Gingival Hyperplasia in a Patient With Hypertension

This case presentation is that of a 47‐year old African American woman referred to the hypertension clinic by her cardiologist for difficult‐to‐treat hypertension. She had previously recorded blood pressure values of 110–235/70–125 mm Hg on multiple occasions. She received nisoldipine 30 mg twice daily, losartan 100 mg daily, metoprolol succinate 200 mg daily, clonidine patch 0.2 mg weekly, and furosemide 40 mg twice daily for at least 4 months prior to her initial visit. Her other medications were nortriptyline, trazodone, simvastatin, citalopram, albuterol, and insulin 70/30. At presentation, her initial blood pressure was 145/93 mm Hg, with a heart rate of 81 beats/min and a body mass index of 31.89 kg/m². ¹ She complained of the inability to eat solid foods because of her swollen gums. She had a history of hypertension since age 13, 2 previous strokes, left ventricular hypertrophy, type 2 diabetes, hyperlipidemia, and positive hepatitis C results secondary to transfusion. She was hospitalized twice for hypertensive emergencies over the past 4 years. She does not smoke or drink alcohol, and she denies the use of drugs. She had a strong family history of hypertension. On review of symptoms, the patient snored and had orthopnea, palpitations, headaches, blurred vision, dizziness, shortness of breath, and extremity swelling.

Over the course of the year prior to her initial visit, the patient noticed her gums beginning to swell and her teeth became loose. Her gums grew to the point that she lost several teeth and could no longer close her lips completely. Eventually, she became unable to chew food and altered her diet to liquids only. She saw a dentist 2 months prior to her consultation who advised her that she should have her remaining teeth removed; he was unable to fit her for dentures due to the dysmorphic changes to her gingival tissue, however. The dentist suspected that her medication may have played a role but was unsure and also recommended that she have better blood pressure control prior to any dental procedures.

Findings of physical examination were negative for carotid and abdominal bruits but positive for a systolic femoral bruit. On cardiac examination, the patient’s point of maximal impulse was normal and there was no murmur, S3 or S4. She also did not have rales and her extremities looked normal. On oral examination, she was unable to close her lips completely and her 2 upper front teeth were protruding forward and in opposing directions. Her upper and lower gingiva were swollen, erythematous, dysmorphic, and tender to palpation but not bleeding (Figure 1).

Figure 1.

 This photo was taken at the initial presentation. The patient’s upper and lower gingiva are swollen, erythematous, and dysmorphic.

The patient was counseled on the likelihood that her gingival hyperplasia (GH) was an uncommon adverse effect of calcium channel blocker (CCB) therapy, and nisoldipine was therefore stopped. Notably, she had been on various CCBs for up to 3 years prior to her presentation. She was given hydralazine 20 mg twice daily, furosemide 60 mg twice daily, losartan 100 mg daily, and metoprolol succinate 100 mg daily.

Two months later, the patient’s GH improved (Figure 2). Her blood pressure was 150/90 mm Hg, and she continued to take her adjusted regimen of medications. Three months after her initial evaluation, her GH improved to the point that her upper front teeth returned to their original position and she was able to close her lips and chew solid food (Figure 3). She was referred back to her dentist for denture fitting and was subsequently discharged back to her primary care physician with a blood pressure value of 125/79 mm Hg on a regimen of losartan 100 mg daily, labetalol 600 mg twice daily, clonidine 0.1 mg three times daily, hydrochlorothiazide 25 mg daily, pioglitazone 15 mg daily, and simvastatin 80 mg daily.

Figure 2.

 This photo was taken 2 months after discontinuation of calcium channel blocker therapy. There is a noticeable decrease in the gingival hyperplasia.

Figure 3.

 This photo was taken 3 months after discontinuation of calcium channel blocker therapy. The patient’s upper front teeth have moved position, permitting closure of her mouth.

Subsequently, 2 prescribers gave the patient amlodipine and nifedipine, presumably without knowledge of her previous history. The patient was instructed to consult the clinic before taking any other CCB. Her final regimen was carvedilol 25 mg twice daily, lisinopril 40 mg twice daily, hydrochlorothiazide 25 mg daily, spironolactone 25 mg daily, doxazosin 8 mg daily, and insulin 70/30. While CCBs have been proven to be effective therapies for lowering blood pressure, like other drugs, they are not without adverse effects. These should be monitored.

CCBs, anticonvulsants, and cyclosporine are known to cause GH. ² Furthermore, genetic polymorphisms such as MDR1 G2677T/A may modify the inflammatory response to CCBs, which may lead to an increase in GH. ¹ The mechanism by which GH occurs is not known, though there are several theories. First, CCBs can induce up‐regulation of keratinocyte growth factor. Second, decreased folic acid uptake decreases the secretion of collagenases and may cause collagen to build up in the gingiva. And third, decreased calcium influx reduces T‐cell proliferation, impairing immune function and allowing uncontrolled bacterial growth. ³ It is unclear whether these mechanisms are isolated or whether they occur concurrently to cause GH. ⁴

The primary treatment for GH is simple. CCBs should be discontinued. Often, this is sufficient to reduce the level of hyperplasia. There are instances, however, in which hyperplasia does not decrease after discontinuing medication. In these cases, surgical intervention is recommended with either a gingivectomy or a periodontal flap. If the drug is eliminated, hyperplasia should not recur. ⁵ A buildup of bacterial plaques has also been noted to increase severity of the condition. Of interest, it remains controversial whether good oral hygiene has any effect on the severity of GH. ⁶ However, a small trial of patients with GH randomized to nifedipine or isradipine for 8 weeks showed that while nifedipine increased GH in 60% of patients, isradipine decreased GH in 66% of patients. ⁷ This suggests that there may be some differences in these agents and the effect on GH.

The true prevalence of GH is not clear. In the literature, there is no reported racial or sexual bias; however, some believe that the severity of GH is greater in younger patients. ⁶ Bhatia and associates ² found that 3.3% of their population had GH with amlodipine 5 mg/d, a dosage that Lafzi and colleagues ³ claimed was not enough to cause GH. It is clear that this adverse effect has not been studied extensively. In 2 large controlled studies of a dihydropyridine CCB—the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) ⁸ and the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) ⁹ —12,337 participants were randomly assigned to amlodipine and nifedipine respectively for 3 to 5 years. Neither of the studies listed GH as a substantial adverse effect. Only ALLHAT leaves room for speculation about GH; it reports 197 patients discontinuing the study due to “symptomatic adverse events” or “other adverse effects”. INSIGHT reported that 539 patients were removed from the trial due to adverse events, none of which were listed as GH. Needless to say, GH was not one of the more common adverse effects in these large trials with close follow‐up.

This case presents a second concern in modern medicine. Communication between patient and provider and provider and provider is an important component of excellent clinical care. When one provider fails to communicate to other providers and patients, all parties involved are at risk. In fact, there are times when doctors ignore patient complaints about adverse effects, even when they know that the effect may be common for a particular drug. ¹⁰ Patient compliance and adherence is associated with strong communication (which entails listening and talking) with care providers. ¹¹ In addition, as the health care system in the United States undergoes major revisions, one of the critical needs is to provide better avenues of communication between providers about an individual patient. Communication is an important factor in reducing the morbidity of uncommon adverse effects.