Exodontia.Info
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.

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.
Photo showing Cyclosporin-Induced Gingival Overgrowth
Photo showing Phenytoin-Induced Gingival Overgrowth
poor 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).