Drug induced gingival enlargement.


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this ppt describes the drugs related to gingival enlargement and some of the mechanisms involved in it

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Drug induced gingival enlargement.

  1. 1. Presented by Guru Ram Tej K Postgraduate Mamata dental college
  2. 2.  INTRODUCTION  CLASSIFICATION  PREVALENCE  MEASUREMENT OF ENLARGEMENT  DRUGS CAUSING ENLARGEMENT  ANTI CONVULSANTS  Pharmaco-dyanamics of anti epileptic drugs  Pharmaco kinetics of phenytoin  Pathogenesis of phenytoin induced gingival enlargement
  3. 3.  IMMUNO-SUPPRESSANTS  Cyclosporine  Pathogenesis  Clinical manifestations  Histological features  CALCIUM CHANNEL BLOCKERS  Pathogenesis  Clinical manifestations  MANAGEMENT OF GINGIVAL ENLARGEMENT  Medical management- drug substitution  Gingivectomy  Laser  CLINICAL RELEVANCE and CASE REPORTS
  4. 4.  Drug induced gingival enlargement  Problems  Risk factors  Age predilection
  5. 5.  Based on location and distribution  Localized  Generalized  Marginal  Papillary  Diffuse  Discrete
  6. 6. Based on etiologic factors and pathologic changes. Inflammatory enlargement  Acute  Chronic Drug induced gingival enlargement  Enlargements associated with systemic diseases or conditions  Conditioned enlargement  Pregnancy  Puberty  Vitamin- C deficiency  Plasma cell gingivitis  Pyogenic granulosa (non-specified conditioned enlargement)  Systemic diseases causing gingival enlargement  Leukemia  Granulomatous diseases(Wegener’s granulomatosis, sarcoidosis
  7. 7.  Neoplastic enlargement  Benign tumors        Malignant tumors Squamous cell carcinoma Epulis Malignant melanoma Fibroma Sarcoma: Papilloma Fibrosarcoma Lymphosarcoma Peripheral gaint cell granuloma Reticulum cell sarcoma Central gaint cell granuloma Kaposis sarcoma Renal cell carcinoma Leukoplakia Hypernephroma Gingival cyst Chondrosarcoma  Other benign masses like nevus, myoblastoma, hemangioma, neurilemmoma, neurifibroma, m ucoceles, ameloblastoma  False enlargement
  8. 8. Bokenkamp A. Bohnhoest B Grade 0 -No signs of gingival enlargement Grade 1 -Enlargement confined the IDP Grade 2 -Enlargement involves papilla and marginal gingiva Grade 3 -Enlargement covers three quarters or more of crown.
  9. 9. Angel poulus and Goaz –1972 According to the amount of gingiva covering anatomic crown • Grade 0 – No hyperplasia • Grade 1 – Hyperplasia covering cervical 3rd of ant. Crown • Grade2 – Hyperplastic gingiva extending the middle 3rd of anatomic crown of Ant. Teeth • Grade 3 – Hyperplastic gingiva covering > 2/3rd of crown of anterior tooth. • Nery et al (1995) modified by adding interproximal area
  10. 10. McGaw et al (1987) Degree of gingival enlargement can be scored as Grade 0: No signs of inflammation Grade 1: GE confined to interdental papilla Grade 2: Enlargement involves papilla &marginal gingiva. Grade 3: Enlargement covers three quarters or more of crown.
  11. 11. Based on assessment of plaster study cast Seymour et al –1985 Included both thickening and encrochment. GO assessed on a plaster model in upper and lower segments. Grade o – Normal Grade 1- Thickening from normal upto 2mm, Grade 2 – Thickening >2mm
  12. 12. Based on Histopathologic examination Barak et al (1985) Grade 1 – Normal width of epithelium 0.30 to 0.50 mm Grade 2 – Slight hyperplasia 0.50 to 1.5 mm Grade 3 - moderate hyperplasia1.50 to 3.0 mm Grade 4 – severe hyperplasia 3 to 4 mm
  13. 13. Miranda and Brunet –2001 Measured GO in buccolingual direction both for buccal and lingual/palatal papilla. 0 – papillary thickness < 1 mm 1 – papillary thickness 1-2 mm 2 – papillary thickness > 2 mm
  14. 14.  Gingival overgrowth has been associated with the use of erythromycin Valsecchi et al in 1992 Lombardi et al in 1989 Oral contraceptives  Norethindrone  Mestranol Response Seymour et al in 1998
  15. 15.  Variation in inter-patient & intra patient pattern  Predilection for anterior gingiva  Higher prevalence in children  Onset within 3 months  Change in the gingival contour leading to modification of gingival size  Enlargement first observed at interdental papilla  Not associated with attachment loss  Reduction in dental plaque can limit severity of lesion.
  16. 16. Seymour et al 1996 Multifactorial model
  17. 17.  Inflammation from bacterial plaque is involved in the pathogenesis of          DIGH An increased amount of GAGs is involved in the pathogenesis of DIGH Immunoglobulins are involved in the pathogenesis of DIGH Phenotvpical differences within gingival fibroblasts are involved in the pathogenesis of DIGH EGF is involved in the pathogenesis of DIGH The pharmacokinetics of inducing drugs and the gingival binding affinities of these drugs are a determinate in the pathogenesis of DIGH The activation of collagenase is involved in the pathogenesis of DIGH Disruption of fibroblast cellular Na/Ca flux - The influence of inducing drugs on gingival fibroblast cellular sodium/calcium flux is involved in the pathogenesis of DIGH Folic acid is involved in the pathogenesis of DIGH An hypothesis is proposed that involves a combination of several of the above hypotheses
  18. 18. MODEER & DAHLOFF divided 59 PHT-treated noninstitutionalized children into three groups 16 intensive 13 moderate 30 no preventive None of the subjects in the intensive program developed GH Dental prophylaxis and "good" oral hygiene can reduce or prevent the expression of DIGH
  19. 19.  Dahloff- ferret- decreased degradation within the fibroblasts  GH represents neither hypertrophy, hyperplasia nor fibrosis, but is an example of uncontrolled growth of a connective tissue of apparently normal cell and fiber composition
  20. 20.  Smith et al IgA in the serum and the oral cavity  Setterstorm et al – IgG, IgA and IgM  Dahloff -T cells  It appears that immunoglobulins may be more a marker than a cause of local cellular immune reactions occuring within the gingiva during periodontal disease
  21. 21.  Hassell and Gilbert in 1983  Hassell and Stanek in 1974  Seymour et al in 2005  Genetic heterogenecity  Differences in cellular ion flux  Receptor binding affinity  Cellular turnover
  22. 22.  Modeer et al- 2pts- 9 months  EGF Receptor metabolism  The steady-state level of EGF-receptor mRNA increased significantly in the cultured fibroblasts derived from the non-responder but decreased significantly in the responder.  Modeer and Anderson
  23. 23.  Salivary glands- Noach et al  Woodbury et al twice in epileptic- serum level  Conrad et al and Mcgaw et al
  24. 24.  Hassell 1982- synthesis of the procollagenase  LIU & BHATNAGAR determined that Phenytoin interfers with prolyl hydroxylase, an enzyme required for the post translational hydroxylation of prolyl residues in the synthesis of collagen  Murphy 1987 and Meikle in 1989- Plasminogen- plasmin MMP cascade
  25. 25.  Kobayashi et al- the proliferation rate of fibroblast- inhibition of calcium uptake  Colombani et al- Cs A
  26. 26.  Drew et al in 1987- folate therapy  Vogel et al in 1980 and Ariel et al- association of the phenytoin and the folate
  27. 27. Phenytoin  Introduced by Merritt & Putnam in 1938  Used to control seizures in patients with epilepsy  Most commonly used because of low cost ,easy availability & effective  Hyperplasic changes were first reported in 1939 by Kimball
  28. 28. Selectively depress the motor cortex of CNS Blocks voltage dependent Na channels Limit the progression of neuronal excitation Blocks high frequency firing seen in seizures
  29. 29.  Shafer (1984) reported that the optimal rate of cell growth at phenytoin concentration 5µg/ml  Hassell & page (1992) demonstrated GO in response to ‘5-Parahydroxyphenyl-5-phenylhydantoin’  Phenytoin sensitive sub population of fibroblasts
  30. 30.  Soreness and tenderness  Initial involvement of interdental papilla  Granulated lobules or pebbly surface
  31. 31.  Acanthosis of squamous epithelium  Numerous young capillaries and fibroblasts and irregularly arranged collagen fibrils with occasional lymphocytes.
  32. 32.  Cyclosporine, a metabolite of fungal species Beauveria Nivea (Borel et al 1976)  The first human clinical trials of CsA in human kidney allograft recipients by CalneV and Powles' groups in 1978  Cyclosporine induced gingival overgrowth was first reported by Rateischak – Pluss et al.
  33. 33.  Specifically, Cyclosporin A inhibits interleukin-2 (IL-2) synthesis, hence inhibits the ability of cytotoxic T lymphocytes to respond to IL-2 at oral dosages of 10-20 mg/kg.  Inhibits the activation of macrophages and preventing the production of IL-1 receptors on the surface of T-helper cells.  Cyclosporin A is water insoluble and absorption depends on the presence of bile salts.
  34. 34.  Wyosocki et al 1983 by fibroblasts sensitive to cyclosporine  Schincaglia et al 1992 – the anti-collagenase activity by decreasing MMPase  Enhanced macrophage platelet derived growth factor gene expression promotes fibroblast proliferation and production of extracellular matrix constituents. Plemonas et al 1996
  35. 35.  Pennu et al 1992 - patient expressing HLA DR1 have protective role against gingival overgrowth from cyclosporine A.
  36. 36.  Affects more frequently to children's & females.  Enlarged gingival tissue is soft, red or bluish red, extremely fragile & bleed easily on probing.  Overgrowth is restricted to width of attached gingiva
  37. 37.  Acanthosis and parakeratinization of the epithelium with pseudoepitheliomatous proliferation.  Inflammatory cells are seen  Mariani et al found that the basal and spinous layers of epithelium show distinct dilatation of the intercellular spaces, characteristic of disease related overgrowth.
  38. 38.  First reported case of GH induced by nifedipine was reported by Ramon et al  Interdental papilla become enlarged  In many areas its shows ulcerations & BOP  False periodontal pockets without bone loss
  39. 39.  Fujii et al (1991) tested the effect of Ca channel blockers on cell proliferation, DNA synthesis and Collagen synthesis  Lucas et al and Jones et al(1994) suggested that GO results from overproduction of extracellular ground substance characterized by increased presence of GAG and collagen  Barelay (1999) noted that the collagenolytic effects of inflammatory cells and synthesis of collagenase are Ca dependent cellular events
  40. 40.  Nifedipine induces gingival hyperplasia in rats through inhibition of apoptosis, which prolongs cell life……………..(Shimizu et al,2001) Nifidepine 5.— reductase activity Stimulates synthesis of DHT from Testosterone in gingival fibroblast Production of large amount of collagen + Inactive from of collagenase Gingival overgrowth
  41. 41.  Epithelium exhibits para keratosis, proliferation and elongation of rete pegs that extends into lamina propria.  Increase in epithelial width, infiltrates of lymphocytes and plasma Nander wall et al 1985  Fibroblasts contain strongly mucopolysaccharides and secretory granules.
  42. 42.  Key strategies in gingival enlargement. periodontal surgical procedures Plaque control medical management multidisciplinary dental care
  43. 43.  CCB’s : Nifedipine with Isradipine ( 20 mg BD) ….(westbrook in 2001) ACE Inhibitors like Captopril (12.5 to 50mgBD), Enalapril (2.5to20 mg OD) to control hypertension  Phenytoin with Phenobarbital(60 mg TDS), Primidone ( 100mg TDS) Carbamezepine (200-400mg TDS) Valproic acid (200-500mg TDS)  Cyclosporin A with Tacrolimus (0.15 to 0.20/kg/d) Rapamycin
  44. 44.  Gingivectomy  Excision of gingiva. Simple & quick technique
  45. 45. Advantages  Permits an adequate contouring of the tissue  Controls hemorrhage Disadvantages  Unpleasant odour  Irreparable damage to bone  Use limited to superficial procedures  Heat generated can cause tissue damage & loss of periodontal support.
  46. 46.  Co2 lasers used for excision of gingiva Advantages  Excellent soft tissue ablation  Haemostatic characteristic Disadvantages  Healing is delayed  Requires precautionary measures  Application to root surface or alveolar bone causes carbonization & major thermal damage
  47. 47.  Silverstain et al 1995 – Nifidepine induced gingival enlargements has been reported around dental implants  Yoon Angela et al in 2006 - Myeloid sarcoma occurring concurrently with drug induced gingival enlargement  Frederic Duffau in 2007 - Gingival enlargement originating from medication and tooth migration
  48. 48.  Ronald S Brown, William T Beaver, and William K Bottomley: On the mechanism of drug induced gingival hyperplasia. J Oral Pathol Med 1991; 20: 201-9  Seymour RA and Heasmen PA: Drugs and the Periodontium. J Clin Periodontol 1998; 15: 1-16  Bettina Dannewitz: proliferation of the gingiva: aetiology risk factors and treatment modalities for gingival enlargement. Quintessence int. 2007;4(2): 83-92  Bhardwaj Amit, Bhardwaj Verma Shalu: Gingival enlargement induced by anticonvulsants, calcium channel blockers and immunosuppresants: a review: Int Res J Pharm; 2012, 3(7)  Valsecchi R, Cainelli T. Gingival hyperplasia induced by erythromycin. Acta Derm Venereol (Stockh) 1992;72: 157.  Roderick I Marshall, P Mark Bartold: A clinical review of drug induced gingival overgrowths: Aus dent Jour. 1999: 44: 4.  Thomas M Hassell and Arthur F Hefti; Drug induced gingival overgrowth: Old Problem, New Problem: critical reviews in Oral Biology and Medicine: 1991: 2(1): 103-137  P M Camargo, Philip R Melnick, Flavia Q M Pirih, R Lagos & Henry H Takei: Treatment of drug induced gingival enlargement: aesthetic and functional considerations. Perio 2000,2001: 27, 131-138
  49. 49.  Kumar and Kumar et al: Drug induced gingival hyperplasia: an updated        review: Int J Pharm & Toxic Science1(1): 2011, 34-42 Omid Panahi, Mohsin Seyed Arab, Kevin Tamson: Amlodipine induced gingival hyperplasia: pakisthanoral dental journal 2010: 30(2) Barbara Anne Taylor: Management of drug induced gingival enlargement: Aust Prescr 2003; 26: 11-13 Miranda J, Brunet L, Roset et al: Reliability of two measurement indices for gingival enlargement: J O P 2012: 47(6): 776-782 Yoon Angela, Pulse Carla et al: Myeloid sarcoma occurring concurrently with drug induced gingival enlargement:J O P 2006: 77(1): 119-122 Alaaddinoglu Emine Elif, Karabay Gulten et al: Apoptosis in cyclosporine A induced gingival overgrowth: A histological study: J O P 2005: 76(2): 166-170 A defect in fibroblasts from an unidentified syndrome with gingival hyperplasia as the predominant feature: B Johnson, M E Guindy, William et al: J O P 1986: 21: 403-413. Johnson BD, Narayanan AS. Pieters HP, Page RC: Effect of cell donor age on the synthetic properties of fihrohlasts obtained from phenytoininduced gingival hyperplasia. J Periodont Res 1990; 25: 74-80.
  50. 50.  Frederic Duffau: Gingival enlargement originating from      medication and tooth migration: quntiscence international, 2007; 4(2): 109-113 Romanos GE. Schroter-Kermani C. Hinz N, Bernimoulin J-P: Distribution of fibronectin in healthy, infiamed and druginduced gingival hyperplasia. J Oral Pathol Med 1992; 21: 256260. Pradhan S, Mishra P, Joshi S: Drug induced gingival enlargement – A review Akhthar: Drug induced gingival enlargement, Bangladesh dental journal 2012 Fatema Akhter and Shaheen:Drug induced gingival enlargement – A review; Bangladesh J Physiol Pharmacol 2009; 25(1&2): 26-29 The pathogenesis of drug induced gingival overgrowth: R A Seymour et al J C P 1996. 23(3), 165-175