Gingival overgrowth is an undesirable outcome of systemic medication and is evidenced by the accretion of collagenous components in gingival connective tissues along with diverse degrees of inflammation. Phenytoin therapy has been found to induce the most fibrotic lesions in gingiva, cyclosporine caused the least fibrotic lesions, and nifedipine induced intermediate fibrosis in drug‑induced gingival overgrowth. In drug‑induced gingival overgrowth, efficient oral hygiene is compromised and has negative consequences for the systemic health of the patients. Toll‑like receptors (TLRs) are involved in the effective recognition of microbial agents and play a vital role in innate immunity and inflammatory signaling responses. TLRs stimulate fibrosis and tissue repairs in several settings, although with evident differences between organs. In particular, TLRs exert a distinct effect on fibrosis in organs with greater exposure to TLR ligands, such as the gingiva. Cumulative evidence from diverse sources suggested that TLRs can affect gingival overgrowth in several ways. Numerous studies have demonstrated the expression of TLRs in gingival tissues and suggested its potential role in gingival inflammation, cell proliferation and synthesis of the extracellular matrix which is crucial to the development of gingival overgrowth. In the present review, we assessed the role of TLRs on individual cell populations in gingival tissues that contribute to the progression of gingival inflammation, and the involvement of TLRs in the development of gingival overgrowth. These observations suggest that TLRs provide new insight into the connection among infection, inflammation, drugs and gingival fibrosis, and are therefore efficient therapeutic target molecules. We hypothesize that TLRs are critical for the development and progression of gingival overgrowth, and thus blocking TLR expression may serve as a novel target for antifibrotic therapy.
Gingival overgrowth is a side effect of certain medications. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, activated gingival fibroblasts synthesize and remodel newly created extracellular matrix. Proteins such as transforming growth factor (TGF), endothelin-1 (ET-1), angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to the development of gingival fibrosis. Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF-β, CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth.
Mast cells (MCs) are multifunctional effector cells that were originally thought to be involved in allergic disorders. Now it is known that they contain an array of mediators with a multitude of effects on many other cells. MCs have become a recent concern in drug-induced gingival overgrowth (DIGO), an unwanted outcome of systemic medication. Most of the studies have confirmed the significant presence of inflammation as a prerequisite for the overgrowth to occur. The inflammatory changes within the gingival tissue appear to influence the interaction between the inducing drug and the fibroblast activity. The development of antibodies to MC-specific enzymes, tryptase and chymase, has facilitated the study of mast cells in DIGO. Many immunohistochemical studies involving MCs have been conducted; as a result, DIGO tissues are found to have increased the number of MCs in the gingiva, especially in the area of fibrosis. At the cellular level, gingival fibrogenesis is initiated by several mediators which induce the recruitment of a large number of inflammatory cells, including MCs. The purpose of this paper is to access the roles played by MCs in gingival overgrowth to hypothesize a relationship between these highly specialized cells in the pathogenesis of DIGO.
Gingival overgrowth is a well-recognized unwanted effect associated with three major drugs / drug groups - phenytoin, cyclosporine and the calcium channel blockers. Cyclosporine is the first-choice immunosuppressant for preventing allograft rejection in patients who have received organ or bone marrow transplants. This report aims to highlight a case in which the patient on cyclosporine therapy had also contracted Hepatitis C virus infection.
Gingival overgrowth (gingival hyperplasia, gingival fibromatosis) can be caused by underlying factors such as taking certain medications or genetic in origin. The extent of the enlargement varies in different individuals and also within the same individuals. Aesthetics and effective plaque control is compromised and part of the objectives of treatment is to help in these aspects. (Copied from article).
Gingival enlargement comprises any clinical condition in which an increase in the size of the gingiva is observed. It is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressant, and calcium channel blockers. Among calcium channel blockers, nifedipine causes gingival enlargement in about 10% of patients, whereas the incidence of amlodipine, a third-generation calcium channel blocker, induced gingival enlargement is very limited. Because the calcium antagonists, albeit to a variable degree, act as inhibitors of P-glycoprotein (P-gp), the gene product of multidrug resistance 1 (MDR1), and inflammation may modify P-gp expression. We hereby, report a case of amlodipine-induced gingival enlargement with MDR1 3435C/T polymorphism, associated with inflammatory changes due to plaque accumulation, in a 50-year-old hypertensive male patient. The genotype obtained for the polymorphism was a heteromutant genotype, thus supporting the contention that the MDR1 polymorphism may alter the inflammatory response to the drug.
A study was undertaken to estimate the histological changes of gingival enlargement induced by
Cyclosporin A (CsA) and Nifedipine, separately and in combination. Twelve adult rabbits were divided equally into four main groups. The first group received 10 mg/kg/day Nifedipine, the second received 10 mg/kg/day CsA, and the third received a combination of 10 mg/kg /day Nifedipine and CsA by gastric feeding. The fourth was regarded as a control group. Animals were given the drugs from day 1 of the experiment until day 70. They were then sacrificed for histological purposes. Results showed increase in the thickness of the epithelium with keratosis and acanthosis, and also increased vascularity. Collagen fibres and fibroblasts at different rates in the three histological groups were observed. Significant alveolar bone resorption with increased marrow spaces filled with fatty tissue were found in the CsA group. Non-significant changes in the alveolar bone of the Nifedipine group while subsequent bone resorption and bone deposition were seen in the combination group. These changes could be due to the effect of both drugs. Significant changes in the gingiva and the alveolar bone were shown in the three experimental groups compared with the control group.
Gingival overgrowth is frequently observed in patients taking certain drugs such as calcium channel blockers, anticonvulsants and immunosuppressant. This can have a significant effect on the quality of life as well as increasing the oral bacterial load by generating plaque retention sites. Amlodipine, a third generation calcium channel blockers has been shown to promote gingival overgrowth although in very limited cases reported. The management of gingival overgrowth seems to be directed at controlling gingival inflammation through a good oral hygiene regimen. However in severe cases, surgical excision is the most preferred method of treatment, followed by rigorous oral hygiene procedures. This case report describes the management of gingival overgrowth in a hypertensive patient taking amlodipine. Combination of surgical gingivectomy and CO2 laser treatment was used to remove the gingival overgrowth. CO2 laser surgery produced good hemostasis and less pain during the procedure and post operatively. This case report has also shown that periodontal treatment alone without a change in associated drug can yield satisfactory clinical response.