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PubMed1977

Familial gingival fibromatosis associated with progressive deafness in five generations of a family.

Gingival hyperplasia may be inherited in a variety of ways, usually in an autosomal dominant or autosomal recessive manner. Additional phenotypic abnormalities are frequently associated with the gingival hyperplasia. To our knowledge, the family described here represents the first instance of autosomal dominantly inherited gingival hyperplasia associated with progressive neural hearing loss.

Adult↗

PubMed2002

Effect of nifedipine on the expression of p53 protein in rat gingiva.

The aim of the present study was to determine the profile of p53 protein expression in gingival tissues after treatment with nifedipine in rats. Rats were treated daily by gastric intubation with or without DMSO alone or DMSO-dissolved nifedipine at concentrations of 15, 30 or 60 mg/kg body weight for 1, 3 or 6 week(s). Gingival width and height were measured macroscopically. Monoclonal antibodies recognizing both wild-type and mutant p53 protein were applied on paraffin-embedded gingival sections using microwave pretreatment and immunohistochemical methods. The gingival width and height were increased in the animals treated with nifedipine at concentrations of 30 and 60 mg/kg body weight. Increased gingival width and height were already seen in the animals treated with 60 mg of nifedipine for 1 week, whereas treatments with 30 mg of nifedipine resulted in increased gingival width and height after treatment for at least 3 weeks. The expression of p53 protein was elevated in the animals treated with 30 or 60 mg of nifedipine. Treatments with nifedipine at the concentration of 60 mg/kg body weight for 1 week induced the expression of p53 protein in the gingival tissues. Treatment with nifedipine in rats led to the inducement of gingival hyperplasia and increase in the numbers of p53-positive gingival epithelial cells by a dose and frequency dependent mechanism, suggesting that p53 protein may play a crucial role in the regulation of nifedipine-induced gingival hyperplasia.

Animals↗

PubMed2004

Differences in patient and transplant professional perceptions of immunosuppression-induced cosmetic side effects.

BACKGROUND: A two-part study was initiated to compare kidney transplant patient and transplant professional perceptions regarding immunosuppression-related physical changes and their impact on transplant recipients. METHODS: Parallel surveys were developed and administered to transplant patients and active transplant clinicians. RESULTS: Eighty percent of surveyed patients reported immunosuppression-induced hirsutism, gingival hyperplasia, acne, alopecia, or cushingoid facies. Hirsutism (94%) and gingival hyperplasia (51%) occurred more frequently in cyclosporine patients (p < 0.01); alopecia (30%) occurred more frequently in tacrolimus patients (p < 0.01). Patient reported incidence of physical changes significantly exceeded observations by professionals for every condition (p < 0.01), however 84.4% of affected patients reported feeling "happy to endure" changes "for the sake of having a transplant." Patients also reported emotional and social effects due to physical changes, an outcome underestimated by transplant professionals (p < 0.01). Patients and professionals communicated about physical changes; however, more than half of affected patients believed communication occurred "rarely/never" while over half of the professionals believed communication occurred "every visit/most of the time." Although most physicians believed changes could be addressed, doctors recommended treatment for less than half of the affected patients. When recommended therapy changes were pursued, treatments were effective in the majority of cases. CONCLUSIONS: Incidence of immunosuppression-related physical changes is high and somewhat dependent on drug regimen. Although patients seem willing to accept cosmetic changes for the sake of having a transplant, physical changes have a psychosocial impact that is underestimated by clinicians. Immunosuppression-related physical changes remain underaddressed; effective interventions offer opportunities for improved care.

Alopecia↗

PubMed1996

Functional and cosmetic reconstruction of the facial lower third associated with placement of the transmandibular implant system.

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.

Adipose Tissue↗

PubMed2002

Oral mucosa alterations induced by cyclosporin in mice: morphological features.

BACKGROUND AND OBJECTIVE: The mechanisms involved in the pathogenesis of cyclosporin A-induced gingival hyperplasia are not well understood. The present work aimed at developing a mouse model with the characteristics of the human process, i.e. time of appearance, dose dependency and the capacity of developing in a variety of genetic backgrounds. This model would present the advantages of using a very well known animal species, small and easy to handle, with a number of experimental reagents (antibodies, etc.) already available against its products. METHODS: Three different strains of mice were used: CBA, F1(C57Bl x DBA), Balb/c. Groups of mice received different concentrations of cyclosporin A (CSA) (10 mg/kg, 25 mg/kg and 40 mg/kg body weight) intraperitoneally five times a week. Anatomical and histological alterations were recorded at various time intervals. RESULTS: All strains of mice presented gingival hyperplasia after 8 weeks of CSA treatment. A dose-dependency was observed with regard to the time of first appearance of alterations. Increased redness was seen in all animals at the sixth week, independent of the dosage used. Histologic examination exhibited increased vascularization, epithelial and connective tissue thickening, edema and a mononuclear infiltrate. CONCLUSIONS: It was possible to develop CSA-induced gingival hyperplasia in mice with the characteristics described in humans and other species. The use of this animal model may help in the elucidation of the process involved in CSA-induced gingival overgrowth.

Animals↗

PubMed2000

Impact of cyclosporin A pharmacokinetics on the presence of side effects in pediatric renal transplantation.

Cyclosporin A (CsA) is a potent immunosuppressant that has many side effects, including hypertrichosis, gingival hyperplasia, and tremor. To evaluate whether there is a relationship between the CsA-pharmacokinetics (PK) and these side effects, their presence and intensity were observed in 46 renal transplanted children/adolescents during two regular visits, and the occurrence of the side effects was correlated with CsA-PK. CsA doses had been unchanged for at least 6 mo. CsA blood concentrations were measured at time 0, and 1, 2, and 4 h after the CsA morning dose. An abbreviated area under the curve (AUC) was calculated using C0, C2, and C4. Hypertrichosis positively correlated with C2, C4, Cmax, and AUC. An AUC > or = 4158 ng/ml per h was the best predictor for the presence of hypertrichosis. Tremor was also positively correlated with C2, Cmax, and AUC. A Cmax > or = 878 ng/ml was the best predictor for the appearance of tremor. These values of Cmax and AUC are within the therapeutic range of CsA as demonstrated by the studies of calcineurin inhibition by CsA. Gingival hyperplasia was not associated with any of the CsA-PK studied parameters. However, it was associated with the concomitant use of nifedipine. These data show that there is a correlation between the CsA side effects and its pharmacokinetics and that it is possible to decrease the incidence and intensity of such side effects by monitoring the CsA-PK parameters, providing they are under or at the proposed cutoff levels. Nifedipine should also be avoided to reduce the presence of gingival hyperplasia.

Adolescent↗

PubMed2003

An unusual oral chronic graft-versus-host disease-like syndrome following a liver transplant.

BACKGROUND: Giving the immunosuppressive drug tacrolimus (FK506) to liver transplant patients has helped to considerably reduce oral side effects such as gingival hyperplasia. Patients taking cyclosporin who suffer from gingival hyperplasia are often switched to tacrolimus. METHODS: We present here a pediatric liver transplantation case study. The patient has been followed for 5.5 years. She developed oral lesions that resulted in the immunosuppressive therapy being changed from tacrolimus to cyclosporin. In clinical terms, the atypical pathology consisted of hyperpigmented patches on the gingival margin, the internal surfaces of the cheeks, and the intraoral surfaces of the lips. When located on the lips, the hyperpigmented patches were associated with pruriginous and edematous lesions. RESULTS: Optical and electronic microscopic examinations of a gingival tissue sample revealed the presence of melanin incontinence and lichenoid lesions with degenerated keratinocytes and a mild infiltrate of lymphocytes. This points to a chronic graft-versus-host disease (cGvHD)-like syndrome linked to tacrolimus. This diagnosis was given further credence by improvement in the lesions following the switch to cyclosporin. CONCLUSION: To our knowledge, this is the first reported case of tacrolimus-associated chronic GvHD-like syndrome occurring in the oral mucosa.

Chronic Disease↗

PubMed1978

Oral use of chlorhexidine gluconate toothpaste in epileptic children.

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.

Administration, Oral↗

PubMed1991

[Periodontal side effects of the immunosuppressant cyclosporin A. Clinical study].

Gingival hyperplasia caused by the immunosuppressant cyclosporin A seems to be another variant of pharmacologically induced gingival enlargements. Clinical studies were carried out to sheed light on the differences and common features of cyclosporin-vs. diphenyl hydantoinate-induced gingival hyperplasia. A marked difference was the pronounced vascularization observed both clinically and histologically in cyclosporin A-induced hyperplasia.

Adolescent↗

PubMed2000

Risk factors in the development of cyclosporine-induced gingival overgrowth.

BACKGROUND: Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of cyclosporine-A (CsA). Using the largest group of renal allograft recipients assembled for this purpose, in this study, we statistically modeled the genetic (HLA), medical, and dental risk factors for the development of GH subsequent to administration of CsA. METHODS: Two hundred thirty-six renal transplant patients underwent full dental examination to quantify the extent and distribution of hyperplasia and dental disease (gingivitis, plaque, and calculus). Computerized data from all patients included pre-transplant medical history and dosage of nifedipine and azathioprine, as well as dose and serum levels of CsA and CsA microemulsion. Donor and host HLA haplotype were studied to investigate potential association of haplotype and donor-host mismatching with the development of GH. We evaluated the data by multivariate regression analysis, using Statistical Package for Social Sciences (SPSS). RESULTS: There was no association with age, sex, duration of renal replacement therapy, or interval since transplantation or pre-transplant disease (P>0.05). There also was no association of disease with host HLA haplotype, but degree of HLA-A mismatching was protective for GH development (P<0.002). GH was associated with the dose and serum levels of CsA (P<0.001) and the last dose of CsA microemulsion (P=0.009) but not nifedipine (P=0.10). Gingival inflammation and plaque were also strongly associated with GH (P<0.0003). In multivariate analysis, however, the last recorded dose of CsA (P<0.0001), presence of local gingival inflammation (P<0.0001), and gingivitis (P<0.003) were the independent predictors of the extent and severity of GH. CONCLUSIONS: Inter-patient variation in the extent and severity of GH is related to CsA dose and serum levels. Differences in host HLA phenotype do not explain individual susceptibility to GH, but donor-host HLA-A mismatching may be important. Inter-site variation in the extent and severity of the disease is related to local gingival inflammation.

Adolescent↗

PubMedDate not supplied

[Significance of hypertrophy, and of hyperplasia with gingival-periodontal localization].

The authors have attempted a study of gingival hypertrophy and hyperplasia as a particular manifestation involving the marginal parodontium, manifested clinically as a proliferative process that could be determined by a variety of local or general etiopathogenic factors. An analysis is made of hypertrophic and hyperplastic changes from the histopathologic and the etiologic viewpoints, of the gingivo-parodontal tissues. A review is also presented of several complete classifications. Clinical and histopathologic aspects are further discussed, of the various forms of gingivo-parodontal hyperplasias. Results obtained in the treatment of 160 forms of hyperplasia found in 1500 patients that were investigated are also discussed. The study concludes on the importance of an early diagnosis of various forms of gingivo-parodontal hyperplasias. This is of particular importance for the treatment of those patients where the therapy is directed against the causative agent, but that should also include the application of antiinflammatory therapies.

Gingival Hyperplasia↗

PubMed2005

Molecular identification of an invasive gingival bacterial community.

A woman with neutropenia developed gingival hyperplasia. Biopsy showed invasion of gingival tissue with mats of filamentous organisms, and molecular analysis by polymerase chain reaction and fluorescence in situ hybridization revealed Capnocytophaga sputigena, Leptotrichia species, and Fusobacterium nucleatum. Oral bacterial flora may cause invasive gingival disease with hyperplasia in immunocompromised patients.

Capnocytophaga↗

PubMed1993

General toxicity of the new calcium antagonist felodipine in dogs.

Felodipine 4-(2,3-dichlorophenyl)-1,4-dihydropyridine-2,6-dimethyl-3,5- dicarboxylic 3-ethyl ester and 5-methyl ester, CAS 72509-76-3) is a new selective calcium antagonist for use in the management of hypertension or other cardiovascular disease, which requires reduction of peripheral vascular resistance. A combined 6- and 12-month study in dogs has been performed as a part of the preclinical safety program. 30 dogs, 5 males and 5 females per group, were treated with felodipine for 12 months. Additional 18 dogs, 3 males and 3 females per group, were interim-sacrificed after 6-month treatment. The dose levels were 2 x 0.38, 2 x 1.2 and 2 x 2.3 mg/kg daily. Initially, 2 x 3.8 mg/kg/d was used as a high dose. At this dose level 2 animals died preterminally after 4 days of dosing. They were replaced and the high dose level was reduced. Two similar control groups were given a placebo formulation for 12 and 6 months, respectively. All animals were treated b.i.d. using a 4-h time interval. Mucosal hyperemia and tachycardia, as an expression of the vasodilating properties of felodipine, were observed in a somewhat variable but dose-related manner. Noninflammatory gingival hyperplasia, similar to that after treatment with phenytoin and the calcium antagonist nifedipine, occurred with a propensity for the males after 12 months of treatment. Slight-degree gingival hyperplasia was also noted after 6 months of treatment. This change occurred dose- and time related in the medium and high dose groups but was absent in the low dose group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed2005

Open prospective multicenter study of conversion to tacrolimus therapy in renal transplant patients experiencing ciclosporin-related side-effects.

The hyperlipidemic and hypertensive effects of ciclosporin constitute a cardiovascular risk. Cosmetic side-effects are known to reduce patients' quality of life. This was a 6-month, open, prospective, multicentre study in 296 adult kidney transplant patients to evaluate the conversion from ciclosporin to a tacrolimus-based regimen. Primary indications for conversion were hyperlipidemia (n =77), hypertension (n = 72), hypertrichosis (n = 32) and gingival hyperplasia (n = 115). At month 6, hyperlipidemia and hypertension were at least moderately improved in 59.1% and 63.5% of patients, and strongly or completely resolved in 29% and 25%. Gingival hyperplasia and hypertrichosis were strongly or completely resolved in 73% and 72% of patients. Mean total cholesterol was reduced from 255 to 218 mg/dl. Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5 mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin-related side-effects resolved or improved after conversion to tacrolimus.

Adult↗

PubMedDate not supplied

Influence of nifedipine on gingiva of Wistar rats.

Noninflammatory hyperplastic growth of gingiva induced by calcium channel blockers, mostly nifedipine, is often seen in everyday dental practice. In order to establish an association of nifedipine and gingival hyperplasia, experimental model was used. Wistar rats were given water solution of nifedipine in different daily doses, using specially designed cannula. At the beginning of the experiment, before the application of nifedipine and in the determined time periods, gingival volume was measured. The volume of lower incisors interdental central papillars, represented multiplied values of vertical height, mesio-distal width, and bucco-lingual depth, expressed in millimeters. The results indicated that gingival hyperplasia was more excessive in the experimental animals, which were given higher doses of the drug for longer time period. Nifedipine is a drug which induces gingival fibroblasts to produce higher quantity of collagen that causes gingival overgrowth.

Animals↗

PubMed1998

Long-term efficacy and adverse event of nifedipine sustained-release tablets for cyclosporin A-induced hypertension in patients with psoriasis.

Thirteen psoriatic patients with hypertension during the course of cyclosporin A therapy were treated for 25 months with a calcium channel blocker, sustained-release nifedipine, to study the clinical antihypertensive effects and adverse events during treatment with both drugs. Seven of the 13 patients had exhibited a subclinical hypertensive state before cyclosporin A therapy. Both systolic and diastolic blood pressures of these 13 patients were decreased significantly after 4 weeks of nifedipine therapy, and blood pressure was maintained within the normal range thereafter for 25 months. The adverse events during combined therapy with cyclosporin A and nifedipine included an increase in blood urea nitrogen levels in 9 of the 13 patients and development of gingival hyperplasia in 2 of the 13 patients. Our findings indicate that sustained-release nifedipine is useful for hypertensive psoriatic patients under long-term treatment with cyclosporin A, but that these patients should be monitored for gingival hyperplasia.

Adult↗

PubMed2001

Cyclosporin A-induced gingival overgrowth is unrelated to allograft function in renal transplant recipients.

BACKGROUND: Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of Cyclosporine-A (CsA). AIM: This study statistically modeled the medical and dental risk factors for the development of GH following CsA administration to determine whether renal function post-transplantation was related to the incidence or extent of GH in 236 consecutive renal transplant patients. METHOD: All patients were at least 6 months post-transplant and medicated with both traditional oral CsA (n=220 individuals) and the new microemulsion form CsA-Me (n=229 individuals). Patients had either received CsA alone (n=45 individuals) or cyclosporine and nifedipine (n=191 individuals). Gingival overgrowth was assessed and computerized data, available for all patients included; pre- and post-transplant medical history and post-transplant renal function, i.e., serum creatinine levels, documented rejection episodes and glomerular filtration rates (GFR). These data together with CsA serum levels and last-recorded dose of CsA, CsA-Me, nifedipine, azathioprine and prednisolone, were analysed by multivariate regression analysis using SPSS. RESULTS: The extent and severity of hyperplasia was significantly correlated with the dosage and serum level of CsA at 3, 6 and 12 months post-transplantation; last recorded dosage, however (p<0.0001), was the most accurate predictor of hyperplasia. Gingivitis (p<0.0001) and plaque (p<0.002), were associated with hyperplasia. Duration of renal replacement therapy, age at transplantation, post-transplant interval serum creatinine levels and documented rejection episodes were unrelated with the extent and severity of GH. Of all the renal variables only the correlation of GFR with last recorded doses of CsA and CsA-Me, approached significance; this was then considered for inclusion in the model. CONCLUSION: In a multiple regression analysis including GFR, however, only last CsA (and CsA-Me) doses and gingivitis score were selected for inclusion in the final model. These data demonstrate that inter-patient variation in the extent and severity of GH and renal function post-transplantation are unrelated and are mediated independently.

Adolescent↗

PubMed1991

Orthodontic therapy in the patient treated with cyclosporine.

Cyclosporine is an immunosuppressive drug that is gaining widespread use in the treatment of a variety of disorders. Gingival hyperplasia, a common side effect of cyclosporine therapy, has significant implications for orthodontic treatment, especially as the drug becomes more widely used to treat diseases prevalent in adolescents. A 5-year study of a group of patients with type 1 diabetes who were receiving cyclosporine treatment revealed a series of findings that are of importance to the orthodontist, including the potential for orthodontic appliances to increase the severity of the induced gingival enlargement and the potential of the gingival hyperplasia to complicate orthodontic therapy. Guidelines to minimize the degree of cyclosporine-induced gingival enlargement in the orthodontic patient are suggested.

Adolescent↗