Oral:Systemic/Systemic:OralIs there a connection?

Roy Eversole DDS MSDOral and Maxillofacial Pathology

Oral Bacterial Diseases• Dental Caries: plaque, Streptococcus

mutans>acid production>dissolution of enamel>pulpitis>osteomyelitis>cellulitis vrs. Space infection

• Periodontal Disease: root surface plaque, dental sulcus, multiple microbial pathogens including anaerobid gram neg rods>alveolar bone resorption>loss

Patients at Risk• Dental Caries

– Children: refined sugar diets– Nonfluorinated water source– Addicts, particularly crystal meth– Xerostomia (post radiation, Sjogren’s, Drugs

• Periodontal Disease– Poor Home Care– Smokers– Diabetics, particularly IDDM– HIV

Caries Sequelae

Periodontal Disease

Crystal Meth Mouth

Pulpitis

Carious Lesions with bacteriaextending into the pulp

Hyperplastic Pulpitis(Pulp Polyp)

Spread of Infection from Pulp to Periapex of Periodontium

• One of three lesions are commonly encountered:

Periapical Granuloma• Chronic Apical

Periodontitis

Periapical Granuloma, Complications

Endo/Perio

Antral Polyp

Apical Periodontal (Radicular) Cyst

Laterally displaced, accessory canal

Cone Beam CTs

Spread from Endodontic Infections

Caries Vaccination

• J Gen Microbiol. 1986 Oct;132(10):2885-92. Links• Demonstration of shared antigenic determinants between

Streptococcus mutans BHT cell membrane, human heart tissue and myosin using monoclonal antibodies to S. mutans.

• Doyle G, Everhart D, Mallett C, Ayakawa G, Bleiweis AS.• Monoclonal antibodies (MAb) raised to intact Streptococcus mutans P-4

cells (serotype e) were used to demonstrate the presence of shared antigenic determinant(s) between S. mutans BHT (serotype b) cell membranes and human heart tissue. MAb binding to both BHT membrane and human heart tissue was demonstrated by ELISA. Common antigens were identified by immunoblot analysis following separation of BHT membrane components and human heart antigens by SDS-PAGE. MAb 22C4 recognized three polypeptides from the BHT membrane preparation, having molecular masses of 42, 56 and 85 kDa. MAb 22C4 also recognized an 85 kDa component and a 200 kDa component from human heart tissue. MAb D159 was specific for a single 82 kDa polypeptide in BHT membrane, and also bound to two high molecular mass components in human heart (165 and 200 kDa). When both MAb D159 and 22C4 were first absorbed with S. mutans P-4 cells, subsequent reactivity to the aforementioned BHT membrane components was inhibited, indicating that these cross-reactive components are found in S. mutans P-4 as well as in S. mutans BHT micro-organisms. Competitive binding analysis showed that both MAb D159 and MAb 22C4 bound to myosin, indicating that S. mutans BHT membrane, human heart tissue and myosin share at least one immunodeterminant. This indicates that myosin could be the cross-reactive tissue component in human heart.

• Protective efficacy of a targeted anti-caries DNA plasmid against cariogenic bacteria infections.

• Xu QA, Yu F, Fan MW, Bian Z, Chen Z, Peng B, Jia R, Guo JH.• Key Laboratory for Oral Biomedical Engineering of Ministry of

Education, School&hospital of Stomatology, Wuhan University, Luoyu Road 237, 430079 Wuhan, Hubei, China.

• We have previously reported that a targeted anti-caries DNA plasmid pGJA-P/VAX which was constructed against the antigenic determinants of Streptococcus mutans (S. mutans) successfully induced antibody responses in mice and monkeys. The present study explored the protective efficacy of pGJA-P/VAX against cariogenic bacterial challenge. Groups of rats were orally challenged with S. mutans or Streptococcus sobrinus (S. sobrinus) and then immunized with pGJA-P/VAX or the vector pVAX1 intranasally. Serum IgG and salivary IgA antibody levels were assessed by an enzyme-linked immunosorbent assay and caries activity was evaluated by the Keyes method. The results showed that specific salivary IgA antibody responses were induced following intranasal vaccination with pGJA-P/VAX. Moreover, immunization with pGJA-P/VAX resulted in significantly reduced enamel and dentinal caries lesions in rats after S. mutans infection and significantly reduced enamel caries lesions after S. sobrinus infection. Thus, pGJA-P/VAX was not only protective toward S. mutans infection, but also provided cross-strain protection against S. sobrinus infection in rats.

• Caries Res. 1999;33(1):4-15. • Secretory immunity in defense against cariogenic mutans

streptococci.• Russell MW, Hajishengallis G, Childers NK, Michalek SM.• Microbiology, University of Alabama at Birmingham, Ala. 35294-

2170, USA. MWR@uab.edu• Specific immune defense against cariogenic mutans

streptococci is provided largely by salivary secretory IgA antibodies, which are generated by the common mucosal immune system. This system is functional in newborn infants, who develop salivary IgA antibodies as they become colonized by oral microorganisms. The mechanisms of action of salivary IgA antibodies include interference with sucrose-independent and sucrose- dependent attachment of mutans streptococci to tooth surfaces, as well as possible inhibition of metabolic activities. The goal of protecting infants against colonization by mutans streptococci might be accomplished by applying new strategies of mucosal immunization that would induce salivary IgA antibodies without the complications of parenteral immunization. Strategies of mucosal immunization against mutans streptococci currently under development include the use of surface adhesins and glucosyltransferase as key antigens, which are being incorporated into novel mucosal vaccine delivery systems and adjuvants. The oral application of preformed, genetically engineered antibodies to mutans streptococcal antigens also offers new prospects for passive immunization against dental caries.

Chronic Inflammatory Periodontitis

• A bacterial infection of the periodontal ligament• Periodontopathic bacteria in dental plaque

– Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Bacteroides

• PDL inflammation with apical migration of the epithelial attachment– Sulcular epithelial hyperplasia, granulation tissue with

plasma cells and lymphocytes in PDL and gingival connective tissues

• Loss of supporting alveolar bone, pocket formation, lossening of teeth, tooth loss

Chronic Periodontitis

PLAQUE

MICROBES

Apical cyst

Horizontal Bone Loss

Periodontal Disease, Diabetes

Periodontitis, Diabetes

Multiple periodontal abscesses

HIV Periodontitis

• Rapidly progressive form of periodontitis seen only in a minority of patients who are HIV infected.

• Skip lesions: Normal areas interposed between lesional areas of periodontium

• No pocket formation: Complete periodontal breakdown with loss of PDL, alveolar bone, gingival soft tissues

HIV Periodontal Disease

HIV GingivitisGeneralized Linear Erythema

Acute Necrotizing ulcerativePeriodontitis

Plaque Microbial Antigens as Immunostimulants

Plaque Organisms as Systemic Pathogens

• Curr Med Res Opin. 2008 Jun;24(6):1635-43. Epub 2008 Apr 30. Links• The potential impact of periodontal disease on general health: a consensus view.• Williams RC, Barnett AH, Claffey N, Davis M, Gadsby R, Kellett M, Lip GY, Thackray S.• University of North Carolina, School of Dentistry, Chapel Hill, NC 27599, USA.

ray_williams@dentistry.unc.edu• BACKGROUND: Evidence for a link between periodontal disease and several systemic diseases

is growing rapidly. The infectious and inflammatory burden of chronic periodontitis is thought to have an important systemic impact. Current evidence suggests that periodontitis is associated with an increased likelihood of coronary heart disease and may influence the severity of diabetes. SCOPE: This paper represents a UK and Ireland cross-specialty consensus review, undertaken by a group of physicians and dentists. The consensus group reviewed published evidence (PubMed search for review and original articles), focusing on the past 5 years, on the contributory role of periodontal disease to overall health. In particular, evidence relating to a role for periodontal disease in cardiovascular disease and in diabetes was considered. FINDINGS: Initial studies of large epidemiological data sets have sought to find links between periodontitis and systemic disease outcomes, but a causal relationship still needs to be demonstrated between periodontal disease, cardiovascular disease and diabetes through prospective studies. There is a need for prospective studies assessing the association between periodontal disease and patients at particular risk of cardiovascular events which will allow assessment of both cardiovascular disease clinical endpoints and surrogate markers of cardiovascular risk. Of note, periodontal disease is also often more severe in subjects with diabetes mellitus, a group at already increased risk for cardiovascular events. CONCLUSIONS: While further research is needed to define the population-attributable risk of periodontal disease to both cardiovascular diseases and to diabetes control and progression, health education to encourage better oral health should be considered as part of current healthy lifestyle messages designed to reduce the increasing health burden of obesity, cardiovascular disease and diabetes.

• Compend Contin Educ Dent. 2008 Sep;29(7):402-8, 410, 412-3. Links• Diabetes mellitus and inflammatory periodontal diseases.• Mealey BL, Rose LF.• Department of Periodontics, University of Texas Health Science Center, San Antonio,

Texas, USA.• THE PURPOSE OF REVIEW: Periodontal diseases are inflammatory conditions that

were once thought to have manifestations localized to the oral cavity alone, and were therefore considered the concern of only dentists and other oral health professionals. Emerging evidence has changed this view and now suggests that periodontal diseases may play a role in numerous conditions that impact systemic well-being, including diabetes mellitus. This review examines the relationships that exist between periodontal diseases and diabetes mellitus, with a focus on potential common pathophysiologic pathways including those associated with inflammation, altered host responses, and insulin resistance. RECENT FINDINGS: Periodontal inflammation is associated with an elevated systemic inflammatory state and an increased risk of major cardiovascular events such as myocardial infarction and stroke, adverse pregnancy outcomes such as preeclampsia, low birth weight, and preterm birth, and altered glycemic control in people with diabetes. Intervention trials suggest that periodontal therapy, which decreases the intraoral bacterial bioburden and reduces periodontal inflammation, can have a significant impact on systemic inflammatory status. Evidence suggests that periodontal therapy is associated with improved glycemic control in many patients with both diabetes and periodontal diseases. SUMMARY: Recognition of the bilateral relationships between oral and systemic health will challenge physicians and dentists to work together closely in the future when managing patients with diabetes and periodontal disease.

HEAD & NECK MANIFESTATIONS OF SYSTEMIC DISEASES

• WHITE• RED• PIGMENTED• VESICULAR• BULLOUS/DESQUAMATIVE• ULCERATIVE• TUMEFACTIVE• RADIOLUCENT• RADIOOPAQUE• MIXED LUCENT/OPAQUE

LUCENCIES AND OPACITIES

PULMONARY• Abscess from aspirated tooth, endodontic

file• Chronic Granulomatous Inflammations

– Tuberculosis– Infectious deep fungi– Sarcoidosis

• Metastatic CA

• All with tumefactive ulcers

Gastrointestinal

• Blood born pathogens (Hepatitis viruses)• Gluten enteropathy aphthous-like ulcers• Pyostomatitis vegetans• Crohn’s nodular granulomas• Peutz-Jegher Syndrome perioral macules• Gardner Syndrome osteomas extra teeth

Autoimmune Collagen Diseases

• Sjogren syndrome parotid enlargement• Scleroderma radiographic changes• Lupus oral red/white discoid lesions• Wegeners strawberry gums

Hematologic• Leukemias, gingival enlargement, bleeding and

petechia• Lymphoma

– Cervical Nodes– MALT Salivary glands– Extranodal MALT and others, palatal mass

• Myeloma, plasmacytoma, jaw lucencies• Hemorrhagic Diatheses, oral petechiae• Pernicious anemia, bald tongue• Sickle cell and Thalassemia radiographic

Renal

• Uremic halitosis (ammonia)• Metastatic RCCA, lucencies, ulcerations

Cutaneous

• Numerous genodermatosis keratoses– White sponge nevus, Grovers, Keratosis follicularis,

• Bullous/desquamative– Erosive lichen planus, pemphigus vulgaris, mucous

membrane pemphigoid, EM, paraneoplastic pemphigus

• Neurofibromatosis, café au lait, masses• Nevoid basal cell carcinoma, jaw cysts• Breast, metastatic cancer

Endocrine• Diabetes,

– advanced periodontal disease with abscess formation– Candidiasis– Mucormycosis

• Addison, oral pigmentation• Cushing Pituitary based, oral pigmentation• MEN III, mucosal neuromas• Hypothyroidism, macroglossia• Hyperparathyroidism (primary and secondary)

brown tumors of jaws

Developmental

• Hundreds of facial dysmorphic syndromes with limb, digit, cutanous, osseous and organ system defects

Drug Induced Oral Lesions• Lichenoid stomatitis• Allergic stomatitis• Erythema multiforme• Gingival enlargement (dilantin, calcium

channel blockers, cyclosporin)• Tetracycline stained teeth• Minocycline oral pigmentation• Xerostomia and root caries

Musculoskeletal

• Muscular dystrophies and facial muscles• Osseous dysplasias

– Osteitis deformans– Fibrous dysplasia– McCune-Albright

• Marble Bone disease radiographic• Vit D Refractory Ricketts• Hypophosphastasia

Neurologic

• Facial Palsy from stroke• Facial pain syndromes• Medulloblastoma, jaw cysts, Gorlin

syndrome

Systemic Infections

• Childhood viral• Shingles• Herpes• Syphilis• HIV