Long-Term Results (24 Years) of the Treatment of Amalgam Tattoo in the Anterior Maxillary Region: A Histologic and Clinical Case Report.

Amalgam tattoos are a serious cosmetic problem for patients. A 35-year-old woman came to a private periodontal practice complaining of black pigmentation (amalgam tattoo) above temporary crowns on the lateral and central maxillary incisors and asked that the cosmetic problem be solved before the new permanent crowns were cemented into place. A full-thickness coronoapical incision was made to raise a thick flap; another incision parallel to the surface of the alveolar mucosa made it possible to remove the pigmented connective tissue, which was sent for histologic examination. Due to the fact that the pigmentation extended into the gingival epithelium, the gingiva of the lateral and central incisors was completely removed, with a horizontal incision in the alveolar mucosa from the ends of the distal releasing incisions. Therefore, partially denuded alveolar bone was used as the recipient site for a free gingival graft (FGG). The histologic analysis revealed the presence of amalgam fragments of different sizes in both connective tissue and epithelium. At 6 months, 3 years, and 24 years postoperatively, the periodontal tissues appeared healthy, and the treated area was pink, without pigmentation or scarring, and was perfectly integrated with the adjacent tissues. The patient was very pleased with her appearance. A one-stage procedure, namely an FGG, should be considered an effective treatment of amalgam tattoo providing positive morphologic and cosmetic outcomes over a 24-year follow-up period.

SPOCK1 is a novel inducer of epithelial to mesenchymal transition in drug-induced gingival overgrowth.

Few studies have investigated the role of extracellular-matrix proteoglycans in the pathogenesis of drug-induced gingival overgrowth (DIGO). SPOCK1 is an extracellular proteoglycan that induces epithelial to mesenchymal transition (EMT) in several cancer cell lines and exhibits protease-inhibitory activity. However, the role of SPOCK1 in non-cancerous diseases such as DIGO has not been well-addressed. We demonstrated that the expression of SPOCK1, TGF-ß1, and MMP-9 in calcium channel blocker-induced gingival overgrowth is higher than that in non-overgrowth tissues. Transgenic mice overexpressing Spock1 developed obvious gingival-overgrowth and fibrosis phenotypes, and positively correlated with EMT-like changes. Furthermore, in vitro data indicated a tri-directional interaction between SPOCK1, TGF-ß1, and MMP-9 that led to gingival overgrowth. Our study shows that SPOCK1 up-regulation in a noncancerous disease and SPOCK1-induced EMT in gingival overgrowth occurs via cooperation and crosstalk between several potential signaling pathways. Therefore, SPOCK1 is a novel therapeutic target for gingival overgrowth and its expression is a potential risk of EMT induction in cancerous lesions.

Establishment and genomic characterization of gingivobuccal carcinoma cell lines with smokeless tobacco associated genetic alterations and oncogenic PIK3CA mutation.

Smokeless tobacco associated Gingivobuccal squamous cell carcinoma (GB-SCC) is a major public health problem but available oral cancer cell lines are mostly from smoking associated tongue SCC raising the need for pertinent GB-SCC cell line models. As part of the International Cancer Genome Consortium (ICGC) Project, 4 novel cell lines, namely, Indian Tata Memorial Centre Oral Cancer (ITOC) -01 to -04 were established and characterized with conventional methods, karyotyping, ultrastructure, in vivo tumourigenicity, Whole exome sequencing (WES) and RNA sequencing. These hyperploid cell lines form xenografts in mice and show metabolically active and necrotic areas on fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. WES of ITOC cell lines recapitulate the genomic tumor profile of ICGC GB-SCC database. We further identified smokeless tobacco associated genetic alterations (PCLO, FAT3 and SYNE2) and oncogenic PIK3CA mutation in GB-SCC cell lines. Transcriptome profiling identified deregulation of pathways commonly altered in cancer and down-regulation of arachidonic acid metabolism pathway, implying its possible role in GB-SCC. Clinical application of high throughput sequencing data depends on relevant cell line models to validate potential targets. Extensively characterized, these oral SCC cell lines are particularly suited for mechanistic studies and pre-clinical drug development for smokeless tobacco associated oral cancer.

Coloración dental por índigo carmín. Excipientes: la asignatura pendiente / Indigo carmine related tooth discolouration. Excipients: a pending subject

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Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura.

BACKGROUND: In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets. METHODS: In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers. RESULTS: The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P=0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period. CONCLUSIONS: Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. (Funded by Ablynx; HERCULES ClinicalTrials.gov number, NCT02553317 .).

Lead exposure may affect gingival health in children.

BACKGROUND: Several studies have reported the harmful effects of lead poisoning. However, the relationship between lead exposure and oral health of children has not been well defined. The aim of this study was to investigate the relationship between blood lead level (BLL) and oral health status of children. METHODS: A total of 351 children (aged 7-15 years) were recruited from the pilot data of the Korean Environmental Health Survey in Children and Adolescents, which was designed to examine environmental exposure and children's health status in South Korea. Blood samples were taken to determine BLLs and oral examinations were performed to assess oral health parameters, including community periodontal index (CPI), gingival index (GI), and plaque index (PI). Information regarding socioeconomic status, oral hygiene behavior, and dietary habits was collected from parents and guardians. RESULTS: The participants were divided equally into four quartiles, with quartile I comprised of children with the lowest BLLs. There were significant differences for PI (p < 0.05) among the quartile groups. Using logistic regression models, we found a significant relationship between BLL and oral health parameters. The crude odds ratios for CPI, GI, and PI in the third quartile were 5.24 (95% CI: 1.48-18.56), 4.35 (95% CI: 1.36-13.9), and 4.17 (95% CI: 1.50-11.54), respectively, while the age and gender-adjusted odds ratios were 7.66 (95% CI: 1.84-31.91), 6.80 (95% CI: 1.80-25.68), and 3.41 (95% CI: 1.12-10.40), respectively. After adjustments for age, gender, parent education level, and frequency of tooth brushing, the adjusted odds ratios were 7.21 (95% CI: 1.72-30.19), 6.13 (95% CI: 1.62-23.19), and 3.37 (95% CI: 1.10-10.34), respectively. CONCLUSIONS: A high BLL might be associated with oral health problems in children, including plaque deposition and gingival diseases.

Allele-specific polymerase chain reaction for the detection of single nucleotide polymorphism in amlodipine-induced gingival enlargement.

WHAT IS KNOWN AND OBJECTIVE: Studies indicate that there is an increased serum concentration of amlodipine (a calcium channel blocker used to treat hypertension and angina) in patients having mutant multidrug resistance 1 (MDR1) gene. Hence, genetic factors may play a very significant role in amlodipine-induced complications including gingival enlargement. CASE DESCRIPTION: Three patients with amlodipine-induced gingival enlargement showed improvement following drug substitution of amlodipine with enalapril (an angiotensin-converting enzyme inhibitor) and non-invasive periodontal therapy. Using allele-specific polymerase chain reaction, single nucleotide polymorphism of MDR1 gene of heterozygous mutant type (CT genotype) was identified in all three cases. WHAT IS NEW AND CONCLUSION: Drug-induced complications can potentially be a result of genetic factors, in combination with various local and systemic factors. Identifying genetic polymorphisms early might help predict adverse reactions and determine prognosis.

Agrandamiento gingival inducido por medicamentos. Reporte de un caso clínico / Drug-Induced Gingival Enlargement. A Clinical Case Report

Antecedentes: El agrandamiento gingival inducido por medicamentos es una condición clínica frecuente en pacientes que ingieren anticonvulsivos, inmunosupresores y bloqueadores de los canales de calcio. La prevalencia de agrandamiento gingival inducido por medicamentos es del 3 % al 20 % en el grupo de las condiciones gingivales inflamatorias. Todos estos medicamentos producen lesiones clínicas y características histológicas indistinguibles unas de otras, que llegan a afectar la función y la estética de los pacientes afectados. Objetivo: Describir el manejo terapéutico integral y el seguimiento a 12 meses de una paciente con agrandamiento gingival inducido por tacrolimus y amlodipino. Descripción del caso: Una mujer de 22 años con discapacidad mental limítrofe y receptora de trasplante renal se remitió al servicio de Odontología del Hospital Infantil Universitario de San José (Bogotá, Colombia) por presentar agrandamiento gingival. El examen clínico mostró un índice de placa de O'Leary del 84,3 %, in flamación generalizada y bolsas gingivales de 4-6 mm. El equipo de trasplante renal revisó el protocolo de tratamiento periodontal que incluyó: trabajo con la familia para red de apoyo, diseño de un programa personalizado de higiene oral, gingivectomía y mantenimientos periodontales periódicos. Esta estrategia terapéutica permitió reducir el índice de placa y lograr un resultado clínico favorable. Conclusión: La condición sistêmica y psicológica de la paciente requirió desarrollar un plan de tratamiento ajustado a sus necesidades. Pacientes susceptibles deben ser instruidos sobre la importancia de tener prácticas adecuadas de higiene oral y ameritan ser incluidos en programas de mantenimiento periodontal.

Background: Gingival enlargement induced by the use of drugs is a frequent clinical condition in patients who take anticonvulsants, immunosuppressive agents and calcium channel blockers. The gingival enlargement prevalence, as induced by drug use, is from 3% to 20% in the group with inflammatory gingival conditions. All these drugs cause clinical lesions and histological characteristics indistinguishable from one another, which eventually affect the function and aesthetics of the patients. Objective: To describe a comprehensive therapeutic management and the 12-month following in a patient with gingival enlargement induced by the use of tacrolimus and amlodipine. Case Description: A 22 year-old woman with Borderline Personality Disorder who also underwent a kidney transplant was referred to the dental service in the Hospital Infantil Universitario de San José (Bogotá, Colombia) due to gingival enlargement. The clinical examination showed an O'Leary plaque index of 84.3%, extended inflammation and gingival pockets about 4-6 mm. The kidney transplant team checked the periodontal treatment protocol that included: partnering with the family as a support network, design of a customized oral hygiene program, gingivectomy and regular periodontal maintenance. This therapeutic strategy allowed to reduce the plaque index and resulted in a favorable clinical condition. Conclusion: The systemic and psychological status of the patient required to design a treatment plan customized to her needs. Susceptible patients should be educated on how important it is to follow the appropriate oral hygiene practices and are eligible for periodontal maintenance programs.

Arsenic trioxide-induced osteo-necrosis treatment in a child: mini-review and case report.

BACKGROUND: Arsenic oxide compounds were traditionally used as devitalizing agents. Due to its toxicity, leakage of such compounds into the periodontium can cause gingival and osteo-necrosis. Their use is forbidden in Europe and the USA for decades, however, some dentists seem to still use it. CASE REPORT: We report the case of a 14-year-old girl referred to the paediatric dentistry department of Toulouse University hospital, France, presenting a bone necrosis following the use of an arsenic trioxide product to accelerate pulp necrosis. TREATMENT: The treatment included surgical removal of necrosis bone sequestrum, complete pulpectomy and an intermediate restoration of the tooth 27. FOLLOW-UP: After 1 week, the clinical conditions greatly improved. A restoration using a ceramic crown was performed after 2 months, and complete healing was observed after 1 year follow-up. CONCLUSION: Although arsenic trioxide is neither appropriate nor permitted for use in modern dentistry, especially in paediatric dentistry, some rare cases of arsenic-induced osteo-necrosis can still be encountered. A clearer message must be given to all dental practitioners against the use of arsenic trioxide in modern endodontic treatment.

Tooth-Bleaching: A Review of the Efficacy and Adverse Effects of Various Tooth Whitening Products.

Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues.

[Side effects of drugs on the oral cavity]. / Reacciones adversas a medicamentos en la cavidad oral.

Although drugs are the most powerful therapeutic tools we have for improving the quality of life of the population, their use is not free of adverse effects. Today there are many polymedicated patients, and it is difficult to find the cause of their adverse effects that increase exponentially when more than 4 drugs are combined. There are a large number of drugs that can result in numerous adverse effects in the oral cavity. The most common are xerostomia, altered taste, gingival enlargement and mucositis caused by cancer treatment. We also review other disorders of the salivary glands, oral mucosal changes, pigmentations, halitosis, osteonecrosis, opportunistic infections and bleeding diathesis.

Cosmetic side effects of antiepileptic drugs in adults with epilepsy.

OBJECTIVE: Cosmetic side effects (CSEs) such as weight gain and alopecia are common, undesirable effects associated with several AEDs. The objective of the study was to compare the CSE profiles in a large specialty practice-based sample of patients taking both older and newer AEDs. METHODS: As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 1903 adult patients (≥16years of age) newly started on an AED. Cosmetic side effects were determined by patient or physician report in the medical record and included acne, gingival hyperplasia, hair loss, hirsutism, and weight gain. We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy. RESULTS: Overall, CSEs occurred in 110/1903 (5.8%) patients and led to intolerability in 70/1903 (3.7%) patients. Weight gain was the most commonly reported CSE (68/1903, 3.6%) and led to intolerability in 63 (3.3%) patients. Alopecia was the second most common patient-reported CSE (36/1903, 1.9%) and was intolerable in 33/1903 (1.7%) patients. Risk factors for CSEs included female sex (7.0% vs. 4.3% in males; p<0.05) and any prior CSE (37% vs. 2.9% in patients without prior CSE; p<0.001). Significantly more CSEs were attributed to valproic acid (59/270; 21.9%; p<0.001) and pregabalin (14/143; 9.8%; p<0.001) than to all other AEDs. Significantly less CSEs were attributed to levetiracetam (7/524; 1.3%; p=0.002). Weight gain was most frequently associated with valproic acid (35/270; 13.0%; p<0.001) and pregabalin (12/143; 8.4%; p<0.001). Hair loss was most commonly reported among patients taking valproic acid (24/270; 8.9%; p<0.001). Finally, gingival hyperplasia was most commonly reported in patients taking phenytoin (10/404; 2.5%; p<0.001). Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13.3 and 5.6% vs. 2.3%; p<0.001). For patients who had been on an AED in monotherapy (n=677), CSEs and ICSEs were still more likely to be attributed to valproic acid (30.2% and 17.1%, respectively) than to any other AED (both p<0.001). SIGNIFICANCE: Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation. Particular attention should be paid to pregabalin, phenytoin, and valproic acid when considering cosmetic side effects. Female patients and patients who have had prior CSE(s) to AED(s) were more likely to report CSEs. Knowledge of specific CSE rates for each AED found in this study may be useful in clinical practice.

Titanium tattooing associated with zirconia implant abutments: a clinical report of two cases.

Worn particulate titanium abraded from a titanium dental implant that discolors the adjacent soft tissues has not previously been reported. Two cases of this gingival tissue "tattooing" are reported here. While the use of zirconia abutments in areas of high esthetic concern is widespread, the effects of particulate titanium being worn from the implant by the much harder abutment material and then taken up in the adjacent soft tissues should be considered as a potential complication and a consideration when selecting the type of abutment to be used.

Gingival and localized alveolar bone necrosis related to the use of arsenic trioxide paste--two case reports.

The leakage of arsenic trioxide paste from tooth fillings has been associated with widespread necrosis of the supporting periodontal tissues. This report describes two cases of arsenic trioxide paste-induced gingival and localized alveolar bone necrosis in the mandible, following the use of arsenic trioxide paste as a pulp-devitalized agent. The first case was a 54-year-old female complaining of a painful white patch on the gingival tissue of the left mandibular second molar (tooth #37) after treatment by a private dentist. She underwent completely debridement of all necrotic soft tissue with physical saline irrigation. The gingival tissue was gradually replaced with vascular tissue and completely healed after 7 weeks. The second case was a 30-year-old female complaining of severe pain and continuous gingival bleeding from the right maxillary first bicuspid (tooth #14) following treatment by a private dentist. She finally accepted debridement of the sequestrum and necrotic alveolar bone with decortication to induce active bleeding. A partial thickness gingival flap was made to cover the wound. Four weeks later, the supporting tissues had completely healed. Arsenic trioxide paste is a cytotoxic agent and may cause harmful adverse effects on adjacent periodontium and supporting hard tissue if leakage occurs, or it is used carelessly. There is no indication for the use of arsenic trioxide paste in modern dental practice.

Drug-induced gingival enlargement.

OBJECTIVES: Side effect of medicamentous treatment in hypertension therapy and angina pectoris with calcium channel blockers related to fibrotic gingival enlargement were examined. METHODS: In our study we deal with clinico-histopathological and microbiological knowledge from this field underpinned by two case reports treated with antihypertensive therapy using calcium channel blockers. In the first case report we were largely concerned with microbiological findings from the area of periodontal pseudopockets diagnosed through a DNA analysis and appropriate antibiotic therapy. In a patient treated with a preparation from amlodipine group we proceeded to a complex treatment involving the change of hypertension therapy, introduction of professional and home oral hygiene and also following surgical and prosthetico-aesthetic rehabilitation. RESULTS: Case Report 1 who was for a long term medicated with a preparation from the nifedipine group of antihypertensives we detected the presence of periodontal pseudopockets with probing depth of 4 to 7 mm with positive BOP and with marked rigid fibrotic gingival enlargement accompanied with considerable foetor ex ore. In a patient from the Case Report 2 who was for a long term medicated with a preparation from the amlodipine group of antihypertensives with large gingival overgrowth angiogenesis was characterized by cuboidal endothelial cell lining. In the samples under a layer of stratified epithelium there was present dense fibrous connective tissue comprising largely of collagen fiber bundles. CONCLUSION: Bacterial composition in the patient with a high degree of gingival enlargement and periodontal pseudopockets 4 to 7 mm deep represented a typical spectrum of bacteria occuring in chronic forms of periodontitis. However, we cannot determine, if such distribution of bacteria was primary before the application of nifedipine antihypertensives, or it originated later after the formation of typical anaerobic setting of false periodontal pockets.

Oral mucosal health in liver transplant recipients and controls.

Immunosuppressive drugs and other medications may predispose patients to oral diseases. Data on oral mucosal health in recipients of liver transplantation (LT) are limited. We, therefore, recruited 84 LT recipients (64 with chronic liver disease and 20 with acute liver failure) for clinical oral examinations in a cross-sectional, case-control study. Their oral health had been clinically examined before transplantation. The prevalence of oral mucosal lesions (OMLs) was assessed in groups with different etiologies of liver disease and in groups with different immunosuppressive medications, and these groups were compared to controls selected from a nationwide survey in Finland (n = 252). Risk factors for OMLs were evaluated with logistic regression. OMLs were more frequent in LT recipients versus controls (43% versus 15%, P < 0.001), and the use of steroids raised the prevalence to 53%. Drug-induced gingival overgrowth was the single most common type of lesion, and its prevalence was significantly higher for patients using cyclosporine A (CSA; 29%) versus patients using tacrolimus (TAC; 5%, P = 0.007); the prevalence was even higher with the simultaneous use of calcium channel blockers and CSA (47%) or TAC (8%, P = 0.002). Lesions with malignant potential such as drug-induced lichenoid reactions, oral lichen planus-like lesions, leukoplakias, and ulcers occurred in 13% of the patients with chronic liver disease and in 6% of the controls. Every third patient with chronic liver disease had reduced salivary flow, and more than half of all patients were positive for Candida; this risk was higher with steroids. In conclusion, the high frequency of OMLs among LT recipients can be explained not only by immunosuppressive drugs but also by other medications. Because dry mouth affects oral health and OMLs may have the potential for malignant transformation, annual oral examinations are indicated.

Epstein-Barr virus-positive oral ulceration simulating Hodgkin lymphoma in a patient treated with methotrexate: case report and review of the literature.

Immunosuppressive therapy for patients diagnosed with rheumatoid arthritis has long been implicated in the development of various neoplastic processes, including leukemia and lymphoma. Methotrexate is a commonly administered antimetabolic medication thought to improve the symptoms of rheumatoid arthritis through its anti-inflammatory effects. Longterm methotrexate therapy and concurrent rheumatoid arthritis have both been independently suggested as risk factors for developing lymphoma. The mechanism has been theorized to be severe immunosuppression and an increased frequency of latent infection with pro-oncogenic viruses, such as the Epstein-Barr virus (EBV). Spontaneous remission of these malignancies has been seen after discontinuation of the methotrexate therapy. In the present study, we report the case of a patient diagnosed with rheumatoid arthritis and treated with methotrexate and prednisone. She developed intraoral ulcerations that histopathologically resembled Hodgkin's lymphoma.

Management of phenytoin-induced gingival enlargement: a case report.

Gingival enlargements may adversely affect speech, mastication, tooth eruption, and esthetics. These enlargements can occur as a result of the administration of certain anticonvulsants, immunosuppressants, and calcium channel blockers. The present case report describes the treatment of a patient with a phenytoin-induced gingival enlargement. A case of gingival enlargement should be treated in a step-wise manner, including consultation with the patient's physician, substitution of the drug, nonsurgical therapy, surgical therapy (if needed), and supportive periodontal therapy after every 3 months. In this case, healing was uneventful, and no recurrences occurred 3 months postoperatively.