Management of amlodipine-induced gingival enlargement: Series of three cases.

Gingival enlargement is one of the side effects associated with certain drugs. Amlodipine, a calcium channel blocker, used as antihypertensive drug has been found associated with gingival hyperplasia. This case series presents diagnosis and management of amlodipine-induced gingival hyperplasia. Amlodipine-induced gingival enlargement was diagnosed and managed by thorough scaling and root planning. Drug substitution and surgical intervention was performed in first two cases. The pathogenesis of gingival enlargement is uncertain and the treatment is still largely limited to the maintenance of an improved level of oral hygiene and surgical removal of the overgrown tissue. Several factors may influence the relationship between the drugs and gingival tissues as discussed by Seymour et al. Meticulous oral hygiene maintenance, switchover to alternative drug, professional scaling and root planning and surgical excision of enlarged gingival tissue may help overcome the effect of these drugs.

INTRODUCTION

Gingival enlargement is one of the side effects associated with the administration of several drugs.[1] Currently, more than 20 drugs are associated with gingival enlargement. Drugs having side effect of gingival enlargement can be broadly divided into three categories: anticonvulsants, calcium channel blockers and immunosuppressants. Many of the calcium channel blockers used as antihypertentive drugs have been implicated in causing gingival enlargement. Amlodipine is dihydropyridine derivative used as antihypertensive drug having longer action and comparatively lesser side effect than Nifedipine (calcium channel blocker). Amlodipine-induced gingival enlargement is comparatively less prevalent among calcium channel blockers. Since pathogenesis of gingival enlargement is not well-understood, it is still a challenge for the periodontists to diagnose and manage the case effectively.

Prevalence

Amlodipine-induced gingival enlargement is comparatively less prevalent than other calcium channel blocker. Jorgensen, 1997 had reported the prevalence of amlodipine-induced gingival enlargement as 3.3%.[2]

CASE REPORT

Case 1

A 47-year-old female was referred to the Department of Periodontia of Dr. R. Ahmed Dental College and Hospital, Kolkata with complaints of gingival enlargement with foul odor, bleeding and fetid discharge from gums since 1 year. General examination revealed normal built. Patient was hypertensive with history of taking amlodipine 5 mg once daily+losartan 50 mg once daily since last 7 years.

Intraoral examination revealed poor oral hygiene, generalized nodular enlargement of gingiva mainly on the facial aspect of teeth. Gingiva was inflammed and soft to firm in consistency [Figure 1a].

Figure 1

Case 1 — (a) intraoral picture at first visit (b) three months after phase-1 therapy (c) after correction of maxillary gingival overgrowth by flap procedure (d) after correction of mandibular gingival overgrowth by external bevel gingivectomy (e) photomicrogragh showing hyperplastic squamous epithelium with few chronic inflammatory cells in connective tissue (f) twelve-month postoperative view

Investigation

Routine blood and orthopantomographical examination were within normal limit.

Treatment

Amlodipine was omitted as per advice of physician, switching over to monotherapy of losartan 50 mg once in a day. Patient was educated and motivated for maintenance of proper oral hygiene. Professional scaling and root planning was performed. After 3 months of phase-1 therapy, remaining excess gingival tissue was planned to correct by surgical intervention. [Figure 1b] Gingivectomy was instituted for maxillary gingival tissue flap procedure and for mandibular gingival tissue [Figure 1c and d].

Histopathological examination

Excised tissue was sent for histopathological examination. Section stained with H and E revealed the presence of hyperplastic squamous epithelium without any dysplastic features. There was mild chronic inflammatory cells infiltrate in the connective tissue [Figure 1e].

Followup visit

On seventh day of follow-up visit periodontal pack was removed. Healing procedure was uneventful. Clinical outcome on 12 months of follow-up visit is shown in [Figure 1f].

Case-2

A female patient of 50 years reported with complaints of gum swelling and generalized sensitivity of teeth since 2 months. Patient was under treatment of essential hypertension for 5 months and was taking amlodipine 5 mg (OD) +telmisartan 40 mg (OD) since 5 months. Intraoral examination revealed very poor oral hygiene; generalized gingival enlargement covering one-third to half of the tooth surface. Gingival enlargement involved marginal, papillary gingiva as well as attached gingiva also. Gingiva was highly inflamed with multiple areas of spontaneous bleeding with generalized abrasion and staining of teeth [Figure 2a].

Figure 2

Case 2 — (a) intraoral picture at first visit (b) ten weeks after phase-1 therapy (c) nine-month postoperative view

OPG revealed generalized horizontal bone loss. Report of hemogram and other blood test were within normal range.

Amlodipine was substituted to telmisartan 40 mg (OD) and verapamil 40 mg (BD). Phase-1 therapy was performed. After 10 weeks of follow-up inflammation was markedly reduced with some reduction in gingival enlargement [Figure 2b]. Remaining excess gingival was corrected by surgical periodontal treatment. Healing was uneventful.

Histopathology

Microscopic picture revealed presence of hyperplastic-straitified squamous epithelium without dysplasia. The underlying connective tissue contained scanty inflammatory cells.

Patient was recalled after every 3 months. The 9-month follow-up visit is shown in [Figure 2c].

Case-3

A 60-year-old female patient presented with generalized gingival enlargement with localized pink fibrous, pedunculated, 2΄3 cm soft tissue mass in relation to maxillary left canine-premolar region. Poor oral hygiene with spacing in maxillary and mandibular anterior teeth was also observed [Figure 3a]. Patient was taking amlodipine 5 mg (OD) since last 10 years. ECG and blood investigation report was within normal limit.

Figure 3

Case 3 — (a) intraoral picture at first visit (b) two months after phase-1 therapy

Oral hygiene maintenance instructions were given to patient. Thorough scaling and root planning were performed and amlodipine was substituted with losartan 50 mg (OD).

After 2 months there was significant reduction in gingival enlargement. Patient is under regular follow-up [Figure 3b].

DISCUSSION

Gingival hyperplasia, with its potential cosmetic implication and tendency to provide niche for further growth of microorganism, possess a serious concern to patients and clinicians. Calcium channel blockers are considered as potential etiological agent for inducing gingival enlargement. Lafzi et al. (2006) had reported rapidly developing gingival hyperplasia in patient receiving 10 mg/day of amlodipine within 2 month of onset.[3] The prevalence of amlodipine-induced gingival overgrowth was reported to be 3.3% (Jogersen, 1997). The underlying mechanism of gingival enlargement still remains to be fully understood. However, two main inflammatory and non-inflammatory pathways have already been suggested. The proposed non-in-flammatory mechanisms include defective collagenase activity due to decreased uptake of folic acid,[4] blockage of aldosterone synthesis in adrenal cortex and consequent feedback increase in ACTH level[5] and upregulation of keratinocyte growth factor.[6] Alternatively, inflammation may develop as a result of direct toxic effects of concentrated drug in crevicular gingival fluid and/or bacterial plaques.[7] This inflammation could lead to the upregulation of several cytokine factors such as TGF-β1.[8] Marked reduction in inflammation and gingival overgrowth was observed in all three cases after phase-1 therapy and substitution of amlodipine to other drug. Meticulous oral hygiene maintenance by patient may also be responsible for reduction in gingival overgrowth. In the first two cases, surgery was performed after a follow-up period of nearly 3 months. In the third case, only a 2-month follow-up report is presented. Marvogiannis et al., 2006 suggested that there may be recurrence of gingival hyperplasia if medication is continued and also persistence of other risk factors.[9] But no recurrence was noted in our case series.

CONCLUSION

Stringent maintenance of oral hygiene, switchover to alternative drugs and surgical therapy if required, remains the main stay of available treatment modalities. Better results were obtained where drug substitution along with oral prophylaxis were followed.