Combined treatment for a combined enlargement.

Calcium channel blockers are widely used in medical practice for the management of hypertension and in the prophylaxis of angina. Gingival overgrowth is now a recognized unwanted effect associated with many of calcium channel blockers. This can have a significant effect on the quality of life as well as increasing the oral bacterial load by generating plaque retention sites. Amlodipine, a third generation calcium channel blockers has been shown to promote gingival overgrowth, although reported in very limited cases. The management of gingival overgrowth seems to be directed at controlling gingival inflammation through a good oral hygiene regimen. However, in severe cases, surgical excision is the most preferred method of treatment, followed by rigorous oral hygiene procedures. This case report describes the management of gingival overgrowth in a hypertensive patient taking amlodipine.

INTRODUCTION

Drug-induced gingival enlargement is a well-documented unwanted side-effect within the literature. It has been associated with the use of three different types of pharmaceutical agents, including phenytoin, cyclosporine and calcium channel blocking agents.

Amlodipine, a dihydropyridine derivative is a third generation of calcium channel blockers, which shown to have longer action and weaker side effect compared to the first generation like nifedipine (Ellis et al., 1993).[1] The prevalence of gingival overgrowth in patients taking amlodipine was reported to be 3.3%,[2] which is lower than the rate in patients taking nifedipine, 47.8%.[3] During the past few years, amlodipine has been used with increasing frequency and also has been reported to promote gingival overgrowth.[4]

CASE REPORT

This was a case report of a 48-year-old female patient who was referred to the Department of Periodontology. The patient complained of extensive gingival swelling along with a foul odor, bleeding and fetid discharge from gums. She also complained of continuous mild pain and a feeling of heaviness in both upper and lower jaws. Medical history revealed that the patient was taking treatment for hypertension and was on Amlodipine 10 mg, once a day for the past 2 years. There was no history of intake of any other drugs. The patient gave a history of progressive gingival enlargement since the commencement of amlodipine therapy.

On intra-oral examination, a generalized and firm overgrowth of the gingiva was found throughout the maxilla and mandible particularly at the buccal side. Marginal and interdental gingival enlargement was well-appreciated covering almost cervical one-third of maxillary and mandibular anterior teeth. Gingiva was red in color with erythematous area and lobulated surface. Margins of the gingiva were rolled out with the loss of normal gingival scalloping. Hypertrophied areas were painless. Poor oral hygiene status of the patient was assessed from the presence of local irritating factors contributing to the inflammatory component of the gingival enlargement, which was especially more pronounced in the maxillary and mandibular anterior region [Figure 1]. The probing of the gingival sulcus revealed a range of probing depth between 5 and 7 mm and elicited the bleeding [Figure 2]. On the basis of the patient's history and clinical features, a clinical diagnosis of amlodipine-induced gingival overgrowth compounded with plaque induced chronic periodontitis was made.

Figure 1

Pre-operative view

Figure 2

Probing of the gingival sulcus presenting 5 mm deep pockets

Radiographic examination

Full mouth intra-oral radiograph and orthopantomographic examination revealed a generalized moderate horizontal bone loss [Figures 3 and 4].

Figure 3

Full mouth intra-oral radiographic series

Figure 4

Orthopantomogram showing generalized horizontal bone loss

Case management

Patient was subjected to Phase I therapy including the planned sessions of scaling and root planning. Patient's physician was consulted regarding drug substitution or withdrawal of the drug. The physician substituted the drug with enalapril (5 mg BD). Patient was instructed to maintain good oral hygiene with the use of chlorhexidine oral rinses. A dramatic response was noticed after 3 weeks of drug substitution and maintenance of regular oral hygiene. There was a regression in the size of gingival enlargement with some amount of fibrotic component left at the end of 3 weeks [Figure 5]. The surgical therapy for the remaining amount of gingival enlargement was then planned. Under local anesthesia, the enlargement was resected segment wise by internal bevel gingivectomy surgical procedure [Figure 6]. There were no post-operative complications and the healing was uneventful. The patient was followed-up regularly and at the end of 6 months patient remains asymptomatic with no signs of recurrence [Figure 7].

Figure 5

Clinical picture after drug substitution and Phase I therapy

Figure 6

Fibrotic component resected by internal bevel gingivevtomy and flaps approximated by 3.0 silk sutures

Figure 7

At 6 months post-operative view

Microscopic inspection of the gingival biopsy specimens demonstrated a connective tissue hyperplasia, acanthosis of overlying epithelium and elongated rete ridges together with few sparse inflammatory cells.

DISCUSSION

Gingival hyperplasia with its potential cosmetic implications and also providing new niches for the growth of microorganisms is a serious concern for both patients and clinician. Calcium channel blockers are considered as potential etiologic agents of drug-induced gingival hyperplasia. Although the incidence of nifedipine-induced gingival hyperplasia is high, very few reports of amlodipine-related gingival hyperplasia exist in the available literature.[56789]

The mechanisms by which calcium antagonists induce gingival hyperplasia have yet to be fully explained. Two main inflammatory and non-inflammatory pathways seem to exist. Among the several proposed mechanisms, the best hypothesis so far under non-inflammatory mechanisms is that calcium antagonists inhibit the influx of calcium ions that is needed for degradation and synthesis of collagen.[10] The accumulated collagen and other extracellular matrix not degraded owing to inhibition of calcium influx by calcium antagonists are suggested to produce gingival hyperplasia. In addition to this mechanism, the importance of good oral hygiene for prevention of gingival hyperplasia is emphasized.[11] Inflammation may develop as a result of direct toxic effects of concentrated drug in crevicular gingival fluid and/or bacterial plaques. This inflammation could lead to the upregulation of several cytokine factors such as transforming growth factor beta 1.[12]

In the present case, the presence of inflammatory component parallels the presence of vertical gingival growth and consequently the presence of periodontal pockets. It is hypothesized that the formation of pocket/pseudopocket assembly is a phenomenon that is associated with gingival inflammation.

The clinician should emphasize plaque control as the first step in the treatment of drug-induced gingival enlargement. Although the exact role played by bacterial plaque in drug-induced gingival enlargement is unclear, there is evidence that elimination of local factors and regular maintenance of good oral hygiene decrease the degree and severity of the gingival enlargement and improve the overall gingival health. In this present case, the local environmental factors such as poor plaque control at the initial presentation may act as risk factors that had contributed to worsen the existing gingival enlargement and therefore complicate the oral hygiene procedures.[13] There was some reduction of the overgrowth observed particularly at the upper arch after the initial Phase I therapy was advocated.

Because not all patients on phenytoin, cyclosporine, or calcium antagonists develop gingival overgrowth, identifying patients at risk is important in order to take the necessary measures to minimize the onset and severity of this condition. Currently, the etiology of drug-induced gingival overgrowth is not entirely understood but is clearly multifactorial. Some of the risk factors known to contribute to gingival overgrowth include the presence of gingival inflammation, presence of dental plaque that may provide a reservoir for the accumulation of drug, the depth of the periodontal pocket on probing and the dose and duration of therapy.[14]

Discontinuation of the related drug has been shown to reduce the gingival overgrowth. However, the growth recurs when the drug is re-administered.[15] In cases where alternate medication can be used, substitution in the related drug has been shown to result in regression of the overgrowth. When these measures fail to cause resolution of the enlargement, surgical intervention is recommended.

In this present case, gingival overgrowth was satisfactorily treated through initial periodontal therapy including oral hygiene instruction and motivation, and drug substitution [Figure 5]. However, due to incomplete resolution of the enlargement internal bevel gingivectomy was carried out [Figure 6]. Patient was recalled every month until first 3 months and then at the end of 6 months. Upon examination at 6 months review, the periodontal pockets were generally reduced to 3 mm. Very mild gingivitis was observed at the labial surface of lower incisors. Regular oral hygiene reinforcement and scaling was carried out during the maintenance phase. At 6 months after completion of the surgery, disappearance of gingival overgrowth and satisfactory periodontal condition were confirmed [Figure 7].

SUMMARY AND CONCLUSIONS

The reported case is an example of slowly progressive periodontitis. This was superimposed by a combined type of gingival enlargement; basically a drug-induced one, complicated by inflammatory changes due to plaque accumulation.