Macrophages and lymphocyte subpopulations in nifedipine- and cyclosporin A-associated human gingival overgrowth.

BACKGROUND: Nifedipine and cyclosporin A (CsA) induce gingival overgrowth. Both drugs have immunomodulating effects. It has been suggested that altered immune response is associated with drug-induced gingival overgrowth. In this study, we evaluated whether there were differences in macrophages and lymphocyte subpopulations in human nifedipine- and CsA-associated gingival overgrowth as compared with those in normal gingiva. METHODS: Biopsy samples of overgrown gingiva were obtained from 9 nifedipine-treated cardiac outpatients, 13 CsA-treated renal transplant recipients including 9 patients who were also receiving nifedipine, and 30 healthy control individuals undergoing dental treatment. Serial 5 microm thick cryostat sections were stained with mAbs for CD20 (B-pan), CD68 (macrophages), CD4 (T-helper/inducer), and CD8 (T-cytotoxic/suppressor) using an avidin-biotin-horseradish peroxidase complex method. Numbers of mAb-labeled and all nucleated cells were determined in 3 areas: the connective tissue beneath the sulcular epithelium, the middle connective tissue, and the connective tissue beneath the oral epithelium. Distributions of each type of cell were expressed as percentages of mAb-labeled cells in relation to total number of nucleated cells in a counting zone. Significances of differences between groups were tested by means of the Kruskal-Wallis test, and between pairs of results by means of the Mann-Whitney U-test. RESULTS: The proportion of CD8-labeled cells was significantly higher in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P = 0.014). In both medicated groups, the proportions of CD68-labeled cells were higher in all counting zones than in the controls, but statistically significantly only in the nifedipine group in the connective tissue beneath the oral epithelium (P = 0.008). No intergroup differences were found with respect to CD4- and CD20-labeled cells. The CD4/CD8 ratio was significantly lower in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P= 0.013). CONCLUSION: The results support the idea that immune response may be altered in drug-induced gingival overgrowth.

The importance of regular dental treatment in patients with cyclic neutropenia. Follow-up of 2 cases.

Data on two patients with cyclic neutropenia are presented. They demonstrate that regular tooth care and professional dental treatment can prevent progressive periodontal breakdown but that neglecting oral hygiene soon leads to periodontal pathology. Regular, monthly professional removal of dental plaque and calculus, and rinsing with 0.2% chlorhexidine gluconate during neutropenia help maintain periodontal attachment level. The caries susceptibility and the apical periodontitis in the intact anterior tooth of the female patient indicate the possibility of cyclic neutropenia playing a role in caries and pulpal pathology.

Effect of periodontal treatment on gingival overgrowth among cyclosporine A-treated renal transplant recipients.

No data exist on any association between combined cyclosporine A (Cy A) and dihydropyridine (DHP) medication and the effect of periodontal treatment on the occurrence of gingival overgrowth (GO) among renal transplant recipients. Clinical data on 27 renal transplant recipients treated with Cy A are presented here, including determinations of serum creatinine, whole blood Cy A concentration, existence of DHP treatment, and periodontal status. GO was classified into four categories according to the clinical changes: score 0 = no GO; score 1 = mild GO; score 2 = moderate GO; and score 3 = severe GO. All participants received hygiene phase periodontal treatment and gingivectomies were performed on 10 who originally had score 2 or 3 GO and pocketing. Fourteen (14) of the recipients had no overgrown gingiva or less than at the initial examination, and none of them had GO score 2 or 3 at the time of re-examination (group A). Thirteen (13) participants had more overgrown gingiva than initially or developed score 2 GO after gingivectomies (group B). Group B included significantly more DHP-medicated recipients than group A (6/13 and 1/14 respectively; P < 0.03). The concomitant administration of Cy A and DHP resulted in a significantly increased percentage of score 2 overgrown gingival units as compared with Cy A alone (P < 0.03). It is concluded that combined treatment with Cy A and DHP is a significant risk factor for progression or recurrence of GO after periodontal treatment among susceptible patients.

Density of CD1a-labeled Langerhans' cells in normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth.

BACKGROUND: The purpose of this study was to compare the distribution of Langerhans' cells in normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth by means of an immunohistochemical study. METHODS: Gingival samples were collected from 11 nifedipine-medicated cardiac patients, 22 triple-medicated (azathioprine, prednisolone, and cyclosporin A) renal transplant recipients, and 28 generally healthy individuals. Patients were grouped into the immunosuppression group, the combined immunosuppression and nifedipine group, the nifedipine group, and the generally healthy control group. Five microm-thick cryostat sections were stained with monoclonal antibody (mAb) for CD1a using an avidin-biotin-enzyme complex (ABC) method. Numbers of CD1a-labeled cells/mm2 were determined in 6 areas: oral epithelium, oral sulcular epithelium, sulcular epithelium, middle connective tissue, connective tissue beneath the oral epithelium, and connective tissue beneath the sulcular epithelium. Significances of differences between the groups were tested by means of the Kruskall-Wallis test, and significances of differences between pairs of results by the Mann-Whitney U-test and the t test. RESULTS: Numbers of CD1a-labeled cells were significantly lower in the medicated groups than in controls in all 3 epithelial areas (P <0.0001) and in the connective tissue beneath the sulcular epithelium (P <0.0021). There were significantly fewer CD1a-labeled cells in the sulcular epithelium in the nifedipine group than in the other medication groups. CONCLUSIONS: The reduced numbers of CD1a-labeled cells found in nifedipine-induced gingival overgrowth were similar to the reduced numbers of CD1a-labeled cells in gingival overgrowth associated with immunosuppressive medication.

Mitotic activity of keratinocytes in nifedipine- and immunosuppressive medication-induced gingival overgrowth.

BACKGROUND: The purpose of the study was to compare mitotic activity in the basal cell layer of normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth. METHODS: Gingival samples were collected from 19 generally healthy individuals, 12 nifedipine-medicated cardiac patients, and 22 immunosuppression-medicated (azathioprine, prednisolone, and cyclosporin A) organ transplant recipients. The transplant recipients were divided into those not taking nifedipine and those taking nifedipine. Cryostat sections were stained with monoclonal antibody for Ki-67, using an avidin-biotin-enzyme complex method. The mitotic activities of epithelial cells were determined as percentages of Ki-67 labeled cells in relation to total numbers of epithelial cells in the basal layer of oral, oral sulcular, and sulcular epithelium. RESULTS: Mitotic activities were significantly higher in all 3 medication groups in the oral epithelium (P < or =0.003), and in the immunosuppression group in the sulcular epithelium (P= 0.032) than in the controls. In the oral sulcular epithelium, mitotic activity was fairly similar in all medication groups. In the nifedipine group a significant negative correlation was found between duration of nifedipine medication and the percentage of Ki-67 labeled cells in the oral epithelium (P= 0.025). CONCLUSIONS: The results suggest that the increased epithelial thickness observed in nifedipine- and cyclosporin A-induced gingival overgrowth is associated with increased mitotic activity, especially in the oral epithelium.

Gingival overgrowth among renal transplant recipients related to immunosuppressive medication and possible local background factors.

The aim of this study was to determine the occurrence of gingival overgrowth (GO) among renal transplant recipients and to analyze possible background factors causing GO among cyclosporine-treated (CsA) patients as compared with others receiving azathioprine (Aza). A total of 32 recipients, 22 treated with CsA and 10 with Aza (ages 22 to 68 years) participated. The examination included determination of renal function, whole blood CsA concentration, and periodontal status. The tooth surface data were analyzed in terms of the given background variables for GO in the whole patient sample by logistic regression analysis. The occurrence of GO was significantly higher in the CsA group as compared with the Aza group (P less than 0.03). The CsA responders had significantly more gingival units overgrown as compared with the Aza responders (P less than 0.005). There were no differences in age, sex, whole blood concentration of CsA, or duration of CsA medication between the responders and non-responders. Expressed as individual means, the gingival inflammation scores were significantly higher among the CsA responders than among the CsA non-responders (P less than 0.005). Analysis of the surface data showed that CsA had an independent major effect on GO. Furthermore, simultaneous gingival bleeding increased the risk of overgrowth (odds ratio = 2). The results show that CsA medication is a significant factor for GO and the risk of the occurrence of GO is further increased by simultaneous gingival inflammation.

Verapamil-induced gingival overgrowth: a clinical, histologic, and biochemic approach.

Verapamil-induced overgrowth was most prominent in the anterior regions and interproximal areas associated with plaque retention. Despite periodontal therapy, overgrowths recurred 1 month after gingivectomy. Discontinuation of the drug resulted in regression of the overgrowths. Histologic findings showed inflamed connective tissue covered by an acanthotic, thickened oral epithelium with long rete pegs containing dyskeratotic pearls. The proliferation rate and protein and collagen production of fibroblasts from the overgrowth sites were markedly lower than in the control cells cultured from healthy gingiva. Incubation of fibroblasts in the presence of verapamil reduced protein and collagen synthesis.

Gingival overgrowth among renal transplant recipients and uraemic patients.

No detailed data exist on an association between combined cyclosporin (CsA) and dihydropyridine (DHP) medication and gingival overgrowth among renal patients. Thirty-five renal transplant recipients treated with CsA and 28 uraemic patients participated in this research. Fourteen of the recipients and 14 of the uraemic patients were receiving DHP. The examination included determination of the duration of the CsA and DHP treatment protocols, the mean daily oral dose of DHP, and periodontal status. Gingival overgrowth was classified into four categories according to the clinical changes: score 0 = no gingival overgrowth, score 1 = mild gingival overgrowth, score 2 = moderate gingival overgrowth, and score 3 = severe gingival overgrowth. The prevalence of clinically obvious gingival overgrowth (scores 2 and 3) was 35% in those treated with CsA and DHP, 24% with CsA and 21% with DHP. The concomitant administration of CsA and DHP resulted in a significantly increased percentage of scores 2 and 3 overgrown gingival units as compared with DHP alone (P < 0.05). Gingival overgrowth (scores 1, 2, 3) did not correlate with either the daily oral dose of DHP or the duration of DHP treatment. Combined treatment with CsA and DHP did not significantly increase the prevalence of gingival overgrowth, but it did increase the severity of it among susceptible patients.