Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 12(1); 50-52, 2019.

DOI: 10.4067/S0719-01072019000100050

CLINICAL REPORT

Systemic and clinical treatment of gingival hyperplasia

associated with use of anticonvulsant
Tiago Martins Feijó Miguelis1, Karoline Von Ahn Pinto1, Luis Eduardo Rilling Nova Cruz1,
Juan Pablo Aitken Saavedra2-3, Josué Martos1*
1. Department of Semiology and Clinics, School of
Dentistry. Federal University of Pelotas, Pelotas, Brazil ABSTRACT
2. Department of Oral Pathology and Medicine, School Anticonvulsants are drugs that can modify the gingival tissues response to inflammatory
of Dentistry, University of Chile, Santiago, Chile.
processes in the presence of dental plaque, inducing gingival overgrowth. Preexisting
3. Post Graduate Program in Dentistry. Federal
gingival inflammation induced by dental plaque seems to be a favorable condition to
University of Pelotas. Pelotas, Brazil
the development and/or expression of gingival overgrowth. This study describes a case
* Corresponding Author: Josué Martos | Department in which the use of phenytoin and phenobarbital anticonvulsant associated with the
of Semiology and Clinics, School of Dentistry, presence of dental plaque provided a large and severe extent of gingival alteration. We
Gonçalves Chaves street. 457, Pelotas, RS 96015- concluded that it was possible to achieve a good result in the patient with an intensive
560, Brazil | Telefax: +55 53 3222 4439 | E-mail: mechanical control of dental plaque, oral hygiene orientations and substitution of the
[email protected] drug for other alternative medication.
Work received on 21/03/2018. KEY WORDS
Approved for publication on 28/04/2018 Gingival hyperplasia; Phenytoin, Phenobarbital, Valproic acid.
Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 12(1); 50-52, 2019.

INTRODUCTION Clinical examination presents a lobulated aspect of the gingiva with

severe gingival enlargement with clinical crowns covered to a large extent,
Gingival enlargement or hyperplasia is an abnormal condition in showing a bucco-lingual dimension greater than 3 mm and a depth of
which the gingiva presents changes in volume and ranges from a slight probing greater than 6 mm (Figure 1). On palpation the gingiva was firm
hyperplasia of the interdental papillae to a growth in which the dental and resilient in consistency. Clinically, the patient still had a visible plaque
crowns remain completely covered by the altered tissue.(1,2) Gingival and visible areas of gingival bleeding (Figure 2a). In the radiographic
hyperplasia is not always linked to the alteration of the amount of tissue examination there were no horizontal bone resorptions, either localized
cells, which may be a consequence of alteration in the volume of the or generalized (Figure 2b).
cellular constituents or of the extracellular matrix.(2)
Regarding gingival enlargement associated with medications, some
systemically administered drugs are capable of modifying the inflammatory
and immune response of periodontal tissues, especially gingival tissue.(3,4)
The first report of drug-associated to gingival hyperplasia was made
by Kimball(5) in whom tissue change was observed after administration of
an anticonvulsive drug based on phenytoin. Subsequently other drugs,
such as calcium channel blockers (nifedipine) and immunosuppressant
(cyclosporin), were also related to this side effect.(6) These drugs are
structurally distinct, but they have in common the action of inhibiting the
cellular uptake of calcium, a mechanism that is considered involved in the
pathogenesis of gingival hyperplasia.
The role of plaque in gingival growth induced by anticonvulsant has
been investigated, and the vast majority of studies show that the presence
of plaque and gingival inflammation are important intervening factors for
the development and/or expression of this clinical situation.(3,7)
The pathogenesis of gingival enlargement induced by systemic
medication depends on multiple factors such as plasma concentration of
the drug, genetic predisposition, presence of bacterial plaque and also a
synergistic effect with other drugs.(8) The differential expression of cytokine Figure 1. Clinical appearance of phenytoin-associated gingival
receptors in fibroblasts may be potentially involved in the pathogenesis of overgrowth.
gingival enlargement secondary to the use of drugs such as phenytoin.
The aim of this study is to report the periodontal therapy carried out in No similar history of gingival enlargement of any family member was
a patient with anticonvulsant drugs based on phenytoin and phenobarbital detected during the anamnesis and the laboratory investigations showed
presenting generalized and severe gingival growth. blood counts within the normal parameters.
In possession of all clinical, radiological and medical informations,
CASE REPORT the patient was diagnosed with drug-induced gingival enlargement,
aggravated by the accumulation of dental biofilm. Due to the extreme
A 24-year-old female patient was referred to the College of Dentistry gingival bleeding, meticulous oral care was promptly instituted while
at Federal University of Pelotas presenting oral bleeding and difficulty awaiting evaluation by the neurologist. The patient was also advised to
feeding. The clinical history revealed that the patient has epilepsy and as a use 0.12% chlorhexidine digluconate mounthwash twice daily.
consequence, used 100mg phenytoin and 100mg phenobarbital every 12 The neurologist was promptly consulted for details of the patient’s
hours, as anticonvulsant drugs like additive pharmacodynamic interaction case and systemic conditions. The treatment plan was divided into three
for the antiepileptic effect. The patient used, although in a precarious and stages; the first one associated with the systemic control of the convulsive
difficult way, a toothbrush and toothpaste for daily oral hygiene. Severe condition with the substitution of the medication previously reported for
oral malodor was present, which prevented the patient from socializing. 125mg valproic acid three times a day, by its neurologist and a second

50 | Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 12(1); 50-52, 2019.
 Systemic and clinical treatment of gingival hyperplasia associated with use of anticonvulsant

Figure 2. (a) Maxillary aspect of the initial case. (b) 1. Orthopantomogram

radiograph.
stage of planning, family counseling and plaque control with supra and
subgingival scraping sessions. A final planning step established that if
necessary, a gingival regrowth surgery would be performed. In addition to
the interdental brush, concomitant use of 0.12% chlorhexidine digluconate
solution twice daily was recommended as an aid to mechanical control.
The patient presented regression of gingival growth and no bleeding
after the first weeks of local and systemic treatment. The maxillary and
mandibular teeth presented their crowns intact and without mobility after
an interval of two months. Maintenance appointments occurred every Figure 4. (a) Plaque-Identifying in frontal view. (b) Immediate aspect after
fortnight in the first semester of treatment and every 30 days from the vigorous washing with water. (c) Right appearance after prophylaxis. (d)
second semester, when deplacement procedures and oral hygiene Left appearance after prophylaxis.
instructions were performed (Figure 3a, 3b, 3c, 3d).

Figure 5. (a) A 24-month periodontal follow-up. (b) Mild hyperplasia

in the upper lateral incisor, as a result of malposition. (c) Orthodontic
treatment for realignment and bite descrucing in the upper right quadrant.
(d) Labial view.

Figure 3. Gingival aspect of maxillary and mandibular 14-months after methods.(10) Besides this, in clinical problem presented, the establishment
initial treatment (a) Frontal view. (b) Approximate maxillary aspect. (c) of an integrated treatment plan involving dental professionals and
Right side view. (d) Left side view. the neurologist was the key point for the resolution, starting with the
substitution of the medication previously used.
After 18 months of clinical follow-up, although the patient presented All stages of the established treatment plan were discussed with the
mild hyperplasia in the upper lateral incisor, as a result of poor dental patient and family so that there was no misunderstanding of information,
position, she presented adequate oral hygiene proven by auxiliary especially at the stage where the patient’s adherence would be a key
methods such as dental plaque disclosing agent, in addition to periodontal and essential point for treatment. Fortunately we have succeeded in
probing (Figure 4a, 4b). There was no recurrence of gingival growth implementing the three phases of the established treatment plan.
and absence of regions with gingival bleeding after periodontal probing Inflammatory changes in the gingival tissues appear to be a significant
(Figure 4c, 4d). The patient is undergoing medical treatment with no determinant of gingival hyperplasia, suggesting that inflammatory
systemic changes due to the change in anticonvulsive drug therapy and mediators influence the entire sequence of events.(11) There is an
an orthodontic treatment plan for realignment and bite descrucing in the interaction between the drug and/or its metabolite and the gingival
upper right quadrant was instituted (Figure 5a, 5b, 5c, 5d). fibroblasts that seems to increase by gingival inflammation. The authors
Oral hygiene maintenance has improved a lot, which has resulted in suggest that the interaction between the drug and the gingival fibroblasts
absence of malodor, thereby significantly increasing the patient’s quality is calcium-dependent. In addition, drugs that affect intracellular calcium
of life. The actual results were found to be extremely satisfactory both metabolism or transport may stimulate gingival fibroblasts.(12)
esthetically and functionally. In the clinical case described, we would have a grade 4, according a
new classification index for gingival overgrowth.(13) At this classification, a
DISCUSSION severe gingival increase with extensive gingival thickening was observed,
the clinical crown being covered to a large extent, having a bucco-lingual
The gingival hyperplasia, with its potential aesthetic implication dimension greater than 3 mm and a depth of probing greater than 6 mm.
complicated by inflammatory changes due to plaque accumulation, Ideally, the best approach for gingival enlargment induced by the
presents an affliction for patients and health professionals. The reported medication would be the discontinuation of the associated medication
case is an exemplification of a progressive gingival enlargement caused used. However, this intervention is often not possible because of the need
by a drug-induced and complicated by inflammatory changes due to to treat the epilepsy.(14) The phenytoin and phenobarbital medications
plaque accumulation. used for the treatment of epilepsy of the patient were replaced effectively
Generally, the treatment plan in cases like the one presented, consist by valproic acid. Accounts of similar clinical cases, had already described
of conservative therapy with education on oral health, meticulous oral phenytoin-induced gingival overgrowth.(15)
hygiene instruction and motivation in combination with scaling and The patient responded very well with the substitution of previously
root planing.(9) The use of a chlorhexidine solution has been shown to used drugs. With regard to medication, some researchers suggested
be a highly beneficial adjunctive regimen to mechanical oral hygiene that sodium valproate may be considered a safe alternative, regarding

Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 12(1); 50-52, 2019. | 51
Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 12(1); 50-52, 2019. Martos J. y cols.

the periodontal aspects, to phenytoin for the treatment of adult-onset replacement and with home oral care. However individuals who show
epilepsy.(16) clinical signs or symptomatology for a long time may experience partial
Among the anticonvulsants, gingival enlargement is seen mostly regression of the change. In cases where the substitution of the drug is
with phenytoin (diphenylhydantoin). The other anticonvulsants that not possible, or even after the change, the professional only observes
have the same effect are vigabatrin, sodium valproate, primidone, partial regression, gingival remodeling becomes essential.
and phenobarbital.(17) According to a report by American Academy Finally, it is important to highlights the importance of multidisciplinary
of Periodontology, occurrence of gingival overgrowth due to sodium management in these cases to achieve success. Interdisciplinary
valproate is rare.(18) It has been described that gingival enlargement is treatment in epileptic patient with a drug-induced gingival hyperplasia is
documented in more that 40% of patients on valproate monotherapy becoming an ever-increasing part of modern-day dental practice.(20)
compared to 16% of patients on phenobarbital.(19) It should also be
considered that, although the case presented evolved satisfactorily, some CONCLUSION
cases have been successfully resolved without the need to change the
drug but using complementary therapies.(15) Intensive mechanical control of dental plaque, oral hygiene orientations
When all the evidences are considered, there appears to be three and switchover to alternative drug for other medication are the best way to
significant factors that are important in the expression of these gingival control the gingival enlargement associated with medications.
changes, namely, drug variables, plaque-induced inflammatory changes in
the gingival tissues, and genetic factors that determine the heterogeneity CONFLICT OF INTEREST:
of the fibroblast.(8) Care such as professional prophylaxis should be
performed frequently during drug administration. Frame regression and None.
improvement of clinical signs generally occur four weeks after drug

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