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Drug-Induced Gingival Hyperplasia
Drug-induced Gingival (gum) Overgrowth occurs as a side effect of some systemic medications.

Many terms have been used to describe gingival overgrowth (GO). The expression gingival hyperplasia
(“
abnormal increase in the number of normal cells in a normal arrangement in an organ or tissue, which increase
in volume”)
and gingival hypertrophy (“enlargement or overgrowth of an organ or part due to an increase in size
of its constituent cells”
) have been also used, although gingival overgrowth is the general term that better
describes this
iatrogenic condition.

The drugs mainly associated with
GO are:

Phenytoin, a drug used for the management of epilepsy, and other anti-convulsants such as sodium valproate,
phenobarbital, vigabatrin.

Ciclosporin, an immuno-suppressant drug used to reduce organ transplant rejection;

Calcium-channel blockers (nifedipine, verapamil, diltiazem, oxodipine, amlodipine), a group of anti-
hypertensive drugs.

Other drugs, such as antibiotics (
erythromycin) and hormones, have been also associated with this side effect.

Not all patients using these drugs are affected by gingival overgrowth and the extent and severity of the overgrowth
is variable in such patients.

The relationship between age and
GO is uncertain.
Useful Websites:


American Academy of Periodontology

Wikipedia

Emedicine (Dermatology)
DermNet NZ (New Zealand Dermatological Society)

Journal of Dental Hygiene 2004.  Treating patients with drug-induced gingival overgrowth.


Useful Articles:

Australian Dental Journal 1999.  A Clinical Review Of Drug-Induced Gingival Overgrowths.

Australian Prescriber 2003.  Management of Drug-induced Gingival Enlargement.

J Periodontol 2004.  Drug-Associated Gingival Enlargement.

Emedicine 2006.  Drug-Induced Gingival Hyperplasia.

Journal of IMAB 2007.  Surgical Approach to Drug-Induced Gingival Enlargement in Renal Transplant Patients – A
Case Report.

Journal of Contemporary Dental Practice 2008.  Current Opinion on Drug-induced Oral Reactions - A
Comprehensive Review.

New England Journal of Medicine 2009.  Medication-Induced Gingival Hypertrophy.

BDJ 2017.  Gingival Overgrowth.  Part 1.  Aetiology & Clinical Diagnosis

BDJ 2017.  Gingival Overgrowth.  Part 2.  Management Strategies
Photo showing Cyclosporin-Induced Gingival Overgrowth
Photo showing Phenytoin-Induced Gingival Overgrowth
Drug-induced gingival swelling is usually aggravated bypoor oral hygiene and starts interdentally, especially
labially (lip-side).  Papillæ (the triangular pieces of gum twixt teeth) are firm, pale and enlarge to form false,
vertical clefts.  This may be associated with
hypertrichosis (hairyness).

The
GO is usually related to the dose of the drug, the duration of drug therapy, the serum concentration (the
concentration of the drug in the blood stream) and the presence of dental plaque.  Clinically, both
marginal gingiva
and
inter-dental papillæ appear enlarged and firm with a surface that may be smooth, stippled, or lobulated with
little or no inflammation.

The
GO may be localised or generalised and can partially or entirely cover the crown of the teeth.  In severe
cases, difficulties in
mastication (chewing) and speech may occur.  The diagnosis is made on the basis of the
medical history and the clinical features.


What are the causes of Drug-Induced Gingival Overgrowth?

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 the drug, the
depth of the
periodontal pocket on probing and the dose and duration of drug therapy.

Other intrinsic risk factors include the susceptibility of some sub-populations of cells such as
fibroblasts and
keratinocytes (cells present in skin) to Phenytoin, Cyclosporine, or Nifedipine and the number of Langerhans cells
(immune cells) present in the
oral epithelium; the latter appears to be related to the presence of inflammation and
dental plaque.


Phenytoin, which is used mainly for the control of grand mal epilepsy and can produce a variable degree of GO.

There is a positive correlation between the severity of the
GO and gingival inflammation, plaque score, calculus
accumulation
and pocket depths.

However, there is no correlation between the extent of
GO and the dose of phenytoin, its serum level or the age
and sex of the patient.

Ciclosporin (cyclosporin) is an immuno-suppressive drug particularly used to suppress the cell-mediated response
after organ transplants and can cause
GO initially affecting the gingival papillæ, but only a third of patients may be
affected, more commonly children.

Calcium-channel blockers, which are mainly used as anti-hypertensive agents (especially nifedipine), cause, in
some individuals,
GO typically affecting the papillæ which become red and puffy and tend to bleed.


How is it diagnosed?

This is usually a clinical diagnosis.  Blood picture or biopsy are rarely indicated.  Tissue biopsy may be indicated if
GO has an unusual clinical presentation or if the patient is not on a medication known to induce GO.


How is it treated?

Treatment of drug-induced GO poses some problems.

The physician may be willing to substitute another drug but, in any event, the patient's level of plaque control often
needs considerable improvement and a
chlorhexidine mouthwash may be helpful.

Excision of enlarged tissue may be indicated, but difficult if the tissue is very firm and fibrous.  Healing may be
slow, possibly hampered by infection of the large wound.  Unfortunately, the
GO readily recurs, although this is less
likely with meticulous oral hygiene, particularly if the drug has been stopped.

Hence:

  • treat pre-disposing factors
  • improve oral hygiene
  • gingivoplasty / gingivectomy where indicated.
  • interruption, modification of the dosage or replacement of the drugs


Treatment of
drug-induced GO includes surgical and / or non-surgical therapies.

Non-surgical treatment, where it is possible, is based on the interruption, modification of the dosage or
replacement of the drugs.

In patients treated with
ciclosporin, it seems that the contemporary use of the antibiotic, azithromycin, may
decrease the severity of
GO. Furthermore, in adult organ transplant patients, dosages of both prednisolone and
azathioprine appeared to afford the patients some degree of “protection” against GO and may also reduce the
severity of this side effect.

Good oral hygiene associated with the use of
chlorhexidine oral rinses and frequent plaque and calculus removal
procedures, could help to reduce the degree of gingival overgrowth.

After the interruption of therapy or the replacement of drugs, follow-up of 6 - 12 months is important to evaluate the
resolution of
GO and / or the necessity of a surgical treatment.

Surgical treatment consists of removing gingival hyperplastic tissues with periodontal surgical techniques of
gingivectomy and / or periodontal flaps.

Gingivectomy is the treatment preferred when the GO involves small areas (up to six teeth), there is no evidence
of attachment loss and there is at least 3 mm of
keratinized tissue.

The
periodontal flap is preferred when the GO involves larger areas (more than six teeth) and there is evidence of
attachment loss combined with
osseous defects.

CO2 or argon-laser surgery has been proposed as surgical treatment of GO because of decreased surgical time
and rapid
post-operative haemostasis.

Good oral hygiene for preventing or retarding the recurrence of the
GO is important after surgery.

Recurrences are frequent, particularly in patients with less than optimal plaque control and when the drug regimens
cannot be modified or reduced.

Complications:

  • Severe GO in patients with poor oral health can lead to early tooth loss.

  • Chlorhexidine 12% mouthwash might cause teeth staining however, brushing teeth prior to rinsing out with
    chlorhexidine can prevent it. The stain can be removed by routine oral prophylaxis.

  • Dental extraction of periodontically compromised teeth is indicated if those teeth may interfere with
    subsequent medical treatment.  It also may be considered if the patient cannot perform prophylactic dental
    care (eg, young epileptic patient).
Last Updated 1st January 2020