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Year : 2021  |  Volume : 19  |  Issue : 1  |  Page : 54-57

Nifedipine-induced gingival enlargement: A case report with review

1 Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, NITTE (Deemed to be University), Mangalore, Karnataka, India
2 Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
3 Department of Oral Medicine and Radiology, Century Dental College, Poinachi, Kerala, India

Date of Submission05-Oct-2020
Date of Decision02-Nov-2020
Date of Acceptance06-Nov-2020
Date of Web Publication13-Jan-2021

Correspondence Address:
Dr. Sajad Ahmad Buch
Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore - 575 018, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmi.cmi_136_20

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Calcium-channel blockers (CCBs) are widely used for the treatment of various cardiac conditions. Although CCBs have gained mass acceptance and popularity among the medical fraternity, their effect on the oral cavity is often under-reported and rarely debated. This group of medication causes gingival enlargement in some patients, affecting normal practice of oral hygiene, masticatory functions, besides causing esthetic concerns. A severe case of gingival enlargement is presented in a 53-year-old female patient with a history of nifedipine use.

Keywords: Calcium channel blockers, drug-induced gingival enlargement, gingival hyperplasia, nifedipine

How to cite this article:
Castelino RL, Buch SA, Laxmana AR. Nifedipine-induced gingival enlargement: A case report with review. Curr Med Issues 2021;19:54-7

How to cite this URL:
Castelino RL, Buch SA, Laxmana AR. Nifedipine-induced gingival enlargement: A case report with review. Curr Med Issues [serial online] 2021 [cited 2022 Aug 15];19:54-7. Available from: https://www.cmijournal.org/text.asp?2021/19/1/54/306936

  Introduction Top

Gingival enlargement, also called as gingival hyperplasia or gingival hypertrophy, can have a myriad of implicating factors. The various factors causing enlargement of gingiva can be included into four groups, namely inflammatory gingival enlargements, drug-induced gingival hyperplasia (DIGH), systemic causes, and hereditary gingival fibromatosis. Drug-induced gingival enlargement mainly results from the drugs that are intended for the disorders of nondental origin. The class of drugs usually implicated in gingival enlargement, in the form of their adverse drug reactions, includes immunosuppressants, anticonvulsants, and calcium channel blockers (CCBs). The various drugs belonging to these groups and often implicated in gingival enlargement are summarized in [Table 1].[1] DIGH, depending upon its severity may cause difficulty in chewing, phonetics, and oral hygiene measures, and can lead to the disfigurement of the gingival tissue. Occasionally, it may lead to increased mobility and migration of the teeth due to alveolar bone loss.
Table 1: Common drugs that cause gingival enlargement

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Fatt and Katz, initiated the work on calcium channels by working on muscle cells of crab, and a further research by Fleckenstein led to the development of a new class of drugs, CCBs, useful in patients with cardiac disorders.[2] CCBs inhibit influx of calcium ion through cell membranes and act on vascular smooth muscles, the cardiac nodes (sinoatrial and atrioventricular nodes), and the cardiac myocytes. They act on L-type calcium channels of these tissues, thereby causing coronary and peripheral arterial vasodilation, reduced heart rate, reduction in myocardial contractibility and oxygen utilization by the myocardium, and slow conduction at atrioventricular nodes.[2],[3] The aforementioned actions of these drugs mandate their use for the management of hypertension, cardiac arrhythmias, angina pectoris, and coronary artery spasms.[3] The pathogenesis underlying gingival enlargement under the influence of CCBs is not clear but is considered as multifactorial. The extent of relationship between CCBs and the effect on gingival tissue depends on age, presence of preexisting plaque, gingival inflammation, and genetic predisposition.[4]

  Case Report Top

A 53-year-old female patient was referred from a rural health clinic to our hospital with a 12-month history of slow-growing mass on the gums. The patient was hypertensive and was on 20 mg nifedipine/day for the past 5 years. Intraoral examination revealed generalized edema of gingival tissues, predominantly involving the interdental papillae, the gingival enlargement was severe in the second quadrant, almost covering the entire crowns of teeth 22, 23, 24, 25, 26, and 28 [Figure 1]a and [Figure 1]b. The enlarged gingiva was firm, nontender, pale pink in color and did not bleed easily on probing while the hard tissue examination revealed increased mobility in relation to 24, 25, 26, and 28. Panoramic radiograph revealed generalized bone loss and floating tooth 26 [Figure 2]a. Patient's complete blood count, bleeding time, clotting time, and platelet count were within the normal limits. The surgical excision of excess gingival tissue over the second quadrant of dentition was planned, but the preliminary phase of treatment began with thorough oral prophylaxis, and extraction of 24, 25, 26, and 28, owing to the poor periodontal status of these teeth, along with meticulous oral hygiene instructions. The general medicine department of our hospital was consulted, and after patient's evaluation, nifedipine was replaced with enalapril 5 mg for hypertension. The patient was evaluated after 1 week and marked improvement was noted except in the upper left quadrant. The excessive gingival tissue in the second quadrant of dentition and its extension on the posterior aspect of the palate were surgically removed in the second phase of treatment. Histopathology revealed stratified squamous epithelium with hyperplasia and acantholysis; the underlying fibro-collagenous connective tissue showed dense mixed inflammatory infiltrate with congested blood vessels [Figure 2]b. The patient was recalled and followed at a 1 week, 1 month, 2 months [Figure 3]a and [Figure 3]b, and 6 months intervals. Extraction of the root stumps in the upper right quadrant and that of impacted 48 was carried out during the follow-up period, and later, the patient was referred for the restorative and prosthetic rehabilitation of the missing teeth. The recall visits showed no signs of any recurrence.
Figure 1: (a and b) Mild lobulated appearance of gingival papillae (lower jaw); severe gingival overgrowth causing esthetic and functional problems (upper jaw).

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Figure 2: (a and b) Panoramic radiograph shows generalized bone loss, which was more severe in the maxillary posterior regions. Histological picture of excised tissue.

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Figure 3: (a and b) Two months postoperative follow-up.

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Informed consent was obtained from the patient for her images and clinical information to be used in a journal publication. It was explained that while the patient's name would not be published, complete anonymity could not be guaranteed.

  Discussion Top

Nifedipine is a very powerful and useful drug for hypertension, but its long-term use causes gingival enlargement in a significant proportion of population. Among all CCBs, nifedipine is the most frequently involved in gingival enlargement. The first reported case of gingival hyperplasia due to nifedipine use was reported by Lederman et al. in 1984.[5] Further studies reported, nifedipine-induced gingival enlargement in the range of 14% to 83%, much higher than other CCBs; verapamil and amlodipine with a prevalence of 4.2% and 3.3%, respectively.[2] The CCBs-induced gingival overgrowth could be detected within the first 3 months of the starting dose. Clinically, it may manifest as a localized or a generalized gingival enlargement, involving the entire dentition. The DIGH usually affects the teeth in the anterior region than the posterior and also affects the facial/buccal sides more than the lingual/palatal aspects.[6] The severe cases present with complete involvement of the papillae and surrounding gingival tissues, resulting in a lobulated appearance. Similar appearance could be seen over the upper left posterior aspect in this case report. The excessive gingival growth creates areas that are difficult to clean during routine tooth brushing. Consequently, the host becomes susceptible to develop, tooth decay, oral infections, and alveolar bone loss. The inability to maintain optimal oral hygiene leads to plaque-induced inflammation that compounds any existing drug-induced gingival enlargement. The importance of this relationship is explained by the fact that the edentulous regions are least affected by drug-induced gingival enlargement. This statement was substantiated in the present case report by the absence of gingival overgrowth in the edentulous areas of the lower jaw.

A number of pathways have been postulated, underlying the pathogenesis of CCBs-induced gingival enlargement. The most credited mechanisms include the role of matrix metalloproteinases, role of pro-inflammatory cytokines, and that of fibroblasts: (1) As, CCBs reduce influx of cellular calcium, the uptake of folic acid is affected, and thus limits the formation of active collagenase;[7] therefore, reduction of collagen degradation ensues, resulting in the increased production of collagen. (2) Another proposed mechanism implicates pro-inflammatory cytokines (interleukin-1b and interleukin-6), enhancing collagen production by fibroblasts of human gingiva.[8] (3) Since, a majority of people taking CCBs show no signs of any gingival overgrowth; therefore, only a subset of fibroblasts may retain the susceptibility to CCBs. In this regards, human lymphocyte antigen may have a role in genetic predisposition of different fibroblasts phenotypes to CCB.[9]

Nifedipine is most often implicated in the gingival overgrowth than any other agent of its group. Patients under nifedipine have a significantly higher rate of gingival overgrowth than amlodipine. Nifedipine and amlodipine are similar structurally; both dihydropyridines but differ in pharmacokinetics. Amlodipine is polarized and is transported along the cell membrane by a much complex transport mechanism, whereas nifedipine is more lipophilic, and therefore, has easy penetrability through the cell membrane. This suggests that the underlying mechanism of drug-cell interaction dictates the pathogenesis of drug-induced gingival enlargement. The differences in the half life and the volume of distribution of amlodipine (34 h and 21 L/kg) and nifedipine (7.5 h and 0.78 L/kg) may also have a role in the predictability of gingival enlargement after their use. These values demonstrate that most of the amlodipine is tissue bound, and hence inactive and is not freely available in the circulation. A certain plasma threshold level is suggested, beyond which gingival overgrowth begins.[10] Nifedipine, unlike amlodipine, tends to attain considerable plasma peak levels, possibly initiating drug-induced gingival enlargement.

The replacement of the offending drug plays a vital role in the successful management of the gingival overgrowth. All the possibilities should be discussed with the patient's physician. Mild-to-moderate overgrowth can be managed by nonsurgical approaches that involve thorough scaling and root planning, to eliminate the inflammatory component. This is followed by a meticulous oral hygiene and home care, followed by periodic professional scaling to prevent further inflammation. Nonsurgical intervention combined with the replacement of the drug can sometimes result in acceptable reduction in the gingival overgrowth, only to be followed with good oral hygiene and regular professional visits. Surgical approach becomes necessary to remove excess tissue, regain appearance and function, as well as to eliminate any pockets; the basic surgical method involves gingivectomy and gingivoplasty. The recurrence of gingival overgrowth can occur irrespective of the treatment provided, if the offending drug is not stopped or replaced with another class of drug.

  Conclusion Top

The CCBs are effectively used for the management of various cardiac conditions including hypertension, however, a serious and often, overlooked side effect; gingival enlargement occurs in a sizeable number of patients. The overgrowth can lead to cosmetic and functional concerns, often affecting quality of life. Replacement of the drug together with nonsurgical (scaling and root planning) and/or surgical approaches should be followed by a good oral hygiene, and home care to maintain the esthetics and functional capacity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Hatahira H, Abe J, Hane Y, Matsui T, Sasaoka S, Motooka Y, et al. Drug-induced gingival hyperplasia: A retrospective study using spontaneous reporting system databases. J Pharm Health Care Sci 2017;3:19.  Back to cited text no. 1
Livada R, Shiloah J. Calcium channel blocker-induced gingival enlargement. J Hum Hypertens 2014;28:10-4.  Back to cited text no. 2
Umeizudike KA, Olawuyi AB, Umeizudike TI, Olusegun-Joseph AD, Bello BT. Effect of calcium channel blockers on gingival tissues in hypertensive patients in Lagos, Nigeria: A pilot study. Contemp Clin Dent 2017;8:565-70.  Back to cited text no. 3
[PUBMED]  [Full text]  
Seymour RA, Thomason JM, Ellis JS. The pathogenesis of drug-induced gingival overgrowth. J Clin Periodontol 1996;23:165-75.  Back to cited text no. 4
Lederman D, Lumerman H, Reuben S, Freedman PD. Gingival hyperplasia associated with nifedipine therapy. Report of a case. Oral Surg Oral Med Oral Pathol 1984;57:620-2.  Back to cited text no. 5
Marshall RI, Bartold PM. A clinical review of drug-induced gingival overgrowths. Aust Dent J 1999;44:219-32.  Back to cited text no. 6
Barclay S, Thomason JM, Idle JR, Seymour RA. The incidence and severity of nifedipine-induced gingival overgrowth. J Clin Periodontol 1992;19:311-4.  Back to cited text no. 7
Johnson RB, Zebrowski EJ, Dai X. Synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts exposed to nifedipine and interleukin-1-beta in vitro. J Oral Pathol Med 2000;29:8-12.  Back to cited text no. 8
Pernu HE, Knuuttila ML, Huttenen KR, Tiilikainen AS. Drug-induced gingival overgrowth and class I1 major histocompatibility antigens. Transplantation 1994;57:1811-13.  Back to cited text no. 9
Ishida H, Kondoh T, Kataoka M, Nishikawa S, Nakagawa T, Morisaki I, et al. Factors influencing nifedipine-induced gingival overgrowth in rats. J Periodontol 1995;66:345-50.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

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1 Nifedipine
Reactions Weekly. 2021; 1843(1): 286
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