Drug induced gingival enlargement - DIGO

DRUG INDUCED GINGIVAL
ENLARGEMENT
PRESENTED BY :
DR. SHREYA MISHRA
MDS 2nd YEAR

CONTENT
1. INTRODUCTION
2. CLASSIFICATION
3. DRUG INDUCED GINIGVAL ENLARGEMENT
(A.) INTRODUCTION
(B.) EPIDEMIOLOGY
(C.) CLINICAL FEATURES
(D.) INDICES
(E.) PATHOPHYSIOLOGY
(F.) ANTI CONVULSANT
(G.) CYCLOSPORIN
(H.) CALCIUM CHANNEL BLOCKERS
4. CONCLUSION
5. REFERENCES

INTRODUCTION
• American Academy of Oral Medicine describes
Gingival Enlargement, also known as gingival
hyperplasia or hypertrophy as an abnormal
overgrowth of gingival tissues.
• Increase in size of gingiva or gingival growth
(Carranza 11th Edition)
• Gingival enlargement and gingival overgrowth are
terms used interchangeably with hyperplasia,

CLASSIFICATION
1.
Inflammatory
Enlargement
(a) Acute
(b) Chronic
2.
Drug Induced
Enlargement
3. Enlargements
associated with
systemic diseases :
a) Conditioned
Enlargement b)
Systemic diseases
causing gingival
enlargements
4.
Neoplastic
Enlargements
(Gingival
Tumors)
5.
False
Enlargement
CARRANZA 11th Edition

(B.) According to Location &
Distribution :
oLocalized : Limited to one or
more (group of) teeth
oGeneralized : The gingiva is
enlarged in the entire mouth
oMarginal : Limited to the
Marginal gingiva
oPapillary : Confined to the
Interdental papilla
oDiffuse : Involves all the parts
of gingiva
oDiscrete : Isolated sessile or
pedunculated tumor-like
enlargement
CARRANZA 11th Edition

• According to the Degree
of Gingival Enlargement
:
o Grade 0 : No signs of
gingival enlargement
o Grade 1 : Enlargement
confined to the
interdental papilla
involving papilla &
marginal gingiva
covering three quarters CARRANZA 11th Edition

SEQUELE OF GINGIVAL
OVERGROWTH
• Aesthetic changes
• Difficulty in maintaining good oral hygiene
• Clinical symptoms like pain
• Speech disturbances
• Abnormal tooth movement
• Occlusion problems
• Enhanced risk of caries & periodontitis
By
Brunnet
et al
(1996) :

DRUG INDUCED GINGIVAL
ENLARGEMENT
• Drug-induced gingival overgrowth (DIGO) also referred to as drug-
induced gingival enlargement and previously known as drug-
induced gingival hyperplasia, is a side-effect of certain drugs where
the gingival tissue is not the intended target organ.
• The key offending drug classes are anticonvulsants,
immunosuppressants and calcium channel blockers.
• As gingival enlargement develops, it affects the normal oral
hygiene practice and may interfere with masticatory functions.
• It gradually becomes a source of pain and the condition often leads
to disfiguration.
Tungare S, Paranjpe AG. Drug-Induced Gingival Overgrowth. [Updated 2022 Sep 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.

Overview of identified factors that may contribute to the expression of drug-
induced gingival overgrowth
Seymour RA, Ellis JS, Thomason JM. Risk factors for drug-induced gingival overgrowth. J Clin Periodontol. 2000 Apr;27(4):217-23

OVERVIEW
Drug category Anti-convulsants Anti-calcineurins
(and
immunosuppress
ants)
CCBAs
Drugs Phenytoin,
carbamazepine,
valproic acid
Cyclosporin, TAC
(azathioprine,
mycophenolate
mofetil)
Amlodipine,
nifedipine,
felodipine,
nitrendipine,
verapimil,
diltiazem
Therapies Treatment of
epilepsy
Immunosuppressi
on
Anti-hypertensive
Incidence of
DIGO
PHT – 10–83% CsA – 7–80% CCBAs – 10–30%
Brown RS, Arany PR. Mechanism of drug-induced gingival overgrowth revisited: a unifying hypothesis. Oral Dis. 2015 Jan;21(1):e51-61

EPIDEMIOLOGY
• DIGE was first reported as far back as 1939 by Kimball, who described
the condition in patients using phenytoin for epilepsy.
• Seymour et al. reported the first case of gingival overgrowth attributed to
amlodipine in 1994.
• Drug-induced gingival overgrowth is most commonly seen in male
children and adolescents with a most prevalent location in the anterior
gingival tissue with Phenytoin, Cyclosporin and Nifedipine are the most
common causes of gingival overgrowth and phenytoin has the highest
prevalence of all.
• Phenytoin-induced overgrowth may be present in 50 to 100% of patients
treated with such drug, whereas cyclosporin and calcium channel
blocker-induced overgrowths seem to be less common, ranging from 15-
85% and 10-30% respectively.
Tungare S, Paranjpe AG. Drug-Induced Gingival Overgrowth. [Updated 2022 Sep 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.

CLINICAL
FEATURES
• Firm, painless, nodular enlargement of the interdental papilla, limited to the
keratinized portions of the gingiva and extending to the facial and lingual
gingival margins.
• In severe cases, a huge fold of hypertrophied gingival tissue is observed
covering the crowns.
• If no secondary inflammation is present, it appears firm and pale pink,
delineated by tissue that does not bleed on touch.
• If secondary inflammation exists, the gingiva appears smooth, and red or
bluish-red.
• The enlargement is generalized, but it is usually greater in the anterior
regions.
• Typically, it is not seen in edentulous areas.
• The gingival overgrowth disappears when teeth are extracted.
However small differences have been described: in cases due to anti-epileptic drugs, gingiva
are firm and pale because of the conspicuous fibrous component, while other drug-induced
gingival enlargements are characterised by a nodular lobulated spongy aspect and
secondary inflammation that may induce oedema, ulcerations and bleeding on brushing.

INDEX FOR DRUG INDUCED GINGIVAL
ENLARGEMENT
Eva and Ingles (1999) introduced a new index for
measuring gingival overgrowth caused due to drugs.
In this index for standardization, the buccal and lingual
papillae were scored separately.
Dubey S, Gattani D, Deotale S, Quazi M. A contemporary review on indices for gingival enlargement. J Adv Med Dent Scie Res 2016;4(4):62-67

GRADE 0 No overgrowth
(firm adaptation of
attached ginigva)
Slight stippling, no
granular
appearance, Knife
edge papilla
present
No increase in
density of gingiva
GRADE 1 Mild overgrowth Marked stippling,
granular
appearance, Tip of
papilla is rounded
Increase density of
gingiva, Probing
depth is less than
or equal to 3mm
GRADE 2 Moderate
overgrowth
Contour of gingival
margin is concave
or straight
Gingival
enlargement has
buccolingual
dimension upto
2mm
Probing depth is
between 3-6 mm
Increased size of
papilla which is
somewhat
retractable
GRADE 3 Marked
overgrowth
Contour of gingival
margin is convex
Gingival
enlargement has
buccolingual
dimension upto
3mm or more
Probing depth is
more than 6mm
Papilla is
retractable
GRADE 4 Severe overgrowth Profound
thickening of the
gingiva
Large % of clinical
crown is covered
Probing depth is
more than 6mm
Papilla is
retractable

INDEX
To define the extent and degree of severity of phenytoin-induced
GE, Seymour et al. (1985) devised an index.
They designated vertical and horizontal (i.e., labio-lingual)
components to the labial and lingual gingiva.
The Seymour index was an indirect and partial mouth index, as
study models were used for assessment, and six maxillary and six
mandibular anterior teeth are selected for measurement.
Hence, there are 20 gingival units in total that are measured in
each patient. The sum of vertical and horizontal components
provides the score for each gingival unit, which can be a maximum
of 5.
The sum of the scores for each gingival unit provides the overall
score, a maximum of which can be 100, and therefore can be
expressed as a percentage.
A GO score of 30% or greater is considered clinically significant
GE requiring surgical intervention.
Tonsekar, P.; Tonsekar, V. Calcium-Channel-Blocker-Influenced Gingival Enlargement: A Conundrum Demystified. Oral 2021, 1, 236-249

• VERTICAL COMPONENT :
(0) no enlargement of interdental papilla on to tooth surface
(1) mild enlargement resulting in a blunted papilla
(2) moderate enlargement involving lateral spread of interdental
papilla onto the tooth surface of up to a quarter of tooth width
(3) marked encroachment of papilla over greater than a quarter of
tooth width
• HORIZONTAL COMPONENT :
(0) normal thickness of gingival margin
(1) mild increase in thickness less than 2 mm from the normal
(2) marked increase in thickness greater than 2 mm from the
normal Tonsekar, P.; Tonsekar, V. Calcium-Channel-Blocker-Influenced Gingival Enlargement: A Conundrum Demystified. Oral 2021, 1, 236-249

EVALUATI
ON
The diagnosis of drug-induced gingival overgrowth is made by clinical
examination and the patient's past medical history.
• A periodontal examination is necessary to evaluate for the presence
of periodontal disease.
• Full mouth IOPA and OPG are required before beginning any
treatment to rule out periodontal disease.
• Complete blood count (CBC) is indicated in patients with gingival
enlargement to rule out anemia and leukemia.
• Tissue biopsy should be carried out in case the presentation of the
disease is unusual or singular.
• Histopathological examination of persisting overgrowths is
mandatory to evaluate malignant changes.
• Also, Candidiasis and other infections may be ruled out by taking a
culture.
Tungare S, Paranjpe AG. Drug-Induced Gingival Overgrowth. [Updated 2022 Sep 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan

PATHOPHYSIOLO
GY
Despite their pharmacological diversity, the three major drug
groups causing gingival overgrowth have similar mechanism of
action at the cellular level, where they inhibit intracellular calcium
ion influx.
An appraisal of the various investigations into the pathogenesis
of drug-induced gingival overgrowth supports the hypothesis that
it is multifactorial.
The severity of gingival enlargement in patients taking
medications correlates well with poor plaque control and is
commensurate with the degree of plaque-induced inflammation.
Bharti V, Bansal C. Drug-induced gingival overgrowth: The nemesis of gingiva unravelled. J Indian Soc Periodontol. 2013 Mar;17(2):182-7.

VARIOUS MECHANISM OF
ACTION
• As suggested by Brown et al in 1991,

•Na+/ Ca2+ ion Flux Drug Mechanisms
Brown et al (1990, 1991a) suggested that it is reasonable to
assume that all the three drug categories possess a particular
commonality with regard to an inhibitory influence upon cation
channels.
Brown RS, Beaver WT, Bottomley WK. On the mechanism of drug-induced gingival hyperplasia. J Oral Pathol Med. 1991a;20:201–209

Study Drug Mechanism
Jones and Wimbish
(1985)
PHT Decreases resting fluxes of Na+ ions
as well as Na+ currents with respect to
action potentials or chemically induced
depolarizations
Colombani et
al (1985)
CsA Interferes with Ca++ interactions
Dretchen et
al (1986)
PHT and CCBAs Inhibition of Ca++ flux into excitable
membranes
Fugii and Kobayashi
(1990)
PHT and CCBAs Inhibition of Ca++ uptake within
gingival fibroblasts
Thomas and Petrou
(2013)
Anti-seizure drugs Reduction in Na+ channel availability
and therefore a decrease in the action
potential amplitude. This causes
reduced Ca2+ entry and a decrease in
Ca2+ activated K+ channels.

•Plaque Buildup
The concentrated drug in GCF or bacterial plaque has a direct toxic
effect on the gingival tissue.
Dental plaque induces inflammation which causes gingival
overgrowth.
Inflammation causes the upregulation of TGF-beta 1.
Hence, control of dental plaque is needed in the treatment and
prevention of DIGO over time.

From the above studies, it can be concluded that inflammation
secondary to dental plaque is a factor for DIGO and plaque control
should be utilized in both DIGO prevention and therapy.
Pilatti and Sampaio (1997) evaluated the effectiveness of 0.12% chlorhexidine
(CHX) in the treatment of cyclosporine induced DIGO in a rat study. The combined
CsA and CHX group exhibited significantly lower GO compared to the cyclosporin
alone treatment group.
Ilgeni et al (1999) evaluated the effectiveness of periodontal therapy in Cyclosporin
and Nifedipine-induced GO. Multiple regression analysis indicated that age, gingival
inflammation and attendance at recall appointments were significant factors
regarding the recurrence of severe DIGO.
Aimetti et al (2005) evaluated non-surgical and supportive periodontal treatment on
transplant patients with DIGO. They concluded that plaque control appeared to be
effective in controlling GO over an extended time period.
Dannewitz et al (2010) evaluated non-surgical disinfection DIGO therapy. They
reported that all clinical parameters improved significantly after therapy.

•Increased production of GAGs
There are a great many studies reporting increased size of connective
tissue and proliferation of gingival fibroblasts secondary to the inducing
drugs as the primary causation of DIGO (Brown et al,
1991a; Seymour et al, 1996).
Kantor and Hassell (1983) reported an increased accumulation of
sulfated GAGs and noted that it could be related to increased synthesis
of inactive collagenase.
Nares et al (1996) and Seymour et al (1996) suggested a defect in
collagen breakdown as a possible mechanistic issue with regard to the
pathogenesis of DIGO.
When the collagen content and composition of human gingiva, enlarged
due to drugs were compared to normal and inflamed gingival tissues,
the PHT-induced hyperplastic gingiva contained significantly higher
amounts of collagen per unit weight (Hassell et al, 1983).

Kataoka et al (2005) suggested that DIGO is due to a disruption of homeostasis of
collagen synthesis and degradation, predominantly through the inhibition of gingival
fibroblastic collagen phagocytosis. They concluded that DIGO is caused by reduced
gingival fibroblastic collagen phagocytosis through an alpha-2 beta-1 cell surface
integrin. They also noted that the actin-binding protein, gelsolin, may be an important
factor, because of it maintains normal tissue integrity through integrin binding affinity
to collagens, an important factor for the regulation of collagen phagocytosis.
Mariani et al (1996), in an ultra-structural and histochemical evaluation of DIGO,
concluded that that CsA caused an increased amount of GAG deposition and that
therefore, increased GAGs appeared to be the main cause of DIGO.

• Folate cellular uptake
Vogel (1977) was the 1st to propose that DIGO may be secondary to a
localized FA deficiency.
Opladen et al (2010) reported the effect of anti-convulsant drugs upon the
folate receptor 1 (FOLR1)-dependent 5-methyltetrahydrofolate (MTHF)
transport. They reported that the metabolic breakdown of anti-convulsants
generates ROS.
At physiologic MTHF concentrations, the high-affinity FOLR1 represented
the predominant mechanism for cellular uptake.
Exposure to phenytoin could lead to higher MTHF uptake; however,
exposure to superoxide and hydrogen peroxide radicals significantly
decreased cellular MTHF uptake.
Therefore, it appears that the FOLR1-dependent 5-MTHF transport could
also be involved with regard to inhibited folate transport and decreased
folate uptake in gingival fibroblasts.

•Matrix metalloproteinases
Kato et al (2005) examined the effect of phenytoin administration upon
collagen degradation. They evaluated gene and protein expressions of
MMPs. They concluded that phenytoin causes impaired collagen
degradation through MMPs/TIMP-1 through particular cellular signaling
pathways of ERK1/2 and nuclear factor kappa B, possibly leading to
collagen accumulation resulting in GO.
Kato et al (2006) investigated TNF-alpha (associated with gingival
inflammation) and phenytoin with regard to mRNA levels for collagen and
MMPs, and TIMPs. They concluded that together TNF-alpha and phenytoin
synergistically caused impaired collagen metabolism by suppression of
enzymatic degradation with MMPs/TIMP-1 resulting in GO.
Vahabi et al (2013) recently reported that at least with regard to children, an
impaired collagenase activation in DIGO was due to an MMP-1/TIMP
pathway.

• E-cadherin, SMAD, AP-1, TIMP-1, MMP-1,
inactive to active collagenase pathway
Decreased cellular folic acid leads to decreased E-cadherin and SMAD, which leads to
decreased AP-1. Decreased AP-1 results in increased TIMP-1 which leads to decreased
MMP-1. As MMP-1 is necessary for the activation of inactivated collagenase to activated
collagenase, the result is a decreased amount of activated collagenase.

ANTICONVULSANTS
• Phenytoin has been used to control seizure disorders in patients with
epilepsy since its clinical introduction by Merritt & Putnam in 1938.
Within a year of its initial clinical use, reports linking phenytoin to
gingival overgrowth appeared in the literature.
• Despite the widespread availability of anticonvulsant drugs,
phenytoin and phenobarbital remain the most commonly prescribed
antiepileptic medications.
• Reports of the incidence of phenytoin-associated gingival overgrowth
range from 0% to 84.5%, with an average effect approximating 50%.
• An increased prevalence of gingival overgrowth has been observed
in children and young adults.

Pharmacokinetics :
Phenytoin selectively depresses the motor cortex of the CNS and is
believed to mediate this action by stabilizing neuronal discharge and
limiting the progression of neuronal excitation by blocking or interfering
with calcium influx across cell membranes.
Although the daily dose, duration of use and blood or salivary levels of
phenytoin have been related to the presence and degree of
overgrowth, several studies have failed to detect any correlation
among these factor.
In a 2-year longitudinal study, Dahllof & Modeer(1986) observed the
clinical onset of gingival overgrowth after 1 month of phenytoin use.
Although overgrowth occurred progressively over the study period, it
continued at a decreased rate during the second year. Associated
gingival overgrowth appears to reach maximum severity 12-18 months
Hallmon WW, Rossmann JA. The role of drugs in the pathogenesis of gingival overgrowth. A collective review of current concepts. Periodontol 2000. 1999 Oct;21:176-96

• Clinical manifestation :
o Affected tissues typically present a granular or pebbly surface, with
the enlarged papillae extending facially and lingually, obscuring the
adjacent tissue and tooth surfaces.
oAffected papillae may become enlarged to the point of contact,
resulting in the clinical presence of pseudoclefts.
oThe facial gingiva of the anteriors is more commonly affected and
often results in aesthetic disfigurement.
o There is no evidence suggesting that sex or race affects the
occurrence of phenytoin- associated gingival overgrowth.
oAlso reports of phenytoin-induced gingival overgrowth prior to the
eruption of the primary teeth are reported which resulted in delayed
eruption.
oAlthough considered rare, phenytoin gingival overgrowth has also

• Histological charateristics :
Histologically, tissues from gingival overgrowth biopsies present
a thick stratified squamous epithelium with long thin rete pegs
that extend deep into the lamina propria.
The lamina propria is characterized by proliferation of fibroblasts
and increased collagen formation, accompanied by an increase
in non-collagenous proteins.

• Prevention & Treatment :
1. With proper instruction, motivation and reinforcement, oral hygiene
may be effectively addressed by the patient during the course of a
supportive treatment to control bacterial plaque.
In a 15-month longitudinal study by Pihlstrom et al. and another study
by Hall et al they studied the effectiveness of a preventive dental
program in outpatients who were taking phenytoin for seizure control.
All patients received professional preventive care after initiating
phenytoin therapy. Although a small increase in gingival enlargement
was observed in the first 6 months, no further enlargement occurred.
The authors concluded that a preventive dental program could
effectively minimize phenytoin- associated gingival enlargement.
In a 2-year longitudinal study, Dahllof & Modeer initiated a preventive

2. Since phenytoin using patients often experience difficulty with
effective oral hygiene maintenance, approaches may need to be
modified to meet patient needs. This includes the use of an electric
toothbrush and adjunctive antimicrobial sprays or mouthrinses.
Shibley et al. prescribed 0.12% chlorhexidine gluconate rinses
twice a day in 30 patients exhibiting drug-associated overgrowth.
Compared with gingival overgrowth patients using a placebo rinse,
the chlorhexidine group had a significant reduction in plaque
accumulation, gingival inflammation and gingival overgrowth.
3. Although scaling and root planing effectively reduces
accompanying inflammation, surgical treatment is often required to
manage the consequences of clinically significant gingival
overgrowth.
The excessive tissue can be removed using surgical techniques
(gingivectomy/ flap), laser gingivectomy or a combination approach.

CYCLOSPORIN
• Cyclosporin A was first isolated in Switzerland in 1970 as a
metabolite of the fungus species Tolypocludium influturn Gams.
and its first reported use in renal transplantation procedures
was by Calne et al.
• Cyclosporin A has been demonstrated to suppress humoral
immunity (B lymphocytes) and to a much greater extent cell-
mediated immunity (T lymphocytes) such as allograft rejection,
delayed hypersensitivity, graft-versus-host disease and
autoimmune diseases.
• The first cases of gingival overgrowth caused by cyclosporin A

oFriskopp & Klintmalm indicated that the overgrowth was restricted to
keratinized gingiva but could extend coronally and interfere with
occlusion, mastication or speech.
oThese enlarged tissues are generally more hyperemic than the
gingival tissues associated with phenytoin-induced overgrowth.
oAlso it is noted that there is an absence of overgrown tissue in
edentulous patients receiving medication.
oThe enlarged gingival tissues is soft, red or bluish-red, extremely
fragile and bleeds easily upon probing.

• Histological manifestation :
The histological features of all drug-induced gingival overgrowth are
comparable, consisting primarily of connective tissue with an overlying
irregular, multi-layered, parakeratinized epithelium.
Epithelial ridges penetrate deep into the connective tissue, creating
irregularly arranged collagen fiber bundles.
Ultrastructural and immunohistochemical examination of cyclosporine
A induced gingival overgrowth shows characteristics of active protein
synthesis.
The dimensional increase in gingival overgrowth is due to an
increased production of amorphous ground substance by the
fibroblasts, containing increased numbers of both sulfated and non-
sulfated GAG.

CALCIUM CHANNEL
BLOCKERS
A group of drugs specifically developed to assist in the
management of cardiovascular conditions, including
hypertension, angina pectoris, coronary artery spasm and cardiac
arrhythmia, has been introduced in recent years.
The pathogenesis of CCB-induced GO is not clearly understood
and is viewed as being multifactorial.
Various risk factors including drug variables (dosage and
duration), age, gender, oral hygiene status, and gingival
inflammation have been associated with this condition.

• Pharmacokinetics :
Calcium channel blockers act by inhibiting calcium ion
influx across the cell membrane of cardiac and smooth
muscle cells, thereby interfering or blocking mobilization
of calcium intracellularly.
In 1990, Brown et al. reported the first case of gingival
overgrowth induced by nitrendipine. At that time, this
agent was being used in an experimental protocol to treat
hypertension and congestive heart failure.
A year later, Lombardi et al. reported gingival overgrowth
in a patient taking felodipine to treat hypertension.

oThe interdental papillae are initially affected,
becoming enlarged and resulting in a lobulated
or nodular morphology.
oThese effects are limited to the attached and
marginal gingiva, and are more frequently
observed anteriorly, especially on the facial
surface.
oAs the tissues become progressively larger,
plaque control becomes more difficult.
oAlthough overgrowth does not appear to affect
edentulous areas, nifedipine-induced gingival
enlargement has been reported around dental
implants.
oThomason et al. and Bokenkamp et al. reported
increased severity of gingival overgrowth when
these two agents were combined, compared

• Histological manifestation :
In a study of 34 biopsies of nifedipine
gingival overgrowth, Barak et al.
described thickening of the spinous cell
layer, slight to moderate hyperkeratosis,
fibroblastic proliferation.
These changes were accompanied by
increased capillary vascularity and slight
perivascular inflammation.
Similar to other drug-induced gingival
overgrowth histological descriptions, the
specimen presented long, tubular rete
pegs that extended deep into the lamina
propria. Tonsekar, P.; Tonsekar, V. Calcium-Channel-Blocker-Influenced Gingival Enlargement: A Conundrum Demystified. Oral 2021, 1, 236-249

TREATMENT
PROTOCOL
Camargo PM, Melnick PR, Pirih FQ, Lagos R, Takei HH. Treatment of drug-induced gingival enlargement: aesthetic and functional considerations. Periodontol 2000. 2001;27:131-8

• Treatment options: nonsurgical
1. Firstly, consideration should be given to the possibility of discontinuing
the drug or of changing medication which should be in conjunction with
the patient’s physician.
2. Alternative medications to Phenytoin include Carbamazepine and
Valproic acid, which have shown a lower rate of gingival enlargement.
3. For patients on Nifedipine, other CCBs such as Diltiazem and Verapamil
may be viable alternatives, since the prevalence of gingival enlargement
associated with those drugs is 20% and 4%, respectively.
4. Regression of Nifedipine induced gingival overgrowth has been reported
following a change in medication to Isradipine
5. Drug substitution options for Cyclosporin are more limited due to the fact
that few of these options exist. Recently, it has been substituted by
Tracolimus.
6. There is also preliminary evidence that the antibiotic Azithromycin may
aid in decreasing the severity of Cyclosporin-induced gingival
enlargement.
If any drug substitution is attempted, it is important to allow for 6–12 months to elapse between
discontinuation of the offending drug and the possible resolution of gingival enlargement before
surgical treatment is implemeted.

7. The clinician should also emphasize on plaque control along
with the treatment of drug induced gingival enlargement.
Adequate plaque control may also aid in preventing the
recurrence of gingival enlargement in surgically treated cases.

•Treatment options: surgical
Gingival enlargement may persist, despite drug substitution attempts and
good plaque control. These cases need to be treated by periodontal surgery,
either gingivectomy or the periodontal flap.
1. In general, small areas (up to six teeth) presenting with DIGE where
there is no evidence of attachment loss (and therefore no anticipated
need to perform osseous surgery) can be effectively treated with the
gingivectomy technique.
2. Larger areas of gingival enlargement (more than six teeth) or areas
where attachment loss combined with osseous defects is present should
be treated with the periodontal flap. Also, any situation in which the
gingivectomy technique may result in the elimination of all keratinized
tissue and consequent creation of mucogingival problems should be

•Maintenance
Recurrence of drug-induced gingival enlargement is a reality in
surgically treated cases. As stated previously, meticulous home
care, chlorhexidine gluconate rinses and professional cleaning
can decrease the rate and the degree at which recurrence
occurs.
Recurrence may occur as early as 3–6 months after the surgical
treatment, but in general, surgical results are maintained for at
least 12 months.

CONCLUSION
Three very different groups of pharmaceutical agents have
been associated with the occurrence of gingival
overgrowth in susceptible individuals.
Despite their pharmacological diversity, they have a similar
mechanism of action and clinical manifestation.
Although many patients respond favorably to nonsurgical
treatment of their gingival enlargement, a significant
number require surgical removal of the overgrown tissues
to accomplish an aesthetic and functional result.
Until the medical community can provide alternative drug
therapy with comparable efficacy that does not induce
gingival overgrowth, dental prac- titioners will be tasked

REFERENCES
1. CARRANZA 11th Edition
2. Tonsekar, P.; Tonsekar, V. Calcium-Channel-Blocker-Influenced Gingival
Enlargement: A Conundrum Demystified. Oral 2021, 1, 236-249
3. Hallmon WW, Rossmann JA. The role of drugs in the pathogenesis of gingival
overgrowth. A collective review of current concepts. Periodontol 2000. 1999
Oct;21:176-96
4. Brown RS, Arany PR. Mechanism of drug-induced gingival overgrowth
revisited: a unifying hypothesis. Oral Dis. 2015 Jan;21(1):e51-61
5. Tungare S, Paranjpe AG. Drug-Induced Gingival Overgrowth. [Updated 2022
Sep 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2023 Jan
6. Bharti V, Bansal C. Drug-induced gingival overgrowth: The nemesis of gingiva
unravelled. J Indian Soc Periodontol. 2013 Mar;17(2):182-7
7. Dubey S, Gattani D, Deotale S, Quazi M. A contemporary review on indices for
gingival enlargement. J Adv Med Dent Scie Res 2016;4(4):62-6
8. Camargo PM, Melnick PR, Pirih FQ, Lagos R, Takei HH. Treatment of drug-
induced gingival enlargement: aesthetic and functional considerations.

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