Littérature scientifique sur le sujet « Drug Induced Gingival Overgrowth, Laser »

There are many reasons for gingival hyperplasia in children. Mostly, proper oral hygiene is sufficient to achieve normal healthy gingiva. In some situations, however, gingival hyperplasia is drug induced or can be a manifestation of a genetic disorder. In the latter, it may exist as an isolated abnormality or as part of a syndrome. Gingival overgrowth is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components with various degrees of inflammation. The complex treatment of gingival overgrowth can include conservative therapy and traditional or laser gingivectomy

Gingival overgrowth/hyperplasia can be attributed to several causes, but drug-induced gingival overgrowth/hyperplasia arises secondarily to prolonged use of antihypertensive drugs, anticonvulsants and immunosuppressants. The management is complex in nature considering the multitude of factors involved such as substitution of drug strict plaque control along with excision of the tissue to be performed under local anesthesia as outpatient. In the recent times, the patient’s psychological fear of the treatment with the use of surgical blade and multiple visits has developed the concept of single visit treatment under general anesthesia incorporating a laser as viable option. The present case highlights the new method of management of gingival overgrowth.

ABSTRACT Gingival overgrowth is a well recognized, unwanted side-effect associated with three major drugs/drug groups – phenytoin, cyclosporine and the calcium channel blockers. Cyclosporine is a potent immunosuppressive compound that has been used increasingly in conjunction with kidney, heart and other transplants. Calcium channel blockers are widely used in medical practice for the management of cardiovascular disorders. Due to their wide range of use, gingival overgrowth is now a recognized side-effect associated with them. Here we discuss a case report dealing with severe gingival overgrowth induced by cyclosporine and amlodipine. A 36-year-old man who underwent renal transplant came with a chief complaint of generalized gingival swelling. He had very severe gingival overgrowth in both arches and required thorough scaling and oral hygiene instructions, followed by supportive periodontal therapy for 4 months, after which radical gingivectomy using electrocautery and CO2 laser was performed. The post operative results were excellent and there was no recurrence at 1 year follow-up.

Gingival overgrowth caused by drug is a well-documented unwanted side effect and mostly caused by Nifedipine. Newer generation calcium channel blocker, amlodipine, has been used with the increasing frequency to overcome the adverse effect of first and second generation dihydropyridine derivatives of Calcium Chanel Blocker. The pathogenesis of gingival enlargement is uncertain and the treatment is still largely limited to the maintenance of an improved level of oral hygiene and surgical removal of the overgrowth tissue. This article reports the amlodipine induced gingival enlargement and its treatment in a 60 years old hypertensive female patient.

La DIGO è stata per la prima volta descritta nel 1939 associata all'uso cronico del farmaco antiepilettico fenitoina. Attualmente, più di 20 farmaci sono associabili all’insorgenza della DIGO, appartenenti alla categoria degli anticonvulsivanti, immunosoppressori, Ca++ antagonisti. La DIGO si manifesta maggiormente nei soggetti di giovane età nelle regioni anteriori della cavità orale, e vede come fattore predisponente la cattiva igiene orale. Clinicamente si manifesta con un’iniziale interessamento delle papille interdentarie, estendendosi fino alla gengiva aderente marginale, non determinando una perdita d’attacco. Istopatologicamente si manifesta con un quadro d’ipertrofia, soprattutto a carico del tessuto connettivo sottoepiteliale, per l’eccessiva deposizione di matrice extracellulare di natura collagenica. Eziopatologicamente vede il coinvolgimento di più fattori, nonostante non sia stato identificato un modello univoco. La terapia della DIGO prevede la sostituzione del farmaco responsabile dell’insorgenza del quadro patologico, una terapia parodontale non chirurgica, ed una terapia chirurgica, caratterizzata da una gengivectomia a bisello esterno volta a ristabilire la corretta anatomia gengivale. In questo studio sono stati valutati parametri clinici relativi agli esiti postoperatori della terapia chirurgica laser assistita della DIGO, con particolare riferimento al dolore postoperatorio ed alla ricrescita clinica della malattia.

Thesis (M.S.)--University of North Carolina at Chapel Hill, 2009.
Title from electronic title page (viewed Sep. 3, 2009). "... in partial fulfillment of the requirements for the degree of Master of Science in the School of Dentistry Periodontology." Discipline: Periodontology; Department/School: Dentistry.

A fim de prevenir a rejeição do órgão transplantado pelo hospedeiro, se faz necessário o uso de drogas imunossupressoras, como a ciclosporina, que pode levar ao aparecimento de efeitos colaterais como hipertensão arterial, nefrotoxicidade, hepatotoxicidade, e hiperplasia gengival medicamentosa (HGM), que pode ser potencializada se bloqueadores de canal de cálcio como a nifedipina forem associados a fim de controlar a pressão arterial. A patogênese da HGM ainda é incerta, entretanto fatores como a presença de cálculo e placa, concentração plasmática da droga, idade e fatores hormonais podem influenciar as características clínicas e o desenvolvimento da HGM. Recentemente, alguns vírus têm sido associados com a HGM. O HPV (Papiloma Vírus Humano) tem sido associado com casos severos de HGM, enquanto que o EBV (Vírus Epstein-Barr) é associado ao aparecimento de desordens linfoproliferativas pós transplante, que se apresentam como HGM. O objetivo deste trabalho foi avaliar a freqüência e o grau da HGM em pacientes transplantados renais (TR), identificar o EBV e HPV na HGM destes pacientes, e correlacionar a HGM, índice de placa, presença de cálculo e presença do EBV e HPV nos pacientes TR. Foram examinados os prontuários de 58 pacientes TR atendidos no CAPEFOUSP, e os dados com relação à medicação imunossupressora em uso e presença ou ausência de HGM foram registrados. Foram contatados 15 pacientes TR, dos quais foram colhidos dados demográficos, história médica, drogas em uso e história dental. No exame intra-oral foram observados o índice de placa, grau da HGM e presença de cálculo. A HGM foi removida e enviada a Disciplina de Patologia Bucal para análise microscópica. Os espécimes removidos foram comparados com um grupo controle composto por 20 casos de hiperplasia gengival inflamatória. Ambos os grupos foram submetidos ao exame de rotina, enfatizando a presença de coilócitos e a análise molecular, com hibridização in situ para o EBV (sondas EBER e Lytic) e HPV (sonda de amplo espectro e tipos 6/11, 16/18 e 31/33 nos casos positivos para a sonda de amplo espectro). 42% dos pacientes apresentaram HGM grau 1, 50% grau 2 e 8% grau 3. Cálculo estava presente em 50% dos pacientes. O índice de placa médio encontrado foi de 72%. Todas as amostras gengivais removidas cirurgicamente apresentaram um quadro histopatológico compatível com HGM. Os coilócitos estavam presentes em 100% dos casos do grupo de estudo e em 80% dos casos do grupo controle. O HPV esteve presente em 20% dos casos do grupo de estudo e em 10% do grupo controle. O EBV estava presente em 100% dos casos do grupo de estudo e em 90% dos casos do grupo controle, para ambas as sondas, entretanto no grupo de estudo foi observada uma expressão maior do EBV, tanto em quantidade de células marcadas, como em áreas mais profundas. Concluímos que a maioria dos pacientes TR apresentou HGM leve a moderada; EBV foi encontrado em todos os pacientes TR, caracterizando uma infecção oportunista, enquanto que o HPV foi encontrado nas mesmas proporções nos pacientes TR e no grupo controle; não foi encontrada correlação entre índice da HGM, índoce de placa, presença de cálculo e presença do EBV e HPV.
In order to prevent graft rejection in organ transplantation, is necessary the use of immunosuppressive drugs, as cyclosporin, that has several side effects, such as high blood pressure, nephrotoxicity, hepatotoxicity and gingival overgrowth (GO), that can be increased if calcium channel blockers, such as nifedipine, are associated in order to control de blood pressure. The pathogenesis of GO is still uncertain, but some factors such as the presence of calculus and plaque, drug plasmatic concentration, age and hormonal factors can influence the clinical aspects and development of GO. Recently some virus have been associated to GO as well. HPV (Human Papilloma Virus) have been associated to severe cases of GO and EBV (Epstein-Barr Virus) have been associated to posttransplantation lymphoproliferative disorders presenting as GO. The aim of this work was to evaluate GO incidence and score in renal transplant patients (RTP), identify EBV and HPV in GO from RTP, and correlate GO, plaque score, presence of calculus, and presence of EBV and HPV in RTP. We reviewed 58 charts from RTP attending to Special Care Dentistry Center (CAPE-FOUSP). Immunosuppressant drugs and presence or absence of GO were registered. 15 RTP were asked to show up in order to be examined. We collected demographic data, medical history, drugs in use and dental history. In intra-oral exam we observed plaque score, GO score and presence of calculus. GO were removed and sent to Oral Pathology Department for microscopic analysis. GO was compared to a control group composed by 20 cases of inflammatory gingival hyperplasia and both groups were submitted to routine exam emphasizing the presence of koilocytes and to molecular analysis with in situ hybridization for EBV (EBER and Lytic probes) and for HPV (wide spectrum probe and 6/11, 16/18, 31/33 types in cases where wide spectrum were positive). 42% of the patients presented GO score 1, 50% score 2 and 8% score 3. Calculus were presented in 50% of the patients. The average of plaque score was 72%.All GO specimens removed had a histopathological exam compatible with drug induced gingival overgrowth. Koilocytes were presented in 100% of study group (SG) and in 80% of control group (CG). HPV were presented in 20% of the SG and in 10% of the CG. EBV was presented in 100% of SG and in 90% of CG, for both probes, but in SG it could be observed in deeper areas of the epithelium and in a more pronounced expression. We concluded that most RTP presented mild to moderate GO, EBV were found in all RTP, characterizing an opportunistic infection, while HPV were found in the same proportions than in the control group and there were no statistical correlation between GO, plaque score, presence of calculus and presence of EBV and HPV.

Gingival overgrowth can be an unpleasant side effect of the commonly prescribed medications nifedipine and cyclosporin. Integrins are transmembrane glycoproteins that mediate cell-to-cell and cell-to-extracellular matrix cell adhesion events. The aim of this study was to characterize epithelial cell integrin phenotype in drug-induced gingival overgrowth tissue. Human gingival biopsies of patients taking nifedipine, cyclosporin, or a combination of both medications were used. Integrins and their ligands were localized in frozen sections using immunohistochemistry. Comparisons between integrin expression in normal and the drug-induced gingival tissue were made. The drug-induced gingival overgrowth tissue exhibited an increase in suprabasal expression of integrins αvβ1, α5β1, and αvβ6 which is similar to the integrin expression during wound healing. The integrin αvβ6 was expressed, however, with similar frequency in both the control and the drug-induced gingival overgrowth groups. Fibronectin, a possible ligand for the α5β1 and αvβ6 integrins, was not only expressed within the connective tissue of all groups, but was also expressed around some of the basal keratinocytes of the control, nifedipine-, and cyclosporin-induced gingival overgrowth groups. No relationship between inflammation and integrin expression could be identified. The results suggest that the epithelium of drug-induced gingival overgrowth tissue exhibit certain changes in its integrin repetoire. This upregulation of certain integrins, which is consistent to one seen during wound healing, could result in controlling the formation of the connective tissue.

碩士
台北醫學院
口腔復健醫學研究所
89
Abstract The purpose of this study is try to compare the androgen receptor+ cell (AR) （﹪）,Th1/Th2 cytokine profile（﹪）:IL-2, IFN-γ, IL-4,IL-10,IL-13 in the patients with healthy periodontium（PD<3mm, age range30-47）,inflammatory tissues of patients with adult periodontitis（P） with PD>5mm,（n=15,age range28-55）,surgically extracted tooth group（S） with PD>9mm,（n=10,age range24-79）and nifedipine induced ginigval overgrowth（NIGO）with probing depth(PD)>5mm,（n=5,age range51-63）.After full ethical approval of patients was achieved , the clinical periodontal parameters - pocket depth（PD）, bleeding on probing（BOP）, and plaque control record were measured around the selected diseasd periodontal area. Gingival samples were harvested during periodontal surgery and fixed in buffered formalin. Gingival biopsies were further processed for immunohistochemical stain with primary antibody of AR,IL-2,IL-4,IFN-γ,IL-10,IL-13 antibody（Santa Cruz biotechnology, Inc. C.A. U.S.A.）by using LSAB® method（Dako） subsequently . The expression of AR,IL-2,IL-4,IFN-γ,IL-10,IL-13 positive cells was counted using grid scan by semiquantitative method. The Kruskall—Wallis test , Mann-Whitney U-test were employed for the statistical analysis. The results revealed that AR, IL-2 ,IL-4,IFN-γ,IL-10,IL-13 was intensively expressed in the nuclei of basal epithelial cells, spinosal cells ,endothelial cell ,inflammatory cells ,and gingival fibroblasts .Strong expression of AR,IFN-γ,IL-2,IL-4 were also found in the NIGO group. Percentage （﹪）of AR labeled cells were significantly higher in the NIGO group of epithelial cells and gingival fibriblasts（58.6+2.3；80.2+10.7） than in the periodontitis group （56.3+3.3；52.5+11.8）and control（38.5+4.6；37.4+11.3）(P<0.05).In the surgically extracted tooth group ,very strong expression of Th2 （IL-4,Il-10,IL-13）type cytokine were found in the inflammatory cell than the Th1（IL-2,IFN-γ） type cytokine .The immuno expression of NIGO group has trend toward to the Th1 type cytokine（IL-2:p<0.01）expression .In the periodontitis group after periodontal phase I therapy was found strongly expression of IFN-γin the inflammatory cell. It seems that as at the quiesence stage of periodontitis , periodontium has the tendency to develope to the direction of tissue repair . Based on these findings , we postulated that AR and cytokine profile might play an important role in the progression of periodontitis and overgrowth of gingiva in NIGO. Key words: gingival overgrowth, androgen receptor, periodontitis, immunohistochemistry, cytokine profile。