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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.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The present study aimed to evaluate the effectiveness of the application of photobiomodulation therapy (PBMT) in the prevention of recurrent herpes labialis (RHL) through a randomized controlled clinical trial. Background data: RHL is a lifelong infection that effects patients' quality of life. In the literature PBMT has shown positive results preventing RHL, decreasing recurrences and severity of lesions. Despite the good results reported, there are still few controlled clinical studies published on the subject. Methods: For this study, 158 volunteers were recruited and were randomly divided into three study groups: Laser 1-1 J/point (L1J): n  = 61, Laser 2-2 J/point (L2J): n  = 50, and placebo-0 J/point: n  = 47. The treatment consisted of a protocol of 15 sessions throughout 6 months and 2 years of follow-up posttreatment. Results: The results showed that L1J presented the most satisfactory results concerning the reduction of the number of lesions per year and less severity of recurrences in the long-term evaluation when compared with L2J. Both Laser Groups (L1J and L2J) were statistically more efficient than placebo in all aspects analyzed. All patients who received laser treatment (L1J and L2J) and presented recurrences had significant improvement in frequency and/or severity of lesions. No patient had side effects from treatment. Conclusions: PBMT can be effective in the reduction of the frequency of recurrences of RHL and in the severity of postirradiation lesions that may appear.

Background: Research results on the efficacy of sunblock sticks in avoiding or reducing Herpes labialis (HL) recurrences are contradictory and has shown mixed results, with some protection reported under experimental conditions that could not be replicated under natural conditions., Objective: The purpose of the present work was to carry out an in vivo test on the effectiveness of a protective lip product in preventing recurrent HL in natural conditions during summer., Methods: An exploratory randomized crossover study was performed on 20 adult volunteers who served as their own controls during the analysis. The study was conducted between May and July 2017 around the summer solstice. During the two-month period, volunteers had to perform normal daily activities and also needed to go to the beach in Sardinia; thirty subjects applying SPF 30 protection and 30 without protection., Results: In individuals with stick protection, the number of HL attacks was significantly reduced. Based on association between different parameters, which emerged from the medical history and the post-test questionnaire, it was found that male individuals over 44 y of age and with Fitzpatrick skin type 2 were the most exposed to recurrence., Conclusion: HL recurrence rate can be reduced by using sunblock stick in summer.

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.

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., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Herpes simplex labialis (HSL), also known as cold sores, is a common disease of the lips caused by the herpes simplex virus, which is found throughout the world. It presents as a painful vesicular eruption, forming unsightly crusts, which cause cosmetic disfigurement and psychosocial distress. There is no cure available, and it recurs periodically., Objectives: To assess the effects of interventions for the prevention of HSL in people of all ages., Search Methods: We searched the following databases up to 19 May 2015: the Cochrane Skin Group Specialised Register, the Oral Health Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), the China National Knowledge Infrastructure (CNKI) database, Airiti Library, and 5 trial registers. To identify further references to relevant randomised controlled trials, we scanned the bibliographies of included studies and published reviews, and we also contacted the original researchers of our included studies., Selection Criteria: Randomised controlled trials (RCTs) of interventions for preventing HSL in immunocompetent people., Data Collection and Analysis: Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion., Main Results: This review included 32 RCTs, with a total of 2640 immunocompetent participants, covering 19 treatments. The quality of the body of evidence was low to moderate for most outcomes, but was very low for a few outcomes. Our primary outcomes were 'Incidence of HSL' and 'Adverse effects during use of the preventative intervention'.The evidence for short-term (≤ 1 month) use of oral aciclovir in preventing recurrent HSL was inconsistent across the doses used in the studies: 2 RCTs showed low quality evidence for a reduced recurrence of HSL with aciclovir 400 mg twice daily (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.13 to 0.51; n = 177), while 1 RCT testing aciclovir 800 mg twice daily and 2 RCTs testing 200 mg 5 times daily found no similar preventive effects (RR 1.08, 95% CI 0.62 to 1.87; n = 237; moderate quality evidence and RR 0.46, 95% CI 0.20 to 1.07; n = 66; low quality evidence, respectively). The direction of intervention effect was unrelated to the risk of bias. The evidence from 1 RCT for the effect of short-term use of valaciclovir in reducing recurrence of HSL by clinical evaluation was uncertain (RR 0.55, 95% CI 0.23 to 1.28; n = 125; moderate quality evidence), as was the evidence from 1 RCT testing short-term use of famciclovir.Long-term (> 1 month) use of oral antiviral agents reduced the recurrence of HSL. There was low quality evidence from 1 RCT that long-term use of oral aciclovir reduced clinical recurrences (1.80 versus 0.85 episodes per participant per a 4-month period, P = 0.009) and virological recurrence (1.40 versus 0.40 episodes per participant per a 4-month period, P = 0.003). One RCT found long-term use of valaciclovir effective in reducing the incidence of HSL (with a decrease of 0.09 episodes per participant per month; n = 95). One RCT found that a long-term suppressive regimen of valaciclovir had a lower incidence of HSL than an episodic regimen of valciclovir (difference in means (MD) -0.10 episodes per participant per month, 95% CI -0.16 to -0.05; n = 120).These trials found no increase in adverse events associated with the use of oral antiviral agents (moderate quality evidence).There was no evidence to show that short-term use of topical antiviral agents prevented recurrent HSL. There was moderate quality evidence from 2 RCTs that topical aciclovir 5% cream probably has little effect on preventing recurrence of HSL (pooled RR 0.91, 95% CI 0.48 to 1.72; n = 271). There was moderate quality evidence from a single RCT that topical foscarnet 3% cream has little effect in preventing HSL (RR 1.08, 95% CI 0.82 to 1.40; n = 295).The efficacy of long-term use of topical aciclovir cream was uncertain. One RCT found significantly fewer research-diagnosed recurrences of HSL when on aciclovir cream treatment than on placebo (P < 0.05), but found no significant differences in the mean number of participant-reported recurrences between the 2 groups (P ≥ 0.05). One RCT found no preventive effect of topical application of 1,5-pentanediol gel for 26 weeks (P > 0.05). Another RCT found that the group who used 2-hydroxypropyl-β-cyclo dextrin 20% gel for 6 months had significantly more recurrences than the placebo group (P = 0.003).These studies found no increase in adverse events related to the use of topical antiviral agents.Two RCTs found that the application of sunscreen significantly prevented recurrent HSL induced by experimental ultraviolet light (pooled RR 0.07, 95% CI 0.01 to 0.33; n = 111), but another RCT found that sunscreen did not prevent HSL induced by sunlight (RR 1.13, 95% CI 0.25 to 5.06; n = 51). These RCTs did not report adverse events.There were very few data suggesting that thymopentin, low-level laser therapy, and hypnotherapy are effective in preventing recurrent HSL, with one to two RCTs for each intervention. We failed to find any evidence of efficacy for lysine, LongoVital® supplementation, gamma globulin, herpes simplex virus (HSV) type I subunit vaccine, and yellow fever vaccine in preventing HSL. There were no consistent data supporting the efficacy of levamisole and interferon, which were also associated with an increased risk of adverse effects such as fever., Authors' Conclusions: The current evidence demonstrates that long-term use of oral antiviral agents can prevent HSL, but the clinical benefit is small. We did not find evidence of an increased risk of adverse events. On the other hand, the evidence on topical antiviral agents and other interventions either showed no efficacy or could not confirm their efficacy in preventing HSL.

A significant portion of the world's population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) over a half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A(∗)24, HLA-B(∗)27, HLA-B(∗)53 and HLA-B(∗)58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B(∗)44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy., (Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Despite intensive efforts in recent decades to develop preventive or therapeutic vaccines against diseases caused by herpes simplex virus (HSV), or varicella-zoster virus (VZV), members of the Alpha herpes virinae subfamily of human herpes viruses,a safe and efficient vaccine has been approved for commercial development only against VZV. The VZV vaccine contains a live attenuated strain, OKA. It consists of amixture of at least 13 subpopulations of viruses, all with deletions, insertions or mutations in the genome; the most common mutations are observed in the open reading frame 62 (ORF62). Experience over more than 30 years in Japan, the USA and other countries where VZV vaccination is provided has demonstrated that the vaccine is safe and the effectiveness of two doses compared to unvaccinated children is 98-99%. When administered in a higher dose to stimulate the declining cell-mediated immunity, the same vaccine has been shown to reduce the incidence and severity of herpes zoster in immunocompetent individuals older than 60 years. Vaccination of immuno-compromised subjects with this VZV vaccine is problematic and various strategies need to be explored. Differences in the pathomechanisms of infection, latency and immune evasion of VZV and HSV, together with host genetic factors, may explain the availability of the successful VZV vaccine and the failures of the past HSV vaccine candidates.

Herpes simplex virus (HSV) prophylaxis may be underutilized in cosmetic surgery at a time when cosmetic procedures are increasing. Our goal is to review the data regarding HSV prophylaxis in order to remind cosmetic surgeons when to consider adding this regimen to their patient perioperative care.

Data Sources: The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Medline and Embase databases were searched together with the reference lists of primary studies, commentaries and reviews. Grey literature resources including the System for Information on Grey Literature in Europe, the Scopus Web and Patent searches, Proquest Dissertations and Theses Fulltext, the Index to Scientific and Technical Proceedings and the clinical trials registry (http://clinicaltrials.gov) were also searched., Study Selection: Randomised controlled trials (RCTs) involving nucleoside antiviral agents for the prevention of recurrent oral herpes in healthy immunocompetent subjects ≥12 years old were included. No language restrictions were applied. Study quality was assessed following Cochrane guidelines., Data Extraction and Synthesis: Data were abstracted using a standardised data extraction form and analysed with meta-analysis carried out only with studies that reported the same outcome measure., Results: Ten studies were included, only one study was considered to have a low risk of bias, five an unclear risk and four a high risk of bias. Oral acyclovir (800-1,600 mg daily) and valacyclovir (500 mg daily for four months) were shown to be effective in the prevention of RHL when taken prior to the appearance of any symptoms or exposure to triggers., Conclusions: This review found support for the use of systemic acyclovir and valacyclovir for the prevention of RHL. However, the findings from this review should be interpreted with caution, because the methodologic assessment of the quality of the included studies showed an unclear risk of bias in five out of the ten included papers, and a high risk of bias in four studies.

Herpes labialis affects one third of the population. We evaluated the topical application of an antiviral compound, hydroxypropyl-β-cyclodextrin (2-HPβCD), in reducing herpes labialis relapses. In this double-blind, randomized, placebo-controlled trial, 40 patients were randomized to a polyethylene glycol (PEG) formulation containing 20% 2-HPβCD or to a vehicle control arm. The gel was applied to the lips twice daily for 6 months. The primary objective was reducing herpes relapses. Surprisingly, the drug group had significantly more relapses than the vehicle group (p = 0.003). While the median numbers of relapses in the preceding year were 12 in the vehicle group and 10 in the drug group, both groups experienced very few relapses during the 6-month treatment period, with a median of 0 in the vehicle group and a median of 2 in the drug group. The impressive reduction of relapses in both groups may be due to a placebo effect or due to the topical treatment with PEG., (Copyright © 2013 S. Karger AG, Basel.)

Background: Herpes simplex virus (HSV) is one of the most common sexually transmisible infections worldwide. HSV-associated stigma negatively impacts emotional and sexual health, suggesting a need for novel approaches to reducing stigma. The aims of this study were to describe the range of destigmatising strategies used by the public in brief online videos, and to describe videos that were successful or unsuccessful in creating a destigmatising message., Methods: A thematic content analysis was performed on 103 publicly produced YouTube videos designed to destigmatise HSV infection for an Australian online contest., Results: Five destigmatising strategies were identified: providing information, normalising through familiarity, promoting disclosure, negating a negative perception and expressing moral indignation. Most videos employed multiple strategies. Regarding the degree of destigmatisation achieved, videos were coded as unsuccessful, successful, mixed or neutral. Unsuccessful and successful videos often employed the same strategies, but differed in their ability to balance positive and negative messages about HSV and to manage affective content. Some videos were successful despite not providing information about HSV. Mixed videos were appreciated differently in different contexts, and the use of humour was especially problematic. Neutral videos tended to exclusively provide information while avoiding affective content., Conclusions: Efforts to reduce HSV-associated stigma may be unsuccessful and may even perpetuate stigma. Special attention must be paid to balance and to affective content, specifically humour, when attempting to convey a destigmatising message. Doing so may help reduce the role stigma plays as a barrier to appropriate care for patients with HSV infection.

A 57-year-old woman with herpes labialis and previously diagnosed with vestibular neuritis experienced recurrences of vertigo and disequilibrium. Initially preceded by oral herpes outbreaks or upper respiratory infections, these recurrences became spontaneous and more frequent. Vestibular function demonstrated a 25% decrease in energy function in the right and the patient had left beating nystagmus on positional maneuver. Her reoccurrences of vestibular disturbances were followed up. Concurrently, she was prescribed daily valacyclovir (500 mg, 1 per day) given for the prevention of herpes labialis outbreaks by her primary care physician. Recurrences of disequilibrium stopped completely as well as oral herpes outbreaks., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to complete a systematic review and, if possible, a meta-analysis on the effectiveness of systemic and topical nucleoside antiviral agents in the prevention of recurrent herpes labialis (RHL) in immunocompetent subjects., Study Design: Multiple comprehensive electronic and manual literature searches without language restrictions identified the studies to be included. Quality assessment and data synthesis methods followed those described in the Cochrane guidelines., Results: Of 2,683 papers reviewed, 10 met the inclusion criteria. Oral acyclovir (800-1,600 mg daily) and valacyclovir (500 mg daily for 4 months) were shown to be effective in the prevention of RHL when taken prior to the appearance of any symptoms or exposure to triggers. Of the 10 papers reviewed, only 1 was determined to have a low risk of bias., Conclusions: This review found support for the use of systemic acyclovir and valacyclovir for the prevention of RHL., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Prior pilot studies support the use of antiviral medications with topical corticosteroids for herpes simplex labialis (HSL). ME-609 (Xerese, Xerclear) is a combination of 5% acyclovir and 1% hydrocortisone developed for the topical treatment of HSL., Objectives: The primary study end point was the prevention of ulcerative HSL lesions., Methods: In all, 2437 patients with a history of HSL were randomized to self-initiate treatment with ME-609, 5% acyclovir in ME-609 vehicle, or ME-609 vehicle (placebo) at the earliest sign of a cold sore recurrence. Cream was applied 5 times/d for 5 days. A total of 1443 patients experienced a recurrence and initiated treatment with ME-609 (n = 601), acyclovir (n = 610), or placebo (n = 232)., Results: Of patients receiving ME-609, 42% did not develop an ulcerative lesion compared with 35% of patients receiving acyclovir in ME-609 vehicle (P = .014) and 26% of patients receiving placebo (P < .0001). In patients with ulcerative lesions, healing times were reduced in the ME-609 and acyclovir groups compared with placebo (P < .01 for both). The cumulative lesion area for all lesions was reduced 50% in patients receiving ME-609 compared with the placebo group (P < .0001). There were no differences among groups in the number of patients with positive herpes simplex virus cultures. The side-effect profile was similar among treatments., Limitations: The study did not contain a group treated with a topical corticosteroid alone., Conclusions: ME-609 prevented progression of cold sores to ulcerative lesions and significantly reduced the cumulative lesion area compared with acyclovir and placebo. ME-609 treatment offers additional therapeutic benefit compared with therapy with topical acyclovir alone., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Herpes labialis (HL) is the most common manifestation of recurrent oral herpes simplex virus type-1 (HSV-1) infection. Between 20% and 40% of the population is affected by recurrent HL. The biological basis for the difference between HSV-1-infected individuals who do and who do not suffer recurrences, has long been investigated. Interferon (IFN)-alpha and IFN-lambda are essential for antiviral immunity, but the precise role of IFN-lambda in vivo is not yet well understood., Methods: Healthy immunocompetent patients with or without a history of recurrent HL were recruited from the Policlinico of the University of Rome Tor Vergata (Rome, Italy), and HSV-1-seronegative individuals were recruited from the Department of Experimental Medicine of the University of Rome Tor Vergata, between July 2007 and December 2008. Participants were interviewed by medically trained investigators and underwent a blood test. Peripheral blood mononuclear cells (PBMCs) were obtained from heparinized blood of patients and stimulated in vitro with intact HSV-1 strain F1 (1 plaque-forming unit/cell). PBMC supernatants were assayed for IFN-alpha, IFN-gamma and IFN-lambda production by ELISA at 24 and 48 h after viral challenge., Results: PBMC from patients with a history of recurrent HL produced markedly lower levels of IFN-lambda and marginally lower levels of IFN-alpha and IFN-gamma than those from the history-negative HSV-1-seropositive controls. Among individuals with HL recurrences, those with more frequent and severe manifestations showed a significant trend towards lower levels of IFN-lambda production., Conclusions: A reduced IFN-lambda response might correlate with the development of recurrent HSV-1 infection in immunocompetent individuals. Testing for IFN-lambda response might be useful to predict individual patterns of antiviral response, contributing to more successful therapeutic or prophylactic interventions.

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.

Introduction: Most episodes of recurrent herpes labialis are self-limited and mild, but can be troublesome when they occur frequently with painful and unsightly lesions. Therefore, there has been much interest in developing agents that can suppress outbreaks in addition to being therapeutically effective. The objective of the present study was to examine the prophylactic and therapeutic efficacy of 1,5-pentanediol (PD) gel in patients with recurrent episodes of herpes labialis., Methods: In this placebo-controlled, randomized, double-blind clinical trial, a total of 105 patients with frequent episodes of recurrent herpes were randomized to either PD or placebo. During the 26-week prophylactic phase of the study, the patients applied PD gel or placebo gel twice daily to both lips. Upon recurrence of an episode, a 5-day therapy phase started during which the gel was to be applied eight times daily. After the therapy phase, the patient resumed prophylactic treatment twice daily until the next herpes episode. The main outcome measures were number of herpes episodes during the prophylactic phase of 26 weeks, and successful therapy of occurring herpes episodes with a 5-day treatment., Results: There was no significant difference in recurrence rate between the two groups (P>0.05). During recurrence there was a statistically significant improvement regarding the therapeutic effect of the symptoms "blistering," "swelling," and "pain" in the PD group. The global evaluation of efficacy by the investigators and patients showed a statistically significant superiority for PD as opposed to placebo (P<0.001)., Conclusion: Under the conditions used in the present study, PD did not show any prophylactic effect against recurrence of herpes episodes. A significantly better therapeutic effect of PD over placebo could be demonstrated on the symptoms "blistering," "swelling," and "pain." PD was very safe as no side effects were observed during the course of the study.

Background: Treatment of herpes simplex labialis (HSL) has been associated with modest benefits. This difficulty results from the rapid resolution of the disease accomplished by the immune system, which narrows the window of therapeutic opportunity. The immune response is also responsible for important clinical manifestations, including oedema and pain. The dual role of immune responses (protection, pathology) is well recognized in other infectious diseases. The addition of corticosteroids to antimicrobial agents has been associated with improvement in some of these diseases., Objective: We evaluated the combination of oral valacyclovir plus topical clobetasol compared to placebo for recurrent HSL., Methods: Eighty-one subjects were screened, randomized, and dispensed medication (valacyclovir 2 g orally twice daily phiomicronrho 1 day and clobetasol gel 0.05% twice daily for 3 days). Forty-two patients developed a recurrence and initiated treatment., Results: There were more aborted lesions in the valacyclovir-clobetasol arm compared to placebo-placebo (50% vs.15.8%, P = 0.04). Combination therapy reduced the mean maximum lesion size (9.7 vs. 54 mm(2), P = 0.002) and the mean healing time of classical lesions (5.8 vs. 9.3 days, P = 0.002). We created a composite statistic, area-under-the-curve (AUC) of classical lesion size versus time. There was a reduction in the AUC in the combination arm compared with placebo (23 vs. 193 mm(2), P < 0.001). Adverse events were minimal. Secondary and post-treatment recurrences were not increased by combination therapy., Conclusions: This pilot study supports the addition of topical corticosteroids to an oral antiviral agent for the treatment of HSL. Larger studies need to confirm the safety and efficacy of this approach.

Background: Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV)., Objectives: To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer., Search Strategy: We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008., Selection Criteria: All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects., Data Collection and Analysis: Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models., Main Results: Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0)., Authors' Conclusions: There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.

Objective: To review the evidence regarding the treatment and prevention of herpes labialis., Quality of Evidence: The evidence relating to treatment and prevention of herpes labialis is derived from randomized controlled trials (level I evidence)., Main Message: Treatment with an indifferent cream (zinc oxide or zinc sulfate), an anesthetic cream, or an antiviral cream has a small favourable effect on the duration of symptoms, if applied promptly. This is also the case with oral antiviral medication. If antiviral medicine (cream or oral) is started before exposure to the triggering factor (sunlight), it will provide some protection. Research on sunscreens has shown mixed results: some protection has been reported under experimental conditions that could not be replicated under natural conditions. In the long term, the number of relapses of herpes labialis can be limited with oral antiviral medication., Conclusion: Only prompt topical or oral therapy will alleviate symptoms of herpes labialis. Both topical and oral treatment can contribute to the prevention of herpes labialis.

A 33-year-old male presented with recurrent outbreaks of perioral herpes of disfiguring nature that remained unresolved following therapy. The first perioral outbreak occurred following a road accident. The psychiatric interview conducted with the patient suggested post-traumatic stress disorder (PTSD) secondary to the accident. Venlafaxine 50 mg/day was initiated and led to resolution of the PTSD symptoms within 8 weeks. The patient did not experience any further herpes outbreaks for about 10 months. Control of stress disorders in recurrent herpes is discussed from a therapeutic perspective.

A range of topical and systemic therapies exists for treating recurrent herpes labialis. Among the topical agents, aciclovir and its derivatives can lessen the symptoms and duration of disease if applied frequently in the proper vehicle and started during the prodromal phase. Delivering these agents to the lesion via novel devices or vehicles may enhance their topical efficacy in the future. Among the systemic agents, new high-dose, 1-day regimens using either famciclovir or valaciclovir offer greater convenience and cost-effectiveness compared with traditional 5-7-day therapy. Combining either topical or systemic antinucleoside agents with topical anti-inflammatories such as corticosteroids may also lead to enhanced efficacy. Novel agents such as docosanol, toll-like receptor agonists, and viral ribonucleoside reductase inhibitors may also play a larger role in the future.

Infection with herpes simplex virus (HSV) has increased in prevalence worldwide over the past two decades, making it a major public health concern. Approximately 90% of recurrent HSV type 1 (HSV-1) infections manifest as non-genital disease, primarily as orofacial lesions known as herpes labialis. Improvements in our understanding of the natural history of herpes labialis support the rationale for early treatment (during the prodrome or erythema stages) with high doses of antiviral agents in order to maximize drug benefit. When evaluating the efficacy of different antiviral and anti-inflammatory agents in clinical trials, episode duration, lesion healing time, reduction in maximum lesion size and the proportion of aborted lesions should be used as the most reliable measures of therapeutic efficacy. There has also been considerable research into the most beneficial treatment for recurrent episodes of herpes labialis in immunocompetent individuals. Data from clinical studies confirm that short-course, high-dose oral antiviral therapy should be offered to patients with recurrent herpes labialis to accelerate healing, reduce pain and most likely increase treatment adherence. Optimal benefits may be obtained when these oral antiviral agents are combined with topical corticosteroids, but more research is needed with this combination. Patients undergoing facial cosmetic procedures (i.e.facial resurfacing) are at risk of HSV reactivation, but further data are required on the actual risk according to the specific procedure. Aciclovir, valaciclovir and famciclovir all provide effective prophylaxis against HSV-1 reactivation following ablative facial resurfacing. However, no definitive recommendations can be made regarding prophylactic therapy for minimally invasive procedures at present.

The literature has been reviewed for evidence of the efficacy of antiviral agents in both the prophylaxis and treatment of recurrent oral herpes simplex virus (HSV) infections and discussed by a panel of experts. Emphasis was given to randomized controlled trials. Management of herpes-associated erythema multiforme and Bell palsy were also considered. The evidence suggests that 5% acyclovir (ACV) in the cream base may reduce the duration of lesions if applied early. Recurrent herpes labialis (RHL) and recurrent intraoral HSV infections can be effectively treated with systemic ACV 400 mg 3 times a day or systemic valacyclovir 500 to 1000 mg twice a day for 3 to 5 days (longer in the immunocompromised). RHL in the immunocompetent can be effectively prevented with (1) sunscreen alone (SPF 15 or above), (2) systemic ACV 400 mg 2 to 3 times a day, or (3) systemic valacyclovir 500 to 2000 mg twice a day. Valacyclovir 500 mg twice a day is also effective in suppressing erythema multiforme triggered by HSV. Further studies are needed to compare treatment efficacy between topical penciclovir, docosanol, and ACV cream for RHL.

Labial herpes is a recurrent muco-cutaneous disorder caused by the herpes simplex virus (HSV), particularly the HSV type I. It affects 10 to 30% of the adult population. The recurrence rate varies from episodic events to monthly recurrences. Several triggering factors have been identified. They include physical factors such as ultraviolet radiations and any local traumatism such as dental and neurosurgical interventions, and dermo-cosmetic procedures of the face. Hormonal factors are also involved including those related to menses and pregnancy. Psychogenic factors, particularly severe stress are also involved. Any other intercurrent infection may also be complicated by recurrent labial herpes. The management of recurrent labial herpes currently relies on the identification and possible avoidance of triggering factors, and on the use of antiviral agents. There is no curative treatment available so far.

Isotretinoin (13-cis-retinoic acid) is one of the synthetic retinoids derived from vitamin A. Vitamin A derivatives demonstrate virucidal activity, both in vivo and in vitro. Isotretinoin has been used for the treatment of recurrent herpes simplex with encouraging results. However, we present a case with frequent attacks of herpes labialis during isotretinoin therapy for acne, who had a marked decrease in frequency of recurrences following strict use of sunscreens.

Background: The objective of this study was to investigate the effect of zinc on recurrent herpes labialis., Materials/methods: Twenty patients (12 females; median age 26.6 years) with a history of recurrent herpes labialis >6 episodes each year were treated with systemic zinc sulphate 22.5 mg twice daily for the months of February, March, September and October. All patients were followed for 12 months., Results: Herpetic lesions reduced to <4 episodes (average 3) for the 12 months and the duration was <7 days for each episode (average 5.7)., Conclusions: Systemic zinc sulphate appeared to reduce both the number of episodes and the time to recovery of herpes labialis.

The present study examined the effectiveness of a hypnotherapeutic treatment program for patients suffering from recurrent orofacial herpes infections. Twenty-one patients were randomly allocated to either an experimental group (n=10) or a control condition (n=11). During five weekly individual therapy sessions the participants received symptom-oriented treatment. In addition, they learnt how to improve their stress coping skills and their management of aversive emotions. The final assessment took place 6 months after treatment. Besides documentation of the frequency and intensity of symptoms, questionnaires were administered to assess stress coping mechanisms (SVF), skin disease-related subjective strain (MHF) and perceptions of control (KKG). A significant reduction of disease intensity could be confirmed. Individual scales of the SVF and MHF also revealed significant results. For an effective treatment of severe herpes infections a mere focus on physical changes appears to be insufficient. A common reflection of a person's sensuality and expectations of closeness and distance seem to influence treatment success remarkably.

Background: Oral herpes simplex virus, or HSV, infections recur after trauma and stress. The prevalence of these infections after dental procedures is not known. Also, it is unclear whether antiviral agents are effective in preventing dental procedure-induced HSV recurrences. This study determined the efficacy and safety of oral valacyclovir in suppressing dentally related cold sore outbreak and HSV shedding., Methods: The authors enrolled 125 otherwise healthy HSV-seropositive adults who reported having recurrent herpes labialis (more than one episode per year and at least one episode in the previous year) in a randomized, double-blind, placebo-controlled study and gave them valacyclovir prophylactically (2 grams taken twice on the day of dental treatment and 1 g taken twice the next day) or a matching placebo. To detect the presence of the virus, the authors used clinical examinations, viral cultures and real-time polymerase chain reaction analysis of saliva., Results: During the one-week observation period after treatment, there were more clinical lesions (20.6 percent versus 11.3 percent), more HSV-1-positive culture specimens (7.9 percent versus 1.6 percent) and more HSV-1-positive saliva specimens (7.9 percent versus 4.0 percent) in placebo than in valacyclovir-treated patients, respectively. The percentage of patients who developed recurrences and shed HSV-1 in saliva 72 hours after dental procedures was significantly smaller in the valacyclovir group than in the placebo group (11.3 percent versus 27 percent; P = .026). The mean time to pain cessation was significantly less in the valacyclovir group (3.2 days) than in the placebo group (6.2 days) (P = .006)., Conclusion: HSV recrudescence after routine dental treatment is suppressed by valacyclovir prophylaxis., Clinical Implications: HSV recrudescence is common after routine dental treatment. Clinicians should consider antiviral therapy for patients at risk of experiencing a recurrence, as well as to minimize transmission of the disease.