GINGIVAL

ENLARGEMENT

Prepared by:

Guided by:

DR. DHWANIT THAKORE

DR. MIHIR SHAH

DR. ARCHITA KIKANI
DR. HIRAL PARIKH
DR. SHILPI SHAH
DR. TEJAL SHETH

DEPARTMENT
OF
PERIODONTOLOGY AND
IMPLANTOLOGY
AHMEDABAD DENTAL COLLEGE & HOSPITAL

Definition
Many terms have been used to describe gingival overgrowth. 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 condition.
Gingival enlargement or gingival overgrowth are strictly clinical descriptive
terms and avoid the erroneous pathologic connotations of terms in the past,
such as "hypertrophic gingivitis" or "gingival hyperplasia."

Classification:
According to etiologic factors and pathologic changes Older classification of
gingival enlargement was:
I.lnflammatory enlargement
A. Chronic
B. Acute
II. Fibrotic enlargement (gingival hyperplasia)
A. Drug-induced
B. Idiopathic
III. Combined enlargement (inflammatory + fibrotic)
IV. Enlargements associated with systemic diseases/conditions
A. Conditioned enlargement
1. pregnancy
2. Puberty
3. Vitamin C deficiency
4. Plasma cell gingivitis
5. Nonspecific conditioned enlargement (granuloma pyogenicum)
B. Systemic diseases causing gingival enlargement
1. Leukemia
2. Granulomatous diseases (Wegener's granulomatosis,
sarcoidosis, etc.)
V. Neoplastic enlargement (gingival tumors)
A. Benign tumors
B. Malignant tumors
VI. False enlargement

The classification system was further modified according to

etiologic factors & pathologic changes into:
I. Inflammatory enlargement
A.Chronic
B.Acute
1. Drug-induced enlargement
2. Enlargements associated with systemic diseases or
conditions
A. Conditioned enlargement
1. Pregnancy
2. Puberty
3. Vitamin C deficiency
4. Plasma cell gingivitis
5. Nonspecific conditioned enlargement
(pyogenic granuloma)
B. Systemic diseases causing gingival enlargement
1. Leukemia
2. Granulomatous diseases (e.g., Wegener's
granulomatosis, sarcoidosis)
IV. Neoplastic enlargement (gingival tumors)
A.Benign tumors
B. Malignant tumors
V. False enlargement
Using the criteria of location and distribution, gingival enlargement is designated as
follows:
Localized: Limited to the gingiva adjacent to a single tooth or group of teeth.
Generalized: Involving the gingiva throughout the mouth.
Marginal: Confined to the marginal gingiva.
Papillary: Confined to the interdental papilla.
Diffuse: Involving the marginal and attached gingivae and papillae.
Discrete: An isolated sessile or pedunculated, tumor like enlargement.

INDICES FOR GINGIVAL ENLARGEMENT:

BOKENKAMP et al (1994) :
GRADE 0 : No signs of gingival enlargement.
GRADE 1 : Enlargement confined to interdental papilla.
GRADE 2 : Enlargement involves papilla and marginal gingival.

GRADE 3 : Enlargement covers three-quarters or more of the crown.

INGLE et al (1999) :
GRADE 0 :
1. No overgrowth; firm adaptation of the attached gingival to the underlying
alveolar bone.
2. Slight stippling; there is no granular appearance or a slightly granular
appearance.
3. There is no increase in the density or size of the gingival.
GRADE 1 :
1. Early overgrowth, as evidenced by an increase in the density of the gingiva with
marked stippling and granular appearance.
2. The tip of papilla is rounded.
3. The probing depth is less than or equal to 3 mm.
GRADE 2 :
1. Moderate overgrowth, manifestated by an increase in the size of papilla and or
rolled gingival margins.
2. Contour of the gingival margin is still concave or straight.
3. Gingival enlargement has a buccolingual dimension of upto 2 mm, measured from
the tip of the papilla outwards.
GRADE 3 :
1. Marked overgrowth, represented by encroachment of gingival margin onto the
crown.
2. The contour of the gingival margin is convex rather concave.
3. Gingival enlargement has a buccolingual dimension of upto 3 mm or more,
measured from the tip of the papilla outwards.
4. The papilla is clealy retractable.
GRADE 4 :
1. Severe overgrowth characterized by a profound thickening of the gingival.
2. A large percentage of clinical crown is covered.
3. Same as for grade 3; Papilla is retractable, probing depth is more than 6 mm, and
the buccolingual dimension is approximately 3 mm.
INFLAMMATORY ENLARGEMENT
Gingival enlargement may result from chronic or acute inflammatory changes;
chronic changes are much more common. In addition, inflammatory enlargements usually
are a secondary complication to any of the other types of enlargement, creating a
combined gingival enlargement. In these cases it is important to understand the double
etiology and treat them adequately

Chronic Inflammatory Enlargement

Etiology:
Chronic inflammatory gingival enlargement is caused by prolonged exposure to
dental plaque. Factors that favor plaque accumulation and retention include poor oral
hygiene, as well as irritation by anatomic abnormalities and improper restorative and
orthodontic appliances.
Clinical Features:
Chronic inflammatory gingival enlargement originates as a slight ballooning of
the interdental papilla and marginal gingiva. In the early stages it produces a life
preserver-shaped bulge around the involved teeth. This bulge can increase in size until it
covers part of the crowns. The enlargement may be localized or generalized and
progresses slowly and painlessly, unless it is complicated by acute infection or trauma.
Occasionally, chronic inflammatory gingival enlargement occurs as a discrete sessile or
pedunculated mass resembling a tumor. It may be interproximal or on the marginal or
attached gingiva. The lesions are slow-growing masses and usually painless. They may
undergo spontaneous reduction in size, followed by exacerbation and continued
enlargement. Painful ulceration sometimes occurs in the fold between the mass and the
adjacent gingiva.
Histopathology:
Chronic inflammatory gingival enlargements show the exudative and proliferative
features of chronic inflammation. Lesions that are clinically deep red or bluish red are
soft and friable with a smooth, shiny surface, and they bleed easily. They also have a
preponderance of inflammatory cells and fluid, with vascular engorgement, new capillary
formation, and associated degenerative changes. Lesions that are relatively firm, resilient,
and pink have a greater fibrotic component with an abundance of fibroblasts and collagen
fibers.

Gingival Changes Associated with Mouth Breathing.

Gingivitis and gingival enlargement are often seen in mouth breathers.The
gingiva appears red and edematous, with a diffuse surface shininess of the exposed area.

The maxillary anterior region is the common site of such involvement. The presence of
marginal gingivitis in mouth breathers was first noticed by Coleyer in 1920.
The severity of the harmful effects produced by mouth breathing on gingiva
with depend on
1) Whether mouth breather is occasional or continuous
2) Duration of this habits
3) Presence or absence of other local irritational factors
4) Systemic background of the patient
The exact manner in which mouth breathing affects gingival changes has not
been demonstrated. Its harmful effect is generally attributed to irritation from surface
dehydration. However, comparable changes could not be produced by air-drying the
gingiva of experimental animals

Clinical features:
1) The labial gingiva of the upper anterior teeth is commonly affected. The
effected gingiva is erythemalous, shiny and enlarged with rolled margins. The
interdental papillae on the labial aspect are red, edematous and bleed on slightest
provocation. At puberty the hypcrplastic tissue may progress to tumors like
masses between the teeth.
2) The colour of the gingival will very with the severity of inflammation from light
red to dark bluish red
3) The effected area is sharply demarcated from the unaffected area and this
junction has been referred by Warwick or tension ridge.

The etiology has been tried to be explained as due to:

i.

Irritation caused by passage of air

ii.

Dehydration of the mucous membrane leading to lowered tissue

resistance

iii.

Saliva about the exposed gingiva becomes viscous, debris collects

on the gingival and tooth surface due to lack of salivary flow

resulting in enormous increase in bacterial population in the oral

cavity.

Acute Inflammatory Enlargement

Gingival Abscess.
A gingival abscess is a localized, painful, rapidly expanding lesion that is usually
of sudden onset. It is generally limited to the marginal gingiva or interdental papilla. In
its early stages it appears as a red swelling with a smooth, shiny surface. Within 24 to 48
hours, the lesion usually becomes fluctuant and pointed with a surface orifice from which
a purulent exudate may be expressed. The adjacent teeth are often sensitive to percussion.
If permitted to progress, the lesion generally ruptures spontaneously.
Etiology:
Acute inflammatory gingival enlargement results from bacteria carried deep into
the tissues when a foreign substance (e.g., toothbrush bristle, piece of apple core, lobster
shell fragment) is forcefully embedded into the gingiva. The lesion is confined to the
gingiva and should not be confused with periodontal or lateral abscesses.
Histopathology:
The gingival abscess consists of a purulent focus in the connective tissue,
surrounded by a diffuse infiltration of polymorphonuclcar leukocytes (PMNs), edematous
tissue, and vascular engorgement. The surface epithelium has varying degrees of intracellular and extracellular edema, invasion by leukocytes, and sometimes ulceration.

Periodontal (Lateral) Abscess.

Periodontal abscesses generally produce enlargement of the gingiva, but they also
involve the supporting periodontal tissues.
Etiology:
1. Extension of infection from a periodontal pocket deeply into the supporting
periodontal tissues.
2. Lateral extension of inflammation from inner surface of a periodontal pocket
into the connective tissue of the pocket wall.

3. In a pocket that describes tortuous course around root, a periodontal abscess

may form in the cul-de-sac. The deep end of which is shut off from the surface.
4. Incomplete removal of calculus during treatment of periodontal pocket.
5. After trauma to the tooth

Periodontal Abscess may occur in the absence of periodontal disease after

trauma to the tooth or perforation of the lateral wall of the root in endodontic therapy.
Clinical features:
The most common symptom is pain. Generalized is mucosal swelling is often
seen in the area of pain. The swelling can vary from a small enlargement of the
gingival unit to a diffuse swelling including the gingiva, alveolar mucous and oral
mucosa and may extend to face & neck. The affected tissues will be red to reddish
blue frequently the tooth is mobile and may even extrude form the alveolar socket and
fell high to the occlusion.
Histopathology:
The entry of bacteria into the soft tissue pocket wall could be the first event to
initiate the periodontal abscess. Inflammatory cells are then attracted by chemotactic
factors released by the bacteria, and the concomitant inflammatory reaction leads to
destruction of the connective tissues (DeWitt et al. 1985),
The encapsulation of the bacterial infection and the production of pus (Carranza
1990). Histologically, intact neutrophils are found surrounding a central area of soft
tissue debris and destroyed leukocytes. At a later stage, a pyogenic membrane, composed
of macrophages and neutrophils, is organised. The rate of destruction in the abscess will
depend on the growth of bacteria inside the foci and its virulence as well as on the local
pH, since an acidic environment will favour the activity of lysosomal enzymes (De- Witt
et al. 1985).
De Witt et al. (1985) studied biopsy punches taken from 12 abscesses. The
biopsies were taken just apical to the area of major fluctuance. They observed, from the
outside to the inside:
(a) a normal oral epithelium and lamina propria;
(b) an acute inflammatory infiltrate;

(c) an intense foci of inflammation (neutrophil-lymphocyte) with the surrounding

connective tissue destroyed and necrotic;
(d) a destroyed and ulcerated pocket epithelium;
(e) a central region, as a mass of granular, acidophilic, and amorphous debris.

Microbiology :
Newman & Sims (1979) described that the most frequent type of bacteria were
gram-negative anaerobic rods and gram-positive facultative cocci. In general, gramnegatives predominated over gram-positives, and rods over cocci (Newman & Sims
1979), with percentages ranging between 40% and 60% for a each group. Culture studies
of periodontal abscesses have revealed high prevalences of Porphyromonas gingivalis
(55100%), Prevotella intermedia (25100%), and Fusobacterium nucleatum (4465%)
(Topoll et al. 1990, Van Winkelhoff et al. 1985, Hafstrm et al. 1994, Newman & Sims
1979).

However,

other

pathogens

have

also

been

reported:Actinobacillus

actinomycetemcomitans (25%) and Campylobacter rectus (80%) (Hafstrm et al. 1994);

Prevotella melaninogenica (22%) (Newman & Sims 1979). Using PCR, high prevalences
of P. gingivalis (100%) and Treponema denticola (71.4%) were also found in a sample of
7 periodontal abscesses (Ashimoto et al. 1998). The periodontal abscess microbiota is
usually indistinguishable from the microflora found in the subgingival plaque in adult
periodontitis.

Drug Induced Gingival Overgrowth/ Enlargement:

There is an ever increasing number of medications which may induce over growth
of the gingiva, although a large range of pathological and idiopathic reactions can also
result in gingival overgrowth. This review concentrates on the various overgrowth s
associated with pharmaceuticals, and their clinical management.
Medication-induced gingival overgrowths occur as a side effect of drugs used
mainly for non-dental treatment for which the gingival tissue is not the intended target
organ. Drugs associated with gingival overgrowth can be categorized broadly into three
major groups according to their therapeutic actions, namely anticonvulsants,
immunosupressants and calcium channel blockers

Some common drugs causing DIGO are:

Anticonvulsants:
Hydantoins

Ethotonin
Mephenytoin
Phenytoin

Succinimides

Ethosuximide
Methsuximide
-

Phensuximide

Valproic acid

Valproic acid

Immunosuppressants:

Cylcosporine A

Calcium channel blockers:

Dehydropyridine derivatives

Amlodipine
Felodipine
Nicardipine
Verapamil
Diltiazem

Other drugs which might cause DIGO are

Clinical Features:
The growth starts as a painless, beadlike enlargement of the interdental papilla
and extends to the facial and lingual gingival margins. As the condition progresses, the
marginal and papillary enlargements unite; they may develop into a massive tissue fold
covering a considerable portion of the crowns, and they may interfere with occlusion.

When uncomplicated by inflammation, the lesion is mulberry shaped, firm, pale

pink, and resilient, with a minutely lobulated surface and no tendency to bleed. The
enlargement characteristically appears to project from beneath the gingival margin, from
which it is separated by a linear groove. However, the presence of the enlargement makes
plaque control difficult, often resulting in a secondary inflammatory process that
complicates the gingival overgrowth caused by the drug.
The resultant enlargement then becomes a combination of the increase in size
caused by the drug and the complicating inflammation caused by bacteria. Secondary
inflammatory changes not only add to the size of the lesion caused by the drug, but also
produce a red or bluish red discoloration, obliterate the lobulated surface demarcations,
and increase bleeding tendency.
The enlargement is usually generalized throughout the mouth but is more severe
in the maxillary and mandibular anterior regions. It occurs in areas in which teeth are
present, not in edentulous spaces, and the enlargement disappears in areas from which
teeth are extracted. Hyperplasia of the mucosa in edentulous mouths has been reported
but is rare.
The enlargement is chronic and slowly increases in size, when surgically removed it
recurs. Spontaneous disappearance occurs within a few months after discontinuation of the drug.

Drug induced enlargement may occur in months with little or no plaque and
maybe absent in mouths with abundant deposits. However the presence of the
enlargement makes plaque control difficult often resulting in a secondary
inflammatory process that complicated the gingival overgrowth caused by the drug.
The resultant enlargement becomes then a combination of the increase in size caused
by the drug. And the complicating inflammation caused by bacteria. Secondary
inflammatory changes not only add to the size of the lesion caused by the drug but also
produce red or bluish red discoloration, obliterate the tabulated surface demarcations
and result on an increased tendency toward bleeding.
Factors effecting drug induced gingival overgrowth:
1) Age
2) Genetic predisposition
3) Role of fibroblasts
4) Role of Cytokines
5) Pharmacokinetics

6) Role of Immune system

7) Drug induction action on growth factors
Age:

Clinical studies suggest that children and adolescents appear more susceptible to
drug induced gingival overgrowth than adults. The studies are limited to both
phenytoin and cyclosporin since there is little of no indication, for the use of calcium
channel blockers in this age group. Fibroblasls obtained from both cyclosporin and
phenytoin induced gingiva! overgrowth cases failed to show an age dependent decrease in
protein synthesis and collagen production.
Genetic predisposition :

Not all patients taking phenytoin, cyclosporin or a

calcium channel blacker develop gingival overgrowth.

The terms 'responders' and 'non-responders' are used to identify those who show or
do not show drug induced gingival changes. Such inter individual susceptibility to these
gingival changes maybe related to a geueiic predisposition. It is now widely
recognized that gingival fibroblasts exhibit functional heterogeneity in response to
various stimuli. From this finding, it was shown subsequently that phenytoin could
react with, phenotypjcally distinct subpopulation of gingival fibroblasts and cause an
increase1 in protein synthesis and cell proliferation rate. Comparable results have also
been shown for cyclosporin and its major metabolite OL-17. Further support for the
presence of different subpopulations of fibroblasts has been provided from animal
studies, where the priming of the gingival tissue with cyclosporin in vivo led to
increased synthetic activity of the fibroblasts in vitro.
Further evidence that genetic factors may relate to the expression of drug
induced gingival overgrowth has come from investigation of human lymphocyte
antigen (HLA) expression. The expression of H L A frequencies was determined in a
group of uraemic patients and renal transplant recipients, 50 of whom were medicated
with cyclosporin, a dihydropyridine or the combination of drugs. The cohort was
further divided into those with or without overgrowth. The group of patients with
moderate or severe overgrowth had significantly lower frequency of HLA-DRI + and
higher frequency of HLA-DR2 + expression, when compared to those with little or no
overgrowth. Patients who expressed HLA-DR I appeared to be afforded a degree of

protection against the development of this unwanted effect, whilst those exhibiting HLADR2 + showed an increased risk for drug induced gingival overgrowth.
Genetic linkage studies of large families have identified more than one locus
related to gingival overgrowth in hereditary gingival fibromatosis (Hart et al., 1998,
2000; Shashi et al., 1999). These findings support the notion that not all forms of
gingival overgrowth are the same, and that more than one biological mechanism is likely
to result in gingival overgrowth. A detailed study of a large Brazilian family has
identified a specific gene mutation that segregates with the hereditary gingival
fibromatosis phenotype (Hart et al., 2002). This study is the first to link a specific gene
mutation to a phenotype of gingival overgrowth. The Sos1 protein is a GTP exchange
factor required for the activity of ras proteins.
A genetic predisposition could influence a variety of factors in the drug cell
plaque induced inflammation interaction. These include gingival fibroblast functional
heterogeneity, collagenolytic activity, drug receptor binding, drug metabolism,
collagen synthesis and many more factors. HLA expression may prove to be a useful
genetic marker for the identification of patients a risk of developing drug induced
gingival overgrowth.

Role of fibroblasts:
Studies on the direct effects of phenytoin, nifedipine, and cyclosporin A on
collagenous and non-collagenous extracellular matrix metabolism by gingival fibroblasts
in culture have provided variable results (Schincaglia et al., 1992). The differences in
these investigations depend in part on culture conditions (James et al., 1998, 2000). While
cyclosporin A was found to increase glycosaminoglycan secretion by fibroblasts (Newell
and Irwin, 1997), and nifedipine and phenytoin increased heparan levels (Saito et al.,
1996), other studies failed to report any differences in vivo (Romanos et al., 1992, 1993;
Rocha et al., 2000; Martins et al., 2003). Several studies demonstrate that these drugs
inhibit gingival fibroblast extracellular matrix production and/or cell proliferation in vitro.
These findings are inconsistent with the in vivo characteristics of drug-induced gingival
overgrowth. Taken together, these studies support the conclusion that direct regulation of

extracellular matrix metabolism or proliferation of gingival fibroblasts by these drugs is

probably not the primary mechanism responsible for gingival overgrowth. As noted
below, deregulated cytokine balances may contribute more significantly to the
development and maintenance of gingival overgrowth. Several studies more consistently
show that cultured human gingival fibroblasts treated with phenytoin, cyclosporin A, and
nifedipine increase production of fibroblast cytokines and prostaglandin E2, although
lymphocytes and macrophages may be important sources of these factors in vivo
In some respects, it is surprising that CTGF is elevated in phenytoin-induced
gingival overgrowth tissues. In human and rodent fibroblast cell lines, PGE2 is a potent
and rapid down-regulator of CTGF, and this effect is mediated by elevated cAMP levels
(Kothapalli et al., 1998; Duncan et al., 1999;). Phenytoin stimulates prostaglandin E2
(PGE2) production by gingival fibroblasts (Moder et al., 1992a), and it is well-known
that human gingival tissues accumulate significant levels of prostaglandins including
PGE2 (Arai et al., 1995). The fact that CTGF is elevated in phenytoin-induced gingival
overgrowth tissues, therefore, is unexpected and raises the notion that human gingival
tissues may be metabolically unique in their response to PGE2.
The effects of PGE2 on fibroblasts are mediated principally by four receptors,
EP1-EP4 (Coleman et al., 1994). PGE2 stimulation of cAMP levels is mediated primarily
by the EP2 receptor (Sarrazin et al., 2001; Yu et al., 2002). Future studies will determine
which PGE2 receptors are expressed by gingival fibroblasts, and whether phenytoin
regulates either the function or the expression of prostaglandin receptors in gingiva in
novel ways. It is very interesting to note that other recent studies support the notion that
gingival fibroblast extracellular matrix metabolism has unique aspects. In healing adult
human gingiva, MMP-13, and not MMP-1, is highly expressed by gingival fibroblasts. In
contrast, MMP-1 is predominantly expressed in adult dermal wounds. Moreover, MMP13 is strongly up-regulated by TGF-1 in human gingival fibroblasts, but is downregulated in human dermal fibroblasts grown under the same conditions (Ravanti et al.,
1999; Leivonen et al., 2002). MMP-13 is a collagenase with wide substrate specificity,
whereas MMP-1 is a collagenase more restricted to hydrolyzing fibrillar collagens.
Differential regulation of these two MMP genes is likely to be of biological importance,
and may be related to the generally lower tendency for scar formation in oral tissues

(Ravanti et al., 1999). In addition, integrin expression patterns differ between gingival
fibroblasts and dermal fibroblasts, whereas periodontal ligament fibroblasts and gingival
fibroblasts are more similar to each other in this respect (Palaiologou et al., 2001). It is
interesting to note that human gingival fibroblasts and periodontal ligament fibroblasts
express a variety of different genes differentially, including members of the CCN family
of genes (Han and Amar, 2002). Unique aspects of gingival fibroblast extracellular matrix
metabolism seem likely to contribute to the etiology of gingival overgrowth. In addition,
metabolic uniqueness of gingival cells may help explain the striking tissue specificity of
drug-induced gingival overgrowth.
The failure of the cell culture investigations to confirm the clinical findings may
be related to a unique fibroblast phenotype or the influence of androgen metabolism.
Monolayer cultures of gingival fibroblasts can readily metabolise labeled
testosterone to the active metabolic 5a-dihydrotestosterone (5a-DHT). When phenytoin
is added to such cultures there is an increase in metabolite formation. Likewise, excised
tissue from nifedipine and cyclosporin induced gingival overgrowth demonstrates a
similar increase in androgen metabolism. It is speculated from these results that a
drug related increase in gingival fibroblast androgen metabolism could be a
significant factor in the pathogenesis of drug induced gingival overgrowth. The active
androgen metabolites could 'target' sub-populations of gingival fibroblasts and
cause either an increase in collagen synthesis and or a decrease in collagcnase
activity. Such changes in androgen metabolism may account for the increased
propensity of this unwanted effect in children and adolescents.
Fibroblast heterogeneity and variations in the distribution of fibroblasts with
different phenotypes have been suggested to contribute to drug-induced and inherited
forms of gingival overgrowth. The presence of myofibroblasts in gingival overgrowth
tissues has been reported, and these are highly differentiated cells that have a strong
synthetic phenotype. The presence and role of myofibroblasts in systemic sclerosis and
skin fibrosis is known. A final outcome of tissue overgrowth and fibrosis is characterized
by the presence of fibroblasts with an activated synthetic phenotype, and the mechanisms
responsible for the presence of these cells may involve reciprocal interactions between
lymphocytes and fibroblasts. Mechanical forces contribute in some way to fibroblast

selection and differentiation. As discussed above, deregulated cytokine expression and

unique aspects of gingival fibroblast metabolism are all likely to be important
contributing factors in gingival overgrowth and development of highly synthetic or
proliferative fibroblast phenotypes. In addition, a reduced rate of apoptosis is reported to
contribute to the accumulation of gingival fibroblasts, perhaps with a greater synthetic or
proliferative phenotype in nifedipine-induced gingival overgrowth, though this is a novel
and understudied area at this time.

Role of cytokines:
Gingival tissues are generally in a state of injury and repair that involves
repetitive cycles of production of chemotactic factors, inflammatory cell recruitment, and
tissue resorption, replacement, and remodeling (Clark, 1998). Collagen turnover is
unusually high in periodontal tissues (Sodek, 1978; Sodek and Ferrier, 1988). Wound
healing and connective tissue turnover are largely controlled by chemokines and
cytokines secreted by inflammatory cells such as macrophages and lymphocytes and, to a
lesser degree, by fibroblasts. Proliferation and differentiation of connective tissue cells
and production of extracellular matrix are controlled by cytokines that initiate signaling
cascades mediated by specific receptors. In addition, extracellular matrix elements
interact with cell-surface receptors, including integrins, that initiate or modulate signaling
cascades (Clark, 1998; Arora et al., 2001).
Recent studies demonstrate abnormally high levels of specific cytokines in
gingival overgrowth tissues. These findings are of great interest, and suggest that
substances that cause gingival overgrowth may do so by altering the normal balance of
cytokines in gingival tissues. Cytokines and growth factors found at elevated levels in
human drug-induced gingival overgrowth include interleukin-6 (IL-6), IL-1, plateletderived growth factor-B (PDGF-B), fibroblast growth factor-2 (FGF-2), transforming
growth factor- (TGF-), and connective tissue growth factor (CTGF) (Williamson et al.,
1994; Uzel et al., 2001).
There is a limited understanding of the mechanisms by which altered cytokine
balances occur in drug-induced gingival overgrowth. A contributing factor may stem
from immunomodulatory effects of the drugs. For example, the increased expression of

the macrophage phenotype marker RM3/1 in phenytoin-induced gingival overgrowth is

consistent with fibroproliferative disease (Iacopino et al., 1997). In contrast, macrophages
in highly inflamed tissues express predominantly the 27E10 marker (Iacopino et al.,
1997). Even though IL-1 levels have not been shown to be increased in cyclosporin-Atreated monocytes/macrophages, there was a significant up-regulation in PDGF-B in
response to cyclosporin A and phenytoin (Plemons et al., 1996; Iacopino et al., 1997).
Similarly, phenytoin, cyclosporin A, and nifedipine gingival overgrowth tissues contain
subpopulations of macrophages and other inflammatory cells that differ from those in
healthy control gingival tissues (Dahllof et al., 1985; Pernu et al., 1994; Cebeci et al.,
1996, 1998; Pernu and Knuuttila, 2001; Bulut et al., 2002; Echelard et al., 2002). Studies
on T- and B-lymphocytes showed that T-cells are increased in the peripheral blood of
organ transplant patients with no apparent shift of subpopulations (Cebeci et al., 1998)
and nifedipine increased lymphocyte counts in blood (Bullon et al., 2001), although these
findings were not found in gingival tissues (Pernu and Knuuttila, 2001). A reduction in
the number of Langerhans cells in nifedipine and cyclosporin A gingival overgrowth
occurs and suggests a modification of an inflammatory reaction that influences the level
of helper T-lymphocytes and cytokine profiles (Nurmenniemi et al., 2001). Inflammatory
cell populations that are altered as a result of drug therapy are likely to modify the
gingival tissue response. At this time, however, there is no consensus regarding functional
relationships between and among drug therapies, the distribution of specific immune
system cell subpopulations, and altered cytokine balances.
CTGF contributes to fibrosis in many different tissues. The hypothesis was
developed that CTGF could play a role in gingival overgrowth and fibrosis. Studies of
CTGF regulation were initiated in vitro in human gingival fibroblast cultures, because
increased collagen and lysyl oxidase biosynthesis induced by TGF-1 occurred only at
modest levels and with slow kinetics compared with effects seen in other cell types. The
working hypothesis was that TGF-1 might induce CTGF, which in turn would stimulate
extracellular matrix production in gingival fibroblasts. Findings indicate that CTGF is
rapidly and potently up-regulated by TGF-1, and that CTGF stimulates insoluble
collagen accumulation in human gingival fibroblast cultures

The occurrence of abnormal cytokine levels does not alone prove a functional
relationship to gingival overgrowth. Studies have begun to investigate functional
relationships between cytokines and gingival extracellular matrix metabolism. These
studies seem likely to result in a greater understanding of the biological mechanisms that
may be unique to human gingival tissues and may be relevant to the development of
therapeutic strategies for either the prevention or treatment of gingival overgrowth. TGF1 is a cytokine secreted by many cell types, including macrophages, and it has an
important regulatory function in collagen metabolism in connective tissues. TGF-1
slowly stimulates collagen and lysyl oxidase biosynthesis in early-passage human
gingival fibroblast cell cultures (Hong et al., 1999), whereas IL-1, IL-6, and PDGF-BB
have little or no effect, and FGF-2 is inhibitory (Hong and Trackman, 2001). In contrast,
PDGF-BB and FGF-2 are potent mitogenic factors and contribute to the proliferation of
gingival connective tissue and epithelial cells. The effects of TGF-1 on gingival collagen
and lysyl oxidase regulation are notable because the magnitude and kinetics of regulation
are unexpectedly smaller and slower compared with studies on other connective tissue
cells performed under the same conditions (Feres-Filho et al., 1995). To understand the
unexpectedly slow kinetics of TGF-1 on extracellular matrix synthesis in gingival
fibroblasts, investigators in recent studies have focused on the presence and role of
connective tissue growth factor (CTGF) as a possible matrix-stimulatory factor
downstream of TGF-1 in gingival overgrowth tissues. CTGF has been proposed to
mediate the effects of TGF- on extracellular matrix metabolism (Duncan et al., 1999).
Before studies performed in gingival cells and tissues are summarized, information on
CTGF and the emerging related CCN family of factors is first offered as background
information.
Pharmacokinetic variables :
The relationship between the incidence and severity of gingivai overgrowth
with various drug pharmacokinetic variables remains a contentious issue.
It seems that a certain threshold concentration of the drug or its metabolite is necessary
to 'activate' gingival fibroblasts. Such a threshold effect was postulated by Daley et al
(1986), who suggested that increasing the levels of the drug above this threshold d i d

not increase the severity of the lesion. Changes in severity would therefore be due to
other factors.
A direct relationship between the degree of salivary phenytoin and gingiva!
overgrowth has been demonstrated in institutionalized epileptic patients. Similar
results have been shown between cyclosporin concentration in stimulated saliva and
the extent of the gingival overgrowth. By contrast, a lack of correlation between
unstimulated salivary cyclosporin levels and gingival overgrowth has been reported.
The possibility that the dental plaque may act as a reservoir for cyclosporin, which is
released by the actions of developing stimulated saliva How, may well explain the
conflicting findings. A role for dental plaque as a reservoir for phenytoinin drug
induced gingivai overgrowth has also been proposed. Cyclosporin dental plaque
concentrations have been shown to be higher than those found in blood and other
tissues. It has been reported thai the oral mucosal exposure to cyclosporin was
approximately 130 times greater when ihe drug was administered as a mixture as
opposed to capsule form.
It has been shown (hat both nifedipine and amlodipine can be detected in GCF
and significant sequestration of the drug occurs in patients exhibiting gingival
overgrowth. The mechanism of such sequestration and its relationship to the gingival
changes remain uncertain. Sequestration of nifedipine in GCF appears to be related to
local pathology of the periodontal

pocket,

in

particular the degree of gingival

inflammation, local concentrations of various inducing drugs in GCF, plaque, or in the

excised overgrowth tissue may provide pertinent information for the expression and
pathogenesis of gingival overgrowth.
Role of Immune system:

Phenytoin also possesses immunosuppressive properties which has led to

investigations into the sub-populations of lymphocytes in phenytoin-indueed gingival
overgrowth comparative study, there were substantially more mononuclear cells in
phenytoin-indueed gingival overgrowth tissue than control healthy or inflamed
gingival, monoclonal antibodies showed the distribution these cells as follows: 69 95% T-lymphocytes 50-64% T-helper cells. 29-46% T-suppressor/cytotoxic cells.
Plasma cells were sparse in the phenytoin-induccd gingival overgrowth tissue when

compared to control. These findings led the authors to speculate that the selective
infiltrate of T-Iyniphoc) u;s would support a T-cell mediated immunologicai
mechanism such may play a role in the pathogenesis of gingival overgrowth.
The number of langerhans cells also increase in gingival epithelium in patients with
phenytoin-indueed gingival overgrowth (Kinane et al. 1990). The relationship between
such an increase ininterleukin-l is related to an increase in Langerhans cells in
chronically inflamed gingival. lnterleukin-1 can stimulate fibroblasts, fibroblast
proliferation in the presence of primary growth factors, thus phenytin-induced gingival
overgrowth and the increased in Langerhans cells may be mediated via interleukin-I
growth factor interaction.
Prostaglandins may also play a role in the pathogenesis of phenytoin-indueed
gingival overgrowth. In a series of cell culture experiments, prostaglandin E2
formation was studied in human gingival fibroblasts derived from 3 patients before
and after 9 months of phenytoin therapy. When cell cultures were incubated with
interleukin-la, p and tumour necrosis factor a, there was a dose-dependent
stimulation of PGE2 formation. However, PGE2 formation was significantly higher in
fibroblasts obtained after 9 months of phenytoin therapy than those before treatment.
The findings suggest that phenytoin therapy results in an upregulation of prostaglandin
formation in gingival fibroblasts. Such an upregulation could cause & increase in
glycosaminoglycan synthesis, which would affect the extracellular gingival matrix.
In an attempt to recreate the plaque-induced inflammation of the gingiva in a
tissue culture model, the direct effect of bacterial lipopolysaccharide on tissue culture
models has been investigated. Lipopolysaccharide is an important component of the
bacterial cell wall which is known to be cytotoxic for fibroblast cell lines.
Cyclosporin, in the presence of lipopolysacchaaride at a concentration that would
normally inhibit fibroblast proliferation, has been shown to negate the inhibitory effect
of the lipopolysaccharidc and maintain the ability of the drug to stimulate fibroblast
proliferation. In a study, total protein synthesis of fibroblasts isolated from
cyclosporin-associated gingival overgrowth was inhibited by lipopolysaccharide. but
again, this could be reversed by the addition of cyclosporin to this system. It has been
suggested that the relationship between severe gingival overgrowth and areas of high

plaque retention may be explained by the ability of cyclosporin to negate the

inhibitory effect of lipopolysaccharide on gingival fibroblasts.heir activation may he
important in the patliogenesis of drug-induced gingival overgrowth. Studies to date
have focused on the drug phcnytoin and its interaction with epidermal growth (actor
(EGF) and platelet derived growth factor (PDGF).
In an initial study, the effect of phenytoin on the metabolism of EGF receptors
was investigated in culture gingival fibroblasts. The findings suggested that phenytoin
causes a down regulation of EGF receptor metabolism in responder patients. Whilst in
non-responders there is an upregulation.
The pathogenesis of phenytoin-induced gingival overgrowth has also been
investigated in relation to gene expression for platelet derived growth factor (PDEF) in
macrophages and monocytes.
The findings suggested that phenytoin induced increased in PDGF secretion
from macrophages could be an important factor in the expression of gingival
overgrowth,. Macrophages play a fundamental role in orchestrating the plaque induced inflammatory changes in the gingival tissues. There is considerable evidence
that such inflammatory changes exacerbate phenytoin-induced gingival overgrowth
Histopathology:
Drug-induced gingival enlargement consists of a pronounced hyperplasia of the
connective tissue and epithelium. There is acanthosis of the epithelium, and elongated
rete pegs extend deep into the connective tissue, which exhibits densely arranged
collagen bundles with an increase in the number of fibroblasts and new blood vessels. An
abundance of amorphous ground substance has also been reported. Structural changes in
the outer epithelial cell surface have been reported in cyclosporine-induced enlargements.
The enlargement begins as a hyperplasia of the connective tissue core of the
marginal gingiva and increases hits proliferation and expansion beyond the crest of the
gingivai margin. An inflammatory infiltrate may be found at the bottom of the sulcus, or
pocket. Cyclosporine enlargements usually have a more highly vascularized connective
tissue with foci of chronic inflammatory cells, particularly plasma cells.
The "mature" phenytoin enlargement has a fibroblast/ collagen ratio equal to that
of normal gingiva from normal individuals, suggesting that at some point in the

development of the lesion, fibroblastic proliferation must have been abnormally high.
Oxytalan fibers are numerous beneath the epithelium and in areas of inflammation.
Recurring phenytoin enlargements appear as granulation tissue composed of numerous
young capillaries and fibroblasts and irregularly arranged collagen fibrils with occasional
lymphocytes.

Anticonvulsants
The first drug-induced gingival enlargements reported were those produced by
phenytoin (Dilantin). Dilantin is a hydantoin, introduced by Merritt and Putnam in 1938
for the treatment of all forms of epilepsy, except petit mal. Shortly thereafter, its
relationship with gingivai enlargement was reported.
Other hydantoins known to induce gingival enlargement are ethotoin (Paganone)
and mephenytoin (Mesantoin). Other anticonvulsants that have the same side effect are
the succinimides (ethosuximide [Zerontin], methsuxinimide [Celontin]), and valproic
acid.
Gingival enlargement occurs in about 50% of patients receiving the drug,although
different authors have reported incidences from 3% to 84.5%.It occurs more often in
younger patients/ Its occurrence and severity are not necessarily related to the dosage
after a threshold level has been exceeded. Phenytoin appears in the saliva. There is no
consensus, however, on whether the severity of the overgrowth is related to the levels of
phenytoin in plasma or saliva. Some reports indicate a relation between the drug dosage
and the degree of gingivai overgrowth.
Tissue culture experiments indicate that phenytoin stimulates proliferation of
fibroblast-like cells and epithelium. Two analogs of phenytoin (l-allyl-5phenylhydantoinate and 5-methyl-5-phenylhydantoinate) have a similar effect on
fibroblast-like cells. Fibroblasts from a phenytoin-induced gingivai overgrowth show
increased synthesis of sulfated glycosaminoglycans in vitro. Phenytoin may induce a
decrease in collagen degradation as a result of the production of an inactive fibroblastic
collagenase.
Experimental attempts to induce gingival enlargement with phenytoin
administration in laboratory animals have been successful only in the cat,56 the ferret, and

the Macaca speciosa monkey In experimental animals, phenytoin causes gingival

enlargement that is independent of local inflammation.
In cats, one of the metabolic products of phenytoin is 5-(parahydroxyphenyl)-5phenylhydantoin; administration of this metabolite to cats also induces gingival
enlargement in some cases. This led Hassell and Page to hypothesize that gingival
enlargement may result from the genetically determined ability or inability of the host to
deal effectively with prolonged administration of phenytoin.
Systemic administration of phenytoin accelerates the healing of gingival wounds
in nonepileptic humans and increases the tensile strength of healing abdominal wounds in
rats. The administration of phenytoin may precipitate a megaloblastic anemia and folic
acid deficiency. PHT stimulates the production of both IL-6 and IL-8 in human gingival
fibroblasts. Furthermore, the drug PHT alone also increases the mRNA level for both IL6 and IL-8 as well as synergistically enhances the production of IL-6 and IL-8 in
presence of IL-1b, at both transcriptional and translational level in gingival fibroblasts.
The upregulation of IL-6 induced by PHT seems to involve a COX-2-dependent pathway
since NS-398, a specific COX-2 inhibitor, strongly reduced the IL-6 production induced
by PHT in the presence of IL-1b.
In conclusion, the pathogenesis of gingival enlargement induced by phenytoin is
not known, but some evidence links it to a direct effect on specific, genetically
predetermined subpopulations of fibroblasts, inactivation of collagenase, and plaqueinduced inflammation.

Immunosuppressants
Cyclosporine is a potent immunosuppressive agent used to prevent organ
transplant rejection and to treat several diseases of autoimmune origin. Its exact
mechanism of action is not well known, but it appears to selectively and reversibly inhibit
helper T cells, which play a role in cellular and humoral immune responses. Cyclosporin
A (Sandimmune, Neoral) is administered intravenously or by mouth, and dosages greater
than 500 mg/day have been reported to induce gingival overgrowth.
Gingival overgrowth was first noticed with Cs therapy in the initial human trials
of the drug but was described in the dental literature in 1983 by both Rateitschak-Plss

and co workers a n d Wysocki et al. s gingival overgrowth is clinically indistinguishable

from that associated with PHT. The overgrowth, which normally begins at the interdental
papillae, is more common in the anterior segments of the mouth and on labial surfaces of
the teeth. Overgrowth is usually confined to the attached gingiva but may extend
coronally and interfere with the occlusion, mastication and speech without necessarily
altering the underlying periodontium . The incidence of Cs gingival over growth ranges
from 13 percent 41 to 81 per cent. As with PHT overgrowth, the reasons for this range
are many and include the nature of the disease being treated, the age of the patient, the
method of assessment, the dosage and duration of Cs and additional medications. Cs
overgrowth has not been described in edentulous patients. The severity of overgrowth
may range from none to a very mild swelling of the interdental papilla, to marked excess
gingiva cove ring at least three quarters of the tooth (affecting 17 per cent of patients).
While it appears that some patients are more susceptible to gingival overgrowth than
others, the relationship to drug dosage and serum concentration is contentious. Plasma
and salivary concentrations, plaque and gingival indices have all been correlated to the
severity of over growth but there is wide individual variation. Whole saliva
concentrations of Cs are higher in patients taking the liquid form of the drug compared
with the capsule form , but salivary concentrations correlate poorly with blood levels.
Gingival over growth is thought to develop in patients within three months of taking Cs.
Cyclosporine-induced gingival enlargement is more vascularized than phenytoin
enlargement. Its occurrence varies according to different studies from 25% to 70%,it
affects children more frequently, and its magnitude appears to be related more to the
plasma concentration than to the patient's periodontal status. Gingival enlargement is
greater in patients who are medicated with both cyclosporine and calcium channel
blockers.
The microscopic finding of many plasma cells plus the presence of an abundant
amorphous extracellular substance has suggested that the enlargement is a
hypersensitivity response to the cyclosporine.
In experimental animals (rats), oral administration of cyclosporine was reported
also to induce abundant formation of new cementum.

In addition to gingival enlargement, cyclosporine induces other major side effects,

such as nephrotoxicity hypertension, and hypertrichosis. Another immunosuppressive
drug, tacrolimus, has been used effectively and is also nephrotoxic, but it results in much
less severe hypertension, hypertrichosis, and gingival overgrowth.

Calcium Channel Blockers

Calcium channel blockers are drugs developed for the treatment of cardiovascular
conditions such as hypertension, angina pectoris, coronary artery spasms, and cardiac
arrhythmias. They inhibit calcium ion influx across the cell membrane of heart and
smooth muscle cells, blocking intracellular mobilization of calcium. This induces direct
dilation of the coronary arteries and arterioles, improving oxygen supply to the heart
muscle; it also reduces hypertension by dilating the peripheral vasculature.
These drugs are the dihydropyridine derivatives (amlodipine, felodipine,
nicardipine,

nifedipine;

the

benzothiazine

derivatives

(diltiazem

and

the

phenylalkylamine derivatives (verapamil)

Some of these drugs can induce gingival enlargement. Nifedipine, one of the most
often used, induces gingival enlargement in 20% of patients. Diltiazem, felodipine,
nitrendipine, and verapamil also induce gingival enlargement. The dihydropyridine
derivative isiadipidine can replace nifedipine in some cases and does not induce gingival
overgrowth. It has been reported in one study that nifedipine concentrates in the gingival
crevicular fluid up to 90 times the serum concentration and, of the nine patients
examined, nifedipine could be found in the crevicular fluid of all five of the patients with
gingiva overgrowth and two of the non-responders. While a male predominance has
been report it should be remembered that most studies in this area have not been
randomized.
It has been speculated that some alteration to Ca++ metabolism is involved, but
others have suggested that nifedipine may act indirectly by stimulating either production
of IL-2 by T cells or metabolites of testosterone. Still other work suggests a role for TGF,
bFGF and heparan sulphate glycosaminoglycan. Regrettably, none of these theories
explain why only some patients develop nifedipine gingival overgrowth. It seems

possible that a number of mechanisms could act synergistically to produce the

overgrowth.
Nifedipine is also used with cyclosporine in kidney transplant recipients, and the
combined use of both drugs induces larger overgrowths. Nifedipine gingival enlargement
has been induced experimentally in rats.

IDIOPATHIC GINGIVAL ENLARGEMENT

Idiopathic gingival enlargement is a rare condition of undetermined cause. It has
been designated by such terms as gingivomatosis, elephantiasis, idiopathic fibromatosis,
hereditary gingival hyperplasia, and congenital familial fibromatosis.

Clinical Features:
The enlargement affects the attached gingiva, as well as the gingival margin and
interdental papillae, in contrast to phenytoin-induced overgrowth, which is often limited
to the gingival margin and interdental papillae. The facial and lingual surfaces of the
mandible and maxilla are generally affected, but the involvement may be limited to either
jaw. The enlarged gingiva is pink, firm, and almost leathery in consistency and has a
characteristic minutely pebbled surface. In severe cases the teeth are almost completely
covered, and the enlargement projects into the oral vestibule. The jaws appear distorted
because of the bulbous enlargement of the gingiva. Secondary inflammatory changes are
common at the gingival margin.
Histopathology:
Idiopathic gingival enlargement shows a bulbous increase in the amount of
connective tissue that is relatively avascular and consists of densely arranged collagen
bundles and numerous fibroblasts. The surface epithelium is thickened and acanthotic
with elongated rete pegs.
Etiology:
The cause is unknown, and thus the condition is designated as "idiopathic." Some
cases have a hereditary basis, but the genetic mechanisms involved are not well
understood. A study of several families found the mode of inheritance to be autosomal

recessive in some cases and autosomal dominant in others. In some families the gingival
enlargement may be linked to impairment of physical development.

ENLARGEMENTS ASSOCIATED WITH SYSTEMIC DISEASES

Many systemic diseases can develop oral manifestations that may include gingival
enlargement. These diseases and conditions can affect the periodontium by two different
mechanisms, as follows:

1. Magnification of an existing inflammation initiated by dental plaque. This group of

diseases, discussed below under "Conditioned Enlargements," includes some hormonal
conditions (e.g., pregnancy and puberty), nutritional diseases such as vitamin C
deficiency, and some cases in which the systemic influence is not identified (nonspecific
conditioned enlargement).

2. Manifestation of the systemic disease independently of the inflammatory status of the

gingiva. This group is described under Systemic Diseases Causing Gingival Enlargement
and Neoplastic Enlargement (Gingival Tumors).

Conditioned Enlargement
Conditioned enlargement occurs when the systemic condition of the patient
exaggerates or distorts the usual gingival response to dental plaque. The specific manner
in which the clinical picture of conditioned gingival enlargement differs from that of
chronic gingivitis depends on the nature of the modifying systemic influence. Bacterial
plaque is necessary for the initiation of this type of enlargement. However, plaque is not
the sole determinant of the nature of the clinical features.

The three types of conditioned gingival enlargement are hormonal (pregnancy,

puberty), nutritional (associated with vitamin C deficiency), and allergic. Nonspecific
conditioned enlargement is also seen.

Enlargement in Pregnancy.
Pregnancy gingival enlargement may be marginal and generalized or may occur as
single or multiple tumor-like masses. During pregnancy there is an increase in levels of
both progesterone and estrogen, which, by the end of the third trimester, reach levels 10
and 30 times the levels during the menstrual cycle, respectively. These hormonal changes
induce changes in vascular permeability, leading to gingival edema and an increased
inflammatory response to dental plaque. The subgingival microbiota may also undergo
changes, including an increase in Prevotella intermedia. The hormonal changes might
result in following changes:
1) Microbial changes
a) Increased ratio of anaerobe to aerobe
b) Increased number of prevotella intermedia
2) Vascular changes
a) Dilated gingival capillaries
b) Increased venule and capillary permeability
3) Cellular changes
a) Stimulated endothelial cells
b) Decreased keratinization
c) Increased epithelial glycogen
d) Altered polymerization of ground substance
e) Inhibited collagen production
I) Increased folate metabolism
4) Immune changes
a) Depressed neulrophil chemotaxis and phagocytosis
b) Depressed antibody response
c) Depressed T-cell response
Stimulated prostaglandin synthesis in macrophages

Marginal Enlargement.
Marginal gingival enlargement during pregnancy results from the aggravation of
previous inflammation, and its incidence has been reported as 10% and 70%. The
gingival enlargement does not occur without the presence of bacterial plaque.
The clinical picture varies considerably. The enlargement is usually generalized
and tends to be more prominent interproximally than on the facial and lingual surfaces.
The enlarged gingiva is bright red or magenta, soft, and friable and has a smooth, shiny
surface. Bleeding occurs spontaneously or on slight provocation.

Tumorlike Gingival Enlargement.

The so-called pregnancy tumor is not a neoplasm; it is an inflammatory response
to bacterial plaque and is modified by the patient's condition. It usually appears after the
third month of pregnancy but may occur earlier. The reported incidence is 1.8% to 5%.
The lesion appears as a discrete, mushroom like, flattened spherical mass that
protrudes from the gingival margin or more often from the interproximal space and is
attached by a sessile or pedunculated base. It tends to expand laterally, and pressure from
the tongue and the cheek perpetuates its flattened appearance. Generally dusky red or
magenta, it has a lesion and usually does not invade the underlying bone. The consistency
varies; the mass is usually semifirm, but it may have various degrees of softness and
friability. It is usually painless unless its size and shape foster accumulation of debris
under its margin or interfere with occlusion, in which case, painful ulceration may occur.
Histopathology:
Gingival enlargement in pregnancy is called angiogranuloma. Both marginal and
tumorlike enlargements consist of a central mass of connective tissue, with numerous
diffusely arranged, newly formed, and engorged capillaries lined by cuboid endothelial
cells, as well as a moderately fibrous stroma with varying degrees of edema and chronic
inflammatory infiltrate. The stratified squamous epithelium is thickened, with prominent
rete pegs and some degree of intracellular and extracellular edema, prominent
intercellular bridges, and leukocytic infiltration.
Although the microscopic findings are characteristic of gingival enlargement in
pregnancy, they are not pathognomonic because they cannot be used to differentiate
pregnant and nonpregnant patients. Most gingival disease during pregnancy can be prevented by the removal of plaque and calculus, as well as the institution of fastidious oral
hygiene at the outset. In pregnancy, treatment of the gingiva that is limited to the removal
of tissue without complete elimination of local irritants is followed by recurrence of
gingival enlargement. Although spontaneous reduction in the size of gingival
enlargement typically follows the termination of pregnancy, complete elimination of the
residual inflammatory lesion requires the removal of all plaque deposits and factors that
favor its accumulation.

Enlargement in Puberty.
Enlargement of the gingiva is sometimes seen during puberty. It occurs in both
male and female adolescents and appears in areas of plaque accumulation.
Clinical features:
The size of the gingival enlargement greatly exceeds that usually seen in
association with comparable local factors. It is marginal and interdental and is
characterized by prominent bulbous interproximal papillae. Often, only the facial
gingivae are enlarged, and the lingual surfaces are relatively unaltered; the mechanical
action of the tongue and the excursion of food prevent a heavy accumulation of local
irritants on the lingual surface.
Gingival enlargement during puberty has all the clinical features generally
associated with chronic inflammatory gingival disease. It is the degree of enlargement
and the tendency to develop massive recurrence in the presence of relatively scant plaque
deposits that distinguish pubertal gingival enlargement from uncomplicated chronic
inflammatory gingival enlargement. After puberty the enlargement undergoes
spontaneous reduction but does not disappear until plaque and calculus are removed. A
longitudinal study of 127 children 11 to 17 years of age showed a high initial prevalence
of gingival enlargement that tended to decline with age.122 When the mean number of
inflamed gingival sites per child was determined and correlated with the time at which
the maximum number of inflamed sites was observed and with the oral hygiene index at
that time, a pubertal peak in gingival inflammation unrelated to oral hygiene factors
clearly occurred. A longitudinal study of sub-gingival microbiota of children between
ages 11 and 14 and their association with clinical parameters has implicated
Capnocytophaga species in the initiation of pubertal gingivitis. Other studies have
reported that hormonal changes coincide with an increase in the proportion of Prevotella
intermedia and Prevotella nigrescens.

Histopathology:
The microscopic appearance of gingival enlargement in puberty is chronic
inflammation with prominent edema and associated degenerative changes.

Enlargement in Vitamin C Deficiency.

Enlargement of the gingiva is generally included in classic descriptions of scurvy.
Acute vitamin C deficiency itself does not cause gingival inflammation, but it does cause
hemorrhage, collagen degeneration, and edema of the gingival connective tissue. These
changes modify the response of the gingiva to plaque to the extent that the normal
defensive delimiting reaction is inhibited, and the extent of the inflammation is
exaggerated, resulting in the massive gingival enlargement seen in scurvy .
Clinical features:
Gingival enlargement in vitamin C deficiency is marginal; the gingiva is bluish
red, soft, and friable and has a smooth, shiny surface. Hemorrhage, occurring either
spontaneously or on slight provocation, and surface necrosis with pseudomembrane
formation are common features.
Histopathology:
In vitamin C deficiency the gingiva has a chronic inflammatory cellular
infiltration with a superficial acute response. There are scattered areas of hemorrhage,
with engorged capillaries. Marked diffuse edema, collagen degeneration, and scarcity of
collagen fibrils or fibroblasts are striking findings.

Plasma Cell Gingivitis.

Plasma cell gingivitis, also referred to as atypical gingivitis and plasma cell
gingivostomatitis, often consists of a mild marginal gingival enlargement that extends to
the attached gingiva. A localized lesion, referred to as plasma cell granuloma, has also
been described.

Clinical features:
The gingiva appears red, friable, and sometimes granular and bleeds easily;
usually it does not induce a loss of attachment. This lesion is located in the oral aspect of
the attached gingiva and therefore differs from plaque-induced gingivitis.
Histopathology:
In plasma cell gingivitis the oral epithelium shows spongiosis and infiltration with
inflammatory cells; ultrastructurally, there are signs of damage in the lower spinous

layers and the basal layers. The underlying connective tissue contains a dense infiltrate of
plasma cells that also extends to the oral epithelium, inducing a dissecting type of injury.
An associated cheilitis and glossitis have been reported. Plasma cell gingivitis is
thought to be allergic in origin, possibly related to components of chewing gum,
dentifrices, or various diet components. Cessation of exposure to the allergen brings
resolution of the lesion.
In rare instances, marked inflammatory gingival enlargements with a
predominance of plasma cells can appear, associated with rapidly progressive
periodontitis.

Nonspecific Conditioned Enlargement (Pyogenic Granuloma).

Pyogenic granuloma is a tumorlike gingival enlargement that is considered an
exaggerated conditioned response to minor trauma. The exact nature of the systemic
conditioning factor has not been identified.
Pyogenic granuloma was originally believed to be a batryomycotic
infection, an infection in horses thought lo be transmissible to man. Subsequent
work suggested that the lesion was due lo a infection by staphylococci or
streptococci partially because it was shown that these microorganisms could
produce colonies with fungus like characteristics. It is now generally agreed
however that the pyogenic granuloma arise as a result of some trauma to the
tissues, which provides a pathway for the invasion of non specific types of
microorganisms. The tissues respond in a characteristic manner to these
organisms of low virulence by the overzealous proliferation of a vascu lar type of
connective tissue. The surface of pyogenic granuloma especially in areas of
ulceration abounds with typical colonies of saprophytic organisms.

Clinical features:
The lesion varies from a discrete spherical, tumorlike mass with a pedunculated
attachment to a flattened, keloid like enlargement with a broad base. It is bright red or
purple and either friable or firm, depending on its duration; in the majority of cases it
presents with surface ulceration and purulent exudation. The lesion tends to involute

spontaneously to become a fibroepithelial papilloma, or it may persist relatively

unchanged for years.

Histopathology:
Pyogenic granuloma appears as a mass of granulation tissue with chronic
inflammatory cellular infiltration. Endothelial proliferation and the formation of
numerous vascular spaces are the prominent features. The surface epithelium is atrophic
in some areas and hyperplastic in others. Surface ulceration and exudation are common
features.
Treatment consists of removal of the lesions plus the elimination of irritating local
factors. The recurrence rate is about 15%. Pyogenic granuloma is similar in clinical and
microscopic appearance to the conditioned gingival enlargement seen in pregnancy.
Differential diagnosis is based on the patient's history.
Systemic Diseases That Cause Gingival Enlargement
Several systemic diseases may result in gingival enlargement through different
mechanisms.
Leukemia
The leukemias are malignant neoplasias of WBC precursors characterized by
(1) diffuse replacement of the bone marrow with proliferating leukemic
cells,
(2) abnormal numbers and forms of immature WBCs in the circulating
blood, and
(3) widespread infiltrates in the liver, spleen, lymph nodes, and other body
sites.

According to the lineage of WBC involved, leukemias are classified as

lymphocytic or myelocytic; a subgroup of the myelocytic leukemias is monocytic
leukemia. According to their evolution, leukemias can be acute, which is rapidly fatal;
subacute; or chronic. In acute leukemia the primitive "blast" cells are released into the
peripheral circulation, whereas in chronic leukemia the abnormal cells tend to be more

mature with normal morphologic characteristics and function when released into the
circulation.

Infiltration:
Leukemic cells can infiltrate the gingiva and less frequently the alveolar bone.
Gingival infiltration often results in leukemic gingival enlargement A study of 1076 adult
patients with leukemia showed that 3.6% of the patients with teeth had leukemic gingival
proliferative lesions, with the highest incidence in patients with acute monocytic
leukemia (66.7%), followed by acute myelocytic-monocytic leukemia (18.7%) and acute
myelocytic leukemia (3.7%).
It should be noted, however, that monocytic leukemia is an extremely rare form of
the disease. Leukemic gingival enlargement is not found in edentulous patients or in
patients with chronic leukemia. Leukemic gingival enlargement consists of a basic
infiltration of the gingival corium by leukemic cells that increases the gingival thickness
and creates gingival pockets where bacterial plaque accumulates, initiating a secondary
inflammatory lesion that contributes to the enlargement of the gingiva.

Clinical Features:
Clinically, the gingiva appears initially bluish red and cyanotic, with a rounding
and tenseness of the gingival margin; then it increases in size, most often in the
interdental papilla and partially covering the crowns of the teeth Acute painful
necrotizing ulcerative inflammatory involvement sometimes occurs in the crevice formed
at the junction of the enlarged gingiva and the contiguous tooth surfaces.
Patients with leukemia may also have a simple chronic inflammation without the
involvement of leukemic cells and may present with the same clinical and microscopic
features seen in patients without the disease. Most cases reveal features of both simple
chronic inflammation and leukemic infiltrate.
True leukemic enlargement often occurs in acute leukemia but may also be seen
in subacute leukemia. It seldom occurs in chronic leukemia.

Histopathology:
Gingival enlargements in leukemic patients show various degrees of chronic
inflammation. Mature leukocytes and areas of connective tissue are infiltrated with a
dense mass of immature and proliferating leukocytes, the specific nature of which varies
with the type of leukemia. Engorged capillaries, edematous and degenerated connective
tissue, and epithelium with various degrees of leukocytic infiltration and edema are
found. Isolated surface areas of acute necrotizing inflammation with a pseudomembranous meshwork of fibrin, necrotic epithelial cells, PMNs, and bacteria are often
seen.
Granulomatous Diseases

Wegener's Granulomatosis.
Wegener's granulo-matosis is a rare disease characterized by acute granulomatous necrotizing lesions of the respiratory tract, including nasal and oral defects. Renal
lesions develop, and acute necrotizing vasculitis affects the blood vessels.
Clinical features:
The initial manifestations of Wegener's granulomatosis may involve the orofacial
region and include oral mucosal ulceration, gingival enlargement, abnormal tooth
mobility, exfoliation of teeth, and delayed healing response. The granulomatous papillary
enlargement is reddish purple and bleeds easily on stimulation.
Etiology:
The cause of Wegener's granulomatosis is unknown, but the condition is
considered an immunologically mediated tissue injury. At one time the usual outcome
was death from kidney failure within a few months, but more recently the use of
immunosuppressive drugs has produced prolonged remissions in more than 90% of
patients.
Histopathology:
Chronic inflammation occurs, with scattered giant cells and foci of acute
inflammation and microabscesses covered by a thin, acanthotic epithelium. Vascular
changes have not been described with gingival enlargement in Wegener's granulomatosis,
probably because of the small size of the gingival blood vessels

Sarcoidosis.
Sarcoidosis is a granulomatous disease of unknown etiology. It starts in
individuals in their 20s or 30s, predominantly affects blacks, and can involve almost any
organ, including the gingiva, where a red, smooth, painless enlargement may appear. It
presents most frequently with hilar lymphadenopathy, pulmonary inflammation, and skin
& eye lesions. There is depression of delayed type hypersensitivity.
Histopathology:
Sarcoid granulomas consist of discrete, noncaseating whorls of epithelioid cells
and multinucleated, foreign body-type giant cells with peripheral mononuclear cells."
NEOPLASTIC ENLARGEMENT (GINGIVAL TUMORS)
Benign Tumors of the Gingiva
Epulis is a generic term used clinically to designate all discrete tumors and
tumorlike masses of the gingiva. It serves to locate the tumor but not to describe it. Most
lesions referred to as "epulis" are inflammatory rather than neoplastic.
Neoplasms account for a comparatively small proportion of gingival enlargements
and make up a small percentage of the total number of oral neoplasms. In a survey of
257 oral tumors, approximately 8% occurred on the gingiva.(Mc Carthy, 1941) In another
study of 868 growths of the gingiva and palate, of which 57% were neoplastic and the
remainder inflammatory, the following incidence of tumors was noted: carcinoma,
11.0%; fibroma, 9.3%; giant cell tumor, 8.4%; papilloma, 7.3%; leukoplakia, 4.9%;
mixed tumor (salivary gland type), 2.5%; angioma, 1.5%; osteofibroma, 1.3%; sarcoma,
0.5%; melanoma, 0.5%; myxoma, 0.45%; fibropapilloma, 0.4%; adenoma, 0.4%; and
lipoma, 0.3%.(Bernick S, 1948)
Fibroma.
It is the most common benign soft tissue neoplasm occurring in the oral cavity. It
is intimately related to fibrous hyperplasia and in many instances, is histologically
indistinguishable from it. A central fibroma of bone, either maxilla or mandible, has been
reported occasionally.

Clinical features:
The fibroma appears as an elevated lesion of normal color with a smooth surface
and a sessile, or occasionally, pedunculated base. The tumor may be small, or in rare
instances, may range up to several centimeters in diameter. Projecting above the surface,
the tumor sometimes becomes irritated and inflamed and may even show superficial
ulceration. it is nearly always a well defined, slowly growing lesion that occurs at any
age, but is most common in the third, fourth and fifth decades. Although arising in a
variety of locations, it most frequently originates on the gingiva, buccal mucosa, tongue,
lips and palate. Fibromas of the gingiva arise from the gingival connective tissue or
from the periodontal ligament. They are slow-growing, spherical tumors that tend to be
firm and nodular but may be soft and vascular. Fibromas are usually pedunculated. Hard
fibromas of the gingiva are rare; most of the lesions diagnosed clinically as "fibromas"
are inflammatory enlargements.
Histopathology:
Fibromas are composed of bundles of well-formed collagen fibers with a
scattering of fibrocytes and a variable vascularity.
The so-called giant cell fibroma contains multinucleated fibroblasts. In another
variant, mineralized tissue (bone, cementum-like material, dystrophic calcifications) may
be found; this type of fibroma is called peripheral ossifying fibroma.

Papilloma.
Papillomas are benign proliferations of surface epithelium associated with the
human papillo-mavirus (HPV). Viral subtypes HPV-6 and HPV-11 have been found in
most cases of oral papillomas. Gingival papillomas appear as solitary, wartlike or
cauliflower-like protuberances. They may be small and discrete or broad, hard elevations
with minutely irregular surfaces.
Clinical features:
The papilloma is an exophytic growth made up of numerous, small finger-like
projections which resull in a lesion with a roughened, verucous or "cauliflower like"
surface. It is a well-circumscribed pedunculatcd tumor, occasionally sessile, and

introrally is found most commonly on the tongue, lips, buccal mucosa, gingiva and palate
particularly that area adjacent to the uvula. The majority of papillomas are only few
millimeters

in

diameter,

but

lesions

may be

encountered

measure

several

centimeters. These growths occur at any age and are seen even in young children.
Histopathology:
The papilloma lesion consists of fingerlike projections of stratified squamous
epithelium, often hyperkeratotic, with a central core of fibrovascular connective tissue.
There is characteristic proliferation of the spinous layer of cells. connective tissue is not
involved.

Peripheral Giant Cell Granuloma.

Giant cell lesions of the gingiva arise interdentally or from the gingival margin,
occur most frequently on the labia surface, and may be sessile or pedunculated. They
vary in appearance from smooth, regularly outlined masses to irregularly shaped,
multilobulated protuberances with surface indentations. Ulceration of the margin is
occasionally seen. The lesions are painless, vary in size, and may cover several teeth.
They may be firm or spongy, and the color varies from pink to deep red or purplish blue.
There are no pathognomonic clinical features whereby these lesions can be differentiated
from other forms of gingival enlargement. Microscopic examination is required for
definitive diagnosis.
In the past, giant cell lesions of the gingiva have been referred to as "peripheral
reparative giant cell tumors." These lesions, however, are essentially responses to local
injury and are not neoplasms; and their reparative nature has not been proved. Therefore,
they are now referred to as peripheral giant cell granulomas. The prefix peripheral is
needed to differentiate them from comparable lesions that originate within the jawbone
(central giant cell granulomas).
In some cases the giant cell granuloma of the gingiva is locally invasive and
causes destruction of the underlying bone. Complete removal leads to uneventful
recovery.

Histopathology:
The giant cell granuloma has a nonencapsulated mass of tissue composed of a delicate
reticular and fibrillar connective tissue stroma containing large numbers of ovoid or spindle
shaped young connective tissue cells and multinucleated giant cells. numerous foci of

multinuclear giant cells and hemosiderin particles in a connective tissue stroma. Areas of
chronic inflammation are scattered throughout the lesion, with acute involvement
occurring at the surface. The overlying epithelium is usually hyperplastic, with ulceration
at the base. Bone formation occasionally occurs within the lesion.
Central Giant Cell Granuloma.
These lesions arise within the jaws and produce central cavitation. They
occasionally create a deformity of the jaw that makes the j gingiva appear enlarged.
Clinical features:
The central giant cells granuloma occurs predominantly in children or young
adults is more common in females than in males. Either jaw may be involved, but the
mandible is affected more often. The lesions are more common in the anterior segments
of the jaws and, not uncommonly, cross the midline. Pain is not a prominent feature of
this lesions, although some local discomfort is usually noted. Slight to moderate bulging
of the jaw due to expansion of the cortical plates occurs in the involved areas, depending
upon the extent to bone involvement. The lesion may present no signs or symptoms and
may be discovered accidentally. A history of trauma is seldom found.
Roentgenographic features :
The central giant cell granuioma is essentially a destructive lesion, producing a
radiolucent area with either a relatively smooth or a ragged border, and sometimes
showing faint trabeculae. Definite loculations are often present, particularly in larger
lesions. The cortical plates of bone arc often thin and expanded and may become
perforated by the mass. Displacement of the teeth by the lesion is seen with some
frequency. The appearance of the giant cell granuloma is not pathognomonic and may be
confused with that of many other lesions of the jaws, both neoplastic and non-neoplastic.

Histologic features:
The central giant cell granuloma is made up of a loose fibrillar connective tissue
stroma with many interspersed proliferating fibroblasts and small capillaries.The collagen
fibers are not usually collected not bundles; however, groups of fibers will often present a
whorled appearance. Multinucleated giant cells are prominent throughout the connective
tissue, but not necessarily abundant. These giant cells vary in size from case to case and
may contain only a few or several dozen nuclei. In addition, there are usually numerous
foci of old extravasated blood and associated hemosiderin pigment, some of it
phagocytized by macrophages. Foci of new trabeculae of osteoid or bone also are often
seen, particularly around the periphery of the lesion.

Leukoplakia.
Leukoplakia is a strictly clinical term defined by the World Health Organization
as a white patch or plaque that does not rub off and cannot be diagnosed as any other
disease. The cause of leukoplakia remains obscure, although it is associated to the use of
tobacco (smoke or smokeless). Other probable factors are Candida albicans, HPV-16 and
HPV-18, and trauma. Leukoplakia of the gingiva varies in appearance from a grayish
white, flattened, scaly lesion to a thick, irregularly shaped, keratinous plaque. On clinical
examination, patches of leukoplakia may vary from a nonpalpable, faintly translucent
while area to thick, fissured, papillomatous, indurated lesions. The surface of the lesion is
often finely wrinkled or shriveled in appearance and may feel rough on palpation. The
lesions arc white, gray 01 yellowish-white but, with heavy use of tobacco, may assume a
brownish yellow color.
Sharp described 3 stages of leukoplakia, the earliest lesion being a non-palpable,
faintly translucent, white discoloration. Later, localized or diffuse, slightly elevated
plaques of irregular outline develop. These are opaque white and may have a fine
granular texture. In some instances the lesions progress to thickened, white lesions,
showing induration, fissuring and ulcer formation.
Most leukoplakias (80%) are benign; the remaining 20% are malignant or
premalignant, and only 3% of these are invasive carcinomas. Biopsy of all leukoplakias is

necessary, selecting the most suspicious area, to arrive at a correct diagnosis and institute
proper therapy.
Histopathology:
Leukoplakia exhibits hyperkeratosis and acanthosis. Premalignant and malignant
cases have a variable degree of atypical epithelial changes that may be mild, moderate, or
severe, depending on the extent of involvement of the epithelial layers. When dysplastic
changes involve all layers, it is diagnosed as a carcinoma in situ, and this may become
invasive carcinoma when the basement membrane is breached. Inflammatory
involvement of the underlying connective tissue is a common associated finding.
Periodontal Cyst:

The periodontal cyst is an uncommon lesion that produces localized destruction of

the periodontal tissues along a lateral root surface, most often in the mandibular caninepremolar area.

The following possible etiologies have been suggested:

1. Odontogenic cyst caused by proliferation of the epithelial rests of Malassez; the
stimulus initiating the cellular activity is not known.
2. Lateral dentigerous cyst retained in the jaw after tooth eruption.
3. Primordial cyst of supernumerary tooth germ.
4. Stimulation of epithelial rests of the periodontal ligament by infection from a
periodontal abscess or the pulp through an accessory root canal.

A periodontal cyst is usually asymptomatic, without grossly detectable changes,

but it may present as a localized, tender swelling.
Radiographically:
An interproximal periodontal cyst appears on the side of the root as a radiolucent
area bordered by a radiopaque line. Its radio-graphic appearance cannot be differentiated
from that of a periodontal abscess.
Histopathology:
A gingival cyst cavity is lined by a thin, flattened epithelium with or without
localized areas of thickening. Less frequently, the following types of epithelium can be

found: unkeratinized stratified squamous epithelium, keratinized stratified squamous

epithelium, and parakeratinized epithelium with palisading basal cells.

Other lesions:
Other benign tumors have also been described as rare or infrequent findings in the
gingiva. They include
1) Nevus:
2) Lipoma
3) Myoblastoma,
4) Hemangioma,
5) Neurilemoma,
6) Neurofibroma,
7) Mucus-secreting cysts (mucoceles), and
8) Ameloblastoma.
9) Verruciform xanthoma
10) Dental lamina cyst of newborn
Malignant Tumors of the Gingiva
Carcinoma.
Oral cancer accounts for less than 3% of all malignant tumors in the body but is
the sixth most common cancer in males and the twelfth in females. The gingiva is not a
frequent site of oral malignancy (6% of oral cancers).
Squamous cell carcinoma is the most common malignant tumor of the gingiva. It
may be exophytic, presenting as an irregular outgrowth, or ulcerative, appearing as flat,
erosive lesions. It is often symptom free, going unnoticed until complicated by
inflammatory changes that may mask the neoplasm but cause pain; sometimes it becomes
evident after tooth extraction. These masses are locally invasive, involving the underlying
bone and periodontal ligament of adjoining teeth and the adjacent mucosa. Metastasis is
usually confined to the region above the clavicle; however, more extensive involvement
may include the lung, liver, or bone.

Malignant Melanoma.
Malignant melanoma is rare oral tumor that tends to occur in the hard palate and
maxillary gingiva of older persons. It is usually darkly pigmented and is often preceded
by localized pigmentation. It may be flat or nodular and is characterized by rapid growth

and early metastasis. It arises from melanoblasts in the gingiva, cheek, or palate.
Infiltration into the underlying bone and metastasis to cervical and axillary lymph nodes
are common.

Sarcoma.
Fibrosarcoma, lymphosarcoma, and reticulum cell sarcoma of the gingiva are
rare; only isolated cases have been described in the literature. Kaposi's sarcoma often
occurs in the oral cavity of patients with acquired immunodeficiency syndrome (AIDS),
particularly in the palate and the gingiva.

Metastasis.
Tumor metastasis to the gingiva occurs infrequently. Such metastasis has been
reported with | various tumors, including adenocarcinoma of the colon, lung carcinoma,
primary

hepatocellular

carcinoma,

renal

cell

carcinoma,

hypernephroma,

chondrosarcoma, and testicular tumor.

The low incidence of oral malignancy should not I mislead the clinician.
Ulcerations that do not resp to therapy in the usual manner, as well as all ging tumors and
tumorlike lesions, must be biopsied submitted for microscopic diagnosis.

FALSE ENLARGEMENT
False enlargements are not true enlargements of gingival tissues but may appear
as such as a result o increases in size of the underlying osseous or dentil tissues. The
gingiva usually presents with no abnormal clinical features except the massive increase in
size of the area.

Underlying Osseous Lesions

Enlargement of the bone subjacent to the gingival area occurs most often in tori
(torus palatinus & torus mandibularis) and exostoses, but it can also occur in Paget's
disease, fibrous dysplasia, cherubism, central giant cell granuloma, ameloblastoma,
osteoma, and osteosarcoma. The gingival tissue can appear normal or may have unrelated
inflammatory changes.

Underlying Dental Tissues

During the various stages of eruption, particularly of the primary dentition, the
labial gingiva may show a bulbous marginal distortion caused by superimposition of the
bulk of the gingiva on the normal prominence of the enamel in the gingival half of the
crown. This enlargement has been termed developmental enlargement and often persists
until the junctional epithelium has migrated from the enamel to the cementoenamel
junction.
In a strict sense, developmental gingival enlargements are physiologic and usually
present no problems. However, when such enlargement is complicated by marginal
inflammation, the composite picture gives the impression of extensive gingival
enlargement. Treatment to alleviate the marginal inflammation, rather than resection of
the enlargement, is sufficient in these patients.

TREATMENT PHASE:
Treatment of gingival enlargement is based on the understanding of the cause and
pathological changes. Enlargement poses problem in plaque control, esthetics, speech and
mastication.

TREATMENT OF INFLAMMATORY ENLARGEMENT:

TREATMENT OF CHRONIC ENLARGEMENT:
Soft and edematous enlargements are treated by scaling and root
planning.
Enlargements with fibrotic components which do not undergo shrinkage
are surgically removed by flap technique or gingivectomy.
Selection of technique depends on size and character of the tissue.
Tumor like enlargements are treated by gingivectomy using a B.P. blade
no.12 separating the gingival from the underlying mucosa at its base.
TRETMENT OF ACUTE ENLARGEMENT:
Gingival abscess:
Fluctuent area is incised with no.15 blade to permit drainage.
Area is cleaned with water and covered with gauge.

 Patient is advised to rinse with warm water every 2 hrs. for 24 hrs.
Analgesics and antibiotics are prescribed.
On next visit scaling is done.
Periodontal abscess:
Purpose of treatment is to alleviate pain, control spread of infection and
establish drainage.
Drainage can be established through the pocket or by means of an
incision from the outer surface, under antibiotic coverage.
After drainage, an acute periodontal abscess becomes chronic, then it is
treated as a periodontal pocket by flap surgery.

TREATMENT OF DRUG INDUCED ENLARGEMENT:

Enlargements has 2 components:
A) Fibrotic: caused by the drug.
B) Inflammatory: induced by bacterial plaque.

TREATMENT OPTIONS:
1. Discontinuation or change of medication (Dongani et al 1993):
- Consultation with patients physician is must.
- It is important to allow for a 6-12 month period of time to elapse between
discontinuation and possible resolution before implementing surgery.
- Alternative medications to :
a) Phenytoin- Carbamazepine, Valproic acid.
b) Nifedipine- Diltiazem, Verapamil ( Prevalence rate- 20% & 4%
respectively Lukk 1995).
c) Cyclosporine- Tacrolimus ( Lucas et al 2005 ).
2. Plaque control:
- First step in treatment is plaque control.
- Good oral hygiene and frequent professional removal of plaque decreases
degree of Pseudopocket formation leads to abundant plaque accumulation.
3. Surgical treatment:
If enlargement persists after above mentioned approaches, surgical
intervention is necessary by-

A. GINGIVECTOMY:
- Pockets are explored with periodontal probe and depth is marked.
- Periodontal knives are used to give incision in a coronal direction starting
from just apical to marked points.
- Incision should be beveled at 45 to the tooth surface.
- Remove excised tissue, granulation tissue and calculus.
- Cover area with surgical pack.
B. FLAP TECHNIQUE:
- Indicated in larger areas (more than 6 teeth), with osseous defects and
attachment loss present.
- After anaesthetizing the area, sounding of alveolar bone is performed with
periodontal probe to determine presence and extent of osseous defects
- Internal bevel incision is given at least 3mm. coronal to the mucogingival
junction.
- Thinning of tissue is done with the same blade.
- Elevate the flap with a periosteal elevator.
- Orban knife is used to give incisions at the base of papilla.
- Remove excised tissue, tissue tags, perform root planing, and contour the
bone as needed.
- Flap is placed at bone tooth junction and is sutured.
- Pack is applied.
- To prevent recurrence, patient is advised to follow a meticulous home care
regimen (Nishikawa et al 1991).
- Recurrence may occur as early as 3-6 months, but in general results are
maintained for at least 12 months.
SELECTION OF TECHNIQUE:
To choose between two techniques, following criteria should be
considered.
- Extension of the area to be operated.
- Presence of periodontitis and osseus defects.
- Amount of attached gingival (atleast 3mm of keratinized tissue must remain
after surgery).
- Small areas (upto 6 teeth) can be treated by gingivectomy.

TREATMENT OF ENLARGEMENT IN PREGNANCY:

In pregnancy emphasis should be ona) Preventing gingival disease before it occurs.
b) Treating existing disease before it worsens, by removal of all local factors by
scaling and curettage.

- Tumor like enlargements should be removed surgically. Surgery in

pregnancy is carried out only if there is interference with mastication or
esthetic disfigurement, that patient wishes to be removed.
- It is prudent to avoid elective dental care during the first trimester and the
last half of third trimester.
- Prolonged chair time should be avoided.
- To prevent supine hypotensive syndrome, a 6 inch soft wedge (rolled towel)
should be placed on the patients right side, when patient is in reclining
position for treatment.
- Second trimester is the safest period.

TREATMENT OF ENLARGEMENT IN PUBERTY:

Scaling, root planing is done.
Surgery if required is done.
Problem is recurrence due to poor oral hygiene, so patient is asked to maintain
good oral hygiene.

TREATMENT OF LEUKEMIC ENLARGEMENT:

Bleeding time, clotting time, platelet count and consultation with a

hematologist is a must.
In acute conditions, initially debris is removed with cotton swab in small
areas.
Patient is asked to rinse with 3% H2O2 and chlorhexidine every 2 hours.
At subsequent visits, scaling and thorough root planing are carried out to
remove local factors under local anesthesia.
Treatment should be confined to small areas to control bleeding.
Antibiotics should be administered systemically the evening before and 48
hours after each treatment.

Conclusion:
Gingival enlargement can be caused by a wide variety of etiologies. The clinician
can often diagnose the cause by a careful history (e.g., drug-induced or pregnancy-induced
enlargement), by location (e.g., mouth-breathing enlargement, around anterior teeth), or by
the clinical presentation (e.g., generalized enlargement with gingival hematoma formation
seen in leukemia). Plaque-induced inflammation can be the sole cause of gingival enlarge-

ment or can be a secondary cause, so in all patients, therapy to control gingival inflammation
is essential.
Thus Correct diagnosis & treatment planning form the most essential part of the
treatment of gingival enlargement to achieve proper functional and esthetic harmony

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Carranza F.A. , Newman M.G. , Takei H.H. : Carranzas Clinical

Periodontology, tenth edition, Saunders, Philadelphia.

Grant Daniel A. et al : Periodontics in the tradition of Orban |& Gottlieb.

Wade Bryan : Basic Periodontology.

Ciancio SG et al : Gingival hyperplasia and diphenyl hydantoin. J

Periodontology 1972 ; 43 : 411.

Angelopoulos AP et al : Incidence of diphenyl hydantoin gingival hyperplasia.

Oral Surg 1972 ; 34 : 898.

Maier AW, Orban B : Gingivitis in pregnancy. J Periodontology 1993 ; 64 :

1092.

Clinical Periodontology, carranza 8th ed.

Textbook of Oral pathology, Shaffers 4th ed.
Clinical Periodontology & Implant Dentistry, Jan Lindhe 4th ed.
A clinical review of drug induced overgrowths, Aust Dent J 1999;44:219-232.
Drug Associated Gingival enlargement. J periodontol 2004;75:1424-1431.
Are Inflammatory Cytokines Potential Mediators of Phenytoin-induced
Gingival Overgrowth?. Turk J Med Sci 2001;31: 41-46.

A Review of Drug-Induced Oral Reactions. J C D P 2002;4:10-32.

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