/ Ciin Pcriodonto! 1997; 24: IRO-imPiinU'cl in Denmark . All rights rcscrwd

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H e a l periodontologyISSN 0303-6979

Vigabatrin-induced gingivalovergrowth

Joseph Katz\ Navot Givol^,Gavriel Chaushu^, Shiomo Taicher^and Joshua Shemer^Departinents of, 'Oral Medicine, -Oral andMaxillofacial Surgery, ^Internal Medicine F,Sheba Medical Center, Tei iHashomer, Israel

Katz J. Glvol N, Chaushii G, Taicher S, Shemer J: Vigabatrin-induced gingivalovergrowth, J Clin Periodontol 1997; 24: 180-182, © Munksgaard, 1997,

Abstract, Vigabatrin is a relatively new medication used in the treatment of epi-lepsia. The present report concerns the use of vigabatrin by a 19-year-old wo-man. The patient manifested marked gingival overgrowth compatible clinicallyand histologically with the overgrowth induced by phenytoin, cyclosporine andcalcium channel blockers. This is the 1st report of vigabatrin-induced gingivalovergrowth. Clinicians should be aware of simiiar lesions in patients using newanticonvulsants.

Key words: vigabatrin; sabril; gingival overgrowth

Accepted for publication 10 May 1996

Vigabatrin (VGB), Sabril. is a relativelynew medication used to treat epilepsia.It is a structural analog of gamma-aminobutiric aeid (GABA) and servesas an enzyme-activated irreversible in-hibitor of GABA aminotransferase, theenzyme responsible for the calabolismof GABA. It causes aeverai-fold in-creases in the concentration of brainGABA. VGB is used to treat certaintypes of drug-resistanl or uncontrolledepilepsy (Mumford & Cahnon 1994,Wolf 1994). Known adverse reactions toVGB include emesis, loose stools, anor-exia, somnolence, fatigue, irritability,dizziness, headaches, depression andpsychosis. Microscopic vacuoiation (in-tramyelinic edema) in the brains oftreated rals, mice and dogs has alsobeen reported (Yarrington et al. 1993,Srinivasan & Richens 1994).

The present report concerns a patientwho manifested marked gingival over-growth, similar to that known to becaused by phenytoin, cyclosporine, cal-cium channel blockers, etc. while underUeatmenV with VGB, To our knowledge,this is the first report of an associationbetween VGB therapy and drug-in-duced gingival overgrowth.

Case Report

A 19-year-old woman was referred toone of the authors (JK) in July 1993 forevaluation of "swollen and bleedinggums" first noticed by her 1 month

earlier. Past medical history includedepilepsy with complex partial seizuressince the age of 5 years. Until March1993, she was treated with Benubid, Ur-amox and Celontin. Due to the diffi-culty in obtaining Celontin. she beganusing Sabril.

VGB therapy, 0,5 mg TID, was ad-ministered in March 1993. Good eon-trol of her seizures was established. InJuly 1993, the patient complained ofprogressive gingival overgrowth. Oralexamination revealed marked buccaland lingual gingival enlargement in theanterior maxillary and mandibular re-gions. The enlargement was more sig-nificant interden tally. Areas of acutegingivitis related to piaque depositswere also identified (Fig. 1),

In January. February and July 1994,biopsies of the gingivae were per-formed. Specimens were from the an-terior maxillary and mandibular areas.The biopsy showed widening of the epi-thelial layer with parakeratinized strati-fied squamous cell epithehum withelongated rete pegs. The connectivetissue was moderately densed with fociof chronic inflammatory cells (Fig. 2),The patient's neurologist was informed,but Sabri! was not substituted sinceVGB was the only successful drug tocontrol her seizures.

The initial treatment included plaquecontrol followed by scaling. Since gingi-val overgrowth showed no regression,gingivectomy was performed lo obtain

esthetic results and to enable the patienteasier plaque control. Follow-up untilApril 1995 revealed recurrency of thelesions.

Discussion

Drug-induced gingival overgrowth isfrequently associated with anlicon-vuisaots, cyciosporine and calciumchannel blockers (Dongari et al. 1993).Incidences vary widely between 0% to84% for phenytoin (Angelopouloa 1975,Hassel et al. 1990), 8% to 70% forcyclosporine (Deliliers et al, 1986,McGaw & Porter 1988, Ross et al,1989), and 15% to 2V'A, for calciumchannel blockers (Barak et al. 1987,Barclay & Seymour 1991). Such lesionsappear after several months of treat-ment and are characterized by iaflam-mation. Marginal gingiva overgrowth ismainly in the anterior region. No pre-cise pathogenic pathway has beenclearly identified. Proposed mechanismsinclude phenytoin-direct stimulation ofgingival fibroblasts or mast cells withsecondary fibroblastic involvement, in-active fibroblastic collagenase, increasein testosterone metabolites with result-ant overgrowth, cyoiosporine increasein either connective tissue or epitheliumby various immunologic mechanisms,calcium channel biockers stimulation offibroblast proliferation by rise in meta-bolic byproducts, and increased suscep-tibility to bacterial infection through

Gingival overgrowth 181

Fig. J. Anterior mandibular teeth showing vigabatrin-induced (gingival overgrowth.

Fig. 2. LOW power photomicrograph showing pesudoepitheliomatous hyperplasia with focalchronic inflammation.

immunosuppression (Dongari et al.

1993).The pharmacologic intraceiluiar ef-

fect is similar, i.e., inhibition of intra-cellular calcium ion infiux (King et al.1976, Seymour 1991). The managementis identical. Plaque control and pro-fessional cleaning are mandatory. Re-sective gingival procedures are oftenperformed to improve function, esthet-ics and access for home care (Liv-ingston 1970, Daley & Wysocki 1984,Hall 1990, Pihlsirom 1990, Seymour &Smith 1991). In our patient, gingival

overgrowth in the anterior region ap-peared shortly after VGB therapy wasinitiated. Professional cleaning afteradequate piaque control was followedby gingivectomy. The histopathologicappearance of the biopsy specimenshowed epithelial hyperplasia with focalchronic inflammation. These histologi-cal features are compatible with thehistopathological features of phenytoin.cyclosporine and calcium channelblockers gingival overgrowth.

Pathogenesis remains to be estab-lished. Recent studies suggest the pres-

ence of a non-neuronal GABA systemin the epithelial cells (Harty el al. I99i,Pietrini et al. 1994), The gingival pres-ence of such a system should be investi-gated. In conclusion, VGB may lead todrug-induced gingival overgrowth andclinicians should be aware of similarlesions in patients using new anticon-vulsants.

Zusammenfassung

Durch Vigabatrin induzierte, zaiindeckundeGingivahypertrophieDie Behandlung mil Vigabatrin stellt eioe re-lativ ncuc medikamentose Therapie dar. diebei der Epilepsiebehandlung Anwendungfindet, Bei dem hier vorliegenden Report gehtes um die Vigabatrinbehandlung einer 19Jahre altcn Frau, Bei der Patientin kam eszu zahndeckender Gingivahypertrophie, kii-nisch und histologisch vergleichbar mit der,durch Phenitoin, Cyclosporin und Kalzium-kaoalblocker induzierten Zahnfltischwuche-rung, Es handclt sich hier um den ersten Be-richt iiber eine, durch Vigabatrin induzierte,zahndeckcnde Hypertrophie der Gingiva,Der Kliniker sollte sich des Vorkommensahnlicher Lasionen bei Palienten bewuBtsein, die neue Antikonvulsiva einnehmen.

Resume

Hypertrophie gingivale induite par la vigciha-trineLa vigabatrine est un medicament rdative-ment neuf utilise dans le trailemcnt de I'epi-lepsie, Lc rapport present, concerne son utili-sation chez une femme agee de 19 ans. Lapatiente avait une hypertrophie gingivalemarquee comparable cliniquement ct histolo-giquement a celle induite par la phenyloine,la cyclosporine ct les bioqueurs du canal ducalcium, Ceci constitue le premier rapportsur I'hypertrophie gingivale induite par la vi-gabatrine, Les clinicicns devraienl faire at-tention a des lesions semblables chez les pa-tients utilisant dc nouveaux anticonvulsifs.

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Address:

Joseph KatzDepartment of Oral MedicineShaha Medica!Tel HashotnerIsrael