Drug-induced Gingival Overgrowth Research Articles

The Unilateral Enigma: An Oral-contraceptive Related Gingival Enlargement

ABSTRACT This article’s goal is to describe a case of oral contraceptives-related drug-induced gingival hypertrophy that was treated with nonsurgical and surgical periodontal therapy. The most prevalent negative side effect of systemic medicine on the periodontal tissues continues to be drug-induced gingival overgrowth. Specific regulatory molecules known as hormones control a variety of bodily processes. Gingival hypertrophies are sometimes linked to oral contraceptives that contain oestrogen and/or progesterone. A 32-year-old female presented with a complaint of swelling of the gingiva with spontaneous bleeding in the maxillary right quadrant region for a period of two months. The medical history documented the use of contraceptives for three months, and a clinical examination revealed the existence of poor oral hygiene and enlarged painful gingival tissues that bled when touched. Intraoral examination revealed that there was unilateral, generalized, diffuse gingival enlargement with pseudo pockets. Patient was diagnosed with gingival fibromatosis a based on the clinical, histological, and radiographic findings. The gingival enlargement was treated by conventional gingivectomy under local anaesthesia. The postoperative result was uneventful. Women who use oral contraceptives are a “risk group” for periodontal infections. On oral contraceptives, not every female reacts the same way. In periodontal therapy, plaque management is the most crucial step. Patient compliance is another element that affects a therapy’s response. The patient demonstrated appropriate oral hygiene practices and adhered to home care guidelines adequately.

Individualized digitally designed surgical template for guided soft tissue surgery in cases with severe gingival enlargement: A clinical application in hereditary gingival fibromatosis.

The purpose of this study was to present the use of computer-assisted periodontal surgery utilizing a novel surgical guide for cases with severe gingival enlargement through a clinical application in a patient with hereditary gingival fibromatosis. The treatment plan included nonsurgical periodontal therapy, surgical periodontal treatment, and regular periodontal maintenance before the initiation of orthodontic treatment. Due to the increased soft tissue thickness, a surgical guide with a novel design was fabricated to facilitate the periodontal surgery since most of the patient's teeth were malpositioned and underexposed due to fibromatosis. For this purpose, the patient's intraoral scan was merged with a CBCT image in order to plan surgical excisions based on the anatomy of the teeth and the bone contour. The customized surgical guide facilitated the gingivectomy by controlling not only the shape of the initial incisions but also their orientation toward the level of the cementoenamel junction, improving the efficiency of the clinical time compared with freehand surgery and assisting in the verification of the final soft tissue shape, based on the treatment plan. Digital technology through the superimposition of multiple data sets can assist in the diagnosis and multidisciplinary management of cases with gingival fibromatosis. The proposed design of the surgical guide can facilitate soft tissue surgery based on the digital treatment plan, leading to more predictable management of the soft tissue, especially in patients with severe gingival enlargement, as in cases with hereditary gingival fibromatosis or drug-induced gingival overgrowth.

Epithelial-to-mesenchymal transition, inflammation, subsequent collagen production, and reduced proteinase expression cooperatively contribute to cyclosporin-A-induced gingival overgrowth development.

Drug-induced gingival overgrowth (DIGO), induced by certain immunosuppressive drugs, antihypertensive agents, and antiepileptic drugs, may contribute to the formation of deeper periodontal pockets and intractableness in periodontitis. To date, multiple factors such as enhanced matrix production, inflammation, and reduced matrix degradation might be involved in the pathogenesis of DIGO. We have previously reported that SPOCK-1, a heparan sulfate proteoglycan, could affect gingival thickening by promoting epithelial-to-mesenchymal transition (EMT) in gingival keratinocytes. However, few studies have investigated whether a combination of these factors enhances the DIGO phenotype in animal models. Therefore, we investigated whether SPOCK-1, periodontal inflammation, and cyclosporin-A (CsA) could cooperatively promote gingival overgrowth. We first confirmed that Spock-1 overexpressing (Spock1-Tg) mice showed significantly thicker gingiva and greater alveolar bone loss than WT mice in response to ligature-induced experimental periodontitis. DIGO was induced by the combination of CsA administration and experimental periodontitis was significantly enhanced in Spock1-Tg mice compared to that in WT mice. Ligature-induced alveolar bone loss in CsA-treated Spock1-Tg mice was also significantly greater than that in CsA-treated WT mice, while being accompanied by an increase in Rankl and Col1a1 levels and a reduction in matrix metalloprotease expression. Lastly, SPOCK-1 promoted RANKL-induced osteoclast differentiation in both human peripheral blood mononuclear cells and murine macrophages, while peritoneal macrophages from Spock1-Tg mice showed less TNFα and IL-1β secretion than WT mice in response to Escherichia coli lipopolysaccharide. These results suggest that EMT, periodontal inflammation, and subsequent enhanced collagen production and reduced proteinase production contribute to CsA-induced DIGO pathogenesis.

Developing novel therapy for drug-induced gingival overgrowth by targeting NR4A1

Developing novel therapy for drug-induced gingival overgrowth by targeting NR4A1

Amlodipine-induced gingival enlargement: A case report

Drug-induced gingival overgrowth (DIGO) is a result of side effect of certain drugs. Among calcium channel blockers, gingival enlargement is more commonly seen with nifedipine. We present a rare case report of amlodipine-induced gingival enlargement which resolved after 4 weeks of stoppage of drug.

Drug-Induced Gingival Overgrowth—Molecular Aspects of Drug Actions

Drug-induced gingival overgrowth (DIGO) is one of the side effects produced by therapeutic agents, most commonly phenytoin, nifedipine and cyclosporin A. However, the precise mechanism of DIGO is not entirely understood. A literature search of the MEDLINE/PubMed databases was conducted to identify the mechanisms involved in DIGO. The available information suggests that the pathogenesis of DIGO is multifactorial, but common pathogenic sequelae of events emerge, i.e., sodium and calcium channel antagonism or disturbed intracellular handling of calcium, which finally lead to reductions in intracellular folic acid levels. Disturbed cellular functions, mainly in keratinocytes and fibroblasts, result in increased collagen and glycosaminoglycans accumulation in the extracellular matrix. Dysregulation of collagenase activity, as well as integrins and membrane receptors, are key mechanisms of reduced degradation or excessive synthesis of connective tissue components. This manuscript describes the cellular and molecular factors involved in the epithelial-mesenchymal transition and extracellular matrix remodeling triggered by agents producing DIGO.

Enhancement of receptor-mediated calcium responses by phenytoin through the suppression of calcium excretion in human gingival fibroblasts.

Gingival overgrowth caused by phenytoin is proposed to be associated with Ca2+ signaling; however, the mechanisms that increase the intracellular Ca2+ concentration ([Ca2+ ]i ) are controversial. The current study aimed to elucidate the mechanism underlying the phenytoin-induced increase in [Ca2+ ]i in human gingival fibroblasts (HGFs). Effects of 100 μM phenytoin on [Ca2+ ]i in HGFs were examined at the single-cell level using fluorescence images of fura-2 captured by an imaging system consisting of an EM-CCD camera coupled to an inverted fluorescence microscope at room temperature. Exposure of HGFs to 100 μM phenytoin induced a transient increase in [Ca2+ ]i in the absence of extracellular Ca2+ , indicating that the phenytoin-induced increase in [Ca2+ ]i does not require an influx of extracellular Ca2+ . In addition, phenytoin increased [Ca2+ ]i in HGFs depleted of intracellular Ca2+ stores by thapsigargin, indicating that neither Ca2+ release from stores nor inhibition of Ca2+ uptake is involved. Furthermore, the phenytoin-induced [Ca2+ ]i elevation was reduced to 18.8% in the absence of extracellular Na+ , and [Ca2+ ]i elevation upon removal of extracellular Na+ was reduced to 25.9% in the presence of phenytoin. These results imply that phenytoin increases [Ca2+ ]i of HGFs by suppressing the Na+ /Ca2+ exchanger. Suppression of intracellular Ca2+ excretion is thought to enhance the Ca2+ responses induced by various stimuli. Analysis at the single-cell level showed that stimulation with 1μM ATP or 3μM histamine increased [Ca2+ ]i in 20-50% of cells, and [Ca2+ ]i increased in many unresponsive cells in the presence of phenytoin. Our findings demonstrate that phenytoin induced increase in [Ca2+ ]i by the inhibition of Ca2+ efflux in HGFs. It was also found that phenytoin strongly enhanced small Ca2+ responses induced by stimulation with a low concentration of ATP or histamine by inhibiting Ca2+ efflux. These findings suggest a possibility that phenytoin causes drug-induced gingival overgrowth by interacting with inflammatory bioactive substances in the gingiva.

Dental management of a child patient with phenytoin-induced gingival overgrowth: report of a case with a brief review of literature

Drug-induced gingival overgrowth is medication-related gingival overgrowth commonly associated with certain systemic medications. Gingival overgrowth is a common adverse effect of phenytoin therapy. The condition is more frequently seen in children as compared to adults, affects both genders equally, and may vary from mild to severe. It may be associated with difficulty in mastication, delayed eruption of teeth, tissue trauma, and secondary inflammation. It can be managed by both surgical and nonsurgical therapies. A case of dental management of phenytoin-induced gingival enlargement in a 7-year-old girl is presented with a brief literature review.

Cyclosporine-induced gingival overgrowth-Review.

Drug-induced gingival overgrowth (DIGO) is an undesirable effect resulting from the therapy of one of the three groups of drugs: phenytoin, calcium channel blockers, and cyclosporine A (CsA). It is caused by a fibrous overgrowth leading to gingivitis, periodontitis, and even tooth loss. Possible consequences include tooth decay worsening, pain and difficulty in eating, bleeding gums, and bad breath. The pathomechanism of the hypertrophy is unknown, but there is a correlation between insufficient oral hygiene and the severity of this phenomenon. The gender and age predilection of gingival hyperplasia as a result of CsA therapy is also noticeable. It is most common in children and adolescents of the male sex. The beneficial effect of the removal of tartar and local irritants in reducing the above symptoms has been demonstrated. One of the treatments for DIGO is conventional gingivectomy. The paper is a review article about cyclosporine-induced gingival hyperplasia.

Photodynamic therapy for the successful management of cyclosporine-related gum hypertrophy: A novel therapeutic option.

Background:Drug-induced gingival overgrowth is associated with the intake of three classes of drugs: anticonvulsants, immunosuppressants, and calcium channel blockers. It is clinically characterized by hyperplasia of the gingival connective tissue which appears edematous, bloody, and purplish-red in color. In more severe cases, drug-induced gingival hyperplasia negatively affects the patient’s quality of life, making it difficult to eat and practice good oral hygiene. Drug-induced gingival overgrowth therapy is controversial and, in fact, no studies in the literature highlight a well-defined therapeutic protocol. The therapies that are described provide primarily for non-surgical periodontal treatment and second-line surgical treatment. The aim of this work is to highlight a case of drug-induced gingival hyperplasia which was completely resolved thanks to photodynamic therapy which is completely free from side effects.Design and Methods:Photodynamic therapy was performed on an 18 year-old female patient with LEDs at a power of 450–470 nm and 5500 mW/cm2 + 7500 mW/cm2, combined with a Curcuma longa-based photosensitizer. A single session was performed, with applications of approximately 30 s for each interdental papilla.Results:The patient improved markedly after only one cycle of PDT. There was an absence of clinically detectable inflammation, edema, and rubor of the involved dental papillae. At the 4, 6, and 12 week follow-ups there were no recurrences.Conclusions:This case report highlights the first case of drug-induced gingival hypertrophy entirely treated with photodynamic therapy to be described in the literature. Therefore, although it is only a case report, this therapy which is free from side effects should be investigated as an alternative to current therapies.

Bibliometric analysis of research trends and characteristics of drug-induced gingival overgrowth.

ObjectivesDrug-induced gingival overgrowth (DIGO) is a frequent adverse medication reaction that is generally caused by cyclosporine, phenytoin, and nifedipine, which belong to the category of immunosuppressants, anticonvulsants, and calcium channel blockers, respectively. This bibliometric analysis aims to depict the main citation characteristics and analyze the research trends in DIGO investigations.MethodsAn exhaustive search was performed in the Scopus database to create the bibliometric list of DIGO in the syntax. Furthermore, the information related to the number of citations, drugs related to DIGO, study topic and design, authorship, publication year, journal, contributing institution, country of origin, and the department was extracted.ResultsIn total, 399 papers on DIGO were retrieved in this study. The total number of citations and that after the removal of self-citations were 7,814 and 7,314, respectively. The mean number of citations was 19.6 in a range of 0–608. The main paper types were articles (76.94%) and reviews (19.55%). A remarkable increasing trend in the number of citations has been observed since 1994. Cyclosporine (44.89%) is the most commonly used drug that shares a close relationship with DIGO, followed by phenytoin (18.22%), nifedipine (17.93%), and amlodipine (6.81%). The review (27.82%) type constituted the most widely used design in the DIGO studies. According to the top 20 keywords, the risk factors and pathogenesis of DIGO have been prominent topics of research works for several years.ConclusionsThis bibliometric analysis will facilitate the understanding of researchers and clinicians, especially those at the beginning of their careers in periodontology on DIGO, by identifying landmark research and providing an overview of this field.

Drug-induced Gingival Overgrowth: Report of Two cases

Drug-induced Gingival Overgrowth: Report of Two cases

Impact of Immunosuppressive Drugs on Fibroblasts: An In Vitro Study.

Background: The aim of this study was to compare the direct impact of different agents for immunosuppressive therapy on mouse fibroblasts as a possible cause of drug-induced gingival overgrowth (DIGO). Methods: 3T3 mouse fibroblasts were cultivated in cell-specific media (2 × 104 cells/mL) and treated for 6, 24, 48 and 72 h with one of three immunosuppressive drugs (IsDs): cyclosporin a (CsA), tacrolimus (TaC) and sirolimus (SiR). Different concentrations (10–750 ng/mL) were used to mimic serum levels under active immunosuppressive therapy conditions. Cell population characteristics (cell number, viability and morphology) were assessed using computer-assisted cell analysis. Expression of pro-collagen type I carboxy-terminal propeptide (PICP) was identified using an ELISA assay. Results: The influence of IsDs on the biological status of 3T3 fibroblasts was time- and dose-dependent. Comparing CsA and TaC, the total cell amount was enhanced using concentrations in the range of 10–150 ng/mL (p > 0.05). In contrast, treatment with SiR resulted in a decrease in the average cell number (p < 0.01). PICP and cell diameter of fibroblasts were not susceptible to IsD treatment (p > 0.05). Conclusions: Our results revealed time-dependent effects of IsDs, with distinct influences on cell number. The cell morphology and the PICP balance of the investigated fibroblast cell line remained unaffected. Hence, the potential role of IsDs is not a unilateral mechanism of action but rather a multifactorial process.

Oral findings in kidney transplant children and adolescents.

Children and adolescents undergoing kidney transplantation may present oral conditions after the procedure, but a few studies have recently described them. To describe the oral conditions of post-renal transplant children and adolescents. Two calibrated dentists examined all the participants by assessing caries experience, enamel defects, periodontal condition and soft tissue lesions. A total of 120 participants were included in the study, in which 63 (52.5%) were male and 57 (47.5%) were female, with a mean age of 12.78±3.9years. Among the participants, 104 (86.7%) showed at least one oral change directly related to kidney disease. The most frequent oral findings were enamel defect (49/120; 40.8%) and drug-induced gingival overgrowth (DIGO) (20/120; 16.7%). Gingival bleeding was observed on probing in 115 (95.8%) participants, whereas 69 (57.5%) presented dental calculus and 51 (42.5%) had caries experience. Gingival bleeding, enamel defects and DIGO were the most frequent oral findings in kidney transplant children and adolescents. The use of amlodipine and anticonvulsants was associated with DIGO, and there was a positive correlation between oral ulcers and use of everolimus.

Amlodipine-Associated Gingival Hyperplasia: A Case Report and Review of Literature

Gingival overgrowth can be adverse reaction of calcium channel blockers. Although nifedipine is commonly associated with this process, some case reports have also implicated amlodipine as a possible etiology. Here we present a case of a 59-yearold Pakistani female who developed gingival hyperplasia secondary to amlodipine use. We believe that the knowledge about amlodipine-associated gingival hyperplasia is necessary for dentists, so they can accurately diagnose this condition and provide appropriate management. KEYWORDS: Drug-induced gingival overgrowth (DIGO), gingival hyperplasia, amlodipine

Assessment of Awareness among Physicians Regarding Gingival Overgrowth Induced by Anticonvulsant, Calcium Channel Blocker, and Immunosuppressant Therapy

Introduction: Drug Induced Gingival Overgrowth (DIGO) is caused due to prolonged use of anti-convulsants, immunosuppressant, and calcium channel blockers given for non dental purpose. It affects the maintenance of oral hygiene and may cause speech, mastication, tooth eruption and aesthetic problems. General physicians can play a key role as they can inform the patient about gingival overgrowth as an adverse effect of these drugs. Aim: To evaluate the awareness regarding drug induced gingival overgrowth and to know the impact of educational qualification on their awareness among physicians. Materials and Methods: This cross-sectional questionnaire survey was conducted from January 2019 to June 2019 in Latur district of Maharashtra, India. A total of 196 practicing physicians were approached with self-structured questionnaire and answers were collected in the presence of the investigator. Survey responses were divided into two groups based on educational qualification as group A: physicians educationally qualified to practice Allopathy, group B: physicians educationally qualified to practice alternative medicine (Ayurveda, Homeopathy etc.,). Comparison of responses for qualitative variables was carried among groups using Chi square test with p-value set as p&lt;0.05 significant. Results: Total 167 (85.20%) general physicians responded willingly and completed the questionnaire. A total of 129 participants were male, and 38 were female, with age ranging from 27 to 61 years. Among total 88.62%, 34.73%, 43.11% of the physicians knew about adverse effect of antiepileptic, antihypertensive, immunosuppressant drug as gingival overgrowth respectively. Around 50.89% physicians’ check the gingival status of their patients and 21.56% refer their patients to dental practitioners for signs and treatment of gingival overgrowth. Overall, 77.25% of participants said that surgical excision with drug substitution should be the line of treatment for these cases. Statistically significant difference was seen on comparative analysis of responses between group A and group B (p&lt;0.05). Conclusion: The findings of the present study showed that even though physicians know about drug induced gingival overgrowth they were unable to mention the accountable drug. Only few of them check gingival status of patients taking these drugs during follow up visits and refer such patients to dental practitioners. Although physicians qualified in allopathy have more knowledge about these drugs, their approach towards this condition was somewhat similar to the physicians qualified in alternative medicine.

Perindopril Arginine, Indapamide, and Amlodipine Fixed Dose Combination Induced Gingival Overgrowth: Two Cases with Specific Clinical Presentation

Drug induced gingival overgrowth (DIGO) is a frequent adverse effect of systemic medications. Amlodipine, although accepted as a safe antihypertensive drug due to its longer duration of action with lower dose and fewer adverse reactions compared to other antihypertensive agents, is among the causative drugs. As the aetiology of hypertension is multifactorial, a fixed dose combination containing amlodipine and other antihypertensive agents is currently preferred by physicians as a new treatment approach. The aim of this article is to report two cases of perindopril arginine, indapamide, and amlodipine fixed dose combination induced gingival overgrowth with an emphasis on the specific clinical presentation. Intraoral examination revealed poor oral hygiene, excessive dental plaque accumulation, and erythematous, oedematous, lobulated, enlarged marginal and interdental gingivae prone to bleeding. It was noteworthy that a red band appearance was present on the enlarged labial marginal gingivae in the patients. One month after the drug substitution, proper oral hygiene education and plaque control, and non-surgical periodontal treatment, a marked regression in DIGO and accompanying inflammatory symptoms were observed. Medical and dental practitioners should be aware that antihypertensive drugs used alone or in combination with other agents have the potential to cause gingival overgrowth.

Gingival overgrowth and associated factors in a population of Nigerian hypertensives

Background: Gingival overgrowth may be idiopathic or secondary. Drug Induced Gingival Overgrowth (DIGO) occurs within 3 months of treatment and is more prevalent in younger age group with predilection for the anterior gingival tissue and usually not associated with attachment loss or tooth mobility unless there is an existing periodontal disease. Methodology: 170 hypertensive patients were recruited for the study; 85 calcium channel blocker (CCB) and 85 non-CCB users. Interviewer-administered questionnaires was used to obtain socio-demographic information as well as medical and drug history. GO was assessed using New Clinical Index for DIGO and data was analyzed with SPSS version 21 (Armonk, NY: IBM Corp). Continuous and nominal variables were described with means, standard deviations and frequencies. Statistical significance was set at P &lt; 0.05. Results: Amlodipine was the most commonly used CCB. The prevalence of DIGO in CCB and non-CCB was the same (49.5%). Gingival enlargement was found equally among both sexes in the CCB and non-CCB groups. A third of the participants with GO were 70 years and above while those without were majorly in the fifth and sixth decade of life. Two-third of those with DIGO had fair oral hygiene status, two-fifth had gingival bleeding and three-fifth had mild gingival inflammation. Those without DIGO in both groups had a slight female predominance and majorly good oral hygiene. Associated factors with DIGO were female sex, 60-69 age group, 10mg drug dosage, been on medication less than 10 years, mild gingival inflammation and generalized gingivitis. Conclusion: There was no difference in the prevalence of DIGO between BBC and non-BBC users. However, there was mild gingival inflammation in all participants with DIGO and amlodipine users were three times more at risk of developing DIGO than nifedipine users. Thus, it is imperative to advise the hypertensives on the importance of maintaining adequate oral hygiene measures and incorporate periodontal care in their management so as to ameliorate the side effects of their medication.

Comprehensive Management of a Patient with Drug Induced Gingival Overgrowth and Metabolic Syndrome

Periodontitis and metabolic syndrome demonstrate a bidirectional relationship complicated by multiple risk factors. Gingival overgrowth (GO) is a manifestation of exaggerated inflammatory response of the gingivae in response to biofilm and varying local and systemic risk factors which include medications such as antihypertentive medication- nifedipine. A patient with multiple dental care needs with GO, complicated by systemic risk factors would invariably benefit from multidisciplinary approach for care. A 57-year-old female was diagnosed with chronic periodontitis, nifedipine-induced GO and metabolic syndrome. Management encompassed initial nonsurgical periodontal therapy, where the patient was educated and guided towards better plaque control, following which, scaling, root debridement, and surgical therapy (gingivectomy and excisional new attachment procedure) were carried out. Along with periodontal therapy, she was also managed through restorative phase where a successful outcome was achieved. She was then followed-up with maintenance care, and nifedipine was substituted with captopril by the Physician to facilitate maintenance. Keywords: Metabolic syndrome, Gingivectomy, Drug-induced gingival overgrowth, Periodontitis, Excisional new attachment procedure

Mechanism of Drug-induced Gingival Overgrowth: Phenytoin Inhibits the Apoptosis of Human Gingival Fibroblasts

Mechanism of Drug-induced Gingival Overgrowth: Phenytoin Inhibits the Apoptosis of Human Gingival Fibroblasts