Recurrent Idiopathic Gingival Enlargement in an Olive Baboon (Papio Anubis)

Recurrent Idiopathic Gingival Enlargement in an Olive Baboon (Papio anubis)

Krishnan Kolappaswamy,1,2,3,* Steven Shipley,1,2 Mark A Reynolds,5 Charles McLeod,1 and Louis DeTolla1, 2,3,4

We here describe a case of recurrent gingival enlargement in an olive baboon (Papio anubis). This baboon (a male breeder that had not undergone any experimental procedures) also had shown mild gingival enlargement the 2 y prior to the current lesion. Clinical and histopathologic findings confirmed a diagnosis of idiopathic gingival enlargement.

The term ‘gingival enlargement’ describes abnormal, exces- tomy 2 y prior to the present report. The baboon was housed sive growth of the periodontal tissues.11 Although gingival in an aluminum enclosure in a room with female baboons (also enlargement is seen and studied in nonhuman primates only in individual enclosures). The male baboon was intermittently rarely, it has been extensively evaluated in humans.15 The pair-housed in his home cage with female baboons for breeding etiology in humans is multifactorial and includes age, genetic purposes; when breeding was complete, the female baboons predisposition, and induction due to drugs (for example, cy- were returned to their individual enclosures. The room tem- closporine, dihydropyridines, calcium channel blockers, sodium perature and humidity was maintained at 68 to 72 °F (20.0 to valproate, erythromycin) or plaque.6,13,14,22,29 22.2 °C) and 30% to 70%, respectively, on a 12:12-h light cycle. Numerous case reports of gingival overgrowth in humans All animals received commercial high-protein primate diet twice have been described during the past decade, but case reports daily, daily additional fruit or vegetable food enrichment, and from nonhuman primates are rare. For example, papillary water ad libitum. gingival enlargement occurred in baboons used to study On initial observation, the baboon was bright, alert, and ac- the physiologic effects of estrogen and progesterone during tive but had difficulty closing his upper lip over the incisors pregnancy.20 The oral anatomy and radiographic presentation and canine teeth, due to the presence of proliferative gingival of baboons exhibits a striking similarity to human dentition.1 tissue. However, the baboon did not show any abnormal be- Similar to that in humans, gingivitis in baboon is characterized havior, such as mouth-breathing or abnormal chewing behavior. by the presence of plaque, calculus, and proliferation of pocket The baboon appeared to be eating normally and had normal epithelium.1,9,18 Baboons also exhibit an age-associated increase urine and feces in the cage pan. The baboon was sedated with in prevalence and severity of periodontitis.9 There are also case ketamine (10 mg/kg IM; Ketaset, Fort Dodge Animal Health, reports of gingival enlargement from rhesus macaques (Macaca Fort Dodge, IA) for examination. On physical examination, mulatta),30 mustache guenon monkeys (Cercopithecus cephus),23 the baboon weighed 35.6 kg and had a heart rate of 82 bpm, stump-tailed macaques (Macaca arctoides),25,26 baboons (Papio rectal temperature of 102.8 °F (39.3 °C), and respiration rate of ssp.),9 gorillas (Gorilla gorilla),5 ferrets (Mustela putorious furo),27,28 24 breaths per minute. No abnormal heart or lung sounds were and dogs (Canis familiaris).21 Most of these reported cases in- ausculted. The peripheral lymph nodes and remainder of the volved animals that had undergone experimental treatments, physical examination were normal. which induced the lesions. Oral examination revealed moderate plaque with mild We present a case report of recurrent idiopathic gingival calculus accumulation, most severe over the upper and lower enlargement in a male olive baboon (Papio anubis) that has not incisors and canines. Generalized diffuse gingival enlargement undergone experimental manipulation. with a smooth surface was noticed on both the maxilla and mandible, involving all canine and incisor teeth. There was Case Report no gingival enlargement in the premolar or molar areas. The A 14-y-old male baboon was reported to the clinical veteri- overgrowth partially extended over the labial surface of the narian for difficulty in labial closure. This animal was part of a upper incisors and canines (Figure 1). Each tooth was evaluated research project approved by the Institutional Animal Care and for the presence of periodontal pockets by using a 15-mL peri- Use Committee at the University of Maryland School of Medi- odontal probe. Periodontal probing verified pseudopocketing cine. The animal in question was used for breeding purposes consistent with the degree of gingival enlargement. The dental only and had not undergone any experimental procedures or radiograph obtained prior to surgery was unremarkable. The manipulations beyond breeding. The baboon had a history of oral examination also revealed mild gingivitis in other areas but mild gingival enlargement that had been treated by gingivec- was otherwise within normal limits. The gingival overgrowth prevented normal closure of the mouth by not allowing the mandibular canines to seat in the maxillary diastema between Received: 03 Feb 2010. Revision requested: 04 Mar 2010. Accepted: 12 Apr 2010. the canine and incisor teeth. 1Program of Comparative Medicine, Departments of 2Pathology, 3Epidemiology and Surgical excision of the excessive gingival growth was chosen Preventive Medicine, and 4Medicine (Division of Infectious Diseases) School of Medicine, and 5Department of Periodontics, Dental School, University of Maryland, Baltimore, as treatment, and blood was drawn for preoperative evalua- Maryland. tion. The results of the biochemical profile and complete blood *Corresponding author. Email: [email protected]

860 Gingival enlargement in baboon

Figure 2. Gingival tissue showing epithelial enlargement with strati- fied squamous epithelium. The dermal ridges are irregular and demon- strate rete pegs interdigitated with overgrown subepithelial connective tissue.

Figure 1. Diffuse gingival enlargement with smooth surface on both tion. This recurrent enlargement may be due to chronic exposure the maxilla and mandible, involving all canine and incisor teeth. to dental plaque and calculus, which may contribute to gingival enlargement, as occurs in dogs and humans.3,15 The incidence count were within normal limits (data not shown), and surgical of gingival enlargement in dogs is increased in various breeds excision of the excessive tissue was scheduled. On the day of and after drug therapy, such as with anticonvulsants, calcium the procedure (approximately 2 wk after the initial evalua- blocking agents and immunosuppressive agents.31 Gingival tion), the baboon was sedated with 10 mg/kg ketamine IM, enlargement due to phenytoin and phenytoin metabolites has and anesthesia was mask-induced with 3% isoflurane. After been reported infrequently in cats.8 intubation with a 7.5-mm endotracheal tube, anesthesia was As in the present report, a previous study on olive and maintained with 1.5% to 2.5% isoflurane in 100% oxygen (1 to gelada baboons found that gingival inflammation (gingivitis) 2 L/min). Excessive gingival tissue was resected back to an ap- occur with no evidence of periodontal pocketing or bone loss.9 proximately normal gingival margin location was performed by However, similar to humans, chronic gingival inflammation using a no. 15 scalpel blade while maintaining an anatomically in nonhuman primates can lead to periodontal pocketing and 15 beveled gingival margin. Supra- and subgingival plaque were attachment loss (periodontitis), as previously reported.1,24 The removed by using hand instruments. At this point anesthesia baboon described in the current report had extensive tissue was discontinued, and the baboon recovered in its home cage. fibrosis with inflammatory infiltrate mainly consisting of plasma For postoperative analgesia and antibacterial prophylaxis, the cells, lymphocytes, and macrophages and vascular and collagen baboon received buprenorphine (0.02 mg/kg IM twice daily proliferation, as noted previously in baboons with similar condi- for 2 d; PharmaForce, Columbus, OH), carprofen (4.4 mg/kg tions.24 Gross lesions in the present case were more localized to IM once daily for 5 d; Rimadyl, Pfizer Animal Health, New the incisors and canines, which also tend to be the more reactive York, NY), and clindamycin (11 mg/kg IM twice daily for 5 d; regions in humans. Hospira, Lake Forest, IL). Softened diet was provided until the Age, local factors, and host response also may play a role baboon was observed eating hard biscuits regularly. in gingival disease in baboons17 and cannot be ruled out as Two weeks after the procedure, the gingiva exhibited excellent possible contributing etiologies in this case. Alternatively the healing and showed a thin margin of redness and progressive present findings may correlate to the form of gingival enlarge- reepithelialization of gingiva. Healing was complete by 4 wk ment known as hereditary gingival fibromatosis, a condition after surgery. Histopathology of the excised gingival tissue that can occur in humans as either isolated disease or as a showed dense collagenous connective tissue fibrosis expanding part of number of syndromes or chromosomal abnormalities.7 and elevating the submucosa, with segmental mucosa indicative Multiple macaque species (M. mulatta,16 M. fascicularis,10 and of gingival enlargement and no evidence of neoplasia or active M. arctoides12) have been used in studies in which gingivitis infection noted. The volume of subepithelial connective tissue and plaque accumulation were induced through provision of a was consistent with gingival overgrowth (Figure 2). softened diet. Variation was present in both lesion location and the histopathologic composition of inflammatory infiltrate. The Discussion prevention and management of recurrent gingival enlargement This case report describes recurrent gingival enlargement in a can include complete periodontal prophylaxis, with supra- and baboon that also had moderate plaque and calculus accumula- subgingival removal of calculus every 3 mo, and topical appli-

861 Vol 49, No 6 Journal of the American Association for Laboratory Animal Science November 2010 cation of 0.12% chlorhexidine.2,4,19 The baboon we report here 16. Listgarten MA, Ellegaard B. 1973. Experimental gingivitis in the will receive regular periodic oral examination, with periodontal monkey: relationship of leucocyte counts in junctional epithelium, prophylaxis and resection of recurrent gingival enlargement sulcus depth and connective tissue inflammation scores. J Peri- as needed to maintain appropriate gingival contour. Further odontal Res 8:199–214. 17. Miller DR, Aufdemorte TB, Fox WC, Waldrop TC, Mealey BL, studies should be directed to the specific etiologies leading to Brunsvold MA. 1995. Periodontitis in the baboon: a potential gingival enlargement in humans and animals. model for human disease. J Periodontal Res 30:404–409. 18. Page RC, Simpson DM, Ammons WF. 1975. Host tissue response References in chronic inflammatory disease IV. The periodontal and dental 1. Avery BE, Simpson DM. 1973. The baboon as a model system for status of a group of aged great apes. J Periodontol 46:144–155. the study of periodontal disease: clinical and light microscopic 19. Pilatti GL, Sampaio JE. 1997. The influence of chlorhexidine on observations. J Periodontol 44:675–686. the severity of cyclosporin A-induced gingival overgrowth. J Peri- 2. Boraz RA. 1989. Dental considerations in the treatment of odontol 68:900–904. Wiskott–Aldrich syndrome: report of case. ASDC J Dent Child 20. Reynolds MA, Aberdeen GW, Pepe GJ, Sauk JJ, Albrecht ED. 56:225–227. 2004. Estrogen suppression induces papillary gingival overgrowth 3. Carranza FA Jr, Hogen EL. 2001. Gingival enlargement. In: New- in pregnant baboons. J Periodontol 75:693–701. man MG, Takei HH, Carranza FA Jr, editors. Carranza’s clinical 21. Rost DR, Baker R. 1978. Gingival hyperplasia induced by sodium periodontology. Philadelphia (PA): WB Saunders. diphenylhydantoin in the dog: a case report. Vet Med Small Anim 4. Dongari-Bagtzoglou A, Research, Science, and Therapy Commit- Clin 73:585–587. tee, American Academy of Periodontology. 2004. Drug-associated 22. Seymour RA, Thomason JM, Ellis JS. 1996. The pathogenesis of gingival enlargement. J Periodontol 75:1424–1431. drug-induced gingival overgrowth. J Clin Periodontol 23:165– 5. Fagan D, Oosterhuis J. 1979. Gingival hyperplasia induced by 175. diphenylhydantoin in a gorilla. J Am Vet Med Assoc 175:960– 23. Sheldon WG. 1967. Fibrous gingival hyperplasia of a mustache 961. guenon monkey (Cercopithecus cephus). Lab Anim Care 17:140– 6. Fourtounas C, Vlachojannis JG. 2009. Gingival hyperplasia and 143. calcium channel blockers. J Clin Hypertens (Greenwich) 11:111. 24. Simpson DM, Avery BE. 1974. Histopathologic and ultrastruc- 7. Hart TC, Pallos D, Bozzo L, Almeida OP, Marazita ML, O’Connell tural features of inflammed gingiva in a baboon. J Periodontol JR, Cortelli JR. 2000. Evidence of genetic heterogeneity for heredi- 45:500–510. tary gingival fibromatosis. J Dent Res 79:1758–1764. 25. Staple PH, Reed MJ, Mashimo PA. 1977. Diphenylhydantoin 8. Hassell TM, Page RC. 1978. The major metabolite of phenytoin gingival hyperplasia in Macaca arctoides: a new human model. (Dilantin) induces gingival overgrowth in cats. J Periodontal Res J Periodontol 48:325–336. 13:280–282. 26. Staple PH, Reed MJ, Mashimo PA, Sedransk N, Umemoto T. 9. Hodosh M, Povar M, Shklar G. 1971. Periodontitis in the baboon 1978. Diphenylhydantoin gingival hyperplasia in Macaca arctoides: (Papio anubis). J Periodontol 42:594–596. prevention by inhibition of dental plaque deposition. J Periodontol 10. Johnson NW, Hopps RM. 1975. Cell dynamics of experimental 49:310–325. gingivitis in macaques: the nature of the cellular infiltrate with 27. Steinberg AD, Allen PM, Jeffay H. 1973. Distribution and metabo- varying degrees of gingivitis. J Periodontal Res 10:177–190. lism of diphenylhydantoin in oral and nonoral tissues of ferrets. 11. Khera P, Zirwas MJ, English JC. 2005. Diffuse gingival enlarge- J Dent Res 52:267–270. ment. J Am Acad Dermatol 52:491–499. 28. Steinberg AD, Alvarez J, Jeffay H. 1972. Lack of relationship 12. Krygier G, Genco RJ, Mashimo PA, Hausmann E. 1973. between the degree of induced gingival hyperplasia and the Experimental gingivitis in Macaca speciosa monkeys: clinical concentration of diphenylhydantoin in various tissues of ferrets. bacteriologic and histologic similarities to human gingivitis. J J Dent Res 51:657–662. Periodontol 44:454–463. 29. Thomason JD, Fallaw TL, Carmichael KP, Radlinsky MA, Calvert 13. Lafzi A, Farahani RM, Shoja MA. 2007. Phenobarbital-induced CA. 2009. Gingival hyperplasia associated with the administration gingival hyperplasia. J Contemp Dent Pract 8:50–56. of amlodipine to dogs with degenerative valvular disease (2004- 14. Lauer G, Mai R, Pradel W, Proff P, Gedrange T, Beyer J. 2006. 2008). J Vet Intern Med 23:39–42. Influence of cyclosporin A on human gingival keratinocytes in 30. Ulland BM, Sibinovic S, Innes JR. 1970. Gingival hyperplasia in vitro. J Craniomaxillofac Surg 34 Suppl 2:116–122. a Macaca mulatta. Lab Anim Care 20:756–758. 15. Lewis JR, Reiter AM. 2005. Management of generalized gingival 31. Waner T, Nyska A, Nyska M, Pirak M, Sela M, Galiano A. 1988. enlargement in a dog–case report and literature review. J Vet Dent Gingival hyperplasia in dogs induced by oxodipine, a calcium 22:160–169. channel blocking agent. Toxicol Pathol 16:327–332.

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