THE UNIVERSITY OF WESTERN AUSTRALIA Oral Pathology module **Infections of Teeth and Jaws** A/Prof Omar Kujan DDS DipOPath MDSc MFDS RCPS FHEA FRCPath FFOMP(RCPA)PhD DENT4217  **Acknowledgement** of country The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge. **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** **Artist: Dr Richard Barry Walley OAM**  **Learning outcomes** 1. Describe common teeth and jaws infections 2. Identify the aetiology of teeth and jaws infections. **Infections** •Microorganisms cause infectious diseases. •Microorganisms: • bacteria • Viruses • Fungi • Prions • Protozoa • Helminthes • arthropods. •Not all microorganisms are **pathogenic** •The most common infectious agents in the oral cavity are **periodontal** pathogens and **cariogenic** microorganisms. 4 **Infections** THE UNIVERSITY OF WESTERN AUSTRALIA • **Opportunistic infection** is caused by microorganisms that usually do not produce disease in a person with a healthy immune system. When the immune system is compromised in some way, and the host’s natural defenses against the pathogen are reduced or eliminated, these microorganisms may cause disease. • **Opportunistic infections** are especially common in patients with immunosuppressive conditions such as AIDS. - Cocci - Bacilli - Spirochetes - Envelope proteins (for attaching to specific cell surfaces) - Capsid - Genetic material (DNA or RNA) - Lipid envelope - Fungal hyphae - Fruiting body - Spores - Spore germination    **Variables affecting outcome of exposure to** **infectious agent** **BBA THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** **Organism** Quantity of exposure Virulence Production of toxins Enzymes **Host defenses** Skin (physical barrier, fatty acids) Mucous membranes (enzymes) Respiratory tract (mucociliary clearance) Gastrointestinal tract (acids, bile detergents, resident microflora) Immune system Outcome **Local environment** pH Temperature Wet or dry Denture wearing Recent antibiotic use 7  ```markdown Flowchart: Pathways from Periodontal Oral Cavity to Pulmonary Infections [Periodontal oral cavity (=10⁹ bacteria/mm³ dental plaque)] ↓ [Oral bacteria form biofilm on ventilation tubing and inoculate the respiratory tract] ↙ ↓ ↘ [Cytokines and [Chronic obstructive [Respiratory pathogens in enzymes transferred pulmonary infections: tracheobronchial tract into lungs] Inhalation pneumonia, colonize the oral and Bacterial pneumonia] pharyngeal tissues] ↓ ↑ [Local inflammation, [Aspiration of oral colonization of pathogens, pharyngeal bacteria] and lung infection] ```  # **Oral dysbiosis and autoimmunity** https://www.frontiersin.org/articles/10.3389/fimmu.2020.591255/full ## THE UNIVERSITY OF WESTERN AUSTRALIA **A. AUTOANTIGENS OVERPRODUCTION** P. **_Gingivalis_** PAD, Cit⁺ H₂O NH₃ Protein citrullination of host and bacteria TCELL ACPAs ACPAs-host protein immune complex RA Inflammation-complement activation **B. MICROBIAL TRANSLOCATION** The oral-intestinal connection P. **_Gingivalis_** induced dysbiotic changes RA Systemic Low grade inflammation Type I diabetes Gut permeability Th17 cells TReg Autoreactive cells **C. MOLECULAR MIMICRY** P. **_Gingivalis_** GroEL HSP60 Coronary and cerebrovascular diseases Anti-GroEL/humanHSP60 antibodies CROSS REACTION Thrombogenic antibodies against Iβ2 Iβ2 SIRVYK from A.A glycoprotein TLRIYT from P.**_Gingivalis_** homology TLALYK from T. **_Denticola_** **D. SUPERANTIGENS** APC TCell Antigen specific activation or superantigen activity Limited repertoire in periodontitis **F. BYSTANDER ACTIVATION** Dysregulation of innate receptors Polyclonal activation of T cells by superantigens Antibodies cross reactivity Cytokines storm **G. TLRS DYSREGULATION** **Activation** Control mechanisms for TLRs: Cooperation with coreceptors Post-translational modifications Cleavage Cellular trafficking Negative regulators 0014 TLR TLR9 Inhibition **PERIODONTITIS** RA **H. CYTOKINES HYPERPRODUCTION** P. **_Gingivalis_** IL-17 IL-6 Trans-differentiation TH1/TH1 Tissue destruction Susceptibility to periodontitis IL-12 Immunosuppressive molecules Proinflammatory microenviroment (Local and systemic) Promotes self antigens presentation **I. EPITOPE SPREADING** Peptide 19 from P.**_Gingivalis_** HSP60 autoantibodies against human neoepitopes Dominant epitope Response to subdominant epitopes Human Autoantigens Hu19 Hu9 **J. AUTOANTIGENS COMPLEMENTARITY** DNA Sense ANCA antigen peptide Antisense Complementary protein-peptide Anti-idiotypic antibodie Idiotypic antibodie +TNFa Possible mimicry PMN degranulation DYSBIOTIC BIOFILM Presence of inflammophilic bacteria in polymicrobial communities UNRESOLVED INFLAMMATION Altered resolution and lack of regulation of the inflammatory responses **BIDIRECTIONAL IMBALANCE** **AUTOIMMUNE MECHANISMS IN PERIODONTAL DISEASE** **E. DYSREGULATION OF CHECKPOINTS** **PERIODONTITIS** P. **_Gingivalis_** PD-1 CD4+ SUPPRESSION Bacterial persistence CD4 HIGHER EXPRESSION CTLA4 Relevance as autoimmunity mechanism 9  **Clinical Signs and Symptoms of Infection** * Signs and symptoms of infection may be caused by the organism directly or by the host response to being infected. * Infections may be localized, systemic, or disseminated. * Localized infections tend to cause pain in a specific body part. For example, if a cut on the skin is infected with bacteria, pain will occur at the site of the infection. The lesion will show redness, swelling, heat, edema, possibly a foul odor, and some form of exudate, such as pus. * Systemic and disseminated infections tend to show extreme fatigue, weight loss, low-grade or spiking fever, night sweats and chills, and generalized body aches. Bacterial infections  # **Dental caries** B2B THE UNIVERSITY OF WESTERN AUSTRALIA | | | |---|---| | Current hypo-salivation | Head & neck radiation | | Oral hygiene practices | Topical fluoride exposure | | Sugary drinks & snacks | Dental attendance | | Social-economical status | Mothers' caries experience | | Patient's level risk factors | Intraoral level risk factors | |---|---| | Active caries lesions | Dry mouth | | PUFA | Caries experience | | Thick plaque | Exposed root surfaces | | Appliances | | https://bmcoralhealth.biomedcentral.com/articles/10.1186/1472-6831-15-S1-S12 12   **Pulpitis** **Causes of pulpitis** * Dental caries * Traumatic exposure of the pulp * Fracture of a crown or cusp * Cracked tooth * Thermal or chemical irritation **Types of pulpitis** * Acute closed pulpitis * Chronic closed pulpitis * Open pulpitis * Chronic hyperplastic pulpitis  **PERIAPICAL PERIODONTITIS,** **ABSCESS AND GRANULOMA** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** • Periapical inflammation is due to spread of infection, bacterial products or other irritants through the apex into the periodontal ligament following death of the pulp. **Causes of apical periodontitis** • Infection • Trauma • Chemical irritation 14  ```markdown - Very rarely pulp remains viable and inflammation resolves. - Only if pulp open to mouth and root apices open, resorbing or incomplete. - Pulp polyp forms → Asymptomatic pulpitis ⇄ Symptomatic pulpitis → Asymptomatic pulp necrosis in one or more canals → Irreversible pulpitis or localised pulp abscess leading to pulp necrosis in one or more canals → Periapical granuloma, chronic persistent inflammation, usually asymptomatic or with periods of exacerbation → Persistence of asymptomatic periapical granuloma → Periapical abscess resulting from establishment of virulent organism, passage of organisms through root apex, or reduced host resistance, always symptomatic → [Three Pathways] 1. Proliferation of rests of Malassez to form radicular cyst, usually asymptomatic until large → Infected cyst caused by virulent organism from pulp or communication with antrum, oral or nasal cavity → Rare but severe complications of low-grade infection: sinus tract, chronic osteitis, swelling, and occasionally death, osteomyelitis 2. Drainage of pus, intraorally or extraorally, reduction in symptoms, leads to chronic persistent infection unless treated → Rare but severe complications of virulent infection: Ludwig’s angina, cavernous sinus thrombosis, septicaemia, and occasionally death 3. Acute soft tissue or facial space infection, abscess, cellulitis or combination → Inadequate or inappropriate treatment with antibiotic, persistent infection → Rare but severe complications of virulent infection: Orofacial infection, necrotising fasciitis, risk of death ```  THE UNIVERSITY OF WESTERN AUSTRALIA Toothache or pain felt in teeth or alveolus Pain of pulpal origin Pain of periodontal ligament origin **Sensitivity to sweet, hot or cold, poorly localised** **Pain on biting or pressure on tooth, usually well localised to one or more teeth** **Neurological or vascular pain** **Neuralgic or psychogenic pain** Dentine hypersentivity | Pulpitis | Cracked tooth or cusp | Periapical periodontitis | Periodontal abscess | Sinusitis ---|---|---|---|---|--- **Tooth is vital or partially vital and may be hypersensitive to testing** | | | | | Pain of short duration more or less limited to period of stimulus, particularly cold | Reversible pulpitis | Shooting or electric shock-like pain on biting, often only on one cusp or in one direction, also when a fracture line involves periodontal ligament | Pain on pressure to single tooth, caries or other cause of pre-existing pulpitis may be present, periapical, lateral canal or furcation radiolucency only in longstanding cases | Pain on pressure to single tooth, tooth vital, abscess in ligament visible or revealed by probing furcation or deep pocket | Tenderness on pressure to teeth with apices near sinus, usually concurrent or recent nasal or sinus symptoms, not usually severe pain | Irreversible pulpitis | | | | Symptoms may be limited to duration of stimulus or persist for varying period afterward, caries or other cause may be evident | Poorly defined entity, usually identified by severe continuous or spontaneous pain | | | | Teeth vital unless previously devitalised for other reasons | Unusual localisation trigger or perceived cause, associated with depression, anxiety or delusional states, teeth vital unless previously devitalised for other reasons Confirm diagnosis by identifying exposed dentine or tooth wear and applying appropriate treatment | May resolve on treating cause but once established may progress to irreversible pulpitis, even after an asymptomatic period | Responds most reliably to extirpation of pulp or extraction | Confirm by identifying crack | Resolves on drainage or extirpation of pulp or extraction | Resolves on drainage and local treatment or extraction | Resolves on treatment of sinusitis | Consider mimics of pulpitis such as trigeminal neuralgia and the prodromal symptoms of facial Herpes zoster infection | Consider atypical odontalgia, atypical facial pain, 'phantom tooth' etc., but only after excluding organic causes  **CHRONIC APICAL PERIODONTITIS AND** **PERIAPICAL GRANULOMA** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** * Chronic periapical granuloma is the most frequent outcome of necrotic pulp. * Most develop without symptoms. * They can also arise from acute apical periodontitis * A periapical granuloma is caused by frustrated healing. * The granuloma itself is sterile in almost all cases, but bacteria and irritants from necrotic tissue remain in the pulp chamber, inaccessible to the host response. * The tooth is non-vital and may be slightly tender to percussion; otherwise, symptoms may be minimal. 17   **Periapical granuloma** • A periapical granuloma is a typical focus of chronic inflammation characterised by lymphocytes, macrophages and plasma cells in loose edematous fibrous tissue. 18    **Periapical granuloma** Possible outcomes of chronic apical periodontitis * Periapical granuloma formation * Radicular cyst formation * Suppuration, sinus formation or spread * Periodic acute exacerbations of inflammation of infection Spontaneous resolution does not occur. 19 ## **Gingivitis and periodontitis** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** **20** **Pathological processes in chronic** **periodontitis** * Chronic inflammation * Destruction of periodontal ligament fibres * Resorption of alveolar bone * Migration of the epithelial attachment to the apex * Formation of pockets around the teeth * Formation of subgingival plaque and calculus    **Acute pericoronitis** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** • Pericoronitis is a localized, intraoral soft tissue infection most commonly associated with erupting lower third molars. • The microflora of pericoronitis is diverse and differs from pathogens that cause periodontitis. • In a study of microbiota of pericoronitis, *Actinomyces oris*, *Eikenella corrodens*, *Eubacterium nodatum*, *Fusobacterium* *nucleatum*, *Treponema denticola*, and *Eubacterium saburreum* were present in high levels • Usually is triggered by trauma from the opposing dentition 21   **Acute pericoronitis** Differential diagnosis * Foreign body impaction * Pyogenic granuloma * Peripheral ossifying fibroma * Dental caries * Periodontitis * Periapical abscess or granuloma 22 Solution: **Gingival inflammatory swellings** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** * **Orofacial granulomatosis** * **Sarcoidosis** * **Acute leukaemia** * **Wegener's granulomatosis** * **Scurvy** 23 **Alveolar osteitis** 24 **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** Key features * The most common painful complication of dental extractions * Loss of clot normally filling extraction socket * Loss of clot may be due to excessive local fibrinolytic action or bacterial enzymes or both * Bare, whitish lamina dura exposed in socket. * Pain relieved by irrigation and repeated dressing of socket * Dead bone usually shed as crumblike fragments * Eventual healing of socket from its base by granulation * Alveolar osteitis develops more frequently after 1%–2% of extractions for lower-third molar extractions. 24  **Predisposing factors for alveolar osteitis** * Excessive extraction trauma * Limited local blood supply * Gingival infection such as acute ulcerative gingivitis, pericoronitis or abscess * Local anaesthesia with vasoconstrictor * Smoking * Oral contraceptives * Osteosclerotic disease: Paget's disease, cemento-osseous dysplasia * Radiotherapy * History of previous dry socket 25 **ACUTE OSTEOMYELITIS** • In acute osteomyelitis bacteria and inflammation spread through the medullary bone from a focus of infection. • The most common cause is spread of infection from a periapical infection. • Adult males who have more dental infections than females are mostly affected. • Almost all cases affect the mandible, which is less vascular than the maxilla. • Early complaints are severe, throbbing, deep-seated pain and swelling with external swelling due to inflammatory edema. Later, distension of the periosteum with pus and, finally, subperiosteal bone formation cause the swelling to become firm. The overlying gingiva and mucosa is red, swollen and tender. Associated teeth are tender 26 **ACUTE OSTEOMYELITIS** THE UNIVERSITY OF WESTERN AUSTRALIA Important predisposing conditions for osteomyelitis **Local damage to or disease of the jaws** * Radiation damage * Causes of osteosclerosis * Paget’s disease * Fibro-osseous lesions, particularly cemento-osseous dysplasia * Osteopetrosis **Impaired immune defences** * Poorly controlled diabetes mellitus * Sickle cell anaemia * Chronic alcoholism or malnutrition * Drug abuse * Tobacco smoking * Malignant neoplasms and their treatment 27 Histological image of acute osteomyelitis showing inflammatory infiltration in bone tissue.  **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** 29  **CHRONIC OSTEOMYELITIS** * More common than acute osteomyelitis and arises from infection by weakly virulent bacteria or in avascular bone. * Most cases develop without a prior acute phase and only rarely does acute osteomyelitis lead to chronic osteomyelitis **Key features** * Mandible mainly affected * Infection of dental origin * Low-grade pain * Sclerosis or avascular bone is often a predisposing factor * Resistant to treatment * Prolonged antibiotic treatment required * Role for surgery to remove sequestra and sclerotic bone 30   **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** 31  Stage I (Medullary osteomyelitis) Necrosis limited to medullary contents and endosteal surfaces. Etiology: Hematogenous Treatment: **Early:** Antibiotics/host alteration **Late:** Unroofing, intramedullary reaming Stage II (Superficial osteomyelitis) Necrosis limited to exposed surfaces. Etiology: Contiguous soft tissue infection Treatment: **Early:** Antibiotics/host alteration **Late:** Superficial debridement/coverage Possible ablation Stage III (Localized osteomyelitis) Well marginated and stable before and after debridement. Etiology: Trauma, evolving stages I and II, Iatrogenic Treatment: Antibiotics/host alteration Debridement, dead space management Temporary stabilization, bone graft optional Stage IV (Diffuse osteomyelitis) Circumferential and/or permeative. Unstable prior to or after debridement Etiology: Trauma, evolving stages I, II, and III, Iatrogenic Treatment: Antibiotics/host alteration Stabilization - ORIF, external fixation (Ilizarov) Debridement, dead space management Possible ablation 32  **DIFFUSE SCLEROSING OSTEOMYELITIS** **Key features** * Affects adults * No sex predilection * Affects mandible almost exclusively * Patchy diffuse sclerosis in the alveolar process * Changes more marked around sites of periapical or periodontal chronic inflammation * Persistent ache or pain but no swelling * Radiographically resembles but is distinct from florid cemento-osseous dysplasia **Pathology** * Bone sclerosis and remodelling * Scanty marrow spaces and little or no inflammatory infiltrate, although adjacent to areas of inflammation   Clinical photographs and radiographic images of a dental case (frontal facial view, intraoral view, and radiographs).  **Focal sclerosing osteomyelitis** **Key features** * Bony reaction to low-grade periapical infection * Children and young adults affected * Premolar or molar region of mandible affected * Bone sclerosis associated with a non-vital tooth * Localised but uniform radiodensity related to tooth with widened periodontal ligament space or periapical area * No expansion of the jaw **Pathology** * Dense sclerotic bone with scanty connective tissue or inflammatory cells   Quiz **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** Join at slido.com #1614 444 36   - Odell E. 2018. Cawson's Essentials of Oral Pathology and Oral Medicine - Woo SB. 2023. Oral Pathology. A Comprehensive Atlas and Text - Sapp JP, Eversole LR, Wysocki GP. 2004. Contemporary oral and maxillofacial pathology. - https://www.hindawi.com/journals/mi/2015/793898/ - https://www.frontiersin.org/articles/10.3389/fimmu.2020.591255/full Cartoon of a dental check-up with humorous dialogue: Dentist: "YOU HAVE ACUTE GINGIVITIS." Patient: "THANK YOU!"