[Proper oral health can protect from developing gingival hyperplasia induced by calcium channel blockers]. / A megfelelo szájegészség megvédhet a kalciumcsatorna-blokkoló készítmények okozta gingivahyperplasia kialakulásától.

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.

Calcium channel blocker-induced gingival enlargement.

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.

Cathepsin B, D, and L regulation in cyclosporin A-mediated gingival hyperplasia of a patient with sarcoidosis.

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.

Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children.

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.

[Oral cavity changes in patients after kidney transplantation and preventive-treatment algorithms]. / Zmiany chorobowe w jamie ustnej u pacjentów po transplantacji nerki i algorytmy postepowania profilaktyczno-leczniczego.

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.

Poor oral hygiene enhances gingival overgrowth caused by calcineurin inhibitors.

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.

Upregulation of heme oxygenase-1 expression in gingiva after cyclosporin A treatment.

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.

Roxithromycin reduces cyclosporine-induced gingival hyperplasia in renal transplant patients.

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.

Gingival hyperplasia around implants in the maxilla and jaw reconstructed by fibula free flap.

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.

Levantamento das biopsias da cavidade oral realizadas no Hospital Universitário - Unidade Presidente Dutra-UFMA da cidade de São Luís - MA, no período de 1992 a 2002 / Survey oral cavity biopsies in the University Hospital(UFMA)- Presidente Dutra's Unity, in São Luis, During the periodo of 1992 -2002

O objetivo deste trabalho foi realizar um levantamento das lesões orais do Hospital Universitário - Unidade Presidente Dutra, da UFMA, no período de 1992 a 2002, sendo analisadas 295 fichas clínicas com seus respectivos laudos de diagnóstico histopatológico. Foram avaliadas a freqüência das lesões orais examinadas, a localização anatômica e a distribuição das mesmas quanto ao tipo, sexo e idade. Cada caso foi classificado em onze diferentes grupos, apresentando-se número e índice percentual das lesões de maiores ocorrências. Os resultados demonstraram um predomínio das lesões proliferativas não neoplásicas, com sessenta casos; a hiperplasia fibrosa inflamatória representou a entidade mais comum, sendo o sexo feminino mais envolvido e na primeira década de vida ocorreu um maior percentual de casos

Drug-induced fibrosis: interference with the intracellular collagen degradation pathway.

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.

Effect of tranilast on matrix metalloproteinase-1 secretion from human gingival fibroblasts in vitro.

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.

Severe gingival bleeding in a myelodysplastic patient: management and outcome.

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.

Manipulation of the peri-implant tissue for better maintenance: a periodontal perspective.

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.

Orofacial granulomatosis with gingival onset.

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.

Reduction of cyclosporine-induced gingival overgrowth following a change to tacrolimus. A case history involving a liver transplant patient.

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 importance of periodontal evaluation in orthodontics]. / De l'importance de l'évaluation parodontale en orthodontie.

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.