tacrolimus and Gingival-Overgrowth

Cyclosporin is a potent immunosuppressant drug commonly used to prevent organ transplant rejection. In recent years, there has been a widening of its therapeutic use and an increase in the number of patients undergoing transplantation. Gingival overgrowth is one of several oral side-effects of cyclosporin, with a quoted prevalence of between 8% and 100%. There is continued debate over the factors which modify the degree of overgrowth, including individual sensitivity, age, dose of drug, duration of drug therapy and the presence of dental plaque. The exact mechanism of gingival overgrowth is still being debated, but appears to be caused by a combination of the proliferation of fibroblasts within the gingival tissue, an increase in the deposition of collagen and extracellular matrix, and a decrease in phagocytosis with a net gain in gingival tissue mass. A number of treatment options are utilized in the treatment of gingival overgrowth, including CO2 laser surgery, improved oral hygiene, the use of antibiotics such as metronidazole and azithromycin, and surgical intervention. In the clinical application of cyclosporin, there is little correlation between cyclosporin dose, serum trough levels and total exposure to the drug, making it difficult to achieve the desired therapeutic response. These problems were previously further complicated by the variability of absorption of the drug via the gastrointestinal tract. The original cyclosporin formulation, Sandimmune, was replaced by a new formulation, Neoral, which has a more reliable absorption, and gives a closer correlation between trough concentration levels and individual bioavailability. There is a conflict of opinion over whether or not the side-effect profile of Neoral varies from its precursor Sandimmune. It has yet to be seen whether the increased bioavailability of Neoral will result in an increased severity and prevalence of gingival overgrowth. An alternative immunosuppressant drug, tacrolimus, which is a macrolide antibiotic with a different side-effect profile, has emerged as a substitute for cyclosporin in organ transplantation. However, there have been conflicting reports of its side-effects and its capacity to cause gingival overgrowth.

Topics: Child; Cyclosporine; Gingival Overgrowth; Humans; Immunosuppressive Agents; Tacrolimus

Unsightly gingival overgrowth affects many individuals immunosuppressed with cyclosporin A (CsA). Current management involves repeated periodontal surgery and intensive hygienist support. Tacrolimus is an effective alternative immunosuppressive agent for renal transplantation which does not appear to produce gingival enlargement.. The purpose of the present study was to monitor the gingival response of 4 renal transplant patients (RTPs), with clinically significant CsA-induced gingival overgrowth, after their immunosuppressive therapy was switched to tacrolimus.. Intra-oral photographs and alginate impressions were taken both prior to the drug conversion and again, 6 to 9 months later. Gingival overgrowth scores were determined, from plaster models on both these occasions.. All of the RTPs experienced significant resolution of their gingival enlargement within the time period studied; however, only one had complete regression.. It is concluded that conversion of RTPs with gingival overgrowth from CsA to tacrolimus may provide an effective management strategy for this clinical problem.

Topics: Adolescent; Adult; Cyclosporine; Drug Therapy, Combination; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Remission Induction; Tacrolimus; Time Factors

Side effects of certain drugs such as cyclosporin A (CsA) and phenytoin may induce gingival overgrowth which in some instances become unacceptable to the patient because esthetic, functional, and other effects. Use of these drugs is related to important medical situations, such as organ transplantation and control and withdrawal of the drugs is contraindicated. Tacrolimus is an immunosuppressant used to prevent graft rejection in organ transplant patients and has been shown to cause fewer oral side effects than CsA. This report deals with a case of probable synergism between the use of CsA and phenytoin which caused an intense gingival overgrowth in a kidney transplant patient. A treatment protocol including very thorough oral hygiene, scaling and root planing, clorhexidine digluconate rinses (0.12%), and substituting CsA with tacrolimus is described. Response to treatment after 6 months of tacrolimus use was excellent with almost complete reversion of the gingival enlargement. One-year follow-up demonstrated a stable gingival situation. The successful substitution of CsA with tacrolimus provides great expectations for the management of CsA-related gingival enlargement.

Topics: Anticonvulsants; Cyclosporine; Drug Synergism; Drug Therapy, Combination; Epilepsy; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Phenytoin; Tacrolimus; Time Factors

This study aims to evaluate the effectiveness of periodontal therapy combined with tacrolimus in the suppression of gingival overgrowth (GO) and the effect on GO of changing from cyclosporin A to tacrolimus.. Sixteen renal transplant patients, averaging 52 years of age, whose kidney function was stable and were receiving treatment with cyclosporin A, were randomly assigned to one of two groups. In the experimental group, patients were instructed in oral hygiene and underwent periodontal treatment, whereas in the control group, only oral hygiene instructions were given. After the first visit and the change of medication from cyclosporine to tacrolimus in both groups, periodic clinical revisions were carried out for 3 months in order to assess the evolution of GO.. All patients showed a progressive decrease in GO. There were no statistically significant differences between the two groups (p>0.05). A greater decrease in GO occurred within the first month after changing the medication.. No improved effectiveness in reducing GO was observed for periodontal therapy in combination with tacrolimus. Tacrolimus is an alternative to cyclosporine when attempting to avoid GO in patients with kidney transplants.

Topics: Adult; Aged; Cyclosporine; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Tacrolimus

Gingival overgrowth associated with immunosuppression following liver transplantation is a commonly recognized clinical problem. The aims of this study were to determine the incidence of gingival overgrowth in a group of children post liver transplantation and to compare gingival overgrowth in children receiving FK506 with those receiving cyclosporin.. Seventy-nine children (aged 15-196 months) undergoing liver transplantation at Birmingham Children's Hospital between October 1998 and October 2000 were studied. Gingival overgrowth was assessed in a blinded fashion and scored in a previously validated manner. Gingival overgrowth scores of the patients on each immunosuppressant drug were then compared.. Fifty-two patients were treated with cyclosporin and 27 treated with tacrolimus. Eighteen children were also receiving nifedipine (also known to cause gingival overgrowth) and were considered separately. Of the 41 children receiving cyclosporin alone, 26 exhibited gingival overgrowth compared to zero of 20 patients receiving tacrolimus alone. Those children treated with immunosuppression plus nifedipine developed gingival overgrowth, however, this was much less marked in the tacrolimus group.. Tacrolimus, unlike cyclosporin, is not associated with gingival overgrowth when used for immunosuppression following liver transplantation in children, and may be the drug of choice for children.

Topics: Adolescent; Analysis of Variance; Calcium Channel Blockers; Child; Child, Preschool; Cyclosporine; Double-Blind Method; Gingiva; Gingival Overgrowth; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Nifedipine; Prospective Studies; Statistics, Nonparametric; Tacrolimus

Topics: Amlodipine; Calcium Channel Blockers; Drug Interactions; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Tacrolimus; Young Adult

It has previously been shown that both cyclosporine A and tacrolimus cause gingival overgrowth in the rat. We proposed that sirolimus may play an important role in decreasing the severity of gingival overgrowth. Therefore, the aim of this study was to evaluate the gingival changes induced by immunosuppressants, in the presence and absence of sirolimus, using histopathology and stereological methods.. Thirty-six male Sprague-Dawley rats were distributed into six treatment groups, each containing six rats, as follows: (i) cyclosporine A for 8 wk; (ii) tacrolimus for 8 wk; (iii) sirolimus for 8 wk; (iv) cyclosporine A + sirolimus for 8 wk; (v) tacrolimus + sirolimus for 8 wk; and (vi) distilled water for 8 wk. Histomorphometric analyses included measurements of epithelial thickness and connective tissue width and height. Stereological analyses included measurements of volumetric densities of fibroblasts (Vf ), collagen fibers (Vcf ) and blood vessels (Vbv ).. Connective tissue width and height were significantly increased in cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05), and epithelial thickness was significantly increased in the cyclosporine A group and tacrolimus group compared with the control group (p < 0.05). Vf was significantly increased in the cyclosporine A group and the tacrolimus group compared with the control group (p < 0.05), whereas Vcf and Vbv were significantly increased in the cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05).. The results of the study suggest that sirolimus seems not to be associated with gingival overgrowth, and combined usage of sirolimus and immunosuppressants decreases the severity of gingival overgrowth.

Topics: Animals; Cyclosporine; Gingiva; Gingival Overgrowth; Immunosuppressive Agents; Male; Rats; Rats, Sprague-Dawley; Sirolimus; Tacrolimus

The aim of the present study was to investigate the effect of cyclosporine-A (CsA) medication on gingival crevicular fluid (GCF) LL-37, human neutrophil peptide (HNP)1-3 and adrenomedullin (ADM) levels.. CsA-treated renal transplant recipients with GO (CsA GO+) and without GO (CsA GO-), tacrolimus-medicated renal transplant recipients (n = 20/group), systemically healthy subjects with gingivitis (n = 21) and individuals free of periodontal and systemic diseases (n = 20) were included in the present study. Periodontal parameters were recorded and GCF samples were obtained from the study participants. GCF LL-37, HNP1-3 and ADM levels were analyzed by enzyme-linked immunosorbent assay.. GCF LL-37 total amount was higher at GO+ sites than the other study sites (p < 0.05). Total amount of GCF HNP1-3 was higher in immunosuppressive treatment groups than healthy and gingivitis groups, regardless of GO presence (p < 0.05). GCF ADM total amount was similar in all study groups. GCF volume, papillary bleeding index and hyperplastic index (p < 0.05) were significantly correlated with GCF LL-37 total amounts (p < 0.05), but not with GCF HNP1-3 and ADM total amount at GO+ sites (p > 0.05).. Neutrophil infiltration due to extended inflammation might have increased GCF LL-37 levels at GO+ sites and contributed to the pathogenesis of CsA-induced GO.

Topics: Adrenomedullin; Adult; alpha-Defensins; Antimicrobial Cationic Peptides; Case-Control Studies; Cathelicidins; Cyclosporine; Enzyme-Linked Immunosorbent Assay; Female; Gingival Crevicular Fluid; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Tacrolimus

Immunosuppressive drugs may induce an increase of the gingival connective tissue in the extracellular matrix. The aim of this study was to assess the effectiveness of nonsurgical periodontal treatment in reducing gingival overgrowth (GO) in transplant patients taking cyclosporin A (CsA) or tacrolimus (Tcr).. An observational cohort study employing 68 transplant patients with diagnosis of GO, 51 taking CsA and 17 in therapy with Tcr, was performed at the Periodontal Unit of the School of Dental Sciences (University of Trieste, Italy). Percentages of plaque index (PI), bleeding on probing (BoP), sites with probing depth (PD) > 3 mm, and hypertrophy index (HI) were registered at baseline, 90 days, 180 days, and at 1 year after nonsurgical periodontal therapy. Furthermore, HI at baseline and after 1 year was investigated by multiple linear regression.. Both groups have significantly improved their clinical parameters: CsA group: PIbaseline = 41.67%; PIyear = 33%; BoPbaseline = 13.88%; BoPyear = 6.94%; PD > 3 mmbaseline = 18.6%; PD > 3 mmyear = 12.96%; HIbaseline = 22%; HIyear = 10%; Tcr group: PIbaseline = 40.73%; PIyear = 38.54%; BoPbaseline = 20.78%; BoPyear = 12.5%; PD > 3 mmbaseline = 21.53%; PD > 3 mmyear = 13.19%; HIbaseline = 12%; HIyear = 6.5%. Age showed a statistical negative correlation with HI at baseline (P < .05), while PD > 3 mm was positively correlated to the baseline HI (P < .001). Only HI at baseline showed a statistically significant negative relation with HI at 1 year (P < .001).. After nonsurgical periodontal therapy no patients needed additional periodontal surgery. Nonsurgical periodontal treatment itself represents an efficacious therapy in transplant patients treated with CsA and Tcr.

Topics: Cohort Studies; Cyclosporine; Dental Plaque Index; Gingival Overgrowth; Humans; Immunosuppressive Agents; Organ Transplantation; Periodontal Index; Tacrolimus

Variances in fibroblasts' α2β1 integrin intensity may lead to altered adhesion to type I collagen and consequently to suppression of phagocytosis which may be one of the mechanisms for drug induced gingival overgrowth. The present study aimed to evaluate the genotype and allele frequencies of α2 integrin +807 gene in renal transplant patients with and without gingival overgrowth.. Seventy renal transplant patients with cyclosporine A (CsA)-induced gingival overgrowth (CsA GO+) were enrolled. Renal transplant patients without GO medicated with CsA (CsA GO-; n=79) and tacrolimus (Tac; n=52) served as controls. DNA was obtained from peripheral blood and ITGA2 +807C/T polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism method. Clinical parameters including probing depth and plaque, papilla bleeding and hyperplasia indexes were recorded. Chi-square, Kruskal-Wallis and Mann-Whitney tests were used in statistical analysis.. Clinical parameters of CsA GO+ group were significantly higher than those of the CsA GO- and Tac groups (p<0.05). ITGA2 807C/T genotype and allele frequencies of study groups were similar (p>0.05).. Within the limits of the present study it can be concluded that ITGA2 +807 gene polymorphism is not associated with susceptibility to CsA-induced GO.

Topics: Adult; Cyclosporine; Female; Gene Frequency; Genotype; Gingival Overgrowth; Humans; Immunosuppressive Agents; Integrin alpha2; Kidney Transplantation; Male; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Tacrolimus

The aim of this study is to compare gingival changes induced by short- and long-term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug-induced gingival overgrowth.. Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8-week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24-week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry.. Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P <0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P <0.001). Vf and Vcf were significantly increased in group 7 compared to group 8 (P <0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P <0.05).. Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's role in the etiology of drug-induced gingival overgrowth.

Topics: Animals; Blood Vessels; Calcium Channel Blockers; Cell Count; Collagen; Connective Tissue; Drug Combinations; Epithelium; Fibroblasts; Gene Expression Regulation, Enzymologic; Gingiva; Gingival Overgrowth; Immunosuppressive Agents; Male; Nifedipine; PTEN Phosphohydrolase; Random Allocation; Rats; Rats, Sprague-Dawley; Tacrolimus; Time Factors

The aim of this study is to make a longitudinal evaluation of the incidence and severity of gingival overgrowth (GO) induced by immunosuppressive agents, such as tacrolimus (Tcr) and cyclosporin A (CsA), in the absence of calcium channel blockers in patients undergoing renal transplantation (RT).. This longitudinal study is conducted in 49 patients with RT who were divided into a CsA group (n = 25) and Tcr group (n = 24). The individuals were assessed at four time intervals: before transplant and 30, 90, and 180 days after RTs. Demographic data and periodontal clinical parameters (plaque index, cemento-enamel junction to the gingival margin, probing depth, clinical attachment level, bleeding on probing [BOP], and GO) were collected at all time intervals.. The mean GO index was significantly lower in the Tcr group compared to the CsA group after 30 (P = 0.03), 90 (P = 0.004), and 180 (P = 0.01) days of immunosuppressive therapy. One hundred eighty days after RTs, a clinically significant GO was observed in 20.0% of individuals in the CsA group and 8.3% of individuals in the Tcr group. However, this difference was not statistically significant (P = 0.41). There was a reduction in periodontal clinical parameters regarding the time of immunosuppressive therapy for PI and BOP (P <0.001) in both groups.. Although there was no statistical difference in the incidences of clinically significant GO after 180 days of immunosuppressive therapy, it was observed that GO occurred later in the Tcr group, and the severity of GO in this group was lower than in patients who used CsA.

Topics: Adult; Analysis of Variance; Calcium Channel Blockers; Cyclosporine; Female; Gingival Overgrowth; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Severity of Illness Index; Statistics, Nonparametric; Tacrolimus; Young Adult

Interleukin-6 (IL-6) may be involved in drug-induced gingival overgrowth (GO). The present study was conducted to assess the association between IL-6 (-174 G/C) gene polymorphism and GO in renal transplant recipients under cyclosporine (CsA), tacrolimus (Tcr), or sirolimus (Sir)-based regimens.. Within an eligible population, 45 unrelated subjects were selected for each CsA, Tcr, and Sir group, totaling a sample of 135 subjects. GO was visually assessed and subjects were assigned as controls (non-responders) or cases (responders) in a post hoc definition. IL-6 gene polymorphism was assessed using the polymerase chain reaction amplification and digestion. The distribution of genotypes and allele frequencies in responders and non-responders were compared using the Chi-squared test.. The number of responders was 27 (60.0%), 13 (28.9%), and 7 (15.6%) in the CsA, Tcr, and Sir groups, respectively. No differences could be observed at frequencies of -174GG, -174CG, and -174CC genotypes when comparing responders to non-responders in the CsA, Tcr, and Sir groups. Similar to genotypes, allele frequencies showed no differences between responders and non-responders in all groups.. No association between IL-6 (-174 G/C) gene polymorphism and gingival overgrowth was observed in renal transplant recipients under CsA, Tcr, or Sir-based immunosuppressive maintenance regimens.

Topics: Adult; Calcium Channel Blockers; Cross-Sectional Studies; Cyclosporine; Cytosine; Dental Plaque Index; Female; Gene Frequency; Genotype; Gingival Overgrowth; Guanine; Humans; Immunosuppressive Agents; Interleukin-6; Kidney Transplantation; Male; Periodontal Index; Polymorphism, Genetic; Sirolimus; Tacrolimus; Time Factors

To assess the prevalence and variables associated with gingival overgrowth (GO) in renal transplant recipients medicated with cyclosporine (CsA), tacrolimus (Tcr), or sirolimus (Sir).. One hundred and thirty-five eligible subjects were divided in CsA, Tcr, and Sir groups comprising 45 subjects each. GO was visually assessed and subjects were assigned as GO+ or GO- in a post hoc definition. Saliva samples were collected and the presence of periodontal pathogens was assessed through polymerase chain reaction. Variables of interest were compared between GO+ and GO- subjects through univariate and multivariate analysis.. Prevalence of GO was of 60.0% for CsA, 28.9% for Tcr, and 15.6% for Sir groups. Within the CsA group, GO was associated with papillary bleeding index (p=0.001); within the Tcr group, GO was associated with CsA previous use (p=0.013), and calcium channel blockers (CCB) use (p=0.003); within the Sir group, GO was associated with papillary bleeding index (p=0.018), and CCB use (p=0.020). A higher frequency of Tannerella forsythia was observed among GO+ subjects medicated with Tcr.. Pharmacological and periodontal variables were associated with GO in different immunosuppressive regimens. Integration between the medical and the dental team may be an important approach in the post-transplant maintenance routine.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Bacteria, Anaerobic; Calcium Channel Blockers; Cross-Sectional Studies; Cyclosporine; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Logistic Models; Male; Middle Aged; Periodontal Index; Saliva; Sirolimus; Statistics, Nonparametric; Tacrolimus; Young Adult

The rationale of this study was to address whether local or systemic changes reflect proteolytic (matrix metalloproteinase-13) or oxidative (myeloperoxidase) stress in renal transplant patients receiving cyclosporine-A (CsA) and having gingival overgrowth (GO), in patients receiving CsA therapy and having no GO and patients receiving tacrolimus therapy.. Gingival crevicular fluid (GCF) samples were collected from sites with (GO+) and without GO (GO-) in CsA patients having GO; GO- sites in CsA patients having no GO; sites from tacrolimus, gingivitis and healthy subjects. GCF and serum myeloperoxidase (MPO) and matrix metalloproteinase-13 (MMP-13) levels were determined by ELISA.. GO+ sites in CsA patients having GO had elevated GCF MPO levels than those of CsA patients having no GO, tacrolimus and healthy subjects (p<0.005), but comparable to those of gingivitis. GCF MPO levels were higher in GO+ compared to GO- sites in CsA patients having GO (p<0.05). Patient groups had similar, but higher GCF MMP-13 levels than healthy group.. These results show that CsA and tacrolimus therapy have not a significant effect on GCF MPO and MMP-13 levels, and gingival inflammation seems to be the main reason for their elevations.

Topics: Adult; Case-Control Studies; Cyclosporine; Enzyme-Linked Immunosorbent Assay; Female; Gingival Crevicular Fluid; Gingival Overgrowth; Gingivitis; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Matrix Metalloproteinase 13; Middle Aged; Normal Distribution; Peroxidase; Statistics, Nonparametric; Tacrolimus; Young Adult

Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies.. The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats.. Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar.. After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P>0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the Vf and Vcf (P<0.05).. Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related.

Topics: Animals; Cell Count; Collagen; Connective Tissue; Epithelium; Fibroblasts; Gingiva; Gingival Hyperplasia; Gingival Overgrowth; Immunosuppressive Agents; Injections, Subcutaneous; Male; Mouth Mucosa; Random Allocation; Rats; Rats, Sprague-Dawley; Tacrolimus; Time Factors

We investigated gingival crevicular fluid (GCF) and serum matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) levels from renal transplant patients receiving cyclosporine-A (CsA) and having gingival overgrowth (GO), from patients receiving CsA therapy and having no GO and patients receiving tacrolimus therapy.. GCF samples were collected from sites with GO (GO+) and without GO (GO-) in CsA patients having GO; and GO- sites in CsA patients having no GO; sites from tacrolimus, gingivitis and healthy subjects. GCF and serum MMP-8 and TIMP-1 levels were determined by a time-resolved immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay.. GO+ sites in CsA patients having GO had elevated GCF MMP-8 levels compared with those of CsA patients having no GO, tacrolimus and healthy subjects (p<0.005), but these levels were similar to those of gingivitis. The GCF MMP-8 level was higher in GO+ compared with GO- sites in CsA patients having GO (p<0.05). GCF TIMP-1 levels were similar between groups. Tacrolimus patients had lower GCF MMP-8 levels than gingivitis (p<0.005), but levels similar to the healthy group.. These results show that CsA and tacrolimus therapy has no significant effect on GCF MMP-8 levels, and gingival inflammation seems to be the main reason for their elevations.

Topics: Adolescent; Adult; Cyclosporine; Epidemiologic Methods; Female; Gingival Crevicular Fluid; Gingival Overgrowth; Gingivitis; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Male; Matrix Metalloproteinase 8; Middle Aged; Radiography; Tacrolimus; Tissue Inhibitor of Metalloproteinase-1

Tacrolimus is a new-generation immunosuppressant as successful as cyclosporin in suppressing organ transplant rejection. Although cyclosporin is known to cause gingival enlargement (GE), tacrolimus has not been associated with this condition. We sought to explore the prevalence of GE among renal transplant recipients (RTRs) in relation to cyclosporin and tacrolimus while controlling for the effect of calcium channel blockers (CCBs) and supragingival plaque.. RTRs were recruited from our institution's Kidney Transplant Unit. Participants completed a standardized questionnaire and received a complete oral examination, including a soft tissue examination and a periodontal examination measuring probing depth, recession, bleeding on probing, plaque index (PI), and GE.. Among 115 RTRs, 39 (34%) presented with GE, with the highest prevalence among those taking cyclosporin and CCBs (76%) and the lowest among tacrolimus users not on a CCB (15%). Tacrolimus was not found to be associated with GE. Cyclosporin was found to be associated with GE in a univariate analysis stratified by the use of CCBs, but multivariate analysis revealed that the only significant risk factors for GE were the use of CCBs and the widespread presence of abundant supragingival plaque (PI > or =2 on >40% of tooth surfaces).. This study confirmed that tacrolimus is not associated with GE. Cyclosporin taken at the currently recommended low dosage and not in combination with a CCB may not be associated with a significant risk for GE in individuals with good oral hygiene. CCBs should be avoided among patients taking cyclosporin and those with poor oral hygiene.

Topics: Adult; Calcium Channel Blockers; Cyclosporine; Dental Plaque; Drug Interactions; Female; Gingival Overgrowth; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Logistic Models; Male; Risk Factors; Statistics, Nonparametric; Surveys and Questionnaires; Tacrolimus

The relationship between gingival overgrowth (GO) induced by cyclosporine A (CsA) and transforming growth factor-beta1 (TGF-beta1) remains unclear. The aims of the present study were to evaluate TGF-beta1 gene expression under different immunosuppressive treatments and its association with TGF-beta1 gene functional polymorphism and GO in renal transplant recipients.. The study included 98 CsA-treated renal transplant recipients (with and without GO) and 44 tacrolimus-treated transplant patients (without GO). TGF-beta1 mRNA expression was measured using a real-time quantitative polymerase chain reaction assay. The levels were correlated with TGF-beta1 gene polymorphisms at codons 10 and 25, with different immunosuppressive treatment and GO.. The level of TGF-beta1 gene expression was insignificantly lower in the CsA-treated group compared with the tacrolimus group, and significantly lower in the group with GO compared with patients without GO. In tacrolimus- and CsA-treated patients, but not in patients with GO, the level of TGF-beta1 gene expression was associated with functional phenotypes of TGF-beta1. The incidence, degree and extent of GO were higher in recipients with lower TGF-beta1 gene expression.. Lower level TGF-beta1 gene expression, not functional polymorphism, in patients treated with CsA may be considered to be a risk factor for GO.

Topics: Adolescent; Adult; Aged; Cyclosporine; Female; Gene Expression; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pilot Projects; Polymorphism, Single Nucleotide; Risk Factors; Tacrolimus; Transforming Growth Factor beta1

To investigate the prevalence of gingival overgrowth(GO) in a group of renal transplant recipients medicated with cyclosporine A(CsA) in comparison to those medicated with tacrolimus(Tcr).. 107 renal transplant recipients ( 85 CsA and 25 Tcr) were recruited into this study. Demographic, pharmacologic and periodontal data was recorded. The prevalence and severity of GO were compared between the two groups. The data was analyzed by SPSS13.0 software package for independent sample t test, chi(2) test, Mann-Whitney U test and stepwise regression analysis.. The prevalence of GO in the CsA group(49%)was significantly higher than that in the Tcr group(16%)(P<0.05). The CsA group showed a higher mean GO score (30.3+/-15.5) compared with the Tcr group(17.5+/-9.6) (P<0.001).In addition, the patients with GO presented a significantly higher plaque index and papilla bleeding index than those without GO in two groups(P<0.05).. The prevalence of GO is higher in renal transplant recipients taking CsA compared to Tcr. Plaque-induced gingival inflammation has a close relation with the severity of GO.

Topics: Cyclosporine; Dental Plaque; Dental Plaque Index; Gingival Overgrowth; Gingivitis; Humans; Immunosuppressive Agents; Kidney Transplantation; Tacrolimus; Transplant Recipients

The aim of this study was to determine the incidence and severity of gingival overgrowth (GO) induced by tacrolimus (Tcr) compared with ciclosporin A (CiA) in the absence of calcium channel blockers (CCB) in renal transplant recipients.. Forty patients (20 Tcr and 20 CiA) were evaluated before and 30 and 90 days after kidney transplantation. Demographic (age, gender) and periodontal parameters were recorded for all patients. Patients taking CCB at any time during the study were excluded from the investigation.. The mean GO score was significantly lower (p=0.014) in the Tcr group (6.4%) compared with the CiA group (17.9%) after 90 days of immunosuppressive therapy. At 90 days post-transplant, clinically significant GO was observed in four patients of the CiA group and in two of the Tcr group. This difference was not statistically significant (0.66).. No significant difference in the incidence of clinically significant GO was observed between the CiA and Tcr groups up to 90 days of immunosuppressive therapy.

Topics: Adult; Anti-Infective Agents; Azathioprine; Calcium Channel Blockers; Cyclosporine; Dental Plaque Index; Female; Follow-Up Studies; Gingival Hemorrhage; Gingival Overgrowth; Gingival Recession; Humans; Immunosuppressive Agents; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Periodontal Index; Periodontal Pocket; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate and compare the possible morphological and histopathological changes in gingival tissue of rats under the administration of cyclosporine and tacrolimus. The present study was motivated by the high prevalence of gingival overgrowth observed in subjects under cyclosporine regimens and by studies reporting a significant decrease in gingival overgrowth after the substitution of tacrolimus.. Five Sprague-Dawley rat groups were administered therapeutic and greater-than-therapeutic doses of cyclosporine and tacrolimus over 54 days. The control group of 10 animals received distilled water as a placebo. The cyclosporine group was divided into two subgroups of 10 animals each, one receiving 10 mg/kg/day (CsA1) and one receiving 30 mg/kg/day (CsA2). The tacrolimus group was also divided in two subgroups of 10 animals each, receiving 3.2 mg/kg/day (Tcr1) or 6.4 mg/kg/day (Tcr2).. Gingival overgrowth was higher in the group that was administered the higher cyclosporine dosage (CsA2) than in the group that received the therapeutic dosage, showing a positive relation between dosage and severity of gingival overgrowth. Hypercellularity, vascular congestion and focal inflammatory exudation were observed in the CsA2 subgroup only. There were no morphological or histological alterations in gingival tissue in either tacrolimus subgroups.. Cyclosporine can induce adverse morphological and histopathological changes in gingival tissue of rats, and these effects are dose-dependent. Tacrolimus induced no gingival alterations in this rat model.

Topics: Animals; Cell Size; Cyclosporine; Disease Models, Animal; Dose-Response Relationship, Drug; Exudates and Transudates; Gingiva; Gingival Overgrowth; Immunosuppressive Agents; Male; Periodontium; Placebos; Rats; Rats, Sprague-Dawley; Tacrolimus; Time Factors

The aim of this study was to compare the morphologic changes in the gingiva brought about by the administration of cyclosporin and tacrolimus in rats.. The study was conducted on 30 six-week-old male Sprague-Dawley rats, divided into three groups of 10 rats each, for a period of 4 weeks. Group I rats received cyclosporin (30 mg/kg body weight), and group II rats received tacrolimus (1.5 mg/kg body weight), by means of a gavage. Group III served as control and received olive oil alone. Impressions of the mandibular incisal region were made weekly, and stone casts were prepared for measuring morphologic changes of the gingiva.. An increase in the measured gingival dimensions was observed in the test groups as early as week 2 after the commencement of drug administration. Intergroup comparison revealed that the increase in the measured dimensions was greater in group I than group II at the end of 4 weeks.. Cyclosporin and tacrolimus were capable of causing gingival enlargement in Sprague-Dawley rats. However, the magnitude of tacrolimus-influenced gingival enlargement seemed to be comparatively less than cyclosporin.

Topics: Animals; Cyclosporine; Dental Impression Technique; Erythema; Gingiva; Gingival Overgrowth; Gingivitis; Immunosuppressive Agents; Male; Models, Dental; Olive Oil; Plant Oils; Random Allocation; Rats; Rats, Sprague-Dawley; Tacrolimus

Cyclosporin A (CsA) induces gingival overgrowth (GO) in patients who seem to be prone to this disorder. It is still impossible to determine which patients will develop GO. Patients treated with the new immunosuppressive drug tacrolimus seem not to have GO. The aims of this study were to investigate transforming growth factor-beta1 (TGF-beta1) gene polymorphisms in renal transplant recipients treated with CsA or tacrolimus and to establish an association between these polymorphisms and TGF-beta1 plasma concentration and the incidence of GO.. The examined group consisted of 134 renal transplant recipients. Ninety-two underwent CsA treatment (50 with and 42 without GO), and 42 underwent tacrolimus treatment. Age, gender, time after transplantation, calcineurin inhibitor total dosage, number of teeth, and sulcus bleeding index were analyzed. TGF-beta1 plasma levels were estimated in 60 CsA- and 30 tacrolimus-treated patients. Two biallelic polymorphisms of the TGF-beta1 gene were studied at codon 10 (at position +869) and at codon 25 (at position +915) in patients from the examined group and in 108 healthy volunteers (the control group).. The distribution of the high, intermediate, and low TGF-beta1 producer phenotypes was comparable in all the studied groups and in the healthy controls. The high producer phenotype was more frequent in patients with GO. TGF-beta1 levels in the CsA group showed correlation with the phenotypes. The lowest incidence of GO was observed in the 10C/C genotype, whereas the highest was observed in the 10T/C genotype.. High and intermediate TGF-beta1 producer phenotypes and heterozygous genotype 10T/C might be considered risk factors for GO in patients treated with CsA.

Topics: Adult; Codon; Cyclosporine; Female; Genotype; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Polymorphism, Genetic; Statistics, Nonparametric; Tacrolimus; Transforming Growth Factor beta; Transforming Growth Factor beta1

The aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant.. A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects.. The results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506.. Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.

Topics: Adult; Calcium Channel Blockers; Candida; Carcinoma, Squamous Cell; Cyclosporine; Drug Therapy, Combination; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mouth Neoplasms; Saliva; Stomatitis, Herpetic; Tacrolimus

Some reports suggest that the prevalence and severity of gingival overgrowth (GO) is lower in patients taking tacrolimus (Tcr) than in those taking cyclosporin A (CsA). The present study was conducted to determine the prevalence and severity of GO in a group of renal transplant recipients treated with Tcr in comparison to those treated with CsA and to evaluate the risk variables associated with the development of GO in these two drug regimens.. A cross-sectional study was conducted in a public hospital in Belo Horizonte City, Brazil. Demographic, pharmacological, and periodontal data were recorded for each subject. Variables from 134 subjects taking Tcr were compared to 451 subjects taking CsA using independent sample t, chi(2) statistic, or Mann-Whitney tests. The effects of potential risk factors on GO severity were determined using forward and backward stepwise regression analysis.. Subjects taking CsA showed a higher mean GO score (29.03% +/- 22.9%) compared to subjects taking Tcr (16.9% +/- 3.4%) (P = 0.0038). In the Tcr group, 17.9% of the subjects had clinically significant GO compared to 38.1% in the CsA group (P = 0.045). In the multivariate final model, papillary bleeding index, azathioprine dosage, and concomitant use of calcium channel blockers (CCB) were significant variables associated with severity of GO in Tcr and CsA groups. In addition, previous CsA use also remained significant for GO in subjects under a Tcr regimen.. The prevalence and severity of GO is lower in transplant subjects taking Tcr compared to CsA. GO severity in both groups was strongly associated with the papillary bleeding index, highlighting the role of inflammation in this condition. Concomitant CCB use, azathioprine dosage, and previous CsA use in the Tcr group reinforces the possible synergistic effects of these pharmacological variables on GO severity.

Topics: Adult; Cyclosporine; Epidemiologic Methods; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Tacrolimus

FK506 is an immunosuppressive agent that, unlike cyclosporin A (CsA), does not induce gingival overgrowth (GO). CsA-induced GO is caused by quantitative modifications of the extracellular matrix components, particularly collagen (COL). Up to now, clinical trials have only investigated FK506 in relation with GO, so we aimed at analysing the effect of FK506 on COL turnover using a molecular approach, to evaluate the expression of genes and proteins related to this process.. Human gingival fibroblasts were incubated with FK506 or its vehicle (VH) for 24, 48 and 72 h. COL type I (COL-I), matrix metalloproteinases (MMP)-1 and 2, tissue inhibitor of MMP (TIMP)-1 and transforming growth factor (TGF)-beta1 mRNA were assayed by Reverse transcriptase polymerase chain reaction; COL-I protein levels were determined by dot blot, MMP-1 and MMP-2 activity by zymography.. Fibroblast proliferation decreased 48 and 72 h after treatment. COL-I gene and protein expression, TGF-beta1 and TIMP-1 mRNA levels were not significantly affected, whereas MMP-1 gene and protein expression and MMP-2 mRNA levels rose significantly in treated fibroblasts compared with VH.. These findings suggest that increased MMP-1 gene and protein expression may be important for regulating COL-I homeostasis in the gingival connective compartment of FK506-immunosuppressed subjects.

Topics: Adult; Analysis of Variance; Cell Proliferation; Collagen; Female; Fibroblasts; Gingival Overgrowth; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Intracellular Signaling Peptides and Proteins; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Reverse Transcriptase Polymerase Chain Reaction; Tacrolimus

Cyclosporin (CsA) and tacrolimus (FK-506) are immunosuppressive drugs that specifically inhibit T-cell activation via calcineurin inhibition. Gingival overgrowth is a common side effect following the administration of CsA. The severity of gingival overgrowth seen in patients taking FK-506 is less than that observed with CsA. Little is known about the involvement of saliva in drug-induced gingival overgrowth. The purpose of this study was to investigate the salivary contents of tumor growth factor beta1 (TGF-beta1), epidermal growth factor (EGF), and interleukin-6 (IL-6) as well as the hystometry of gingival tissue obtained from rats treated with either FK-506 or CsA.. For 30 or 60 days rats received daily subcutaneous injection doses of either CsA or FK-506 (10 mg/kg). The concentrations of TGF-beta1, EGF, and IL-6 in saliva were determined by enzyme-linked immunosorbent assay, and after histological processing, the oral epithelium and connective tissue were assessed at the region of the lower first molars.. The levels of TGF-beta1, EGF, and IL-6 in saliva were not significantly altered by any of the treatments after 30 days. After 60 days of treatment with CsA, gingival overgrowth and significant increase in salivary TGF-beta1, EGF, and IL-6 concentrations were observed; no statistically significant changes were induced by FK-506.. Within the limits of this experimental study, it can be concluded that CsA, but not FK-506, induced gingival overgrowth associated with an increase of the salivary levels of the cytokines TGF-beta1, EGF, and IL-6.

Topics: Animals; Cyclosporine; Cytokines; Epidermal Growth Factor; Gingival Overgrowth; Immunosuppressive Agents; Interleukin-6; Male; Rats; Rats, Sprague-Dawley; Saliva; Tacrolimus; Transforming Growth Factor beta; Transforming Growth Factor beta1

The study aims to determine the prevalence and severity of gingival overgrowth in a group of adult organ transplant recipients immunosuppressed with tacrolimus in comparison with ciclosporin, and to examine various risk factors for the development of gingival overgrowth.. Forty patients taking tacrolimus were compared with 197 ciclosporin patients. Demographic, pharmacological and periodontal data were recorded for all patients. Comparison between the groups was made using independent sample t-tests, chi2 statistic or Mann-Whitney test. The effects of risk variables on overgrowth severity were examined using forward and backward stepwise regression analysis.. Those taking tacrolimus had a significantly lower mean gingival overgrowth score (14.1%) compared with ciclosporin (22.4%). Fifteen percent of the tacrolimus group had clinically significant gingival overgrowth compared with 30% in the ciclosporin group (p=0.053).. The prevalence and severity of gingival overgrowth is less in adult transplant patients taking tacrolimus compared with ciclosporin. Concomitant use of calcium channel blockers and previous medication with ciclosporin are significant risk factors for the presence and severity of gingival overgrowth. Patients who have alteration of their immunosuppressant from ciclosporin to tacrolimus may persist in demonstrating gingival overgrowth attributable to their ongoing therapy with calcium channel blockers.

Topics: Adolescent; Adult; Aged; Azathioprine; Calcium Channel Blockers; Chi-Square Distribution; Cyclosporine; Drug Interactions; Female; Gingival Overgrowth; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Organ Transplantation; Prednisolone; Regression Analysis; Risk Factors; Statistics, Nonparametric; Tacrolimus

Induction of the pro-fibrotic growth factor TGF-beta1 has been suggested as a possible mechanism through which immunosuppressant drugs may induce gingival overgrowth. This study aims to investigate plasma levels of TGF-beta1 and relate them to the development and severity of gingival overgrowth in immunosuppressed transplant patients.. One hundred and thirty-two ciclosporin-treated and 13 tacrolimus-treated transplant patients and 24 drug-free control subjects underwent a full periodontal examination including a determination of the presence and severity of gingival overgrowth.. Plasma TGF-beta1 concentrations were determined by ELISA, and were found to be significantly elevated in samples from the transplant patients (mean=29.1 ng/ml) as compared with controls (mean=6.1 ng/ml, p<0.0001). There was no significant difference between the levels of plasma TGF-beta1 in the ciclosporin- and tacrolimus-treated patient groups.. Furthermore, concomitant treatment with calcium channel blockers did not influence the levels of plasma TGF-beta1 in the patients group. The relationship between gingival overgrowth, independent periodontal variables and TGF-beta1 plasma concentrations was examined using univariate and multivariate regression analyses; low TGF-beta1 plasma concentrations were found to be a risk factor for gingival overgrowth in immunosuppressed patients concomitantly receiving a calcium channel blocker.

Topics: Age Factors; Analysis of Variance; Calcium Channel Blockers; Cohort Studies; Cyclosporine; Enzyme-Linked Immunosorbent Assay; Female; Gingival Overgrowth; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Regression Analysis; Tacrolimus; Transforming Growth Factor beta; Transforming Growth Factor beta1; Transplantation

Gingival enlargement (GE) is a frequent side effect that occurs in organ transplant recipients (OTR) after the administration of cyclosporin A (CsA). The availability of new drugs used to suppress graft rejection in OTR offers an opportunity to manage GE non-surgically. This preliminary case series aimed to analyze the effect of CsA withdrawal and its substitution by another immunosuppressant in OTR with severe GE.. Four organ transplant recipients who had received a liver or renal allograft were recruited for this study. All OTR had developed clinically severe CsA-induced GE. GE scores were assessed for each patient at baseline and at weeks 2, 4, 8, 12, 16, and 54 following conversion to tacrolimus. Scaling and root planing were initially performed and repeated monthly during the first 6 months. Careful polishing of the teeth was carried out once every 2 weeks until month 6 and then monthly until month 12. Hygiene instructions and reinforcement to optimize oral hygiene were maintained throughout the study.. The four patients showed a rapid decrease in their gingival symptoms and in the size of the gingivae. This change was clinically evident 8 weeks after conversion to tacrolimus. One year later, all the patients experienced GE regression, although some anatomic irregularities persisted in the interdental papillae of one of the patients. No adverse effects from tacrolimus were observed during the study except in one patient who presented headaches.. It seems that CsA withdrawal and its conversion to tacrolimus in organ transplant recipients who develop severe gingival enlargement, together with an extensive plaque control program, provide an effective means to control/eliminate gingival hyperplasia, with minimal risk of graft dysfunction.

Topics: Adult; Analysis of Variance; Cyclosporine; Female; Gingival Overgrowth; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Pilot Projects; Tacrolimus

Cyclosporin A is used extensively to prevent the rejection of allogenic renal transplants. However, it is associated with a variety of undesirable side effects including gingival overgrowth. Tacrolimus (FK506), has been marketed as an effective alternative immunosuppressant to cyclosporin A and recent subjective reports suggest patients taking it complain infrequently of gingival problems. This clinical investigation was undertaken to confirm whether or not tacrolimus adversely affected the gingival health of renal transplant recipients.. Renal transplant patients (RTPs) under the care of the Renal Transplantation Service at the Manchester Royal Infirmary, who had received a renal allograft at least 18 months earlier, were recruited for this study. All but one of the RTPs had been taking tacrolimus since transplantation. The other had commenced tacrolimus therapy two months after receiving her allograft. A hospital based control group was recruited from non transplanted individuals attending the Turner Dental School, Manchester. Each patient underwent a detailed dental assessment and had dental impressions taken. The extent of gingival overgrowth was determined from plaster models.. 25 renal transplant recipients and 26 control patients were included in the study. None of the individuals in either the tacrolimus or control groups had clinically significant overgrowth. The patients in the tacrolimus group with the highest overgrowth scores were those also taking calcium antagonists as treatment for hypertension.. This study demonstrates that tacrolimus has no adverse effects on the gingival tissues and thus has potential as an alternative immunosuppressant for individuals susceptible to developing cyclosporin A-induced gingival overgrowth.

Topics: Adult; Antihypertensive Agents; Calcium Channel Blockers; Case-Control Studies; Dental Plaque Index; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Tacrolimus

Immunosuppression by cyclosporin A (CsA) is associated with adverse side-effects, including nephrotoxicity, neurotoxicity and gingival overgrowth. Tacrolimus (TAC/FK506) is a new immunosuppressive agent, recently approved for use in solid-organ transplants. The mode of action of TAC is similar to that of CsA and the toxicity profile of CsA is duplicated by TAC. The effect of TAC on the gingival tissue is not yet conclusive.. Gingival overgrowth was assessed in 30 liver transplant children, 20 boys and 10 girls, aged 2-19 years. Seventeen children (10 boys, seven girls) were on a CsA-based immunosuppressive regimen whereas 13 children (10 boys, three girls) were on TAC for at least 1 year (mean 4.3 +/- 2.7).. In the CsA group, 35% of children exhibited gingival overgrowth characterized by one or more units with increased sulcus probing depth (> or = 4 mm), i.e. pseudopockets. In contrast to the CsA group, none of the children in the TAC group exhibited gingival overgrowth. The occurrence of enamel hypoplasia was observed in 11 children (36%) and enamel opacities were found in 23 children (76%). Six of the 12 children (50%) with hyperbilirubinaemia biliary atresia exhibited a marked greenish discoloration of the teeth. Caries experience (dmft/DMFT) among these children was 2.0 +/- 2.8.. No difference in caries experience or enamel defect was observed between the CsA and TAC group.

Topics: Adolescent; Adult; Biliary Atresia; Child; Child, Preschool; Cyclosporine; Dental Enamel; Dental Enamel Hypoplasia; Dental Plaque Index; DMF Index; Female; Follow-Up Studies; Gingival Overgrowth; Gingivitis; Humans; Hyperbilirubinemia; Immunosuppressive Agents; Liver Transplantation; Male; Mouth Diseases; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Statistics as Topic; Statistics, Nonparametric; Tacrolimus; Tooth Discoloration; Tooth Diseases

To determine the prevalence of dental caries in children undergoing liver transplantation and to compare the plaque, gingivitis, and gingival overgrowth indices and oral mucosal lesions in children before and after liver transplantation.. Patients undergoing liver transplantation at King's College Hospital were examined before transplantation, at 3 and 106 days post-transplantation. Healthy children from the Greenwich Health District, south-east London, were matched to the liver transplant patients by age, gender, socio-economic factors and the presence or absence of active dental caries.. Twenty-seven liver transplant patients (mean age: 7 years and 10 months; SD 3 years and 5 months) and 27 controls (mean age: 8 years and 6 months; SD 3 years and 7 months) were examined. The mean dmft and DMFT scores were 2.3 (SD 4.1) and 0.8 (SD 1.4), respectively, in the liver transplant patients, and 1.2 (SD 2.2) and 0.9 (SD 1.5), respectively, in the controls. There were no significant differences between either the mean plaque or gingivitis indices for the primary and permanent teeth in patients before and after transplantation. There were no significant differences between the liver transplant patients and the controls for either mean plaque or gingivitis indices at each examination time. Gingival overgrowth was present in 41% of liver recipients receiving cyclosporin with or without nifedipine, but not in the majority receiving tacrolimus at the final examination. Oral mucosal lesions were absent in both the patients and controls at each examination time.. The oral health of the children undergoing liver transplantation was inadequate. Funding and implementation of an oral health care programme must become a priority for all children before and after liver transplantation.

Topics: Adolescent; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; Cyclosporine; Dental Caries; Dental Plaque; Dental Plaque Index; DMF Index; Female; Follow-Up Studies; Gingival Overgrowth; Gingivitis; Humans; Immunosuppressive Agents; Liver Failure; Liver Transplantation; Male; Nifedipine; Periodontal Index; Prevalence; Reproducibility of Results; Socioeconomic Factors; Statistics as Topic; Statistics, Nonparametric; Tacrolimus; Tooth, Deciduous

Gingival overgrowth is a well documented and common side-effect of cyclosporin therapy. Gingival swelling in this condition hinders efficient oral hygiene and is of aesthetic concern to patients. This case report outlines rapid and dramatic reduction in overgrowth when tacrolimus replaced cyclosporin as the immunosuppressive agent in a renal transplant patient with established overgrowth.

Topics: Adult; Cyclosporine; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Tacrolimus

To determine the oral health status, oral microflora and the effect of non-surgical periodontal treatment on gingival overgrowth of renal allograft recipients receiving either cyclosporin A (CsA) or FK506 (Tacrolimus) as an immunosuppressant.. A total of 47 patients receiving CsA (mean age 43.1 years) and 10 receiving FK506 (mean age 40.1 years) were included in the study. Stone casts were taken for measurement of gingival overgrowth. An oral rinse technique was used to investigate the prevalence of yeasts, and aerobic and facultatively anaerobic Gram-negative rods (AGNR).. The CsA and FK506 patients exhibited a Gingival Overgrowth Index (GOI) of 45.2%, and 25.1%, respectively (p < 0.05). The CsA patients had a GOI of 15.2% after one year of non-surgical periodontal treatment. The difference between pre- and postoperative gingival overgrowth indices was significant (p < 0.0001). Candida albicans and Klebsiella pneumoniae were the most notable yeast and AGRN found.. Renal transplant patients, being immunocompromised, constitute a high-risk group for gingival overgrowth. However, the FK506 regime appeared to ameliorate this effect, compared with CsA. Non-surgical periodontal treatment was effective in reducing established gingival overgrowth in both CsA and FK506 patients (p < 0.05). Adequate pre- and post-transplant oral health care is recommended, for these patients, irrespective of the drug regime.

Topics: Adult; Aged; Candida; Cohort Studies; Cyclosporine; DMF Index; Enterobacteriaceae; Follow-Up Studies; Gingival Overgrowth; Gram-Negative Aerobic Rods and Cocci; Gram-Negative Facultatively Anaerobic Rods; Health Status; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mouth; Oral Health; Periodontal Diseases; Periodontal Index; Risk Factors; Statistics as Topic; Tacrolimus; Transplantation, Homologous

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.

Topics: Cyclosporine; Gingival Hyperplasia; Gingival Overgrowth; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Tacrolimus