Cyclosporin A effects on extra oral connective tissue in heart transplanted patients

Gingival overgrowth (GO) is an adverse side-effect of Cyclosporin A (CsA) therapy. There is wide evidence that fibroblasts are the primary cellular influence on GO and it has been hypothesised that people developing GO have fibroblasts with an abnormal susceptibility to CsA. The purpose of the study was to analyse, on a macroscopic scale, the Cyclosporin effects on soft connective tissues in order to show whether subjects with an abnormal gingival connective reaction to Cyclosporin may have macroscopic signs of a similar reaction in connective tissues other than oral cavity. Twenty-two heart transplanted patients were enrolled in the study. All patients had been on a CsA-based immunosuppression regimen for at least six months (33.2 +/- 20.5). Hyperplastic Index (HI) was considered as the periodontal parameter relating to GO. Macroscopic evidence of the residual cicatrix following thoracotomy (P1) and connective tissue hyperproduction in the subclavian region conditioning the difficulty in probing the vein during myocardial biopsies (P2) were considered as the parameters relating to extraoral cicatricial activity. Both non parametric statistical analysis (Mann Whitney U-test, linear correlation by Spearman) and parametric analysis (Student t-test) were used to investigate the relationship between HI (dependent variable) and P1, P2 (independent variables). Results failed to demonstrate any significant correlation between gingival overgrowth and cicatricial tissue hyperproduction in sites other than the oral cavity. We conclude that the hyperproduction of collagen leading to GO in a certain percentage of subjects treated with CsA is a reaction limited to the oral cavity and not a consequence of a systemic fibroblastic hyperactivity. Our data suggest that the collagen disregulation at gingival level may be a consequence of a local perturbation whose aetiological factors are however still not known.