GINGIVAL ENLARGEMENT

CONTENTS

• Introduction • Classification• Indices • Inflammatory Enlargement• Enlargements associated with systemic diseases • Neoplastic enlargement• Drug-induced enlargement• Idiopathic gingival enlargement • False enlargement• Conclusion• References

INTRODUCTION

Hypertrophic gingivitis

Gingival hyperplasia

Gingival enlargement

Gingival overgrowth

CLASSIFICATION

A] Based on etiologic factors and pathologic changes

I. Inflammatory Enlargement - Acute

- ChronicII. Drug-induced enlargement

III. Enlargements associated with systemic diseases

IV. Neoplastic enlargement (gingival tumors) Benign tumors Malignant tumorsV. False enlargement

ii) Systemic diseases causing gingival enlargement 1. Leukemia 2.Granulomatous diseases (Wegener's granulomatosis, sarcoidosis)

i) Conditioned enlargement 1. Pregnancy

2. Puberty 3. Vitamin C deficiency 4. Plasma cell gingivitis 5. Nonspecific conditioned enlargement

B] Based on location and distribution I. Localized

II. Generalized

III. Marginal

IV. Papillary

V. Diffuse

VI. Discrete

INDICES

Bokenkamp & Bohnhorst 1994

Grade 0 No signs of gingival enlargement

Grade 1 Enlargement confined to IDP

Grade 2 Enlargement involves IDP & marginal gingiva

Grade 3 Enlargement covers three quarters / more of

crown

Degree of gingival hyperplasia according to modified index by Angelopoulos & Goaz 1972

Grade Hyperplasia Size Tooth coverage

0 No Normal No

1 Minimal <2 mm Cervical 3rd or less

2 Moderate 2-4 mm Middle 3rd

3 Severe >4 mm More than 2/3rd

Gingival overgrowth index- Mc Gaw et al 1987

Grade 0 No overgrowth, feather edge gingival margin

Grade 1 Blunting of gingival margin

Grade 2 Moderate gingival overgrowth (one third crown

length)

Grade 3 Marked gingival overgrowth (more than one

thirds of crown)

Clinical index for drug induced gingival overgrowth Ingles et al 1999

Grade 0

Grade 1

Grade 2

Grade 3

Grade 4

1.No overgrowth

2. slight stippling, no/slight granular appearance

3. knife edge margin

4. no increase in the density or size

1. Early overgrowth slight increase in density

2.marked stippling and granular appearance

3.tip of the papillae is round

4.probing depth ≤ 3mm

1.Moderate overgrowth increase

in size of the papillae and rolled

gingival margins

2. The contour concave or straight

3. buccolingual dimension of upto

2mm

4. Probing ≤ 6mm

5. Papillae retractable

1. Marked overgrowth

encroachment on the clinical

crown

2. The contour convex

3. Buccolingual dimension

≥ 3 mm

4. The probing depth ≥ 6mm

5. Papillae retractable

1. Severe overgrowth, profound

thickening of gingiva

2. Large % of the clinical crown

is covered

3. Papillae - retractable

4. Probing depth ≥ 6mm

5.buccolingual dimension 3mm

1. INFLAMMATORY ENLARGEMENT

CHRONIC

ACUTE

INFLAMMATORY Gingival abscess

Periodontal abscess

a. Chronic inflammatory enlargement

Etiology

Plaque accumulation &

retention

Poor oral hygiene

Anatomic abnormalities

Improper restoration

Orthodontic appliances

Malocclusion

Clinical Features 1.

Slight ballooning of IDP & marginal gingiva

Life preserver shaped bulge

Smooth , edematous , bleed easily

Localised / generalised

Progress- slowly and painlessly

Pseudopockets

Discrete sessile or pedunculated tumor like mass

Interproximal / marginal or attached gingiva

Slow growing and painless

Clinical Features

1. 2.

Histopathology

1.Soft and friable

2.Firm and resilient

B. ACUTE INFLAMMATORY ENLARGEMENT

1. GINGIVAL ABSCESSEtiology Foreign substances

Clinical features Marginal gingiva or IDP Red swelling smooth shiny surface Fluctuant and pointed with

a surface orifice expresses purulent exudate

2. PERIODONTAL ABSCESSLateral abscess / parietal abscess

Depending on location - Gingival

- Periodontal (Acute / Chronic)- Pericoronal

Meng et al ’99Depending on number - Single - Multiple

Etiology

PERIODONTITIS RELATED

Extension of infection from PD pocket

Lateral extension of inflammation

Pocket with a tortuous course

Incomplete removal of calculus

Etiology NON PERIODONTITIS

RELATED

Impaction of foreign bodies

Endodontic perforation

Lateral cyst infection

Factors affecting morphology of root

Signs and symptoms

Acute abscess

- Mild to severe discomfort- Localized red, ovoid swelling- Periodontal pocket- Mobility- Tooth elevation in the socket- Tenderness to percussion or

biting- Suppuration - Elevated temperature- Regional lymphadenopathy

Chronic abscess

- No pain or dull pain- Localized inflammatory lesion- Slight tooth elevation- Intermittent exudation- Fistulous tract often associated with deep pocket- Usually without systemic involvement

ENLARGEMENTS ASSOCIATED WITH SYSTEMIC DISEASES

Two mechanisms

1. Magnification of an existing inflammation initiated by dental plaque

- conditioned enlargement

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

- systemic disease causing enlargement

1. Conditioned enlargement

• Systemic condition exaggerates or distorts usual gingival response to plaque

• Bacterial plaque

Types 1. Hormonal – pregnancy , puberty2. Nutritional – vitamin C deficiency3. AllergicNon specific conditioned

1. Marginal and generalised enlargement2. Single or multiple tumor like masses

Hormonal changes - Progesterone and estrogen- Vascular permeability – edema , inflammatory response

Subgingival microbiota – P. intermedia

a. Enlargement in pregnancy

1. Marginal enlargement

- Generalised , more prominent

interdentally

- Bright red or magenta colour

- Friable , smooth & shiny

surface

- Bleeding – spontaneously or

on slight provocation

“ Pregnancy rhinitis”

2. Tumor like gingival enlargement“Pregnancy tumor”

- Discrete mushroomlike , flattened

spherical mass

- Dusky red or magenta , smooth

glistening surface

- Doesnot invade underlying bone

- Semifirm – soft , friable

- sessile or pedunculated

- Painless unless its size and shape foster

accumulation of debris

Angiogranuloma Thickened epilthelium

Newly formed, engorged capillaries

Fibrous stroma

Inflammatory infiltrate

Histopathology

Treatment

• Removal of plaque and calculus

• Tumor like gingival enlargement - surgical excision and

SRP

• Recurrence

• Spontaneous reduction – termination of pregnancy

• Male and female adoloscents

• Areas of plaque accumulation

• Facial surface

• Marginal and interdental

Histopathology

- Similar to Chronic

inflammation

Difference

b. Enlargement in puberty

c. Enlargement in vitamin C deficiency

Clinical features - Bluish red , soft , friable, boggy- smooth & shiny surface- Haemorrhage – spontaneous /

slight provocation- Surface necrosis with

pseudomembrane formation

• Classic description of scurvy• Acute deficiency – hemorrhage , collagen degeneration , edema • modify response to plaque

d. Plasma cell gingivitis

• Atypical gingivitis / plasma cell gingivostomatitis• Plasma cell granuloma – localised form• Allergic in origin

Clinical features

• Pyogenic granuloma

Clinical features • Discrete spherical , tumorlike mass , pedunculated ,

smooth surface• Bright red or purple , friable or firm• Painless• Hemorrhage

e. Nonspecific conditioned enlargement

2.Systemic Disease That Cause Gingival Enlargement

1. Leukemiamalignant neoplasia of WBC precursors - diffuse replacement of bone marrow – proliferating leukemic cells

- abnormal number and forms of immature WBCs- widespread infiltrates

Acute myeloid leukemia

Clinical features• Diffuse / marginal • Localised / generalised• Overextension of marginal

gingiva• Discrete tumorlike

interproximal mass• Bluish red , shiny surface• Firm • Hemorrhage

Leukemic infiltration

Leukemic cell infiltration of gingival corium

Gingival thickness

Gingival pockets

Plaque accumulation

Secondary inflammatory lesion

Histopathology - Connective tissue – dense mass of immature and

proliferating leukocytes , engorged capillaries , edema

- Epithelium – degree of leukocytic infiltration and edema

2. Granulomatous diseasea.Wegeners granulomatosis

- Acute granulomatous necrotising lesions of respiratory tract , nasal and oral defects

- Acute necrotising vasculitis

Clinical features-oral mucosal ulcerations -delayed healing-Papillary enlargement – reddish purple ,- bleeds easily-Strawberry gingiva

Etiology - Unknown - Immunologically mediated tissue injury

Histopathology

b. Sarcoidosis- Unknown etiology- Involve any organ

Clinical features

NEOPLASTIC ENLARGEMENT

1. Benign tumors of gingiva Epulis

a. Fibroma

i) Giant cell fibromaii) Peripheral ossifying fibroma

b. Papilloma- Proliferations of surface epithelium associated with HPV- HPV 6 & 11

c. Peripheral Giant Cell GranulomaPeripheral giant cell tumors

d.Central Giant Cell Granuloma- Arise within the jaw – central cavitation

e. Leukoplakia• WHO: White patch or plaque that does not rub off & cannot be diagnosed as any other disease

• Associated use of tobacco Other probable factors: Candida, HPV-16, HPV-18 &

Trauma

Gingival Cyst:Develop from odontogenic epithelium or traumatically implanted sulcular epithelium

2. Malignant tumors of gingiva

Squamous cell carcinoma:• 90% of all Oral cancer• 6th –most common cancer in males • 12th - females • Most common malignant tumor of gingiva

Malignant melanoma:

• Rare tumor hard palate, maxillary gingiva -older persons

• Darkly pigmented, rapid growth, early metastasis

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GINGIVAL ENLARGEMENT

Contents • Introduction • Classification• Indices • Inflammatory Enlargement• Enlargements associated with systemic diseases • Neoplastic enlargement• Drug-induced enlargement• Idiopathic gingival enlargement • False enlargement• Conclusion• References

Drug induced gingival enlargement

• Side effect – non dental treatment• First case – Kimball 1939

Drugs associated with gingival overgrowth

Anticonvulsants

PhenytoinSodium valproatePhenobarbitone

Vigabatrin

Immunosuppressants

Cyclosporin

Calcium channel blockers

Dihydropyridines Nifedipine

Felopdipine Amlodipine

Phenylalkylamine Verapamil

Benzothiazepine Diltiazem

Prevalence of DIGO

• 50 % - phenytoin ( Angelopoulous & Goaz 1972)

• 30% - Cyclosporine • 10% - Nifedipine

(Seymour 1987 , Barclay 1992)

• In India, 57% of epileptic children - aged 8-13 years - phenytoin therapy

Prasad et al 2002

Risk factors for DIGO

Risk factors

Age

Sex

Drug variables

Concomitant medication

Genetic factors

Periodontal variables

•Early studies on phenytoin – teenagers , hospitalised or institutionalised•Two community based studies – 1. mean age 40.6 years –

Thomason 19922.Younger age – Casetta 1997 •Cyclosporin - children

(Daley 1994)•Calcium channel blockers – not applicable •Middle age and older

Circulating androgen + gingival fibroblasts

Testosterone – 5α dihydrotestosterone

PHT – enhances metabolism

Circulating androgen – adoloscents and teenagers

Age

•Phenytoin – no difference

Hassell 1981

•CsA- Male

•CCBs – male 3 times more

Sex Concomitant medication

•Nifedipine + cyclosporin –

increases prevalence but not the

severity

•Polypharmacy – PHT –

metabolised by P450

•other anticonvulants – induce

P450 isoenzyme

Drug variables

1. Drug dosage – poor predictor•Dose / pts body weight•PHT & CCB – therapeutic drug level 7-10 days•Cyclosporin – trough concentration•Area under plasma/ serum concentration time curve (AUC)

2. Type of preparation CsA – solution - 37 % - early onset – higher in saliva capsules – 43%

(Wondimu 1996)3. Salivary concentration PHT &CsA – salivary concentration positive correlation with OG

4. GCF – nifedipine

Genetic factors

Cytochrome P450 gene

polymorphism

HLA- DR1 – protection against

OG

HLA-DR2 – OG susceptible

Pernu 1994

Periodontal variables

Plaque scores & gingival inflammation – exacerbate OG

General features of DIGO

Painless beadlike enlargement of IDP

Marginal gingiva

Massive tissue fold

Plaque control difficult

Secondary inflammatory process

Combined enlargement

• Generalised

• Not in edentulous areas

• Chronic , slow

• Recurs

• Discontinuation of drug – spontaneous reduction

Histopathology

Anticonvulsants

• Epilepsy –

• First antiepileptic drug – phenytoin – DOC

• Merritt & Putman 1938

• 1st DIGO case

• Active metabolite – 5 parahydroxyphenyl – 5

phenylhydantoin

• Other hydantoins – ethotoin , mephenytoin

• Other anticonsulvant – succinimides , valproic acid

Anticonvulsant properties

1. Reduces excessive discharge2. Reduces spread of excitation Stabilising neuronal membraneNa – prevents influx K – blocks outward flow Ca – decreases calcium influx

• Clinical features

1. Esthetic disfigurement, 2. Malpositioning of teeth, 3. Interfere masticatory function, 4. Speech, 5. Oral hygiene

Theories of pathogenesis

1. Gingival fibroblasts1. High activity2. Low activity

Hasell 1983

2. Lack of collagen breakdown• FBS – inactive collagenase• mRNA collagenase levels are diminished• Gene expression of MMP-1, 2, and 3 was reduced by

phenytoin administration, • the TIMP-1 mRNA was markedly augmented

2005, Kato et al

• macrophages pretreated with phenytoin - lower production of MMPs

• intracellular pathway - related to a lower expression of α2β1-integrin

3. Non collagenous matrix

• Non collagenous matrix – 20% of dry weight

• Increased hexoamine , uronic acid

• Increased sulphated GAG

• Higher volume density of non collagenous protein

compared to collagenousDahllof et al 1984

4. Role of growth factors

• TGF-β - stimulating collagen biosynthesis

• latency-associated protein (LAP) - TGF-β inactive

• CTGF levels are increased

• Epithelial mesenchymal transition

• PDGF – PHT facilitated expression of PDGF B

– 6 times

5.Immunosuppression

sIgA - decreased

Repair process

Gingival overgrowth

6. PHT and Adrenal gland

Suppression of ACTH production

Suppression of adrenocortical function

Reduction of glucocorticoid synthesis

compensatory increase in the Somatotrophic hormone

Fibroblast proliferation

7. PHT and folic acid depletion

Decreases absorption of

folic acid

Blocks transport - intestinal epithelium

Enzyme folate reductase

Folic acid – DNA synthesis

Impaired maturation – sulcular epithelium

CT susceptible to inflammation

Cyclosporin induced gingival overgrowth

• Cyclosporin (CsA) - 1972 James Borel

• Organ transplantation , autoimmune disease

• Monotherapy - CsA• 2 drugs – CsA + cortisone / dihydropyridine• 3 drugs – CsA + cortisone + azathiprine

• Cyclosporin-induced gingival overgrowth – 1983 Rateitschak- Plu¨ss et

al

Cyclosporin and T cells

• a) Inhibits T cell helper function to accessory cells - interleukin 1

• b) Prevents the formation of receptors to interleukin I on the membrane of the T-cell.

• c) Renders T-cells unresponsive to - interleukin 2 .

Pathogenesis of Cs GO

Cyclosporin

Cytokines

Extracellular matrix

metabolism

Cell proliferationApoptosis

SynthesisDegradation -I/C pathway-E/C pathway

• More in labial aspect

• Soft, red or bluish-red, extremely fragile and bleed easily, more hyperemic than PIGO

Histopathology

Calcium channel blockers

• CCB’s introduced in 1980’s

• Used extensively in the management of CV disorders(HTN, angina, coronary artery spasm, cardiac arrythmia)

• NIFEDIPINE angina, mild to moderate HTN

• Relaxes smooth muscles and dilates the coronary arteries

• NIGO 1984 by Lederman et al

Pathogenesis: Nifedipine• Affects calcium metabolism similar to phenytoin• Role of TGF beta• Heparan GAG

Verapamil Subpopulation of fibroblast

• IDPmarginal attached

• Lobulated and nodular

• Anteriorly, facial surface

• Inflammation Combination enlargement

Idiopathic gingival enlargement

• Gingivomatosis , Elephantiasis, Idiopathic fibromatosis, Hereditary gingival hyperplasia , Congenital familial fibromatosis , Hereditary gingival fibromatosis

• rare oral disease • autosomal dominant

• hypertrichosis, mental retardation and epilepsy

• Nodular form• Symmetric form- most common type• During eruption of permanent teeth

• most common effects• diastemas, • Malpositioning of teeth • prolonged retention of primary teeth• cover the dental crowns • the alveolar bone is not affected (Bittencourt et al. 2000).

TGF 1

Increased proliferationHGF cells

Low levels of MMP 1, MMP 2

Myofibroblasts

High level of extracellular

matrix proteins (collagen)

TGF 1

Gingival overgrowth

False enlargement

a. Underlying osseous lesions• Commonly Tori, Exostosis

• Also seen in Paget’s disease, Fibrous dysplasia, Cherubism, Central giant cell granuloma, Ameloblastoma, Osteoma and Osteosarcoma

b. Underlying dental lesions• Various stages of eruption of primary dentition labial

gingiva• Developmental enlargement

Conclusion

Gingival enlargement are multifactorial and complex in nature , which may be in respone to various interaction between host and environment. GO considerably reduce the quality of life and may result in serios emotional and social problems due to esthetics and functionality hence the prevention and treatment based on the understanding the cause and underlying pathologic changes ,

References

• Newman MG , Takei HH , Klokkevold PR , Carranza FA . Carranza’s Clinical Periodontology, 10th edition

• Marshall R , Bartold M A clinical review of drug induced gingival overgrowth Australian dental journal 1999 ;44:4 219-232

• Seymour RA, Ellis JS, Thomason JM: Risk factors for drug-induced gingival overgrowth.J Clin Periodontol 2000; 27: 217–223.

• Seymour RA , Thomasan JM Pathogenesis of Drug Induced Gingival Overgrowth- J Clin Periodontol 1996;23:165-175

• Strawberry –like gingival tumor as first sign of Wegener’s Granulomatosis. J Periodontol 2008; 79: 1297-1303

• Seymour RA and Heasman PA: Drugs and the periodoniium. J Clin Periodontol 1988: 15: 1-16

• Jˆoice Dias Corrˆea et al Phenytoin-Induced Gingival Overgrowth: A Review of the Molecular, Immune, and Inflammatory Features ISRN Dentistry 2011,1-8

• Williamw . Hallmo&n J Effrey A. Rossmann The role of drugs in the pathogenesis of gingival overgrowth A collective review of current concepts Periodontology 2000, Vol. 21, 1999, 176-196

• Paulom. Camargo, Philip R.Melnick, Flavia Q. M. Pirih, Rodrigo Lagos & Henry H. Takei Treatment of drug-induced gingival enlargement: aesthetic and functional considerations Periodontology 2000, Vol. 27, 2001, 131–138

• Dustin Tedesco and Lukas Haragsim Cyclosporine: A Review Journal of Transplantation Volume 2012

• Bitu CC, Sobral LM, Kellermann MG, Martelli-Junior H, Zecchin KG, Graner E, Coletta RD. Heterogeneous presence of myofibroblasts in hereditary gingival fibromatosis. J Clin Periodontol 2006; 33: 393–400

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