Editing Periodontal disease (section)

==Signs and symptoms==
[[File:Periodontal terms diagram gingival recession.png|thumb|right|'''1''': Total loss of attachment (clinical attachment loss, CAL) is the sum of '''2''': Gingival recession, and '''3''': Probing depth]]
In the early stages, periodontitis has very few symptoms, and in many individuals the disease has progressed significantly before they seek treatment.

Symptoms may include:
* Redness or bleeding of gums while brushing [[tooth|teeth]], using [[dental floss]] or biting into hard food (e.g., apples) (though this may also occur in [[gingivitis]], where there is no attachment loss gum disease)
* Gum swelling that recurs
* Spitting out blood after brushing teeth
* [[Halitosis]], or bad breath, and a persistent metallic taste in the mouth
* Gingival recession, resulting in apparent lengthening of teeth (this may also be caused by heavy-handed brushing or with a stiff toothbrush)
* Deep pockets between the teeth and the gums ([[gingival and periodontal pockets|pockets]] are sites where the attachment has been gradually destroyed by [[collagen]]-destroying enzymes, known as [[collagenases]])
* Loose teeth, in the later stages (though this may occur for other [[occlusal trauma|reasons]], as well)

Gingival inflammation and bone destruction are largely painless. Hence, people may wrongly assume painless bleeding after teeth cleaning is insignificant, although this may be a symptom of progressing periodontitis in that person. 
[[File:Periodontal_Disease.png|thumb|Periodontal disease]]

===Associated conditions===
Periodontitis has been linked to increased [[inflammation]] in the body, such as indicated by raised levels of [[C-reactive protein]] and [[interleukin-6]].<ref>{{cite journal | vauthors = D'Aiuto F, Parkar M, Andreou G, Suvan J, Brett PM, Ready D, Tonetti MS | title = Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers | journal = Journal of Dental Research | volume = 83 | issue = 2 | pages = 156–60 | date = February 2004 | pmid = 14742655 | doi = 10.1177/154405910408300214 | s2cid = 34329326 }}</ref><ref>{{cite journal | vauthors = Nibali L, D'Aiuto F, Griffiths G, Patel K, Suvan J, Tonetti MS | title = Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: a case-control study | journal = Journal of Clinical Periodontology | volume = 34 | issue = 11 | pages = 931–7 | date = November 2007 | pmid = 17877746 | doi = 10.1111/j.1600-051X.2007.01133.x }}</ref><ref>{{cite journal | vauthors = Paraskevas S, Huizinga JD, Loos BG | title = A systematic review and meta-analyses on C-reactive protein in relation to periodontitis | journal = Journal of Clinical Periodontology | volume = 35 | issue = 4 | pages = 277–90 | date = April 2008 | pmid = 18294231 | doi = 10.1111/j.1600-051X.2007.01173.x }}</ref><ref>{{cite journal | vauthors = D'Aiuto F, Ready D, Tonetti MS | title = Periodontal disease and C-reactive protein-associated cardiovascular risk | journal = Journal of Periodontal Research | volume = 39 | issue = 4 | pages = 236–41 | date = August 2004 | pmid = 15206916 | doi = 10.1111/j.1600-0765.2004.00731.x }}</ref> It is associated with an increased risk of stroke,<ref>{{cite journal | vauthors = Pussinen PJ, Alfthan G, Jousilahti P, Paju S, Tuomilehto J | title = Systemic exposure to Porphyromonas gingivalis predicts incident stroke | journal = Atherosclerosis | volume = 193 | issue = 1 | pages = 222–8 | date = July 2007 | pmid = 16872615 | doi = 10.1016/j.atherosclerosis.2006.06.027 }}</ref><ref>{{cite journal | vauthors = Pussinen PJ, Alfthan G, Rissanen H, Reunanen A, Asikainen S, Knekt P | title = Antibodies to periodontal pathogens and stroke risk | journal = Stroke | volume = 35 | issue = 9 | pages = 2020–3 | date = September 2004 | pmid = 15232116 | doi = 10.1161/01.STR.0000136148.29490.fe | doi-access = free }}</ref> [[myocardial infarction]],<ref>{{cite journal | vauthors = Pussinen PJ, Alfthan G, Tuomilehto J, Asikainen S, Jousilahti P | title = High serum antibody levels to Porphyromonas gingivalis predict myocardial infarction | journal = European Journal of Cardiovascular Prevention and Rehabilitation | volume = 11 | issue = 5 | pages = 408–11 | date = October 2004 | pmid = 15616414 | doi = 10.1097/01.hjr.0000129745.38217.39 | s2cid = 34400631 }}</ref> [[atherosclerosis]]<ref>{{cite journal | vauthors = Ford PJ, Gemmell E, Timms P, Chan A, Preston FM, Seymour GJ | title = Anti-P. gingivalis response correlates with atherosclerosis | journal = Journal of Dental Research | volume = 86 | issue = 1 | pages = 35–40 | date = January 2007 | pmid = 17189460 | doi = 10.1177/154405910708600105 | s2cid = 5567995 }}</ref><ref>{{cite journal | vauthors = Beck JD, Eke P, Heiss G, Madianos P, Couper D, Lin D, Moss K, Elter J, Offenbacher S | title = Periodontal disease and coronary heart disease: a reappraisal of the exposure | journal = Circulation | volume = 112 | issue = 1 | pages = 19–24 | date = July 2005 | pmid = 15983248 | doi = 10.1161/CIRCULATIONAHA.104.511998 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Scannapieco FA, Bush RB, Paju S | title = Associations between periodontal disease and risk for atherosclerosis, cardiovascular disease, and stroke. A systematic review | journal = Annals of Periodontology | volume = 8 | issue = 1 | pages = 38–53 | date = December 2003 | pmid = 14971247 | doi = 10.1902/annals.2003.8.1.38 }}</ref><ref>{{cite journal | vauthors = Wu T, Trevisan M, Genco RJ, Dorn JP, Falkner KL, Sempos CT | title = Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study | journal = Archives of Internal Medicine | volume = 160 | issue = 18 | pages = 2749–55 | date = October 2000 | pmid = 11025784 | doi = 10.1001/archinte.160.18.2749 }}</ref><ref>{{cite journal | vauthors = Beck JD, Elter JR, Heiss G, Couper D, Mauriello SM, Offenbacher S | title = Relationship of periodontal disease to carotid artery intima-media wall thickness: the atherosclerosis risk in communities (ARIC) study | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 21 | issue = 11 | pages = 1816–22 | date = November 2001 | pmid = 11701471 | doi = 10.1161/hq1101.097803 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Elter JR, Champagne CM, Offenbacher S, Beck JD | title = Relationship of periodontal disease and tooth loss to prevalence of coronary heart disease | journal = Journal of Periodontology | volume = 75 | issue = 6 | pages = 782–90 | date = June 2004 | pmid = 15295942 | doi = 10.1902/jop.2004.75.6.782 }}</ref><ref>{{cite journal | vauthors = Humphrey LL, Fu R, Buckley DI, Freeman M, Helfand M | title = Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis | journal = Journal of General Internal Medicine | volume = 23 | issue = 12 | pages = 2079–86 | date = December 2008 | pmid = 18807098 | pmc = 2596495 | doi = 10.1007/s11606-008-0787-6 }}</ref> and [[hypertension]].<ref>{{cite journal | vauthors = Martin-Cabezas R, Seelam N, Petit C, Agossa K, Gaertner S, Tenenbaum H, Davideau JL, Huck O | title = Association between periodontitis and arterial hypertension: A systematic review and meta-analysis | journal = American Heart Journal | volume = 180 | pages = 98–112 | date = October 2016 | pmid = 27659888 | doi = 10.1016/j.ahj.2016.07.018 }}</ref> It is also linked in those over 60 years of age to impairments in delayed memory and calculation abilities.<ref>{{cite journal | vauthors = Noble JM, Borrell LN, Papapanou PN, Elkind MS, Scarmeas N, Wright CB | title = Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 80 | issue = 11 | pages = 1206–11 | date = November 2009 | pmid = 19419981 | pmc = 3073380 | doi = 10.1136/jnnp.2009.174029 }}</ref><ref>{{cite journal | vauthors = Kaye EK, Valencia A, Baba N, Spiro A, Dietrich T, Garcia RI | title = Tooth loss and periodontal disease predict poor cognitive function in older men | journal = Journal of the American Geriatrics Society | volume = 58 | issue = 4 | pages = 713–8 | date = April 2010 | pmid = 20398152 | pmc = 3649065 | doi = 10.1111/j.1532-5415.2010.02788.x }}</ref> Individuals with [[impaired fasting glucose]] and [[diabetes mellitus]] have a higher degrees of periodontal inflammation and often have difficulties with balancing their blood [[glucose]] level, owing to the constant systemic inflammatory state caused by the periodontal inflammation.<ref name="glucose">{{cite journal | vauthors = Zadik Y, Bechor R, Galor S, Levin L | title = Periodontal disease might be associated even with impaired fasting glucose | journal = British Dental Journal | volume = 208 | issue = 10 | pages = E20 | date = May 2010 | pmid = 20339371 | doi = 10.1038/sj.bdj.2010.291 | doi-access = free }}</ref><ref name="DM">{{cite journal | vauthors = Soskolne WA, Klinger A | title = The relationship between periodontal diseases and diabetes: an overview | journal = Annals of Periodontology | volume = 6 | issue = 1 | pages = 91–8 | date = December 2001 | pmid = 11887477 | doi = 10.1902/annals.2001.6.1.91 }}</ref> Although no causal association was proven, there is an association between chronic periodontitis and [[erectile dysfunction]],<ref name="ED">{{cite journal | vauthors = Zadik Y, Bechor R, Galor S, Justo D, Heruti RJ | title = Erectile dysfunction might be associated with chronic periodontal disease: two ends of the cardiovascular spectrum | journal = The Journal of Sexual Medicine | volume = 6 | issue = 4 | pages = 1111–6 | date = April 2009 | pmid = 19170861 | doi = 10.1111/j.1743-6109.2008.01141.x | s2cid = 3421903 }}</ref> [[inflammatory bowel disease]],<ref>{{Cite journal|last1=Poyato-Borrego|first1=M.|last2=Segura-Egea|first2=J.-J.|last3=Martín-González|first3=J.|last4=Jiménez-Sánchez|first4=M.-C.|last5=Cabanillas-Balsera|first5=D.|last6=Areal-Quecuty|first6=V.|last7=Segura-Sampedro|first7=J.-J.|date=27 August 2020|title=Prevalence of endodontic infection in patients with Crohn´s disease and ulcerative colitis|journal=Medicina Oral, Patologia Oral y Cirugia Bucal|volume=26|issue=2|pages=e208–e215|doi=10.4317/medoral.24135 |pmid=32851982|pmc=7980298|doi-access=free}}</ref> and heart disease.<ref>{{cite journal |last1=Perk |first1=J. |last2=De Backer |first2=G. |last3=Gohlke |first3=H. |last4=Graham |first4=I. |last5=Reiner |first5=Z. |last6=Verschuren |first6=M. |title=European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR) |journal=European Heart Journal |date=3 May 2012 |volume=33 |issue=13 |pages=1635–1701 |doi=10.1093/eurheartj/ehs092 |pmid=22555213 |doi-access=free }}</ref>
==== Diabetes and periodontal disease ====
A positive correlation between raised levels of glucose within the blood and the onset or progression of periodontal disease has been shown in the current literature.

Data has also shown that there is a significant increase in the incidence or progression of periodontitis in patients with uncontrolled diabetes compared to those who do not have diabetes or have well-controlled diabetes. In uncontrolled diabetes, the formation of [[reactive oxygen species]] can damage cells such as those in the connective tissue of the periodontal ligament, resulting in cell [[necrosis]] or [[apoptosis]]. Furthermore, individuals with uncontrolled diabetes mellitus who have frequent exposure to periodontal pathogens have a greater immune response to these bacteria. This can subsequently cause and/or accelerate periodontal tissue destruction leading to periodontal disease.<ref>{{Cite journal |last1=Nascimento |first1=Gustavo G. |last2=Leite |first2=Fábio R. M. |last3=Vestergaard |first3=Peter |last4=Scheutz |first4=Flemming |last5=López |first5=Rodrigo |date=July 2018 |title=Does diabetes increase the risk of periodontitis? A systematic review and meta-regression analysis of longitudinal prospective studies |journal=Acta Diabetologica |volume=55 |issue=7 |pages=653–667 |doi=10.1007/s00592-018-1120-4 |issn=1432-5233 |pmid=29502214|s2cid=3689420 }}</ref>

===Oral cancer and periodontal disease===

Current literature suggests a link between periodontal disease and oral cancer. Studies have confirmed an increase in systemic inflammation markers such as [[C-reactive protein|C-Reactive Protein]] and [[Interleukin 6|Interleukin-6]] to be found in patients with advanced periodontal disease. The link between systemic inflammation and oral cancer has also been well established.

Both periodontal disease and cancer risk are associated with genetic susceptibility and it is possible that there is a positive association by a shared genetic susceptibility in the two diseases.

Due to the low incidence rate of oral cancer, studies have not been able to conduct quality studies to prove the association between the two, however future larger studies may aid in the identification of individuals at a higher risk.<ref>{{Cite journal |last1=Michaud |first1=Dominique S. |last2=Fu |first2=Zhuxuan |last3=Shi |first3=Jian |last4=Chung |first4=Mei |date=January 2017 |title=Periodontal Disease, Tooth Loss, and Cancer Risk |journal=Epidemiologic Reviews |volume=39 |issue=1 |pages=49–58 |doi=10.1093/epirev/mxx006 |pmc=5868279 |pmid=28449041}}</ref>

===Systemic implications===

Periodontal disease (PD) can be described as an inflammatory condition affecting the supporting structures of the teeth. Studies have shown that PD is associated with higher levels of systemic inflammatory markers such as Interleukin-6 (IL-6), C-Reactive Protein (CRP) and Tumor Necrosis Factor (TNF). To compare, elevated levels of these inflammatory markers are also associated with cardiovascular disease and cerebrovascular events such as ischemic strokes.<ref>{{Cite journal |last1=Gomes-Filho |first1=Isaac Suzart |last2=Freitas Coelho |first2=Julita Maria |last3=da Cruz |first3=Simone Seixas |last4=Passos |first4=Johelle Santana |last5=Teixeira de Freitas |first5=Camila Oliveira |last6=Aragão Farias |first6=Naiara Silva |last7=Amorim da Silva |first7=Ruany |last8=Silva Pereira |first8=Milena Novais |last9=Lima |first9=Thiago Lopes |last10=Barreto |first10=Maurício Lima |date=July 2011 |title=Chronic periodontitis and C-reactive protein levels |journal=Journal of Periodontology |volume=82 |issue=7 |pages=969–978 |doi=10.1902/jop.2010.100511 |issn=1943-3670 |pmid=21189085}}</ref>

The presence of a wide spectrum inflammatory oral diseases can increase the risk of an episode of stroke in an acute or chronic phase. Inflammatory markers, CRP, IL-6 are known risk factors of stroke. Both inflammatory markers are also biomarkers of PD and found to be an increased level after daily activities, such as mastication or toothbrushing, are performed. Bacteria from the periodontal pockets will enter the bloodstream during these activities and the current literature suggests that this may be a possible triggering of the aggravation of the stroke process.<ref>{{Cite journal |last=Loos |first=Bruno G. |date=November 2005 |title=Systemic markers of inflammation in periodontitis |journal=Journal of Periodontology |volume=76 |issue=11 Suppl |pages=2106–15 |doi=10.1902/jop.2005.76.11-S.2106 |issn=0022-3492 |pmid=16277583}}</ref>

Other mechanisms have been suggested, PD is a known chronic infection. It can aid in the promotion of atherosclerosis by the deposition of cholesterol, cholesterol esters and calcium within the subendothelial layer of vessel walls.<ref>{{Cite journal |last1=Libby |first1=Peter |last2=Ridker |first2=Paul M. |last3=Hansson |first3=Göran K. |last4=Leducq Transatlantic Network on Atherothrombosis |date=2009-12-01 |title=Inflammation in atherosclerosis: from pathophysiology to practice |journal=Journal of the American College of Cardiology |volume=54 |issue=23 |pages=2129–38 |doi=10.1016/j.jacc.2009.09.009 |issn=1558-3597 |pmc=2834169 |pmid=19942084}}</ref> Atherosclerotic plaque that is unstable may rupture and release debris and thrombi that may travel to different parts of the circulatory system causing embolization and therefore, an ischemic stroke. Therefore, PD has been suggested as an independent risk factor for stroke.

A variety of cardiovascular diseases can also be associated with periodontal disease. Patients with higher levels of inflammatory markers such as TNF, IL-1, IL-6 and IL-8 can lead to progression of atherosclerosis and the development and perpetuation of atrial fibrillation,<ref>{{Cite journal |last1=Harada |first1=Masahide |last2=Van Wagoner |first2=David R. |last3=Nattel |first3=Stanley |date=2015 |title=Role of Inflammation in Atrial Fibrillation Pathophysiology and Management |url=http://dx.doi.org/10.1253/circj.cj-15-0138 |journal=Circulation Journal |volume=79 |issue=3 |pages=495–502 |doi=10.1253/circj.cj-15-0138 |pmid=25746525 |pmc=4457364 |issn=1346-9843}}</ref> as it is associated with platelet and coagulation cascade activations, leading to thrombosis and thrombotic complications.

Experimental animal studies have shown a link between periodontal disease, oxidative stress and cardiac stress. Oxidative stress favours the development and progression of heart failure as it causes cellular dysfunction, oxidation of proteins and lipids, and damage to the deoxyribonucleic acid (DNA), stimulating fibroblast proliferation and metalloproteinases activation favouring cardiac remodelling.<ref>{{Cite journal |last1=Tsutsui |first1=Hiroyuki |last2=Kinugawa |first2=Shintaro |last3=Matsushima |first3=Shouji |date=December 2011 |title=Oxidative stress and heart failure |journal=American Journal of Physiology. Heart and Circulatory Physiology |volume=301 |issue=6 |pages=H2181–90 |doi=10.1152/ajpheart.00554.2011 |issn=1522-1539 |pmid=21949114|s2cid=25334639 }}</ref>

During SARS Covid 19 pandemic, Periodontitis was significantly associated with a higher risk of complications from COVID‐19, including ICU admission, need for assisted ventilation and death and increased blood levels of markers such as D‐dimer, WBC and CRP which are linked with worse disease outcome.<ref>{{cite journal |last1=Marouf |first1=Nadya |title=Association between periodontitis and severity of COVID-19 infection: A case–control study |journal=Journal of Clinical Periodontology |date=2021 |volume=48 |issue=4 |pages=483–491 |doi=10.1111/jcpe.13435 |pmid=33527378|pmc=8014679 }}</ref>