INTRODUCTION:
Gingival enlargement is one of the most
common adverse side-effects associated with certain medications. The three major
groups of drugs that are known to cause drug induced gingival enlargement are
anticonvulsants (mainly phenytoin),
calcium channel blockers and immunosuppressants
(cyclosporine A)[1]. Although the primary target for these drugs is
completely different, the secondary target coincides and is found to be the
connective tissue of the gingiva.[2] The
pathogenesis is not completely understood but they cause the same clinical and histopathological findings[2] with the
significant risk factor being poor plaque control. It can pose a cosmetic
problem, create difficulty in speech or mastication, cause malocclusion or
interfere with effective tooth cleaning.[3]
There are different approaches in treating
gingival enlargement and they can be through non-surgical or surgical methods
depending on the severity of the disease.
Clinical
Presentation
It has been found that males are more
commonly affected than females in the ratio of 3:1[4], and its
occurrence is inversely proportional to age.[5] It occurs within the
first 3 months of starting drug therapy. Some of the symptoms include pain,
bleeding, tenderness, higher susceptibility to infection and hence increased
rate of occurrence of caries and periodontal problems.[6] Halitosis
and suppuration may also be seen due to plaque and food accumulation.[7] The growth starts at the interdental
papilla as a painless, bead-like enlargement and extends to the facial and
lingual margins of the gingiva. It can cover
considerable portions of the crown and hence interfere with occlusion. It is
rarely seen in edentulous areas.[8]
Based on Gomez et al’s
clinical study,[9] (clinical report on treatment of cyclosporine
induced gingival hyperplasia, 1997) 4 categories of gingival growth have been
classified: no gingival growth (0),
mild overgrowth with blunt marginal gingiva (1), moderate overgrowth, extending to
the middle of the tooth crown (2)
and severe overgrowth, two-thirds of the tooth crown is covered and the whole
attached gingiva is affected (3). According to Bokenkamp in 1994[10],
Grade 0- No sign of gingival
enlargement, Grade I- Enlargement
confined to interdental papilla, Grade II- Involves papillae and marginal gingiva,
and Grade III- Enlargement covers
three-quarters or more of the tooth crown.[8]
In the absence of inflammation, the lesion
is characteristically mulberry-shaped, pale pink, firm and resilient with a lobulated surface and no sign of bleeding. Complication
of the growth occurs when there is a secondary inflammatory process caused by
plaque accumulation.[8] This can be calculated using Silness and Loe gingival index[11]
and the quantity of oral debris and calculus can be calculated using the
Simplified oral hygiene index[12].
Investigations
To evaluate the status of the periodontal
tissue and any other compromised teeth, intra-oral periapical
radiographs are taken. To rule out the possibility of anaemia
and leukaemia, complete blood count is taken. Culture
is taken to differentiate it from oral candidiasis.
Tissue biopsy is essential to check for any unusual clinical presentation. Histologic findings will reveal a highly vascular
connective tissue with focal accumulation of inflammatory cells, irregular and
multilayered overlying epithelium and increase in the number of Langerhan cells. Acanthosis and parakeratosis have also been reported.
Treatment
In managing drug induced gingival
enlargements, plaque control, medical or non-surgical management, surgical
management, dental care and follow-up are of immense importance. Treatment
planning becomes more complicated when drug induced gingival enlargement is
accompanied by periodontal disease. The treatment options should be wisely
chosen by the dentist based on the clinical presentation, the severity of the
overgrowth, medical status of the patient and patient compliance.
Non-Surgical Methods
The objective of using a non-surgical
method for treating drug induced gingival enlargement is to reduce the
inflammatory component.[13]
·
Oral hygiene maintenance: Plaque accumulation is the
primary etiologic factor that causes inflammation of the gingival tissues.
Plaque control, therefore, becomes essential in reducing the inflammatory
component. Chemical and mechanical methods are available to control the
accumulation of plaque. Using chlorhexidine mouth
wash (0.12%) is one such chemical method that helps in reducing plaque and rate
of recurrence after surgery.[2,7,13] Rinsing the mouth with chlorhexidine twice or thrice a day along with mechanical
plaque control gradually reduces the amount of oral debris and plaque in the
mouth. Brushing twice everyday and using electronic or power-driven brushes
also have been advocated for this purpose. Interdental
plaque can be removed using careful flossing.[7,13] Another chemical
agent which has been found to be efficient in preventing recurrence of phenytoin-induced gingival enlargement is folic acid mouth
wash.[13] Folate used topically may also
decrease gingival inflammation.
·
Oral prophylaxis: Performing scaling and root planing every two to three months also helps in keeping
gingival inflammation under control.[14]
·
Systemic antibiotics: Studies on organ transplant
patients have shown that short courses of antibiotics azithromycin
and metronidazole have reduced cyclosporine induced
gingival overgrowth.[2,13] But there have been studies that
contraindicate the same. Systemic administration was found to be much more
effective than a local delivery preparation.[13] Two mechanisms by
which azithromycin may act are reduction of bacterial
infection which in turn reduces inflammation[15] and increase in the
phagocytic activity of fibroblasts in the gingiva which decreases the ability of cyclosporine to
reduce degradation of collagen.[16] There are concerns about
repeated doses of antibiotics due to the high recurrence rate of drug induced
gingival enlargement.
·
Drug substitution: The most obvious solution to
this disease is to substitute the drug causing the enlargement. Prior to drug
substitution, it is of vital importance to evaluate its feasibility. The
patient’s overall health status must be given more importance in comparison to
the periodontal problems. Consultation with the physician is an absolute
necessity before going ahead with drug substitution, especially in case of
patients who have undergone organ transplantation as replacing cyclosporine can
jeopardize the patient’s condition.
o Phenytoin (anticonvulsant) can be
replaced with Vigabatrin, Lamotrigine,
Gabapentine, Suthiame, Topiramate,[2] Carbamazepine,
Ethosuximide, Sodium Valproate.[13]
This has been possible because of the addition of new generation of
drugs.
o An antihypertensive drug, nifedipine (calcium channel blocker) has been found as the
most common drug, among the rest, to cause gingival overgrowth. Drug
substitution using verapamil, amlodipine
and felodipine have been effective in some gingival
enlargement cases.[2] But in many cases drug substitution with
structurally different antihypertensive drugs have been reported as a drug
alternative which is preferred, such as, thiazide
diuretics, atenolol (beta-blocking drug), enalapril (angiotensin converting
enzyme inhibitor)[13], losartan[17].
o Among immunosuppressants,
cyclosporine is a drug that induces overgrowth of gingiva.
It is given to organ transplant patients as a life saving drug. Therefore, for
many years this could not be used as a treatment option for cyclosporine
induced gingival enlargement. Reduction in dose of cyclosporine was found to be
beneficial in certain cases[18], but dose reduction in transplant
patients is not an option. Although new immunosuppressants
like tacrolimus, mycophenolate
mofetil and rapamycin are
available, they have not been reported in association with enlargement of gingiva.[2]
Surgical Methods
Surgical methods of management of gingival
enlargement are performed for cosmetic needs and when there is interference in
mastication and speech.
Whether the surgery should be performed
under local anaesthesia or general anaesthesia should be carefully assessed by the dentist
based on the patient’s compliance, medical status and the severity of the
overgrowth.[17]
The surgical method to be used depends on
the clinical presentation of the gingival tissues. It depends on the amount of
enlargement, the number of teeth it is involved with, the attachment loss,
presence of any bone loss or osseous defects and the abundance of keratinised tissue. Based on the clinical findings, either
a gingivectomy or a periodontal flap surgery can be
performed.
·
Gingivectomy
Gingivectomy is basically surgical excision
of the gingiva. This method is used when less than 6
teeth are involved in the oral cavity and there is adequate width of attached gingiva. It is a simple and quick method which helps in
restoring the gingival contour. It can be done using a scalpel, electrosurgery or laser surgery.
Scalpel surgery
can be done using periodontal knives and #11 and #12 Bard-Parker blades. It is
a simple procedure that is done with the blade placed on the marginal gingiva in the coronal direction to a point between the
base of the pocket and the alveolar crest and the excess gingival tissue is
excised. Soft tissue pockets are also eliminated here.[8] One of the
main disadvantages of using scalpel is excessive peri-operative
bleeding which is more significant in case of highly vascularised
and inflamed tissues.[13]
Electrosurgery reduces haemorrhage
and is found to be effective for about fifteen years and eliminates problems
associated with conventional surgical excision[19] but its use is
limited because it causes a surrounding zone of thermal necrosis which delays
healing due to accumulation of excessive latent heat.[13]
Laser gingivectomy is more advantageous than other techniques
because of its ability to cut accurately, promotes healing by forming a layer
of coagulated tissue along the incision, causes very little or no bleeding,
minimal scarring and post-operative swelling, sterilises
the operating field, minimises the need for sutures,
reduces post-operative pain and can be used in patients who are on
anticoagulant therapy.[13] CO2 lasers, diode lasers and
ND:YAG lasers are most commonly used lasers in dentistry.
·
Flap surgery
Flap surgery is
the treatment option in case of gingival enlargement involving more than 6 teeth
and there is extensive loss of attached gingiva and
bone along with osseous defects. It reduces the chance of post-operative
complications.[2]
#15 Bard-Parker
blade is used to make an internal bevel incision at least 3 mm coronal to the mucogingival junction and the gingival tissues are thinned
out in a bucco-lingual direction. A full thickness or
a split thickness flap is elevated and the base of the papilla is incised
connecting the lingual and facial incisions using an Orban’s
knife. The excised tissues are removed with a curette and the flap is replaced
and sutured.[8] Periodontal
pack is positioned in place for a period of one week and the patient is
prescribed mouth wash postoperatively.
The rate of
recurrence in case of drug induced gingival enlargement is generally found to
be high. In such cases, repeated surgeries may be required along with vigorous
maintenance of good oral hygiene.
Treatment
options of gingival enlargement caused due to drugs have been summarised in figure 1.
CONCLUSION:
Drug induced gingival enlargement is a well
known side effect of anticonvulsants, calcium channel blockers and immunosuppressants. It must be diagnosed at the earliest
stage possible and plaque control measures must be taken and such patients must
be subjected to drug substitution to remove the inflammatory component which
increases the severity of the disease. Those individuals who have been
prescribed these drugs must be well informed by the physician about its
ill-effects on the periodontium and a complete
periodontal assessment must be indicated to eliminate any risk factors. The
choice of treatment to be taken by the dentist must take all aspects of the
patient’s health and mental status into account along with the clinical
presentation and other risk factors.