Phenytoin-induced Gingival Hyperplasia Research Articles

Phenytoin-induced gingival hyperplasia

Phenytoin-induced gingival hyperplasia

Association of Galactose Single‐Point Test Levels and Phenytoin Metabolic Polymorphisms with Gingival Hyperplasia in Patients Receiving Long‐Term Phenytoin Therapy

To evaluate whether the occurrence or severity of gingival hyperplasia is associated with liver function test results or phenytoin metabolism. Prospective analysis. University-affiliated medical center in Taipei, Taiwan. Sixty-six patients (mean age 37.9 yrs) with epilepsy who were receiving phenytoin for more than 1 year. Intervention. Four blood samples were drawn from each patient for liver function testing, concentrations of phenytoin and its metabolites R-5-(4'-hydroxyphenyl)-5-phenylhydantoin (R-HPPH) and S-HPPH, and genotyping of cytochrome P450 (CYP) 2C9 and 2C19. Plasma concentrations of phenytoin and its metabolites were determined by a high-performance liquid chromatography method. The CYP2C9 and CYP2C19 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Conventional liver function assays and a quantitative liver function test--galactose single-point (GSP) measurement--were performed. Statistical analyses were performed to evaluate the association between liver function test results as well as metabolic phenotype and the occurrence and severity of gingival hyperplasia. Among liver function tests, only GSP levels showed a significant difference between patients with and those without gingival hyperplasia. Patients with an elevated GSP level (> or = 280 microg/ml) had a significantly higher odds ratio (OR 4.51) for the occurrence of gingival hyperplasia. In addition, increased R-HPPH (OR 1.02) and phenytoin (OR 1.09) concentrations were associated with an increased occurrence of gingival hyperplasia. However, only increased GSP and R-HPPH concentrations had significantly higher ORs (2.84 and 1.02, respectively) associated with the severity of gingival hyperplasia. Although mean +/- SD plasma R-HPPH concentration was significantly lower in CYP2C19 poor metabolizers compared with CYP2C9 and CYP2C19 extensive metabolizers and CYP2C9 poor metabolizers (30.38 +/- 16.73 vs 68.22 +/- 44.75 and 78.95 +/- 51.67 microg/ml, respectively), no significant association between genotype and gingival hyperplasia was found. Increased GSP, phenytoin, and R-HPPH concentrations were associated with increased occurrence of phenytoin-induced gingival hyperplasia; only increased GSP and R-HPPH concentrations were associated with increased severity of this adverse effect.

The subgingival microflora in phenytoin-induced gingival hyperplasia.

Microbial flora and gingival conditions were compared between a group of patients with phenytoin-induced gingival hyperplasia as a test group, a control group of patients who were administered phenytoin without gingival hyperplasia and a blank group who took no phenytoin and no gingival hyperplasia in mentally retarded patients. Subgingival plaque samples were collected from a PHT-induced overgrown gingival pocket and microbiological experiments were performed by culture and PCR methods. The predominant genera in total cultivable bacteria from subgingival plaque samples were streptococcus and actinomyces with recovery ranges of 37.6-42.1% and 23.4-25.5% of total bacteria, respectively, in all groups. The test group showed a significantly higher level of obligate Gram-negative rods than the control and blank groups. Black-pigmented obligate anaerobic Gram-negative rods were detected in 10.3% of total cultivable bacteria in the test group. The black-pigmented rods were predominantly Prevotella intermedia in the test group and Prevotella nigrescens in the control and blank groups. Porphyromonas gingivalis and Porphyromonas endodontalis were also detected in the test group with small values. These results suggested that black-pigmented rods, particularly P. intermedia, could be habitable in the environment of gingival hyperplasia.

Phenytoin Induced Hyperplasia Found in Edentulous Patients

Phenytoin-induced gingival hyperplasia is usually associated with teeth, but it’s described here in two edentulous patients, both with dentures.

The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia: A double-blind, randomized, placebo-controlled, parallel study

Twenty severely retarded institutionalized epileptic adults with phenytoin-induced gingival hyperplasia were divided into two groups and received a daily 3 mg capsule of either folic acid or lactose for 16 weeks in a randomized, double-blind, parallel study. Serum folate and phenytoin levels were recorded at baseline and on completion of the study. Twelve areas of the gingiva on each patient were graded at 4-week intervals for 16 weeks with respect to the three indexes: hyperplasia, gingival health, and plaque index. There were no significant differences between treatment groups for any of the three indexes over time. The poststudy serum folate levels were three times baseline levels for the active drug group ( p < 0.001) but unchanged in the placebo group. Phenytoin blood levels that began within the therapeutic window (10 to 20 μg/ml) tended to remain within the therapeutic window for both groups, with no reported seizure activity. A single daily oral 3 mg capsule of folic acid did not show efficacy as the sole therapeutic agent in the reduction of phenytoin-induced gingival hyperplasia.

Langerhans cells in human chronic gingivitis and phenytoin-induced gingival hyperplasia

Langerhans cell numbers in oral epithelium increase as dental plaque accumulates. The anti-convulsant drug phenytoin predisposes to gingival hyperplasia in certain patients who take this medication for epilepsy and who also have poor oral hygiene. In this study 7 patients with phenytoin-induced gingival hyperplasia were compared with 5 subjects with chronic marginal gingivitis. On initial examination and on completion of the hygiene phase of periodontal therapy (a period ranging from 3.0 to 4.25 months), clinical indices of plaque and gingivitis were recorded and biopsies were taken from the lower anterior labial gingiva. Frozen sections were stained by an immunoperoxidase technique using the monoclonal antibody OKT6, and the number of Langerhans cells in a defined cross-sectional area was counted. In phenytoin-induced gingival hyperplasia there was a marked increase in Langerhans cells (13.8 ± 0.45) when compared with chronic gingivitis (7.7 ± 0.31; p < 0.05). Both groups showed marked reductions in their plaque and gingival indices and numbers of Langerhans cells once treatment had been completed. However, levels of Langerhans cells in the drug-induced hyperplasia remained significantly higher (3.5 ± 0.26) than in chronic gingivitis (1.5 ± 0.22; p < 0.05).

New developments in understanding phenytoin-induced gingival hyperplasia

In approximately half of the patients taking phenytoin, gingival fibroblasts proliferate, causing tissue overgrowth and gingival hyperplasia. Recent clinical and basic research is reviewed, describing the conditions associated with phenytoin therapy and gingival hyperplasia.