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.

Global burden of skin disease as reflected in Cochrane Database of Systematic Reviews.

IMPORTANCE: Research prioritization should be guided by impact of disease. OBJECTIVE: To determine whether systematic reviews and protocol topics in Cochrane Database of Systematic Reviews (CDSR) reflect disease burden, measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 project. DESIGN, SETTING, AND PARTICIPANTS: Two investigators independently assessed 15 skin conditions in the CDSR for systematic review and protocol representation from November 1, 2013, to December 6, 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. An official publication report of all reviews and protocols published by the Cochrane Skin Group (CSG) was also obtained to ensure that no titles were missed. There were no study participants other than the researchers, who worked with databases evaluating CDSR and GBD 2010 skin condition disability data. MAIN OUTCOMES AND MEASURES: Relationship of CDSR topic coverage (systematic reviews and protocols) with percentage of total 2010 DALYs, 2010 DALY rank, and DALY percentage change from 1990 to 2010 for 15 skin conditions. RESULTS: All 15 skin conditions were represented by at least 1 systematic review in CDSR; 69% of systematic reviews and 67% of protocols by the CSG covered the 15 skin conditions. Comparing the number of reviews/protocols and disability, dermatitis, melanoma, nonmelanoma skin cancer, viral skin diseases, and fungal skin diseases were well matched. Decubitus ulcer, psoriasis, and leprosy demonstrated review/protocol overrepresentation when matched with corresponding DALYs. In comparison, acne vulgaris, bacterial skin diseases, urticaria, pruritus, scabies, cellulitis, and alopecia areata were underrepresented in CDSR when matched with corresponding DALYs. CONCLUSIONS AND RELEVANCE: Degree of representation in CDSR is partly correlated with DALY metrics. The number of published reviews/protocols was well matched with disability metrics for 5 of the 15 studied skin diseases, while 3 skin diseases were overrepresented, and 7 were underrepresented. Our results provide high-quality and transparent data to inform future prioritization decisions.

Drugs for discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic. OBJECTIVES: To assess the effects of drugs for discoid lupus erythematosus. SEARCH STRATEGY: In June 2009 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2009), MEDLINE, EMBASE, LILACS, and online ongoing trials registers. The reference lists of relevant reviews were searched. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials. SELECTION CRITERIA: We included all randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine, thalidomide, topical calcineurin blockers (pimecrolimus and tacrolimus), and biological agents (etanercept, efalizimab, infliximab, and rituximab). DATA COLLECTION AND ANALYSIS: Two reviewers independently examined each retrieved study for eligibility. MAIN RESULTS: Two trials involving 136 participants were included. No new trials were included in this update.In a cross-over study of 12 weeks duration, fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be better than hydrocortisone 1% cream (a mild corticosteroid) when the first arm of the trial involving 78 participants was analysed at 6 weeks. Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 0.0 to 0.34, NNT (Number needed to treat) 6).In the second trial, acitretin (50mg/day) was compared with hydroxychloroquine (400mg/day) in 58 people in a parallel trial of 8 weeks duration. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine but there was no significant difference between the 2 interventions. The adverse effects were more frequent and more severe in the acitretin group. In this trial clearing of erythema was measured and found to be better in the hydroxychloroquine group (RR 0.61, 95% CI 0.36 to 1.06). AUTHORS' CONCLUSIONS: Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus.