Efficacy of photobiomodulation therapy in recurrent herpes labialis management: a randomized controlled trial.

OBJECTIVES: This study is aimed at assessing the therapeutic efficacy of photobiomodulation therapy (PBMT) for the management of recurrent herpes labialis (RHL) by evaluating both pain and clinical recovery. MATERIAL AND METHODS: A randomized, double-blind, controlled trial was conducted on 40 patients with RHL, and they were randomly divided into two groups, where 20 patients received treatment with PBMT (650 nm, 100 mW, 4.7 J/cm2), continuous mode, for 120 s, and placebo cream, while another 20 patients (control group) were treated with acyclovir cream 5% (5 times/5 days) and passive laser. Pain was assessed at five different times. The day when the complete disappearance of the pain was observed and the day when the crust fell off spontaneously were also recorded. RESULTS: The pain level in the control group was significantly higher than that in the PBMT group after the second application of the laser, while the differences were not significant between the two groups at other times. The pain in the PBMT group disappeared faster than that in the control group, but the difference was not significant in terms of clinical recovery. CONCLUSIONS: Photobiomodulation therapy of herpes labialis reduced pain significantly faster than acyclovir, but there was no difference in healing time between the groups in light of the parameters used in this study. CLINICAL RELEVANCE: PBMT is a promising treatment that may be an effective alternative to acyclovir in the management of recurrent herpes labialis. TRIAL REGISTRATION ISRCTN: com ID: ISRCTN87606522.

Non-Thermal Plasma Reduces HSV-1 Infection of and Replication in HaCaT Keratinocytes In Vitro.

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. The antiviral effect of NTP was investigated using an in vitro model of HSV-1 epithelial infection that involved the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. It was found that NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggests the potential of NTP as a therapeutic agent effective against HSV-1 infection.

THE COMBINATION OF ORAL VALACYCLOVIR WITH TOPICAL CLOBETASOL THERAPY WAS THE MOST EFFECTIVE IN REDUCING THE TIME TO HEAL FROM HERPES LABIALIS.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Koe KH, Veettil SK, Maharajan MK, Syeed MS, Nair AB, Gopinath D. comparative efficacy of antiviral agents for prevention and management of herpes labialis: A systematic review and network meta-analysis. J Evid Based Dent Pract. 2023 Mar; 23(1):101778. doi: 10.1016/j.jebdp.2022.101778. Epub 2022 Sep 14. PMID: 36914303. SOURCE OF FUNDING: None. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.

Causal associations between prodromal infection and neuromyelitis optica spectrum disorder: A Mendelian randomization study.

BACKGROUND AND PURPOSE: Prodromal infections are associated with neuromyelitis optica spectrum disorder (NMOSD), but it remains unclear which type of infection has a causal association with NMOSD. We aimed to explore the causal associations between four herpesvirus infections (chickenpox, cold sores, mononucleosis and shingles) and NMOSD, as well as between other types of infections and NMOSD. METHODS: For data on infections, we used the genome-wide association study (GWAS) summary statistics from the 23andMe cohort. For outcomes, we used the GWAS data of participants of European ancestry, including 215 NMOSD patients (132 anti-aquaporin-4 antibody [AQP4-ab]-positive patients and 83 AQP4-ab-negative patients) and 1244 normal controls. Single-nucleotide polymorphism (SNP) identification and two-sample Mendelian randomization (MR) analyses were then performed. RESULTS: In the 23andMe cohort, we identified one SNP for chickenpox (rs9266089 in HLA-B gene), one SNP for cold scores (rs885950 in the POU5F1 gene), one SNP for mononucleosis (rs2596465 in the HCP5 gene), and three SNPs for shingles (rs2523591 in the HLA-B gene; rs7047299 in the IFNA21 gene; rs9260809 in the MICD gene). The association between cold sores and AQP4-ab-positive NMOSD reached statistical significance (odds ratio [OR] 745.318; 95% confidence interval [CI] 22.176, 25,049.53 [p < 0.001, Q < 0.001]). The association between shingles and AQP4-ab-positive NMOSD was also statistically significant (OR 21.073; 95% CI 4.271, 103.974 [p < 0.001, Q < 0.001]). No significant association was observed between other infections and AQP4-ab-positive or AQP4-ab-negative NMOSD. CONCLUSION: These findings suggest there are positive associations between cold sores and shingles and AQP4-ab-positive NMOSD, indicating there may be causal links between herpes simplex virus and varicella-zoster virus infection and AQP4-ab-positive NMOSD.

Vitamin D serum level in participants with positive history of recurrent herpes labialis.

AIM: Vitamin D plays an important role in immune system regulation, also its deficiency is assumed to affect the patients' predisposition to viral diseases such as recurrent herpes labialis. In this cross-sectional study, we tried to compare the mean serum level of vitamin D in participants with a positive history of recurrent herpes labial lesions and healthy controls. MATERIALS AND METHODS: The vitamin D serum level of 43 participants with a positive history of recurrent herpes labial lesions who were referred to the Motahhari laboratory in Shiraz during 2020-2022, was compared with 42 healthy controls. It was assessed by an Elisa kit. An Independent T-test was used to compare the vitamin D serum level between two genders. In order to assess the mean age value and gender distribution, an independent T-test and Pearson Chi-Square were used, respectively for the two groups. The serum vitamin D level was compared between both control and test groups. RESULTS: There was no significant difference between vitamin D mean serum levels in the two evaluated groups (p.value = 0.72). Although the age (p.value = 0.09) and recurrence (p.value = 0.13) of herpes labialis had no statistically significant relation to the vitamin D serum level, the healing duration of herpes labialis was inversely related (p.value = 0.01). Lower-level of serum vitamin D were accompanied by a longer healing duration of the lesions. CONCLUSION: Although the vitamin D serum level of participants with a history of recurrent herpes labialis had no relation with age and herpes virus recurrence frequency, a longer healing duration of lesions had been reported in patients with lower serum levels of vitamin D.

[What is known about the diagnosis and treatment of herpes labialis?] / Wat is er bekend over de diagnostiek en behandeling van herpes labialis?

Herpes labialis is one of the most common skin infections. In most people it is asymptomatic or mildly symptomatic, but very severe cases do occur. Herpes remains latent and can recur. Herpes labialis is a clinical diagnosis. If in doubt, additional testing can be carried out, usually polymerase chain reaction. There are no treatments that can eliminate the virus. In case of more severe symptoms and frequent recurrences, there may be an indication for treatment. In case of mild complaints, topical zinc sulphate/zinc oxide and analgesics (systemic or topical lidocaine) will suffice. More severe complaints and frequent recurrences can be treated with antiviral creams (Aciclovir) or with systemic antiviral medication (Valaciclovir). In frequent recurrences, prophylactic Valaciclovir can also be given for a period of many months. Treatment should be started as soon as possible and will slightly shorten the duration of the disease.

COMPARATIVE EFFICACY OF ANTIVIRAL AGENTS FOR PREVENTION AND MANAGEMENT OF HERPES LABIALIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

OBJECTIVE: To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical trials. METHODS: A systematic search was performed in Ovid Medline PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Clinicaltrials.gov for randomized controlled trials (RCTs) reporting a comparison of antiviral agents in the management and prevention of herpes labialis in healthy/immunocompetent adults. The data extracted from the selected RCTs were assessed and a network meta-analysis (NMA) was performed. The interventions were ranked according to the surface under the cumulative ranking (SUCRA). RESULTS: A total of 52 articles were included for qualitative synthesis and for the quantitative part, 26 articles were analyzed for the primary treatment outcome and 7 studies were analyzed for the primary prevention outcome. The combination therapy of oral valacyclovir and topical clobetasol was the best ranked with a mean reduction in healing time of -3.50 (95% CI -5.22 to -1.78) followed by vidarabine monophosphate of -3.22 (95% CI -4.59 to -1.85). No significant inconsistencies, heterogeneity, and publication bias were reported for TTH outcome analysis. For primary prevention outcomes, only 7 RCTs fulfilled the inclusion criteria, and none of the interventions was shown to be superior to each other. The absence of adverse events was reported by 16 studies, whereas other studies reported mild side effects only. CONCLUSION: NMA highlighted that several agents were effective in the management of herpes labialis among which the combination of oral valacyclovir with topical clobetasol therapy was the most effective in reducing the time to heal. However, further studies are required to determine which intervention is the most effective in preventing the recurrence of herpes labialis.

Uncommon cause of trigeminal neuritis and central nervous system involvement by herpes labialis: a case report.

BACKGROUND: Trigeminal neuropathy is characterized by numbness in the region innervated by the trigeminal nerves, with or without neuropathic weakness in the muscles of mastication. Trigeminal neuritis is a form of trigeminal neuropathy in which the lesion is caused by an inflammation. Herein, we report a patient with trigeminal neuritis due to central nervous system (CNS) involvement of herpes labialis (HL) infection, which was successfully treated with anti-viral and anti-inflammatory agents. CASE PRESENTATION: A young healthy female presented with numbness in the left hemiface for two weeks. She had a preceding typical HL infection on left facial lip one week before the sensory symptom onset. Brain magnetic resonance imaging revealed high signal intensities and asymmetrical thickening with enhancement along the cisternal segment of the left trigeminal nerve. Additionally, brain MR angiography showed multifocal stenoses in the M1 segment of the middle cerebral artery and the cavernous portion of the internal carotid artery. Cerebrospinal fluid (CSF) examination showed mild pleocytosis with normal protein level, glucose ratio, but CSF polymerase chain reaction assay for specific anti-viral antibodies including herpes simplex virus was negative, and CSF culture also did not identify a specific pathogen. The results of serologic testing including tumor markers and autoimmune markers were all unremarkable. A tentative diagnosis of trigeminal neuritis as a complication of HL involving the CNS was made considering the clinical, neuroradiological, and laboratory findings of the patient. Therefore, the patient was treated with intravenous methylprednisolone and acyclovir for 10 days. After the treatments, her sensory disturbance was markedly improved. Brain MRI at the 3-month follow-up also demonstrated improvement of previously identified high signal intensity lesions and multifocal intracerebral artery stenoses. CONCLUSION: HL is usually a self-limiting, benign disease without complications, but rarely presents as trigeminal neuritis due to CNS involvement. Therefore, meticulous evaluation may be necessary if trigeminal neuritis or CNS involving symptoms occur after HL.

Is low-level laser therapy effective in the treatment of herpes labialis? Systematic review and meta-analysis.

The objective of this systematic review is to evaluate the effectiveness of low-level laser therapy in the treatment of herpes labialis. The searches were carried out independently by 2 researchers and the articles were selected through the electronic databases according to the inclusion and exclusion criteria previously established. Initially, 480 articles were found, of which 7 randomized clinical trials and 1 clinical trial were selected. In total, 928 patients were included. In the meta-analysis, the mean healing time for laser use was significant, showing a mean reduction of 1.37 [CI 95% = 0.92 to 1.82] days for tissue healing (p < 0.0001). In the meta-analysis to evaluate the time for crust formation, there was no significant difference between the groups and no significant reduction in the mean time for crust formation (p = 0.150). Only one of the selected studies had a low risk of bias. The use of low-level laser proved to be effective in the treatment of herpes labialis. However, due to the high risk of bias in the included studies, there is a need to carry out new standardized studies to prove the effectiveness of this therapy.

Oral manifestations related to malaria: A systematic review.

OBJECTIVE: To generalize the oral manifestations related to malaria and discuss their clinical significance for health professionals. MATERIALS AND METHODS: The bibliographic databases of Public MEDLINE, Embase, Web of Science and Scopus were employed to retrieve publications online from January 1781 to August 2019. Original research articles, clinical trials, and case reports published in English were included. RESULTS: A small number of studies reported oral manifestations of malaria (n = 29), including gingival bleeding, glossitis, oral ulcer, abnormal oral pigmentation, pericoronitis, herpes labialis, herpes gingivostomatitis, bitter taste, sore throat, Burkitt lymphoma of the jaw, alveolar bone resorption, and enamel hypoplasia. CONCLUSION: Oral manifestations may be important indicators for identification of malaria. Dental and general professionals should pay more attention to oral manifestations in malaria cases, and guide them for specialized examination, diagnosis, and management.

The Origin of the Idea That Herpes Labialis Is of Prognostic Importance in Bacterial Meningitis.

OBJECTIVE: The aim of the work was to study the origin of the idea that herpes labialis (HL) in patients with pneumonia and meningitis was believed to be of prognostic importance. BACKGROUND: HL is caused by a primary infection or reactivation of herpes simplex type I. In the past, it has been related to pneumonia and meningitis; moreover, HL was believed to be of prognostic importance. METHODS: A selection of 19th- and 20th-century textbooks and referred articles was consulted. The relation between meningitis and herpes, type of meningitis, and attributed diagnostic and prognostic importance were studied. In addition, the HL-pneumonia association was studied. RESULTS: The Strasbourg physician Charles-Polydore Forget was the first to describe the HL-meningitis association in 1843. Tourdes (1843), Drasche (1859), and Salomon (1864) attributed a favorable prognostic importance to the HL-meningitis relation. In a comprehensive monograph (1866), August Hirsch, although confirming the association, denied the prognostic importance through critical analysis of the data. Few authors attributed a diagnostic importance to the occurrence of HL, suggesting meningococcal meningitis. CONCLUSIONS: The HL-meningitis relation, but not the prognostic importance, has been mentioned in most neurological textbooks since then. In contrast to meningitis, in which a prognostic attribution of HL was only a short-lived 19th-century idea, the favorable prognostic importance of HL in pneumonia continued to be described until the 1950s. A possible protective effect of herpesviruses has been found in recent years. One could speculate that the disappearance of the prognostic HL-pneumonia relation could be related to the introduction of antibiotics in the late 1940s.

Evaluation of Allergic Diseases, Symptom Control, and Relation to Infections in a Group of Italian Elite Mountain Bikers.

OBJECTIVES: This study estimates the prevalence of allergic diseases in a group of Italian elite mountain bikers, compares the prevalence of infectious episodes between allergic and nonallergic athletes, and evaluates asthma and rhinitis symptom control in allergic athletes. DESIGN: Two hundred twenty-six Italian nonsmoking mountain bikers received by mail the Allergy Questionnaire for Athletes (AQUA) and completed it. The RhinAsthma Patient Perspective (RAPP) questionnaire was sent to the 108 participants with a positive AQUA score and 104 returned the questionnaire. METHODS: Athletes with an AQUA score ≥5 or <5 were defined AQUA+ (allergic) or AQUA- (nonallergic), respectively. RhinAsthma Patient Perspective questionnaire total score ≥15 was indicative of a poor control of symptoms. RESULTS: Of the 226 athletes, 47.8% were AQUA+, whereas 52.2% were AQUA-. A higher number of AQUA+ athletes reported frequent upper respiratory tract infections (URTIs) and herpes labialis than AQUA- athletes (P < 0.001), and the prevalence of URTI was greater in the subgroup of AQUA+ athletes who trained ≥3 hours per session. According to RAPP questionnaire score, 21.1% of AQUA+ mountain bikers had a poor control of asthma and rhinitis symptoms. CONCLUSIONS: Our study shows a high prevalence of allergy among Italian elite mountain bikers whose asthma and rhinitis symptoms are poorly controlled in about a fifth of the sample. Allergic athletes, mainly those training more than 3 hours per session, are at higher risk of URTI and herpes labialis. Screening programs to detect allergic diseases and to evaluate symptom control in athletes should be strongly encouraged.

Comparative study of serum zinc concentration in recurrent herpes labialis patients and healthy individuals.

BACKGROUND: Recurrent herpes labialis (RHL) is a common recurrent infective vesiculoulcerative disease. Topical and systemic administration of Zinc compounds has been indicated to have preventive and therapeutic effects. The purpose of this study was to evaluate the serum level of zinc in the patients with RHL and healthy individuals and also to investigate the correlation of this level with various parameters of the patient and disease course. METHODS: This cross-sectional study was performed on 43 patients with a history of recurrent herpers labialis and 42 subjects without any previous experience of the lesion. Blood samples were taken, and serum zinc level was measured using colorimetry (spectrophotometry) method. Chi-Square test was used to compare the qualitative relationships, and for comparing the quantitative relationships, independent T-test was used. To observe the relationship of quantitative factors including serum zinc level, the number of relapses, and recovery rates, correlation test was taken. RESULTS: The results show that, serum zinc level has no significant difference between healthy subjects and the patients (p > 0.05). Also, zinc level was not related to age and sex factors and frequency of relapse (p > 0.05). However surprisingly, there was a significant relationship between zinc level and recovery period in the RHL patients. The lower the serum zinc level, the higher the duration of recovery (p = 0.009). CONCLUSION: The results of this study indicate that, zinc deficiency can be considered as a risk factor for increasing the duration of herpes labialis lesions. Therefore, the evaluation of serum zinc level in the subjects with RHL and subsequent administration of zinc are recommended in these kind of patients.

Resolution of Recurrent Oro-facial Herpes Simplex Using a Topical Botanical Gel: A Case Report.

Oral herpes labialis, more commonly known as cold sores, are a common encountered viral infection involving herpes simplex virus-1 (HSV-1). Although relatively benign, these lesions can be both unsightly and clinically difficult to manage. Prescription standards of care and over-the-counter agents, such as docosonal, have often shown only limited efficacy in both decreasing lesional pain and reducing duration of lesional symptomology and are not without potential side effects. Despite some success with acute remediation, recurrent episodes often occur, with seemingly no imparted protection or suppression against future outbreaks. This case report involves the successful treatment of oro-facial herpes labialis with a synergistic botanical blend with marked reduction in symptoms, pain score, and lesion duration. Monitoring and evaluation post-treatment and application during future prodromal symptoms was also performed demonstrating additional reduction in the frequency of subsequent outbreaks. This case report supports the use of this treatment for prodromal and acute treatment of oro-facial herpes infection and appears to impart a reduction in the frequency of future outbreaks.

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.

[Intracellular transport of Alphaherpesvirinae]. / Transport intracellulaire des Alphaherpesvirinae.

The Alphaherpesvirinae sub-family includes viruses primarily associated with cold sores, genital herpes, chicken pox and shingles in humans, but are responsible for several other pathologies and additionally infect many animals. These viruses are large entities that travel through various cellular compartments during their life cycle. As for the transport of cellular cargoes, this involves several budding and fusion steps as well as transport of viral particles along the cytoskeleton. Though the entry of these viruses in cells is generally well understood at the molecular level, the egress of newly assembled viral particles is poorly characterized. Albeit several viral genes have been implicated, their mode of action and the contribution of the cell remain to be clarified. The present review updates our current knowledge of the transport of herpes viruses and pinpoints open questions about the mechanisms they exploit.

Erythema multiforme: Differences between HSV-1 and HSV-2 and management of the disease-A case report and mini review.

Erythema multiforme (EM) is an immune-mediated reaction characterized by target lesions and with possible mucosal involvement. Its most frequent cause is HSV, with HSV-1 more common than -2. It is usually self-limited but it can show recurrences. We report a peculiar case of recurrent herpes-associated erythema multiforme (HAEM) in a 35-year-old man. The patient was affected by both herpes labialis and genitalis, but the typical target lesions were only associated with recurrent herpes labialis. Here, we hypothesize about the pathogenic differences between HSV-1 and HSV-2, and discuss the therapeutic management of HAEM.

The controversial natural history of oral herpes simplex virus type 1 infection.

The natural history of oral herpes simplex virus type 1 (HSV-1) infection in the immunocompetent host is complex and rich in controversial phenomena, namely the role of unapparent transmission in primary infection acquisition, the high frequency of asymptomatic primary and recurrent infections, the lack of immunogenicity of HSV-1 internalized in the soma (cell body) of the sensory neurons of the trigeminal ganglion, the lytic activity of HSV-1 in the soma of neurons that is inhibited in the sensory neurons of the trigeminal ganglion and often uncontrolled in the other neurons, the role of keratin in promoting the development of recurrence episodes in immunocompetent hosts, the virus-host Nash equilibrium, the paradoxical HSV-1-seronegative individuals who shed HSV-1 through saliva, the limited efficacy of anti-HSV vaccines, and why the oral route of infection is the least likely to produce severe complications. The natural history of oral HSV-1 infection is also a history of symbiosis between humans and virus that may switch from mutualism to parasitism and vice versa. This balance is typical of microorganisms that are highly coevolved with humans, and its knowledge is essential to oral healthcare providers to perform adequate diagnosis and provide proper individual-based HSV-1 infection therapy.