Treatment of angular cheilitis: A narrative review and authors' clinical experience.

Angular cheilitis (AC) is a clinical entity first described in the XIX century, characterized by erythema, rhagades, ulcerations, and crusting of one or both lip commissures and perilabial skin, responsible of an unpleasant and painful discomfort. Aim of this manuscript was to examine and evaluate the therapeutic options actually available for AC. Despite antifungals being the first-line treatment for most of clinicians, very limited scientific evidence supports their reliability, with just two RCTs published between the 70's and the 80's. Furthermore, alternative topical treatments, various techniques of occlusal vertical dimension restoration, B-vitamin supplementation, anti-drooling prosthetic device, and photodynamic therapy have been experimented and proposed, mostly in the form of case reports or case series on a small number of individuals. Our group found in 1% isoconazole nitrate (ISN) and 0.1% diflucortolone valerate (DFV) ointment the most consistent AC treatment, due to the broad spectrum of ISN against many species of dermatohpytes and bacteria, and the anti-inflammatory properties displayed by DFV. However, further and well-designed trials on larger samples of patients are needed to assess the differential profile of consistency of the treatments outlined in literature and claimed by the authors of this paper.

Interventions for dry mouth and hyposalivation in Sjögren's syndrome: A systematic review and meta-analysis.

OBJECTIVES: Systematic review with meta-analysis of interventions for dry mouth symptoms and hyposalivation of Sjögren's syndrome (SS). MATERIALS AND METHODS: We searched MEDLINE, Cochrane Central and EMBASE up to February 2018 for randomized trials of interventions for dry mouth and hyposalivation of SS. The primary outcome was the mean change in xerostomia symptoms. The secondary outcomes included changes in salivary flow and quality of life. We used the Cochrane risk of bias tool for individual studies and the GRADE method to summarize the quality of evidence across studies for the included outcomes. RESULTS: Thirty-six studies (3,274 patients) were included in the systematic review. Results from the meta-analyses showed high-quality evidence that pilocarpine was superior to placebo in reducing dry mouth symptoms. We found moderate quality of evidence that pilocarpine, rituximab and interferon-alpha were more effective than placebo in increasing salivary flow, with the relevant effect size being large for pilocarpine, and notably smaller for rituximab and interferon-alpha. CONCLUSION: Clinicians should be very confident in the beneficial effects of pilocarpine upon dry mouth symptoms of SS and moderately confident that pilocarpine, rituximab and interferon-alpha can have beneficial effects upon salivary flow. Adverse events are common. The use of other treatment modalities cannot be supported on the basis of current evidence.

Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis.

INTRODUCTION: Salivary gland hypofunction is a common and permanent adverse effect of radiotherapy to the head and neck. Randomised trials of available treatment modalities have produced unclear results and offer little reliable guidance for clinicians to inform evidence-based therapy. We have undertaken this systematic review and meta-analysis to estimate the effectiveness of available interventions for radiotherapy-induced xerostomia and hyposalivation. METHODS: We searched MEDLINE, Cochrane Central, EMBASE, AMED, and CINAHL database through July 2016 for randomised controlled trials comparing any topical or systemic intervention to active and/or non-active controls for the treatment of radiotherapy-induced xerostomia. The results of clinically and statistically homogenous studies were pooled and meta-analyzed. RESULTS: 1732 patients from twenty studies were included in the systematic review. Interventions included systemic or topical pilocarpine, systemic cevimeline, saliva substitutes/mouthcare systems, hyperthermic humidification, acupuncture, acupuncture-like transcutaneous electrical nerve stimulation, low-level laser therapy and herbal medicine. Results from the meta-analysis, which included six studies, suggest that both cevimeline and pilocarpine can reduce xerostomia symptoms and increase salivary flow compared to placebo, although some aspects of the relevant effect size, duration of the benefit, and clinical meaningfulness remain unclear. With regard to interventions not included in the meta-analysis, we found no evidence, or very weak evidence, that they can reduce xerostomia symptoms or increase salivary flow in this population. CONCLUSIONS: Pilocarpine and cevimeline should represent the first line of therapy in head and neck cancer survivors with radiotherapy-induced xerostomia and hyposalivation. The use of other treatment modalities cannot be supported on the basis of current evidence.

Interventions for treating oral leukoplakia to prevent oral cancer.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that, in a small proportion of people, precedes the development of oral cancer. Most leukoplakias are asymptomatic; therefore, the primary objective of treatment should be to prevent onset of cancer. This review updates our previous review, published in 2006. OBJECTIVES: To assess the effectiveness, safety and acceptability of treatments for leukoplakia in preventing oral cancer. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 16 May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 4), MEDLINE Ovid (1946 to 16 May 2016), Embase Ovid (1980 to 16 May 2016) and CancerLit via PubMed (1950 to 16 May 2016). We searched the metaRegister of Controlled Trials (to 10 February 2015), ClinicalTrials.gov (to 16 May 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (to 16 May 2016). We placed no restrictions on the language or date of publication when searching electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with a diagnosis of oral leukoplakia and compared any treatment versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: We collected data using a data extraction form. Oral cancer development, demonstrated by histopathological examination, was our primary outcome. Secondary outcomes were clinical resolution of the lesion, improvement of histological features and adverse events. We contacted trial authors for further details when information was unclear. When valid and relevant data were available, we conducted a meta-analysis of the data using a fixed-effect model when we identified fewer than four studies with no heterogeneity. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). We assessed risk of bias in studies by using the Cochrane tool. We assessed the overall quality of the evidence by using standardised criteria (Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE)). MAIN RESULTS: We included 14 studies (909 participants) in this review. Surgical interventions, including laser therapy and cryotherapy, have never been studied by means of an RCT that included a no treatment or placebo arm. The included trials tested a range of medical and complementary treatments, in particular, vitamin A and retinoids (four studies); beta carotene or carotenoids (three studies); non-steroidal anti-inflammatory drugs (NSAIDs), specifically ketorolac and celecoxib (two studies); herbal extracts (four studies), including tea components, a Chinese herbal mixture and freeze-dried black raspberry gel; bleomycin (one study); and Bowman-Birk inhibitor (one study).We judged one study to be at low risk of bias, seven at unclear risk and six at high risk. In general, we judged the overall quality of the evidence to be low or very low, so findings are uncertain and further research is needed.Five studies recorded cancer incidence, only three of which provided useable data. None of the studies provided evidence that active treatment reduced the risk of oral cancer more than placebo: systemic vitamin A (RR 0.11, 95% CI 0.01 to 2.05; 85 participants, one study); systemic beta carotene (RR 0.71, 95% CI 0.24 to 2.09; 132 participants, two studies); and topical bleomycin (RR 3.00, 95% CI 0.32 to 27.83; 20 participants, one study). Follow-up ranged between two and seven years.Some individual studies suggested effectiveness of some proposed treatments, namely, systemic vitamin A, beta carotene and lycopene, for achieving clinical resolution of lesions more often than placebo. Similarly, single studies found that systemic retinoic acid and lycopene may provide some benefit in terms of improvement in histological features. Some studies also reported a high rate of relapse.Side effects of varying severity were often described; however, it seems likely that interventions were well accepted by participants because drop-out rates were similar between treatment and control groups. AUTHORS' CONCLUSIONS: Surgical treatment for oral leukoplakia has not been assessed in an RCT that included a no treatment or placebo comparison. Nor has cessation of risk factors such as smoking been assessed. The available evidence on medical and complementary interventions for treating people with leukoplakia is very limited. We do not currently have evidence of a treatment that is effective for preventing the development of oral cancer. Treatments such as vitamin A and beta carotene may be effective in healing oral lesions, but relapses and adverse effects are common. Larger trials of longer duration are required to properly evaluate the effects of leukoplakia treatments on the risk of developing oral cancer. High-quality research is particularly needed to assess surgical treatment and to assess the effects of risk factor cessation in people with leukoplakia.

Efficacy behind activity--phytotherapeutics are not different from pharmaceuticals.

CONTEXT: When evaluating bioactivity, efficacy, and toxicology of plant products, attention should be paid on pre-clinical versus clinical research. OBJECTIVE: To emphasize an evidence-based approach in the field of phytotherapy research. METHODS: The pyramid of scientific evidence was used in order to assess the quality of phytotherapy studies. RESULTS AND CONCLUSION: In terms of evidence-based phytotherapy, a step-by-step approach, ascending the "pyramid" of scientific evidence, is essential in order to collect correct information useful to clinicians and physicians, leant on the robust foundations of in vitro/in vivo studies.

Acupuncture and burning mouth syndrome: a pilot study.

Burning mouth syndrome (BMS) is a chronic condition most common in middle-aged and elderly women, with prevalence rates in the general population ranging from 0.5% to 5%. Defined by the International Headache Society as "an intraoral burning sensation for which no medical or dental cause can be found," BMS is considered a form of neuropathic pain. The management of BMS remains unsatisfactory. In this pilot study, we investigated the use of acupuncture in a small group of BMS patients. The study group, after 4 refusals, was composed of 10 BMS patients (9 females and 1 male; mean age, 65.2 years; range, from 48 to 80 years; mean duration of BMS, 2.6 years; SD ± 0.8 years). Oral pain/burning sensation (primary outcome) was measured using a visual analogue scale (VAS). Health-related quality of life (secondary outcome) was measured using the 36-item Short-Form Health Survey (SF-36). Acupuncture treatment lasted 8 weeks and consisted of 20 sessions. Patients reported a mean reduction in pain of 0.99 points on the VAS (max 2.1-min 0.1), which, although slight, was statistically significant (Wilcoxon test P < 0.009). No significant improvement in the overall score for quality of life was observed, although subjects receiving acupuncture treatment seemed better able cope with their oral symptoms.

Interventions for treating oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common chronic autoimmune disease associated with cell-mediated immunological dysfunction. Symptomatic OLP is painful and complete healing is rare. OBJECTIVES: To assess the effectiveness and safety of any form of therapy for symptomatic OLP. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 26 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 26 January 2011) and EMBASE via OVID (1980 to 26 January 2011). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: All randomised controlled clinical trials (RCTs) of therapy for symptomatic OLP which compared treatment with a placebo or between treatments or no intervention were considered in this review. DATA COLLECTION AND ANALYSIS: The titles and abstracts of all reports identified were scanned independently by two review authors. All studies meeting the inclusion criteria were assessed for risk of bias and data were extracted. For dichotomous outcomes, the estimates of effects of an intervention were expressed as risk ratios (RR) together with 95% confidence intervals. For continuous outcomes, mean differences (MD) and 95% confidence intervals were used to summarise the data for each group. The statistical unit was the patient. Meta-analyses were done only with studies of similar comparisons reporting the same outcome measures. MAIN RESULTS: 28 trials were included in this review. Pain is the primary outcome of this review because it is the indication for treatment of OLP, and therefore this review indicates as effective, only those treatments which significantly reduce pain. Although topical steroids are considered first line treatment for symptomatic OLP, we identified no RCTs that compared steroids with placebo. There is no evidence from the three trials of pimecrolimus that this treatment is better than placebo in reducing pain from OLP. There is weak evidence from two trials, at unclear and high risk of bias respectively, that aloe vera may be associated with a reduction in pain compared to placebo, but it was not possible to pool the pain data from these trials. There is weak and unreliable evidence from two small trials, at high risk of bias, that cyclosporin may reduce pain and clinical signs of OLP, but meta-analysis of these trials was not possible.There were five trials that compared steroids with calcineurin inhibitors, each evaluating a different pair of interventions. There is no evidence from these trials that there is a difference between treatment with steroids compared to calcineurin inhibitors with regard to reducing pain associated with OLP. From six trials there is no evidence that any specific steroid therapy is more or less effective at reducing pain compared to another type or dose of steroid. AUTHORS' CONCLUSIONS: Although topical steroids are considered to be first line treatment, we identified no RCTs that compared steroids with placebo in patients with symptomatic OLP. From the trials in this review there is no evidence that one steroid is any more effective than another. There is weak evidence that aloe vera may reduce the pain of OLP and improve the clinical signs of disease compared to placebo. There is weak and unreliable evidence that cyclosporin may reduce pain and clinical signs of OLP. There is no evidence that other calcineurin inhibitors reduce pain compared to either steroids or placebo. From the 28 trials included in this systematic review, the wide range of interventions compared means there is insufficient evidence to support the effectiveness of any specific treatment as being superior.

Hypericum perforatum extract in burning mouth syndrome: a randomized placebo-controlled study.

Burning mouth syndrome (BMS) or stomatodynia is characterized by a spontaneous burning pain in the oral mucosa without known cause or recognized treatment. This double-blind, randomized, placebo-controlled, single-center study evaluated the effects of systemic Hypericum perforatum extract in patients with BMS. Forty-three patients participated, of whom 39 (35 women, four men, aged 64.9 +/- 4.7 years) completed the study. The patients took indistinguishable 300-mg capsules containing either H. perforatum extract (hypericin 0.31% and hyperforin 3.0%) or placebo three times a day for 12 weeks. The intensity of burning pain was evaluated using a 10-cm visual analog scale (VAS) before the first dose and at visits after 4, 8, and 12 weeks. Furthermore, we also recorded the number of oral mucosa sites with reported burning symptoms and the self-reported descriptions of the patient's condition before and after the treatment. Pain, measured using the VAS, was similar at the beginning of the study and even though a slightly better performance in the test group, the difference was not statistically significant (P = 0.2216). The results failed to demonstrate that 300 mg of H. perforatum extract taken three times a day for 12 weeks improved the pain of BMS patients, although the general reduction in the number of sites with reported burning sensation, a less accurate and objective score, was significant.

Systematic review of randomized trials for the treatment of oral leukoplakia.

Oral leukoplakia is a relatively common oral lesion that, in a varying proportion of cases, undergoes malignant transformation. The aim of this review was to assess the effectiveness of treatments for leukoplakia. Randomized controlled trials (RCTs) enrolling patients with a diagnosis of oral leukoplakia were identified by searching biomedical databases, hand-searching relevant oral medicine journals, and contacting oral medicine experts through a European mailing list. The methodological quality of included studies was assessed on the basis of the method of allocation concealment, blindness of the study, and loss of participants. Data were analyzed by calculating relative risk. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. Six RCTs were included in the review. Vitamin A and retinoids were tested in four RCTs; the other agents tested were bleomycin, mixed tea, and beta carotene. Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with placebo. Treatment with beta carotene and vitamin A or retinoids was associated with better rates of clinical remission, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients since drop-out rates were similar between treatment and control groups. It is noteworthy that the possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has apparently never been studied by means of an RCT. To date, in conclusion, there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion; however, relapses and adverse effects are common.