**3.3 Drug-induced gingival enlargement**

The growth starts as painless bead like enlargement in the papillary region which extends on the facial and lingual region. As the overgrowth increases the massive fold of tissue can be observed covering considerable or entire portion of crown. This will result in one or more problems like difficulty in oral hygiene maintenance and mastication, may alter tooth eruption, interference of speech and esthetic issues [7, 8].

The clinical appearance reveals firm and fibrotic component unless superimposed by secondary infection because of lack of oral hygiene and biofilm accumulation. These secondary changes include change in color of gingiva, increased bleeding tendency and superimposed inflammation obliterates the demarcation of the lobules [6].

Phenytoin induced gingival overgrowth (**Figure 3**) is characterized by granular or pebbly surface with enlargement of interdental papilla to an extent they result in pseudoclefts. The growth diminishes as they reach to the mucogingival junction but continue to grow in coronal direction resulting in partial or complete obscure of teeth [9]. The systemic administration of phenytoin accelerates the healing of gingival wounds in nonepileptic humans and increases the tensile strength of healing abdominal wounds in rats [10]. Cyclosporin induced enlargement appears to be more prominent on the labial surface, hyperemic, soft, friable and has high bleeding tendency. Calcium channel blocker (**Figure 4**) affects papillary region initially resulting into a lobular and nodular morphology extending to attached and marginal gingival. The inflammatory changes are associated leading to poor plaque control and esthetic concerns [11]. Gingival enlargement is greater in patients

**93**

**Figure 4.**

*Nifedipine induced gingival enlargement.*

*Treatment of Gingival Enlargement*

*DOI: http://dx.doi.org/10.5772/intechopen.82664*

ity response to the cyclosporine [13].

*Phenytoin induced gingival enlargement.*

**Figure 3.**

who are medicated with both cyclosporine and calcium channel blockers [12]. The microscopic finding of many plasma cells plus the presence of an abundant amorphous extracellular substance has suggested that the enlargement is a hypersensitiv-

The probable mechanism include role of fibroblasts, inflammatory cytokines

A synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts was found when these cells were simultaneously exposed to nifedipine and interleukin-1β (IL-1β), a proinflammatory cytokine that is elevated in inflamed gingival tissues. In addition to IL-1β, IL-6 may play a role in the fibrogenic responses of the gingiva to these medications. A reported histologic feature of cyclosporininduced gingival lesions is a elevation in the expression of IL-6 by cells within the gingival connective tissue. IL-6 appears to target connective tissue cells such as fibroblasts both by enhancing proliferation and by exerting a positive regulation on

It was also assumed that these drugs may interfere with the synthesis and function of collagenases. In support of this hypothesis, a recent in vitro study has shown that human gingival fibroblasts treated with clinically relevant cyclosporin doses

and matrix metalloproteinases (MMP). It has been seen that not all patients treated with these drugs show alteration in size of gingival rather some have very pronounced effect. It has been hypothesized that these individuals have fibroblasts with an abnormal susceptibility to the drug. Fibroblasts from overgrown gingiva in phenytoin-treated patients are characterized by elevated levels of protein synthesis, most of which is collagen. The susceptibility to enlargement is governed by presence

of fibroblast subsets which are reactive to these medications [14].

collagen and glycosaminoglycan synthesis [14].

**Figure 2.** *Periodontal abscess.*

*Treatment of Gingival Enlargement DOI: http://dx.doi.org/10.5772/intechopen.82664*

*Gingival Disease - A Professional Approach for Treatment and Prevention*

The growth starts as painless bead like enlargement in the papillary region which extends on the facial and lingual region. As the overgrowth increases the massive fold of tissue can be observed covering considerable or entire portion of crown. This will result in one or more problems like difficulty in oral hygiene maintenance and mastication, may alter tooth eruption, interference of speech and esthetic

The clinical appearance reveals firm and fibrotic component unless superimposed by secondary infection because of lack of oral hygiene and biofilm accumulation. These secondary changes include change in color of gingiva, increased bleeding tendency and superimposed inflammation obliterates the demarcation of

Phenytoin induced gingival overgrowth (**Figure 3**) is characterized by granular or pebbly surface with enlargement of interdental papilla to an extent they result in pseudoclefts. The growth diminishes as they reach to the mucogingival junction but continue to grow in coronal direction resulting in partial or complete obscure of teeth [9]. The systemic administration of phenytoin accelerates the healing of gingival wounds in nonepileptic humans and increases the tensile strength of healing abdominal wounds in rats [10]. Cyclosporin induced enlargement appears to be more prominent on the labial surface, hyperemic, soft, friable and has high bleeding tendency. Calcium channel blocker (**Figure 4**) affects papillary region initially resulting into a lobular and nodular morphology extending to attached and marginal gingival. The inflammatory changes are associated leading to poor plaque control and esthetic concerns [11]. Gingival enlargement is greater in patients

**3.3 Drug-induced gingival enlargement**

*Chronic inflammatory enlargement.*

issues [7, 8].

**Figure 1.**

the lobules [6].

**92**

**Figure 2.** *Periodontal abscess.*

**Figure 3.** *Phenytoin induced gingival enlargement.*

who are medicated with both cyclosporine and calcium channel blockers [12]. The microscopic finding of many plasma cells plus the presence of an abundant amorphous extracellular substance has suggested that the enlargement is a hypersensitivity response to the cyclosporine [13].

The probable mechanism include role of fibroblasts, inflammatory cytokines and matrix metalloproteinases (MMP). It has been seen that not all patients treated with these drugs show alteration in size of gingival rather some have very pronounced effect. It has been hypothesized that these individuals have fibroblasts with an abnormal susceptibility to the drug. Fibroblasts from overgrown gingiva in phenytoin-treated patients are characterized by elevated levels of protein synthesis, most of which is collagen. The susceptibility to enlargement is governed by presence of fibroblast subsets which are reactive to these medications [14].

A synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts was found when these cells were simultaneously exposed to nifedipine and interleukin-1β (IL-1β), a proinflammatory cytokine that is elevated in inflamed gingival tissues. In addition to IL-1β, IL-6 may play a role in the fibrogenic responses of the gingiva to these medications. A reported histologic feature of cyclosporininduced gingival lesions is a elevation in the expression of IL-6 by cells within the gingival connective tissue. IL-6 appears to target connective tissue cells such as fibroblasts both by enhancing proliferation and by exerting a positive regulation on collagen and glycosaminoglycan synthesis [14].

It was also assumed that these drugs may interfere with the synthesis and function of collagenases. In support of this hypothesis, a recent in vitro study has shown that human gingival fibroblasts treated with clinically relevant cyclosporin doses

**Figure 4.** *Nifedipine induced gingival enlargement.*

exhibit significantly reduced levels of MMP-1 and MMP-3 secretion; these reduced levels may contribute to the accumulation of extracellular matrix components [15].

### **3.4 Idiopathic gingival enlargement**

It is an uncommon benign hereditary condition with no specific cause. It is characterized by slow progressive firm and fibrous enlargement of gingiva. Synonyms are hereditary gingival fibromatosis, elephantiasis gingivae, congenital hypertrophy of gingiva, fibromatosis gingivae, congenital macrogingivae and hypertrophic gingiva. The color of the tissue appears pale pink, has characteristic leathery consistency and pebbled surface (**Figures 5** and **6**). Exaggerated stippling is observed. The enlargement poses esthetic and functional irregularities. It may also lead to displacement of teeth. It affects attached, marginal and interdental gingiva. The genetic mechanisms are not well understood [16]. The gingival enlargement usually begins at the time of eruption of the permanent dentition but can develop with the eruption of the deciduous dentition and rarely is present at birth [17].

#### **3.5 Conditioned enlargement**

It occurs when the patient response to plaque accumulation is magnified because of the systemic condition of the patient.

Enlargement in pregnancy: it occurs as single or multiple tumor like masses in the marginal or attached gingiva. The hormonal change in the pregnancy leads to increased vascular permeability, gingival edema and increased response to dental plaque. The lesion appears as mushroom like, bleed easily, sessile or pedunculated, protruding from the margin or interproximal area. The lesion does not invade the bone and has pinpoint markings on the surface (**Figure 7**). The lesion usually grows till third trimester after which it may regress spontaneously [2]. The hormonal changes induce changes in vascular permeability, which leads to gingival edema and an increased inflammatory response to dental plaque. The subgingival microbiota may also undergo changes, including an increase in Prevotella intermedia [18].

Enlargement in puberty: Due to change in hormones during adolescences leads to aggravated response during puberty in areas of plaque accumulation. It is manifested as bulbous enlargement in the papillary region leading to enlargement in facial region, lingual region is relatively unaffected. The tendency for recurrence into massive enlargement in presence of scanty deposits differentiates it from chronic inflammatory enlargement [2].

A longitudinal study of 127 children between the ages of 11 and 17 years demonstrated a high initial prevalence of gingival enlargement that tended to decline with

**95**

**Figure 7.**

*Enlargement in pregnancy.*

*Treatment of Gingival Enlargement*

**Figure 6.**

*DOI: http://dx.doi.org/10.5772/intechopen.82664*

with rapidly progressive periodontitis [22].

*Idiopathic gingival enlargement (right lateral).*

**3.6 Nonspecific conditioned enlargement**

**3.7 Systemic diseases that cause gingival enlargement**

age [19]. Studies have reported that hormonal changes coincide with an increase in

Plasma cell gingivitis: synonyms are atypical gingivitis and plasma cell gingivostomatitis, it exhibits enlargement in marginal gingiva extending onto attached gingiva. Gingiva appears reddish, soft, friable, and sometimes granular and has high bleeding tendency; no loss of attachment is seen (if not periodontally involved). It is located in the facial aspect of the attached gingiva and thus distinguished from plaque-induced gingivitis [6]. In rare instances, marked inflammatory gingival enlargements with a predominance of plasma cells can appear; these are associated

Pyogenic granuloma: it is a tumor-like enlargement of gingiva which is considered to be exaggerated conditioned response to minor trauma. The exact nature of the systemic conditioning factor has not been identified [23]. The lesion varies from a discrete spherical, tumor-like mass with a pedunculated attachment to a flattened, keloid-like enlargement with a broad base. It is bright red or purple and either friable or firm, depending on its duration; in the majority of cases it presents with surface ulceration and purulent exudation (**Figure 8**). The lesion tends to involute spontaneously to become a fibroepithelial papilloma, or it may persist relatively unchanged for years [6].

Leukemia: leukemic enlargement is prominently because of accumulation of leukemic cells in the gingival. It manifests as diffuse or solitary and localized or

the proportion of Prevotella intermedia and Prevotella nigrescens [20, 21].

**Figure 5.** *Idiopathic gingival enlargement (left lateral).*

*Treatment of Gingival Enlargement DOI: http://dx.doi.org/10.5772/intechopen.82664*

*Gingival Disease - A Professional Approach for Treatment and Prevention*

eruption of the deciduous dentition and rarely is present at birth [17].

**3.4 Idiopathic gingival enlargement**

**3.5 Conditioned enlargement**

of the systemic condition of the patient.

chronic inflammatory enlargement [2].

*Idiopathic gingival enlargement (left lateral).*

exhibit significantly reduced levels of MMP-1 and MMP-3 secretion; these reduced levels may contribute to the accumulation of extracellular matrix components [15].

It is an uncommon benign hereditary condition with no specific cause. It is characterized by slow progressive firm and fibrous enlargement of gingiva. Synonyms are hereditary gingival fibromatosis, elephantiasis gingivae, congenital hypertrophy of gingiva, fibromatosis gingivae, congenital macrogingivae and hypertrophic gingiva. The color of the tissue appears pale pink, has characteristic leathery consistency and pebbled surface (**Figures 5** and **6**). Exaggerated stippling is observed. The enlargement poses esthetic and functional irregularities. It may also lead to displacement of teeth. It affects attached, marginal and interdental gingiva. The genetic mechanisms are not well understood [16]. The gingival enlargement usually begins at the time of eruption of the permanent dentition but can develop with the

It occurs when the patient response to plaque accumulation is magnified because

Enlargement in pregnancy: it occurs as single or multiple tumor like masses in the marginal or attached gingiva. The hormonal change in the pregnancy leads to increased vascular permeability, gingival edema and increased response to dental plaque. The lesion appears as mushroom like, bleed easily, sessile or pedunculated, protruding from the margin or interproximal area. The lesion does not invade the bone and has pinpoint markings on the surface (**Figure 7**). The lesion usually grows till third trimester after which it may regress spontaneously [2]. The hormonal changes induce changes in vascular permeability, which leads to gingival edema and an increased inflammatory response to dental plaque. The subgingival microbiota may also undergo changes, including an increase in Prevotella intermedia [18]. Enlargement in puberty: Due to change in hormones during adolescences leads to aggravated response during puberty in areas of plaque accumulation. It is manifested as bulbous enlargement in the papillary region leading to enlargement in facial region, lingual region is relatively unaffected. The tendency for recurrence into massive enlargement in presence of scanty deposits differentiates it from

A longitudinal study of 127 children between the ages of 11 and 17 years demonstrated a high initial prevalence of gingival enlargement that tended to decline with

**94**

**Figure 5.**

**Figure 6.** *Idiopathic gingival enlargement (right lateral).*

age [19]. Studies have reported that hormonal changes coincide with an increase in the proportion of Prevotella intermedia and Prevotella nigrescens [20, 21].

Plasma cell gingivitis: synonyms are atypical gingivitis and plasma cell gingivostomatitis, it exhibits enlargement in marginal gingiva extending onto attached gingiva. Gingiva appears reddish, soft, friable, and sometimes granular and has high bleeding tendency; no loss of attachment is seen (if not periodontally involved). It is located in the facial aspect of the attached gingiva and thus distinguished from plaque-induced gingivitis [6]. In rare instances, marked inflammatory gingival enlargements with a predominance of plasma cells can appear; these are associated with rapidly progressive periodontitis [22].
