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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 11  |  Issue : 1  |  Page : 32-36

Is drug substitution always a solution? Phenytoin induced gingival enlargement – A case report


Department of Periodontology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India

Date of Submission22-Jul-2018
Date of Acceptance03-Nov-2018
Date of Web Publication6-Mar-2019

Correspondence Address:
Himani Sharma
A1, Vijeta Apartments, Pallavpuram Phase 1, Meerut - 250 110, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jorr.jorr_19_18

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  Abstract 


Gingival enlargement is the most common side effect which is reported with the administration of the anti-epilepsy drug phenytoin (PHT). It is of vital importance as it greatly affects the esthetics and also interferes with the mastication and oral hygiene practices. It is now well known that the presence of gingival inflammation resulting from poor oral hygiene acts as a major risk factor and leads to worsening the condition. Therefore, the patients taking PHT should be made aware of the possible outcomes and the importance of maintaining oral hygiene and periodontal maintenance therapy. This case report describes a case of PHT-induced gingival enlargement in which surgical intervention was done to correct the gingival enlargement, and in spite of patient not discontinuing the drug (PHT), no recurrence of enlargement was seen even after 1 year.

Keywords: Gingival enlargement, maintenance phase, phenytoin


How to cite this article:
Gupta C, Arora R, Sharma H. Is drug substitution always a solution? Phenytoin induced gingival enlargement – A case report. J Oral Res Rev 2019;11:32-6

How to cite this URL:
Gupta C, Arora R, Sharma H. Is drug substitution always a solution? Phenytoin induced gingival enlargement – A case report. J Oral Res Rev [serial online] 2019 [cited 2019 Mar 25];11:32-6. Available from: http://www.jorr.org/text.asp?2019/11/1/32/253426




  Introduction Top


Epilepsy is the most common chronic neurological disorder in the world. It is characterized by recurrent unprovoked seizures, due to abnormally excessive or synchronous neuronal activity in the brain.[1] Since 1937, phenytoin (PHT) is widely used for the treatment of epilepsy, due to nonsedative, nonaddictive activity, and ability to regulate cellular bioelectrical activity.[2]

The long-term usage of PHT is associated with various side effects; PHT-induced gingival enlargement (PGE) being one of them.[3] It becomes a source of pain, disfigures the esthetics, and interferes with the routine oral hygiene practices, thus leading to the formation of new niches for periodontopathogenic bacteria.[4]

Drug substitution is considered the most effective treatment of PGE. However, the major factor responsible for exaggeration of PGE is lack of oral hygiene. Various studies have demonstrated that a preventive dental program is able to effectively minimize the incidences of PGE.[5],[6]

This case report describes a case of PGE and also discusses the treatment options and factors to prevent recurrence in these cases.


  Case Report Top


A 35-year-old male reported with massive gingival enlargement covering more than one-third of his teeth. He also complained of a persistent dull, gnawing pain in his teeth, and bleeding from gums along with fetid odor from his mouth. The medical history revealed that he has been taking PHT (100 mg) and phenobarbital (50 mg) combination for the treatment of epilepsy since the age of 20. The gingival tissues were enlarged, firm, pale pink, fibrotic [Figure 1] and [Figure 2]. A radiograph was taken to check for any periodontal destruction; however, no underlying bone loss was revealed. Based on the medical history and periodontal examination, a diagnosis of drug-induced gingival enlargement was made.
Figure 1: Preoperative photograph – Frontal view. Note the bead-like gingival enlargement involving all of the dentition

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Figure 2: Preoperative photograph – Lateral view (a) first and third quadrant (b) second and forth quadrant

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Surgical management

The patient was referred to his physician for substitution of PHT with some other drug with lesser reported side effects. After 3 weeks with the consultation with the patient's physician, surgical intervention for the PGE was planned. Informed consent was obtained from the patient. Local anesthesia was administered. With the help of a pocket marker, bleeding points were marked on the external surface of the gingiva for the external bevel incision. This was followed by a sulcular incision, and the enlarged tissue was excised using curettes. Gingivoplasty was then carried out using electrosurgical unit [Figure 3]. Meticulous scaling and root planing was carried out and a periodontal dressing was placed [Figure 4]. Similar procedure was carried out in all the quadrants. The patient was prescribed an antibiotic (amoxicillin 500 mg and clavulanic acid 125 mg BD for 5 days) and anti-inflammatory analgesic drugs (ibuprofen 400 mg and paracetamol 325 mg TID for 5 days). The patient was recalled after 1 week after surgery, and the healing was uneventful. After 3 months, the patient revealed that he did not discontinue the drug despite counseling; however, there was no recurrence of the enlargement, the tissues appeared pink and healthy, and the patient was also satisfied with the esthetic outcome [Figure 5] and [Figure 6]. The patient was kept on maintenance every 3 months to keep a check on recurrence. Even after completion of 9 months, no signs of recurrence or periodontal destruction were found [Figure 7].
Figure 3: External bevel gingivectomy performed using electrosurgical electrodes in the first quadrant

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Figure 4: Periodontal dressing placed

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Figure 5: 1-month postoperative photograph – Frontal view. Note the resolution of gingival enlargement

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Figure 6: 1-month postoperative photograph – Lateral view. (a) first and third quadrant (b) second and forth quadrant

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Figure 7: 9-month postoperative picture. Note the complete resolution of gingival enlargement with no sign of recurrence

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  Discussion Top


Gingival enlargement is a common side effect seen among the patients who are under PHT therapy for the treatment of epilepsy. It was first reported by Kimball in 1939.[3] It can develop as early as within 1–3 months of starting the medication and may reach a state of equilibrium often within the 1st year.[7]

It is more prevalent in children and teenagers but is not affected by gender or ethnic groups. It has a greater severity on the buccal surface of both upper and lower anterior teeth. This soft tissue enlargement starts as a painless, bead-like, diffuse swelling at the region of the interdental papilla, which gradually enlarges, involves marginal gingiva, and becomes a nodular form of swelling, covering a huge portion of the crown of the tooth.[4]

In this report, the patient was male in his thirties. He was taking PHT for 15 years. However, he started having discomfort from 6 months. Secondary inflammatory changes induced mainly by the dental plaque accumulating at the gingival margin cause increase in its size and tenderness of the lesion. Further, it gives this lesion a red or bluish red discoloration due to venous stasis and increases its bleeding tendency. A significant correlation has also been found between the incidence and severity of gingival enlargement and the amount of accumulated dental plaque and calculus.[8],[9]

PHT is absorbed slowly from the gastrointestinal tract and is metabolized in the liver by hepatic enzymes. The major metabolite of this drug is 5-p-hydroxyphenyl hydantoin. The possible mechanism suggested for PGE can be the ability of PHT metabolite to induce cell proliferation of fibroblasts further, causing accumulation of immature proteins in extracellular matrix (ECM), particularly collagen, which can be due to an imbalance between the synthesis and the degradation of ECM. This may lead to gingival overgrowth. However, various other studies also demonstrate the possibility of defective intracellular calcium metabolism exchange, molecular mechanisms, inactivation of collagenase enzyme, and genetic predisposition[10] [Figure 8].
Figure 8: Pathogenesis of phenytoin-induced gingival enlargement

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Drug substitution such as by lamotrigine, gabapentin, sulthiame, and topiramate is one of the most important steps in treating and preventing recurrence of gingival enlargement. However, in this case, report, the patient continued with the drug despite counseling, due to the fear of having episodes of seizure, and was maintaining his oral hygiene and no recurrence was seen. Therefore, it can be stated that major factor responsible for exaggeration of gingival enlargement is lack of oral hygiene. It has been seen that, if a patient is kept on preventive dental program and is maintaining his oral hygiene effectively, the chances of PGE are minimized.[5],[6] Howsever, it does not eliminate the growth that has previously been occurred. Therefore, the initiation of non-surgical followed by surgical periodontal therapy is recommended. The type of periodontal surgery required can be determined by, evaluating the extent of the area to be treated, if any osseous defect is present along with the gingival enlargement and position of the base of the pocket in relation to the existing mucogingival junction. Laser or electrosurgery can also be used in these patients for proper adaptation of the gingival margins as was used in the current case.

The recurrence of drug-induced gingival enlargement is very common even in surgically treated cases. It can occur as early 3–6 months, but usually surgical results can be maintained for at least 12 months.[11],[12] However, the patient should be on regular periodontal maintenance therapy visits. These visits should be at 3-month interval and should include updating medical history, re-evaluation of the clinical periodontal parameters, and detailed oral hygiene instructions along with supra- and sub-gingival calculus removal as required.[13] However, these modalities have not been proven to be completely effective in arresting the gingival enlargement and some amount of recurrence is always seen.[14]

In the present case, the patient was able to implement meticulous home care, chlorhexidine gluconate rinses, and professional cleaning was also done timely, and no recurrence was seen till 9 months.


  Conclusion Top


PHT-induced gingival enlargement is a problem which is faced widely by the individuals under PHT therapy for the treatment of epilepsy. The effective control of this problem includes drug substitution, removal of other local factors such as plaque and calculus. After that, periodontal surgeries can also be done to provide the patient with better esthetics and comfort. However, maintaining good oral hygiene remains the most important factor to prevent recurrence, which is very common. Hence, the patient should be placed on recall visits for professional maintenance for arresting recurrence.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sridharan R. Epidemiology of epilepsy. Curr Sci 2002;82:664-70.  Back to cited text no. 1
    
2.
Hassell TM. Epilepsy and the oral manifestations of phenytoin therapy. Monogr Oral Sci 1981;9:1-205.  Back to cited text no. 2
    
3.
Kimball OP. The treatment of epilepsy with sodium diphenyl hydantoinate. JAMA 1939;112:1244-5.  Back to cited text no. 3
    
4.
Corrêa JD, Queiroz-Junior CM, Costa JE, Teixeira AL, Silva TA. Phenytoin-induced gingival overgrowth: A review of the molecular, immune, and inflammatory features. ISRN Dent 2011;2011:497850.  Back to cited text no. 4
    
5.
Pihlstrom BL, Carlson JF, Smith QT, Bastien SA, Keenan KM. Prevention of phenytoin associated gingival enlargement – A 15-month longitudinal study. J Periodontol 1980;51:311-7.  Back to cited text no. 5
    
6.
Hall WB. Dilantin@ hyperplasia: A preventable lesion? Compendium Contin Educ Dent 1990:ll:502-5.  Back to cited text no. 6
    
7.
Nayyar AS, Mubeen Khan M, Subhas GT, Nataraju B, Vijayalakshmi KR, Raghvendra BM. Gingival enlargement in epileptic patients on phenytoin therapy – An evidence based approach. J Neurol Neurophysiol 2012;3:2.  Back to cited text no. 7
    
8.
Marshall RI, Bartold PM. A clinical review of drug-induced gingival overgrowths. Aust Dent J 1999;44:219-32.  Back to cited text no. 8
    
9.
Keith DA, Paz MA, Gallop PM. The effect of diphenylhydantoin on fibroblasts in vitro. J Dent Res 1977;56:1279-83.  Back to cited text no. 9
    
10.
Johnson BD, Narayanan AS, Pieters HP, Page RC. Effect of cell donor age on the synthetic properties of fibroblasts obtained from phenytoin-induced gingival hyperplasia. J Periodontal Res 1990;25:74-80.  Back to cited text no. 10
    
11.
Camargo PM, Melnick PR, Pirih FQ, Lagos R, Takei HH. Treatment of drug-induced gingival enlargement: Aesthetic and functional considerations. Periodontol 2000 2001;27:131-8.  Back to cited text no. 11
    
12.
Rees TD, Levine RA. Systematic drugs as a risk factor for periodontal disease initiation and progression. Compendium 1995;16:20, 22, 26.  Back to cited text no. 12
    
13.
Parwani RN, Parwani SR. Management of phenytoin-induced gingival enlargement: A case report. Gen Dent 2013;61:61-7.  Back to cited text no. 13
    
14.
Hall EE. Prevention and treatment considerations in patients with drug-induced gingival enlargement. Curr Opin Periodontol 1997;4:59-63.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]



 

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