Treatment of calcium channel blocker-induced gingival overgrowth without modifying medication

Abstract

Gingival overgrowth is a common side effect of calcium channel blockers used in the treatment of cardiovascular diseases. While controversial, management includes discontinuing the calcium channel blocker. We report the case of a 66-year-old Japanese man with hypertension and type 2 diabetes mellitus who was diagnosed with severe periodontitis covering almost all the teeth. The patient had been on nifedipine (40 mg/day) and amlodipine (10 mg/day) medication for 5 years. With his physician’s consent, nifedipine was discontinued during his treatment for periodontitis, which consisted of oral hygiene instructions and scaling and root planing on all areas. Gingivectomy was performed on the areas of hard fibrous swelling. Nifedipine was resumed during periodontal treatment when the patient’s hypertension worsened. His periodontal scores improved when he resumed treatment. We report that significant improvement in gingival overgrowth can occur with basic periodontal treatment, surgery and sustained intensive follow-up without adjusting calcium channel blockers.

Background

Calcium channel blockers (CCBs), including nifedipine and amlodipine, are widely used in the management of cardiovascular disorders. One of the side effects of CCB medication is gingival overgrowth (GO). GO is detrimental to oral health, can cause pain, interfere with mastication and affect an individuals’ aesthetic. When cases of drug-induced GO occur, dentists often consult the prescribing physician regarding the adjustment of any CCBs currently administered at the start of periodontal treatment.^{1 2} However, substituting or discontinuing CCBs may adversely affect chronic health conditions. Some studies have reported that the CCB nifedipine is most frequently implicated in drug-induced GO, accounting for 6%–15% of such cases,^{3 4} while others say that nifedipine accounts for 20%–83% of cases.^5–7 Although the incidence varies with severity or sampling technique, GO is a widely recognised side effect of CCB and needs to be addressed. A recent review and a cross-sectional study have concluded that cases of amlodipine-induced GO have been increasing.^{8 9} Important risk factors for drug-induced GO include poor oral hygiene and plaque-induced gingival inflammation.^{3 10} Therefore, periodontal treatment with thorough oral hygiene practices for CCB-induced GO may be desirable over adjusting needed pharmacotherapy. Here, we report the successful management of CCB-induced GO and improvements without modifying medication.

Case presentation

A 66-year-old Japanese man visited our clinic with complaints of swelling, gingival pain and overgrowth. He was on medication for hypertension, type 2 diabetes mellitus and prophylaxis for cerebral infarction. His drug regimen for hypertension included nifedipine (40 mg/day), amlodipine (10 mg/day), arotinolol (10 mg/day) and irbesartan (200 mg/day). His regimen for type 2 diabetes mellitus included vildagliptin (50 mg/day), glimepiride (500 mg/day) and metformin hydrochloride (250 mg/day).

Investigations

Intraoral examination revealed poor oral hygiene with a high plaque score and formation of dental calculus. The gingival tissue was nodular, irregular, firm, non-tender, pink and resilient with a lobulated surface. Enlargement was accompanied with spontaneous bleeding and pus discharge across the maxilla and mandible (figure 1). At some sites, the gingiva covered most of the dental crown, and oral malodour accompanying anaerobic bacteria was present. Clinical examination revealed a pocket depth ≥7 mm, which suggested severe periodontal destruction, reaching up to 28%. Full mouth periapical radiograph revealed horizontal alveolar bone resorption and localised vertical bone resorption at the mesial side of 21 (Federation Dentaire Internationale System) and 35 (figure 2). We detected multiple dental caries lesions under the GO.

Figure 1.

Intraoral clinical appearance before treatment. Severe gingival overgrowth is seen in the maxillary and mandibular teeth regions. Fibrous gingival swelling covering the crown in the mandibular anterior teeth.

Figure 2.

Bone loss and intrabony defects before treatment. Dental periapical radiography revealing generalised bone loss throughout the dentition and intrabony defects are seen at 21 and 35.

Treatment

According to standard protocol, we asked the patient’s physician to consider a substitute for the CCBs nifedipine and amlodipine. Nifedipine was substituted with methyldopa (500 mg/day) by the physician, but amlodipine medication was continued. Periodontal treatment was provided to the patient at the same time as medication adjustment and included intensive oral hygiene instructions to reduce the O’Leary plaque control record (53%). For the debridement of subgingival biofilm, scaling and root planing on all areas was conducted. To remove the hard-fibrotic gingival swelling, a gingivectomy was performed with an electric scalpel. We extracted 16 and 47 due to root fractures and severe dental caries that reached the bone crest. We observed significant reduction in the GO after basic periodontal therapy (figure 3). We found multiple teeth with severe caries that were covered with the GO. Since direct pulp capping had failed, 26 and 27 required endodontic therapy. Re-evaluation of the clinical parameters indicated significant improvement in severe periodontitis and GO status. To address the intrabony defect of 35, we conducted periodontal surgery with autogenous bone graft. Although the intrabony defect had ameliorated after periodontal surgery, the mesial root of 36 was fractured and then extracted. To address the problem of deep periodontal pockets, we conducted periodontal flap surgery for 25, 26 and 27. During the period of the periodontal treatment, the patient’s hypertension worsened, and his physician resumed nifedipine medication during the ongoing periodontal treatment.

Figure 3.

Intraoral view after basic periodontal treatment. Significant improvement in severe gingival overgrowth is noted.

Outcome and follow-up

We did not observe the recurrence of GO in subsequent follow-ups. Seventeen months after periodontal flap surgery, the patient’s GO and periodontitis conditions had improved and the final prosthesis, a removable partial denture, was set. The patient was recalled for supportive periodontal therapy (SPT) every month to check for the recurrence of GO and severe periodontitis. Recurrence can occur as early as 3–6 months following a surgical intervention and can affect up to 40% of the patients.¹¹ Our patient has shown no signs of recurrence after thirteen sessions of monthly SPT (figure 4A, B). The O’Leary plaque control record was maintained at good control levels (23.9%). Radiography at the thirteenth SPT session showed significant improvement of the alveolar bone defect when compared with his initial evaluation (figure 5).

Figure 4.

Intraoral clinical appearance after thirteen months of supportive periodontal therapy. (A) There is no recurrence of gingival overgrowth. (B) The removable partial denture has worked well in the mouth.

Figure 5.

Bone loss and intrabony defect status after 13 months of supportive periodontal therapy. Dental periapical radiography showing recovery of intrabony defects at 21 and 35.

Discussion

GO and periodontal disease can be treated by thorough intensive periodontal treatment without requiring changes in the regimen of CCB medication. Furthermore, patients with GO have a high risk of developing dental caries due to poor plaque control. Dental caries under proliferating gingiva cannot be detected, and it can progress to severe stages. Treatment for caries, a basic periodontal treatment, is hindered under GO-conditions due to factors such as the leakage of saliva and microbes. Therefore, careful scrutiny for the detection and treatment of caries under proliferating gingiva is essential.

CCBs are drugs developed for the management of cardiovascular diseases, and GO associated with nifedipine was first reported in the early 1980s.¹² Successive studies reported cases of GO associated with different CCBs, such as diltiazem and verapamil, and rare cases with amlodipine and felodipine.^{4 13} A community-based study that investigated the prevalence of CCB-induced GO revealed that 6.3% of patients taking nifedipine medication had clinically significant GO and that gingival inflammation was an important factor in its development.³

GO causes deterioration of periodontal health and includes pain, difficulty in brushing teeth, interference with speech and mastication and aesthetic problems. According to standard practice, the most effective treatment for oral lesions is discontinuation of the offending medication and substitution with another class, or a cocktail, of antihypertensive drugs.^{1 12 14} CCBs are among the first-choice drugs for the treatment of cardiovascular and related diseases.^{15 16} Although existing literature suggests that substituting nifedipine with an antihypertensive of the same class, such as isradipine, may result in the regression of GO,¹⁷ exacerbation of hypertension and increased risk of developing angina due to the substitution of key drugs cannot be ruled out. We opine that dentists should avoid changing medical treatments due to dental side effects. There are some reports that indicate that a safer option is substitution with another drug that has a lower risk of inducing GO, such as isradipine, verapamil β-blockers or angiotensin-converting enzyme inhibitors.^17–19 Physicians and patients are often reluctant to switch their regimen. If regimen change is not feasible, the lesions should be managed with or without surgical intervention. In our case, following the referral for nifedipine substitution, another class of antihypertensive drugs was prescribed for the duration of periodontal treatment. However, nifedipine medication was resumed due to poor blood pressure control. Furthermore, amlodipine, another CCB that is reported to induce GO,^{8 9} was being administered for the entire duration of treatment from initial consultation to SPT phase. Our case suggests that treatment of GO may be possible without altering CCB medication. The pathogenesis of drug-induced GO is not fully understood; some studies suggest that inflammation of gingival tissue is a prerequisite for the development of GO where the levels of plaque formation and gingival inflammation appear to be associated.^20–22 Overproduction of inflammatory cytokines (interleukin-1b and interleukin-6), fibroblast activity and dysregulation of matrix metalloprotease expression are three of the most cited causes and risk factors of GO.²¹ Among these key risk factors, overproduction of interleukin-6 could be the most probable cause of pathogenesis in our case, as it has been shown to target connective tissue cells by enhancing their proliferation and increasing collagen production and glycosaminoglycan synthesis.²³ This highlights the role of the accumulated bacterial biofilm that develops in poor oral hygiene conditions. Another reason could be that overgrown tissue creates pockets harbouring pathogenic bacteria that are beyond the reach of a toothbrush or dental floss. This impairs optimal oral hygiene and can lead to increased host susceptibility to oral infection, caries and periodontal disease. With these possibilities in mind, the dentist should assess the responsiveness of GO by prioritising periodontal treatment, beginning with thorough plaque control, before considering discontinuation or substitution of CCBs. In case periodontal intervention does not improve GO, then modifications in the medication for hypertension may be considered. Hancock et al²⁴ reported improvement of GO under non-surgical therapy with no alteration in the antihypertensive treatment. We obtained good clinical results despite continuing CCB medication throughout the entire duration of periodontal treatment.

It has previously been reported that the risk of tooth loss is higher in cases where periodontal disease and diabetes mellitus coexist than in cases where diabetes is not present.²⁵ Previous case reports have also mentioned the association between diabetes and the induction of CCB-induced GO.^{26 27} Although the mechanism by which diabetes mellitus affects GO remains unclear, it has been hypothesised that hyperglycaemia is related to an increased inflammatory response which may play a role in the pathogenesis of GO.²⁸ Additionally, ‘poor oral hygiene’ is a commonly reported factor in several case reports regarding diabetes and the development of GO, including ours, and is a key factor which causes gingival inflammation.

In our case, the patient also suffered from type 2 diabetes along with hypertension and was taking oral diabetic medication for poor oral hygiene at the beginning of the GO treatment. HbA1c during active periodontal treatment and subsequent SPT remained in the approximate range of 5.5%–6.0%, with the highest value being 7.4%. Although HbA1c remained stable throughout the periodontal treatment period, hyperglycaemic condition may have been a factor in the development of GO in this case as well.

It has also been reported that a hyperglycaemic environment, due to the high glucose concentration, can increase the presence of candida albicans in vitro, so nutritional guidance as part of oral care may also be important for periodontal patients with concomitant diabetes who are susceptible to infections.²⁹ In a case report regarding a patient with diabetes mellitus and a history of stroke and myocardial infraction with developing amlodipine-induced GO, full-mouth disinfection and thorough supragingival and subgingival plaque control was performed, resulting in an improvement in GO without periodontal surgery. There were also reports of a reduction in HbA1c from 7.7% to 7.3% with periodontal treatment.³⁰ Therefore, for CCB-induced GO comorbid with diabetes, the blood glucose levels diagnosis should be considered, closely monitored and close collaboration with a physician may be necessary.

Patients with GO have a higher risk of developing dental caries due to poor plaque control. Dental caries cannot be detected and confirmed under proliferating gingiva and could progress in severity unnoticed. In the caries treatment, it is critical to prevent the leakage of saliva from the gingiva in order to provide reliable treatment. GO is thought to facilitate the leakage of saliva from the gingiva to the site of caries.

Attention should be paid to the detection and treatment of caries under the proliferating gingiva, more so because the appearance of the enlarged gingiva has a high impact and could become the sole focus of dentists. As already mentioned, accumulation of microbial plaque is one of the important characteristics of GO.^20–22 Therefore, mild to severe dental caries under the GO must be anticipated. In the case presented here, we found severe caries at 26 and 27 under the GO.

To conclude, GO with a high probability of development of periodontal disease is a side effect of CCB medication for hypertension and other cardiovascular disorders. However, in our case, drug-induced GO could be effectively managed by thorough periodontal treatment, including proper plaque control and optimal oral hygiene instructions, without discontinuing or substituting CCB medication for the duration of the periodontal treatment. Drug-induced GO can be clinically cured without interfering with medication for chronic disorders. Attention should also be paid to the detection and treatment of dental caries beneath the proliferating gingiva.

Patient’s perspective.

I was aware that my gums had been swollen before, but I had left it alone. Eventually, the pain when eating and brushing my teeth increased and I began to bleed a lot. The treatment was long, and the oral care guidance was strict, but I am glad that these things have improved after this treatment.

Learning points.

• Gingival overgrowth (GO) and periodontal disease could be treated by thorough intensive periodontal treatment without requiring changes in the regimen of calcium channel blocker (CCB) medication. Therefore, although previous reports have implicated CCBs in drug-induced GO, alteration in their administration is unnecessary for the treatment of such cases of GO and GO-associated periodontal disease.

• Considering the risks of developing angina pectoris, stroke and other complications due to the discontinuation of CCBs, it is prudent to first attempt purely periodontic treatment for CCB-induced GO. Adjusting a patient’s medication should only be discussed with a physician should periodontic treatment fail.

• Patients with GO also have a high risk of developing dental caries due to poor plaque control. In particular, dental caries under proliferating gingiva cannot be detected and could easily progress to severe stages.