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Preeti Moda1, Aman Moda2, Pallavi Pandey3 1 Reader, Department of Periodontics, Government Dental College, Raipur, Chattisgarh, India 2 Reader, Department of Pedodontics, Guru Gobind Singh College of Dental Sciences, Burhanpur, Madhyapradesh, 3 Senior Lecturer, Department of Pedodontics, Career Dental College, Lucknow, U.P., India Address for Correspondence
Intr oduc tion: Gingiva l overgrowth, recognized since long as a deleterious side-effect of chronic phenytoin therapy,
whenever occurs, lasts throughout the period of drug therapy and is difficu lt to manage owing to its insidiously progressive nature, leading to frequent recurrences. Methods: This case report documents a case of severe gingival enla rge ment associated with periodontitis in a
patient under antiepileptic therapy, along with b rie f revie w of lite rature concerning etiopathogenesis, and provides a rational model for its clinica l manage ment. Conclusions: It is important that clinic ians become awa re of the potential etio logic agents of drug induced gingival
enlarge ment and its characteristic features in order to be able to prevent, diagnose and successfully manage it. Ke y wor ds: periodontitis; phenytoin; gingival enlargement; periodontal therapy
gingiva, along with reinfo rce ment of good home care Phenytoin is an anti-epileptic drug co mmon ly used as oral hygiene regimens and periodic professional a therapeutic agent in patients with ep ilepsy, either surgical e xc ision of hyperplastic gingivae. [4] alone or in comb ination with other anticonvulsant This case report clearly describes the challenges that oral and medica l health practit ioners face when effectiveness, low cost, availability, and frequency of developing appropriate prevention and treatment administration. Among the side effects of phenytoin programs for epileptic patients, particularly those therapy, gingival enlargement is a well-recognized adverse effect, occurring on average among mu ltid isciplinary planning for the prevention and approximately 50% of patients receiving this drug . treatment of gingiva l lesions in these medica lly [1] A summary of estimated prevalence rates for drug (anticonvulsants) -associated gingival enlarge ment is Figure 1- Phenytoin induced gingival enlarge ment- Figure 2- Preoperative intraora l vie w of the Although several studies have been conducted pathogenesis of this gingival lesion still is not CAS E HIS TORY
association between phenytoin-induced gingival A 20-year-old fe ma le reported to the outpatient enlarge ment and a variety of conditions, inc luding progressive swelling in the gums since one year. The accumulat ion, host genetic predisposition, and patient had been taking phenytoin over a period of reduced serum folate levels. [3] [Figure : 1] four years, for seizure control. Intraora l e xa mination revealed moderate-to-severe overgrowth of a firm, understanding etiopathogenesis of the condition. dense and fibrotic consistency that involved both the Drug-induced gingival hyperplasia may imp rove with ma xillary and mandibula r arches.[Figures: 2-3]Full- substitution of other drugs that min ima lly a ffect the mouth periodontal charting, including assessment of probing depth and clinical attachment level, revea led deep pockets throughout the mouth, and abundant surgery in all four quadrants utilizing an internal plaque and calculus deposits. The radiographic bevel gingivectomy [Figure :5]co mbined with open- findings, wh ich corroborated those of the clin ical flap debride ment.[Figure-6]The patient was fo llo wed e xa mination, revealed generalized alveolar bone loss. up regularly; no recurrence of gingival overgrowth was observed six months after the surgery. [Figures: Figure 3- Preoperative intraoral vie w of the Figure 5- Internal bevel gingivectomy procedure on Figure 4- Preoperative panora mic rad iograph of the Me dical and de ntal manage ment:
The patient init ially underwent phase 1 periodontal Histopathologic Findi ngs:
therapy that comprised scaling, root planning and The microscopic evaluation of these sections oral hygiene instructions. The neurophysician gradually tapered phenytoin over a period of one acanthotic epithelia with thin long rete ridges month replacing it with phenobarbitone. The patient e xtending into the connective tissue. The underlying was we ll co mpensated showing no episode of connective tissue showed dense wavy bu ndles of recurrent seizure activity. One month later Phase 2 collagen fibres containing numerous fibrocytes and fibroblasts. So me sections in the connective tissue e xhibited infiltration of chronic infla mmatory cells, a heterogeneity of the gingival fibroblasts . [7] Based few scattered mult inucleated giant ce lls and areas of upon this knowledge, a co mbined treat ment med ication adjustments is required for prevention and manage ment of phenytoin-induced gingival Figure 7- Frontal vie w of the ma xilla ry and mandibula r arches 2 wee ks after surgery Figure 9 - Photomicrograph of h istopathological specimen illustrating the presence of a thickened acanthotic epitheliu m with e longated rete ridges and Clin ical manifestation of gingival en large ment frequently appears within one to three months after initiat ion of treat ment with phenytoin .Gingival Figure 8- Frontal vie w of the ma xilla ry and overgrowth normally begins at the interdental mandibula r arches 6 months after surgery papillae and is more frequently found in the anterior segment of the labia l surfaces. Gradually, g ingival DISCUSS ION
lobulations are formed increasing the plaque retentive Gingiva l en large ment in individuals using phenytoin areas which in turn, pred ispose to the development first was described in 1939.[5] The prec ise and/or enhancement of the overgrowth. Disfiguring gingival overgrowth triggered by these medications is not only esthetically displeasing but often impa irs understood, although a number of hypothesis have nutrition and access for oral hygiene, resulting in an increased susceptibility to oral infection, ca ries, and Three significant factors, which are important in the e xpression of these gingival changes, and can be Severa l studies have demonstrated the benefits of a considered, are: drug variables, plaque-induced preventive periodontal progra m, inc luding a dental infla mmatory changes in the gingival tissues and prophylaxis and reinforce ment of oral hygiene at genetic factors – the latter determin ing the frequent intervals, for patients taking phenytoin.[9]A preventive dental progra m should be init iated for In the present case, the patient’s neurologist patients as soon as they begin taking phenytoin, prescribed phenobarbitone as a substitute for especially when periodontal attachment loss is phenytoin. Phenobarbital re mains a commonly present, because although gingival enlarge ment that prescribed alternative anti-epileptic medication that occurs can be treated, the alveolar bone loss is has some association with gingival overgrowth; however, compared to phenytoin, this side effect apparatus permanently. Recently, the feasibility of phenytoin substitution has increased with the addition Phenytoin withdrawal and scaling and root planing of a new generation of anticonvulsants such as reduced gingival hyperplasia and infla mmat ion lo matrigine, gabapentin, sulthia me, and topira mate. Reducing the dose of the drug or suppressing it and treatment was required to eliminate residual g ingival substituting another are the logica l options for overgrowth. The re ma ining e xcess tissue and calculus controlling gingival en large ment induced by anti- were re moved using a conventional flap a fter the physician determined the patient’s risk status in Phar mac ologic
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relation to proposed surgical procedures. After surgery, healing was uneventful and significant hyperplasia, and periodontal pockets) was observed. The patient was p laced on a ma intenance and follo w- up program to prevent recurrence of periodontitis and hyperplasia. A three month interval for periodontal ma intenance therapy has been recommended for patients taking drugs associated with gingival The maintenance progra m consisted of a med ical history update, re-evaluation of clin ical periodontal parameters, p rophyla xis, and addit ional instruction (Anticonvulsants)-Associated Gingiva l En large ment according to the most frequently reported Prevalence CONCLUS ION
theoretical re lationship. J Theor Bio l 1977;67:269- Current studies on the pathogenetic mechanism of phenytoin-induced gingival enlargement are focusing 4.Marshall RI, Bartold PM. A clinica l rev iew of on the direct and indirect e ffects of these drugs on drug-induced gingival overgrowth. Aust Dent J If possible, treatment is generally targeted on drug 5.Kimba ll OP. The treat ment of epilepsy with sodium diphenyl hydantoinate. J Am Med.Assoc. 1939; infla mmatory factors such as plaque and calculus. When these measures fail to cause resolution of the enlarge ment, surgical intervention is reco mmended. The present case reflects the co mple xity of managing Incidence, c lin ical features and histopathology. J Can cases of phenytoin-induced gingival en large ment associated with periodontitis and reinforces the need for mu ltid isciplinary treat ment care and more rational 7. Sey mour RA, Tho mason JM, Ellis JS. The pathogenesis of drug induced gingival overgrowth. J REFERENCES
8. Hallmon WW, Rossmann JA. The role of drugs in 1. Bro wn RS, Beaver WT, Bottomley WK. On the the pathogenesis of gingival over- growth. A collective revie w of current concepts. Periodontol hyperplasia. J Ora l Pathol Med 1991;20:201- 9. Hall EE. Prevention and treatment considerations in patients with drug-induced gingival enla rge ment. Informational paper: drug associated gingival enlarge ment. J Periodontol. 2004; 75:1424-31. 10. Pih lstrom BL. Prevention and treatment of 3.Voge l R.I.: Ging ival hyperplasia and folic acid deficiency fro m anticonvulsive drug therapy: A


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J. Am. Chem. Soc. 2000, 122, 11212-11218 Highly Enantioselective 1,2-Addition of Lithium Acetylide-EphedrateComplexes: Spectroscopic Evidence for Reaction Proceeding via a2:2 Tetramer, and X-ray Characterization of Related Complexes Feng Xu,* Robert A. Reamer,* Richard Tillyer, Jordan M. Cummins, Edward J. J. Grabowski, Paul J. Reider, David B. Collum,† and John C. Huffman‡ Cont

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