eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Drug-Induced Gingival Hyperplasia

Author: Piamkamon Vacharotayangul, DDS, PhD, Lecturer, Division of Oral Medicine, Department of Oral Surgery and Oral Medicine, Faculty of Medicine, Sri Nakharinwirot University School of Dentistry, Bangkok, Thailand
Coauthor(s): Francina Lozada-Nur, DDS, MS, MPH, Professor Emeritis of Clinical Oral Medicine, Step VII, Department of Orofacial Sciences, Division of Oral Medicine, Oral Pathology and Oral Radiology, School of Dentistry, Former Director of Advance Program Oral Medicine, University of California at San Francisco School of Dentistry
Contributor Information and Disclosures

Updated: Dec 15, 2006

Introduction

Background

Gingival overgrowth (GO), also known as gingival hyperplasia secondary to drugs, was first reported in the dental literature in the early 1960s in institutionalized epileptic children who were receiving therapy with phenytoin (Dilantin) for the treatment of seizures. Recently, cyclosporine (a potent immunosuppressant widely used since the early 1980s in organ transplant recipients and for psoriasis) and numerous calcium channel blocker agents (especially nifedipine) have been associated with GO. Nifedipine appears to have an additive effect when used together with cyclosporine in transplant recipients with hypertension.

Because not all patients on phenytoin, cyclosporine, or calcium antagonists develop GO, identifying patients at risk is important in order to take the necessary measures to minimize the onset and severity of this condition.

Currently, the etiology of drug-induced GO is not entirely understood but is clearly multifactorial. One of the main reasons for this is that clinical and epidemiologic studies on the role of drugs in GO are retrospective.

Some of the risk factors known to contribute to GO include the presence of gingival inflammation (gingivitis due to poor oral hygiene), presence of dental plaque that may provide a reservoir for the accumulation of phenytoin or cyclosporine, the depth of the periodontal pocket on probing, and the dose and duration of cyclosporine therapy.

Other intrinsic risk factors include the susceptibility of some subpopulations of fibroblasts and keratinocytes to phenytoin, cyclosporine, or nifedipine, and the number of Langerhans cells present in oral epithelium. The latter appears to be related to the presence of inflammation and dental plaque.

Because most of the studies reported so far observed patients who had GO at the time of the study, it is quite difficult to determine the true effect of the medication independent of cofactors (ie, severity of the underlying disease, oral health status prior to the onset of GO [premature tooth loss, periodontal disease, routine oral hygiene], socioeconomic status, education); however, it is clear that the status of oral/dental health prior to onset of GO combined with medication are involved in the onset of this condition.

Pathophysiology

Several studies have shown that the interaction of phenytoin, cyclosporine, and nifedipine with epithelial keratinocytes, fibroblasts, and collagen can lead to an overgrowth of gingival tissue in susceptible individuals. Phenytoin has been shown to induce GO by its interaction with a subpopulation of sensitive fibroblasts. Cyclosporine has been suggested to affect the metabolic function of fibroblast (eg, collagen synthesis, breakdown), whereas nifedipine, which potentiates the effect of cyclosporine, reduces protein synthesis of fibroblasts. A review of existing literature shows that a cofactor clearly is needed to induce GO.

Frequency

United States

GO is a rare condition, and no population-based or epidemiologic studies exist in the United States. Incidence rates are reported from case-series studies. The prevalence of phenytoin-induced GO is estimated at 15-50% in patients taking the medication. The prevalence for cyclosporine transplant recipient patients is 27%; however, these numbers should be interpreted with caution. The incidence of gingival hyperplasia has been reported as 10-20% in patients treated with calcium antagonists in the general population. Clinicians should look at the population represented within each particular study (ie, young persons with epilepsy, recipients of transplants).

International

No incidence or prevalence epidemiologic data is available on GO worldwide. In India, 57% of epileptic children aged 8-13 years who were undergoing phenytoin monotherapy developed GO within 6 months of treatment.

Mortality/Morbidity

No mortality is associated with gingival enlargement. Morbidity can be severe in some cases because of gross overgrowth of gingival tissue, which can lead to gingival bleeding, pain, teeth displacement, and periodontal disease.

Race

No racial predilection exists for the onset of drug-induced GO.

Sex

No sexual predilection exists for drug-induced GO, although in one study, males were 3 times more likely than females to develop GO with calcium antagonists.

Age

No age predilection exists for the onset of drug-induced GO; however, phenytoin-induced GO appears to be more frequent in young patients with epilepsy. Most likely, this may be related to the age of the population, the nature of the disease, and poor oral hygiene.

Clinical

History

The onset of drug-induced GO in susceptible individuals is insidious. GO is asymptomatic, except in the presence of poor oral hygiene and dental plaque because patients may develop bleeding with tender and swollen gums. Patients with malpositioned teeth, periodontal disease, and poor oral hygiene are at risk of developing GO. Severity varies depending on the oral/dental health prior to the beginning of therapy; however, not all patients with poor oral hygiene develop drug-induced GO.

• Phenytoin-induced GO
  • This is more likely to occur in patients with gingivitis and dental plaque.
  • Increased dental plaque has been suggested to induce local inflammation and to serve as a reservoir for phenytoin.
• Cyclosporine-induced GO
  • In susceptible patients (ie, presence of dental plaque, swollen gums, high dose of cyclosporine), GO may develop by the third month of therapy.
  • Patients with poor oral hygiene and displaced teeth tend to develop bleeding gums upon probing.
  • Aggressive plaque control and routine oral hygiene help in maintaining gums but may not prevent the onset of GO in susceptible individuals.
  • Cyclosporine-induced GO is reversible once therapy is discontinued or when the dose is reduced.
• Cyclosporine- and nifedipine-induced GO: Nifedipine potentiates the adverse effect (ie, GO) of cyclosporine.
• Calcium antagonist–induced GO
  • Oral hygiene plays a decisive role in the development of gingival enlargement.
  • Substantial evidence in the dental literature indicates that gingival enlargement can be controlled successfully, even under the continuous administration of calcium antagonists, by meticulous professional and individual oral hygiene.

Physical

• Gingival enlargement occurs primarily on the labial gingival mucosa and in between the teeth (interdental papillae area).
• GO is more pronounced on the labial aspect of the maxillary gingiva and in the interdental papillae.

Causes

Potential risk factors for drug-induced GO include the following:

• Poor oral hygiene
• Periodontal disease
• Periodontal pocket depth
• Gingival inflammation
• Degree of dental plaque
• Duration and dose of cyclosporine

• Search for CME/CE on This Topic »

• Gingivitis Overview
• Gingivitis Symptoms
• Gingivitis Treatment
• Teeth and Mouth Center
• Gingivitis Causes
• When to Visit the Dentist - Introduction