Gingival Overgrowth In Patients Research Articles

Comparison of Three Different Calcium Channel Blockers on Gingival Overgrowth in Hypertensive Patients

Introduction: Calcium Channel Blockers (CCBs) like Nifedipine is the most widely used drug in many countries in the management of hypertension, with other drugs also in use like Amlodipine, and Felodipine. Gingival hyperplasia is the common adverse effect of the three classes of CCBs used commonly as dihydropyridine calcium antagonists. Aim: To compare the effect of three different CBCs on gingival overgrowth in hypertensive patients. Materials and Methods: The present cross-sectional study was carried out in the Department of Periodontics, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh. The study was conducted between September 2020 and February 2022. A total of 206 patients with hypertension taking CCBs, were enrolled and divided into three groups based on the patient’s medication as Group-I (nifedipine; n=83), Group-II (amlodipine; n=71) and Group-III (felodipine; n=52). Gingival Overgrowth (GOG) was graded and periodontal parameters like Plaque Index (PI), Gingival Index (GI), and Probing Pocket Depth (PPD) were recorded. One-way analysis of variance and Tukey’s post-hoc test were done to evaluate and compare between the groups. Results: Mean age of the patients in group-I was 60.81±4.13 years, in group-II was 62.70±4.19 years, and in group-III was 59.54±3.42 years. No significant difference in PI scores and GI scores was seen between the groups. The mean score for PPD in group-I was 5.91±0.14 mm, in group-II score was 5.76±0.14 mm and in group-III the score was 5.13±0.22 mm. A statistically significant difference (p<0.001) was observed in group-I when compared with group-II and group-III. The mean GOG scores in group-I, group-II, and group-III were 3.49±0.22, 2.98±0.3, and 2.74±0.16. A statistically significant (p=0.001) increase in GOG scores was observed in group-I followed by group-II and group-III. Conclusion: Nifedipine was the most prescribed drug with high amount of gingival overgrowth in patients with hypertension, compared with amlodipine and felodipine.

Amlodipine induced Gingival Overgrowth in Patients at a Tertiary Level Hospital of Nepal

Background: Amlodipine is a commonly prescribed anti-hypertensive in clinical practice. Gingival overgrowth is a rare side effect of this drug; with a reported prevalence of 1.7-3.3% in literature. Gingival overgrowth can cause aesthetic and functional problems as well as cause hindrance to maintain proper oral hygiene, thereby deteriorating the periodontal condition of the patient. The prevalence of Amlodipine induced gingival overgrowth is poorly defined in our country.
 Aim: This study aims to assess Amlodipine induced gingival overgrowth in a tertiary level referral hospital of Nepal Army.
 Materials and Methods: This study was conducted on hypertensive patients with amlodipine therapy under regular follow up in the Department of Internal Medicine of Shree Birendra Hospital from September to December 2017. The data from record keeping was used for the study. Ethical clearance from Institutional Review committee of Nepal Army Institute of Health Sciences was obtained before conducting the study.
 Results: Out of 507 patients taking amlodipine, 240 were eligible for study and six (2.5%) were found to have amlodipine induced gingival overgrowth. These patients were on a dose of 5-10 mg over six months to 25 years. The gingival overgrowth was correlated with dose and duration which was statistically significant (p<0.05).
 Conclusion: Low prevalence of amlodipine induced gingival overgrowth and correlation with dose and duration was seen in this short-term study. However further large-scale follow-up studies may be required to assess the severity of the problem.

Influence of 3 calcium channel blockers on gingival overgrowth in a population of severe refractory hypertensive patients.

The aim of the current study was to assess the association between 3 different calcium channel blockers (CCBs) (nifedipine, amlodipine and felodipine) and gingival overgrowth in patients with a diagnosis of severe refractory hypertension. One hundred and sixty-two patients with severe refractory hypertension, taking CCBs, were selected. Gingival overgrowth was graded and periodontal measurements were recorded (probing pocket depth, clinical attachment level, plaque index and bleeding on probing). Unconditional multivariable binary logistic regression analyses were performed to assess the association between CCB intake and gingival overgrowth after adjusting for potential confounders. Of the 162 patients, 26 (16.0%) were current smokers and 101 (62.3%) were females. The mean age (SD) was 54.1 (8.5) years and the median age (range) 52.5 (39-78) years. Gingival overgrowth was observed in 55 patients (34.0%). Nifedipine was the most common medication (35.2%; 57 of 162). The results of multiple binary logistic regression showed statistically significant associations between CCB intake (exposure) and gingival overgrowth (outcome) after adjusting for the variables treatment time with antihypertensive and plaque index. Patients with gingival overgrowth were 2.5 (odds ratio=2.46; 95% confidence interval: 1.04-5.82) and 4.0 (odds ratio=3.90; 95% confidence interval: 1.47-10.35) times more likely to be taking nifedipine and amlodipine, respectively, than patients without gingival overgrowth. On the other hand, this significant association was not observed for felodipine. Nifedipine and amlodipine, but not felodipine, were associated with gingival overgrowth in patients with severe refractory hypertension.

Effect of chlorhexidine varnish on gingival growth in orthodontic patients: a randomized prospective split-mouth study.

Introduction: Fixed orthodontic appliances patients suffer limitations on the effective control of biofilm by mechanical methods, bringing the need of a coadjutant in the control of inflammation and oral health improvement. Objective: The aim of this prospective split-mouth blind study was to analyze the effect of a 40% chlorhexidine (CHX) varnish on gingival growth of patients with orthodontic fixed appliances. Methods: Healthy teenage patients with fixed orthodontic appliances and increased gingival volume were recruited (n = 30). Each individual was his own control, having in the maxilla one control side and one treatment side. An application of varnishes occurred on the vestibular area of the upper premolars and first molar crowns, on the control side (placebo varnish) and on the experimental side (EC40(r) Biodentic CHX varnish). The varnishes and sides were randomly chosen and its identification and group was kept by a third party observer and it was not revealed to the researchers and participants until the end of study. In order to establish a baseline registration, digital photographs were taken by a trained photographer before varnish application at baseline (T0), as well as 14 days (T14) and 56 days (T56) after the application. The gingival volume was calculated indirectly using the vestibular areas (mm2) of the upper second premolars' clinical crowns by RapidSketch(r) software, at all study times. The data were analyzed using ANOVA and the Turkey-Krammer test. Results: It was observed, in the final sample of 30 individuals, that at T0, the control and treatment groups were similar. At T14 and T56, a progressive reduction of the clinical crown area was seen in the control group, and an increase in the average area was detected in the experimental group (p < 0,05). Conclusions: The use of 40% CHX varnish decreases the gingival overgrowth in patients undergoing orthodontic treatment. Further studies are necessary to set the action time and frequency of application.

Prevalence of gingival enlargement secondary to calcium channel blockers in patients with cardiovascular diseases - (Retracted)

Aim:The purpose of the present study was to determine the prevalence and extent of gingival overgrowth in patients treated with calcium channel blockers for cardiovascular diseases.Background:Calcium channel blockers are widely used in the treatment of hypertension, vasoplastic angina, and cardiacarrythmias. Gingival overgrowth resulting from the use of calcium channel blockers is of primary concern to dentists. The purpose of the present study is to determine the prevalence and extent of gingival overgrowth in patients treated with calcium channel blockers for various cardiovascular diseases, to assess their periodontal status and to correlate the factors like age, sex, duration, dosage, type of drugs that result in gingival overgrowth.Materials and Methods:A cross-sectional study was done in cardiac patients treated with calcium channel blockers, visiting The Railway hospital, Perumbur, Chennai. Information regarding medical history, type, duration, dosage of medication were recorded and analyzed. The periodontal condition of the patients was assessed using the plaque index, gingival index, calculus index, papillary bleeding index, and extent of gingival overgrowth using appropriate indices. The data was later subjected to statistical analysis.Results:In this study, a total of 213 cardiac patients (145 males and 68 females) who met the inclusion and exclusion criteria were screened. The patients were between 19 and 69 years.Conclusions:From the results of the present study it can be concluded that gingival overgrowth does occur with calcium channel blockers. Elderly males appeared to be more susceptible to the development of drug-induced gingival overgrowth, which was independent of dosage, duration of drug administered but the presence of local factors seemed to aggravate the same.

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.

Interleukin‐6 gene polymorphism in renal transplant patients with and without gingival overgrowth

To determine whether there is an association between genotypes of interleukin-6 (IL-6) and gingival overgrowth in kidney transplant patients. Sixty-three unrelated kidney transplant patients suffering from gingival overgrowth as well 125 control transplant patients without overgrowth were enrolled into the study. Gingival overgrowth was assessed by two independent periodontal specialists at 6 months after transplantation. During the post-transplant period, all patients were given medication, which included cyclosporin A, diltiazem or verapamil, prednisone, and azathioprine. IL-6 polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism assay. In kidney transplant patients suffering from gingival overgrowth mean score of gingival overgrowth was 1.41+/-0.64, whereas in control subjects it was 0.0. Patients with gingival overgrowth induced by immunosuppressive medication were characterized by genotypes similar to the controls distribution of IL-6. There were no significant differences of analyzed genotypes' distribution, i.e. -174G/G, -174G/C and -174C/C between patients with gingival overgrowth 33.3%, 39.7%, 27.0% and without gingival overgrowth 30.4%, 49.6% and 20.0%, respectively. The risk of gingival overgrowth was the highest among patients carrying -174C/C genotype (OR 1.48), but did not differ markedly from the other genotypes, i.e. -174G/G (OR 1.15) and -74G/C (OR 0.67). Similar to genotypes, the distribution of alleles was similar in patients with gingival overgrowth and healthy gingiva. The -174G allele was found in 53.2% and 46.8% of subjects whereas -174C allele was revealed in 46.8% and 44.8% of patients with and without gingival overgrowth, respectively. The evaluated risk of gingival overgrowth in patients with -174G allele was 1.09 versus those with healthy gingiva. The medication regimen administered in both groups of the study was comparable. No association between the IL-6 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered cyclosporin A as a principal immunosuppressive agent.

Risk factors for gingival overgrowth in patients medicated with ciclosporin in the absence of calcium channel blockers

This study investigates the effect of a range of potential risk factors on the severity of gingival overgrowth in transplant patients medicated with ciclosporin in the absence of any calcium channel blockers. One hundred dentate solid organ transplants medicated with ciclosporin (but not calcium channel blockers or phenytoin) were recruited for the study. Demographic, pharmacological and periodontal data were recorded and gingival overgrowth assessed from stone models. Univariate analysis identified the duration of transplant, papilla bleeding index, creatinine serum concentration, azathioprine and prednisolone dosage as risk factors for overgrowth severity. Multivariate modelling, excluding the periodontal parameters, gave a predictive model that included dosages of ciclosporin, azathioprine, prednisolone and weight (p<0.0001, adjusted-R2=19%). Adding the periodontal variables strengthened the model (p<0.0001, adjusted-R2=34.5%). The explanatory models in this study contain a number of variables that moderate inflammation (azathioprine and prednisolone) or are markers of it (papilla bleeding index). Dosage of each of the three immunosuppressants was identified as a risk factor for the severity of gingival change. This observation appears to have been masked by the effects of the calcium channel blockers in earlier studies.

Prevalence and risk of gingival overgrowth in patients treated with diltiazem or verapamil

This study was conducted to determine the prevalence and risk factors for gingival enlargement in patients treated with diltiazem or verapamil. A cross-sectional study was conducted and data from 46 patients actually taking diltiazem or verapamil were compared with 49 cardiovascular controls that never received any of these drugs. All patients were examined for the presence of gingival enlargement using two different indices, the vertical gingival overgrowth (GO) index, and horizontal Miranda & Brunet (MB) index in the inter-dental area. Gingival index, plaque index, and probing depth were also evaluated. The total study population was 95:32 diltiazem-treated, 14 verapamil-treated and 49 cardiovascular control subjects. Gingival enlargement occurred in 31% (GO index) and 50% (MB index) of the patients taking diltiazem. Gingival enlargement in the verapamil-treated group was 21% for the GO index and 36% for the MB index. The prevalence of gingival enlargement was higher in the diltiazem- and verapamil-treated patients than in controls for both indices. The difference between the diltiazem-treated group and control was statistically significant (p=0.022 for GO and p=0.001 for MB), while the difference between the verapamil-treated group and controls was not significant. The risk of gingival enlargement (OR--Odds Ratio) associated with diltiazem therapy was 4.0 (1.2-13.1) for the GO index and of 6.0 (2.1-17.3) for the MB index. When the OR were adjusted for gingival index (GI) values, the risk of gingival enlargement was 3.5 (1.0-12.4) for the GO index and 6.2 (1.9-20.0) for the MB index. In the verapamil-treated group the OR values were not significant. The level of concordance between GO and MB indices in all three groups showed a kappa-value of 0.72 (p<0.001). Patients taking diltiazem are at high risk for gingival enlargement and gingivitis has a stronger effect than the drug treatment on gingival enlargement risk.

P‐glycoprotein drug transporter MDR1 gene polymorphism in renal transplant patients with and without gingival overgrowth

To determine whether there is association between genotypes of drug transporter multidrug resistant (MDR)1 gene coding drug transporter P-glycoprotein and gingival overgrowth in kidney transplant patients. Fifty-four unrelated kidney transplant patients suffering from gingival overgrowth as well 120 control transplant patients without overgrowth were enrolled into the study. Gingival overgrowth was assessed by two independent periodontal specialists at 6 months after transplantation. During the post-transplant period all patients were given medication, which included cyclosporine A, diltiazem or verapamil, prednisone, azathioprine. MDR1 C3435T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism assay. In kidney transplant patients suffering from gingival overgrowth mean score of gingival overgrowth was 1.43 +/- 0.63, whereas in control subjects was 0.0. Patients with gingival overgrowth induced by immunosuppressive medication were characterized by similar distribution of MDR1 genotypes. There were no significant differences of 3435CC, 20.4% and 22.5%, 3435CT, 61.1% and 54.2% and 3435TT, 18.5% and 23.3% genotypes (frequencies) between patients with and without gingival overgrowth. The risk of gingival overgrowth was the highest among patients carrying 3435CT genotype (OD 1.33), but did not differ markedly from the other genotypes, i.e. 3435CC (OD 0.88) and 3435TT (OD 0.75). Likewise to genotypes, distribution of alleles was similar in patients with gingival overgrowth and healthy gingiva. The wild-type allele 3435C was found in 50.9% and 49.6% of subjects whereas the mutated allele 3435T was revealed in 49.1% and 50.4% of patients with and without gingival overgrowth, respectively. The evaluated risk of gingival overgrowth in patients with 3435C allele was 1.06 versus 0.95 in those with healthy gingiva. The medication regimen administered in both groups of the study was comparable. Immunohistochemical studies revealed expression of P-glycoprotein in ducts of the salivary gland. No association between the MDR1 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered cyclosporine A as a principal immunosuppressive agent. Further studies are needed to elucidate the role of P-glycoprotein in drug transport in salivary glands.

Nifedipine pharmacological variables as risk factors for gingival overgrowth in organ-transplant patients.

The prevalence and severity of gingival overgrowth in organ-transplant patients medicated with cyclosporin are greater in patients concomitantly medicated with nifedipine; however, no relationship between the gingival overgrowth and any of the nifedipine pharmacological variables has been demonstrated. The study examined the effect of five nifedipine pharmacological variables (nifedipine dosage, plasma concentration and gingival crevicular fluid concentration, M1 metabolite plasma concentration and the nifedipine: M1 ratio). The effect of the nifedipine variables on the gingival overgrowth score were examined using univariate and multivariate regression analysis. Adjustment for the effect of other risk factors was made by adding the distribution of each of the nifedipine variables in turn to a stepwise regression model containing previously identified risk factors for this condition. Despite the high levels of nifedipine sequestered in the GCF, only the plasma concentration of nifedipine was identified as a risk factor for the severity of gingival overgrowth in these patients (P = 0.01) once adjusted for other known risk factors (R2 for the model = 55%).

Regulation of human gingival fibroblast growth and synthetic activity by cyclosporine‐A in vitro

Gingival overgrowth is an adverse side-effect seen in a proportion of patients taking cyclosporin-A which indicates that cyclosporine-A may modulate the activities of cells other than T lymphocytes. Therefore, the effect of cyclosporine on human gingival fibroblasts has been studied in vitro. Cyclosporine-A was found to stimulate DNA synthesis and the proliferative activity of these cells with maximal stimulation noted at a concentration of 10(-9) g/ml. Although this stimulation was most noticeable in the presence of 10% fetal calf serum, proliferation still occurred in serum-free medium. In the presence of lipopolysaccharide, at a concentration which normally inhibits gingival fibroblast proliferation, cyclosporine retained its capacity to stimulate proliferative activity. Fibroblasts isolated from overgrown gingival tissue responded to a greater extent than those isolated from a healthy site from the same individual. This stimulatory effect was not restricted to gingival fibroblasts, since human foreskin fibroblasts responded in a similar fashion. Cyclosporine-A did not significantly alter protein or proteoglycan production by these cells. These responses are considered to reflect the in vivo response of gingival overgrowth in patients taking cyclosporine-A. The reversal of lipopolysaccharide inhibition of gingival fibroblast proliferation by cyclosporine-A may explain, in part, why gingival overgrowth is most prominent in areas of heavy dental plaque accumulation.

Phenytoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin do not alter the effects of bacterial and amplified plaque extracts on cultures of fibroblasts from normal and overgrown gingivae.

Local irritation of gingival tissue by plaque is among the factors which affect development of gingival overgrowth in patients undergoing chronic phenytoin (PHT) therapy. Variability in the cytotoxicity of plaque components or of plaque substances plus PHT and/or its metabolites toward gingival fibroblasts may relate to whether gingival overgrowth forms in a particular patient. Fibroblasts from healthy and overgrown gingivae were incubated with (a) PHT and its major human metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), (b) microbial and "amplified" plaque extracts, and (c) microbial and "amplified" plaque extracts plus PHT and HPPH. Cell numbers and cell-associated protein were determined for each incubation preparation. A wide range in cytotoxic response to a particular microbial or plaque extract occurred among cell strains. Plaque extracts from different subjects had variable cytotoxicity toward a cell strain. The differences among fibroblast strains in response to an extract and the variability in cytotoxicity of different plaque extracts toward a cell strain were not related to their source from normal or overgrown gingivae. Cell numbers and cell-associated protein were similar for incubation mixtures containing extracts with and without PHT and HPPH. These data do not show differences among cytotoxicity levels of plaque extracts, the response of particular gingival fibroblast strains to plaque components, or interaction between drugs and certain plaque samples which explain development of gingival overgrowth in some subjects receiving chronic PHT therapy.