic infection, and indication of response to Skinner herpes vaccine in human subjects. It is suggested that consideration should be given to measurement of IVR antibody in both clinical and epidemiological studies of herpes and other virus infections.

Recurrences after oral and genital herpes simplex virus infection. Influence of site of infection and viral type.

We prospectively followed 39 adults with concurrent primary herpes simplex virus (HSV) infection (12 with HSV type 1 and 27 with HSV type 2) of the oropharynx and genitalia, caused by the same virus in each person, to evaluate the influence of viral type (HSV-1 vs. HSV-2) and site of infection (oropharyngeal vs. genital) on the frequency of recurrence. The subsequent recurrence patterns of HSV infection differed markedly according to viral type and anatomical site. Oral-labial recurrences developed in 5 of 12 patients with HSV-1 and 1 of 27 patients with HSV-2 (P less than 0.001). Conversely, genital recurrences developed in 24 of 27 patients with HSV-2 and 3 of 12 patients with HSV-1 (P less than 0.01). The mean rate of subsequent genital recurrences (due to HSV-1 and HSV-2) was 0.23 per month, whereas the mean rate of oral-labial recurrences was only 0.04 per month (P less than 0.001). The mean monthly frequencies of recurrence were, in order, genital HSV-2 infections, 0.33 per month; oral-labial HSV-1 infections, 0.12 per month; genital HSV-1 infections, 0.020 per month; and oral HSV-2 infections, 0.001 per month (P less than 0.01 for each comparison). We conclude that the likelihood of reactivation of HSV infection differs between HSV-1 and HSV-2 infections and between the sacral and trigeminal anatomical sites. The sixfold more frequent clinical recurrence rate of genital HSV infections as compared with oral-labial HSV infections may account for the relatively rapid increase in the prevalence of clinically recognized genital herpes in recent years.

Iontophoresis of vidarabine monophosphate for herpes orolabialis.

The cutaneous application of antiviral agents was studied by iontophoresis, a process that increases penetration of most drugs 20- to 60-fold. Twenty-seven subjects with vesicular orolabial herpes were treated one time in a double-blind, placebo-controlled clinical study: nine received vidarabine monophosphate (ara-AMP), nine received acyclovir (ACV), and nine received NaCl. Ara-AMP-treated lesions yielded lower titers of virus after 24 hr compared with lesions treated with NaCl or ACV (P less than .05). Ara-AMP significantly decreased the duration of shedding of virus (P less than .05) and time to dry crust (P less than .05) compared with the other two agents. There was a trend toward decreased healing time after ara-AMP treatment.

Hypothesis: the gingival tissue as a reservoir for herpes simplex virus.

The reservoir site of Herpes simplex virus (HSV), from the primary infection until reactivation and in between recurrences was found to be in the dorsal roots of the trigeminal ganglion or in the sensory root ganglion. However, the triggering of viral genome in the ganglion does not exclusively explain the recurrences and appearance of skin lesions. Other sites cannot, therefore, be excluded, and virus may well be occult also in extraneural tissues. Herpes virus antigens were found by us in the sulcular epithelium of approximately 60% of patients with clinically healthy gingivae; we therefore hypothesised that the epithelial cells might act as the preferential site for latent HSV. In order to prove this assumption, viral genome should be traced in cells of oral tissues, and efforts should be made to rescue virus.