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Cardiovascular diseases including hypertension affect 40% of the adult population in Hungary. Calcium channel blockers are frequently prescribed for the treatment of hypertension either in monotherapy or in fixed-combination therapy. Their main effect is vasodilatation with gingival hyperplasia as a side effect. Our aim is to draw our colleagues' attention to the practical importance of the fact that calcium channel blocker-induced gingival hyperplasia correlates closely with the dental status and the quantity of plaque on the surface of teeth and dental implants. Once established, gingival hyperplasia makes it more difficult for the patient to maintain individual tooth cleaning and increases plaque formation. Thus proliferation of Gram-negative bacteria is enabled in the plaque which promotes gingival overgrowth and can pose a risk factor for further cardiovascular diseases. If proper individual oral hygiene and professional interventions are carried out, healthy and hyperplasia-free gingival state can be sustained in the long term in most cases, even with calcium channel blocker therapy. In order to protect patients' oral health, a closer cooperation of internists and dentists would be desirable. Orv Hetil. 2018; 159(29): 1183-1187.

Despite the popularity and wide acceptance of the calcium channel blockers (CCBs) by the medical community, their oral impact is rarely recognized or discussed. CCBs, as a group, have been frequently implicated as an etiologic factor for a common oral condition seen among patients seeking dental care: drug-induced gingival enlargement or overgrowth. This enlargement can be localized or generalized, and can range from mild to extremely severe, affecting patient's appearance and function. Treatment options for these patients include cessation of the offending drug and substitution with another class of antihypertensive medication to prevent recurrence of the lesions. In addition, depending on the severity of the gingival overgrowth, nonsurgical and surgical periodontal therapy may be required. The overall objective of this article is to review the etiology and known risk factors of these lesions, their clinical manifestations and periodontal management.

Objective: Gingival overgrowth is an important adverse effect of phenytoin (PHT) therapy, occurring in about half of the patients. This study aimed to evaluate the effect of oral folic acid supplementation (0.5 mg/day) for the prevention of PHT-induced gingival overgrowth (PIGO) in children with epilepsy aged 6-15 years on PHT monotherapy for 6 months., Methods: This was a randomized, double-blind, placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009. Children aged 6-15 years started on PHT monotherapy within last 1 month were eligible for inclusion. Preexisting gingival overgrowth, use of other folic acid antagonists, and macrocytic anemia were exclusion criteria. Trial subjects were randomized to receive either folic acid or placebo. The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy. The trial was registered with clinicaltrials.gov (NCT00781196)., Results: A total of 120 children were recruited, 62 and 58, respectively, in folic acid and placebo arms. The 2 arms were comparable at baseline. Twenty-one percent of patients in the folic acid arm developed PIGO, as compared with 88% receiving placebo (p < 0.001). Absolute risk reduction of PIGO by folic acid was 67% (95% confidence interval 54%-80%), and relative risk reduction was 0.76., Conclusions: Oral folic acid was found to decrease the incidence of PIGO in children on PHT monotherapy, in a statistically significant and clinically relevant manner., Classification of Evidence: This study provides Class I evidence that folic acid supplementation, 0.5 mg/day, is associated with prevention of gingival overgrowth in children taking PHT monotherapy.

Background: Cyclosporin A (CsA) is an immunosuppressant with side effects including gingival hyperplasia. Sarcoidosis is a systemic disease characterized by granulomas. Here, we report on a rare case of sarcoidosis with gingival hyperplasia to clarify whether clinical observation corresponds to in vitro results., Methods: Gingival fibroblasts (HGFs) were isolated from healthy gingiva and cultured with CsA. Total RNA was collected and expression of mRNAs examined using semi-quantitative RT-PCR analysis. Cathepsin B, D, and L expression in overgrown gingiva of the patient was examined by immunohistochemistry., Results: Cathepsin D, L, and vascular endothelial growth factor (VEGF)165 mRNA were markedly suppressed in CsA-treated HGFs, whereas cathepsin B, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA were not reduced. Next, the decrease of cathepsin B and L expression in enlarged gingiva was observed, whereas an increase of cathepsin D expression was observed. Clinically, the enlarged gingival lesions were fully resolved by performing oral infection control., Conclusions: Cathepsins regulation might be an important factor in the development of CsA-mediated gingival hyperplasia.

Kidney transplantation is the best option of treatment for patients with end-stage renal failure. However, following kidney transplantation many stomatological abnormalities are frequently reported. It is mainly due to immunosuppressive therapy and subsequent impaired immune response. There is an increased risk of infections and malignancies. The most frequent findings in the oral cavity include: aphthae, erosions of bacterial, viral and fungal origin, lichen-like or leukoplakia-like changes. The another type of change is gingival hyperplasia and its periodontologial consequences. In this review etiology, clinical symptoms of periodontological changes are described together with algorithm of pre- and posttransplant management of oral healthy is provided.

Aim: To estimate the prevalence of gingival overgrowth in kidney allograft recipients in southern Switzerland and to determine the factors associated with it. We hypothesized that poor oral hygiene was a risk factor., Methods: We assessed the level of oral hygiene among renal transplant patients and determined whether a good level of information and regular dental checkups in addition to good oral hygiene could prevent gingival hyperplasia. Seventy-six adults who had undergone kidney transplantation were examined. The level of oral hygiene, gender, age, time elapsed from transplantation, medication and dose were recorded., Results: In general the level of oral hygiene was average. We found a significant association between the severity of gingival overgrowth and the level of oral hygiene. No statistical relationship between gingival hyperplasia and the other recorded variables was detected. Patients on tacrolimus had a tendency to have less gingival hyperplasia. Patient education, along with regular dental checkups and a good level of oral hygiene, should prevent gingival hyperplasia or maintain it at an acceptable level., Conclusion: Intensive motivation of patients to maintain good oral hygiene is necessary to reduce the incidence of gingival hyperplasia.

Background: Heme oxygenase (HO)-1 is a stress-inducible protein that confers cytoprotection, but its role in gingiva during cyclosporin A (CsA) therapy is unknown. We used in vivo and in vitro models to investigate the expression of mRNA and protein for HO-1 in gingiva upon CsA treatment., Methods: Twenty-six male Sprague-Dawley rats were assigned to two groups after the establishment of edentulous ridges. Rats in the CsA group received CsA, 30 mg/kg/day for 4 weeks, whereas control rats received mineral oil only. All rats were killed after 4 weeks, and the edentulous gingivae were excised. mRNA and protein expression of HO-1 in gingivae were determined using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), respectively. For the in vitro study, cultured human gingival fibroblasts were harvested after treatment with various concentrations of CsA, and HO-1 mRNA and protein expression were determined using RT-PCR and Western blotting, respectively., Results: Mean gingival HO-1 mRNA expression was greater in the CsA group than in the control animals (P = 0.076). IHC staining for HO-1 protein was significantly greater in the gingivae of CsA-treated rats than in those of the control group. In fibroblast cultures, expression of HO-1 mRNA and protein also increased significantly after CsA treatment., Conclusion: CsA upregulates the gingival expression of HO-1, which may exert a cytoprotective effect.

Gingival overgrowth (GO) is a common side effect of chronic cyclosporine use. The average prevalence of GO is about 30%, ranging from 10% to 85% in various series, due to diverse aggravating risk factors: drug interactions with calcium channel blockers, age, cyclosporine dose, bacterial plaque, and genetic predisposition. Recent studies have demonstrated elevated levels of specific cytokines particularly transforming growth factor-beta (TGF-beta) in hyperplastic gingival tissue, suggesting that this growth factor plays a role in the accumulation of the extracellular matrix. Until recently treatment for this complication was only surgical. Nowadays, several studies have been performed to evaluate the effects of antibiotic treatment on the regression of GO. In the present study, we used roxithromycin, a macrolide antibiotic that has inhibitory effect on TGF-beta production by inflammatory cells. The results suggested that roxithromycin may be an important therapeutic tool to reduce cyclosporine-induced GO.

A recurring problem during prosthetic rehabilitation following reconstruction by means of a vascularized fibula flap, after ablation of tumors affecting the facial skeleton, is the hyperplastic granulomatous reactive tissue that forms around the prosthetic abutments of the implant. The features of this phenomenon seem to be directly related to the characteristics of the peri-implant tissue and to the material from which the prosthetic abutments are manufactured. Two main ways of avoiding this are proposed. 1) Skin grafts around implants seem to inhibit the overgrowth of granulomatous tissue. 2) Acrylic provisionals should be avoided and substituted with complete metal-ceramic restoration.

Drug-induced fibrosis and overgrowth of the extracellular matrix are high prevalence lesions of the oral mucosa. Drugs, such as dilantin, cyclosporin A and nifedipine can cause the gum tissues to overgrow, thereby preventing normal mastication and promoting infection. The causes of these disorders are poorly understood but recent evidence suggests that a common pathway targeted by these three drugs is the regulation of the intracellular pathway of collagen degradation. In this review, recent data that implicate calcium deregulation of the critical actin-dependent binding step of collagen phagocytosis will be discussed. These new insights highlight the need for a greater choice of medications for the treatment of transplant rejection and epilepsy to reduce the side effect of gingival overgrowth.

Background: Some drugs such as phenytoin, calcium blockers, or cyclosporins are known to cause gingival fibrous hyperplasia, an unwanted side effect. Decreased collagen catabolism in overgrown gingival tissue has been proposed as one of the reasons causing the disease. The effect of tranilast, which suppresses collagen synthesis and cell proliferation, on matrix metalloproteinase (MMP-1) secretion from human gingival fibroblast, was studied in vitro., Methods: Human gingival fibroblasts were cultured from specimens taken from healthy, periodontal, and overgrown gingival tissues. The effects of tranilast on cell proliferation and MMP-1 secretion from gingival fibroblast were assessed. Inhibitory effect of transforming growth factor (TGF)-beta secretion from gingival fibroblast by tranilast was also evaluated., Results: Tranilast did not interfere with cell proliferation at the low concentrations. MMP-1 concentration significantly increased at the lower doses of tranilast up to about 2-fold compared to controls (P < 0.05). In contrast, higher doses of tranilast significantly decreased activity to 30% and 20%, respectively. MMP-1 secretion was inhibited significantly by phenytoin, nifedipine, and cyclosporin A and the depressed MMP-1 recovered to the control level with tranilast. The amount of secretion from normal and periodontitis gingival fibroblast specimens did not differ, but that from the overgrown gingiva was significantly less than the other types. Moreover, TGF-beta secretion was significantly inhibited by 300 microM of tranilast., Conclusions: Tranilast upregulates the expression of type 1 collagenase suppressed by gingival overgrowth-inducing drugs, and inhibits TGF-beta secretion from gingival fibroblasts. Therefore, tranilast could be considered as an agent for controlling gingival over-growth.

Background: The myelodysplastic syndromes (MDS) are a group of stem cell disorders characterized by a reduction in one or more elements of the peripheral blood. Oral manifestations of the disease and oral complications of medical management may result in significant symptoms and have an impact on the systemic condition of the patient. The removal of the infectious focus, such active teeth infection or severe periodontal disease, remains controversial in these patients, due to the increased risk of bleeding and systemic infection., Methods: This paper reports a case of MDS with spontaneous gingival hemorrhage and generalized gingival hyperplasia associated with periodontal disease. This patient underwent several platelet transfusions due to these oral complications. The patient received periodontal therapy, resulting in an improvement of the oral clinical situation and a decrease of gingival hyperplasia., Results: The patient did not present any episode of gingival hemorrhage after the periodontal treatment., Conclusion: The results of this study suggest that periodontal therapy should be performed in MDS patients presenting thrombocytopenia, gingival hyperplasia, and gingival bleeding, with the intent of preventing further hemorrhagic episodes and possible systemic infection.

Enhancement of peri-implant soft tissue is an essential factor in implant survival. As in periodontal tissue, the integrity of the attached gingiva, plus gingival contour, color, shape, size, consistency, and bleeding upon probing, is an indicator of bacterial activity that will eventually lead to gingivitis and periodontitis. The trajectory of peri-implant tissue is different from that of periodontal tissue because of periodontal ligament fibers, the absence of which makes the implant-bone interface weaker than that of natural dentition. The destruction of peri-implant tissue can be a faster and more devastating process, so maintenance of the peri-implant tissue is a must in implant therapy to avoid a potentially massive destruction of the understructure. The treatment of inadequately attached gingiva, gingiva hyperplasia, and peri-implant gingivitis is discussed with techniques that can alleviate these problems.

Background, Aims: Orofacial granulomatosis (OFG) is a descriptive term used for granulomatous disorders of the face and oral cavity that may occur for a variety of reasons, some of which result in significant morbidity and mortality. Although rarely, a granular enlargements of the gingiva may be the first clinical manifestation of OFG, preceding other local or systemic manifestations., Method: We will report a case of OFG that showed an atypical and monosymptomatic onset with a generalized hyperplastic gingivitis that preceded other facial and mucosal features by several weeks., Result: Considering the variable clinical onset of OFG and its apparent increase in incidence, we emphasize that in some cases, the periodontologist, as first consulted health care professional, plays an important role to detect this disorder. Early diagnosis of OFG is a crucial step to prevent and cure its unsightly sequelae and sometimes avoid progression of systemic potentially life-threatening OFG-related diseases., Conclusion: Thus, when none of the common causes of gingival enlargement can be detected, OFG diagnosis should be suspected.

During immunosuppression with cyclosporine, gingival overgrowth, a minor secondary effect, may appear in the first weeks of treatment. In certain cases it may affect the function and/or esthetic appearance in a manner intolerable to the patient. A new immunnosuppressive molecule, tacrolimus, presently used as a treatment of second choice to control acute corticoresistant rejection, may bring oral comfort to these patients, since it reduces gingival overgrowth to negligible levels.

The orthodontist is in fact a periodontal-therapist since his aim is to move the teeth with and through the periodontal tissues. It is most important for the orthodontist to be able to determine at the initial clinical examination what are the various periodontal risk factors. When the pathology is obvious with inflammation, periodontal pockets, gingival hyperplasia, edema of the papillae, gingival recessions, the need for periodontal treatment is manifest. But many times, the periodontal evaluation is complicated by the presence of slight variations of the quality of the marginal tissue that represent a risk of developing periodontal defects during the orthodontic treatment. The aim of this presentation is to put forward the importance of the periodontal evaluation during the initial examination of the patient so that, if necessary, an adequate periodontal therapy can be initiated to stabilize the periodontal tissues and thus improves the esthetical outcome.

Patients with nifedipine-induced gingival hyperplasia (GH) often require continued calcium channel blocker therapy. Switches to diltiazem and verapamil have been described; however, these drugs are of a different chemical class and present therapeutic limitations in some patients. The purpose of this study was to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine derivative with a low incidence of GH. Fourteen patients with nifedipine-induced GH were given a medical exam and a periodontal exam. The following parameters were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT), plaque index (PI), and gingival index (GI). Intraoral photographs, study models, and a gingival biopsy for histological examination were taken. Following baseline measures, patients were randomized to continued treatment with nifedipine or an equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected to receive 4 weeks of open label isradipine therapy, with biweekly examination continuing through the open label phase. The isradipine treatment arm showed a mean decrease in PD of 0.59 mm at week 8 (P < 0.05). No other measured parameter (GM, GT, PI, GI) was significantly changed, compared either to baseline or to the alternate treatment arm. Clinically, 60% of patients treated with isradipine exhibited a decrease in hyperplasia, while 66% of patients treated with nifedipine demonstrated an increase in hyperplasia, a significant difference (P < 0.05). When combined with open label data, patients switching therapy to isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an increase in gingival overgrowth. All patients exhibited adequate control of hypertension. We conclude that in hypertensive patients with nifedipine-induced GH, switching hypertensive therapy to isradipine may result in a regression of GH. When coupled with aggressive oral hygiene treatment, this drug may provide a reasonable option for patients requiring dihydropyridine treatment.

Purpose: Conventional preprosthetic procedures have typically focused on improvement of denture base stability and retention and have ignore patients' concerns about facial appearance and articulation difficulties. Soft tissue procedures have been developed, combined with insertion of the transmandibular implant (TMI) system through a submental incision, for functional and cosmetic reconstruction of the lower face to improve speech and facial esthetics, and prevent gingival hyperplasia along the lateral posts of the implant., Patients: The surgical procedure was evaluated in 146 patients with slight, moderate, severe, and extreme mandibular atrophy classified according to the proportion of muscle origin loss on the edentulous mandible. Preoperative, 3-month, and 1-year postoperative full-face and profile photographs were taken. Patients also were questioned about their satisfaction with their facial appearance and speech at these intervals. Gingival hyperplasia along the TMI posts was scored as present or absent., Results: Satisfaction with the soft tissue reconstruction in 146 patients treated according to this protocol was high, with almost every patient describing the positive comments they had received from their friends and relatives. Postoperatively, none of the patients requested a temporary denture to use during the 12-week incorporation period, although this was a common cosmetic and speech concern preoperatively. Gingival hyperplasia secondary to muscle pull was controlled satisfactorily., Conclusions: With the described technique for placement of the TMI system, not only is masticatory function improved, but also the lower third soft tissues of the face are functionally and cosmetically reconstructed to the satisfaction of the patients.

Gingival hyperplasia is a common disorder associated with phenytoin and cyclosporine therapy. However, induction of this condition by calcium channel blockers is less well known. Inflammation of the gingival tissue from bacterial plaque and the subsequent development of gingival crevicular fluid may allow sequestration of the calcium channel blocker, thus predisposing the tissue to a localized toxic effect and the development of gingival hyperplasia. Calcium channel blockers have cellular effects similar to those of phenytoin and cyclosporine, including the production of a localized folic acid deficiency. All of the available calcium channel blockers have been reported to cause gingival hyperplasia. Treatment options include meticulous plaque control, and in severe cases, gingivectomy. Gingival hyperplasia can be prevented with meticulous plaque control or avoidance of the offending medication.

Nifedipine increases the frequency and severity of gingival hyperplasia associated with CyA therapy in renal transplant recipients and this effect appears to be independent of whole-blood CyA levels. De novo malignancies have been reported arising in areas of gingival hyperplasia, in a group already at high risk of malignancy. Patients receiving CyA and nifedipine should receive advice regarding the need for strict oral hygiene to control the initial development of gingival hyperplasia, with severe cases being promptly referred for gingivectomy and histological examination.

Gingival enlargement due to the immunosuppressive drug, cyclosporin A (CsA), will resolve following discontinuation of drug therapy or extraction of adjacent teeth. This report presents a clinical observation on a patient in whom CsA-induced gingival enlargement failed to resolve with improved plaque control and scaling, but resolved quickly following reduction in the daily dosage of CsA. Despite less than optimal plaque control, the CsA-induced gingival enlargement did not recur on the reduced drug dosage over a 2-year observation period. This finding raises the possibility that reduction of CsA dosage below a certain critical level may lead to resolution of CsA-induced gingival enlargement.

The purpose of the present study was to investigate, on a longitudinal basis, the effectiveness of a specific preventive dental program for patients who are taking phenytoin for seizure control. The results confirm that a preventive dental program, consisting on frequent prophylaxis and plaque control, is effective in minimizing clinically gingival enlargement associated with phenytoin therapy, even in patients who present histological aspects of gingival hyperplasia.

This study examined the effect of folic acid supplementation on the recurrence of phenytoin-induced gingival overgrowth following gingivectomy. 8 residents of an institution for the developmentally disabled were randomly assigned to a treatment (N = 4) or control (N = 4) group. Subjects in the treatment group received an oral supplementation of 5 mg of folic acid daily during the study; those in the control group did not. A gingivectomy with an external beveled incision made to the crest of the alveolus was completed by quadrants. The following data were obtained prior to gingivectomy, 2 weeks following the last quadrant of surgery, and at 3 and 6 months post-surgery: plaque and gingival index scores, red blood cell folic acid levels, free phenytoin blood levels, photographs, and impressions. % change in overgrowth was determined from cross-sectional area measurements made on dies obtained from bucco-lingual cuts on stone models. Differences across time between and within groups were tested by a two-factor repeated measure analysis of variance. The groups did not differ in plaque and gingival index scores or free phenytoin blood levels. The treatment group had significantly higher red blood cell folic acid levels (p less than or equal to 0.0001). Reduction in gingival overgrowth as a result of surgery was similar in both groups. Although the treatment group had significantly less recurrence of gingival overgrowth (p less than or equal to 0.05), the mean differences amounted to only 6-7% at 3 and 6 months.

Recent advances in surgical technique and chemotherapeutic procedures have greatly increased the survival rates of organ transplantation patients. Of dental importance is the widespread use of the immunosuppressive agent cyclosporine in this special-patient population, a drug that has the potential to cause severe gingival hyperplasia as a side effect. A case is presented illustrating the use of the plaque-inhibitor chlorhexidine as a therapeutic adjunct in possibly arresting this gingival condition.

Cyclosporine is a relatively new immunosuppressive agent which has been used successfully to prevent organ transplant rejection, to treat type-I diabetes mellitus as well as several other autoimmune disorders. It is anticipated that the therapeutic use of cyclosporine will progressively increase in the future to include the treatment of numerous other disorders. As its clinical use broadens, more health professionals will need to become familiar with the beneficial effects as well as some of the undesirable side-effects of cyclosporine therapy. Two side-effects of the drug which are of interest to the periodontist are gingival hyperplasia and transient perioral hyperaesthesia. It is anticipated that the dental profession, particularly periodontists, will be called upon to help prevent, control or treat these side effects. The purpose of this paper is to familiarize the periodontist with cyclosporine and to discuss its anticipated impact on the practice of periodontics.

The purpose of this clinical study was to evaluate the effect of a 3-min daily toothbrushing with 1% chlorhexidine gluconate toothpaste on dental plaque, gingivitis and gingival hyperplasia in 30 mentally retarded epileptic children treated with phenytoin. A double-blind cross-over technique was used. Brushing once daily for 2 months with 1% chlorhexidine gluconate toothpaste resulted in significantly lower Pl I and G I values. Gingival hyperplasia was not significantly reduced by the use of the chlorhexidine toothpaste.

The effect of a plaque control program on the development of phenytoin(PHT)-induced gingival overgrowth was studied in 16 epileptic children, 8-16 years of age during a 2-year longitudinal study. The parameters studied were: visible plaque index (VPI), gingival bleeding index (GBI), probing depth and gingival overgrowth. A preventive program was instituted before the start of the PHT-medication and included oral hygiene instruction and frequent professional tooth cleaning during the observation period. When gingival overgrowth was evaluated on the basis of probing depth, no patients on PHT therapy for 2 years developed pseudopockets (greater than or equal to 4 mm). During the 2-year observation period, there was a statistically significant increase (p less than 0.01) in the thickness of the marginal gingiva bucco-lingually in all patients. This gingival enlargement was already evident (p less than 0.01) after 1 month. The degree of gingival enlargement in this patient group did not increase significantly after the 1st year of PHT-medication and was not significantly correlated to the plasma concentration of PHT. The results of this study show that the development of PHT-induced gingival overgrowth could not be prevented by this specific plaque control program.

Gingival overgrowth frequently occurs in patients medicated with phenytoin (5,5-diphenylhydantoin) to control epileptic seizures. In a recent study, gingival overgrowth was observed in a patient in an experimental group evaluating an automatic toothbrushing system for severely disabled patients. During the evaluation period, which included an oral hygiene regimen provided by an attendant or housemate and a regimen with the Mississippi Dental Care System (MDCS), the patient's gingival overgrowth was noticeably reduced. The results of this study indicate that control of local factors with the MDCS is significantly better than the routine home care regimen, and that the phenytoin-associated gingival overgrowth in this patient was reduced by MDCS.