Risk factors in the development of cyclosporine-induced gingival overgrowth.
BACKGROUND
Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of cyclosporine-A (CsA). Using the largest group of renal allograft recipients assembled for this purpose, in this study, we statistically modeled the genetic (HLA), medical, and dental risk factors for the development of GH subsequent to administration of CsA.


METHODS
Two hundred thirty-six renal transplant patients underwent full dental examination to quantify the extent and distribution of hyperplasia and dental disease (gingivitis, plaque, and calculus). Computerized data from all patients included pre-transplant medical history and dosage of nifedipine and azathioprine, as well as dose and serum levels of CsA and CsA microemulsion. Donor and host HLA haplotype were studied to investigate potential association of haplotype and donor-host mismatching with the development of GH. We evaluated the data by multivariate regression analysis, using Statistical Package for Social Sciences (SPSS).


RESULTS
There was no association with age, sex, duration of renal replacement therapy, or interval since transplantation or pre-transplant disease (P>0.05). There also was no association of disease with host HLA haplotype, but degree of HLA-A mismatching was protective for GH development (P<0.002). GH was associated with the dose and serum levels of CsA (P<0.001) and the last dose of CsA microemulsion (P=0.009) but not nifedipine (P=0.10). Gingival inflammation and plaque were also strongly associated with GH (P<0.0003). In multivariate analysis, however, the last recorded dose of CsA (P<0.0001), presence of local gingival inflammation (P<0.0001), and gingivitis (P<0.003) were the independent predictors of the extent and severity of GH.


CONCLUSIONS
Inter-patient variation in the extent and severity of GH is related to CsA dose and serum levels. Differences in host HLA phenotype do not explain individual susceptibility to GH, but donor-host HLA-A mismatching may be important. Inter-site variation in the extent and severity of the disease is related to local gingival inflammation.
Thomas
D W
DW
Department of Oral Surgery Medicine and Pathology, University of Wales College of Medicine, Cardiff, United Kingdom. woadwt@cf.ac.uk
Newcombe
R G
RG
Osborne
G R
GR
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood; D005260:Female; D005885:Gingival Hyperplasia / Q000139:chemically induced* / Q000453:epidemiology* / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index
D006680:HLA Antigens; D016572:Cyclosporine