Defense Mechanisms of the Oral Cavity (Periodontal disease & Salivary Gland Infection) 2024 PDF

MOSDOH 5303 Defense Mechanism of the Oral Cavity Periodontal disease & Sialadenitis Fall 2024...

MOSDOH 5303 Defense Mechanism of the Oral Cavity Periodontal disease & Sialadenitis Fall 2024 Topic 55 Priscilla Phillips, PhD Copyright © 2024, A.T. Still University/Missouri School of Dentistry & Oral Health. This presentation is intended for ATSU/Missouri School of Dentistry & Oral Health use only. No part of this presentation may be distributed, reproduced or uploaded/posted on any Internet web sites. Copyright Disclaimer : Certain figures/tables are included under the fair use exemption of the U.S. Copyright Law and have been prepared according to the educational multimedia fair use guidelines and are restricted from further use.  1) Gingivitis and periodontitis defined 2) The etiology / ecology of Periodontal periodontal disease Disease American Academy of Periodontology and the European Federation of Periodontology https://doi.org/10.1002/JPER.17-0719  Definition of Periodontal Disease Recall: The microflora of the healthy gingival crevice is relatively sparse due to regular maintenance (oral hygiene) and composed mainly of Streptococcus species and very low numbers of obligate anaerobes Periodontal disease includes all disorders of the supporting structures of the teeth (periodontium), including the gingiva, periodontal ligament, and alveolar bone Periodontal disease can be divided into two broad groups: ◆ Gingivitis: reversible inflammation of the gingiva alone ◆ Periodontitis: Loss of periodontal tissue support due to inflammation o Each subtype of periodontitis has a defined level of interdental clinical attachment loss (CAL), complexity, extent, and oral distribution Most cases of periodontal disease is caused by inflammation inducing subgingival biofilm where severity is associated with biofilm containing a high population proportion of obligate anaerobes.  historical Gingivitis Classic definition: reversible inflammation of gingival tissue Classification: it is historically subclassified by presentation and associated risk factors (Armitage GC. Ann. Periodontol. 1999;4:1–6). Host risk factors: drugs, hormones, stress, oral habits, hygiene, predisposing diseases/health conditions, immune response to microbial infection (e.g., MMPs)  Biofilm-Induced Periodontal Disease Typically displays chronological disease progression 1. Chronic Sulcus/Crevice Subgingival Periopathogens ** inflammation residing in plaque 2. Progressive (Biofilm) plaque destruction of periodontal Gingiva ligament and supporting bone by host Alveolar and bacterial Periodontal Bone factors Ligament 3. May result in Health Gingivitis Periodontitis tooth loss A chronic infection  In search for the microbial etiology of periodontal disease  Using the “experimental gingivitis in man” model, Loe et al.(1965) demonstrated that the development and accumulation of dental plaque per se can be correlated with clinically demonstrable gingivitis. Furthermore, increasing age was associated with development of periodontal disease, leading to the original non-specific plaque hypothesis of the Plaque Model  Advancements in culturing methods and the realization that bacteria in “normal” flora can become pathogens under certain conditions led to the specific plaque hypothesis of the Plaque Model (Loesche, 1976) and the search for periodontal pathogens. Koch’s postulates - 1884 Classic scientific method to determine the causative organism of a specific infectious disease The specific pathogen should: 1. be isolated from all cases and should not be found in healthy individuals. 2. be isolated from the diseased individual and grown in pure culture on an artificial medium. 3. reproduce the specific disease when inoculated into a healthy individual. Heinrich Hermann Robert 4. be re-isolated from the experimental infection. Koch -Physician HOWEVER: These postulates do not take in account uncultivable bacteria and host factors (e.g., immune response), and thus modifications have been made to this guideline since the 1950’s Socransky’s Postulates An alternative set to Koch’s postulates, it is the criteria that was used to identify periodontal pathogens (S. Socransky & A. Haffajee 1992): 1. Association with disease based on increased numbers of the pathogen at sites of disease pathology 2. Elimination or decreased numbers of the pathogen at treated sites that demonstrate a return to clinical health 3. Evidence of a host immune response to the pathogen 4. Pathogenic potential of the pathogen as demonstrated in animal model systems 5. Possession of virulence factors with the potential to contribute to periodontal tissue destruction Dr. Socransky, DDS & Dr. Haffajee, BDS Forsyth Institute Periodontal Pathogens In a landmark study (Socransky et al. 1998), specific species of bacteria were found to correlate into 5 clusters relative to severity of periodontal disease. Outcome: While gingivitis is generally accepted to be caused by plaque accumulation per se, periodontitis has a microbial ecology component These results, obtained from examination of >13K subgingival plaque samples from 185 adults for 40 known species, has held up fairly well against later studies using modern molecular methods. Periodontal Pathogens: The complexes ◆ Species associated with disease - Associated does not mean required for disease, rather, they are a good predictor when present at high numbers. ◆ Members in a complex (e.g., red, orange, yellow, green, blue) tend to found together in a site (Socransky et al. 1998). 1st red complex (high riska): Porphyromonas gingivalis* ,Tannerella forsythia*, Treponema denticola* , when together are associated with all types of periodontitis. (P. gingivalis dominance is considered a marker for severe periodontal disease in adults- a keystone pathogen). They have been shown to display mutualistic behaviors that promote growth and survival, and/or increased expression of factors that lead to greater pathology (2021. PMID: 34950607) Updatea: Currently suspected periodontal pathogens in susceptible individuals among the original complex categorized species: *Gram negative obligate anaerobe ⌘Gram negative facultative anaerobe #Gram positive obligate anaerobe 2nd orange complex (Moderate riska; also associated with infection of non-periodontal sites): Fusobacterium nucleatum*, Prevotella intermedia*, Prevotella nigrescens*, Parvimonas micra#, Eubacterium nodatum#, Campylobacter rectus⌘, Campylobacter showae, Campylobacter gracilis, Streptococcus constellatus Updatea: Currently suspected periodontal pathogens in susceptible individuals among the original complex categorized species: *Gram negative obligate anaerobe ⌘Gram negative facultative anaerobe #Gram positive obligate anaerobe 3rd yellow complex (Low riska; tend to be associated with each other than with red or orange and not associated with bleeding upon probing): Streptococcus intermedius#, Streptococcus sanguinis, Streptococcus oralis, Streptococcus mitis, Streptococcus gordonii Updatea: Currently suspected periodontal pathogens in susceptible individuals among the original complex categorized species: *Gram negative obligate anaerobe ⌘Gram negative facultative anaerobe #Gram positive obligate anaerobe Other important disease associated species not identified as part of the first 3 complexes in Socransky et al. 1998 Form synergistic/mutualistic interactions with P. ginigivalis: ◆ Aggregatibacter actinomycetemcomitans - a capnophilic Gram negative facultative anaerobe and ungrouped outlier in the original study; associated with aggressive periodontitis, particularly in adolescents. (Considered a marker for severe periodontal disease in adolescents – a keystone pathogen). ◆ Filifactor alocis - a previously unrecognized emerging asaccharolytic Gram positive obligate anaerobe associated with aggressive periodontitis, endodontitis, and peri-implantitis. (Proposed marker for increased risk of failed endodontic treatment and failed dental implants). ◆ Selenomonas* species (e.g., Selenomonas sputigena), and Eikenella corrodens⌘, grouped in the green complex in the original study, has since been associated with periodontitis. o Selenomonas* spp. along with Fusobacterium nucleatum* has been associated with necrotizing periodontal disease. Updatea: Currently suspected periodontal pathogens in susceptible individuals among the original complex categorized species: *Gram negative obligate anaerobe ⌘Gram negative facultative anaerobe #Gram positive obligate anaerobe Question: Members of the red complex that was identified as periodontal pathogens using the criteria outlined in Socransky’s postulates include 1. Porphyromonas gingivalis, Treponema pallidum 2. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans 3. Tannerella forsythia, Treponema denticola Oral Biofilm Ecology is Influenced by Oral pH In context of Periodontal disease associated species: ❖ MOST periodontal pathogens are sensitive to low pH (e.g., Gram negative P. gingivalis is susceptible to pH 90% cs). ◆ Oral bacteria are normally prevented from ascending the parotid duct and causing retrograde infection by the natural flushing activity of saliva. Single Bilateral  Acute Bacterial Parotitis Presentation & Diagnosis: Oral: Sudden onset of firm edema (swelling) and erythema (redness). Severe local pain. Milking of the parotid duct produces a thick, purulent discharge. Other: May be febrile (fever) with chills and have leukocytosis Therapy: Antibiotics. Some cases surgical drainage Milking of the parotid duct  Acute Bacterial Parotitis Subtypes 1. Adult Chronic Bacterial Parotitis Differential Etiology & Pathology: Chronic primary infective sialadenitis of the parotid gland due to either: o Microorganisms recalcitrant to therapy o Damaged glands (e.g., patients with Sjogrens syndrome, xerostomia [dry mouth], allergies to intra-oral appliances such as dentures) Therapy: May require parotidectomy  Acute Bacterial Parotitis Subtypes 2. Juvenile Chronic Bacterial Parotitis Differential Etiology & Pathology: Primary infective sialadenitis of the parotid gland in children. The exact etiology is often unclear. Some predisposing factors: o congenital abnormalities (may require surgical correction) o foreign body obstructions in the ductal system o trauma from orthodontic appliances o damaged glands due to mumps infection Therapy: Most cases resolve spontaneously with puberty  Viral parotitis: Mumps Etiology: mumps virus Pathology: Benign viral parotitis. Patient is highly infectious before and after appearance of parotitis.Transmission by direct saliva contact and aerosolized droplet. Therapy / Prevention: Supportive. MMR vaccine (measles, mumps, rubella) administered at ~1y and 4-6y (66-95% effective)  Viral parotitis: Mumps Presentation: Oral: sore throat, erythema at the parotid duct, tenderness on pressure at the angle of jaw, jelly-like edema. Followed by painful edema of Health one or both parotid gland, then the submandibular glands (often). Other: Fever, headache, myalgia, malaise Diagnosis: Presentation. With atypical presentation, diagnosis may be confirmed by detection of IgM antibodies to mumps virus. Complications: mumps meningitis (~45%); earache (~35%); ovary inflammation (oophoritis) and post- pubertal testicular inflammation (epididymoorchitis) Mumps potentially resulting in infertility; deafness (1/15K); fetal death Same child with and w/o mumps  Secondary Sialadenitis due to HIV Etiology / Epidemiology / Presentation: human immunodeficiency virus (HIV) ◆ ~10% of HIV+ patients show xerostomia and sialadentitis (enlarged salivary glands). Diagnosis: Positive HIV immunoassay Prognosis: Reduced saliva production may lead to other oral microbial diseases Lymphoepithelial parotid cyst in HIV+ pt. Secondary Sialadenitis due to Mycobacteria 1. Tuberculosis (TB, primary infection) Etiology & Epidemiology: Mycobacterium tuberculosis. ◆ Salivary glands are very rarely involved in TB. When observed, it is associated with immunocompromised patients. Presentation: Firm, non-tender edema Diagnosis: Mantoux tuberculin skin test (PPD immunoreactive test) and NAAT test (M. tuberculosis specific PCR detection of bacterial DNA). Secondary Sialadenitis due to Mycobacteria 2. Non-tubercular (atypical) mycobacterial infection of the parotid Etiology & Epidemiology: Non-tubercular Mycobacterium spp. e.g., M. intracellulare Very rare overall; more often in parotid of children Presentation: Facial or cervical masses. May develop spontaneous draining sinuses (image). Diagnosis: NAAT test (non-tubercular mycobacteria specific PCR detection of bacterial DNA). Secondary Sialadenitis due to Actinomycosis Etiology & Epidemiology: Actinomyces israelii (typically), and other Actinomyces spp. bacteria. ◆ Anaerobic Gram-positive filamentous bacilli that commonly colonize the mucosa. ◆ NOT considered an opportunistic pathogen. Rather, once it is established, it is not easily cleared (e.g., survives phagocytosis). ◆ Seen in ~10% of cases of cervicofacial actinomycosis (comorbidity = tooth decay) ** ▪ Differential: Nocardiosis, Commonly associated Propionibacterium with certain bacteria Eikenella corrodens propionicum infection; Rare in children Malignant growths and elderly Secondary Sialadenitis due to Actinomycosis Presentation: aka. “lumpy jaw”, the cervicofacial region is the most common site of infection. A slowly progressive granulomatous disease with development of communicating sinus tracts between indurant (hard) abscesses. When it infects the salivary glands, it resembles other types of bacterial sialadenitis. Initially relatively painless unless untreated. Lymph nodes are usually not enlarged. Secondary Sialadenitis due to Actinomycosis Diagnosis: ◆ Purulent discharge with characteristic yellow sulfur granules. ◆ Microscopy: Central mass of autoaggregated actinomycyes filaments, neutrophils, and debris, with a mid-zone of interlacing bacterial filaments surrounded by an outer zone of eosin stained radiating club-shaped filaments. Question: A salivary gland infection by a microorganism that is a normal colonizer of the oral cavity. 1. Mumps 2. HIV parotitis 3. Tuberculosis parotitis 4. Non-tubercular parotitis 5. Actinomycosis sialadentitis  Oral Hairy leukoplakia Etiology: triggered by Epstein–Barr virus (EBV) infection EBV infection is associated with a range of pathologies in the oral cavity including: 1. Infectious mononucleosis (aka. Mono; most common) 2. Oral Hairy leukoplakia (primarily in immunocompromised pt.) 3. Oral cancer (potential complication of an EBV infection)  Oral Hairy leukoplakia Pathology: primarily affects immunocompromized due to medications or disease, especially HIV/AIDS. Presentation: fuzzy, white patches that resemble folds or ridges on the sides of your tongue that do not wipe away (unlike thrush). Diagnosis: Classic test for an EBV infection is the monospot heterophile antibody test, or the newer anti-EBV antibody test. Differentials: Candidiasis (thrush), syphilis, tuberculosis, lichen planus (autoimmune condition), etc. ANSWER KEY  Question: Members of the red complex that was identified as periodontal pathogens using the criteria outlined in Socransky’s postulates include 1. Porphyromonas gingivalis, Treponema pallidum 2. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans ** 3. Tannerella forsythia, Treponema denticola  Question: A salivary gland infection by a microorganism that is a normal colonizer of the oral cavity. 1. Mumps Mumps virus 2. HIV parotitis Human immunodeficiency virus 3. Tuberculosis parotitis Mycobacterium tuberculosis 4. Non-tubercular parotitis Mycobacterium intracellulare ** 5. Actinomycosis sialadentitis Actinomyces israelii