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.

Resolution of recurrent aphthous ulcers after discontinuation of cow's milk protein intake.

BACKGROUND AND OVERVIEW: Authors of published studies have reported elevated levels of circulating antibodies to cow's milk protein (CMP) in patients with recurrent aphthous ulcers (RAUs), and authors of case reports have described resolution of RAU after dairy elimination. CASE DESCRIPTION: A 10-year-old girl and an 11-year-old boy, both with 5-year histories of frequent RAU episodes, with multiple ulcerations, underwent dairy elimination trials. Both were free of oral ulcers within 2 weeks of discontinuing CMP and remained so with a CMP-free diet. In addition, the first patient had recurrence of ulcerations after occasional ingestion of CMP-containing foods. She showed elevated blood levels of immunoglobulin E in reaction to CMP and soy. Soy intake did not trigger the ulcerations. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The proportion of patients with RAU in whom CMP acts as a trigger is unknown. However, CMP elimination trials are safe and feasible and, therefore, should be considered, particularly before use of medications with potential side effects.

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.

Management of Pemphigus Vulgaris.

INTRODUCTION: Pemphigus vulgaris (PV) is a chronic, autoimmune, vesiculobullous disease. As a result of the relative rarity of PV, published randomized controlled trials (RCTs) are limited, which makes it difficult to evaluate the efficacy of different treatment regimens in this disease. This also precludes conduct of a meta-analysis. METHODS: English-language publications describing treatment outcomes of patients with PV were identified by searches of electronic databases through May 2015, and additionally by review of the bibliography of these publications. A total of 89 papers, which included 21 case reports, 47 case series, 8 RCTs, and 13 observational studies, were identified. The findings from these publications, including information on disease course and prognosis, medications used, treatment responses, and side effects, are summarized in the tables and text of this review. RESULTS: Prior to availability of corticosteroid therapy, PV had a high fatality rate. Early publications from the 1970s reported high-dose, prolonged corticosteroid use and significant associated side effects. Later reports described use of corticosteroids along with steroid-sparing adjuvants, which allows a reduction in the total dose of corticosteroids and a reduction in observed mortality and morbidity. For the majority of patients in these reports, a long-term course on medications lasting about 5-10 years was observed; however, subgroups of patients requiring shorter courses or needing longer-term therapy have also been described. Early diagnosis of PV and early initiation of treatment were prognostic factors. In recent publications, commonly used initial regimens include corticosteroids in combination with mycophenolate or azathioprine; whereas, for patients with inadequate response to these regimens, adjuvants such as intravenous immunoglobulin (IVIg) or rituximab are used. CONCLUSION: The review findings emphasize the importance of early diagnosis, early initiation of treatment, and use of steroid-sparing adjuvants to allow a reduced total dose and duration on corticosteroids. Also highlighted is the need for more RCTs.

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.

Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score: a multicenter development and reliability assessment.

BACKGROUND: Epidermolysis bullosa (EB) is a genetic mucocutaneous disorder characterized by blister formation upon mild trauma. All 4 EB types may show oropharyngeal lesions involving either hard or soft tissues. Currently, there are very few data on EB scoring that include the oropharyngeal cavity. OBJECTIVES: We sought to develop an oropharyngeal severity score that was objective, valid, reliable, reproducible, easy to perform, and appropriate for all EB types. METHODS: In this study, oral medicine specialists developed a new score, the EB Oropharyngeal Severity (EBOS) score. This measured oropharyngeal disease activity (erythema, atrophy, blisters, erosion/ulceration) and structural damage (microstomia, ankyloglossia, scarring phenotype beyond microstomia and ankyloglossia, enamel hypoplasia). It was tested on 92 patients with different types/subtypes of EB, and interobserver and intraobserver reliability were assessed. RESULTS: The EBOS mean total score was 12.9 ± 10.9 (range: 0-34). Both interobserver and intraobserver reliability for total score on all patients with EB were considered excellent (intraclass correlation coefficient 0.94; 95% confidence interval 0.90-0.96 and intraclass correlation coefficient 0.90; 95% confidence interval 0.84-0.94, respectively). Even analyzing each single parameter of the disease activity and structural damage, a substantial to excellent correlation was found in the interobserver (except for 4 sites) and intraobserver reliability. A significant correlation was found between EB types/subtypes and the EBOS median score (P < .001), but not between age and the EBOS mean total score in each group. LIMITATIONS: The sample size was small and the number of EB subtypes was limited. CONCLUSIONS: The EBOS score seems to represent an instrument capable of truly quantifying the oropharyngeal severity in different types/subtypes of EB, demonstrating excellent interobserver and intraobserver reliability.

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.

Changes in emerging cardiac biomarkers after an intensive lifestyle intervention.

The present study evaluated the changes in emerging cardiac biomarkers, cognitive function, and social support measures after a comprehensive lifestyle intervention that included a low-fat, whole-foods, plant-based diet, exercise, stress management, and group support meetings. We conducted a prospective cohort study of 131 participants (59.2% women and 43.1% with diabetes mellitus), 56 with coronary heart disease (CHD) (37.5% women and 27.3% diabetes mellitus), and 75 at high risk with ≥3 CHD risk factors and/or diabetes mellitus (76% women and 54.7% diabetes mellitus). The measurements were taken at baseline and 3 months after the intervention. Improvement in all targeted health behaviors was seen in both high-risk and CHD groups (all p <0.001) at 3 months, with reductions in body mass index, systolic and diastolic blood pressure, waist/hip ratio, C-reactive protein, insulin, low-density lipoprotein, high-density and total cholesterol, apolipoproteins A1 and B (all p <0.009) were observed. Nuclear magnetic resonance spectroscopy analysis of lipoprotein subclass particle concentrations and diameters showed a reduction in large very-low-density lipoprotein particles, size of the very-low-density lipoprotein particles, total low-density lipoprotein particles; total, large, and small high-density lipoprotein particles (all p <0.009) and small very-low-density lipoprotein particles (p <0.02). Increases in fibrinogen (p <0.03) and B-type natriuretic peptide (p <0.001) were seen, and these changes correlated inversely with the changes in the body mass index. The observed increase in B-type natriuretic peptide can be explained by the metabolic changes related to adipose tissue lipolysis. The quality of life, cognitive functioning, and social support measures significantly improved. In conclusion, lifestyle changes can be followed by favorable changes in traditional and emerging coronary heart disease biomarkers, quality of life, social support, and cognitive function among those with, or at high risk, of CHD.

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.

Relation of B-type natriuretic peptide levels to body mass index after comprehensive lifestyle changes.

Cross-sectional studies have reported inverse associations of B-type natriuretic peptide (BNP) with the body mass index (BMI). We evaluated whether changes in the BMI are associated with changes in BNP. A nested prospective cohort study of a lifestyle intervention (low-fat, whole-foods diet, exercise, stress management, and social support) was conducted. BNP, BMI, and other biomarkers were measured at baseline and 3 months. A total of 131 subjects, 56 with coronary heart disease (CHD) and 75 at high risk, with > or =3 CHD risk factors and/or diabetes mellitus, were enrolled. At 3 months, the mean BMI had decreased (34.4 to 31.7 kg/m(2), p <0.001), BNP had increased (median 18 to 28 pg/ml, p <0.001), and low-density lipoprotein, C-reactive protein, apolipoprotein B (all p <0.002), and angina frequency (p = 0.017) and severity (p = 0.052) had decreased. The subjects' physical limitations had decreased and their physical functioning had improved (all p <0.001). The percentage of change in BNP was inversely associated with the percentage of change in insulin (r = -0.339, p = 0.005, n = 63 nondiabetics). It was also inversely associated with the percentage of change in BMI (r = -0.28, p = 0.002, n = 116), and this association remained significant (p = 0.029) in multiple regression analyses controlling for age, gender, CHD, diabetes mellitus, percentage of change in lifestyle index, and beta-blocker use. The metabolic changes related to adipose tissue lipolysis could explain these findings. In conclusion, BNP increased in subjects experiencing weight loss while following a lifestyle intervention, and angina pectoris, physical limitations, and other CHD risk factors decreased. Therefore, in this context, increasing BNP might not indicate worsening disease or a worsening prognosis. Thus, the proposed use of BNP in monitoring disease progression should take into account changes in the BMI during the same period.

Immunosuppressants.

This paper provides a brief introduction to some of the common immunosuppressants used in oral medicine, the prevention and treatment of oral adverse effects of immunosuppressants, and considerations for dental treatment in patients taking immunosuppressants.