sirolimus and Gingival-Overgrowth

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

Drug-induced gingival overgrowth (DIGO) is an oral clinical manifestation associated with certain medications such as immunosuppressants that are administered to organ transplant patients to prevent graft rejection. In patients with cardiac transplants, management of DIGO is critical. In such patients, plaque biofilm accumulation at the gingival interface might be detrimental as it may lead to transient bacteremia as well as systemic inflammation resulting in thromboembolic events. This case report describes the management of DIGO in a cardiac transplant recipient by change of immunosuppressant medication, non-surgical periodontal therapy and laser-assisted gingivectomy.

Topics: Adult; Cyclosporine; Dental Scaling; Follow-Up Studies; Gingival Overgrowth; Gingivectomy; Gingivoplasty; Heart Transplantation; Humans; Immunosuppressive Agents; Laser Therapy; Lasers, Semiconductor; Male; Oral Hygiene; Root Planing; Sirolimus

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

Although the prevalence of gingival overgrowth (GO) in calcineurin-inhibitor (CNI) immunosuppressive regimens has been well documented, to the best of our knowledge data from sirolimus (SIR) regimens have not been described. We sought to investigate the gingival status of renal transplant recipients under SIR-based regimens with regard to the prevalence and potential risk variables associated with GO.. A cross-sectional study was conducted at a public hospital in Belo Horizonte, MG, Brazil. Of 886 transplant recipients, an eligible sample of 144 subjects was selected. Medical, pharmacologic, and periodontal variables were recorded for each subject. GO was assessed through visual inspection and was evaluated in relation to variables of interest by univariate and multivariate analyses.. Although not clinically significant, 20.8% of the samples had GO, with a mean GO score of 5.0% +/- 3.98% (range, 0% to 19%) and mean GO score per papilla of 0.378 +/- 0.361 (range, 0.1 to 1.9); the percentage of papilla affected by GO was 14.35% +/- 9.86% (range, 5% to 45%). The multivariate final model, excluding periodontal variables, showed that the concomitant use of calcium channel blockers (P = 0.033) and the interaction between time since transplant and previous CNI use (P <0.001) were associated with GO. Adding periodontal variables to the model improved its accuracy and retained papillary bleeding index as being strongly associated with GO (P <0.001).. GO was observed in a considerable number of subjects under SIR-based immunosuppressive regimens, although the relationship was not clinically significant. Findings point to the importance of cooperation between medical and dental health care personnel in the maintenance of renal transplant recipients under SIR-based immunosuppressive regimens.

Topics: Adolescent; Adult; Aged; Brazil; Calcium Channel Blockers; Cohort Studies; Cross-Sectional Studies; Dental Care for Chronically Ill; Female; Gingival Overgrowth; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Periodontal Index; Severity of Illness Index; Sirolimus; Young Adult