Localized CO2 laser treatment of a recalcitrant oral ulceration in pemphigus vulgaris.

INTRODUCTION: Recalcitrant oral lesions of pemphigus vulgaris (PV), an autoimmune blistering disease, can result in significant discomfort, difficulty in eating, and maintaining oral hygiene. Increasing the dosage of systemic medications to control such localized lesions results in an increased risk of adverse effects. CASE PRESENTATION: We describe a male patient diagnosed at age 51 with PV by oral biopsy that included a direct immunofluorescence examination. After further baseline laboratory testing, he was started on prednisone and mycophenolate. These medications were slowly tapered with adjustments guided by clinical signs. Mycophenolate was replaced with intravenous immunoglobulin monthly infusions due to adverse effects about 2 years after initiation. During the 4.5-year follow-up period after diagnosis, his oral and skin lesions were well-controlled apart from minor transient flares. However, a painful ulcerated lesion on the facial gingiva between #11 and 12 was nonresponsive, even with the use of topical clobetasol in trays. A carbon dioxide (CO2 ) laser was used to vaporize the recalcitrant lesion under local anesthesia. The procedure resulted in complete healing of ulceration with no recurrence until the most recent examination, 2 years postlaser surgery. CONCLUSION: Adjunctive procedures that can facilitate a decrease in the cumulative dosage of corticosteroids and immunosuppressants have great value in the management of PV. CO2 laser vaporization is safe, with minimal morbidity and no long-term side effects. It should be considered an adjunctive treatment option for the management of recalcitrant lesions in patients with oral PV. KEY POINTS: Why is this case new information? To our knowledge, this is the second report on the use of a CO2 laser in the treatment of recalcitrant oral lesions of PV and the first report with a documented long-term resolution of the treated lesions. What are the keys to the successful management of this case? A localized recalcitrant lesion was treated with this approach. All other mucosal and cutaneous sites were well controlled on the patient's systemic medication regimen. What are the primary limitations to success in this case? This approach is only relevant for the management of recalcitrant lesions in patients whose disease activity is otherwise well controlled. The availability of specialized equipment and trained clinicians is necessary.

Amlodipine-Induced Gingival Overgrowth With Unusual Presentation as a Gingival Mass and Rapid Regression After Dose Reduction.

INTRODUCTION: Gingival overgrowth, a known side effect of calcium channel blockers, particularly nifedipine, usually presents as a diffuse overgrowth. An unusual presentation of amlodipine-induced gingival overgrowth is presented here, with a large, erythematous gingival mass as the most prominent feature, and rapid, almost complete resolution of the mass after reduction of amlodipine dosage. CASE PRESENTATION: A boy, aged 7 years, presented with a gingival mass first noticed a week previously, with no associated discomfort or bleeding. His medical history was significant for Wiskott-Aldrich syndrome, bone marrow transplant 5 years previously, and subsequent development of severe chronic graft-versus-host-disease. His medication included: 1) amlodipine; 2) enalapril; 3) tacrolimus; 4) sulfamethoxazole/trimethoprim; 5) voriconazole; 6) hydrocortisone cream; and 7) intravenous immunoglobulin infusions. Allergies included: 1) vancomycin; 2) metoclopramide; 3) clonidine; and 4) latex. Examination revealed mild generalized gingival overgrowth and the presence of a large, erythematous, sessile, soft, non-tender mass on the mandibular right gingiva between the primary lateral incisor and canine, resembling a pyogenic granuloma. No suppuration, bleeding on probing, or radiographic abnormalities were noted. A recommendation was made to the physician of the patient to replace amlodipine with a different class of antihypertensive. In response, amlodipine dosage was decreased by 50% to 2.5 mg daily. At a 2-week follow-up visit, considerable reduction in size of the gingival mass had occurred, and shortly after complete resolution was reported by his parents. No other intervention, such as scaling or excision, had been performed. CONCLUSION: Discontinuation or reduction of the amlodipine dose to <5 mg daily prior to any surgical intervention should be considered in patients taking amlodipine presenting with a gingival mass.

Oral Squamous Cell Carcinoma Mimicking Peri-Implantitis.

INTRODUCTION: Peri-implantitis is inflammation and alveolar bone loss around a dental implant. Published case reports have described squamous cell carcinoma (SCC) development around dental implants. CASE PRESENTATION: A 60-year-old female presented with two small fistulas on the alveolar ridge of missing tooth #18. The mucosa around the fistulas appeared normal otherwise, with no hyperplasia, erythema, or keratotic changes. The patient had a 14-year history of recurrent erythroleukoplakia (with microscopic dysplasia) on the left tongue that had been managed by surgical removal (scalpel and carbon dioxide laser), biopsies, and close follow-up. She had no other medical conditions. She reported that she had an implant placed to replace tooth #18 4 years ago that had been removed without flap reflection, curettage, or biopsy 1 year previously as a result of peri-implantitis. Periapical radiographs showed that the peri-implant radiolucency in the region of tooth #18 was unchanged in dimensions from the time of implant removal 1 year ago. Curettage and biopsy of the area were performed and showed the presence of a well-differentiated SCC. CONCLUSIONS: This is a case of peri-implant SCC development in a patient at high risk for oral SCC. The carcinoma was present within the alveolar defect in the area of a failed implant that had been removed 1 year previously. The overlying surface mucosa did not show the clinical changes typically seen in carcinoma. This case and others demonstrate the importance of periodic oral and radiographic examination after implant placement. Although rare, neoplasia must be considered in the evaluation of peri-implant pathology.

Clinical predictors of oral leukoplakia recurrence following CO2 laser vaporization.

OBJECTIVE: The objective of this study was to determine whether risk of early leukoplakia recurrence (within 3 months) following carbon dioxide (CO2) laser removal varies by clinical characteristics including lesion size, site and accessibility of margins. MATERIALS AND METHODS: A retrospective cohort study included patients with oral leukoplakia who had their first CO2 laser surgery for removal of oral leukoplakia between 2005 and 2010 at the UCSF oral medicine clinic. Twenty-six patients with 32 separate lesions met the eligibility criteria after a clinic database search was followed by review of clinical notes and biopsy reports from existing patient charts. Data analysis included computation of summary statistics, and logistic regression analyses to evaluate recurrence of leukoplakia by clinical characteristics of the lesions. RESULTS: Patient data and the characteristics of lesions were evaluated as possible predictors of early recurrence following laser removal; these included age, sex, duration, size, appearance and histopathology of the lesion. The only one that reached statistical significance was poor accessibility of the margins of the lesion (vs. good accessibility, OR = 24.57 (95% CI: 1.59-16.68), p = 0.016); the probability for trend for good, questionable, and poor accessibility was 0.0028. This finding remained significant after controlling for age, sex, duration and size of lesion. Four out of five lesions with poor accessibility showed recurrence at 3 months. Of these, three involved the gingiva and one the lateral tongue. CONCLUSIONS: This study has identified poor accessibility of the lesion margins as a predictor for early recurrence of leukoplakia following laser removal. Other variables evaluated did not reach statistical significance, possibly due to lack of power.

Oral leukoplakia development in patients with pre-existing oral lichen planus.

Oral leukoplakia and oral lichen planus are conditions that have the potential to transform into squamous cell carcinoma. This article describes a series of nine patients with an initial clinical-microscopic diagnosis of lichen planus. During close follow-up, these patients developed localized areas of leukoplakia at intervals ranging from one and a half to six and a half years. While both conditions may present with white and red oral mucosal changes, their management differs with leukoplakia requiring surgical intervention, therefore accurate diagnosis is imperative.

Oropharyngeal carcinoma arising after methotrexate and etanercept therapy for rheumatoid arthritis.

Etanercept is an anti-tumor necrosis factor α receptor agent used to treat inflammatory conditions. Previous reports described rapid development of skin squamous cell carcinoma (SCC) after etanercept use. This report describes a novel case of oropharyngeal SCC associated with the use of etanercept. A 45-year-old man with rheumatoid arthritis developed oropharyngeal pain within 2 months after the start of etanercept therapy and was diagnosed with tonsillar carcinoma. This patient had other exposures that increase the risk of oropharyngeal cancer, such as tobacco and alcohol use. However, owing to the timing of onset of his initial symptoms, etanercept should be considered as a possible factor in the etiology or progression of his tumor, especially in the context of reported skin SCC after etanercept therapy in patients at risk for SCC. Clinicians should be alert to signs of malignancy in patients on etanercept, particularly those at high risk for skin or head and neck cancers.

Lesion characteristics and responses after CO2 laser vaporization in five patients With gingival leukoplakia.

Gingival leukoplakia, a premalignant condition, can pose difficulties to surgical access because of the presence of teeth and potential extensions into the periodontal ligament. We present a series of five patients with gingival leukoplakia who were treated with carbon dioxide laser vaporization. We describe lesion characteristics and recurrence patterns suggesting that presence of gingival leukoplakia on facial and palatal/lingual aspect through the interproximal areas may increase the risk of recurrence after conservative surgical removal.

Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study.

BACKGROUND: Telomere shortness in human beings is a prognostic marker of ageing, disease, and premature morbidity. We previously found an association between 3 months of comprehensive lifestyle changes and increased telomerase activity in human immune-system cells. We followed up participants to investigate long-term effects. METHODS: This follow-up study compared ten men and 25 external controls who had biopsy-proven low-risk prostate cancer and had chosen to undergo active surveillance. Eligible participants were enrolled between 2003 and 2007 from previous studies and selected according to the same criteria. Men in the intervention group followed a programme of comprehensive lifestyle changes (diet, activity, stress management, and social support), and the men in the control group underwent active surveillance alone. We took blood samples at 5 years and compared relative telomere length and telomerase enzymatic activity per viable cell with those at baseline, and assessed their relation to the degree of lifestyle changes. FINDINGS: Relative telomere length increased from baseline by a median of 0·06 telomere to single-copy gene ratio (T/S)units (IQR-0·05 to 0·11) in the lifestyle intervention group, but decreased in the control group (-0·03 T/S units, -0·05 to 0·03, difference p=0·03). When data from the two groups were combined, adherence to lifestyle changes was significantly associated with relative telomere length after adjustment for age and the length of follow-up (for each percentage point increase in lifestyle adherence score, T/S units increased by 0·07, 95% CI 0·02-0·12, p=0·005). At 5 years, telomerase activity had decreased from baseline by 0·25 (-2·25 to 2·23) units in the lifestyle intervention group, and by 1·08 (-3·25 to 1·86) units in the control group (p=0·64), and was not associated with adherence to lifestyle changes (relative risk 0·93, 95% CI 0·72-1·20, p=0·57). INTERPRETATION: Our comprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up, compared with controls, in this small pilot study. Larger randomised controlled trials are warranted to confirm this finding. FUNDING: US Department of Defense, NIH/NCI, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, Prostate Cancer Foundation.

A case report of conservative management of extensive proliferative verrucous leukoplakia using a carbon dioxide laser.

OBJECTIVE: The purpose of this report was to describe a clinical case of conservative management of extensive proliferative verrucous leukoplakia (PVL) using a carbon dioxide laser, as an alternative to complete glossectomy, which led to a sustained successful outcome over a 12-year follow-up period. BACKGROUND DATA: Patients with oral PVL, a high risk premalignant condition, are often treated by wide surgical excision. This approach can lead to significant morbidity and compromised quality of life. CASE DESCRIPTION: A 50-year-old male with PVL and superficially invasive carcinoma, who had previously refused a complete glossectomy, presented for treatment. A baseline MRI and careful clinical evaluation by symptom review, inspection, palpation, toluidine blue staining, and biopsy were performed at baseline and at each follow-up to rule out invasive carcinoma. The PVL was treated on an outpatient basis by serial carbon dioxide laser excisions and/or vaporizations. This approach resulted in good clinical response and decreased morbidity over a 12-year follow-up period, as compared with the option of wide surgical excision. CONCLUSIONS: This case illustrates the benefit of a more conservative treatment approach than wide surgical excision for PVL with superficially invasive carcinoma. This approach requires greater skills, training, and experience in the evaluation of oral premalignant or malignant changes. However, decreased long-term morbidity and improved quality of life make it a valuable treatment option for PVL.

High-dose curcuminoids are efficacious in the reduction in symptoms and signs of oral lichen planus.

BACKGROUND: Curcuminoids are components of turmeric (Curcuma longa) that possess anti-inflammatory properties. OBJECTIVE: We sought to study the efficacy of curcuminoids in controlling the signs and symptoms of oral lichen planus, at doses of 6000 mg/d (3 divided doses), and their safety at this dose. METHODS: Twenty consecutive, eligible patients who consented were enrolled into this randomized, double-blind, placebo-controlled clinical trial in 2007 through 2008. Measurement of symptoms and signs of oral lichen planus using the Numerical Rating Scale (NRS) and the Modified Oral Mucositis Index (MOMI), respectively; complete blood counts; liver enzymes; C-reactive protein; and interleukin-6 levels was done at baseline and day 14. Two-sided P values are reported. RESULTS: In the placebo group, the percentage changes from baseline in NRS (median [interquartile range] = 0.00 [-29 to 16.7], P > .99), erythema (0.00 [-10 to 16.7], P = .98), ulceration (0.00 [0.00 to 26.7], P = .63), and total MOMI scores (-3.2 [-13 to 9.09], P = .95) were not statistically significant, whereas they were statistically significant in the curcuminoids group: NRS (-22 [-33 to -14], P = .0078); erythema (-17 [-29 to -8.3], P = .0078), ulceration (-14 [-60 to 0.00], P = .063), MOMI (-24 [-38 to -11], P = .0039). The curcuminoids group showed a greater reduction in clinical signs and symptoms as compared with the placebo group, measured by percentage change in erythema (P = .05) and total MOMI score (P = .03), and proportion showing improvement in NRS (0.8 vs 0.3, P = .02) and total MOMI score (0.9 vs 0.5, P = .05). Adverse effects were uncommon in both groups. LIMITATIONS: The small sample size resulted in limited power, particularly for multivariate analyses. CONCLUSIONS: Curcuminoids at doses of 6000 mg/d in 3 divided doses are well tolerated and may prove efficacious in controlling signs and symptoms of oral lichen planus.

A case-control study of burning mouth syndrome and sleep dysfunction.

OBJECTIVE: The objective of this study was to evaluate whether sleep dysfunction is a risk factor for burning mouth syndrome (BMS). STUDY DESIGN: An age- and sex-matched case-control study of patients with BMS and controls with various oral conditions was conducted. A numerical rating scale for oral discomfort and the sleep scale from the medical outcomes study were used for measurements, and statistical analyses included use of logistic regression models. RESULTS: The odds ratios for lowest versus highest quartiles were sleep disturbance (OR = 9.7, P = .0095), sleep problems index (SLP)6 (OR = 7.5, P = .032), and SLP9 (OR = 27, P = .0058), which remained significant after controlling for age and number of sedating medications. CONCLUSIONS: Findings from this cross-sectional study, although unable to establish a causal relationship, demonstrate that patients with BMS report a greater degree of sleep problems as compared with controls, and suggest that sleep dysfunction may be a risk factor for BMS and a possible target for treatment.

Diet and prevention of oral cancer: strategies for clinical practice.

BACKGROUND: Oral health care professionals can play an important role in preventing oral cancer by performing oral mucosal examinations to detect pre-cancerous changes and by educating patients about oral cancer prevention strategies, including dietary approaches. CONCLUSIONS: Current evidence supports a diet high in fruits, vegetables and plant-based foods for prevention of oral cancer. Dietary supplements-including vitamins and minerals-have not been shown to be effective as substitutes for a diet high in fruits and vegetables. CLINICAL IMPLICATIONS: In addition to discussing tobacco and alcohol use with patients (and, if relevant, betel nut and gutka consumption), as well as the risk of sexual transmission of human papillo-mavirus, clinicians should provide dietary advice for the prevention of oral cancer as part of routine patient education practices.

Validation of instruments to measure the symptoms and signs of oral lichen planus.

OBJECTIVE: The aim of this study was to validate the visual analog scale (VAS), numeric rating scale (NRS), and change in symptoms scale (CSS) in measuring symptoms of oral lichen planus, and the modified oral mucositis index (MOMI) in measuring the signs of oral lichen planus. STUDY DESIGN: Criterion validity, construct validity, and internal consistency reliability were evaluated using data from a randomized, double blind, placebo-controlled clinical trial of curcuminoids in oral lichen planus. RESULTS: Moderate to high correlations were found between VAS, NRS, and CSS. Correlations of symptom scores with clinical signs ranged from minimal to high. Correlation of NRS with clinical signs was stronger than that of VAS with clinical signs. Significant changes from baseline at each follow-up in NRS, VAS, and MOMI scores were seen. The Cronbach alpha for erythema and ulceration scores from the MOMI were 0.66. CONCLUSIONS: This study gives some evidence of the validity of NRS, VAS, CSS, and MOMI for use in oral lichen planus. The NRS has better construct validity than VAS, based on higher correlations with clinical signs. Erythema plus ulceration is a better measure than ulceration alone.

Hepatitis C virus and lichen planus: a review.

INTRODUCTION: The relationship between hepatitis C virus (HCV) infection and oral lichen planus (OLP) remains a matter of controversy. It is important to determine whether there is an association between OLP and HCV infection so that guidelines regarding the routine HCV testing of patients with OLP can be developed for clinicians. OBJECTIVES: The objective of this article was to review and summarize the published literature on the association between OLP and HCV and to describe future directions. METHODS: A search of the computerized database MEDLINE (1966-June 2003) was conducted. The bibliographies of articles identified by means of MEDLINE were also searched. Any studies reporting the prevalence of HCV in a group of patients with LP either with or without a control group were included in this review. Also included were studies comparing the clinical and histologic features of LP among patients with and without HCV infection, studies on the presence of HCV within LP lesions, and studies of HCV genotypes among patients with LP. RESULTS: Thirty-two studies conducted in various parts of the world were identified. Study types included prevalence studies on HCV exposure among patients with OLP (0%-62%), prevalence of OLP among patients with HCV infection (1.6%-20%), and case-control studies of this association. In addition, the results from 3 studies on the replication of HCV in the oral mucosa, 3 studies on the genotype of HCV in OLP patients, and 4 studies comparing the clinical and histologic features of OLP in HCV-infected and uninfected individuals have been summarized. CONCLUSION: At present, studies on the association of OLP and HCV provide enough information to raise a number of interesting questions about this association. Important biases-including selection bias; investigator bias due to lack of blinding and the possible resultant nondifferential misclassification of disease; and possible confounding by age in the studies published-make it difficult to draw firm conclusions. However, the need for future studies that take into consideration all these factors in the study methodology is highlighted by this review.

Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa).

INTRODUCTION: Tumeric is a spice that comes from the root Curcuma longa, a member of the ginger family, Zingaberaceae. In Ayurveda (Indian traditional medicine), tumeric has been used for its medicinal properties for various indications and through different routes of administration, including topically, orally, and by inhalation. Curcuminoids are components of tumeric, which include mainly curcumin (diferuloyl methane), demethoxycurcumin, and bisdemethoxycurcmin. OBJECTIVES: The goal of this systematic review of the literature was to summarize the literature on the safety and anti-inflammatory activity of curcumin. METHODS: A search of the computerized database MEDLINE (1966 to January 2002), a manual search of bibliographies of papers identified through MEDLINE, and an Internet search using multiple search engines for references on this topic was conducted. The PDR for Herbal Medicines, and four textbooks on herbal medicine and their bibliographies were also searched. RESULTS: A large number of studies on curcumin were identified. These included studies on the antioxidant, anti-inflammatory, antiviral, and antifungal properties of curcuminoids. Studies on the toxicity and anti-inflammatory properties of curcumin have included in vitro, animal, and human studies. A phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for 3 months found no toxicity from curcumin. Five other human trials using 1125-2500 mg of curcumin per day have also found it to be safe. These human studies have found some evidence of anti-inflammatory activity of curcumin. The laboratory studies have identified a number of different molecules involved in inflammation that are inhibited by curcumin including phospholipase, lipooxygenase, cyclooxygenase 2, leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein, tumor necrosis factor (TNF), and interleukin-12 (IL-12). CONCLUSIONS: Curcumin has been demonstrated to be safe in six human trials and has demonstrated anti-inflammatory activity. It may exert its anti-inflammatory activity by inhibition of a number of different molecules that play a role in inflammation.

Diet and oral, pharyngeal, and esophageal cancer.

Cancers of the upper digestive tract, including those arising in the oral cavity, pharynx, and esophagus, present a significant public health problem worldwide. These cancers are associated with high morbidity and mortality, and identification of protective factors is very important. A number of epidemiological studies have examined the association between vegetables, fruits, carotene, vitamin A, vitamin C, and vitamin E and oral, pharyngeal, and esophageal cancers. The results of 35 epidemiological studies, including one prospective cohort study, one nested case-control study, two randomized controlled trials, nine population-based case-control studies, and 22 hospital-based case-control studies, in addition to in vitro and animal studies, were examined to determine whether the criteria for causal assumption were satisfied for a protective role of these dietary components against development of oral, pharyngeal, and esophageal cancers. There is enough evidence to point to a preventive role of vegetable intake, including green vegetables, cruciferous vegetables, and yellow vegetables, total fruit intake, and citrus fruit intake. Yellow fruits are likely to be protective. Carotene, vitamin C, and vitamin E are protective, most likely in combination with each other and other micronutrients. The role of vitamin A is not clear because of conflicting findings in the studies reviewed.