Gingival enlargement is an increase in the size of the

gingiva The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health. Structure The gums are part of the soft tissue l ...

(gums). It is a common feature of gingival

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

. Gingival enlargement can be caused by a number of factors, including inflammatory conditions and the side effects of certain medications. The treatment is based on the cause. A closely related term is epulis, denoting a localized

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

(i.e. lump) on the gingiva.

Classification

The terms gingival

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferatio ...

and gingival

hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J. ...

have been used to describe this topic in the past. These are not precise descriptions of gingival enlargement because these terms are strictly histologic diagnoses, and such diagnoses require

microscopic The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded as the scale be ...

analysis of a tissue sample. Hyperplasia refers to an increased number of

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s, and hypertrophy refers to an increase in the size of individual cells. As these identifications cannot be performed with a clinical examination and evaluation of the tissue, the term ''gingival enlargement'' is more properly applied. Gingival enlargement has been classified according to cause into 5 general groups: * Inflammatory enlargement * Drug induced enlargement * Enlargement associated with systemic diseases or conditions * Neoplastic enlargement * False enlargement.

Causes

Inflammatory enlargement

Gingival enlargement has a multitude of causes. The most common is chronic inflammatory gingival enlargement, when the

e are soft and discolored. This is caused by tissue

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...

and infective

cellular infiltration Infiltration is the diffusion or accumulation (in a tissue or cells) of foreign substances in amounts excess of the normal. The material collected in those tissues or cells is called infiltrate. Definitions of infiltration As part of a disease p ...

caused by prolonged exposure to

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

l plaque, and is treated with conventional

periodontal Periodontology or periodontics (from Ancient Greek , – 'around'; and , – 'tooth', genitive , ) is the specialty of dentistry that studies supporting structures of teeth, as well as diseases and conditions that affect them. The supporting ...

treatment, such as

scaling and root planing Scaling and root planing, also known as conventional periodontal therapy, non-surgical periodontal therapy or deep cleaning, is a procedure involving removal of dental plaque and calculus (scaling or debridement) and then smoothing, or planing, o ...

Gingivitis Gingivitis is a non-destructive disease that causes inflammation of the gums. The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms (also called plaque) that is attac ...

and gingival enlargement are often seen in mouth breathers, as a result of irritation brought on by surface dehydration, but the manner in which it is caused has not been demonstrated. The accumulation and retention of plaque is the chief cause of inflammatory gingival enlargement. Risk factors include poor

oral hygiene Oral hygiene is the practice of keeping one's mouth clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and cleaning between the teeth. It is important that oral hygiene be carried ou ...

, as well as physical irritation of the gingiva by improper restorative and orthodontic appliances.

Drug-induced enlargement

This type of gingival enlargement is sometimes termed "drug induced gingival enlargement" or "drug influenced gingival overgrowth", abbreviated to "DIGO". Gingival enlargement may also be associated with the administration of three different classes of drugs, all producing a similar response: Gingival overgrowth is a common side effect of phenytoin, termed "Phenytoin-induced gingival overgrowth" (PIGO). *

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

s (such as

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...

lamotrigine Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut sy ...

vigabatrin Vigabatrin, brand name Sabril, is a medication used to treat epilepsy. It became available as a generic medication in 2019. It works by inhibiting the breakdown of γ-aminobutyric acid (GABA). It is also known as γ-vinyl-GABA, and is a stru ...

, ethosuximide,

topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for genera ...

and primidone NOT common for valproate) *

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s (antihypertensives such as

nifedipine Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate), sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Ra ...

amlodipine Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure and coronary artery disease. It is taken by mouth. Common side effects include swelling, feeling tired, ...

, and verapamil). The dihydropyridine derivative isradipidine can replace nifedipine and does not induce gingival overgrowth. *

cyclosporine Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...

, an

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified in ...

. Of all cases of DIGO, about 50% are attributed to phenytoin, 30% to cyclosporins and the remaining 10-20% to calcium channel blockers. Drug-induced enlargement has been associated with a patient's

genetic predisposition A genetic predisposition is a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. In medicine, genetic susceptibili ...

, and its association with inflammation is debated. Some investigators assert that underlying inflammation is necessary for the development of drug-induced enlargement, while others purport that the existing enlargement induced by the drug effect compounds plaque retention, thus furthering the tissue response. Careful attention to oral hygiene may reduce the severity of gingival hyperplasia. In most cases, discontinuing the culprit drug resolves the hyperplasia.

Enlargement associated with systemic factors

Many systemic diseases can develop oral manifestations that may include gingival enlargement, some that are related to conditions and others that are related to disease: * Conditioned enlargement **

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a ...

vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...

deficiency ** nonspecific, such as a

pyogenic granuloma A pyogenic granuloma or lobular capillary hemangioma is a vascular tumor that occurs on both mucosa and skin, and appears as an overgrowth of tissue due to irritation, physical trauma, or hormonal factors. It is often found to involve the gum ...

* Systemic disease causing enlargement **

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

** granulolomatous diseases, such as

granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis (WG), is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is a form of vasculitis ...

sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...

, or

orofacial granulomatosis Orofacial granulomatosis (OFG) is a condition characterized by persistent enlargement of the soft tissues of the mouth, lips and the area around the mouth on the face, causing in most cases extreme pain. The mechanism of the enlargement is granulo ...

. **

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

***

benign Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

neoplasms, such as

fibroma Fibromas are benign tumors that are composed of fibrous or connective tissue. They can grow in all organs, arising from mesenchyme tissue. The term "fibroblastic" or "fibromatous" is used to describe tumors of the fibrous connective tissue. Whe ...

papilloma A papilloma (plural papillomas or papillomata) ('' papillo-'' + '' -oma'') is a benign epithelial tumor growing exophytically (outwardly projecting) in nipple-like and often finger-like fronds. In this context, papilla refers to the projection c ...

s and giant cell granulomas ***

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

neoplasms, such as a

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoderm ...

malignant melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ...

** false gingival enlargements, such as when there is an underlying bony or dental tissue

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classif ...

Mechanism

Drug Induced gingival overgrowth: * Fibrotic type: ** Elevated CTGF (a.k.a. CCN2) which is a matricellular protein known to be reliable for

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

. ***

TGF-β Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other s ...

increases drives CTGF/CCN2 (current molecular mechanisms unknown), but supports TGF-β as a therapeutic target. *** CTGF is not down regulated in presence of inflammatory mediators (such as PGE₂), unlike other tissues' fibroblasts (such as kidney) which have their CTGF levels down regulated by the same PGE₂. * Inflammatory Type

Management

The first line management of gingival overgrowth is improved

, ensuring that the irritative plaque is removed from around the necks of the teeth and gums. Situations in which the chronic inflammatory gingival enlargement include significant fibrotic components that do not respond to and undergo shrinkage when exposed to scaling and root planing are treated with surgical removal of the excess tissue, most often with a procedure known as

gingivectomy Gingivectomy is a dental procedure in which a dentist or oral surgeon cuts away part of the gums in the mouth (the '' gingiva''). It is the oldest surgical approach in periodontal therapy and is usually done for improvement of aesthetics or p ...

. In DIGO, improved oral hygiene and plaque control is still important to help reduce any inflammatory component that may be contributing to the overgrowth. Reversing and preventing gingival enlargement caused by drugs is as easy as ceasing drug therapy or substituting to another drug. However, this is not always an option; in such a situation, alternative drug therapy may be employed, if possible, to avoid this deleterious

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

. In the case of immunosuppression,

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

is an available alternative which results in much less severe gingival overgrowth than cyclosporin, but is similarly as

nephrotoxic Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxins ...

. The dihydropyridine derivative isradipidine can replace nifedipine for some uses of calcium channel blocking and does not induce gingival overgrowth.

Epidemiology

Gingival enlargement is common.

Other animals

It is commonly seen in

Boxer dogs The Boxer is a medium to large, short-haired dog breed of mastiff-type, developed in Germany. The coat is smooth and tight-fitting; colors are fawn, brindled, or white, with or without white markings. Boxers are brachycephalic (they have bro ...

and other brachycephalic breeds, and in the

English Springer Spaniel The English Springer is a breed of gun dog in the Spaniel group traditionally used for flushing and retrieving game. It is an affectionate, excitable breed with a typical lifespan of twelve to fourteen years. They are very similar to the Wels ...

. It usually starts around middle age and progresses. Some areas of the gingiva can become quite large but have only a small attachment to the rest of the gingiva, and it may completely cover the teeth. Infection and inflammation of the gingiva is common with this condition. Under anesthesia, the enlarged areas of gingiva can be cut back with a scalpel blade or CO₂ laser, but it often recurs. Gingival enlargement is also a potential sequela of

gingivitis Gingivitis is a non-destructive disease that causes inflammation of the gums. The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms (also called plaque) that is attac ...

. As in humans, it may be seen as a side effect to the use of

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...

. Gingival enlargement is an autosomal recessive disease with predominance in males, and is correlated with selection for superior fur quality in European farmed foxes

References

External links

{{Oral pathology Periodontal disorders Dog diseases