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.

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.

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.

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.

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.

Doxycycline: An option in the treatment of ulcerated oral lesions?

WHAT IS KNOWN AND OBJECTIVES: In addition to its antimicrobial effect, doxycycline has potent anti-inflammatory activity. In view of these pharmacological characteristics, its use in the management of inflammatory, autoimmune and granulomatous diseases has been proposed. The objective of this study was to investigate, through a systematic literature review, the effect of doxycycline on pain and healing of ulcerated lesions of the mouth. METHODS: An electronic search was performed in accordance with PRISMA guidelines in PubMed, Cochrane Central Register, Web of Science, Bireme/LILACS and Scopus databases. Controlled, randomized clinical trials were selected. The concentration of doxycycline, frequency of application, pain relief and clinical remission of the lesions were analysed. RESULTS AND DISCUSSION: According to the inclusion criteria, five articles were selected. In four of these studies, doxycycline was used in the treatment of aphthous stomatitis, and in one study, it was used in the treatment of herpes labialis. In all studies, the drug was used topically, both as a hydrogel and as a crushed tablet (along with a prosthetic adhesive). The groups treated with doxycycline showed faster healing of lesions and lower pain scores compared to placebo. WHAT IS NEW AND CONCLUSION: The present study suggests that topical doxycycline has a positive effect on the treatment of recurrent aphthous ulceration and herpes labialis. Experimental animal studies and double-blind randomized clinical trials should be performed on other oral lesions, such as traumatic ulcers and mucositis.

Recurrent herpes labialis in the pediatric population: Prevalence, therapeutic studies, and associated complications.

Recurrent herpes labialis (RHL) is an incredibly common condition, though the medical literature evaluating pediatric aspects is limited. This paper assesses prevalence and therapeutic studies of pediatric RHL as well as disease complications. A comprehensive literature search of English-language citations based on PubMed queries of selected terms was performed, with exclusion if methodology was not discussed, or if studies had 10 or fewer patients. RHL prevalence in pediatrics has been assessed by measures of point and periodic prevalence, though methodologic limitations may under- or over-estimate the true prevalence of RHL. Studies have been conducted to evaluate therapeutic safety, tolerability, and efficacy of antivirals in the pediatric population. Pediatric RHL point prevalence ranges from 0.72% to 5.2% depending on the population study and the methodologies used. Pediatric RHL carries a significant public health burden and is often implicated in patients with eczema herpeticum, erythema multiforme, reactive infectious mucositis eruptions, and hypersensitivity reactions. There are few studies that evaluate the rates of occurrence of these sequelae associated with pediatric RHL.

Lip creams with propolis special extract GH 2002 0.5% versus aciclovir 5.0% for herpes labialis (vesicular stage) : Randomized, controlled double-blind study.

A lip cream with special propolis extract GH 2002 at a concentration of 0.5% (199 patients) was tested against aciclovir 5% (198 patients) in the treatment of episodes of herpes labialis under double-blind conditions. Upon inclusion, all patients were in the vesicular phase. Application was five times daily of approximately 0.2 g of cream to the entire upper and lower lip. The primary parameter was the difference in time between groups to complete encrustation or epithelization of the lesions. Secondary endpoints were the course of typical herpes symptoms (pain, burning and itching, tension and swelling), the global assessment of efficacy and the safety of application. The predefined clinical situation was reached after a (median) 3 days with propolis and 4 days with aciclovir (p < 0.0001). Significant differences in favor of propolis were also found for all secondary parameters. No allergic reactions, local irritations or other adverse events occurred.

Efficacy of low-level laser therapy in management of recurrent herpes labialis: a systematic review.

Recurrent herpes labialis (RHL) is a highly prevalent viral infection that affects the oro-facial region. Current treatment options have limited efficacy in reducing healing time and recurrence rate of the disease. Recently, low-level laser therapy has been proposed as a potential treatment alternative for the management of RHL with no side effects. This systematic review aims to evaluate the effectiveness of laser therapy in the management and prevention of RHL. A comprehensive search of Medline/PubMed, Scopus, and Web of Science was carried out to identify published clinical trials comparing laser intervention to active and/or non-active controls for the treatment of RHL. Due to marked heterogeneity of available data, studies were assessed qualitatively, and no statistical analysis was performed. Of the retrieved 227 articles, six clinical trials met the eligibility criteria. The wavelengths, the power output, and energy density ranged between 632.5-870 nm, 5-80 W, and 2.04-48 J/cm2, respectively. All included studies found laser to be effective in the management and prevention of RHL, without any side effects. The findings of this review suggest that laser is potentially a safe and effective treatment alternative for the management of RHL. However, due to high variability in study designs and inconsistency in laser parameters among the included studies, more well-designed randomized clinical trials with standardized laser parameters are highly warranted.

Comparative Study with a Lip Balm Containing 0.5% Propolis Special Extract GH 2002 versus 5% Aciclovir Cream in Patients with Herpes Labialis in the Papular/Erythematous Stage: A Single-blind, Randomized, Two-arm Study.

BACKGROUND AND OBJECTIVES: This controlled single-blind trial compared the efficacy of a lip balm with propolis special extract GH 2002 at a concentration of 0.5% in the treatment of episodes of herpes labialis with that of 5% aciclovir cream. METHODS: Patients in the erythematous/papular stage were randomized: 189 patients were treated with propolis cream, 190 patients were treated with aciclovir cream (intention-to-treat population). Application was 5 times daily. The primary parameter was the difference in median time to complete encrustation or epithelialization of lesions. Secondary parameters were the development of typical herpes symptoms (eg, pain, burning and itching, tension, and swelling), the global assessment of efficacy, and the safety of application. RESULTS: The predefined clinical situation was reached after a median of 4 days with propolis and after 5 days with aciclovir (P < 0.0001). Significant differences in favor of the study preparation were found with all secondary parameters and symptoms. No allergic reactions, local irritations, or other adverse events were observed. CONCLUSIONS: A formulation of 0.5% propolis GH 2002 extract lip balm was found to be superior in the treatment of episodes of herpes labialis over 5% aciclovir cream in patients in the papular/erythematous phase upon inclusion. EudraCT Registration No. 2006-001971-38.

Skin changes during pregnancy. Is that an important issue for pregnant women?

OBJECTIVES: The aim of the study was to investigate the prevalence of self-reported skin complaints during pregnancy, applied treatment and the impact on well-being of pregnant women. MATERIAL AND METHODS: We asked 1935 women that were maximum 4 years after labor to fill in our questionnaire. The questionnaire included questions concerning the course of pregnancy, observed skin lesions, applied treatment and influence on the quality of life. RESULTS: Skin changes during pregnancy were reported by 1447 patients (74.78%). The prevalence of self-reported skin complaints were as follows: stretch marks (77.4%), acne (21.6%) and recurrent herpes labialis (11.6%). In 43.67% (n = 632) of women who reported dermatological problems during pregnancy the disease caused significant deterioration in their well-being. Only 168 patients (11.61%) received dermatological treatment from their obstetricians. Dermatological con-sultation required 217 patients (14.99%). For 133 of treated women (25.68%) the recommended treatment was expensive. However, in the majority of patients (379; 73.15%) who received treatment the skin changes resolved after therapy. Skin symptoms resolved significantly faster in the treated group (3.5 ± 4.3 week vs 5.8 ± 6.2 week; p < 0.001). CONCLUSIONS: Self-reported skin complaints seem to be a relevant problem during pregnancy. Proper skin care as well as appropriate treatment applied by obstetricians and/or dermatologists may help women to recover.

Efficacy and safety of nucleoside antiviral drugs for treatment of recurrent herpes labialis: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the effectiveness and safety of nucleoside antiviral drugs for the treatment of recurrent herpes labialis. METHODS: Randomized controlled trials that examined the effectiveness and/or safety of nucleoside antiviral drugs for recurrent herpes labialis were identified via a literature search. The parameters used to measure efficacy were time to healing of classic and all lesions, time to resolution of pain, and percentage of aborted lesions. Safety was assessed by evaluating the adverse events reported during treatment. Subgroup analyses based on the mode of application (topical/systemic) and type of nucleoside antiviral drugs were performed, as were sensitivity analyses of studies with a low risk of bias. RESULTS: Our analysis included 16 publications reporting 25 randomized controlled trials (8453 patients). Nucleoside antiviral drugs decreased the time to healing of all lesions (mean difference: -0.74 days; 95% confidence interval: -0.86, -0.62), especially classic lesions (mean difference: -1.09 days; 95% confidence interval: -1.27, -0.92). They also reduced the time to resolution of pain (mean difference: -0.38 days; 95% confidence interval: -0.58, -0.18) and increased the percentage of aborted lesions (rate ratio: 1.15; 95% confidence interval: 1.07, 1.23). Valaciclovir more effectively reduced the time to healing of all lesions and the time to resolution of pain than did aciclovir. Both nucleoside antiviral drugs increased the percentage of aborted lesions, whereas penciclovir and famciclovir did not. CONCLUSIONS: Nucleoside antiviral drugs are safe and beneficial for the treatment of recurrent herpes labialis; both systemic and topical formulations are recommended. Valaciclovir is more effective than aciclovir, especially in reducing the time to healing of lesions.

Calcium spirulan derived from Spirulina platensis inhibits herpes simplex virus 1 attachment to human keratinocytes and protects against herpes labialis.

BACKGROUND: Chronic infections with herpes simplex virus (HSV) type 1 are highly prevalent in populations worldwide and cause recurrent oral lesions in up to 40% of infected subjects. OBJECTIVE: We investigated the antiviral activity of a defined Spirulina platensis microalga extract and of purified calcium spirulan (Ca-SP), a sulfated polysaccharide contained therein. METHODS: The inhibitory effects of HSV-1 were assessed by using a plaque reduction assay and quantitative PCR in a susceptible mammalian epithelial cell line and confirmed in human keratinocytes. Time-of-addition and attachment experiments and fluorescence detection of the HSV-1 tegument protein VP16 were used to analyze the mechanism of HSV-1 inhibition. Effects of Ca-SP on Kaposi sarcoma-associated herpesvirus/human herpes virus 8 replication and uptake of the ORF45 tegument protein were tested in human retinal pigment epithelial cells. In an observational trial the prophylactic effects of topically applied Ca-SP were compared with those of systemic and topical nucleoside analogues in 198 volunteers with recurrent herpes labialis receiving permanent lip makeup. RESULTS: Ca-SP inhibited HSV-1 infection in vitro with a potency at least comparable to that of acyclovir by blocking viral attachment and penetration into host cells. Ca-SP also inhibited entry of Kaposi sarcoma-associated herpesvirus/human herpes virus 8. In the clinical model of herpes exacerbation, the prophylactic effect of a Ca-SP and microalgae extract containing cream was superior to that of acyclovir cream. CONCLUSION: These data indicate a potential clinical use of Ca-SP containing Spirulina species extract for the prophylactic treatment of herpes labialis and suggest possible activity of Ca-SP against infections caused by other herpesviruses.

Efficacy of adjuvant photobiomodulation therapy in recurrent herpes labialis, a randomized clinical trial study.

OBJECTIVE: This study aimed to determine the effect of Photobiomodulation therapy (PBMT) in the treatment of recurrent herpes labialis (RHL), one of the most common herpes simplex virus type 1 infections. MATERIAL AND METHODS: In this randomized double blind controlled trial, Twenty-two symptomatic patients with RHL were enrolled. The patients were randomly allocated into one group (5 % acyclovir cream with 940±10 nm wavelength and 4 J/cm2 energy density and 100 mW output power) and another group (5 % Acyclovir 5 times/5 days and sham laser). Lesion size, and pain intensity were considered as the outcome at baseline, 1st 2nd and 3rd days postoperatively. RESULTS: Pain intensity in PBM + Acyclovir group was significantly lower than Acyclovir without PBM group in both two and three days after intervention (p < 0.001). The lesion size in case group was significantly lower on 7 and 10 days (p < 0.05). Patients in the treatment group were significantly more satisfied with their treatment process (p = 0.008). CONCLUSION: PBMT can be used as an adjuvant tool to acyclovir cream, due to higher potential in reducing postoperative pain, lesion size and also patients satisfaction.