Title: Gingival enlargement

{{Short description|Increase in size of the gums}}
{{Infobox medical condition (new)
| name          = Gingival enlargement
| synonyms      = Gingival overgrowth (GO), hypertrophic gingivitis, gingival hyperplasia, gingival hypertrophy
| image         = Gingivitis (crop).jpg
| caption       = [[Gingivitis]], a common cause of inflammatory gingival enlargement.
| pronounce     = 
| field         = Periodontology
| symptoms      = increase in gum size
| complications = 
| onset         = 
| duration      = 
| types         = 
| causes        = inflammatory conditions, Drug-induced, genetic
| risks         = 
| diagnosis     = 
| differential  = 
| prevention    = 
| treatment     = 
| medication    = 
| prognosis     = 
| frequency     = 
| deaths        = 
}}

'''Gingival enlargement''' is an increase in the size of the [[gingiva]] (gums). It is a common feature of gingival [[disease]].&lt;ref name=&quot;Newman 2012&quot; /&gt; 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.&lt;ref name=&quot;Newman 2012&quot; /&gt; A closely related term is [[epulis]], denoting a localized [[tumor]] (i.e., lump) on the gingiva.

==Classification==
The terms gingival [[hyperplasia]] and gingival [[hypertrophy]] have been used to describe this topic in the past.&lt;ref name=&quot;Newman 2012&quot;&gt;{{cite book|veditors= Newman MG, Takei HH, Klokkevold PR, Carranza FA|title=Carranza's clinical periodontology|url= https://archive.org/details/carranzasclinica00newm_586|url-access= limited|year=2012|publisher=Elsevier/Saunders|location=St. Louis, Mo.|isbn=978-1-4377-0416-7|pages=[https://archive.org/details/carranzasclinica00newm_586/page/n131 84]–96|edition=11th}}&lt;/ref&gt; These are not precise descriptions of gingival enlargement because these terms are strictly [[histology|histologic]] [[medical diagnosis|diagnoses]], and such diagnoses require [[microscope|microscopic]] analysis of a tissue sample. Hyperplasia refers to an increased number of [[cell (biology)|cell]]s, and hypertrophy refers to an increase in the size of individual cells.&lt;ref&gt;Merriam-Webster's Medical Desk Dictionary, 2002, {{ISBN|1-4018-1188-4}}, page 367-368.&lt;/ref&gt; As these identifications cannot be performed with a clinical examination and evaluation of the tissue,&lt;ref&gt;Oral Pathology Lecture Series Notes, New Jersey Dental School, 2004–2005, page 24.&lt;/ref&gt; the term ''gingival enlargement'' is more properly applied. Gingival enlargement has been classified according to cause into five general groups:&lt;ref name=&quot;Newman 2012&quot; /&gt;
 
* 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 (medicine)|chronic]] [[inflammation|inflammatory]] gingival enlargement, when the [[gingiva]]e are soft and discolored. This is caused by tissue [[edema]] and [[infection|infective]] [[cellular infiltration]] caused by prolonged exposure to [[bacteria]]l plaque, and is treated with conventional [[periodontics|periodontal]] treatment, such as [[scaling and root planing]].&lt;ref name=&quot;Newman 2012&quot; /&gt;

[[Gingivitis]] and gingival enlargement are often seen in [[mouth breathing|mouth breathers]],&lt;ref&gt;{{Cite journal | doi = 10.1016/0030-4220(55)90106-7 | pmid = 14370764 | issn = 0030-4220 | volume = 8 | issue = 4 | pages = 382–391 | last = Lite | first = Theodore |author2=Dominic J. DiMaio |author3=Louis R. Burman | title = Gingival pathosis in mouth breathers: A clinical and histopathologic study and a method of treatment | journal = Oral Surgery, Oral Medicine, Oral Pathology | year = 1955 }}&lt;/ref&gt; as a result of irritation brought on by surface dehydration, but the manner in which it is caused has not been demonstrated.&lt;ref name=&quot;Newman 2012&quot; /&gt;

The accumulation and retention of [[dental plaque|plaque]] is the chief cause of inflammatory gingival enlargement. Risk factors include poor [[oral hygiene]],&lt;ref&gt;{{cite journal |author=Hirschfield, I |title=Hypertrophic gingivitis; its clinical aspect|journal=Journal of the American Dental Association |issue=19 |page=799 |year=1932}}&lt;/ref&gt; as well as physical irritation of the gingiva by improper [[dental restoration|restorative]] and [[orthodontic appliance]]s.&lt;ref name=&quot;Newman 2012&quot; /&gt;

===Drug-induced enlargement===
{{main article|Drug-induced gingival enlargement}}
This type of gingival enlargement is sometimes termed &quot;drug induced gingival enlargement&quot; or &quot;drug influenced gingival overgrowth&quot;,&lt;ref name=&quot;Lindhe 2008&quot; &gt;{{cite book|veditors=Lindhe J, Lang NP, Karring T|title=Clinical periodontology and implant dentistry|url=https://archive.org/details/clinicalperiodon00lind|url-access=limited|year=2008|publisher=Blackwell Munksgaard|location=Oxford|isbn=978-1-4051-6099-5|pages=[https://archive.org/details/clinicalperiodon00lind/page/n667 641]|edition=5th}}&lt;/ref&gt; abbreviated to &quot;DIGO&quot;.&lt;ref name=&quot;Subramani 2013&quot;&gt;{{cite journal|last=Subramani|first=T|author2=Rathnavelu, V |author3=Yeap, SK |author4= Alitheen, NB |title=Influence of mast cells in drug-induced gingival overgrowth.|journal=Mediators of Inflammation| date=Feb 2013 |volume=2013|article-number=275172|doi=10.1155/2013/275172|pmid=23431239|pmc=3569901|doi-access=free}}&lt;/ref&gt; Gingival enlargement may also be associated with the administration of three different classes of drugs, all producing a similar response:&lt;ref&gt;{{cite journal |vauthors=Butler RT, Kalkwarf KL |title=Drug-induced gingival hyperplasia: phenytoin, cyclosporine, and nifedipine|journal=Journal of the American Dental Association |volume=114|issue=1 |pages=56–60 |year=1987|doi=10.14219/jada.archive.1987.0050|pmid=3468168}}&lt;/ref&gt; Gingival overgrowth is a common side effect of phenytoin, termed &quot;Phenytoin-induced gingival overgrowth&quot; (PIGO).&lt;ref name=&quot;Arya 2012&quot;&gt;{{cite journal|last=Arya|first=R|author2=Gulati, S|title=Phenytoin-induced gingival overgrowth.|journal=Acta Neurologica Scandinavica|date=March 2012|volume=125|issue=3|pages=149–55|pmid=21651505|doi=10.1111/j.1600-0404.2011.01535.x|s2cid=6274158|doi-access=free}}&lt;/ref&gt; 
* [[anticonvulsant]]s (such as [[phenytoin]], [[phenobarbital]], [[lamotrigine]], [[vigabatrin]], [[ethosuximide]], [[topiramate]] and [[primidone]] NOT common for valproate)&lt;ref name=&quot;bolognia&quot;&gt;{{cite book |author=Bolognia, Jean L. |title=Dermatology |publisher=Mosby |location=St. Louis |year=2007 |isbn=978-1-4160-2999-1 }}&lt;/ref&gt; 
* [[calcium channel blocker]]s (antihypertensives such as [[nifedipine]], [[amlodipine]], and [[verapamil]]). The dihydropyridine derivative isradipidine can replace nifedipine and does not induce gingival overgrowth.&lt;ref name=&quot;bolognia&quot;/&gt;
* [[cyclosporine]], an [[Immunosuppressive drug|immunosuppressant]].&lt;ref name=&quot;bolognia&quot;/&gt;

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]],&lt;ref&gt;{{cite journal |author=Hassell, T.M. |title=Hypertrophic Oral problems and genetic aspects of individuals with epilepsy|journal=Periodontology 2000|issue=1 |pages=68–78 |year=1994 |doi=10.1111/j.1600-0757.1994.tb00027.x |pmid=9673171|volume=6 |last2=Burtner |first2=A. Paul |last3=McNeal |first3=Donald |last4=Smith |first4=Robert G.}}&lt;/ref&gt; and its association with inflammation is debated. Some investigators assert that underlying inflammation is necessary for the development of drug-induced enlargement,&lt;ref&gt;{{cite journal |author=Ciancio, SG |title=Gingival hyperplasia and diphenylhydantoin |journal= Journal of Periodontology|volume=43 |issue=7 |pages=411–4|year=1972|doi=10.1902/jop.1972.43.7.411 |pmid=4504524 }}&lt;/ref&gt; while others purport that the existing enlargement induced by the drug effect compounds plaque retention, thus furthering the tissue response.&lt;ref&gt;Carranza'a Clinical Periodontology, 9th Ed. W.B. Saunders 1996 {{ISBN|0-7216-8331-2}}, page 282.&lt;/ref&gt; Careful attention to oral hygiene may reduce the severity of gingival hyperplasia.&lt;ref name=&quot;ReferenceA&quot;&gt;{{cite book|editor1=Brian K. Alldredge|display-editors=etal|title=Applied therapeutics: the clinical use of drugs.|date=2013|publisher=Wolters Kluwer Health/Lippincott Williams &amp; Wilkins|location=Baltimore|isbn=978-1-60913-713-7|page=1403|edition=10th}}&lt;/ref&gt; In most cases, discontinuing the culprit drug resolves the hyperplasia.&lt;ref name=&quot;ReferenceA&quot;/&gt;

===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:&lt;ref&gt;Carranza'a Clinical Periodontology, 9th Ed. W.B. Saunders 1996 {{ISBN|0-7216-8331-2}}, page 285.&lt;/ref&gt;
* Conditioned enlargement
** [[pregnancy]]
** [[puberty]]
** [[vitamin C]] deficiency
** nonspecific, such as a [[pyogenic granuloma]]
* Systemic disease causing enlargement
** [[leukemia]]
** granulolomatous diseases, such as [[granulomatosis with polyangiitis]], [[sarcoidosis]], or [[orofacial granulomatosis]].&lt;ref name=&quot;Leão 2004&quot;&gt;{{cite journal|last=Leão|first=JC|author2=Hodgson, T |author3=Scully, C |author4= Porter, S |title=Review article: orofacial granulomatosis.|journal=Alimentary Pharmacology &amp; Therapeutics|date=Nov 15, 2004|volume=20|issue=10|pages=1019–27|doi=10.1111/j.1365-2036.2004.02205.x|pmid=15569103|doi-access=free}}&lt;/ref&gt; 
** [[neoplasm]]
*** [[benign]] neoplasms, such as [[fibroma]]s, [[papilloma]]s and [[giant cell granuloma]]s
*** [[malignant]] neoplasms, such as a [[carcinoma]] or [[melanoma]]
** false gingival enlargements, such as when there is an underlying [[alveolar bone|bony]] or dental tissue [[lesion]]

== Mechanism ==
Drug Induced gingival overgrowth:
* Fibrotic type:
** Elevated [[CTGF|CTGF (a.k.a. CCN2)]] which is a matricellular protein known to be reliable for [[fibrosis]].&lt;ref&gt;{{Cite journal|last1=Trackman|first1=P.C.|last2=Kantarci|first2=A.|date=2017-03-22|title=Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth|journal=Journal of Dental Research|volume=94|issue=4|pages=540–546|doi=10.1177/0022034515571265|issn=0022-0345|pmc=4485217|pmid=25680368}}&lt;/ref&gt;
*** [[Transforming growth factor beta|TGF-β]] increases drives [[CTGF|CTGF/CCN2]] (current molecular mechanisms unknown), but supports TGF-β as a therapeutic target.&lt;ref&gt;{{Cite journal|title=The Possible Potential Therapeutic Targets For Drug Induced Gingival Overgrowth|journal=Mediators of Inflammation|volume=2013|pages=1–9|year=2013|doi=10.1155/2013/639468|pmid = 23690667|pmc=3652200|last1=Subramani|first1=Tamilselvan|last2=Rathnavelu|first2=Vidhya|last3=Alitheen|first3=Noorjahan Banu |doi-access=free }}&lt;/ref&gt;
*** CTGF is not down regulated in presence of inflammatory mediators (such as [[Prostaglandin E2|PGE&lt;sub&gt;2&lt;/sub&gt;]]), unlike other tissues' fibroblasts (such as kidney) which have their CTGF levels down regulated by the same [[Prostaglandin E2|PGE&lt;sub&gt;2&lt;/sub&gt;]].
* Inflammatory Type

==Management==
The first line management of gingival overgrowth is improved [[oral hygiene]], 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 [[fibrosis|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]].&lt;ref name=&quot;Newman 2012&quot; /&gt;

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 [[Adverse effect|side effect]]. In the case of immunosuppression, [[tacrolimus]] is an available alternative which results in much less severe gingival overgrowth than cyclosporin, but is similarly as [[nephrotoxicity|nephrotoxic]].&lt;ref&gt;{{cite journal |author=Spencer, CM |title=Tacrolimus: an update of its pharmacology and drug efficacy in the management of organ transplantation |journal=Drugs |issue=6 |pages=925–75 |year=1997 |pmid=9421697 |last2=Goa |first2=KL |last3=Gillis |first3=JC |volume=54 |doi=10.2165/00003495-199754060-00009}}&lt;/ref&gt; The dihydropyridine derivative isradipidine can replace nifedipine for some uses of calcium channel blocking and does not induce gingival overgrowth.&lt;ref&gt;{{cite journal |author=Westbrook, P |title=Regression of nifedipine-induced gingival hyperplasia following switch to a same class calcium channel blocker, isradipine |journal= Journal of Periodontology|volume=68 |issue=7|pages=645–50|year=1997|doi=10.1902/jop.1997.68.7.645 |pmid=9249636 }}&lt;/ref&gt;

==Epidemiology==
{{Expand section|date=January 2019}}
Gingival enlargement is common.&lt;ref name=&quot;Livada 2012&quot;&gt;{{cite journal|last=Livada|first=R|author2=Shiloah, J|title=Gummy smile: could it be genetic? Hereditary gingival fibromatosis.|journal=The Journal of the Michigan Dental Association|date=December 2012|volume=94|issue=12|pages=40–3|pmid=23346694}}&lt;/ref&gt;

==Other animals==
[[File:Gingival hyperplasia.JPG|thumb|Gingival hyperplasia]]
It is commonly seen in [[Boxer (dog)|Boxer dogs]] and other [[cephalic index|brachycephalic]] breeds,&lt;ref&gt;{{cite web | title = Gingival Fibroma and Epulides | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/20410.htm | access-date = 2007-03-08 | archive-date = 2015-05-01 | archive-url = https://web.archive.org/web/20150501024658/http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm%2Fbc%2F20410.htm | url-status = dead }}&lt;/ref&gt; and in the [[English Springer Spaniel]].&lt;ref&gt;{{cite web | last = Gorrel | first = Cecilia | title = Periodontal Disease | work = Proceedings of the 28th World Congress of the World Small Animal Veterinary Association | year = 2003 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2003&amp;PID=6522&amp;O=Generic | access-date = 2007-03-25 }}&lt;/ref&gt; 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 [[Carbon dioxide laser|CO&lt;sub&gt;2&lt;/sub&gt; laser]], but it often recurs.&lt;ref&gt;{{Cite news|url=https://www.aesculight.com/case-studies/laser-gingival-enlargement-treatment/|title=Use CO2 laser on gingival enlargement|last1=Bellows|first1=Jan|date=2017-02-01|last2=McMorran|first2=Elizabeth|language=en-US|access-date=2017-02-02}}&lt;/ref&gt; Gingival enlargement is also a potential sequela of [[gingivitis]]. As in humans, it may be seen as a side effect to the use of [[ciclosporin]].&lt;ref&gt;{{cite journal |vauthors=Guaguère E, Steffan J, Olivry T |title=Cyclosporin A: a new drug in the field of canine dermatology |journal=Veterinary Dermatology |volume=15 |issue=2 |pages=61–74 |year=2004 |pmid=15030555 |doi=10.1111/j.1365-3164.2004.00376.x}}&lt;/ref&gt;

{{-}}

==References==
{{Reflist}}

== External links ==
{{Medical resources
| DiseasesDB      = 
| ICD10           = K06.1 ([[ILDS]] K06.100)
| ICD9            = 
| ICDO            = 
| OMIM            = 
| MedlinePlus     = 
| eMedicineSubj   = 
| eMedicineTopic  = 
| MeshID          = 
}}
{{Periodontology}}
{{Oral pathology}}

[[Category:Periodontal disorders]]
[[Category:Dog diseases]]