Degree Of Gingival Overgrowth Research Articles

Idiopathic Gingival Enlargement and its Management: A Case Report

Idiopathic or hereditary gingival fibromatosis (HGF) is a relatively rare disease characterized by the enlargement of the gingiva, resulting in functional, esthetics and psychological disturbances. The degree of gingival overgrowth can be defined as: grade 0: no sign of gingival enlargement; grade I: enlargement confined to interdental papilla; grade II: enlargement involves papilla and marginal gingiva; and grade III: enlargement covers three quarters or more of the crown. This case report describes the case of a 16-year-old girl suffering from HGF with chief complaint of gingival swelling. Intraoral examination exhibited diffuse and grade III gingival enlargement in both jaws and also in both surfaces of buccal and lingual/palatal. Treatment included surgery (internal and external gingivectomy) in six sessions, and prescription of antibiotics and 0.2% chlorhexidine mouthwash. Moreover, gingivoplasty was performed in the esthetic zone of maxilla after performing all the surgeries in the mouth. The patient was under regular follow-up visits. The treatment outcomes after six months were satisfactory and no symptoms of recurrence were observed.

Diagnosis and management of nonsyndromic hereditary gingival fibromatosis in a 13 year old girl: Report of a rare case

Hereditary gingival fibromatosis is a rare condition characterized by various degree of gingival overgrowth. It usually develops as an isolated disorder but can manifest with multisystem syndrome. We are here presenting a case of a 13-year-old girl who presented with severe enlargement of gingiva covering all most the entire crown involving both maxillary and mandibular arches. Differential diagnosis includes drug-induced and idiopathic gingival enlargement. Excess gingival tissue was removed by full mouth gingivectomy and sent for histopathological examination. Postoperative course was uneventful and patient's esthetics improved significantly. A 12 month postoperative period shows no recurrence.

Low prevalence of gingival overgrowth associated to new imunossupressive protocols with cyclosporin

Gingival overgrowth (GO) is a frequent finding in patients treated with cyclosporine (CsA). This study investigated the prevalence and severity of GO in patients who received kidney transplant and CsA therapy, as well as associations with pharmacological and clinical factors. This cross-sectional study included 63 kidney transplant recipients who were treated with CsA in a university hospital. Demographic, pharmacological, and periodontal data were collected. The primary variable was GO. Independent sample t- and chi-square tests were used to compare means in groups with versus without GO. The response rate was 86.3%. Overall, 40% of patients had some degree of GO. Eleven individuals presented GO scores > 10%, and 5 individuals reached 30%. The mean GO percentage was low (6.79 ± 15.83). Patients that were concurrently under nifedipine treatment showed a non-significant trend toward a greater prevalence of GO. Mean CsA dosage and serum levels were 3.20 ± 0.94 mg/kg/d and 156.12 ± 162.75 ng/mL, respectively. There were no statistically significant differences between patients with versus without GO nor between the groups receiving nifedipine, no drug, or verapamil. The GO prevalence and severity rates were lower than those reported in previous studies and seemed to be independent of drug interactions.

Cyclosporine‐induced gingival overgrowth correlates with NFAT‐regulated gene expression: a pilot study

To determine whether incidence and severity of cyclosporine A (CsA)-induced gingival overgrowth (GO) is related to expression nuclear factor of activated T cells-regulated genes (NFAT-regulated genes). Expression of NFAT-regulated genes was determined in 36 transplant patients medicated with CsA by real-time PCR before and 2 h after drug intake and residual NFAT activity was estimated as ratio of both measurements. Demographic, periodontal and pharmacologic parameters were recorded and GO assessed from models. Subjects were divided into two groups according to the degree of GO (responders: GO score≥10%). Groups were compared using parametric and non-parametric tests. The association of various CsA-specific and periodontal parameters on incidence and extent of GO were determined using regression analysis. Responders had a more than twofold lower residual NFAT activity than non-responders (7.9% and 18.1%, respectively; p<0.001). Multiple regression analysis revealed gingival inflammation, salivary CsA concentration, and residual NFAT activity to be significant factors influencing the expression of GO. Seventy-seven percent of the variability of GO could be explained by these parameters. This study showed that pharmacodynamic parameters such as residual NFAT activity may be promising prognostic indicators to identify patients with increased risk for GO.

Clinical and pharmacological variables as a risk factor for nifedipine‐induced gingival overgrowth

Gingival enlargement is usually noted within one to two months after the initiation of nifedipine therapy. The aetiology of nifedipine-induced gingival overgrowth is uncertain. The aim of this study was to determine the relationship between plasma and gingival crevice fluid (GCF) nifedipine concentrations and the degree of gingival overgrowth in patients treated with nifedipine, and also to assess the correlations between clinical and pharmacological variables. Eighteen patients taking nifedipine in regular doses for at least six months participated in the study. Gingival enlargement was evaluated with two indices to score vertical and horizontal overgrowth. Gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), probing depth (PD) and clinical attachment level (CAL) were also evaluated. GCF and plasma nifedipine concentrations were determined by using high performance liquid chromatography. There was no significant difference between responders and non-responders for PI, GI and GBTI. The mean concentration of nifedipine in GCF was significantly greater than concentration in plasma. No significant difference was observed for GCF and plasma nifedipine concentration between responders and non-responders. The present study showed that neither GCF nor plasma nifedipine levels appeared to be a risk factor for nifedipine-induced gingival overgrowth. Improving the oral hygiene in patients using nifedipine may help control the degree of drug-induced gingival enlargement.

Plasma and Gingival Crevicular Fluid Phenytoin Concentrations as Risk Factors for Gingival Overgrowth

Gingival enlargement is one of the side effects associated with the administration of phenytoin. The mechanism by which phenytoin induces gingival enlargement is not well understood. This study was conducted to investigate the relationship between plasma and gingival crevicular fluid (GCF) phenytoin concentrations and the degree of gingival overgrowth in patients with similar gingival and plaque indices and also to determine the risk factors for gingival enlargement. Eighteen patients taking phenytoin in regular doses > or =6 months prior to the investigation participated in the study. Gingival enlargement was evaluated with two indices to score vertical and horizontal overgrowth. The gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), probing depth (PD), and clinical attachment level (CAL) were also evaluated. GCF and plasma phenytoin concentrations were determined by using high-performance liquid chromatography (HPLC). There was no significant difference between responders and non-responders for PD, CAL, PI, GI, and GBTI. Phenytoin was detected in all of the GCF and plasma samples using the HPLC analysis method. The mean concentration of phenytoin in GCF was significantly greater than the concentration of phenytoin in plasma. No significant difference was observed for the concentration of GCF phenytoin between responders and non-responders. However, the concentration of plasma phenytoin was significantly higher in responders than non-responders. This study showed that plasma phenytoin level appeared to be a risk factor for phenytoin-induced gingival overgrowth.

Cyclosporin‐Induced Gingival Overgrowth: A Clinical–Epidemiological Evaluation of 121 Italian Renal Transplant Recipients

Although other immunosuppressive agents have been recently introduced (e.g., tacrolimus), it has been calculated that in the next decade about 1 million people will still be taking cyclosporin (CsA). The association between gingival overgrowth (GO) and the use of CsA is still not clear. In the present study we evaluated the prevalence and the degree of GO in a group of Italian renal transplant patients and the possible relationship between gingival lesions and demographic, oral, systemic, and pharmacological variables. One hundred twenty-one renal transplant recipients receiving immunosuppressive therapy with CsA were evaluated in this study. Patients were classified in two groups. In the first (screening group), we included all those patients referred by the Parma University Renal Transplant Center for a general oral checkup, with no specific indications for GO. The second group (non-screening group) included all those patients who specifically had been referred to the Oral Pathology and Oral Medicine Unit because of GO. We considered the following variables: gender, daily CsA dose, duration of immunosuppressive treatment, CsA plasma concentration, concomitant use of another immunosuppressive agent (azathioprine), use of other GO inducers (calcium channel blockers, anti-epileptic drugs), oral hygiene scores, and other drugs taken at the time of oral examination. Fisher's exact test and chi square test demonstrated that in the screening group, duration of immunosuppressive treatment and oral hygiene scores were associated both with the prevalence and the high GO scores (P (1) (DIT) <0.0001; P (2) (DIT)=0.0023; P (1) (hyg)=0.0084; P (2) (hyg)=0.0068). In the screening group, concomitant use of CsA and azathioprine is related to a low development degree of GO (P=0.0088). In the non-screening group, we found a significant association between poor oral hygiene and high degree of GO (P=0.0349). In addition to a probable genetic predisposition, duration of immunosuppressive treatment and oral hygiene status are the most important variables related to development and degree of GO during the use of CsA in this study.

Effectiveness of periodontal therapy on the severity of cyclosporin A‐induced gingival overgrowth

The purpose of the present study was to evaluate the clinical effects of aetiological periodontal treatment in a group of transplant patients medicated with cyclosporin A (CsA) who exhibited severe gingival overgrowth. Twenty-one patients received oral hygiene instructions, supra- and subgingival scaling and periodontal maintenance therapy and were monitored for 12 months. Full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), periodontal probing depth and degree of gingival overgrowth (Seymour index GO) were recorded at baseline, 6 and 12 months after treatment. Statistical evaluation revealed that all clinical variables significantly decreased compared with baseline. At baseline 18 out of 21 treated patients (85.71%) exhibited clinically significant overgrowth. Initial GO score of 2.38+/-1.92 in the anterior sextants and of 1.29+/-1.59 in the posterior segments were reduced to 0.56+/-0.83 and to 0.45+/-0.84 at 12 months (p<0.001). A difference of 1.82 and 0.84 in the severity of treated GO was accompanied by a 42% and 34% decrease in FMPS and FMBS, respectively. Aetiological periodontal treatment and regular maintenance therapy were effective in resolving the inflammation and in eliminating the need for surgical treatment in patients receiving CsA.

Gingival Overgrowth in Children: Epidemiology, Pathogenesis, and Complications. A Literature Review

Gingival overgrowth is the enlargement of the attached gingiva due to an increased number of cells. The most prevalent types of gingival overgrowth in children are drug-induced gingival overgrowth, hereditary gingival fibromatosis (HGF), and neurofibromatosis I (von Recklinghausen disease). Gingival overgrowth induced by drugs such as phenytoin, nifedipine, and cyclosporin develops due to an increase in the connective tissue extracellular matrix. According to epidemiologic studies, it is more prevalent in male children and adolescents. There is an additive effect of those drugs on the degree of gingival overgrowth. Genetic heterogeneity seems to play an important role in the development of the disease. Functional difficulties, disfigurement, increased caries, and delayed eruption of permanent teeth are the main complications of drug-induced gingival overgrowth. HGF is the most common syndromic gingival enlargement in children. This autosomal dominant disease usually appears at the time of eruption of permanent dentition. Histologically, it is characterized by highly collagenized connective tissue. The most important complications are drifting of teeth, prolonged retention of primary dentition, diastemata, and poor plaque control. Neurofibromatosis I is an autosomal dominant disease more common in mentally handicapped individuals. Gingival overgrowth is caused by the formation of plexiform neurofibromas in the connective tissue of the gingiva. Plexiform neurofibromas are pathognomonic of the disease and consist of hypertrophic nerves arranged as lobules in the connective tissue. Complications of the disease are multiple and severe due to neurofibromas and their occasional malignant transformation.

Subgingival microflora associated with nifedipine-induced gingival overgrowth.

The purpose of this study was to examine the composition of subgingival plaque of 140 periodontal lesions in 35 patients with cardiovascular disorders who were administered nifedipine and manifested nifedipine-induced gingival overgrowth (GO). Age was inversely associated with the GO. Plaque index and bleeding index showed a significant association with GO, while nifedipine dosage and duration of nifedipine therapy were not found to be significant predictors of GO. The gingival inflammation as expressed in the logistic regression model by the interaction term color x tone was found to be significantly associated with the GO. Statistically significant differences between the groups of comparable probing depth and different degrees of GO were detected for Propionibacterium acnes, Capnocytophaga gingivalis, Capnocytophaga ochracea, Capnocytophaga sputigena, Bacteroides gracilis, Fusobacterium mortiferum, Fusobacterium nucleatum, Fusobacterium varium and Selenomonas sputigena in deep and enlarged lesions. Significantly more frequently isolated were the bacterial species Eubacterium alactolyticum, Campylobacter concisus, C. gingivalis, C. ochracea, C. sputigena, F. mortiferum, F. nucleatum, and F. varium from the more enlarged lesions (GO >3).

Increased bFGF level in the serum of patients with phenytoin-induced gingival overgrowth.

To elucidate the involvement of bFGF (basic fibroblast growth factor) in the pathogenesis of phenytoin-induced gingival overgrowth, we measured the concentration of bFGF in the serum of 36 epileptic patients taking phenytoin and in 94 normal volunteers by enzyme-linked immunosorbent assay technique. The concentration of phenytoin in serum was determined by high-performance liquid chromatography. In 34 of 36 patients taking phenytoin in this investigation, apparent gingival overgrowth was noticed. The mean concentration of bFGF was 33.9+/-18.5 pg/ml in the overgrowth group and 10.6+/-5.2 pg/ml in the volunteer group (p<0.01). The serum phenytoin level did not correlate (r=0.22, p=0.2) with the degree of gingival overgrowth but there was a significant correlation (r=0.38, p=0.023) between the degree of gingival overgrowth and the serum bFGF level. However, no correlation was observed among age, daily phenytoin dose, total phenytoin dose, duration of phenytoin therapy, serum phenytoin level, or serum bFGF level. The results suggested that enhanced serum bFGF level was implicated in the pathogenesis of phenytoin-induced gingival overgrowth.

The pharmacokinetics of phenytoin in gingival crevicular fluid and plasma in relation to gingival overgrowth

The aim of this study was to determine whether phenytoin (PHT) could be detected in gingival crevicular fluid (GCF), and to relate its concentration to both plasma level and degree of gingival overgrowth. 23 patients medicated with phenytoin for at least 6 months were clinically examined for signs of periodontal disease and gingival overgrowth. 12 patients out of these demonstrated clinically significant overgrowth and their plaque scores and gingival inflammation were greater than for the non-overgrowth group (p < 0.001). Phenytoin concentrations were determined by high performance liquid chromatography, and was detected in GCF. There was a significant correlation between the GCF and plasma phenytoin concentrations (p < 0.05), but it was not related to the extent of gingival overgrowth. Inflammation increased the GCF volume, but was not a determinant of GCF phenytoin concentration. It is concluded that effusion of phenytoin into GCF is regulated by the plasma levels of the drug, but its concentration in GCF is not related to the incidence of gingival overgrowth.

Gingival overgrowth induced by nifedipine and cyclosporin

In this study, we developed a quantitative method with digital image analysis to evaluate the degree of gingival overgrowth (GO), and compared GO in kidney transplant patients treated with cyclosporin A (CsA) (n = 21) or CsA+nifedipine (n = 8) and a group of healthy controls (n = 30). The method was reproducible and reliable. Our findings showed significant differences in papillary and gingival surface between controls and transplant patients treated with GO inducers. Gingival overgrowth index also differed significantly between controls and each patient group (p < 0.01, Kruskal-Wallis test). The administration of the calcium channel blocker nifedipine potentiated the adverse effect of CsA: comparison of the morphometric findings revealed significant differences between patients treated with CsA alone and CsA+nifedipine in papillary area, dental area, and GO index (p < 0.01, Mann-Whitney U-test). We conclude that the method of image analysis we developed is useful in assessing the degree of GO.

Factors influencing nifedipine-induced gingival overgrowth in rats.

Factors such as age, the dose of nifedipine administered in the diet, serum drug level, duration of drug administration, and sex which may influence nifedipine-induced gingival overgrowth were examined in a rat model using 20-, 50-, and 90-days-old male and female rats. Oral administration of nifedipine (50 to 250 mg/kg diet) increased the serum level of the drug in a dose-dependent manner in both males and females. However, a higher serum level was required in females than males to attain the same degree of gingival overgrowth. The minimum dietary concentrations of the drug required to elicit gingival overgrowth in males and females were 150 and 100 mg/kg, respectively, which gave respective minimum serum levels of 800 and 1100 ng/ml. The degree of overgrowth depended on the serum concentration of the drug after it had reached the required minimum in male and female animals. Administration of nifedipine (250 mg/kg diet) for 20 days was enough to induce maximal overgrowth, but this induction occurred only in rats that started to receive the drug when they were 20 days old, not in those that started at 50 and 90 days of age for the same administration period of 55 days, and the overgrowth regressed and the gingiva were normal 40 days after ceasing drug administration. These results suggest that gingival overgrowth occurred in accordance with the drug concentration in the diet, as well as that in the serum, and was more likely to occur in males and younger individuals.

Immunohistochemical study of 30 cases of cyclosporin A-induced gingival overgrowth.

Immunohistochemical techniques were used to study the presence of cyclosporin A (CsA) and leukocyte subsets in 30 gingival biopsies of renal transplant subjects with gingival overgrowth (GO). Statistical analysis revealed significant differences in the total number of inflammatory cells determined by monoclonal antibody CD45, the monocyte/macrophage (CD68) subset, the plasmatic cells (EMA), and the total of T-lymphocytes (CD3) (P < 0.001, Student t test) between the treated subjects and the healthy control group. Differences were found in the helper/inducer T lymphocytes CD4 (P < 0.001 Student t test) and cytotoxic/suppressor T lymphocyte (CD8) (P < 0.01, Student t test) subsets between both groups. The CD4/CD8 ratio was greater in the transplant subjects than in the control group (1.82 +/- 0.16 versus 1.35 +/- 0.05 respectively) (P < 0.05 Student t test). There was no significant difference in the populations CD16+, CD57+, and CD20+. The CD45+ CD4+, and CD68+ cells increased in number along with the degree of GO. The number of epithelial cells/mm2 which displayed a deposit of CsA increased in accordance with the degree of GO (P < 0.05, Kruskal-Wallis's test). Likewise, the intraepithelial deposit of CsA in the GO region was found to be related to the inflammatory infiltrate CD4+, CD8+, and CD68+ (r = 0.7432; r = 0.7346; r = 0.77005, respectively). Our findings suggest that the intraepithelial deposit of CsA and the inflammatory infiltrate play a predominantly pathogenic role and are both related to the degree of GO.

Nifedipine‐induced gingival overgrowth in the presence or absence of gingival inflammation in rats

One adverse effect of nifedipine, a long-acting vasodilator, is gingival overgrowth. Preexisting gingival inflammation and/or dental plaque has been suggested to be responsible for the progression of this side effect, but the precise mechanism is uncertain because of a lack of suitable animal models. A study was therefore done to establish an experimental model of gingival overgrowth in rats and to investigate the possible involvement of gingival inflammation and/or dental plaque in its development. Specific pathogen-free Fischer rats (male, 14 days old) were used. Gingival inflammation and dental plaque accumulation were induced by infection with Streptococcus mutans MT8148R. The nifedipine-treated rats (experimental group) were fed a caries-inducing diet containing nifedipine either with or without infection, while the nifedipine-untreated rats (control group) were fed the same diet, similarly with or without the infection. Marked gingival overgrowth was induced in the mandibular molar region of nifedipine-treated rats regardless of S. mutans infection, although the infection resulted in a further increase in the degree of gingival overgrowth. Histological examination of the gingival overgrowth revealed the presence of redundant subepithelial connective tissue in the treated rats, and inflammatory cell infiltration was apparent only in the tissue of the S. mutans-infected rats regardless of the nifedipine administration. These findings suggest that nifedipine induces gingival overgrowth in rats either in the presence or absence of gingival inflammation and/or dental plaque, although these factors can augment the effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Diphenylhydantoin (dilantin) gingival hyperplasia: drug-induced abnormality of connective tissue.

Various degrees of gingival overgrowth may occur in individuals taking diphenylhydantoin, a drug used widely in the treatment of epilepsy. The tissue overgrowth is made up predominantly of collagen, and may therefore be a useful model for analysis of fibrosis and some other connective tissue abnormalities. Fibroblasts derived from the overgrown tissue exhibit a level of protein synthetic activity approximately twice that of comparable cells obtained from nonepileptic control individuals and from the gingiva of age-matched epileptics taking the drug but not exhibiting gingival enlargement. In addition, 20% of the protein synthesized by cells from the affected tissue is collagen, whereas collagen accounts for only about 11% of the total protein produced by control cells of both types. The drug appears to induce or select for fibroblasts characterized by enhanced levels of protein synthesis and collagen production. This alteration persists through several cell replications in vitro in the absence of drug.