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Home , Calculus (dental), Exudate, Gingival enlargement, Periodontal abscess, Prevotella intermedia

Unusual Clinical Presentation of Generalised – A Report of 3 Cases

Smitha Rani Thada, Vineetha R, Keerthilatha M Pai

International Journal of Collaborative Research on Internal Medicine & Public Health Vol. 4 No. 4 (April 2012)

International Journal of Collaborative Research on Internal Medicine & Public Health (IJCRIMPH)

ISSN 18404529 | Journal Type: Open Access | Volume 4 Number 4

Journal details including published articles and guidelines for authors can be found at: http://www.iomcworld.com/ijcrimph/

Correspondence concerning this article should be addressed to Dr. Smitha Rani Thada; Flat no 204, Anand apartments, Karangalpady, Mangalore – 575003, Karnataka, India | Mobile no – 09880813732 | Email – [email protected]

240 International Journal of Collaborative Research on Internal Medicine & Public Health

Unusual Clinical Presentation of Generalized Gingival Enlargement – A Report of 3 Cases

Smitha Rani Thada (1) *, Vineetha R (2), Keerthilatha M Pai (3)

1) MDS; Assistant Professor; Manipal College of Dental Sciences, Manipal, India 2) MDS; Reader; Manipal College of Dental Sciences, Manipal, India 3) MDS; Professor & Head, Department of Oral Medicine & Radiology, Manipal College of Dental Sciences, Manipal, India

* Corresponding Author

ABSTRACT

Gingival is an aesthetically disfiguring condition causing psychological & masticatory disturbance of the oral cavity. There are wide varieties of causes of gingival enlargement ranging from most common causes like plaque accumulation, poor to serious systemic illnesses including blood dyscrasias, syndromes & side effects of several drugs. Here we report a case series of a neoplastic, a syndrome associated & a drug induced gingival enlargement along with a concise review on various etiologies, pathogeneses of gingival enlargement & an emphasis on the multidisciplinary approach required for the management of such distressing & functionally compromising gingival pathologies.

Keywords: Gingival enlargement, Chronic Myeloid , Zimmermann–Laband syndrome,

Introduction dentist to establish an accurate diagnosis. We report 3 cases of aesthetically disfiguring GE, Gingival enlargement (GE) is defined as an where all the three seem to have a varying abnormal overgrowth of gingival tissues. As the etiology. GE is not merely due to increase in number or size of cells but due to inflammatory component as well, the term “gingival overgrowth” or “gingival CASE 1: enlargement” is preferred over hyperplasia & 1,2 . GE is an unusual condition causing A 48 years old female presented with a complaint aesthetic, functional, & psychological disturbance of gradual enlargement of the entire upper & lower in an individual. It may be easy for a dentist to since 3 years. The enlargement was so arrive at a clinical diagnosis of GE if the cause is extensive that it interfered with her speech, clearly evident, but at times it becomes necessary mastication & mouth closure. She also reported of to seek medical advice to explore the cause and & occasional bleeding of gums. She identify the underlying , drug interactions was a known hypertensive, receiving 20 mg of or the natural body changes & to develop an Nifedipine twice daily since 2 years. Patient had a effective treatment plan. When the exact cause convex profile with open bite and incompetent cannot be elucidated, it becomes challenging to the

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with nodular masses of gingiva protruding molars in all the quadrants were not clinically between the teeth (Figure 1). Intraoral visible. However on the panoramic radiograph, examination revealed of bulbous, fibrotic full complement of teeth was present with mild enlargement of gingiva showing cobble stone interdental bone loss & increased spacing between appearance & areas of gingival . Two the teeth. Provisional diagnosis of generalized GE third portions of almost all the teeth crowns were associated with an unidentified syndrome was covered with growing gums with resultant given. displacement of teeth & midline shift (Figure 2). On the panoramic view all complement of teeth was present with moderate amount of interdental bone loss & increased spacing between the teeth CASE 3: was seen. A clinical diagnosis of combined effect A 46 years old male, a known case of chronic of drug induced (Nifedipine) & inflammatory GE myeloid leukemia reported with gum enlargement was given. since 2 months. He noticed an increase in the size of his gums after removal of decayed lower right & left back teeth. There was associated pain of CASE 2: gums while chewing & severe bleeding while brushing. He was not able to maintain a good oral A 17 year old girl reported with a complaint of hygiene. He was diagnosed with Chronic Myeloid gum enlargement since 4 years of age. She gave a Leukemia (CML) (blast crisis) 2½ years back & history of few embedded milk teeth in the gums was on Tab Imatinib since then. He had mild which were surgically extracted at the age of 6 Bell’s palsy on left side of face (Figure 6). Intra years. Even the permanent teeth were covered by orally, there was presence of generalized the overgrowing gums soon after their eruption erythematous bulbous GE with spontaneous making it difficult for her to maintain her oral bleeding & exudate from gums (Figure 7). His oral hygiene. Surgical exposure of all anterior teeth hygiene was poor. Panoramic view showed was done 11 years back but it recurred. She also moderate interdental bone loss & increased presented with delayed milestones, challenged spacing between the teeth with no bone changes. speech & hearing since childhood. Her medical Clinical diagnosis of leukemia induced GE was records revealed of a single episode of epileptic made. attack 1 ½ years back for which she was on sodium valproate since then. Her parents had consanguineous marriage. Discussion On examination, she was well oriented & Various causes of GE can be grouped as follows: cooperative. She had a short stature with short & 1) Inflammatory, 2) Medicationinduced, 3) stout fingers & toes (Figure 3), mild facial Idiopathic gingival fibromatosis , depressed nasal bridge, thick lips & (hereditary/syndrome associated), 4) Systemic a nodular iatrogenic scar on the right lower causes of GE, 5) False GE (underlying osseous (Figure 4). On intra oral examination, there was , dental tissues) & 6) Others (mouth generalized irregular fibrotic enlargement of breathers). GE can be inflammatory or fibrotic in gingiva covering two third of most of the teeth nature. Inflammatory GE is the most common & is with areas of inflammation, resultant displacement completely reversible in otherwise healthy of teeth & midline shift (Figure 5). Second & third

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individuals if the local causative agent, microbial inflammatory enlargement is usually in the form plaque; is regularly & effectively removed by of gingival & periodontal . Gingival mechanical teeth cleaning procedures. abscess is a purulent involving marginal Hereditary, drug related, & syndrome associated or interdental gingiva which is mainly caused by GE are usually fibrotic in nature. 2,3 Oral that are carried deep into the tissues by prophylaxis alone will not be sufficient to control brush bristles or orthodontic appliances. the fibrotic gingival overgrowth, but even surgical Initially it begins as a small red painful swelling excision of hyperplastic tissues is essential. with smooth/shiny surface. In 24 48 hours, swelling becomes fluctuant & pointed. If allowed GE can be localized or generalized. Initially it may to progress, it will rupture spontaneously with involve just the papillary & marginal portion of release of purulent discharge. gingiva but may slowly progress to involve the is caused due to the extension of infection from attached gingiva; if the causative factor is still pocket into supporting periodontal tissues which persisting. GE can also be present as discrete results in gingival swelling with presence of deep forms either as pedunculated or sessile masses. pocket & affected tooth can be depressed into the socket. may drain through sulcus (or) orifice. GE can be graded by three methods – Cast Diffuse gingival/periodontal abscess are preferably 4 5,6 method , Photographic method & Clinical managed through drainage along the sulcus along 2,7 measurement method . The scoring for GE is with removal of the etiological agent but when given by many authors, but the most accepted one abscess is pointed then vertical stab incision & 8 is given by Bokenkamp in 1994 as – Grade 0 – no drainage is preferred followed by systemic signs of enlargements; Grade 1 – enlargement antibiotics & NSAID’s depending on patient’s confined to ; Grade 2 – condition. enlargement involves papilla & marginal gingiva; Grade 3 – enlargement covering three quarters or more of the . 2) Medication induced GE

1) Inflammatory GE The three main groups of drugs that cause GE are , immunosuppressants, & Inflammatory GE may result from chronic or acute channel blockers. 1,2,9 Theoretically, all the drugs of changes. Chronic inflammatory GE is caused by these groups can cause gingival overgrowth, but prolonged exposure to , chronic few drugs like sodium (50%), irritation due to improper restorative & cyclosporine (30%), nifedipine (10%), 2 are orthodontic appliances, or habit. associated with high prevalence of overgrowths. Initially, lifepreserver shaped enlargement is seen Apart from these drugs, some authors 2 have in marginal gingiva. It slowly increases in size & reported overgrowths after long term use of involves the papilla. Gingiva is soft, friable & erythromycin for . Among the anti deep red in colour with increased tendency to convulsants, phenytoin is the most common drug bleed. This can be treated by removal of local associated with GE & its incidence rate ranges factors with scaling & root planing after which the from 0 89%. 10,11,12 It is commercially available as gingiva shrinks & becomes firm. The persisting Dilantin Sodium. Kinball 13 was the first to report a soft GE even after the conventional therapy is best case of Phenytoin induced GE. Other treated by while the persisting firm anticonvulsants associated with overgrowth are GE is best treated by flap surgery. Acute carbamazepine, , ,

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, methosuximide, valproic acid. 1 documented that nifedipine induced GE may be Minimal plasma level needed for seizure control is reduced within one week upon discontinuation of 10 20µg/ml & minimal concentration of drug the drug. 2 Furthermore, once drug induced GE sets needed to produce overgrowth is higher than this in; it usually does not respond well to plaque concentration. 14 It usually starts after 3 6 months control thus requiring surgical excision of of therapy depending upon the periodontal status hyperplastic tissues. The patient should be & may reach maximum in 9 18 months. 15 Among motivated to maintain strict plaque control the immunosuppressants, cyclosporine is more regimen following the periodontal surgery, often associated with gingival overgrowth. 1,2 To including regular professional cleaning then the maintain immunosuppression, oral therapeutic hyperplastic gingival lesions may not recur inspite dose of 10 – 20mg/kg body weight/day is required. of continuation of drug. 2 It will result in a concentration of 100 – 400ng/ml. Investigations by Daley et al (1986), 16 In the first case reported here, the patient had found that all patients taking more than 700 mg of inflammatory GE to begin with, due to poor oral cyclosporine per day displayed at least mild GE & hygiene. The gingival overgrowth became severe suggested a "threshold" dose exists above which when she was started on GE occurs. Overall incidence of cyclosporine (Nifedipine), 2 years back for the treatment of induced GE is 25% to 81%. 17 The major side hypertension, due to the unwanted effects of the effect of cyclosporine is & drug. Hence the clinical diagnosis of combined hypertension. 2 To counteract these side effects, effect of drug induced (Nifedipine) & usually nifedipine is given. This combination in inflammatory GE was made for this case. turn increases the severity of gingival overgrowth.8 Calcium channel blocking agents are used The mechanism of pathogenesis of GE is an extensively for the management of cardiovascular enigma that has intrigued researchers for decades. conditions & hypertension. Nifedipine is the most Several hypotheses have been proposed by prescribed pharmacologic agent in this group & different investigators on the mechanisms of drug 19,20 was the first documented to be associated with GE induced GE. Seymour et al in their review on in 1984. 18 The onset of GE usually becomes the pathogenesis of drug induced gingival clinically apparent within two months following overgrowth; consider it as a multifactorial model; initiation of therapy with nifedipine. Incidence rate involving an interaction of several factors like the of nifedipine induced GE is around 15% – 21%. 2 age, gender, genetic predisposition, Other calcium channel blockers that cause GEs are pharmacokinetic variables, drug interactions, & , Diltiazem, & . 1,2 periodontal status.

Drug induced gingival overgrowth starts as a bead like fibrotic generalized papillary enlargement & 1. Age & gender – GEs are seen in any age groups involves the attached gingiva in later stages. depending on the drug intake. Children, teenagers Enlargement create pesudopocket resulting in are at increased risk of developing phenytoin plaque accumulation giving a clinical picture of induced GE as epilepsy is more prevalent in this combined enlargement (fibrous & inflammatory). age group, middle & older age group individuals Withdrawal or substitution of the offending are prone for GE secondary to calcium channel medication is the prime treatment choice but it blockers & cyclosporine induced GE is seen in all should be considered after discussing with the age groups. Gender & age are not important risk patient’s general physician. It has been factors, however males are three times as likely to

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develop drug induced gingival overgrowth, & age of gingival overgrowth 2,16,26,27 others have failed to is inversely correlated. 2,20,21,22,23 substantiate these findings. 2,22,28

2. Genetic Predisposition Not all patients taking 4. Drug interactions Interactions between phenytoin, cyclosporine or a calcium channel simultaneously administered medications affecting blocker develop GE. Following mechanisms were GE have also been reported. Chronic co put forward to explain the genetic basis: medication with phenytoin & other agents does not affect the degree of GE in adult 1) P-450-gene polymorphism:- All the epileptic patients. 2 However, cyclosporine treated above drugs are metabolized in liver by patients are often on prednisolone or azathioprine cytochrome p450 group of enzyme. Genetic as well, which can modify the severity of GE. 2 On polymorphism in p450 gene will result in altered the other hand, patients on cyclosporine A, who metabolic activity of these drugs resulting in gum are also receiving a calcium channel blocker 20 enlargement. present with a greater severity of the gingival 2) HLA-polymorphism:- patients who lesions than patients medicated with cyclosporine express HLADR1 show protection against alone. 2 cyclosporine overgrowth & patients who express HLADR–2 are susceptible to develop 5. Periodontal variable - Even though gingival cyclosporine overgrowth, 24 however a different overgrowth can occur in absence of plaque, school of thought was proposed saying presence of plaque & gingival inflammation examination of tissue typing data in transplant appears to exacerbate the severity of enlargement. recipients has shown that HLAB37 positive patients are significantly more likely to show Although drug induced GE has been extensively severe GE, whereas the opposite is true about studied, the pathogenesis of this disorder has not HLADR1 positive patients. 2 been clarified to date. To explain this, several 3) Fibroblasts heterogenicity:- phenytoin & mechanisms were put forward – its major metabolite 5(4hydroxyphenyl)5 phenylhydantoin (4HPPH) react with a) Role of growth factor It has been phenotypically distinct subpopulation of gingival suggested that healthy gingiva is in a continuous fibroblasts & cause an increase in state of wound repair due to constant insult from synthesis & cell proliferation rate. 19 bacterial plaque & that growth factor may play an 4) phenotypes:- Responders important role in this reparative or maintenance usually contain different phenotypic process. Thus one might expect to find cells in which produce proliferative , resulting in normal gingiva producing growth factors alteration of connective tissue metabolism. 25 associated with such as platelet derived growth factor B chain (PDGFB). One 3. Pharmacokinetics of drugs - It would seem that might also expect to find increased numbers of certain threshold concentrations of the drug or its these cells or increased amounts of these growth metabolite is necessary to activate gingival factors in conditions which involve increased fibroblasts or to alter connective tissue tissue volume such as drug induced gingival homeostasis, but this concentration may vary overgrowth. Such growth factors are obvious markedly between patients. Some studies suggest targets for drugs & their activation may be that whole blood & salivary concentrations of the important in the pathogenesis of drug induced 2,19 drug are important determinants in the expression gingival overgrowth.

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b) Inflammation from plaque Oral prophylaxis & pathogenesis. 28 Aarli (1976) 31 reported that good oral hygiene reduces the severity & phenytoin induces significant increase in both recurrence rate after excision of gingival salivary IgA levels & the IgA rate by parotid overgrowth. This highlights the role of gland. inflammatory mediators as follows e) Collagenase activation In vitro studies, o Patient with phenytoin therapy show increase showed that phenytoin induced GE may be more number of langerhans cells which in turn is related related to a lack of collagen breakdown as opposed to increase in Interleukin – 1 (IL1) & Tumour to an increase in collagen production. 2 Factor (TNF) – α. This induces a dose f) Gingival fibroblast phenotypes

dependent stimulation of E 2 in Phenytoin reacts with some of phenotypically fibroblasts resulting in increase in fibroblastic distinct subpopulation of gingival fibroblasts & proliferation in presence of primary growth resultant clinical picture is a reference of such factors. 29 population 32 o Cyclosporine upregulates IL 6 expressions. IL – g) Description of fibroblast cellular Na + 6 appear to target gingival connective tissue cells Ca +2 function All three groups of drugs influence both by enhanced proliferation & by positive the Ca +2 /Na + flux. Inhibition of Ca +2 intake by regulation of collagen & glycosaminoglycan fibroblasts may be correlated with the rate of synthesis. 1 fibroblastic proliferation & overgrowth. 33 o Also cyclosporine, nifedipine, phenytoin were h) Folic acid is involved in the synthesis of found to synergize with IL – β to further enhance purines & pyrimidines which are necessary for secretion of this by gingival fibroblasts in DNA synthesis. Folic acid is also required for the vitro there by resulting in increased collagenous activation of collagenase. This folic acid taken up protein synthesis. 30 by cells through Na + coupled, Na + dependent c) Drug - induced Alterations in Gingival active transport. Phenytoin interferes with Ca +/Na + Connective Tissue Homeostasis the connective transport at cellular level, resulting in decreased tissue in phenytoin overgrowth has a significantly uptake of folic acid. High doses of folic acid (IV) higher volume density of noncollagenous matrix gives protection against phenytoin overgrowth. 34 It than of collagenous matrix. 28 A further was explained by: investigation into the tissue contents of 1. Close structural resemblance between proteoglycans & glycosaminoglycans has folic acid & phenytoin. Folic acid could act as confirmed this finding. 2 The effect of cyclosporine competitive antagonist. & nifedipine on noncollagenous matrix has been 2. Folic acid – decrease the metabolite of investigated with respect to ‘Hglucosamine phenytoin resulting in decrease in severity & utilisation. 2 Fibroblasts obtained from a patient incidence of enlargement. with gingival overgrowth secondary to both 3. Folic acid binds to plaque – derived nifedipine & cyclosporine therapy metabolised ‘H endotoxin & prevents stimulation of endotoxin glycosamine differentially from those exposed to complement immune system. This will decrease cyclosporine in vitro & normal gingival local hyperplastic changes fibroblasts. Extrapolation of these results to the in i) Combination hypothesis Combination of vivo situation would suggest that both several factors like the drug intake, periodontal cyclosporine & nifedipine can cause increased status & tooth sulcular epithelial integrity is also tissue level of nonsulphated glycosaminoglycans. responsible for gingival overgrowth. d) Immunoglobulins immunological reaction mediated by Tcells may play a role in

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In the second case reported here, the 17 year old been observed but most forms are without defects, girl presented with gingival overgrowth since other than GE. Consanguinity has been observed childhood which affected both her primary & in recessive form. 39 permanent teeth, the cause for which was not known. Even though the patient was on Genetic conditions often present at birth (all are anticonvulsant for 1 ½ years at the time of rare conditions) & which are associated with presentation, drug induced GE was not considered, hereditary fibromatosis include Icell , as the primary cause for childhood presentation mucopolysaccharidoses, fucosidosis, aspartyl was not known. Several complications of sodium glucosaminuria, Pfeiffer’s syndrome, infantile valproate are known 35 but GE as a potential side systemic hyalinosis, & primary amyloidosis. effect was discussed only in very few case reports. Those which cause localised GE include Fabry’s Several authors implicated the role of mast cells in syndrome, Cowden’s syndrome, tuberous the pathogenesis of GE due to sodium valproate. 4 sclerosis, Sturge Weber angiomatosis & gingival In contrary, the effect of sodium valproate on the granular cell tumor. periodontal & oral health of epileptic patients has been carried out in few prospective studies which Hereditary Gingival Fibromatosis (HGF) is rare, 40 showed no unwanted effects on oral & dental affecting only one in 7,50,000 people. Gingival health. 4,36 Fibromatosis is most commonly associated with hypertrichosis with or without mental 41 retardation. Syndromes such as Murray–Puretic– 3) Idiopathic gingival fibromatosis Drescher (juvenile hyaline fibromatosis) present with multiple hyaline , osteolysis of Idiopathic gingival fibromatosis is a rare terminal phalanges, recurrent infection, stunted hereditary condition that has no definite cause. 37,38 growth & premature death. Cross syndrome This condition may manifest as an autosomal presents with microphalmia, mental retardation, dominant or, less commonly, an autosomal athetosis, & hypopigmentation. Ruthufard recessive mode of inheritance, either as an isolated syndrome is associated with corneal dystrophy. disorder or as part of a syndrome. Autosomal Jones syndrome presents with progressive dominant forms of gingival fibromatosis are deafness. 42 Zimmermann–Laband syndrome is usually nonsyndromic. Idiopathic gingival characterized by abnormalities of the nose &/or fibromatosis is a gradually progressive benign ears, absence &/or hyperplasia of the nails or enlargement that affects the marginal, interdental, terminal phalanges of the hands & feet, & attached gingiva. The fibromatosis may hyperextensibility of joints, hepatosplenomegaly, potentially cover the exposed tooth surfaces, mild hirsutism, & mental retardation. 43 The thereby hampering the functioning of the condition results from autosomal dominant stomatognathic system. The gingival tissues are inheritance & involves a highly variable usually pink & nonhemorrhagic & have a firm, phenotype. 43 fibrotic consistency. The autosomal dominant form is often associated with hypertrichosis, The interesting feature in the third case presented corneal dystrophy, nail defects, deafness, & here was that the patient was short statured girl craniofacial deformities. Children suffering from with short, stout fingers & toes, with mild facial autosomal dominant form may suffer from mental hypertrichosis. She also had delayed milestones. retardation & epilepsy. In autosomal recessive Her parents had a consanguineous marriage. form facial anomalies with hypertelorism have Considering all these features, we found it appropriate to give a clinical diagnosis as

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idiopathic or syndrome associated GE & all these effects of local irritants on gingival connective clinical features presented by patient fits into the tissue. 44 Enlargement in occurs in both description of Zimmermann–Laband syndrome. male & female adolescents & appear in areas of However our patient did not present with hepato or plaque accumulation. After puberty the splenomegaly but she was suffering from epilepsy. enlargement undergoes spontaneous reduction but Zimmermann–Laband syndrome associated with does not disappear until plaque & are epilepsy has not been reported so far. Hence removed. Incidence of in identification of the genetic pathways & varies from around 50% to 100%.45 Pregnancy mechanisms of Zimmermann–Laband syndrome does not alter healthy gingiva; it affects the will be useful in clarifying this disorder. In the severity of previously inflamed area. Kornman & present case, GE began when the patient was less Loesch (1980) 46 have reported that the subgingival than 1 year old, & she had gingivectomy & flora changes to a more anaerobic flora as at 6 years. But the GE recurred pregnancy progresses. “ intermedia” is again to greater extent by 17 years of age. The the only that increases timing of gingivectomy & gingivoplasty for significantly during pregnancy. They also stated gingival fibromatosis patients is controversial. that the increase is due to elevations of levels of According to several authors, the ideal time is systemic estradiol & progesterone, which, by the when all permanent dentition has erupted, because end of the third trimester, reach levels ten & thirty the risk of recurrence is higher before this. Growth times the levels during the menstrual cycle, may worsen through adolescence, suggesting the respectively. It is generally accepted that increase influence of sex hormones. 43 In some cases, delay in gingival inflammation typically begins in the in surgical treatment may lead to deciduous second month & reach the maximal level during dentition retention, alveolar bone resorption, the eighth month of pregnancy. 44 This altered mastication difficulties, disadvantageous esthetic gingival tissue response to plaque is due to & phonation effects, & psychological problems. 43 depression of the maternal Tlymphocyte. 47 These For the patient in this study, the local & inflammatory changes may lead to gingiva that psychological benefits & risk of recurrence were appears oedematous, hyperplastic & erythematous. considered & early treatment was suggested. The changes may be localized or generalized, & are usually noted on the marginal gingiva & interdental papilla, prevalence rate being 10% according to Butter (1987), 48 & 70% according to 4) Systemic causes of GE Ziskin (1933) 49 respectively. In some cases the inflamed gingiva forms a discrete mass referred to Systemic causes of GE may be further classified as as pregnancy tumor. It is non neoplastic conditioned enlargement (hormonal, nutritional, enlargement that usually appears during first or allergic, nonspecific enlargement – pyogenic second trimester. Its incidence is 1.8% 5%. ) & enlargement secondary to systemic Pregnancy does not cause the condition, but the diseases (leukemia, granulomatous diseases) altered tissue metabolism in pregnancy 44 A. Conditioned enlargement accentuates the response to local irritants. Therefore, the maintenance of oral hygiene before Hormonal - Hormonal changes occurring during & during pregnancy is very important in order to pregnancy & puberty, however, have long been reduce the incidence & the severity of gingival known to be associated with varying types of GE. inflammation. Lesions that do not cause Hormonal changes can significantly potentiate the significant functional or esthetic problems should

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not be excised during pregnancy because, first, usually ranges between 0.5 cm – 2 cm, & they they may reoccur &, secondly they may resolve may grow at an alarming rate reaching that size in spontaneously postpartum. 44 just 4 7 days. There are 2 types of Lobular hemangioma (LCH) Nutritional - Enlargement of the gingiva is sessile form (66%) & Non – LCH pedunculated generally included in classic description of scurvy form (77%). 50 Bright red / purple in colour with a but incidence of occurrence of scurvy is rare in the friable (or) firm consistency & bleeds on slight present generation population. Acute vitamin C provocation. Sometimes growth may involute deficiency itself does not cause gingival spontaneously on its own. The is treated by inflammation, but it causes hemorrhage, collagen removal of irritating factor like calculus, root degeneration & oedema of the gingival connective stumps, overhanging restorations, followed by tissue. These changes modify the response of the surgical excision of lesion. Recurrence rate is gingiva to plaque to the extent that the normal around 15%. 50 delimiting reaction is inhibited & the extent of inflammation is exaggerated resulting in the B. Enlargement secondary to systemic massive GE. Enlargement of marginal gingiva is diseases usually seen with gingiva appearing bluish red, a. Granulomatous diseases - Wegener’s soft & friable & has a smooth shiny surface. Granulomatosis is a pathologic triad of Spontaneous bleeding on slight provocation, necrotizing of nose, paranasal sinuses hemorrhagic areas & surface necrosis with & lungs, vasculitis & glomerulonephritis. Growth pseudomembrane formation are common features. is either localized / generalized. It is referred as Allergic - (Synonyms: “Overripened strawberry” appearance due to Atypical gingivitis, Plasma cell gingivostomatitis) reddish purple colour & tendency to bleed. As it is is considered to be an allergic response or an immunologically mediated tissue injury, hypersensitivity reaction to some component of corticosteroids or immunosuppressants are the , dentifrices or diet. It is commonly drug of choice for the treatment of the disease. seen in young females. It is associated with Other granulomatous diseases producing burning sensation, intense & oedema enlargement are: , Chrohn’s disease, of free & interdental gingival. Patient usually Merkellson – Rosenthal syndrome etc. gives a history of shifting to new / oral rinse or chewing gum. Identification of allergic b. Neoplastic GE: Neoplastic enlargement agent & removal from diet / ideally use is the first consists of 8% of all oral . The most treatment strategy along with scaling & root common benign tumors that cause GE include planning. , , Peripheral granuloma etc. They are usually treated by Nonspecific enlargement – Pyogenic granuloma surgical excision. Among the malignant lesions, is a non neoplastic inflammatory hyperplasia of leukemia is the most common that skin & oral cavity. Various etiologic factors such produces gingival overgrowths. as chronic low grade local irritation, trauma, hormonal changes, certain drugs, bone marrow Leukemia - Leukemia is a malignant neoplasm of transplant, & reactions to grafts have shown to WBC characterized by infiltration of leukemic induce its initiation. The most common intraoral cells in the bone marrow & other tissues. site is the gingiva (nearly 75%), but it also affects Leukemia is classified based on cell involvement the lips, mucosa, & tongue. The size of the lesion as Lymphocytic, Monocytic, & Myelocytic &

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based on the course of the disease as acute & chronic. Leukemic infiltration of gingiva may Conclusion produce GE in these patients with a prevalence 51 rate of 3.6%. Highest incidence of GE is seen in Eventhough generalized GE can result from acute monocytic leukemia (66.7%). Chronic multiple causes, the clinical manifestation appear Myeloid Leukemia (CML) is a of the similar in many cases. Identification of the cause myeloid line of cells in the bone marrow. The usually poses no great challenge to the clinicians, three clinical stages of CML include chronic provided they have thorough knowledge regarding phase, acceleratedphase & blasticphase. Extra those causative conditions. Rarely, diagnosis medullary involvement with myeloid cells in CML becomes difficult when associated with syndromes is a rare but may be seen in blastic stage. The most or has unusual pattern of presentation. Moreover, common sites involved with extramedullary the esthetic disfigurement & the functional disease are lymph nodes (10 61%), bone (33 impairment resulting from severe gingival 51 37%) & soft tissues (30%). overgrowth can have a negative impact in the 52 Dreizen et al studied the clinicopathologic & physical social & emotional well being of the histopathologic features of leukemic gingival & patient. This article puts an effort in highlighting cutaneous infiltrates in 1,076 adults hospitalized the various causes & pathogeneses of GE & an for cancer chemotherapy but found no cases of emphasis on the multidisciplinary approach gingival involvement with CML, thus making the required for the management of such distressing & case reported in this article particularly interesting. aesthetically & functionally compromising To the best of our knowledge, this case reported gingival pathologies. by us is the first report of bimaxillary aggressive GE as the presenting feature of CML. Imatinib is the drug of choice in treatment of CML. Imatinib Conflict of interest: None to declare. is the first member of a new class of agents that act by specifically inhibiting a certain enzyme that is characteristic of a particular cancer cell. Usage References of Imatinib has no side effects on gingiva or oral

tissues.

1. DongariBagtzoglou A. Informational Paper 5) False GE : – “DrugAssociated Gingival Enlargement. J

Periodontol 2004; 75:1241431. They relate to apparent increase in the size of 2. Pradhan S, Mishra P, Joshi S. Drug induced gingiva due to increase in size of underlying gingival enlargement – A review. PGNM, osseous & dental tissues. Gum enlargement due to 2009; Volume 8, Number 2. underlying osseous lesions like Tori, exostosis, 3. Ricardo D. Coletta, Edgard Graner. Fibrous dysplasia, Central cysts, Central Hereditary Gingival Fibromatosis: A neoplasms (Neurofibroma, Hemangioma, Systematic Review. J Periodontol, May Neurilemmoma, squamous cell etc.) & 2006; Volume 77, Number 5, page 753764. gum enlargement due to underlying dental tissues 4. Seymour RA, Smith DG, Turnbull DN. The like at time of eruption of teeth, or effects of phenytoin & sodium valproate on “Developmental enlargement” due to the periodontal health of adult epileptic superimposition of bulk of gingiva on the normal patients. J Clin Peridontol 1985; 12:413419. prominence of enamel.

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5. J. S. Ellis, R. A. Seymour, P. Robertson, T. 15. R. Arya, S. Gulati. Review Article J. Butler & J. M. Thomason. Photographic Phenytoininduced gingival overgrowth. scoring of gingival overgrowth. J Clin Acta Neurol Scand DOI: 10.1111/j.1600 Periodontol 2001; 28: 81–85. 0404.2011.01535.x page 1 7 6. Abdul Aziz Hasan, Sebastian Ciancio. 16. Daley. T, Wysocki. G & Day. C. Clinical & Relationship between Amphetamine pharmacologic correlations in cyclosporine Ingestion & Gingival Enlargement. Pediatric induced gingival hyperplasia. Oral Surgery. , 2004; 26:5, 396400. Oral Medicine. Oral Pathology 1986; 62, 7. Cliciane Portela Sousa, ClaudiaMaria 417421. Navarro, & Maria Regina Sposto, Research 17. Hessam Nowzari; & Sandra K. Rich. The Article Clinical Assessment of Nifedipine Impact of Systemic DiseaseAssociated Induced Gingival Overgrowth in a Group of Gingival Enlargement on Pediatric Patients. Brazilian Patients. ISRN Dentistry Volume Compendium January | February 2008— 2011, Article ID 102047, 5 pages. Volume 29, Number 1 8. Bo¨kenkamp A, Bahuharst B, Beier C, Albers N, Offner G, Brondehl J. Nifedipine 18. Lee H. Silverstein, J. Paul Koch, Michael D. aggravates cyclosporine Ainduced gingival Lefkove, Jerry J. Garnick, Baldev Singh, hyperplasia. Pediatr Nephrol 1994; 8: 181– David E. Steflik. Nifedipine – induced 185. Gingival Enlargement around Dental 9. Masatoshi Kataoka, Junichi Kido, Yasuo Implants: A Clinical Report. Journal of Oral Shinohara, & Toshihiko Nagata. Drug Implantology, Vol XXI, No : 2, 1995, page Induced Gingival Overgrowth—a Review. 116 120. Biol. Pharm. Bull. 28(10) 1817—1821 (2005). 19. Seymour RA, Thomason JM, Ellis JS. The 10. Prasad VN, Chawla HS, Goyal A, Gauba K, pathogenesis of druginduced gingival Singhi P. Incidence of phenytoin induced overgrowth”. J Clin Periodontol 1996; gingival overgrowth in epileptic children: a 23:16575. six month evaluation. J Indian Soc Pedod 20. Robin A. Seymour. Effects of medications Prev Dent 2002; 20:73–80. on the periodontal tissues in health & 11. Angelopoulos AP, Goaz PW. Incidence of disease. 2000, Vol. 40, diphenylhydantoin gingival hyperplasia. 2006, 120–129. Oral Surg Oral Med Oral Pathol 1972; 34:898–906. 21. Seymour RA, Heasman PA. Drugs & the 12. Arya R, Gulati S, Kabra M, Sahu JK, Kalra . J Clin Periodontol 1988: 15: V. Folic acid supplementation prevents 1–16. phenytoin induced gingival overgrowth in children. Neurology 2011; 76:1338–43. 22. King G. N, Fullinfaw R, Higgins T. J, 13. Kimball OP, Horan TN. The use of Dilantin Walker R. G, Francis D. M & Wiesenfeld D. in the treatment of epilepsy. Ann Intern Med Gingival hyperplasia in renal allograft 1939; 13:78793. recipients receiving cyclosporin A & 14. Joyce M. Brewer, Patricia A. Waltman. calcium antagonists. Journal of Clinical Epilepsy & Pregnancy: Maternal & Fetal Periodontology 1993; 20, 286–293. Effects of Phenytoin. Critical Care Nurse, April 2003; 23:2, 9398.

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23. Ellis J, Seymour R, Steele J, Robertson P, 30. SinhaMorton R, DongariBagtzoglou AI. Butler T & JM T. Prevalence of gingival Regulation of gingival fibroblast interleukin overgrowth induced by calcium channel 6 secretion by cyclosporine A. J Periodontol blockers: a community based study. Journal 1999; 70:14641471. of Periodontology 1999; 70, 63–67. 31. Aarli J.A, Phenytoininduced depression of 24. Pernu E. H, Knuuttila M. L. E, Huttenen K. salivary IgA & gingival enlargement. R. H & Tiilikainen A. S. K. Druginduced Epilepsia 1976; 17:283291. gingival overgrowth & class II major histocompatibility antigens. Transplantation 32. Hassell T. M. & Hefti A. F. Drug induced 1994; 57, 1811–1813. gingival overgrowth: old problem, new problem. Critical Reviews in Oral Biology 25. Petri K. Nurmenniemi, Hilkka E. Pernu, & Medicine, 1991; 2, 103–137. Paivi Laukkanen, & Matti L.E. Knuuttila. Macrophage subpopulations in gingival 33. Fujii A, Kobayashi S. Nifedipine inhibits overgrowth induced nifedipine & calcium uptake of nifedipine sensitive immunosuppressive medication. J gingival fibroblasts. J Dent Res 1990; 69: Periodontol November 2002, 73 (11): 1323 332. 1330. 34. Timothy D. Poppell, Stephen D. Keeling, J. 26. Hassell T, O’Donnell J, Pearlman J, Tesini Frank Collins, Thomas M. Hassell. Effect of D, Best H & Murphey T. Salivary phenytoin folic acid on recurrence of phenytoin levels in institutionalised epileptics. Journal induced gingival overgrowth following of Chronic Diseases 1983; 36, 899–906. gingivectomy. Journal of Clinical Periodontology, February 1991; Volume 18, 27. Hefti A. F, Eshenaur A. E, Hassell T. M. & Issue 2, pages 134–139. Stone C. Gingival overgrowth in cyclosporine A treated multiple sclerosis 35. M Behari, Letter to Editor “Gingival patients. Journal of Periodontology 1994; hyperplasia due to sodium valproate”, 65, 744–749. Journal of Neurology, Neurosurgery, & Psychiatry, 1991; 54: page 279 – 283. 28. Dahllof G. & Mode´er T. The effect of a plaque control program on the development 36. EegOllofsson O, Lundstrom A, Hamp SE, of phenytoininduced gingil overgrowth. A 2 “Oral state of children with epilepsy on year longitudinal study. Journal of Clinical treatment with sodium valproate”, Scand J Periodontology 1986; 13, 845– 984. Dent Res 1983; 91: page 21923.

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Legends of Pictures

Case 1

Figure 1

Figure 1 – Extra oral examination showing

convex profile of teeth with open bite and

incompetent lips with nodular masses of

gingiva seen between the protruded teeth.

Figure 2

Figure 2 Bulbous, fibrotic enlargement of both

maxillary and mandibular gingiva with cobble stone

appearance superadded with inflammatory components

as well. Two third portions of almost all the teeth crowns

covering with growing gums with resultant displacement

of the teeth and a midline shift.

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Case 2

Figure 3

Figure 3 – Short and stout fingers and toes.

Figure 4

Figure 4 – Facial examination revealed mild hypertrichosis, depressed nasal bridge and a nodular scar on the right lower lip.

Figure 5

Figure 5 Maxillary and mandibular gingiva covering two third of most of the teeth with resultant displacement of the

teeth and a midline shift with areas of inflammation and erythema of gingiva

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Case 3

Figure 6

Figure 6 Patient with CML presenting with

mild Bell’s palsy on left side of face.

Figure 7

Figure 7 – Generalized erythematous bulbous gingival enlargement of both upper and lower arches with spontaneous bleeding and exudate from gums

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