Gingival Enlargement in Antihypertensive Medication

Introduction: Drug-induced gingival enlargement is a well documented side effect with the use of phenytoin, cyclosporine and calcium channel blockers. The prevalence of gingival enlargement induced by calcium channel blockers is uncertain. Several studies show confl icting results ranging from 20% to 83%. This study was conducted to determine the prevalence of gingival enlargement in patients taking antihypertensive medication.


INTRODUCTION
2][3][4][5][6][7][8] It was fi rst reported in 1939 6 with chronic usage of phenytoin.CCBs, Angiotensin converting enzyme (ACE) inhibitors and β-blockers are the most commonly prescribed antihypertensives.It has been reported in patients treated with CCBs like nifedipine, [9][10][11][12][13] nitrendipine, 14 nicardipine, 15 felodipine, 16 and amlodipine. 17,18GE presents with similar clinical and microscopic appearance.It begins within 3 months as a fi rm, nodular enlargement limited to keratinized portions of interdental papilla.Histologically, it is characterized by an increase in connective tissue component.Gingival infl ammation also appears to be an important predisposing factor suggesting that the lesion is a consequence of interaction between gingival fi broblasts, cellular and biochemical mediators of infl ammation and drug metabolites.The present study aims to determine the prevalence and severity of DIGE in patients taking antihypertensive drugs and their relation with oral hygiene status of the patients.

METHODS
A cross sectional study was carried out among all consecutive patients attending the out patient department (OPD) of dental surgery, Bir Hospital, Nepal Academy of Medical Sciences (NAMS) from July 2008 to December 2008.Ethical approval and patient consent was obtained.Patients presenting with dental problems on antihypertensive agents were included.Gingival enlargement was considered to be present if visible enlargement was present in interdental papilla, marginal gingiva and/or attached gingiva and graded according to the severity into mild (only interdental papilla involved), moderate (marginal gingiva also involved) and severe (attached gingiva also involved).Patients were divided into 4 groups based on the duration of drug consumption viz. group I (0-1 yr), group II (1-5y), group III (5-10 years) and group IV (>10 years).
Plaque index was considered as described by Quigley  and Hein (1962) and divided into good, fair and poor plaque index. 18A standard periodontal probe (Michigan O probe with William markings) was used to measure the probing depth.
Prevalence rate was determined.It was analysed as per severity; oral hygiene status and duration of drugs consumption using Statistical Package for Social Sciences (SPSS) 13.0 Chi-square test was used to determine statistical signifi cance.

RESULTS
Total 150 patients taking antihypertensive agents were included.Signifi cant enlargement was seen in 81.2%.The prevalence of gingival enlargement was higher in patients taking CCBs (71.1%) followed by ACE inhibitor (21.5%) and β-blockers (7.4%).Mild gingival enlargement was seen in 19%, moderate in 71.9% and severe in 9.1%.Among the CCB users 18.6% had mild, 74.4% had moderate and 7.0% had severe gingival enlargement.Signifi cant difference was not seen in patients using different antihypertensive agents (P>0.05) which possibly shows the effect of poor oral hygiene on gingival enlargement (Table 1).Patients taking antihypertensive agents for 5 to 10 years showed the most severe gingival enlargement (Table 2).
Plaque index was either poor or fair in all patients.None had good plaque index.Among patients with poor oral hygiene, mild gingival enlargement was seen in 10.6%, moderate in 66.4% and severe in 7.1% (P<0.05)(Table 3).Poor plaque index was seen among 73.6% using CCBs, 19.8% using ACE inhibitors and 6.6% using βblockers (Table 4).

DISCUSSION
In the study population, prevalence of DIGE was seen in 71.1% treated with CCBs 21.5% with ACE Inhibitors group and 7.4% with β-blockers.Most patients had moderate severity moderate severity which could be attributed to the poor oral hygiene as well.It is thus diffi cult to establish whether the high plaque scores observed are the cause or the consequence of the DIGE.Therefore mild enlargement may be a very important factor taken into account for early detection of DIGE in such patients.
Ellis et al in a group of 911 patients treated with CCBs, showed a prevalence lower than in previous studies, with marked differences between the different drugs like nifedipine (6.3%), amlodipine (1.7%) and diltiazem (2.2%) and with higher risk for developing clinically signifi cant gingival enlargement in the patients treated with nifedipine, than in those taking either amlodipine or diltiazem. 19ten drug-induced gingival enlargement involves a form of combined gingival enlargement, with the effect of the drug and the infl ammatory status and, therefore, it is diffi cult to determine the contribution of each factor.Some authors have reported a relationship of gingival enlargement with both gingival index and plaque index 5,12,20,21 indicate that risk factors for DIGE are: drug variables, concomitant medications, periodontal variables, age, gender and genetic factors.
The results of present study suggest that gingival infl ammation has a stronger effect than drug treatment itself in patients treated with antihypertensive.This study also refl ects the higher tendency of physicians to prescribe calcium channel blockers for patients with hypertension.We must highlight the great number of calcium antagonists, that are being studied and that may have an effect on the gingiva, such as verapamil, 22 nitrendipine, 14 felodipine, 16 oxodipine in rats. 23e logical approach in the control of gingival enlargement induced by drugs should be reduction of the dose of the drug or substitution of the drug.Reduction in gingival enlargement has been reported where a different calcium channel blocker, such as Verapmil has been substituted for nifedipine, 9 but more usually where substitution is made by a structurally different antihypertensive drug, such as the angiostensinconverting enzyme inhibitor, enalapril, 24 the β-blocking drug, atenolol, [25][26][27] or thiazide diuretics. 17,28Change in medication should only be considered for those patients where the new medication can offer some advantage for control of their hypertension, which present with clinically signifi cant enlargement and are at high risk from either corrective surgery or recurrence after gingivectomy. 29Reduction in the size of the gingival enlargement has been reported within a week of drug withdrawal, 30 and may lead to full resolution.

CONCLUSIONS
Patients on CCBs had a higher prevalence of DIGE.DIGE was also seen in patients taking antihypertensive agents like ACE inhibitors and β-blockers.However, poor oral hygiene could also have contributed to develop gingival enlargement in such patients.

Table 4 . Relation between plaque index and drugs used
In Nepal very few studies has been carried out till date to our knowledge and this study could signifi cantly contribute in dealing patients with antihypertensive drugs and create awareness among treating physicians.However, in-depth study with larger sample size to determine the actual prevalence of gingival enlargement with different types of calcium channel blockers, ACE Inhibitors and β-blockers is required.