[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.

Photobiomodulation for Preventive Therapy of Recurrent Herpes Labialis: A 2-Year In Vivo Randomized Controlled Study.

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.

Do sunscreen prevent recurrent Herpes labialis in summer?

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.

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

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

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.

Interventions for prevention of herpes simplex labialis (cold sores on the lips).

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-ß-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.

Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine.

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.

Varicella-zoster virus vaccine, successes and difficulties.

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.

A randomized, double-blind, placebo-controlled study to test the efficacy of topical 2-hydroxypropyl-Beta-cyclodextrin in the prophylaxis of recurrent herpes labialis.

Herpes labialis affects one third of the population. We evaluated the topical application of an antiviral compound, hydroxypropyl-ß-cyclodextrin (2-HPßCD), 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-HPßCD 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.

Systemic nucleoside antiviral agents may be effective in prevention of recurrent herpes labialis.

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.

Are we too cavalier about antiviral prophylaxis?

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.

Reducing the stigma of herpes simplex virus infection: lessons from an online video contest.

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.

Effectiveness of antiviral agents for the prevention of recurrent herpes labialis: a systematic review and meta-analysis.

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.

Prophylactic valacyclovir in a patient with recurrent vestibular disturbances secondary to vestibular neuritis.

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.

Early treatment of cold sores with topical ME-609 decreases the frequency of ulcerative lesions: a randomized, double-blind, placebo-controlled, patient-initiated clinical trial.

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.