09_Cyclosporine and Amlodipine Induced Severe Gingival Overgrowth

9
34 JOHCD www.johcd.org January 2012;6(1) Cyclosporine and Amlodipine Induced Severe Gingival Overgrowth - Etiopathogenesis and Management of a Case with Electrocautery and Carbon-Dioxide(CO 2 ) Laser Rashmi Hegde 1 , Rahul Kale 2 , A Sanjay Jain 3 Contact Author Dr. Rashmi Hegde [email protected] J Oral Health Comm Dent 2012;6(1)34-42 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 CO 2 laser was performed. The post operative results were excellent and there was no recurrence at 1 year follow-up. Keywords: Cyclosporine, Amlodipine, Gingival overgrowth, Gingivectomy, Electrocautery, Carbon-dioxide (CO 2 ) laser CASE REPORT Journal of Oral Health Community Dentistry & INTRODUCTION G ingival overgrowth is a well rec ognized unwanted side-effect as sociated with three major drugs/ drug groups – phenytoin, cyclosporine and the calcium channel blockers. The preva- lence of this unwanted effect varies be- tween drugs, and a variety of risk factors have been identified in relation to the ex- pression of drug-induced gingival overgrowth(1). It has been estimated that gingival overgrowth occurs in about 50% of patients taking phenytoin, 25-80% of patients taking cyclosporine, and 15-20% of patients taking calcium channel blockers like Nifedipine and Amlodipine, but se- vere cases with nifedipine and amlodipine 1 MDS, Senior Lecturer, Dept of Periodontology and Implantology M.A.Rangoonwala College of Dental Sciences and Research Centre, Pune, Maharashtra, India 2 MDS, Senior Lecturer, Dept of Periodontology and Implantology, M.A.Rangoonwala College of Dental Sciences and Research Centre, Pune, Maharashtra, India 3 MDS, Professor Dept of Periodontology and Implantology, M.A.Rangoonwala College of Dental Sciences and Research Centre, Pune, Maharashtra, India alone, occur in less than 1 %(2, 3). Gingival enlargement is thought to arise from over- production of the ground substance formed by the fibroblasts (4). Cyclosporine is a potent immunosuppres- sive compound that has been used increas- ingly in conjunction with kidney, heart and other transplants, and has been reported to be better tolerated than conventional therapy such as corticosteroids and cyto- toxic drugs(5). To date, cyclosporine has been tested for treatment of insulin-de- pendent diabetes mellitus(6), Behcet’s syn- drome(7,8), Psoriasis (9), Systemic Lupus Erythematosus(10), and other diseases(9). The major adverse reactions to cyclosporine

description

09_Cyclosporine and Amlodipine Induced Severe Gingival Overgrowth

Transcript of 09_Cyclosporine and Amlodipine Induced Severe Gingival Overgrowth

  • 34 JOHCD www.johcd.org January 2012;6(1)

    Cyclosporine and AmlodipineInduced Severe Gingival Overgrowth -Etiopathogenesis and Managementof a Case with Electrocautery andCarbon-Dioxide(CO2 ) LaserRashmi Hegde1, Rahul Kale2, A Sanjay Jain3

    Contact Author

    Dr. Rashmi [email protected]

    J Oral Health Comm Dent 2012;6(1)34-42

    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 arewidely 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 transplantcame 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.

    Keywords: Cyclosporine, Amlodipine, Gingival overgrowth, Gingivectomy, Electrocautery,

    Carbon-dioxide (CO2) laser

    CASE REPORTJournal of Oral HealthCommunity Dentistry

    &

    INTRODUCTION

    Gingival overgrowth is a well rec

    ognized unwanted side-effect as

    sociated with three major drugs/

    drug groups phenytoin, cyclosporine and

    the calcium channel blockers. The preva-

    lence of this unwanted effect varies be-

    tween drugs, and a variety of risk factors

    have been identified in relation to the ex-

    pression of drug-induced gingival

    overgrowth(1). It has been estimated that

    gingival overgrowth occurs in about 50%

    of patients taking phenytoin, 25-80% of

    patients taking cyclosporine, and 15-20%

    of patients taking calcium channel blockers

    like Nifedipine and Amlodipine, but se-

    vere cases with nifedipine and amlodipine

    1MDS, Senior Lecturer,Dept of Periodontology and ImplantologyM.A.Rangoonwala College of Dental Sciences andResearch Centre, Pune, Maharashtra, India

    2MDS, Senior Lecturer,Dept of Periodontology and Implantology,M.A.Rangoonwala College of Dental Sciences andResearch Centre, Pune, Maharashtra, India

    3MDS, ProfessorDept of Periodontology and Implantology,M.A.Rangoonwala College of Dental Sciences andResearch Centre, Pune, Maharashtra, India

    alone, occur in less than 1 %(2, 3). Gingivalenlargement is thought to arise from over-production of the ground substance

    formed by the fibroblasts (4).

    Cyclosporine is a potent immunosuppres-

    sive compound that has been used increas-ingly in conjunction with kidney, heart andother transplants, and has been reported

    to be better tolerated than conventionaltherapy such as corticosteroids and cyto-toxic drugs(5). To date, cyclosporine has

    been tested for treatment of insulin-de-pendent diabetes mellitus(6), Behcets syn-drome(7,8), Psoriasis (9), Systemic Lupus

    Erythematosus(10), and other diseases(9).The major adverse reactions to cyclosporine

  • JOHCD www.johcd.org January 2012;6(1) 35

    therapy are nephrotoxicity, hepatoxicity,tremors, hirsutism, hypertension, mildanemia, gingival overgrowth and, in rare

    instances, lymphoma (11). Due to its vari-ety of uses, cyclosporine-induced gingivalovergrowth could become more common

    and thus of increasing interest to the peri-odontist. Of particular concern for the den-tal profession is the management of

    cyclosporine-induced gingival overgrowth,first reported in the dental literature in1983(12). Cyclosporin selectively inhibits

    T-cell function, while having a minimal ef-fect on humoral immunity (13).

    Gingival over growth is also commonlyassociated with the use of many of thecalcium channel blockers. Of this large

    group of drugs, the dihydropyridines arethe agents most frequently implicated (14).Amlodipine, a newer agent of

    dihydropyridine, used for treatment ofhypertension and angina, was first reportedfor causing gingival overgrowth as a side

    effect, by Seymour et al in 1994 (15).

    Approximately 2530% of patients medi-

    cated with cyclosporine experience this un-wanted effect at a level severe enough towarrant surgical reduction of the gingival

    tissues (16). An increased prevalence of thecondition occurs in patients concomitantlymedicated with amlodipine (17). (18). The

    effect of calcium channel blockers on theseverity of gingival overgrowth is nowlargely accepted (19) and appears to be re-

    lated to the plasma concentration of thedrug (20). A range of other risk factors forcyclosporine-induced gingival overgrowth

    has been identified (21) including age, sex,duration of therapy, gingival inflamma-tion, genetic factors like cytochrome

    P450

    ,CSA-HLA DR1,CSA-HLA DR

    2,CSA-

    HLA A19

    ,CSA-HLA B37

    and creatinine se-rum concentration. There is a wealth of

    literature relating directly to the role ofcyclosporine in this effect but relatively lit-tle is known of the function of other im-

    munosuppressive agents in gingivalovergrowth.

    MECHANISM OF ACTION

    Cyclosporine is a selective immunosuppres-sant with a weak antimicrobial activity (22)

    and can be administered orally,intramuscularly or intravenously (23).Themain use of cyclosporine is to prevent graft

    rejection in organ transplantation. Severalstudies have shown that cyclosporine se-lectively acts on the T-lymphocyte response,

    with little or no action on B lymphocytes(24).

    Role of Cyclosporine in Inhibition

    of Graft Rejection

    The pharmacodynamics of cyclosporine

    mainly involves the T-cell response. So it isessential to know the role of Tlymphocytes in graft rejection(25). The

    mechanisms by which the T-lymphocytesreject the graft are shown in Figure 1.

    Cyclosporine inhibits many of the stagesshown in Figure 1, acting at both a cellularand molecular level. At low concentrations

    (10-20 ng/ml), it inhibits IL-2 synthesis,thereby limiting clonal amplification of cy-totoxic T- lymphocytes. At a higher con-

    centration (100 ng/ml), cyclosporine inhib-its the ability of cytotoxic T- lymphocytesto respond to IL-2.The mechanism of this

    inhibition is uncertain, but may be due tothe drug blocking the induction of IL-2

    receptors on these cells. By contrast,cyclosporine has a sparing effect on sup-pressor T lymphocytes (26).Thus, T sup-

    pressor cells seem to be resistant tocyclosporine, whereas cytotoxic Tlymphocytes and T-helper cells are sensi-

    tive to the drug (27).

    Within the T-lymphocyte, cyclosporine

    binds to several proteins, in particularcalmodulin and cyclophilin. It has beenpostulated that the resistance or sensitivity

    of T lymphocytes to cyclosporine may berelated to the proportionate intracellularconcentrations of calmodulin (involved in

    activation of T-lymphocytes) andcyclophilin (27). An increase in cyclophilinwill increase cyclosporine binding, and thus

    prevent the drug from interacting withcalmodulin. Conversely, low levels ofcyclophilin will allow cyclosporine to bind

    to calmodulin and inhibit its formationand subsequent T-lymphocyte activation.

    CYCLOSPORIN AND GINGIVAL

    OVERGROWTH:

    The precise mechanism of cyclosporine-

    induced gingival overgrowth is uncertain.Various investigations for pathogenesis of

    Figure 1 : Role of t-lymphocytes in graft rejection(25)

    CYCLOSPORINE AND AMLODIPINE INDUCED GINGIVAL OVERGROWTH

  • 36 JOHCD www.johcd.org January 2012;6(1)

    gingival overgrowth support the hypoth-esis that it is multifactorial(19). A possiblemodel is shown in Figure 2(19).

    Cell culture studies have shown that bothcyclosporine and cyclosporine metabolites

    have direct effects on gingival fibroblastproliferation, protein synthesis and colla-gen production(25). Also, there exists a

    genetically determined subpopulation ofcyclosporine sensitive gingival fibroblasts.Indeed, the terms responders and non-

    responders have appeared in literature toidentify those who show or do not showdrug induced gingival changes (32). Both

    findings are important in the pathogenesisof cyclosporine-induced gingivalovergrowth.

    The results from clinical studies suggestthat the incidence and severity of gingival

    overgrowth in cyclosporine treated patientsis dependent upon the interaction of sev-eral factors. These include plaque control,

    the level of gingival inflammation and ex-tent of periodontal destruction; the dos-age and duration of cyclosporine therapy;

    plasma and tissue concentrations of thedrug and metabolites; age of the patientand perhaps the underlying medical condi-

    tion (25).

    Some authors suggest that there is a sig-

    nificant relationship between amount oftime without plaque control and develop-ment of gingival overgrowth (28), whereas

    others say no significant relation betweencyclosporine induced gingival overgrowthand plaque scores (29). It is well known

    that lipopolysaccharide is an importantcomponent of bacterial cell wall which isknown to be cytotoxic for fibroblasts.

    Cyclosporine enhances fibroblast DNA

    synthesis and cell proliferation and negates

    the effect of lipopolysaccharide on

    fibroblast cultures indicating a possible rea-

    son for the observed relationship between

    areas of prominent gingival overgrowth

    and dental plaque(30).

    Cyclosporine-induced gingival overgrowth

    commences as a papillary enlargement

    which is more pronounced on the labial

    aspects of the gingiva than the palatal or

    lingual surfaces (31). The papillary enlarge-

    ment increases and adjacent papillae appear

    to coalesce. This gives the gingival tissues a

    lobulated appearance. Overgrowth is re-

    stricted to the width of attached gingiva,

    but can extend coronally and interfere with

    the occlusion, mastication and speech.

    Cyclosporine induced gingival overgrowth

    has not been reported in edentulous sub-

    jects (32).

    The hyperplastic gingival tissues often

    show marked inflammatory changes. They

    bleed readily on probing and are generally

    more hyperaemic than the gingival tissue

    from phenytoin-induced gingival

    overgrowth (25).

    AMLODIPINE AND GINGIVAL

    OVERGROWTH

    The pathogenesis of gingival overgrowth

    is uncertain and a number of factors affect

    the relationship between drug and gingival

    overgrowth.

    Role of Fibroblasts

    As only a subset of patients treated with

    amlodipine develop gingival overgrowth,

    it has been hypothesized that these indi-

    viduals have fibroblasts with an abnormal

    susceptibility to the drug and the fibroblasts

    from overgrown gingiva in these patients

    are characterized by elevated levels of pro-

    tein synthesis, most of which is collagen

    (33). It also has been proposed that sus-

    ceptibility or resistance to pharmacologically

    induced gingival enlargement may be gov-

    erned by the existence of differential pro-

    portions of fibroblast subsets in each in-

    dividual which exhibit a fibrogenic response

    to amlodipine (34, 35).

    Figure 2 : Schematic diagram to suggest potential multifactorial features andinteractions in pathogenesis of cyclosporin induced gingival overgrowth19

    CYCLOSPORINE AND AMLODIPINE INDUCED GINGIVAL OVERGROWTH

  • JOHCD www.johcd.org January 2012;6(1) 37

    Role of Inflammatory Cytokines

    A synergistic enhancement of collagenousprotein synthesis by human gingival

    fibroblasts was found when these cells weresimultaneously exposed to amlodipineand interleukin-1b (36). In addition to IL-

    1b, IL-6 may play a role in the fibrogenicresponses of the gingiva to amlodipine(37).

    Role of Matrix Metalloproteinase

    (MMP) Synthesis and Function

    Because most types of pharmacologicalagents implicated in gingival enlargementhave negative effects on calcium ion influx

    across cell membranes, it was postulatedthat such agents may interfere with the syn-thesis and function of collagenases(38).

    PREVENTION AND TREATMENT OF

    GINGIVAL ENLARGEMENT

    Prevention

    In the susceptible patient, drug-associatedgingival enlargement may be ameliorated,

    but not prevented by elimination of localfactors, meticulous plaque control, andregular periodontal maintenance therapy.

    A 3-6 month interval for periodontal main-tenance therapy has been recommended forpatients taking drugs associated with

    gingival enlargement (39). Each recall ap-pointment should include detailed oralhygiene instructions and thorough prophy-

    laxis, with supra-and subgingival calculusremoval as needed (40).

    It is important that the dental professionalencourages improved tooth cleaning in asupportive and positive manner, as well as

    providing information about the role ofdental plaque in promoting gingivalovergrowth. Mild gingival enlargement will

    often diminish with removal of plaque andcalculus deposits. Even moderate gingivalenlargement may reduce enough to avoid

    surgical intervention. Attempts at improv-ing oral hygiene are of limited benefit insevere gingival enlargement, as surgical

    gingival excision is generally indicated (41).

    TREATMENT

    Drug Substitution/withdrawal

    The most effective treatment of drug-re-lated gingival enlargement is withdrawal

    or substitution of medication. Many casesof gingival enlargement will respond tolocal treatment, but consideration should

    be given to altering the medication ifgingival enlargement covers more thanabout a third of the tooth surface. When

    possible, reducing the dose or changing toanother drug may bring about partial orcomplete regression of the lesion. Most

    patients will observe an alteration in thesoft tissues within a few days(41). Whenthis treatment approach is taken as sug-

    gested by another case report, it may takefrom 1 to 8 weeks for resolution of gingivallesions (42). Unfortunately, not all patients

    respond to this mode of treatment, espe-cially those with long standing gingivalovergrowth (43).

    Non-surgical Treatment

    Mild gingival enlargement may only require

    local management as improvement in oralhygiene, together with professional clean-ing of the teeth, can lead to resolution of

    inflammation and reduction in gingivalenlargement. Professional debridementwith scaling and root planing as needed

    has been to shown to offer some relief ingingival overgrowth patients (44).

    Treatment planning becomes more com-plex where there is periodontitis associatedwith gingival enlargement, which poses a

    cosmetic or functional problem. Periodon-titis alone can be treated using conventionalclinical care, but when associated with the

    gingival enlargement, may require changesin the medication regimen, periodontalsurgery(flap technique)pocket elimination

    along with removal of excess tissue, or acombination of the two (41).

    Surgical Periodontal treatment

    Because the anterior labial gingiva is fre-quently involved, surgery is commonly

    performed for esthetic reasons before anyfunctional consequences are present. Theclassical surgical approach has been the ex-

    ternal bevel gingivectomy(33). However atotal or partial internal gingivectomy ap-proach has been suggested as an alterna-

    tive (44). This is a more technically demand-ing approach, which has the benefit of lim-iting a large denuded connective tissue

    wound that results from the external gin-givectomy, thereby minimizing postopera-tive inflammation, pain and bleeding.

    The use of electrocautery and carbon diox-ide lasers has shown some utility for re-

    ducing gingival enlargement, an approachwhich provides rapid post operativehemostasis(33). Consultation with the

    patients physician prior to surgical treat-ment regarding antibiotic and steroid cov-erage should take place in the

    immunosuppressed patient (44).

    CASE REPORT

    CHIEF COMPLAINT

    A 36-year-old male patient reported to theDepartment of Periodontolgy and

    Implantology, M.A.Rangoonwala collegeof Dental Sciences and Research Centre,Pune with a chief complaint of gingival

    swelling all over his mouth. The swellingcaused difficulties in speaking and eatingand it also had obvious implications for

    his aesthetic appearance. Besides these,other complaints were pain, bleeding fromgums, halitosis, and inability to brush and

    maintain his oral hygiene.

    CASE HISTORY FINDINGS

    Patients medical history revealed that hesustained renal failure secondary to neph-rotic syndrome in September, 1998. The

    patient was on hemodialysis since then for3 years during 1998 to 2001. Renal trans-plantation was carried out on 20/9/2001,

    where the donor was his mother. He alsohad hypertension since 8 years and was onmedication for the same. At the time the

    case history was recorded; the patient wason the medication as seen in table 1. Hereported that the problem of gingival en-

    largement had begun 45years before, withslow progression to the present conditionas seen in Figures 3 A, B, C.

    CLINICAL PRESENTATION

    The extraoral examination revealed a

    dismorphic face.The patient was unable toclose his lips because of the protrusion ofthe enlarged tissues.

    The intraoral examination revealed gener-alized, severe grade III gingival enlarge-

    CYCLOSPORINE AND AMLODIPINE INDUCED GINGIVAL OVERGROWTH

  • 38 JOHCD www.johcd.org January 2012;6(1)

    ment, as per the Bokenkamp gingivalovergrowth index (45), involving both the

    mandibular and maxillary arches. In themaxilla and mandible, only the incisal andocclusal surfaces of the teeth, surrounded

    by large amounts of gingival tissue, werevisible. The gingiva was highly inflamed,

    with a firm and dense consistency. Clinicalexamination revealed the presence of abun-dant local factors. There was spontaneous

    bleeding and in addition, halitosis was ac-centuated.

    INVESTIGATIONS

    The investigations carried out were com-plete haemogram, orthopantogram and

    biopsy. Haemogram: The haemogram

    showed all values within the normal

    variable range. Orthopantogram : There was mild

    bone loss associated, as revealed by

    orthopantogram in Figure 4 Biopsy : The histopathology slide as

    seen in Figure 5.

    Histopathology report: The reportshowed pseudoepitheliomatous pro-liferation, collagenous material with

    thickening of epithelium, highly vas-cularized connective tissue and foci ofinflammatory cells.

    Management of the gingival

    overgrowth

    Non-surgical Management

    After obtaining prior consent from thepatient and physician, and controlling theother systemic factors, the patient was given

    intensive oral hygiene instruction whichincluded tooth brushing three times a day,CHX mouthrinse 0.2% for 15 days twice

    daily and warm saline gargles three to fourtimes a day. A thorough scaling using anultrasonic scaler (EMS-Minipiezon) was

    performed at intervals of two weeks, for aperiod of 3 months.

    Figure 6 shows the post operative view 1month after Phase I therapy. Then the pa-tient was treated with external bevel gingi-

    vectomy using electrocautery with loop andneedle electrode (Whaledent, Perfect TCS)in the first quadrant and the other three

    quqdrants were not treated. The electro-

    Figure 3A: Frontal view(Preoperative view)

    Figure 3B: Maxillary occlusal view(Preoperative view)

    Figure 3C: Mandibular occlusalview (Preoperative view)

    Figure 4: Orthopantogram revealing mild bone loss

    Figure 5: Gingival hyperplasia asseen histopathologically

    Table 1: Medication of the patient

    Drug Dosage

    Liq. Neoral ( Cyclosporine) 0.8 ml b.dTab. Azoran (Azithromycin) 50 mg o.d.Tab. Wysolone (Corticosteroid) 10 mg o.d.Tab. Amtas ( Amlodipine) 10 mg o.d.Tab. Ecosprin (Aspirin) 325 mg o.dSyrup Kesol (Ketoconazole) 2 tsp b.d.Candid mouth pain (Nystatin) t.d.s

    CYCLOSPORINE AND AMLODIPINE INDUCED GINGIVAL OVERGROWTH

  • JOHCD www.johcd.org January 2012;6(1) 39

    cautery was used in cutting and coagula-

    tion mode at the settings of 4. This wasdone so as to compare the effect of surgi-cal versus non surgical treatment on the

    gingival overgrowth. Then the patient waskept on Supportive periodontal therapy for3 months. It was observed, that at the end

    of 4 months following Phase I therapy,the tissues appeared pink, firm, and de-void of any signs of inflammation. The

    non surgical therapy had shown a consid-erable reduction in the size of theovergrowth however, the amount of en-

    largement that persisted, warranted surgi-cal intervention for its resolution, as seenin Figure 7. Because the patient was un-

    happy with the appearance of his gingivaeand there was persistent residualovergrowth, it was decided to treat theproblem surgically by using the gingivec-

    tomy technique for excision of the gingivalovergrowth.

    Surgical Management

    The use of a traditional scalpel surgical ap-proach was contraindicated by the phycisian

    because it was considered that bleedingwould have been more severe and healingslow, with increased chances of post-op-

    erative infection in an immunosuppressed

    patient. As per the physician, the drug re-gime for the patient could not be changedor modified, as all the drugs were essential

    for the patient. So the drug dosage werenot reduced, neither was the drug substi-tuted. The patient was on aspirin, which

    was stopped 10 days prior to the surgicalprocedure.

    The overgrowth was then excised by exter-nal bevel gingivectomy using electrocauterywith loop and needle electrode (Whaledent,

    Perfect TCS). The electrocautery was usedin cutting and coagulation mode at the set-tings of 4 (Figure 8). Very good immedi-

    ate post-operative result was obvious. Af-ter 1 month, following healing, gingivo-plasty was carried out using CO

    2

    laser(Union Medical, Korea) at 2-4 Watts,

    continuous wave, and in the focused mode(Figure 9 A,B,C).

    The patient maintained excellent oral hy-giene and six months later, was free ofplaque and gingivitis in the area of his sur-

    gery (Figure 10). One year follow up (Fig-ure 11) revealed that there were no signs ofrecurrence of the gingival overgrowth and

    the tissues appeared remarkably healthy.Figure 12 and 13 shows the preoperative

    and postoperative results.

    DISCUSSION

    This is a review and report of a case ofcyclosporine and amlodipine inducedgingival overgrowth. A number of features

    of this case merit discussion.

    First, prevention of dental plaque accumu-

    lation by tooth brushing three times a day,oral rinsing with antiseptic solutions andultrasound scaling whenever necessary make

    the reccurrence of inflammation andgingival overgrowth less likely. In this casereport, the reccurrence of inflammation

    and gingival overgrowth is not seen as thepatient maintained excellent oral hygiene.Gingival inflammation following bacterial

    plaque seems to exacerbate drug-inducedgingival overgrowth. Poor oral hygiene isan important risk factor for the expression

    of drug induced gingival overgrowth (46,47, 48, 49). Most reports on the relation-ship between bacterial plaque and gingival

    overgrowth have been derived from cross-sectional studies, but there is no clear evi-dence that bacterial plaque is a contributory

    factor or a consequence of the gingivalchanges (50, 51, 52). However, it can be

    Figure 6: 1 month post operativescaling and root planing

    (B)

    CYCLOSPORINE AND AMLODIPINE INDUCED GINGIVAL OVERGROWTH

    Figure 8: Gingivectomy usingelectrocautery

    Figure 9 A,B,C: Gingivoplasty using CO2 laser

    (A) (B)(A) (B) (C)

    Figure 7: 4 months postoperativescaling and root planing

  • 40 JOHCD www.johcd.org January 2012;6(1)

    assumed that adequate oral hygiene could

    delay the development of cyclosporine andamlodipine induced gingival overgrowth,possibly by eliminating the lesion-specific

    inflammatory component. Nevertheless, itmay well be that improved oral hygienealone cannot prevent gingival overgrowth

    (19, 49, 50).

    Second, it should be noted that post-op-

    erative bleeding was insignificant. Electro-surgery techniques have been used in den-tistry for the past 70 years. Although such

    techniques produce adequate haemostasis,they have the disadvantage of causing asurrounding zone of thermal necrosis,

    which may impede wound healing (53).Reports in the literature have confirmeddelayed healing of electrosurgery wounds

    when compared with scalpel wound heal-ing (54). This is probably due to the pro-duction and accumulation of excessive la-

    tent heat, which can be significant if elec-trosurgery is performed inappropriately.The amount of latent heat produced is

    dependant upon instrumentation vari-ables, such as type of waveform, size ofcutting electrode, time required for incision

    and the energy produced at operating site(55). Nevertheless, surgical intervention

    using conventional means (scalpel) may

    sometimes be technically difficult and/orimpractical for example in children or men-tally handicapped, or in immunosuppresed

    patients or those suffering from impairedhaemostasis. In these situations, the useof electrosurgery may be advantageous (56).

    This therapy is only slightly invasive, theaesthetic improvement is immediate, andsutures and dressings are unnecessary (54).

    Following the procedure, the patient re-ported that pain from the gingivalovergrowth disappeared, bleeding was al-

    most absent, and consequently the pa-tients discomfort was eliminated. The factthat electrocautery surgery ensures disinfec-

    tion, sterilisation of dental tissues withreduction of bacterial viability, and rapidhaemostasis is an important consideration

    with regard to the prevention of post-op-erative infection, especially inimmunosuppressed patients.

    Third, there was no reccurrence of thegingival overgrowth even after one year

    follow up in our case report. There are highchances of recurrence of gingivalovergrowth, when the excision is done by

    external bevel gingivectomy as the effectsof cyclosporine and calcium channelblockers are seen on more extensive and

    unprotected healing area (57). Laser treat-ment on oral soft tissues results in a thinlayer of carbonized tissue and formation

    of collagen slough that protects the un-derlying tissue (58).The chances for recur-rence of gingival overgrowth are minimized

    or delayed when laser gingivectomy is done,as cellular mitotic activity starts from withinthe connective tissue, therefore more time

    will be required for gingival enlargementto manifest clinically as compared to scal-pel gingivectomy(59). In a study by

    Seymour et al 2006, where he comparedscalpel gingivectomy with flap surgery andNd:YAG laser gingivectomy, he found that

    the recurrence following laser therapy wasleast as compared to other groups during1-3 months duration(60). Our case report

    coincides with this study as gingivoplastyby CO

    2 laser resulted in no recurrence. It

    was also attributed to the excellent oral

    hygiene maintainence by the patient.

    It was thus significant that CO2 laser gin-

    givoplasty in combination with excellentoral hygiene resulted in no recurrence ofthe gingival overgrowth.

    The patient in this case report practisedgood oral hygiene after ultrasonic scaling

    and professional cleaning, and this clearlydemonstrated a beneficial effect. Excisionof the overgrown tissue resulted in the

    total removal of the gingival overgrowth.

    CONCLUSIONS

    Gingival overgrowth is a side-effect of thelong-term administration of cyclosporineand amlodipine and may also be influenced

    by other predisposing factors, such as bac-terial plaque. In this case report, inspite ofthe effect of Polypharmacy, using combi-

    nation of various drugs like cyclosporineand amlodipine aggravating the gingivalovergrowth in the presence of plaque and

    other local factors, the use of non surgicaltherapy and surgical therapy facilitated op-timal reduction of overgrown gingival tis-

    sue, with very good results, improvedesthetics and no overgrowth after one yearfollow up. It needs to be emphasized that

    elimination of local factors followed bythorough maintainance has a definitive sig-nificant inhibitory effect on gingival

    Figure 12. Preoperative view Figure 13: 1 year Post-operative view

    CYCLOSPORINE AND AMLODIPINE INDUCED GINGIVAL OVERGROWTH

    Figure 10: 6 months postoperativegingivectomy

    Figure 11: 1 year Post-operativeview

  • JOHCD www.johcd.org January 2012;6(1) 41

    overgrowth. Surgical treatment to excise andremodel the gingival contour should beconsidered whenever gingival overgrowth

    causes aesthetic and functionalproblems.The use of an electrocautery andCO

    2 laser for removal of gingival

    overgrowth surgically decreases intra-op-erative haemorrhage and has excellent post-operative results.

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