Calcium Channel Blockers- Induced Iatrogenic Gingival Hyperplasia: Case Series

ABSTRACT

Hypertension rightfully termed as “Silent killer” is associated with increase in morbidity and mortality when left untreated. Calcium channel blockers are the most commonly prescribed first-line anti-hypertensive drugs in India. Calcium channel blockers are known to cause gingival hyperplasia but with lower incidence rates compared to the other two groups causing iatrogenic gingival overgrowth, immunosuppressants, and anticonvulsants. Nifedipine administration, among the calcium channel blockers, has been frequently associated with iatrogenic gingival hyperplasia. Incidence of amlodipine-induced gingival hyperplasia which has similar pharmacodynamic action like nifedipine, had been reported rarely. Here, we present a case series of drug induced gingival overgrowth caused by calcium channel blockers used for the management of hypertension. All the patient’s condition improved after withdrawal of the offending drug, oral prophylaxis and intervention, and alternate drug from other first-line drugs were started for managing hypertension.

INTRODUCTION

Hypertension is a rising global public health concern affecting 1.4 billion people worldwide.[1] The JNC-8 guidelines recommend ACEI, ARB, Thiazide, or CCB either as monotherapy or in combinations.[2] Drug induced gingival overgrowth (DIGO) is the agreed term for iatrogenic gingival hyperplasia and is defined as, “an overgrowth or increase in size of the gingiva resulting in whole or in part from systemic drug use.” Anticonvulsants, calcium channel blockers and immunosuppressants cause DIGO.[3] The incidence of gingival hyperplasia was seen in 19.6% patients on CCB’s, in 12.5% patients on ARB and in 7.5% of patients on ACEI.[4] Gingival enlargement has a higher impact on patients’ oral health-related quality of life and aesthetics.[5] We have discussed 4 cases of gingival hyperplasia encountered in hypertensive patients on CCB’s.

CASE REPORTS

Case 1

A 55-year-old male presented with complaint of swelling in the upper and lower gums for three months with intermittent gum bleeding [Figure 1a and b]. Newly diagnosed hypertensive on amlodipine (5 mg) OD, diagnosis of DIGO was made ruling out other causes. Amlodipine was stopped and tablet Hydrochlorothiazide 12.5 mg OD was started for hypertension. Scaling and root planning were done. The patient reviewed after 1 month and the improvement was drastic and stepwise surgical intervention was carried.

Figure 1.

Case No. 1 showing amlodipine induced gingival hyperplasia

Case 2

A 63-year-old female presented with complaints of loose tooth in the back lower right side for 2 months. The patient had difficulty in mastication, bleeding on brushing for the past 6 months with bad breath. Patient had poor oral hygiene [Figure 2a and b]. Known hypertensive for the past 2 years, on amlodipine 5 mg OD. Diagnosed as DIGO. The offending drug amlodipine was substituted with Tablet. Telmisartan 20 mg OD. Scaling and root planning was done. On review, though hyperplasia had reduced, gingivectomy was performed leading to full recovery.

Figure 2.

Case No. 2 showing amlodipine induced gingival hyperplasia

Case 3

A 73-year-old male presented with complaints of growth in the upper and lower gums for the past 6 months. H/o bad breath and difficulty in chewing. Known case of hypertension and ischemic heart disease for the past 5 years, on nifedipine 20 BD, Aspirin 75 mg. The patient was diagnosed as DIGO [Figure 3a and b]. Nifedipine was substituted with telmisartan + Hydrochlorthiazide combination.

Figure 3.

Case No. 3 showing amlodipine induced gingival hyperplasia

The patient was advised to stop Aspirin for a week for dental intervention. On review, scaling, and root planning with gingivectomy was done.

Case 4

A 63-year-old female presented with complaints of pain and swelling in the gums for the past two weeks. On examination, grade 3 mobility seen in 11, 22, 23, 24, and 26 of upper arch. Known hypertensive for the past 15 years on Nifedipine 20 mg BD. Diagnosed as DIGO [Figure 4a and b]. Drug was substituted, extraction of periodontally compromised teeth, SRP followed by prosthetic replacement of missing teeth was done stepwise.

Figure 4.

Case No. 4 showing amlodipine induced gingival hyperplasia

DISCUSSION

Gingival overgrowth, also known as gingival hypertrophy or hyperplasia, is characterized by an abnormal overgrowth of gingival tissues. Based on etiology gingival hyperplasia can be divide into: 1) inflammatory 2) Drug-induced 3) hereditary, and 4) systemic cause associated.[6] Poor oral hygiene and genetic factors play an important role in the susceptibility for DIGO.[7,8]

Prevalence of CCB-induced DIGO

The first case was reported in 1984.[9] Gopal S et al.[10] in Hyderabad, India, showed a prevalence rate of 75% in patients on nifedipine, 31.4% in patients on amlodipine and 25% in patients on amlodipine + metoprolol.

Pathogenesis of CCB-induced DIGO

All forms of DIGO have similar histopathologic characteristics, a parakeratinized squamous epithelium with acanthosis with connective tissue penetrated by elongated rete pegs. Increased vascularity, inflammatory cells infiltration, collagen fibrosis with variable fibroblasts, and changes in the glycosaminoglycans are seen in the lamina propria.[11]

Various hypotheses have been put forward in the pathogenesis of DIGO due to CCB’s usage. Individuals with genetically predisposed fibroblasts have been identified. Such fibroblast heterogeneity affects the composition of the extracellular matrix components, i.e., production of fibroblastic cytokines and their response to different environmental stimuli.[12]

The possible role of amlodipine in the inflammatory response was confirmed by Lauritano D et al.[13]

Sukkar TZ performed an in-vitro study and determined that nifedipine attenuated the upregulation of matrix metallo-proteinases 1 (MMP-1) by pro-inflammatory cytokines and thus the interaction accounting for the synergism between inflammation and nifedipine induced DIGO.[14]

Prevention of CCB-induced DIGO

The measures for minimizing DIGO include regular periodontal recall, conscientious oral hygiene, and elimination of the local irritants. Regular 6 monthly periodontal maintenance therapy is recommended for patients taking drugs causing gingival overgrowth.[15]

Management of CCB-induced DIGO

Drug withdrawal/substitution

Plethora of evidences infers that drug substitution/withdrawal has a major impact on the disease recurrence and progression. Even the substitution of the drug from the same group which has lower propensity to cause DIGO influences disease regression.[16] In this case series, all the patients showed significant reduction in gingival growth following drug substitution.

Non-surgical management

For all patients, scaling and root planning when offered resulted in reduction of both clinical gingival hyperplasia index and histological improvement seen as reduction in the number of inflammatory infiltrates.[17] Hence, it would be prudent to implement non-surgical interventions like SRP in all cases of DIGO.

Surgical management

The surgical modalities include: conventional scalpel gingivectomy, flap procedures, electrocautery, and laser therapy.[18]

Prognosis of CCB-induced DIGO

Recurrence of DIGO in surgically treated cases occurs within an average interval of 6-12 months in susceptible patients, needing secondary surgical procedure. In a study conducted by Fardal et al.[19] had recurrence in 47.2% of cases needing repeated surgeries. Lower rates of recurrence were seen with Laser therapy; however, conventional and modified forms of conventional gingivectomy procedure remain the gold standard.[20]

Hence, Physicians should be aware of the possibility of iatrogenic gingival hyperplasia caused by CCB’s, even at lower doses given for a shorter duration in patients with associated risk factors.

CONCLUSION

Periodontal assessment is recommended among hypertensive patients started on CCB’s for early detection and management of DIGO. Patients’ education is key in keeping the local factors at ease; warning of such adverse effect should be given which will encourage the patient to take proper oral hygiene measures.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.