tacrolimus and Gingivitis

Desquamative gingivitis (DG) is a clinical condition characterized by red, painful, glazed, and friable gingiva, which might be a manifestation of some autoimmune mucocutaneous diseases. The time from the development of initial signs of DG to diagnosis can vary from months to years. Based on a literature search, no data concerning patients with DG without signs of autoimmune disease were available.. The aim of this trial was to compare the efficacy and tolerability of monotherapy with topical tacrolimus 0.1% in pectin ointment versus clobetasol propionate 0.5% ointment in adults affected by DG.. This randomized, double-blind clinical trial was conducted at the Dipartimento di Medicina Clinica e Sperimentale, Universita di Verona, Verona, Italy. Patients aged > or =18 years were selected using the department's electronic medical records based on a clinical diagnosis of moderate to severe DG. After a 2-week washout period, patients were randomly assigned to receive 2 mL of tacrolimus 0.1% in pectin (equivalent to 0.2 mg of tacrolimus) or 2 mL of clobetasol propionate 0.5% ointment (equivalent to 1 mg of clobetasol) QD for 4 weeks. Evaluations were performed before treatment (baseline), after the treatment period (week 4), and at 2 follow-up visits at weeks 6 and 8. The signs of DG (ie, erythema [atrophy] and desquamation [erosions/ulceration]) were quantified by a blinded investigator using a calculated score based on their surface extension, using a drawing in which the areas of various zones of the mouth were indicated as a percentage of the whole oral mucosa. Severity of erythema and desquamation was rated on a 4-point scale (0 = absent; 1 = involvement of <5% of surface [mild]; 2 = 5%-15% [moderate]; and 3 = >15% [severe]). The primary end point was the number of patients who achieved remission (severity score of 0) in either sign; the secondary end point was the proportions of patients achieving improvement (severity score of 0 or 1) in either sign. Before and after treatment, we measured the serum concentrations of tacrolimus and its metabolites with an immunoenzymatic assay kit. Tolerability was assessed using hematology, biochemistry, urinalysis, measurements of systolic/diastolic blood pressure and heart rate, patient interview, and spontaneous reporting.. A total of 24 patients (18 women, 6 men; all white of Italian origin; age range, 21-65 years; 12 patients per treatment group) were enrolled in the study. In the tacrolimus group, 11 (91.7%) patients achieved remission of erythema and/or desquamation at weeks 4 and 6; at week 8, these rates were 9 (75.0%) and 8 (66.7%), respectively; none of the patients in the clobetasol group achieved remission of either sign at any time point (all, P < 0.001). At weeks 4, 6, and 8, significantly greater proportions of patients treated with tacrolimus had improved erythema and desquamation compared with those treated with clobetasol (all, P < 0.001). At week 4, all patients had undetectable serum tacrolimus concentrations (<1.5 microg/L). Six (50.0%) patients in the tacrolimus group reported a mild oral burning sensation, and 6 (50.0%) patients in the clobetasol group reported mild mouth dryness. No other adverse events were reported.. The results of this small study suggest that topical tacrolimus 0.1 % in pectin was more effective compared with clobetasol propionate 0.5% ointment in the treatment of DG. Both treatments were generally well tolerated in the population studied.

Topics: Administration, Topical; Adult; Aged; Clobetasol; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Gingivitis; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Pectins; Severity of Illness Index; Tacrolimus; Treatment Outcome

Abstract.

Topics: Administration, Topical; Clobetasol; Gingivitis; Humans; Lichen Planus, Oral; Tacrolimus; Treatment Outcome

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

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

Gingival crevicular fluid (GCF) levels of transforming growth factor-beta(1) (TGF-beta(1)) have been previously investigated in relation to the pathogenesis of cyclosporine-A (CsA)-induced gingival overgrowth (GO) but no clinical data are available regarding the GCF levels of TGF-beta(1) in patients treated with tacrolimus (Tac). However, as gingival inflammation is pronounced at sites of GO and this consequently may lead to an elevation in TGF-beta(1) levels the present study aimed to evaluate gingival crevicular fluid (GCF) TGF-beta(1) levels in renal transplant patients using CsA or Tac without GO.. GCF TGF-beta(1) levels were investigated in 30 renal transplant patients without GO medicated with either CsA (n=15) or Tac (n=15). Sixteen gingivitis patients and 15 periodontally healthy subjects were selected as controls. Periodontal status was evaluated by measuring probing depth, plaque index and papilla bleeding index. The TGF-beta(1) levels were analysed by enzyme-linked immunosorbent assay.. Both CsA and Tac groups had significantly elevated GCF TGF-beta(1) total amount compared to gingivitis and healthy groups (p<0.008). GCF TGF-beta(1) total amount of CsA and Tac groups was similar (p>0.008). Gingivitis and healthy groups had also similar GCF TGF-beta(1) total amount (p>0.008).. Within the limits of the present data it is unlikely that TGF-beta(1) is an exclusive mediator of CsA- or Tac-induced GO. However, pathogenesis of GO is multifactorial and contribution of TGF-beta(1) to the interrelations between cytokines and growth factors with fibrogenic potential cannot be disregarded.

Topics: Adult; Cyclosporine; Enzyme-Linked Immunosorbent Assay; Female; Gingival Crevicular Fluid; Gingivitis; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Periodontal Index; 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

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Clobetasol; Dose-Response Relationship, Drug; Double-Blind Method; Gingivitis; Humans; Immunosuppressive Agents; Ointments; Patient Selection; Pectins; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Tacrolimus

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

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