Phenytoin-Induced Gingival Overgrowth: A Review of the Molecular, Immune, and Inflammatory Features

Gingival overgrowth (GO) is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressant, and calcium channel blockers. GO is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components, with varying degrees of inflammation. One of the main drugs associated with GO is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. Nevertheless, the pathogenesis of such drug-induced GO remains fulfilled by some contradictory findings. This paper aims to present the most relevant studies regarding the molecular, immune, and inflammatory aspects of phenytoin-induced gingival overgrowth.

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Amlodipine Induced Gum Hypertrophy – A Rare Case Report

Current Drug Safety ◽

10.2174/1574886316666211122125215 ◽

2021 ◽

Vol 16 ◽

Author(s):

Suryanarayana Challa Reddy ◽

Naresh Midha ◽

Vivek Chhabra ◽

Deepak Kumar ◽

Gopal Krishna Bohra

Keyword(s):

Calcium Channel ◽

Side Effect ◽

Antihypertensive Drugs ◽

Case Reports ◽

Diagnostic Procedures ◽

Channel Blockers ◽

Gingival Hyperplasia ◽

Drug Induced ◽

Duration Of Action ◽

Gingival Overgrowth

Background: DIGO or drug-induced gingival overgrowth occurs as a side effect of certain drugs. Until now, the etiology of drug-induced gingival overgrowth is not clearly understood. Among the calcium channel blockers, nifedipine has been shown to be most frequently associated with drug-induced gingival hyperplasia. Amlodipine is a comparatively newer calcium channel blocker that witha longer duration of action and lesser side effects as compared to nifedipine. There are only certain case reports of amlodipine-induced gum hyperplasia. Case presentation: We report a case of amlodipine-induced gum hyperplasia in a 66-year-old hypertensive patient taking amlodipine at a dose of 5 mg once a day. There was significant regression of gum hypertrophy after substitution of amlodipine by Losartan. Conclusion: Amlodipine is one of the commonly prescribed antihypertensive drugs, and gingival hyperplasia is one overlooked side effect in patients taking amlodipine. Awareness of this potential side effect of amlodipine may be helpful to reduce the anxiety of patients and the cost of diagnostic procedures.

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Drug-Induced Gingival Overgrowth - A Review

Bangladesh Journal of Physiology and Pharmacology ◽

10.3329/bjpp.v25i1.5743 ◽

1970 ◽

pp. 26-29

Author(s):

Mst Fatema Akhter ◽

Shaheen Lipika Quayum ◽

Afrin Bintal Ali ◽

Zia Mamoon

Keyword(s):

Extracellular Matrix ◽

Collagen Synthesis ◽

Immunosuppressive Agents ◽

Channel Blockers ◽

Gingival Fibroblasts ◽

Connective Tissues ◽

Drug Induced ◽

Gingival Overgrowth ◽

Collagen Phagocytosis ◽

Synthesis And Degradation

Drug-induced gingival overgrowth is a side effect associated with 3 types of drugs: anticonvulsants (phenytoin), immunosuppressive agents (cyclosporine A), and various calcium channel blockers for cardiovascular diseases. Gingival overgrowth is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components with various degrees of inflammation. Although the mechanisms of these disorders have not been elucidated, recent studies suggest that these disorders seem to be induced by the disruption of homeostasis of collagen synthesis and degradation in gingival connective tissue, predominantly through the inhibition of collagen phagocytosis of gingival fibroblasts. In this review, we focus on collagen metabolism in drug-induced gingival overgrowth, focusing on the regulation of collagen phagocytosis in fibroblasts. DOI: 10.3329/bjpp.v25i1.5743Bangladesh J Physiol Pharmacol 2009; 25(1&2) : 26-29

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Cyclosporine A and amlodipine induced gingival overgrowth in a kidney transplant recipient: case presentation with literature review

BMJ Case Reports ◽

10.1136/bcr-2019-229587 ◽

2019 ◽

Vol 12 (5) ◽

pp. e229587 ◽

Cited By ~ 8

Author(s):

Tarun Nanda ◽

Baljeet Singh ◽

Parul Sharma ◽

Karandeep Singh Arora

Keyword(s):

Calcium Channel ◽

Kidney Transplant ◽

Cyclosporine A ◽

Calcium Channel Blockers ◽

Kidney Transplant Recipient ◽

Kidney Transplant Patient ◽

Channel Blockers ◽

Drug Induced ◽

Gingival Overgrowth ◽

Gingival Enlargement

Drug-induced gingival overgrowth is a condition caused by side effects of treatment with one of three types of drugs: phenytoin (used in epilepsy treatment), cyclosporine A (used in transplantology after allogenic organ transplants) and calcium channel blockers (used in the treatment of hypertension). Gingival overgrowth leads to inflammation within the gums and periodontium and can amplify the existing periodontal disease leading to tooth loss. Patients who have undergone kidney transplant are given immunosuppressants to prevent transplant rejection and mostly it is accompanied with calcium channel blockers to treat hypertension associated with kidney transplant. This article reports a case of recent gingival enlargement associated with cyclosporine A and amlodipine given to a kidney transplant patient from the past 11 years.

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EFFECTIVENESS OF NON-SURGICAL PERIODONTAL THERAPY ON AMLODIPINE INDUCED GINGIVAL ENLARGEMENT: A CASE REPORT

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v3i11.722 ◽

2019 ◽

Vol 3 (11) ◽

Author(s):

Dagar Mona ◽

Kataria Prerna

Keyword(s):

Case Report ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Normal State ◽

Periodontal Therapy ◽

Channel Blockers ◽

Scaling And Root Planing ◽

Drug Induced ◽

Gingival Overgrowth ◽

Gingival Enlargement

Gingival enlargement, [sometimes abbreviated to GO (gingival overgrowth)] is an increase in the size of the gingiva. It is a common feature of gingival disease. Gingival enlargement is a well known side-effect of drugs like anticonvulsants, calcium channel blockers and immunosuppressant. A case of amlodipine induced gingival enlargement was reported and after drug substitution when the patient was treated non-surgically (scaling and root planing), the enlargement subsides to a normal state which suggested the effectiveness of non-surgical periodontal therapy in the treatment of drug induced gingival enlargement. Keywords: Anticonvulsants, Immunosuppressants, Calcium channel blockers, gingival enlargement

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A rare case of accelerated gingival overgrowth with high dose amlodipine therapy

Journal of Pharmacovigilance and Drug Research ◽

10.53411/jpadr.2021.2.1.8 ◽

2021 ◽

Vol 2 (1) ◽

pp. 39-41

Author(s):

Rakesh B M ◽

Sahithi Sharma ◽

Chandana K H

Keyword(s):

Calcium Channel ◽

Calcium Channel Blockers ◽

Rare Case ◽

Immunosuppressive Drugs ◽

High Dose ◽

Channel Blockers ◽

Gingival Hyperplasia ◽

Limited Evidence ◽

Drug Induced ◽

Gingival Overgrowth

Introduction: Gingival overgrowth represents an over-exuberant response to a variety of local and systemic conditions. Certain anticonvulsants, immunosuppressive drugs, and a number of calcium channel blockers have been shown to produce similar gingival overgrowth in susceptible patients. Case report: We report a case of accelerated drug-induced gingival overgrowth in a 60-year-old hypertensive patient taking amlodipine at a dose of 10 mg. Conclusions: Among the calcium channel blockers, nifedipine is most frequently associated with gingival overgrowth. Whereas, there is limited evidence of amlodipine-induced gingival hyperplasia.

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Cyclosporine and Amlodipine Induced Severe Gingival Overgrowth - Etiopathogenesis and Management of a Case with Electrocautery and Carbon-Dioxide(CO2) Laser

Journal of Oral Health and Community Dentistry ◽

10.5005/johcd-6-1-34 ◽

2012 ◽

Vol 6 (1) ◽

pp. 34-42 ◽

Cited By ~ 2

Author(s):

Rashmi Hegde ◽

Rahul Kale ◽

A Sanjay Jain

Keyword(s):

Calcium Channel ◽

Calcium Channel Blockers ◽

Side Effect ◽

Channel Blockers ◽

Gingival Overgrowth ◽

Supportive Periodontal Therapy ◽

Wide Range ◽

Carbon Dioxide Co2 ◽

Oral Hygiene Instructions

ABSTRACT Gingival overgrowth is a well recognized, unwanted side-effect associated with three major drugs/drug groups – phenytoin, cyclosporine and the calcium channel blockers. Cyclosporine is a potent immunosuppressive compound that has been used increasingly in conjunction with kidney, heart and other transplants. Calcium channel blockers are widely used in medical practice for the management of cardiovascular disorders. Due to their wide range of use, gingival overgrowth is now a recognized side-effect associated with them. Here we discuss a case report dealing with severe gingival overgrowth induced by cyclosporine and amlodipine. A 36-year-old man who underwent renal transplant came with a chief complaint of generalized gingival swelling. He had very severe gingival overgrowth in both arches and required thorough scaling and oral hygiene instructions, followed by supportive periodontal therapy for 4 months, after which radical gingivectomy using electrocautery and CO2 laser was performed. The post operative results were excellent and there was no recurrence at 1 year follow-up.

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Connective Tissue Metabolism and Gingival Overgrowth

Critical Reviews in Oral Biology & Medicine ◽

10.1177/154411130401500305 ◽

2004 ◽

Vol 15 (3) ◽

pp. 165-175 ◽

Cited By ~ 91

Author(s):

P. C. Trackman ◽

A. Kantarci

Keyword(s):

Extracellular Matrix ◽

Connective Tissue ◽

Oral Hygiene ◽

Tissue Specificity ◽

Gingival Fibroblast ◽

Drug Induced ◽

Gingival Overgrowth ◽

Connective Tissue Metabolism ◽

Matrix Metabolism ◽

Systemic Health

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth.

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Drug-Induced Gingival Overgrowth: A Pilot Study on the Effect of Diphenylhydantoin and Gabapentin on Human Gingival Fibroblasts

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17218229 ◽

2020 ◽

Vol 17 (21) ◽

pp. 8229

Author(s):

Dorina Lauritano ◽

Giulia Moreo ◽

Luisa Limongelli ◽

Elena Tregambi ◽

Annalisa Palmieri ◽

...

Keyword(s):

Extracellular Matrix ◽

Direct Action ◽

Human Fibroblasts ◽

Matrix Metalloproteases ◽

Channel Blockers ◽

Gingival Hyperplasia ◽

Drug Induced ◽

Gingival Overgrowth ◽

Matrix Deposition ◽

Extracellular Matrix Deposition

Introduction. The administration of several classes of drugs can lead to the onset of gingival overgrowth: anticonvulsants, immunosuppressants, and calcium channel blockers. Among the anticonvulsants, the main drug associated with gingival overgrowth is diphenylhydantoin. Materials and Methods. In this study, we compared the effects of diphenylhydantoin and gabapentin on 57 genes belonging to the “Extracellular Matrix and Adhesion Molecule” pathway, present in human fibroblasts of healthy volunteers. Results. Both molecules induce the same gene expression profile in fibroblasts as well as a significant upregulation of genes involved in extracellular matrix deposition like COL4A1, ITGA7, and LAMB3. The two treatments also induced a significant downregulation of genes involved in the expression of extracellular matrix metalloproteases like MMP11, MMP15, MMP16, MMP24, and transmembrane receptor ITGB4. Conclusions. Data recorded in our study confirmed the hypothesis of a direct action of these drugs at the periodontium level, inducing an increase in matrix production, a reduction in its degradation, and consequently resulting in gingival hyperplasia.

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