- Email: [email protected]
Systemic diseases and oral health
i n d i a n j o u r n a l o f m e d i c a l s p e c i a l i t i e s 5 ( 2 0 1 4 ) 1 0 7 e1 1 1
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/injms
Review Article
Systemic diseases and oral health Shilpa Ramesh, Prasanna Neelakantan* Undergraduate Clinic 6, Saveetha Dental College and Hospitals, Saveetha University, Chennai, India
article info
abstract
Article history:
Oral health is an important and often overlooked component of a person's general health
Received 31 July 2013
and well-being. Systemic conditions noted to occur with oral manifestations include dia-
Accepted 1 June 2014
betes, cutaneous diseases, hereditary disease, joint disease, immunocompromised states like HIV, AIDS, etc. Several studies have linked poor oral health with cardiovascular dis-
Keywords:
ease, poor glycemic control in diabetics, low birth-weight pre-term babies, and a number of
Bacteremia
other conditions, including rheumatoid arthritis and osteoporosis, respiratory diseases,
Coronary disease
etc. This review is to stress on the importance of considering both systemic and oral health
Dental caries
when treating an individual.
Diabetes mellitus
Copyright © 2014, Indian Journal of Medical Specialities. Published by Reed Elsevier India
Periodontal diseases
1.
Introduction
The effect of oral health on the rest of the body was stated by the Assyrians as early as the seventh century B.C.1 There is much more than beautiful teeth aligned perfectly in the oral cavity when it comes to oral health. Oral health, in essence, refers to the freedom from chronic oral-facial pain, orofacial lesions, birth defects such as cleft lip and palate, and other diseases and disorders that affect the craniofacial complex.2 Socio-economic considerations often serve as barriers to obtain dental care in a private practice dental delivery system, and it has been noticed that, this population experiences greater levels of both dental and systemic disease.3 The most prevalent and non-transmissible infectious disease experienced by most of the people all over the world is dental caries which is nothing but the bacterial infection and degradation of the tooth structure.4 Colonization of the oropharyngeal region is always linked with several systemic diseases5 such as cardiovascular disease,6 chronic obstructive
Pvt. Ltd. All rights reserved.
pulmonary disease,7 endocarditis8 and bacteremia.9 Considerable controversy surrounds the focal infection theory, which says that the mouth is a bacterial reservoir from where infection can spread through blood to cause infections at distant sites, besides, it can stimulate the immune response and the circulating inflammatory mediators will cause damage throughout the body.10 This review discusses the influence that oral health has on systemic diseases and vice-versa. The role of salivary biomarkers has also been presented.
2. The relationship between oral health and systemic diseases Various diseases or problems like stroke, infective endocarditis, bacterial pneumonia, low birth weight, myocardial infarction, congestive heart failure etc., are caused mainly by oral infections or oral health.11
* Corresponding author. 1500, 16th Main Road, Anna Nagar West, Chennai 600040, Tamil Nadu, India. E-mail address: [email protected] (P. Neelakantan). http://dx.doi.org/10.1016/j.injms.2015.02.003 0976-2884/Copyright © 2014, Indian Journal of Medical Specialities. Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
108
2.1.
i n d i a n j o u r n a l o f m e d i c a l s p e c i a l i t i e s 5 ( 2 0 1 4 ) 1 0 7 e1 1 1
Stroke
Stroke is a cerebrovascular disease that affects blood vessels supplying blood to the brain. It occurs when a blood vessel bringing oxygen and nutrients to the brain bursts or is clogged by local thrombus formation or by aggregates of bacteria and fibrin from other sources such as the heart. Studies on the pathology of stroke indicate that 80e85% of these lesions are due to cerebral infarction; 15e20% are caused by hemorrhage. The periodontium when inflamed releases bacterial byproducts, inflammatory cytokines, lipopolysaccharides (LPS) and bacteria into the circulation. It advances atherosclerosis and it may affect the coagulation of blood, the normal platelet functions and prostaglandin synthesis, thus abetting the onset of stroke. A case control study demonstrated poor oral health in patients with cerebral infarction as compared to the control group.12 This could further set up a vicious cycle because of periodontal inflammation.
2.2.
Infective endocarditis
Bacterial infection of the heart valves or the endothelium of the heart is called as infective endocarditis. It is caused due to bacteria gaining entry in to the bloodstream and getting lodged on abnormal heart valves or damaged heart tissue.13 It is a fatal systemic disease, when untreated and has always been connected with dental diseases and their treatment, during which the bacteria enter the blood stream and there are more chances of them getting lodged in the heart. Recently there were three controlled studies conducted and all showed a link between dental procedures and bacterial endocarditis.14e16 The commonly implicated dental procedures are oral prophylaxis (scaling and root planning) and extractions. Endodontic treatment is considered to be safe in these patients.
2.3.
Low birth weight
Pregnancy gingivitis is a condition which is due to the changes in the hormone levels during pregnancy resulting in inflammation of gingiva.17 It has been elucidated that gram negative periodontal infections can have an influence on the outcome of pregnancy. Considering local factors like plaque in such a case during the second trimester of pregnancy, these gram negative anaerobic bacteria produce several bioactive molecules that have a direct negative impact on the host. For example, the lipopolysaccharide component of the cell wall of gram negative bacteria activate macrophages and help in the production of several cytokines like interleukins 1 and 6, tumor necrosis factor (TNF), and prostaglandin E2 (PGE2), in addition to matrix metalloproteinases. These molecules have the ability to cross the placental barrier, augment the levels of PGE2 and TNF in the amniotic fluid and induce premature labor. Low birth weight infants are more likely to die during the neonatal period when compared to normal birth weight infants18 and even if they survive they will face neurodevelopmental disturbances,19 problems with respiration20 and congenital anomalies.21
2.4.
Diabetes mellitus
Periodontal disease often occurs in co-existence with diabetes mellitus. Recent research focusses on the possibility that periodontal disease can either predispose or exacerbate diabetes. This is based on findings that when mechanical periodontal treatment [scaling, root planing and curettage] alone is provided, regardless of the severity of periodontal disease or degree of diabetes control, the treatment outcome is improvement in periodontal status only i.e., it is a localized effect. However, when systemic antibiotics are included in addition to the mechanical therapy, an improvement in diabetes control is achieved which is evident by a reduction in glycosylated hemoglobin or a reduction in insulin requirements.22 Diabetics are more likely to develop severe periodontal disease than non-diabetics and it is a well realized point.22 There is an increased risk of poor glycemic control in diabetic patients with periodontitis when compared to the diabetics without periodontitis.23 Dental check up should be made periodic for diabetic patients to check their periodontal health status.24
2.5.
Bacterial pneumonia
Potential pathogens can be cultured from the oral cavity in critically ill patients in the intensive care units, and these microorganisms in the mouth can move along the respiratory tract and colonize the lung resulting in ventilator-associated pneumonia.25 This incidence can be reduced by removing the dental plaque.
2.6.
Patients in the critical care unit
Unlike the healthy persons, dental plaque in patients in the Intensive Care Unit may serve as a reservoir for the pathogens and can be easily colonized by respiratory pathogens like methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.26,27 Bacteria gain easy entry from the oropharynx through an open glottis to the lower part of the respiratory tract along the endotracheal tubes. These tubes also help in colonization, by interfering with the cough reflex. Decreasing the number of microorganisms in the mouth will help in reducing the organisms which are available for the passage to and colonization of the lung. Commonly used material by the nurse to provide mouth care to patients who cannot provide their own care are the foam swabs,28 which are not effective in plaque control but still they provide stimulation of mucosa.29
2.7.
Cancer
Pancreatic carcinogenesis is influenced by periodontal diseases which increase the generation of carcinogens like nitrosamines.30 There is evidence of elevated levels of oral bacteria and levels of nitrosamine in the oral cavity of the patients with periodontal disease.31 Smoking leads to oxidative stress and triggers a series of events that could contribute to cell transformation.32
i n d i a n j o u r n a l o f m e d i c a l s p e c i a l i t i e s 5 ( 2 0 1 4 ) 1 0 7 e1 1 1
2.8.
Denture wearers
Proper cleaning of the dentures will prevent these from being a chronic source of potentially harmful bacteria and fungi which may cause oral and systemic diseases. Many of the denture wearers are seen to be experiencing stomatitis caused by Candida albicans, Candida glabrata and other pathogens which are present on dentures and are also implicated in respiratory and gastrointestinal infections.
3. Influence of systemic diseases on oral health 3.1.
Helicobacter pylori infection
Greater plaque index and higher incidence rate for gingivitis is observed in individuals with gastric H. pylori infections.33 In fact, the oral cavity may be considered as the first place where colonization of the microbe may happen followed by infection of the gastric mucosa. Furthermore, studies have been able to isolate the bacteria from supragingival and subgingival plaque as well as saliva, and hence the oral cavity may be considered as an extragastric reservoir for this bacterium. This digestive infection is successfully curable by systematic antibiotic therapy and can be highly [up to 80e90%] eradicated after a therapeutic regimen called “Triple Therapy”. It is hypothesized that the extragastric reservoir is capable of inducing a reinfection. In patients who are treated for H. pylori infection, eradication therapy should also involve dental care, else, it may result in reinfection. H. pylori in the oral cavity is considered as extragastric reservoir. Dental treatment along with systemic therapy could be a promising therapeutic approach. But a recent systematic review showed that there is not enough evidence to support or refute this approach.34
3.2.
Cardiovascular disease
Cardiovascular disease is indicated by the build up of inflammatory plaques which cause thrombosis and in the long run may cause myocardial infarction. Thickening and hardening of the arteries are produced by this plaque build up in atherosclerosis. It shows a chronic inflammatory response which may cause injury to the endothelium of elastic and muscular arterial tissue.35 From a common pathological process, the occurrence of periodontitis and increased atherosclerotic risk in patients simulateneously indicates relationship between two different organ systems.36 Periodontal therapy produced remarkable changes in the lipid profiles of subjects which reinforces the link between periodontitis and cardiovascular disease.37
3.3.
Caries and its associations
Caries may be associated with cardiovascular diseases,38 oesophageal cancer39 and asthma.40 There are studies to suggest that asthmatic patients demonstrate a higher index of caries,41 while some studies refute the same.42 It has been noted that individuals with asthma accumulate higher
109
amounts of dental biofilms with higher salivary levels of mutans streptococci. It has also been demonstrated that b2 agonists decrease salivary secretion rate and patients on these medications have increased levels of lactobacilli and mutans streptococci.43 Epileptic patients also show a higher caries incidence as was shown in a Finnish population. The medication given for epilepsy has been blamed for the same.44 This result however may be challenged in that there are studies that demonstrate no significant difference in the caries incidence of epileptics and non-epileptic patients.45 This needs further research.
3.4.
Salivary markers of systemic diseases
The human saliva is an invaluable tool in the diagnosis of several local and systemic pathologies. Salivary biomarkers are non-invasive diagnostic methods. The multiple components within saliva help us by providing clues to local and systemic diseases and conditions apart from protecting the oral tissues.46 Saliva is increasingly used in the diagnosis of systemic diseases that affect the function of salivary glands € gren's syndrome, sarcoidosis, and its composition e.g., Sjo cystic fibrosis, alcoholic cirrhosis, diabetes mellitus47 and diseases of the adrenal cortex. Oral fluids act as a source of microbial DNA for detecting viruses (e.g., the herpes virus in Kaposi's sarcoma) and bacteria with the help of polymerase chain reaction methods (e.g., H. pylori, in gastritis, peptic ulcers and stomach cancer). Severity and onset of infections can be determined by detecting the presence of antibodies to the microorganisms found in saliva. Researchers in the past decade have demonstrated the saliva tests for antibodies to HIV.48 The saliva test is reliable and is potentially useful in initial detection of breast cancer49,50 and in diabetic patients.51 Altered levels of certain mRNA molecules have been detected in saliva in oral cancer patients and of certain proteins in several cancers.52
3.5. Pathways for oral disease-systemic disease communication There are three possible pathways that link oral infections to systemic effects.53 First evidence is the metastatic spread of infection from the oral cavity into systemic circulation as a result of bacteremia, then the metastatic injury produced from the effects of circulating oral microbial toxins and finally the metastatic inflammation caused by the immunological injury induced by the microorganisms. Periodontitis may affect the host's susceptibility to systemic diseases in three main ways namely by shared risk factors, by subgingival biofilms acting as reservoirs of gram negative bacteria and through periodontium which acts as a reservoir of inflammatory mediators.54 The medical practitioners should encourage the patients to maintain their oral hygiene to prevent systemic infections by giving them advice to brush and floss regularly.55
4.
Conclusion
The mouth is a significant source of infection and inflammation that contributes to the total burden of disease, and to
110
i n d i a n j o u r n a l o f m e d i c a l s p e c i a l i t i e s 5 ( 2 0 1 4 ) 1 0 7 e1 1 1
overall health, which should be systematically taken into account by all clinicians. Patients, dental hygienists, dentists, dental specialists and other health care providers should be aware of the consistent relationships between oral inflammation and systemic diseases and should be able to value the need to modify assessment, prevention, and treatment protocols to improve oral health as well as total health of the patients they treat in the office each day. Maintenance of oral health is a special challenge for medically compromised patients or those with acute illness. Hence, both the dentist and the physician must clearly understand this relation before diagnosis and planning the treatment.
Conflicts of interest All authors have none to declare.
references
1. Herzberg MC, Meyer MW. Effects of oral flora on platelets: possible consequences in cardiovascular diseases. J Periodontol. 1996;67:1138e1142. 2. Kay EJ. How often should we go to the dentist? Br Med J. 1999;319:204e205. 3. Riley III JL, Gilbert GH, Heft MW. Socioeconomic and demographic disparities in symptoms of orofacial pain. J Public Health Dent. 2003;63:166e173. 4. Petersen PE. The World Oral Health Report 2003. Continuous improvement of oral health in the 21st century e the approach of the WHO Global Oral Health Programme. 1e37. 5. Loesche WJ. Association of the oral flora with important medical diseases. Curr Opin Periodontol. 1997;4:21e28. 6. Scannapieco FA, Genco RJ. Association of periodontal infections with atherosclerotic and pulmonary diseases. J Periodontal Res. 1999;34:340e345. 7. Scannapieco FA, Papandonatos GD, Dunford RG. Associations between oral conditions and respiratory disease in a national sample survey population. Ann Periodontol. 1998;3:251e256. 8. Carmona IT, Diz Dios P, Scully C. An update on the controversies in bacterial endocarditis of oral origin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93:660e670. 9. Lockhart PB. An analysis of bacteremias during dental extractions: a double-blind, placebo-controlled study of chlorhexidine. Arch Intern Med. 1996;156:513e520. 10. Gendron R, Grenier D, Maheu-Robert L. The oral cavity as a reservoir of bacterial pathogens for focal infections. Microbes Infect. 2000;2:897e906. 11. LiX Kolltveit KM, Tronstad L, Olsen L. Systemic diseases caused by oral infection. Clin Microbiol Rev. 2000;13:547e558. 12. Syrjanen J, Peltola J, Valtonen V, Iivanainen M, Kaste M, Huttunen JK. Dental infections in association with cerebral infarction in young and middle-aged men. J Intern Med. 1989;225:179e184. 13. Poveda Roda R, Jimenez Y, Carbonell E, Gavalda C, Margaix Munoz MM, Sarrion Perez G. Bacteremia originating in the oral cavity: a Review. Med Oral Patol Oral Cir Bucal. 2008;13:355e362. 14. Nayak S, Nayak P. Systemic diseases associated with oral infection-a review. Indian J Dent Sci. 2010;2:20e27. 15. Lacassin F, Hoen B, Leport C, et al. Procedures associated with infective endocarditis in adults: a case-control study. Eur Heart J. 1995;16:1968e1974.
16. Van der Meer JT, Van Wijk W, Thompson J, Vandenbroucke JP, Valkenburg HA, Michel MF. Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis. Lancet. 1992;339:135e139. 17. Loe H, Silness J. Periodontal disease in pregnancy: prevalence and severity. Acta Odontol Scand. 1963;21:533e551. 18. Shapiro S, McCormick MC, Starfield BH, Krischer JP, Bross D. Relevance of correlates of infant deaths for significant morbidity at 1 year of age. Am J Obstet Gynecol. 1980;136:363e373. 19. Fitzharding PM. Follow-up studies of the low birth weight infant. Clin Perinatol. 1976;3:503e516. 20. McCall MG, Acheson ED. Respiratory disease in infancy. J Chronic Dis. 1968;21:349e359. 21. Van den Berg BJ, Yerushalmy J. The relationship of the rate of intrauterine growth of infants of low birth weight to mortality, morbidity, and congenital anomalies. J Pediatr. 1966;69:531e545. 22. Papapanou PN. Periodontal diseases: epidemiology. Ann Periodontol. 1996;1:1e36. 23. Taylor GW, Burt BA, Becker MP, et al. Severe periodontitis and risk for poor glycemic control in patients with non-insulindependent diabetes mellitus. J Periodontol. 1996;67:1085e1093. 24. Jain N, Bhargava M, Agarwal S. Periodontal disease and diabetes mellitus. Indian J Med Specialities. 2013;4:138e140. 25. Munro CL, Grap MJ. Oral health and care in the intensive care unit: state of the science. Am J Crit Care. 2004;13:25e33. 26. Scannapieco FA, Stewart EM, Mylotte JM. Colonization of dental plaque by respiratory pathogens in medical intensive care patients. Crit Care Med. 1992;20:740e745. 27. Muncro CL, Grap MJ. Oral health and care in the intensive care unit: state of the science. Am J Crit Care. 2004;13:65e74. 28. Grap MJ, Munro CL, Ashtiani B, Bryant S. Oral care interventions in critical care: frequency and documentation. Am J Crit Care. 2003;12:113e118. 29. Adams R. Qualified nurses lack adequate knowledge related to oral health, resulting in inadequate oral care of patients on medical wards. J Adv Nurs. 1996;24:552e560. 30. Nualart Grollmus ZC, Morales Chavez MC, Silvestre Donat FJ. Periodontal disease associated to systemic genetic disorders. Med Oral Patol Oral Cir Bucal. 2007;12:E211eE215. 31. Nair J, Ohshima H, Nair UJ, Bartsch H. Endogenous formation of nitrosamines and oxidative DNA-damaging agents in tobacco users. Crit Rev Toxicol. 1996;26:149e161. 32. Soory M. Oxidative stress induced mechanisms in the progression of periodontal diseases and cancer: a common approach to redox homeostasis. Cancers. 2010;2:670e692. ~ o MB, Martins LC, Melo Barbosa HP, et al. 33. Assumpc¸a Helicobacter pylori in dental plaque and stomach of patients from Northern Brazil. World J Gastroenterol. 2010;16:3033e3039. 34. Navabi N, Aramon M, Mirzazadeh A. Does the presence of the Helicobacter pylori in the dental plaque associate with its gastric infection? A meta-analysis and systematic review. Dent Res J. 2011;8:178e182. 35. Schwartz CJ, Valente AJ, Sprague EA, Kelley JL, Nerem RM. The pathogenesis of atherosclerosis: an overview. Clin Cardiol. 1991;14:1e6. 36. Prakash N, Narang P. Periodontal and cardiovascular diseases: an intriguing association. Indian J Med Specialities. 2010;1:6e7. 37. Tandon S, Dhingra MS, Lamba AK, Verma M, Munjal A, Faraz F. Effect of periodontal therapy on serum lipid levels. Indian J Med Specialities. 2010;1:19e25. 38. Holm-Pedersen P, Avlund K, Morse DE, et al. Dental caries, periodontal disease, and cardiac arrhythmias in communitydwelling older persons aged 80 and older: is there a link? J Am Geriatr Soc. 2005;53:430e437. 39. Dye BA, Wang R, Lashley R, et al. Using NHANES oral health examination protocols as part of an esophageal cancer
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40.
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screening study conducted in a high-risk region of China. BMC Oral Health. 2007;17:7e10. Botelho MP, Maciel SM, Cerci Neto A, Dezan CC, Fernandes KB, de Andrade FB. Levels of cariogenic microorganisms and oral conditions of asthmatic children. Caries Res. 2011;45:386e392. Stensson M, Wendt LK, Koch G, Oldaeus G, Birkhed D. Oral health in preschool children with asthma. Int J Paediatr Dent. 2008;18:243e250. € f G, Hedlin G, Lindell M, Mode er T. Effect Bjerkeborn K, Dahllo of disease severity and pharmacotherapy of asthma on oral health in asthmatic children. Scand J Dent Res. 1987;95:159e164. €a € L, Ra € ttya € J, et al. Tooth by tooth Rajavaara P, Vainionpa survival analysis of dental health in girls with epilepsy. Eur J Paediatr Dent. 2003;4:72e77. € m A, Hamp SE. Oral state of children Eeg-Olofsson O, Lundstro with epilepsy on treatment with sodium valproate. Scand J Dent Res. 1983;91:219e223. Slavkin HC. Toward molecular based diagnostics for the oral cavity. J Am Dent Assoc. 1998;129:1138e1143. Reilly TG, Poxon V, Sanders DS, Elliot TS, Walt RP. Comparison of serum, salivary, and rapid whole blood diagnostic tests for Helicobacter pylori and their validation against endoscopy based tests. Gut. 1997;40:454e458. Soares MS, Barista Filho MM, Pimentel MJ, Passos IA, Chimenos-Kustner E. Determination of salivary glucose in
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healthy adults. Med Oral Patol Oral Cir Bucal. Oct 2009;14:510e533. Malamud D. Oral diagnostic testing for detecting human immunodeficiency virus-1 antibodies: a technology whose time has come. Am J Med. 1997;102:9e14. Streckfus C, Bigler L, Dellinger T, et al. Reliability assessment of soluble c-erbB-2 concentrations in the saliva of healthy women and men. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:174e179. Zimmermann BG, Wong DT. Salivary mRNA targets for cancer diagnostics. Oral Oncol. 2008;44:425e429. Sreedevi, Shashikanth MC, Shambulingappa P. Comparison of serum glucose and salivary glucose in diabetic patients. J Indian Acad Oral Med Radiol. 2008;20:9e13. Streckfus C, Bigler L, Dellinger T, Dai X, Kingman A, Thigpen JT. The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study. Clin Cancer Res. 2000;6:2363e2370. Thoden van Velzen SK, Abraham-Inpijn L, Moorer WR. Plaque and systemic disease: a reappraisal of the focal infection concept. J Clin Periodontol. 1984;11:209e220. Page RC. The pathobiology of periodontal diseases may affect systemic diseases: inversion of a paradigm. Ann Periodontol. 1998;3:108e120. Togoo RA. Poor oral hygiene and systemic diseases: role of medical practitioners. Indian J Med Specialities. 2012;3:112e113.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/injms
Review Article
Systemic diseases and oral health Shilpa Ramesh, Prasanna Neelakantan* Undergraduate Clinic 6, Saveetha Dental College and Hospitals, Saveetha University, Chennai, India
article info
abstract
Article history:
Oral health is an important and often overlooked component of a person's general health
Received 31 July 2013
and well-being. Systemic conditions noted to occur with oral manifestations include dia-
Accepted 1 June 2014
betes, cutaneous diseases, hereditary disease, joint disease, immunocompromised states like HIV, AIDS, etc. Several studies have linked poor oral health with cardiovascular dis-
Keywords:
ease, poor glycemic control in diabetics, low birth-weight pre-term babies, and a number of
Bacteremia
other conditions, including rheumatoid arthritis and osteoporosis, respiratory diseases,
Coronary disease
etc. This review is to stress on the importance of considering both systemic and oral health
Dental caries
when treating an individual.
Diabetes mellitus
Copyright © 2014, Indian Journal of Medical Specialities. Published by Reed Elsevier India
Periodontal diseases
1.
Introduction
The effect of oral health on the rest of the body was stated by the Assyrians as early as the seventh century B.C.1 There is much more than beautiful teeth aligned perfectly in the oral cavity when it comes to oral health. Oral health, in essence, refers to the freedom from chronic oral-facial pain, orofacial lesions, birth defects such as cleft lip and palate, and other diseases and disorders that affect the craniofacial complex.2 Socio-economic considerations often serve as barriers to obtain dental care in a private practice dental delivery system, and it has been noticed that, this population experiences greater levels of both dental and systemic disease.3 The most prevalent and non-transmissible infectious disease experienced by most of the people all over the world is dental caries which is nothing but the bacterial infection and degradation of the tooth structure.4 Colonization of the oropharyngeal region is always linked with several systemic diseases5 such as cardiovascular disease,6 chronic obstructive
Pvt. Ltd. All rights reserved.
pulmonary disease,7 endocarditis8 and bacteremia.9 Considerable controversy surrounds the focal infection theory, which says that the mouth is a bacterial reservoir from where infection can spread through blood to cause infections at distant sites, besides, it can stimulate the immune response and the circulating inflammatory mediators will cause damage throughout the body.10 This review discusses the influence that oral health has on systemic diseases and vice-versa. The role of salivary biomarkers has also been presented.
2. The relationship between oral health and systemic diseases Various diseases or problems like stroke, infective endocarditis, bacterial pneumonia, low birth weight, myocardial infarction, congestive heart failure etc., are caused mainly by oral infections or oral health.11
* Corresponding author. 1500, 16th Main Road, Anna Nagar West, Chennai 600040, Tamil Nadu, India. E-mail address: [email protected] (P. Neelakantan). http://dx.doi.org/10.1016/j.injms.2015.02.003 0976-2884/Copyright © 2014, Indian Journal of Medical Specialities. Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
108
2.1.
i n d i a n j o u r n a l o f m e d i c a l s p e c i a l i t i e s 5 ( 2 0 1 4 ) 1 0 7 e1 1 1
Stroke
Stroke is a cerebrovascular disease that affects blood vessels supplying blood to the brain. It occurs when a blood vessel bringing oxygen and nutrients to the brain bursts or is clogged by local thrombus formation or by aggregates of bacteria and fibrin from other sources such as the heart. Studies on the pathology of stroke indicate that 80e85% of these lesions are due to cerebral infarction; 15e20% are caused by hemorrhage. The periodontium when inflamed releases bacterial byproducts, inflammatory cytokines, lipopolysaccharides (LPS) and bacteria into the circulation. It advances atherosclerosis and it may affect the coagulation of blood, the normal platelet functions and prostaglandin synthesis, thus abetting the onset of stroke. A case control study demonstrated poor oral health in patients with cerebral infarction as compared to the control group.12 This could further set up a vicious cycle because of periodontal inflammation.
2.2.
Infective endocarditis
Bacterial infection of the heart valves or the endothelium of the heart is called as infective endocarditis. It is caused due to bacteria gaining entry in to the bloodstream and getting lodged on abnormal heart valves or damaged heart tissue.13 It is a fatal systemic disease, when untreated and has always been connected with dental diseases and their treatment, during which the bacteria enter the blood stream and there are more chances of them getting lodged in the heart. Recently there were three controlled studies conducted and all showed a link between dental procedures and bacterial endocarditis.14e16 The commonly implicated dental procedures are oral prophylaxis (scaling and root planning) and extractions. Endodontic treatment is considered to be safe in these patients.
2.3.
Low birth weight
Pregnancy gingivitis is a condition which is due to the changes in the hormone levels during pregnancy resulting in inflammation of gingiva.17 It has been elucidated that gram negative periodontal infections can have an influence on the outcome of pregnancy. Considering local factors like plaque in such a case during the second trimester of pregnancy, these gram negative anaerobic bacteria produce several bioactive molecules that have a direct negative impact on the host. For example, the lipopolysaccharide component of the cell wall of gram negative bacteria activate macrophages and help in the production of several cytokines like interleukins 1 and 6, tumor necrosis factor (TNF), and prostaglandin E2 (PGE2), in addition to matrix metalloproteinases. These molecules have the ability to cross the placental barrier, augment the levels of PGE2 and TNF in the amniotic fluid and induce premature labor. Low birth weight infants are more likely to die during the neonatal period when compared to normal birth weight infants18 and even if they survive they will face neurodevelopmental disturbances,19 problems with respiration20 and congenital anomalies.21
2.4.
Diabetes mellitus
Periodontal disease often occurs in co-existence with diabetes mellitus. Recent research focusses on the possibility that periodontal disease can either predispose or exacerbate diabetes. This is based on findings that when mechanical periodontal treatment [scaling, root planing and curettage] alone is provided, regardless of the severity of periodontal disease or degree of diabetes control, the treatment outcome is improvement in periodontal status only i.e., it is a localized effect. However, when systemic antibiotics are included in addition to the mechanical therapy, an improvement in diabetes control is achieved which is evident by a reduction in glycosylated hemoglobin or a reduction in insulin requirements.22 Diabetics are more likely to develop severe periodontal disease than non-diabetics and it is a well realized point.22 There is an increased risk of poor glycemic control in diabetic patients with periodontitis when compared to the diabetics without periodontitis.23 Dental check up should be made periodic for diabetic patients to check their periodontal health status.24
2.5.
Bacterial pneumonia
Potential pathogens can be cultured from the oral cavity in critically ill patients in the intensive care units, and these microorganisms in the mouth can move along the respiratory tract and colonize the lung resulting in ventilator-associated pneumonia.25 This incidence can be reduced by removing the dental plaque.
2.6.
Patients in the critical care unit
Unlike the healthy persons, dental plaque in patients in the Intensive Care Unit may serve as a reservoir for the pathogens and can be easily colonized by respiratory pathogens like methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.26,27 Bacteria gain easy entry from the oropharynx through an open glottis to the lower part of the respiratory tract along the endotracheal tubes. These tubes also help in colonization, by interfering with the cough reflex. Decreasing the number of microorganisms in the mouth will help in reducing the organisms which are available for the passage to and colonization of the lung. Commonly used material by the nurse to provide mouth care to patients who cannot provide their own care are the foam swabs,28 which are not effective in plaque control but still they provide stimulation of mucosa.29
2.7.
Cancer
Pancreatic carcinogenesis is influenced by periodontal diseases which increase the generation of carcinogens like nitrosamines.30 There is evidence of elevated levels of oral bacteria and levels of nitrosamine in the oral cavity of the patients with periodontal disease.31 Smoking leads to oxidative stress and triggers a series of events that could contribute to cell transformation.32
i n d i a n j o u r n a l o f m e d i c a l s p e c i a l i t i e s 5 ( 2 0 1 4 ) 1 0 7 e1 1 1
2.8.
Denture wearers
Proper cleaning of the dentures will prevent these from being a chronic source of potentially harmful bacteria and fungi which may cause oral and systemic diseases. Many of the denture wearers are seen to be experiencing stomatitis caused by Candida albicans, Candida glabrata and other pathogens which are present on dentures and are also implicated in respiratory and gastrointestinal infections.
3. Influence of systemic diseases on oral health 3.1.
Helicobacter pylori infection
Greater plaque index and higher incidence rate for gingivitis is observed in individuals with gastric H. pylori infections.33 In fact, the oral cavity may be considered as the first place where colonization of the microbe may happen followed by infection of the gastric mucosa. Furthermore, studies have been able to isolate the bacteria from supragingival and subgingival plaque as well as saliva, and hence the oral cavity may be considered as an extragastric reservoir for this bacterium. This digestive infection is successfully curable by systematic antibiotic therapy and can be highly [up to 80e90%] eradicated after a therapeutic regimen called “Triple Therapy”. It is hypothesized that the extragastric reservoir is capable of inducing a reinfection. In patients who are treated for H. pylori infection, eradication therapy should also involve dental care, else, it may result in reinfection. H. pylori in the oral cavity is considered as extragastric reservoir. Dental treatment along with systemic therapy could be a promising therapeutic approach. But a recent systematic review showed that there is not enough evidence to support or refute this approach.34
3.2.
Cardiovascular disease
Cardiovascular disease is indicated by the build up of inflammatory plaques which cause thrombosis and in the long run may cause myocardial infarction. Thickening and hardening of the arteries are produced by this plaque build up in atherosclerosis. It shows a chronic inflammatory response which may cause injury to the endothelium of elastic and muscular arterial tissue.35 From a common pathological process, the occurrence of periodontitis and increased atherosclerotic risk in patients simulateneously indicates relationship between two different organ systems.36 Periodontal therapy produced remarkable changes in the lipid profiles of subjects which reinforces the link between periodontitis and cardiovascular disease.37
3.3.
Caries and its associations
Caries may be associated with cardiovascular diseases,38 oesophageal cancer39 and asthma.40 There are studies to suggest that asthmatic patients demonstrate a higher index of caries,41 while some studies refute the same.42 It has been noted that individuals with asthma accumulate higher
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amounts of dental biofilms with higher salivary levels of mutans streptococci. It has also been demonstrated that b2 agonists decrease salivary secretion rate and patients on these medications have increased levels of lactobacilli and mutans streptococci.43 Epileptic patients also show a higher caries incidence as was shown in a Finnish population. The medication given for epilepsy has been blamed for the same.44 This result however may be challenged in that there are studies that demonstrate no significant difference in the caries incidence of epileptics and non-epileptic patients.45 This needs further research.
3.4.
Salivary markers of systemic diseases
The human saliva is an invaluable tool in the diagnosis of several local and systemic pathologies. Salivary biomarkers are non-invasive diagnostic methods. The multiple components within saliva help us by providing clues to local and systemic diseases and conditions apart from protecting the oral tissues.46 Saliva is increasingly used in the diagnosis of systemic diseases that affect the function of salivary glands € gren's syndrome, sarcoidosis, and its composition e.g., Sjo cystic fibrosis, alcoholic cirrhosis, diabetes mellitus47 and diseases of the adrenal cortex. Oral fluids act as a source of microbial DNA for detecting viruses (e.g., the herpes virus in Kaposi's sarcoma) and bacteria with the help of polymerase chain reaction methods (e.g., H. pylori, in gastritis, peptic ulcers and stomach cancer). Severity and onset of infections can be determined by detecting the presence of antibodies to the microorganisms found in saliva. Researchers in the past decade have demonstrated the saliva tests for antibodies to HIV.48 The saliva test is reliable and is potentially useful in initial detection of breast cancer49,50 and in diabetic patients.51 Altered levels of certain mRNA molecules have been detected in saliva in oral cancer patients and of certain proteins in several cancers.52
3.5. Pathways for oral disease-systemic disease communication There are three possible pathways that link oral infections to systemic effects.53 First evidence is the metastatic spread of infection from the oral cavity into systemic circulation as a result of bacteremia, then the metastatic injury produced from the effects of circulating oral microbial toxins and finally the metastatic inflammation caused by the immunological injury induced by the microorganisms. Periodontitis may affect the host's susceptibility to systemic diseases in three main ways namely by shared risk factors, by subgingival biofilms acting as reservoirs of gram negative bacteria and through periodontium which acts as a reservoir of inflammatory mediators.54 The medical practitioners should encourage the patients to maintain their oral hygiene to prevent systemic infections by giving them advice to brush and floss regularly.55
4.
Conclusion
The mouth is a significant source of infection and inflammation that contributes to the total burden of disease, and to
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overall health, which should be systematically taken into account by all clinicians. Patients, dental hygienists, dentists, dental specialists and other health care providers should be aware of the consistent relationships between oral inflammation and systemic diseases and should be able to value the need to modify assessment, prevention, and treatment protocols to improve oral health as well as total health of the patients they treat in the office each day. Maintenance of oral health is a special challenge for medically compromised patients or those with acute illness. Hence, both the dentist and the physician must clearly understand this relation before diagnosis and planning the treatment.
Conflicts of interest All authors have none to declare.
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