Viral Genetics Modulate Orolabial Herpes Simplex Virus Type 1 Shedding in Humans.

BACKGROUND: Orolabial herpes simplex virus type 1 (HSV-1) infection has a wide spectrum of severity in immunocompetent persons. To study the role of viral genotype and host immunity, we characterized oral HSV-1 shedding rates and host cellular response, and genotyped viral strains, in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 29 MZ and 22 DZ HSV-1-seropositive twin pairs were evaluated for oral HSV-1 shedding for 60 days. HSV-1 strains from twins were genotyped as identical or different. CD4+ T-cell responses to HSV-1 proteins were studied. RESULTS: The median per person oral HSV shedding rate was 9% of days that a swab was obtained (mean, 10.2% of days). A positive correlation between shedding rates was observed within all twin pairs, and in the MZ and DZ twins. In twin subsets with sufficient HSV-1 DNA to genotype, 15 had the same strain and 14 had different strains. Viral shedding rates were correlated for those with the same but not different strains. The median number of HSV-1 open reading frames recognized per person was 16. The agreement in the CD4+ T-cell response to specific HSV-1 open reading frames was greater between MZ twins than between unrelated persons (P = .002). CONCLUSION: Viral strain characteristics likely contribute to oral HSV-1 shedding rates.

Decreased Labial Herpes Simplex Virus Outbreaks Following Botulinum Neurotoxin Type A Injection: A Case Report.

Herpes Labialis results from reactivation of latent herpes simplex virus (HSV-1 or HSV-2) harbored in the trigeminal ganglion during times of psychological stress, cutaneous injury or photo exposure. Following reactivation, the virus is anterogradely transported through axonal termini to the skin where the virus is released and replicates causing a clinical outbreak. Botulinum neurotoxin A (BoNTA) is known to inhibit presynaptic neuropeptide and neurotransmitter release. Whether it has the capacity to interfere with viral shedding and delivery into the skin remains unclear. We were interested in determining whether BoNTA could serve as a potential therapeutic or prophylactic treatment approach for frequent and severe HSV recurrences. We describe a clinical case report in which a patient successfully maintained a sustained absence of HSV outbreaks in regions where BoNTA was intradermally administered. BoNTA may offer a novel therapeutic approach for preventing recurrent HSV disease. J Drugs Dermatol. 2018;17(10):1127-1129.

The alpha-herpesviridae in dermatology : Herpes simplex virus types I and II.

This review on herpes simplex virus type I and type II (HSV­I, HSV­II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV­I infection; HSV-related folliculitis; verrucous HSV­I and HSV­II lesions; the role of recurrent HSV­I infection in burning mouth syndrome; HSV­I and HSV­II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV­I or HSV­II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV­I and anti-HSV­II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV­I and HSV­II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.

[Prevention and treatment of Herpes Labialis]. / Herpès labial: Comment le soigner? Comment l'éviter?

Herpes labialis, more commonly known as cold sores or fever blisters, is the most common clinical manifestation of infection with Herpes simplex virus type 1. It is a highly contagious and widespread infection. Generally benign, cold sores may however disturb those who suffer from them, because of the symptoms they cause or their unsightly and frequent appearance. The pharmacist is often consulted to relieve cold sore recurrences. As for any request for advice, the pharmacist will assess if he can help the patient himself or if medical advice is more appropriate. Besides a possible symptomatic treatment, the pharmacist will also advise the patient to prevent recurrence and the contamination of other people.

Recent approval of Xerese in Canada: 5% acyclovir and 1% hydrocortisone topical cream in the treatment of herpes labialis.

Herpes labialis is a frequently occurring viral infection of the lips and oral mucosa. Recurring lesions are induced by viral reactivation and replication, but the symptoms leading to morbidity, such as pain and inflammation, are immune-mediated. The introduction of 5% acyclovir/1% hydrocortisone in a topical cream (Xerese™) represents a therapeutic strategy directed at both of these pathogenic processes. Applied at the onset of prodromal symptoms, this combination treatment has a good safety profile and is more effective in reducing healing time than antiviral or anti-inflammatory agents alone. Although it was US FDA-approved for herpes labialis in 2009, Xerese™ has only recently been approved for use in Canada in October 2013. Herein, we review the basic science and clinical studies that support the efficacy of this topical combination acyclovir-hydrocortisone product in treating herpes labialis and examine its safety profile, as well as touch upon other therapies that have been shown to be effective in treating this common viral condition.

[Cycloferon and management of herpes virus infection].

The treatment of patients with various forms of herpes requires a complex approach with using chemo- and immunotropic drugs. The use of Cycloferon, an interferon inductor (12.5% injection solution, 150 mg tablets or 5% liniment) was shown efficient. It had antiviral and immunotropic action in the mono- and combination therapy of herpes simplex of the skin and mucosa, genital herpes, ophthalmoherpes, herpes zoster, infectious mononucleosis. Cycloferon lowered the level and period of the disease clinical signs, prolonged the remission, corrected the immunity shifts, prevented the complications. The results of the study presented a conclusive proof for recommending such a use of Cycloferon in wide medical practice.

Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections.

AIMS: To quantify and compare the expression of Langerhans cells (LCs) in the tongue mucosa of AIDS patients with different opportunistic infections, and from acquired immune deficiency syndrome (AIDS) and non-AIDS patients with normal tongues, using autopsy material. METHODS AND RESULTS: Human leucocyte antigen D-related (HLA-DR), CD1a and CD83 antibodies were used to identify and quantify LCs by immunohistochemistry in tongue tissue of 40 AIDS patients (10 with lingual candidiasis, 10 with lingual herpes, 10 with oral hairy leukoplakia and 10 with no lesions) and 23 tongues from human immunodeficiency virus (HIV)-negative control patients. Quantification was performed by means of conventional morphometry in four different regions (anterior, middle, posterior and lateral) of the tongue. The results were expressed as positive cells per area of epithelium. The AIDS patients presented a lower density of CD1a(+) cells (P < 0.001), HLA-DR (P < 0.003) and CD83 (P < 0.001) in all regions of the tongue compared to the non-AIDS control group. However, no differences in any of the markers were found when AIDS patients with different opportunistic infections were compared with AIDS patients without tongue infection. CONCLUSIONS: Advanced stage AIDS patients showed a depletion of LCs in the tongue mucosa. HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections.

C21orf91 genotypes correlate with herpes simplex labialis (cold sore) frequency: description of a cold sore susceptibility gene.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) infects >70% of the United States population. We identified a 3-megabase region on human chromosome 21 containing 6 candidate genes associated with herpes simplex labialis (HSL, "cold sores"). METHODS: We conducted single nucleotide polymorphism (SNP) scans of the chromosome 21 region to define which of 6 possible candidate genes were associated with cold sore frequency. We obtained the annual HSL frequency for 355 HSV-1 seropositive individuals and determined the individual genotypes by SNPlex for linkage analysis and parental transmission disequilibrium testing (ParenTDT). RESULTS: Two-point linkage analysis showed positive linkage between cold sore frequency and 2 SNPs within the C21orf91 region, 1 of which is nonsynonymous. ParenTDT analysis revealed a strong association between another C21orf91 SNP, predicted to lie in the 3' untranslated region, and frequent HSL (P = .0047). C21orf 91 is a predicted open reading frame of unknown function that encodes a cytosolic protein. CONCLUSIONS: We evaluated candidate genes in the cold sore susceptibility region using fine mapping with 45 SNP markers. 2 complementary techniques identified C21orf91 as a gene of interest for susceptibility to HSL. We propose that C21orf91 be designated the Cold Sore Susceptibility Gene-1 (CSSG1).

Focused review: neuraxial morphine and oral herpes reactivation in the obstetric population.

Neuraxial morphine administration is a common strategy for providing postcesarean delivery analgesia. Morphine delivered via this route increases the risk of herpes labialis (oral herpes) reactivation, a disease common in women of childbearing age. A primary concern is risk of transmission to the neonate from maternal reactivation. The benefits to the mother of this form of analgesia outweigh the risk of neonatal herpes acquired postpartum from maternal recurrence because serious neonatal morbidity from recurrent herpes has not been described.

Prevention of ulcerative lesions by episodic treatment of recurrent herpes labialis: A literature review.

There are substantial difficulties involved in carrying out clinical studies of recurrent herpes labialis, since the disease has a rapid onset, short-lasting viral shedding period and is rapidly self-healing. The aim of this paper was to critically assess published reports of episodic treatment of herpes labialis and to review biological and methodological problems involved in such studies. Limited, but statistically significant, results have been shown with topical antivirals, such as acyclovir and penciclovir, improving healing times by approximately 10%. Orally administrated antivirals, such as valaciclovir and famciclovir, have subsequently found clinical use. However, these two oral medications have different profiles in phase 3 studies. Famciclovir showed additional improvement of efficacy in terms of lesion healing time, but no effect on prevention of ulcerative lesions, while valaciclovir appeared to have similar efficacy to that of acyclovir cream on lesion healing, but some additional efficacy with respect to prevention of ulcerative lesions. A formulation of acyclovir/hydrocortisone showed further improvement in prevention of ulcerative lesions, while retaining efficacy with respect to lesion healing.

Detection of herpes simplex virus DNA in plasma of patients with primary but not with recurrent infection: implications for transfusion medicine?

Among the family of herpes viruses, only cytomegalovirus (CMV) and, to a lesser extent, human herpes virus 8 (HHV-8) are of relevance in transfusion medicine. Due to neutropism, herpes simplex viruses (HSV) types 1 and 2 are considered to be of minor relevance. However, several reports gave evidence that a HSV DNAemia might occur and HSV could therefore be transmissible by blood products. The aim of our study was to collect data about prevalence of HSV antibodies among blood donors and to clarify whether HSV DNAemia is possible. HSV antibody states of 653 blood donors were investigated. Blood specimens of 46 patients with primary and recurrent HSV infection were tested for HSV-1 and HSV-2 DNA using TaqMan polymerase chain reaction. In 505 of the 653 blood donors HSV antibodies were detectable, most of which were HSV-1 antibodies. HSV DNA was detected in plasma, but not in peripheral blood mononuclear cells (PBMCs) of seven rather seriously ill patients with primary herpes genitalis. No HSV viraemia was detectable in otherwise healthy patients with recurrent herpes labialis. Thus, HSV DNAemia is possible, but seems to be limited to primary infections and could not be detected in the recurrent infection. Therefore, blood donors with primary herpes infection should be deferred from donation. Blood donors with recurrent HSV infection are probably not at risk of transmitting HSV, but further studies are necessary to prove this hypothesis. Detection of HSV DNA in PBMCs as described formerly could not be confirmed by this study.

Treatment of herpes labialis by photodynamic therapy: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Lesions of herpes labialis are caused by the herpes simplex virus type 1 and cause pain and aesthetic compromise. It is characterized by the formation of small vesicles that coalesce and rupture forming extremely painful ulcers, that evolve to crusts, dry desquamations until their complete remission. Currently the treatment of these lesions is done with acyclovir. Although it diminishes the symptomatology, it causes viral resistance and does not prevent the recurrence of the lesions. It is known that antimicrobial photodynamic therapy (aPDT) has numerous advantages, among them: the reduction of the time of remission, and does not cause resistance. This protocol will determine the effectiveness of PDT in lesions of herpes labialis. MATERIALS AND METHODS: A total of 30 patients with herpes labialis in the prodromal stage of vesicles, ulcers, and crusts will be selected to participate in the study and randomized into 2 groups: G1 control and G2 experimental. After signing Research Ethics Committee and TA, patients in group G1 will undergo the standard gold treatment for herpes labialis with acyclovir and simulated PDT treatment. Patients in the experimental G2 group will be treated simulating the gold standard treatment of herpes labialis (placebo) and PDT. In all patients, saliva samples will be collected for analysis of cytokines, and will be performed exfoliative cytology in the lesions. The pain will be assessed through a pain scale and a questionnaire of quality of life related to oral health (OHIP-14) will be given to them. Patients will continue to be followed up after 7 days, 1 month, 3 months, and 6 months; if there is a recurrence of the lesion, they will contact the researchers.Clinical registration: clinicaltrials.gov - NCT04037475. Registered on July 2019.

Herpes simplex virus type I-infected disorders alter the balance between Treg and Th17 cells in recurrent herpes labialis patients.

Recurrent herpes labialis (RHL) is a common skin disease that is often caused by herpes simplex virus type I (HSV-1), but its immunology and pathogenesis remain unclear. The balance of Th17/Treg cells is crucial for maintaining immune homeostasis. This study aimed to investigate whether the balance of Th17/Treg cells and related cytokines may be a determinant occurrence in patients with RHL. This is a clinical experimental research based on clinical observation and analysis. We collected RHL patients from the outpatient clinic of the Department of Dermatology of Zhejiang Chinese Medical University (Hangzhou, China) in 2017, conducted questionnaire survey and signed informed consent. Peripheral blood was collected from 30 patients with RHL and 30 healthy volunteers. Flow cytometry was used to detect the percentages of Treg cells and Th17 cells. Protein microarrays coated with 20 cytokines related to T-cell subsets were performed. Enzyme-linked immunosorbent assay (ELISA) assay was conducted to further verify the expression levels of the cytokines that were screened by protein microarrays. Percentages of Th17/Treg cells in peripheral blood of RHL patients were significantly increased compared to those in healthy volunteers. The fold changes of GM-CSF, IL-4, TGF-ß, IL-12, IL-10, IL-17F, and TNF-α were significantly increased compared with healthy volunteers. In addition, the expression of IL-4, IL-10, and TGF-ß in the serum of RHL patients increased significantly. Our results indicated an imbalance of Th17/Treg cells in RHL, and this imbalance is probably an important factor in the occurrence, development, and recovery of RHL.

Practical management measures for patients with recurrent herpes labialis.

Recurrent herpes labialis (RHL) is a common condition associated with the formation of vesicles around the mouth, often preceded by prodromal symptoms including tingling and burning. Treatment is targeted toward individual episodes, but in severe cases, suppressive therapy may be indicated. At present, no cure exists for this troublesome condition. The purpose of this article is to serve as a practical guide in the management of RHL by summarizing current treatments and discussing potential new therapies.

Oral herpes simplex virus infection in pregnancy: what are the concerns?

Although epidemiologic data and the potentially serious effects of transmission of genital herpes from mother to infant during birth have been widely reported, published reports on oral herpes disease in pregnancy remain scarce and no clear management guidelines exist. Thus, questions remain about acquisition, transmission and outcome of infection, especially with respect to acute gingivostomatitis in pregnancy. In response to these questions, we summarize previous reports on herpes simplex virus 1 (HSV-1) oral disease in pregnancy and, briefly, present 2 cases of primary gingivostomatitis in the first trimester of pregnancy, resulting in a favourable outcome for both mother and infant. We also point out the most recent data on rare, potentially severe in outcome, but treatable, primary central nervous system HSV-1 infection in later stages of pregnancy. Finally, we emphasize a multidisciplinary approach to oral HSV disease in pregnancy, with dentist participation in the diagnosis and treatment.

Herpes Simplex Reactivation After Surgical Treatment of Trigeminal Neuralgia: A Retrospective Cohort Study.

BACKGROUND: Herpes simplex virus (HSV) reactivation after surgery for trigeminal neuralgia has long been recognized. Only a few studies to date have focused on this complication, and its actual incidence remains unknown. The aim of this study was to investigate the incidence of postoperative herpes labialis (HL) in a cohort of patients treated with either percutaneous balloon compression or microvascular decompression to identify potentially significant differences between different treatments. METHODS: A total of 92 patients who were operated on for TN with microvascular decompression (group A) or percutaneous balloon compression (group B) in the period 2010-2017 were retrospectively evaluated. The 2 subgroups of patients were compared according to history of previous HL and incidence of postoperative HL. RESULTS: The final cohort comprised 56 male and 36 female patients. Average age was 58.50 years; 30 male patients belonged to group A and 26 male patients belonged to group B. Lifetime incidence of episodes of HL before surgery in 18/58 patients in group A (31.0%) and 12/34 patients in group B (35.3%), with no statistically significant difference among subgroups. Postoperatively, 1/56 patients in group A (1.7%) experienced HL compared 5/34 patients in group B (14.7%), with a strongly statistically significant difference between the 2 subgroups. CONCLUSIONS: In our clinical experience, herpes simplex virus reactivation after surgery for trigeminal neuralgia is not so rare and is still not completely understood. Postoperative herpes simplex virus reactivation could be due to a direct mechanical injury on gasserian ganglion neurons, which is more common after percutaneous balloon compression.

Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features.

Herpes Simplex Virus Type 1 (HSV-1) is a nuclear replicating enveloped virus, usually acquired through direct contact with infected lesions or body fluids (typically saliva). The prevalence of HSV-1 infection increases progressively from childhood, the seroprevalence being inversely related to socioeconomic background. Primary HSV-1 infections in children are either asymptomatic or following an incubation period of about 1 week gives rise to mucocutaneous vesicular eruptions. Herpetic gingivostomatitis typically affects the tongue, lips, gingival, buccal mucosa and the hard and soft palate. Most primary oro-facial HSV infection is caused by HSV-1, infection by HSV-2 is increasingly common. Recurrent infections, which occur at variable intervals, typically give rise to vesiculo-ulcerative lesions at mucocutaneous junctions particularly the lips (herpes labialis). Recurrent HSV-1 infection within the mouth is uncommon in otherwise healthy patients, although in immunocompromised patients, recurrent infection can be more extensive and/or aggressive. The diagnosis of common herpetic infection can usually be based upon the clinical history and presenting features. Confirmatory laboratory diagnosis is, however, required when patients are, or may be, immunocompromised.