Recurrent Phenytoin-Induced Gingival and Lip Hyperplasia Following Rat Killer Paste Poisoning: A Rare Case Report

Abstract

Phenytoin-induced gingival hyperplasia is a well-documented adverse drug reaction, usually occurring after prolonged use. However, recurrence or rapid reappearance following re-exposure is uncommon. We report a case of a 36-year-old male, a known epileptic patient on irregular phenytoin therapy, who developed acute gingival and lip swelling after receiving intravenous phenytoin during treatment for rat killer paste poisoning. The episode highlights the potential for acute flare-up of gingival hyperplasia in previously sensitized patients, especially under conditions affecting drug metabolism, such as hepatic dysfunction or hypoalbuminemia. Withdrawal of phenytoin and substitution with sodium valproate resulted in gradual regression of swelling.

Keywords

Introduction

Phenytoin is a widely used antiepileptic drug, known to cause gingival hyperplasia in 10–50% of long-term users (1). This reaction is dose-dependent and typically develops after prolonged exposure, often months after therapy initiation (2). The pathogenesis involves fibroblast proliferation, collagen accumulation, and reduced folic acid uptake within gingival tissues (3).

Although chronic gingival hyperplasia is well-documented, cases of rapid or recurrent gingival and lip enlargement following short-term re-exposure are rarely reported. Factors such as hepatic dysfunction, hypoalbuminemia, and altered phenytoin metabolism can lead to elevated unbound drug concentrations, enhancing susceptibility to adverse reactions (4).

This case report describes a rare recurrence of gingival and lip hyperplasia following intravenous phenytoin administration in a patient with rat killer paste poisoning, with prior intermittent exposure to phenytoin for seizure disorder.

CASE PRESENTATION

A 36-year-old male with a known history of seizure disorder for five years presented to the emergency department following rat killer paste ingestion of unknown compound. He had a single episode of generalized tonic-clonic seizure lasting about 5 minutes. There was no prior history of chronic liver disease, allergies, or other systemic illness. He was not on regular antiepileptic therapy, but reported intermittent use of phenytoin in the past.

Initial management included Inj. N-acetylcysteine (3 g in 5% dextrose over 4 hours), Inj. Vitamin K 10 mg IV TDS, Inj. Ranitidine 50 mg IV BD, and Inj. Ondansetron 4 mg IV BD. For seizure control, he received Inj. Phenytoin 300 mg IV loading dose in 100 mL NS, followed by Inj. Phenytoin 100 mg IV TDS.

Clinical Observation and Progress

Within 2–3 days of initiating IV phenytoin, the patient developed diffuse swelling of both upper and lower lips associated with pain and difficulty in chewing. The swelling gradually extended to the gingival margins. No urticaria, dyspnea, or systemic allergic signs were noted.

The clinical presentation suggested acute exacerbation of phenytoin-induced gingival hyperplasia rather than angioedema. Phenytoin therapy was immediately discontinued and substituted with T. Sodium Valproate 200 mg PO 1-0-2. Supportive therapy with Inj. Vitamin K 10 mg IV TDS was continued.

Over the following days, the lip and gingival swelling subsided gradually, confirming phenytoin as the probable causative drug.

Laboratory Interpretation

Laboratory tests revealed mild elevation of liver enzymes (AST/ALT), prolonged prothrombin time, and low serum albumin levels, indicating transient hepatic stress possibly due to rat poison toxicity. These findings likely increased the free plasma concentration of phenytoin, enhancing toxicity. Other parameters were within normal limits.

Diagnosis

Based on temporal association, clinical features, and improvement after drug withdrawal, a diagnosis of rat killer poisoning with seizure disorder – phenytoin induced gingival and lip hyperplasia (recurrent type) was made.

The Naranjo causality assessment score was 7, indicating a probable adverse drug reaction.

Treatment Course and Outcome

Phenytoin was permanently discontinued. The patient was maintained on sodium valproate, and symptomatic relief was achieved within five days. The swelling completely resolved over the following week. He was advised to maintain oral hygiene and avoid future phenytoin use.

Observed Adverse Drug Reaction (ADR)

RESULT

The patient demonstrated complete recovery after discontinuation of phenytoin and initiation of sodium valproate. Follow-up at one week showed resolution of gingival and lip swelling with no recurrence.

DISCUSSION

Phenytoin-induced gingival hyperplasia usually presents after chronic oral therapy, with incidence ranging from 10–50% (1,2). However, in patients with previous exposure, short-term re-administration may provoke acute inflammatory enlargement due to reactivation of sensitized gingival fibroblasts (5).

The pathogenesis is multifactorial—phenytoin alters calcium influx in gingival fibroblasts, increases collagen synthesis, and decreases collagenase activity (6). Genetic predisposition and poor oral hygiene are recognized risk factors (7).

In this patient, liver dysfunction and hypoalbuminemia following rat killer paste poisoning may have contributed to elevated free phenytoin levels, precipitating the reaction. The rapid onset within three days likely represents an acute flare-up rather than a de novo chronic reaction.

Early recognition and drug discontinuation are critical, as continuation may lead to irreversible fibrotic overgrowth requiring surgical excision. Switching to alternative antiepileptics such as valproate or levetiracetam prevents recurrence (8).

This case underscores the need for careful monitoring of phenytoin therapy, particularly in patients with hepatic impairment or prior exposure.

CONCLUSION

This case highlights a rare recurrence of phenytoin-induced gingival and lip hyperplasia following re-exposure during treatment for rat killer paste poisoning. The reaction was likely precipitated by prior phenytoin sensitization and elevated unbound drug levels due to hepatic dysfunction. Clinicians should exercise caution when reinitiating phenytoin in patients with previous exposure or compromised liver function.

ACKNOWLEDGEMENT

The author declares no conflict of interest related to this manuscript. No financial or institutional support influenced the preparation of this report. The authors sincerely thank the Department of Medicine and the Clinical Pharmacology Unit, for their guidance and support in reporting this case. We also acknowledge the Pharmacovigilance Programme of India (PvPI) for facilitating ADR documentation through the WHO-VigiFlow portal.

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