Stereologic study of cyclosporin A‐induced gingival overgrowth in renal transplant patients

Abstract

Gingival biopsies were taken from 13 renal transplant patients (mean age 26.5 yr), 11 of whom exhibited cyclosporin A (CsA)-induced gingival overgrowth. Control material was obtained from seven volunteers (mean age 28 yr). Gingival tissue components were analyzed by quantitative microscopy (stereology) on 5-microns-thick sections of interdental papillae. The volume density (Vv) of different tissue components and the surface density of epithelial ridges were calculated by conventional point and intersection counting. The study showed that the volume density of oral epithelium and the surface density of the epithelial ridges in the CsA-induced gingival overgrowth were significantly increased compared to normal gingival tissue. The connective tissue of the lesion exhibited a significant increase in volume density of cells, blood vessels and non-collagenous matrix with a corresponding decrease in the collagenous matrix. These results indicate that CsA-induced gingival overgrowth represents a tissue with an altered composition characterized by increased thickness of oral epithelium and relatively increased amount of cells, vessels, non-collagenous matrix and decreased collagenous matrix in the connective tissue.

Increased Expression of Vascular Endothelial Growth Factor in Cyclosporin A‐Induced Gingival Overgrowth in Rats

“…The relationship between CsA treatment and gingival overgrowth has been reported in human and some experimental models, 2,6,8,31‐35 although the exact etiology is not understood. The pathophysiological mechanisms of CsA‐induced gingival overgrowth may include features such as an increase in the epithelial thickness and an increase in the proliferation of connective tissue components 4,6,8,9 . The other important feature of gingival overgrowth tissue is increased vascularization, and previous studies have shown that CsA increases the cross‐sectional area of blood vessels in GCT 8,9 …”

“…Various side effects associated with CsA therapy have been described, including nephropathy, hepatotoxicity, neurotoxicity, hypertension, and gingival overgrowth 3,4 . Gingival overgrowth is characterized by increased epithelial thickness, enlargement of connective tissue, and increased vascularization 5‐9 . According to previous histomorphometric studies, CsA‐induced gingival overgrowth shows increases in the mean cross‐sectional area of epithelium, connective tissue, and blood vessel profile 4,6,8,9 …”

“…CsA also produces antiproliferative and proapoptotic effects mediated by the caspase pathway in microvascular endothelial cells derived from human skin 27 . However, in gingival tissues, the drug increases the histomorphometric profiles of blood vessels, 8,9 but its biochemical findings in CsA‐induced gingival overgrowth are not understood. The aim of this experimental study was to examine the role of VEGF in the pathogenesis of CsA‐induced gingival overgrowth.…”

Prevalence and clinical aspects of drug-induced gingival enlargement

“…The volume density of oral epithelium significantly increased in cyclosporine A-induced gingival overgrowth as compared to non-medicated controls [20]. Epithelial thickening, induced by nifedipine [21] and cyclosporine A, is related to thickening of spinous layer [20].…”

“…Epithelial thickening, induced by nifedipine [21] and cyclosporine A, is related to thickening of spinous layer [20]. Brown, Beawer, Bottomlay [22] suggested a functional heterogenecity between subgroups of fibroblasts in normal tissues.…”