stuart g. dashper, alf nastri, and paul v. abbott · 2020. 9. 11. · odontogenic bacterial...

Odontogenic Bacterial Infections

Stuart G. Dashper, Alf Nastri, and Paul V. Abbott

AbstractThe oral cavity is home to over 700 species ofbacteria, known as the human oral microbiome.The oral cavity is an ideal environment for bac-terial colonization and growth. Although themajority of these bacteria are beneficial tohuman health and do not cause disease, underparticular circumstances, bacterial infections canoccur. The most common bacterial diseases thatoccur in the oral cavity are in the form of dentalcaries, periodontal diseases, and pulp, root canal,and periapical diseases. These diseases are over-whelmingly due to bacteria that are part of thenormal oral microbiota, not exogenous patho-gens. Pulp and root canal diseases can lead toperiradicular conditions such as apical periodon-titis, apical abscesses, facial cellulitis (with pos-sible airway involvement), and osteomyelitis.

Management of these diseases is based initiallyon obtaining a complete history and performinga thorough clinical and radiographic examina-tion in order to develop an accurate diagnosis.Various treatment procedures can be provided,depending on the diagnosis – these range fromsimple dental restorations, periodontal treatment(scaling, root planning), or root canal treatmentto extraction of the tooth. Various medical andsurgical procedures plus the use of antimicrobialdrug therapy are required in cases with severeinfections and/or systemic signs of the infection.Other conditions such as osteonecrosis of thejaws must be differentiated from oral infectionsbut they may have secondary bacterialinvolvement.

KeywordsOral microbiome • Dental caries • Periodontaldiseases • Gingivitis • Pulpitis • Apical peri-odontitis • Apical abscesses • Facial cellulitis •Oesteomyelitis • Osteonecrosis

ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Oral Microbiome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Summary of the Recent Advances in Characterization

of the Human Oral Microbiome . . . . . . . . . . . . . . . . . . . . 3Culture Independent Analyses and the Discovery of

New Species Associated with Healthand Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Overview of the Diversity of the Human OralMicrobiome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

S.G. Dashper (*)Melbourne Dental School, Oral Health CooperativeResearch Centre, The University of Melbourne,Melbourne, Australiae-mail: [email protected]

A. NastriDepartment of Maxillofacial Surgery, Royal MelbourneHospital, The University of Melbourne, Melbourne,Australiae-mail: [email protected]

P.V. AbbottUWA Dental School/Oral Health Centre of WesternAustralia (OHCWA), The University of Western Australia,Nedlands, Australiae-mail: [email protected]

# Springer International Publishing AG 2017C.S. Farah et al. (eds.), Contemporary Oral Medicine,https://doi.org/10.1007/978-3-319-28100-1_45-1

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mailto:[email protected]



https://doi.org/10.1007/978-3-319-28100-1_45-1

Oral Bacterial Ecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Genetic Diversity and Physiological Flexibility . . . . . . 4Growth as Polymicrobial Biofilm Communities

and Interactions Between Species . . . . . . . . . . . . . . . . . 5Escape from the Oral Cavity and Life

on the Inside . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Common Bacterial Associated Diseases of the OralCavity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Polymicrobial Nature of Diseases . . . . . . . . . . . . . . . . . . . . 6Periodontal Diseases: Gingivitis and Chronic

Periodontitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Dental Caries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Significant Bacterial Species . . . . . . . . . . . . . . . . . . . . . . . . . . 12

The Dental Pulp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Pulp, Root Canal, and Periapical Infections . . . . . . . 20

Management of Pulp, Root Canal, and PeriapicalConditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Assessment/Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25Managing Pulpitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27Managing Infected Root Canal Systems . . . . . . . . . . . . . . 29

Periapical Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Antibiotics: When and When Not to Use . . . . . . . . . . 35

Treatment and Prevention of OdontogenicMaxillofacial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Principles of Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36Medical Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37Antibiotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38Surgery and Drainage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38Airway Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39Prevention of Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Osteomyelitis, Osteoradionecrosis (ORN), andAntiresorptive Agent-Induced Osteonecrosisof the Jaws (ARONJ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Osteomyelitis of the Jaws . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40Osteoradionecrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42Antiresorptive Agent-Induced Osteonecrosis of

the Jaws (ARONJ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Conclusion and Future Directions . . . . . . . . . . . . . . . . . . 45

Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

Introduction

Bacterial infections are common causes of humandisease. The oral cavity is home to over 700 spe-cies of bacteria, known as the human oral micro-biome. The oral cavity is an ideal environment forbacterial colonization and growth, and the dentalhard and soft tissues are commonly exposed to the

effects of such bacterial infections. Dental cariesis one of the most prevalent dental diseases in theworld, the prevalence and severity of which variesaround the world. Despite improvements in thelast 20–30 years, there is considerable evidence ofpoor oral health. Bacterial infections affectingdental hard tissues, the pulp, and the periodontaltissues are common place in various populationand socioeconomic groups. Recent trends suggestchanges in diet and behavior, such as increasedconsumption of bottled water, sports drink, andsoft drinks, may be having negative impacts onoral health. Low-income households have a muchhigher prevalence of toothache, periodontal dis-ease, tooth decay, and missing teeth. Over half ofthe population over the age of 65 years have gumdisease or periodontitis, and almost 20% of thoseover the age of 65 years have complete tooth lossas a consequence of dental caries and periodontaldisease. Indigenous populations are over 150%more likely to be hospitalized for potentiallypreventable dental conditions compared to non-indigenous populations. Additionally, more thanhalf of children aged 6 have experienced decay intheir primary teeth, and almost half of childrenaged 12 have experienced decay in their perma-nent teeth.

Pulp disease is a direct result of the presence ofbacteria in the tooth, and typically this is a directconsequence of progression of caries throughenamel and dentine into the pulp, although bacte-ria can also find their way through fractures oraccessory canals. Once the root canal systembecomes infected, the periapical tissues respondinitially with inflammation and this can then pro-gress to other conditions such as extraradicularinfections, apical abscesses, facial cellulitis, andosteomyelitis.

Periodontal diseases range from the relativelymild form, gingivitis, to the more aggressiveforms, including aggressive and chronic peri-odontitis, which are characterized by the destruc-tion of the tooth’s supporting structures. Chronicperiodontitis is by far the most prevalent bacterialassociated inflammatory disease of the supportingtissues of the tooth resulting in irreversible alveo-lar bone loss and, if left untreated, in tooth loss.

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Nearly 80% of people exhibit clinical signs ofperiodontal disease and between 20% and 40%have periodontitis, with those aged over 65 yearsmore likely to demonstrate moderate to severeforms of the disease.

Bacterial odontogenic infections and diseasescan be treated by a variety of medical or surgicalmeans that are common place in dental practice.The oral medicine specialist must be aware ofcomplications of these conditions and be preparedto distinguish their sequalae from other more sin-ister pathologies affecting the teeth, periodontaltissues, and bone.

Oral Microbiome

Summary of the Recent Advancesin Characterization of the Human OralMicrobiome

Some observers see the human body as a mobileecosystem, with bacterial cells outnumberinghuman cells by somewhere between 1.3:1 and10:1, and this is before fungi, viruses, archaea,and other microorganisms that share our bodyspace are taken into account (Sender et al. 2016).Indeed, live bacteria constitute between 1 and 2 kgof the human body mass, and considering that thegenes contained in the microbiome exceed thehuman genome by one to two orders of magni-tude, this makes humans more microbial thanhuman. Bacteria are not just passengers in, andon, the human body but play a major role in bodilyfunctions, including immunity, digestion, andnutrition. Lederberg and McCray (2001) firstused the term microbiome at the start of thiscentury “to signify the ecological community ofcommensal, symbiotic, and pathogenic microor-ganisms that literally share our body space andhave been all but ignored as determinants ofhealth and disease.” Colonization of the humanbody by microorganisms occurs at the beginningof life, and it is becoming increasingly obviousthat unless correct colonization and bacterial com-munity development occurs, a range of chronicdiseases and syndromes will ensue.

The human oral cavity contains a significantnumber of distinct hard and soft tissues, includingthe teeth, tongue, buccal mucosa, hard and softpalates, gingival mucosa, and tonsils. Thesediverse parts of the oral cavity of humans areinhabited by a diverse range of microbial species,including bacteria, viruses, fungi, archaea, andprotozoans, that collectively are known as thehuman oral microbiome. Largely in this chapterthe term microbiome will be used to describe thebacterial diversity of the human oral cavity. Theoral cavity offers many opportunities for bacterialgrowth, and on the whole, it is a warm, moistenvironment that provides surfaces for attachmentand growth, and a constant supply of nutrients inthe form of saliva. In addition, regular dietaryintake provides times of excess nutrient supply.As a consequence, the oral cavity has a unique,varied, and large microbiome, second only to thelower gastrointestinal tract in humans.

Oral bacteria were the first single celled organ-isms to be examined when, in the latter half of theseventeenth century, Anton van Leeuwenhoekdeveloped a novel way of producing high magni-fication glass lenses and turned them to examinesmall instead of distant objects. Described as thefather of microbiology, he famously wrote “Thereare more animals living in the scum on the teeth ina man’s mouth than there are men in the wholekingdom.” Oral bacteria were also tied to diseaseearly when Miller in the 1880s described dentalcaries as a chemoparasitic process (Miller 1890).Interestingly, Miller believed that all bacteria inthe oral cavity had equal cariogenic potential. Thebacteria that will be discussed in this chapter arelargely part of the normal oral microbiome and notexogenous pathogens. Bacteria involved in frankinfections of the oral cavity and systemic diseasesthat affect the oral cavity are dealt with in thechapter on Nonodontogenic Bacterial Infections.

Culture Independent Analysesand the Discovery of New SpeciesAssociated with Health and Disease

Until relatively recently bacteria were character-ized solely using isolation, laboratory culture, and

Odontogenic Bacterial Infections 3

biochemical techniques. Current estimates indi-cate that this only enabled a third of all oral bac-terial species to be identified. The recentapplication of DNA-based culture independentmethodologies coupled with advanced computa-tional techniques (bioinformatics) has shown thatthe oral microbiome is much more species richand diverse than was thought at the turn ofthe century. The oral microbiome has now beenextensively characterized by cultivation- andculture-independent molecular methods such as16S rRNA gene sequencing. This gene encodesribosomal RNA that is essential for all bacteriallife. The gene contains some sections that arehighly conserved and other highly variableregions that enable the classification of bacteriato a species level. Unfortunately, the majority ofnewly discovered unnamed oral taxa have onlybeen assigned identifying numbers and lack taxo-nomic names (Dewhirst et al. 2010). It is nowestimated that there are more than 700 differenttypes of bacteria that can be isolated from themouth but that more than 50% of these cannotcurrently be grown in pure culture in the labora-tory (Marsh 2010).

In parallel with its use for the discovery of newuncultivated bacterial species, DNA sequenceanalysis has also revolutionized bacterial taxon-omy and phylogeny. In the long term, this willenable a clearer picture of bacterial infections tobe determined and will greatly help the develop-ment of efficacious treatments and preventiveregimes. In the short term, it does create confusionregarding the names of bacterial species and read-ing of the scientific and clinical literature. Keep-ing abreast of taxonomic revisions is a majorundertaking. However, these changes are impor-tant to both clinicians and clinical microbiolo-gists, since taxonomic placement is a useful toolthat can be an indicator of virulence potential orantimicrobial resistance.

Overview of the Diversity of the HumanOral Microbiome

The human oral microbiome is comprised of wellover 600 prevalent species of bacteria (Dewhirst

et al. 2010). Due to the distinct bacterial habitatswithin the oral cavity, distinct subsets of speciesform ecological communities or consortia at dif-ferent sites. A curated phylogeny-based database,the Human Oral Microbiome Database (www.homd.org), provides comprehensive informationon the more than 700 prokaryote species that arepresent in the human oral cavity. Currently,13 phyla of bacteria are known from the humanoral cavity with a divergent evolution includingFirmicutes, Bacteroidetes, Spirochaetes, and Syn-ergistes. The oral cavity has one of the highestdiversities of bacterial species of any region of thehuman body. Although over 700 species of bacte-ria have been identified as components of thehuman oral microbiome, many are quite rare andby most estimates 400–450 species account foraround 95% of the bacterial cells in an individ-ual’s oral cavity.

Commensalism is too mild a term to describethe relationship between many oral bacteriaand their human host. A commensal relationshipimplies that one partner benefits from the relation-ship while the other is unaffected, and it was longbelieved that while they did us little harm, oralbacteria also did us little good. However, recentevidence indicates that mutualism is a more aptdescription, since both the bacteria and the humanexperience increased fitness as a result of therelationship (Backhed et al. 2005). This has beenelegantly demonstrated recently with regard tobeneficial nitrite production by oral bacterial spe-cies resulting in a decrease in systemic bloodpressure (Kapil et al. 2013). Oral bacteria canalso be seen as an arm of the innate immuneresponse in that they exclude potentially patho-genic exogenous bacteria from colonizing the oralcavity.

Oral Bacterial Ecology

Genetic Diversity and PhysiologicalFlexibility

Bacterial cells singly are small in size andtheir genome is correspondingly diminutive.Most spherical (coccoid) bacterial cells range in


http://www.homd.org/

http://www.homd.org/

size from 0.4 to 2.0 μm, while elongate speciescan reach 15 μm in length. Most genomes forbacteria that are associated with humans are inthe range of 500–4,000 genes. This is in contrastto the human genome of over 30,000 genes and aeukaryotic cell of 50–100 μm in diameter. Assuch, bacteria have a fairly narrow range of hab-itats that they can effectively exploit on their owndue to their limited ability to encode complexmetabolic pathways. However, when coexistingwith a range of other species they can potentiallycollaborate and use their distinctive genomes forsymbiosis, allowing them a greater degree ofphysiological flexibility. This, for example, mayenable them to cooperatively breakdown host pro-teins by providing a complete catabolic pathwaylacking in the individual species. In addition, thelocalization of a large number of species andstrains of bacteria in a polymicrobial biofilm cangreatly enhance genetic exchange between spe-cies, enabling them to rapidly acquire new char-acteristics such as antibiotic resistance or theability to catabolize new energy sources. There-fore, polymicrobial communities can rapidlyrespond to changing environmental conditions.

Growth as Polymicrobial BiofilmCommunities and Interactions BetweenSpecies

Dental plaque consists of a complex microbialcommunity found on the tooth surface, embeddedin a matrix of polymers of bacterial and salivaryorigin (Fig. 1). Biofilms are defined as matrix-enclosed bacterial populations adherent to eachother and/or to surfaces or interfaces (Costertonet al. 1995). Polymicrobial biofilms are complex,dynamic microbial communities formed by two ormore bacterial species that are important for thepersistence and proliferation of participatingmicrobes in the environment. Interspecies adher-ence, which often involves bacterial surface-associated molecules, and communications areessential in the spatial and temporal developmentof a polymicrobial biofilm, which in turn is nec-essary for the overall fitness of a well-organizedmultispecies biofilm community. The vast

majority of bacteria in the oral cavity exist ascomponents of polymicrobial biofilms. Supra-gingival and subgingival plaques are poly-microbial biofilms (Fig. 2) accreted to thenonshedding surfaces of the tooth. The non-shedding nature of teeth is unique in the humanbody and they allow the buildup of considerablebacterial biofilms that act as reservoirs of poten-tially infectious agents. The high numbers of bac-terial cells in these biofilms can provide largeinocula for infection under the right (or wrong)circumstances. The ability to form tenaciousbiofilms is a predisposing factor for oral bacteriato become established in other parts of the bodyshould the opportunity arise.

Fig. 1 Dental plaque smear Gram stain. (Image courtesyof Professor Camile Farah, UWA Dental School, Univer-sity of Western Australia, Perth WA, Australia)

Fig. 2 Supragingival plaque accumulating on teeth, par-ticularly around the gingival margins (Image courtesy ofAssociate Professor Robert Anthonappa, UWA DentalSchool, University of Western Australia, Perth WA,Australia)


Escape from the Oral Cavity and Lifeon the Inside

There is increasing evidence that the oral cavity isrelatively porous to oral bacteria. Chronic peri-odontitis sufferers in particular have been shownto have bacterial DNA or viable oral bacteriadispersed throughout their bodies in atheroscle-rotic plaques and the placenta, for example. Thetissue disruptive effects of periodontal diseases inthe periodontal pocket that is home to a largenumber of bacterial cells and species lead to tran-sient bacteremia events. Many oral bacteria havebeen shown to be able to colonize and survive, ifnot thrive, once in the vascular system. Oralviridans streptococci, for example, can colonizedamaged heart valves and are the most commoncause of subacute bacterial endocarditis.

A number of oral bacterial species have beenshown to be internalized by oral epithelial cellsand some can reproduce within these host cells, aswell as move between these cells and reemergeunder favorable environmental conditions. Thiscapacity may also predispose them to similarlyinvade and persist within endothelial and otherhost cell types once inside the body. Other species,in particular the oral spirochaetes that are some ofthe only motile bacteria in the mouth, can pene-trate oral epithelial layers in vitro, thereby raisingthe possibility that under particular conditionsthey are tissue invasive which could lead to theircolonization of the vascular system.

One of the best studied examples of an oralbacterium that can enter the host and cause arange of infections is Fusobacterium nucleatum.This bacterium is a common component of bothsupra- and subgingival dental plaque. It is aninvasive, adherent, and pro-inflammatory anaero-bic Gram-negative bacterium. It has been associ-ated with cerebral abscesses and pericarditis andimplicated in acute appendicitis. More recently,F. nucleatum has been shown to be involved in thepromotion of colorectal cancer (Castellarin et al.2012). Recently, F. nucleatum has been shown totarget the placenta and has been implicated inadverse pregnancy outcomes that are sometimesassociated with maternal periodontal disease sta-tus (Stockham et al. 2015). F. nucleatum, like

many other oral bacteria, can invade endothelialand epithelial cells and is preadapted to grow at37 �C and to evade the host immune response.These preadaptations make the transition from theoral cavity to inside host tissues relatively easy forsome oral bacteria.

Common Bacterial Associated Diseasesof the Oral Cavity

Polymicrobial Nature of Diseases

The major oral bacterial diseases of dental cariesand periodontitis arise not from an extrinsic infec-tion but from an imbalance, or dysbiosis, in thebacterial species composition of the complexpolymicrobial biofilms attached to the tooth sur-face. A change in environmental conditions leadsto changes in the relative abundances of bacterialspecies in the biofilm enabling a subset of morepathogenic species to become dominant. In thecase of dental caries, this is believed to be due toincreased frequency of sugar intake. Periodontitisand dental caries account for ~90% of all toothloss in developed countries, indicating thatchronic periodontitis is a major public healthproblem.

In the case of chronic periodontitis, the poly-microbial nature of disease was first made clearby Socransky and coworkers who demonstratedthe consistent association of groups of particularspecies with the severity of periodontal disease.In particular, they defined a climax communityof three bacterial species, Porphyromonasgingivalis, Treponema denticola, and Tannerellaforsythia, that they referred to as the Red Complexthat was associated with clinical indicatorsof advanced chronic periodontitis (Socranskyet al. 1998). Since their pioneering research, theadvent of new DNA-based technologies forthe identification and enumeration of bacteriahas resulted in many other species being associ-ated with disease initiation and/or progression,including Filobacter alocis (Hajishengallis andLamont 2012).


Periodontal Diseases: Gingivitisand Chronic Periodontitis

Periodontal diseases are classified into a numberof discrete forms ranging from the relatively mildform, gingivitis, to the more aggressive forms,including aggressive and chronic periodontitis,which are characterized by the destruction of thetooth’s supporting structures that can lead to toothloss (Armitage 1999). Amore detailed descriptionof periodontal disease classification can be foundin the chapter on odontogenic pathology, butis also outlined in Table 1. Gingival lesions aredetailed in a separate chapter on gingival pathol-ogy. This chapter will focus on the microbiologi-cal basis of odontogenic diseases.

Chronic periodontitis is by far the most preva-lent of the destructive forms of the disease.Chronic periodontitis is a bacterial associatedinflammatory disease of the supporting tissues ofthe tooth. It results in irreversible alveolar boneloss and, if left untreated, can result in tooth loss.It is often preceded by gingivitis which is a non-specific inflammatory response to a buildup ofbacteria in dental plaque at the gingival margins(Figs. 3 and 4). An oral health survey ofAustralians found that in the 30–34 age groupmore than 80% of people exhibited clinicalsigns of periodontal disease and over 20% hadperiodontitis (Armfield et al. 2000). Eke et al.(2012) determined in 2010/2011 that over 47%of American adults, or 64.7 million people, hadperiodontitis that was distributed as 8.7% mild,

Table 1 Classification of bacterially induced peri-odontal diseases, adapted from Armitage (1999). Somerarer forms of periodontal disease relate to a dysfunctionalhost immune response to systemic diseases or conditionsand have little involvement of oral bacteria, and these are

not dealt with in this Table. Many of these disease formsare exacerbated by host structure and immune response andthe presence of systemic diseases and conditions and ther-apies for unrelated diseases

Classification Subclassification Notes

Gingivitis Nonspecific inflammation related to plaque accumulation at thegingival margin that does not lead to host tissue destruction.Treatable by plaque removal. Likely to result from proliferationof Gram-negative bacteria as plaque thickens

Chronic periodontitis A. LocalizedB. Generalized

The commonest form of periodontitis initiated by specificbacteria in subgingival plaque that induce a destructiveinflammatory response. Usually a slowly progressing diseasecan be refractory to treatment. Treatment is largely plaqueremoval by scaling and root planning, sometimes with minorsurgery to improve access followed by antibiotic therapy.Replaced the confusing and ambiguous term “AdultPeriodontitis”

Aggressive periodontitis A. LocalizedB. Generalized

Has a different bacterial aetiology to chronic periodontitis andis more likely to involve Actinobacillusactinomycetemcomitans. Can be rapidly progressing and resultin rapid tooth loss if untreated. Replaced the confusing andambiguous term “Early Onset Periodontitis”

Necrotizing periodontaldiseases

A. Necrotizingulcerative gingivitis(NUG)B. Necrotizingulcerative periodontitis(NUP)

The bacterial aetiology of these conditions remains in disputeas does the influence of underlying systemic conditions.Characterized by necrotic lesions. NUP, unlike NUG, results inbony tissue destruction

Abscesses of theperiodontium

A. Gingival abscessB. Periodontal abscessC. Pericoronal abscess

Abscesses present diagnostic and treatment challenges and areclassified apart from other periodontal diseases

Periodontitis associatedwith endodontic lesions

Combined periodontic-endodontic lesions

Has pulpal involvement. The lesion can either be the result ofan endodontic infection or the consequence of periodontallyassociated bacteria gaining entry to the pulp chamber


30.0% moderate, and 8.5% severe. More than64% of Americans aged 65 years and older hadeither moderate or severe periodontitis.

In conjunction with the direct symptoms ofdisease, chronic inflammatory molecules also cir-culate throughout the body, and chronic inflam-mation is considered to be one of the major causesof early death (Ritchie et al. 2015). Clinical indi-cators of periodontal disease, such as tooth loss

and bleeding gums, are associated with a greaterrisk of certain cancers as well as systemic diseasesand disorders such as cardiovascular disease, pre-term and underweight birth. Periodontitis hasrecently been associated with an increased riskof squamous cell carcinoma of the head, neck,and esophagus, cancer of the tongue, pancreaticcancer, and systemic inflammation in solid-organtransplant recipients. There are also correlationsbetween periodontal disease severity and diabetesand rheumatoid arthritis (Meyer et al. 2008).

The bacterial aetiology of chronic periodontitisis still somewhat controversial but is widelyacknowledged to be polymicrobial in nature.While the concepts of the roles of particular oralbacterial species in disease have changed over thepast two decades, there is consensus that anaero-bic, proteolytic, amino acid fermenting species,especially Porphyromonas gingivalis, Treponemadenticola, and Tannerella forsythia, play a crucialrole in both initiation and progression of disease(Darveau 2010; Hajishengallis and Lamont2012). A recent study of the bacterial compositionof subgingival plaque in individuals with chronicperiodontitis showed that P. gingivalis andT. denticola and T. forsythia were routinelyfound together in subgingival plaque (Byrneet al. 2009). P. gingivalis has recently been pro-posed to be a “keystone pathogen” that manipu-lates the host response to allow proliferation of theplaque bacterial biofilm community which thenresults in dysbiosis and disease (Hajishengalliset al. 2011). Interactions between key oral bacte-rial species are essential for the progression ofchronic periodontitis. The unifying features ofthese three bacteria are their extracellular proteo-lytic activity, their complex anaerobic fermenta-tions of amino acids, production of toxicmetabolites, and outer membrane (or sheath) ves-icles. Of the three species, only the treponeme ismotile and able to respond chemotactically toenvironmental stimuli.

In vivo, P. gingivalis and T. denticola are fre-quently found to coexist in deep periodontalpockets, and they increase in numbers at similartimes, suggesting possible interbacterial interac-tions that contribute towards disease. In a longi-tudinal human study, the imminent progression of

Fig. 4 Gingivitis demonstrating generalised inflammationin the underlying connective tissues (�). (Image courtesyof Professor Camile Farah, UWA Dental School, Univer-sity of Western Australia, Perth WA, Australia)

Fig. 3 Marginal gingivitis with blunting of the interdentalpapilla, gingival inflammation with erythematous changeand plaque formation around the gingival margins (Imagecourtesy of DrMarie AnneMatias, Periodontist, PerthWA,Australia)


chronic periodontitis could be predicted byincreases in the relative proportions ofP. gingivalis and T. denticola in subgingivalplaque (Byrne et al. 2009). The motility and che-motactic ability of T. denticola, although not con-sidered as classic virulence factors, are likely to beimportant in the synergistic biofilm formationwith P. gingivalis (Dashper et al. 2011). Directmicroscopy of freshly prepared samples of peri-odontal pocket biofilms often reveals spirochaetesswimming on the surface of the adjacent biofilmthat has a sessile population of the samemorphotypes (Ellen and Galimanas 2005; Zijngeet al. 2010). In vitro, P. gingivalis and T. denticoladisplay a symbiotic relationship in nutrient utili-zation and growth promotion (Tan et al. 2014).P. gingivalis and T. denticola microcolonies co-localized in the surface layers of subgingivalplaque adjacent to the periodontal pocket epithe-lium help explain why emergence of relativelylow proportions of these opportunistic pathogenscan be associated with disease (Zijnge et al. 2010).When co-inoculated in animal models of peri-odontitis, P. gingivalis and T. denticola exhibit asynergistic virulence (Orth et al. 2011). Togetherthese data suggest there is an intimate relation-ship between these two species that has evolved

to enhance their survival and virulence (Nget al. 2016).

Current diagnosis of chronic periodontitisis based on clinical (Fig. 5) and radiographic(Figs. 6, 7 and 8) detection of tissue damage(Fig. 9). Treatment relies on the nonspecificremoval of the pathogenic subgingival biofilmby scaling and root planning and antibiotic ther-apy when indicated. There are currently no spe-cific treatments available, and prevention ofdisease progression relies on an increased

Fig. 5 Chronic periodontal disease in a older male withcalculus formation on the lower incisors and associatedbone loss, with erythematous swollen gingiva (Image cour-tesy of Dr Marie Anne Matias, Periodontist, Perth WA,Australia)

Fig. 6 Orthopantomograph demonstrating horizontalbone loss in a patient with chronic adult periodontitis.Note minimal calculus deposits, some caries, and retainedroot fragments, excluding other radiographic features

not described (Image courtesy of Dr Marie Anne Matias,Dento-maxillofacial Radiologist, Qscan RadiologyClinics, Brisbane QLD, Australia)


attention to oral hygiene by the sufferer and reg-ular maintenance visits to a clinician.

Dental Caries

Dental caries is a dynamic process that occurs inthe polymicrobial biofilms accreted to the surfacesof the tooth. The net result is a disturbance to theequilibrium between tooth substance and the sur-rounding fluid that results in mineral loss from the

tooth surface (Figs. 10 and 11). Acidic pH is themain culprit in the dissolution of enamel, and incaries this is produced by the fermentation ofsugars by oral bacteria as elegantly demonstratedin 1867 by Emil Magitot. Streptococcus mutans isoften named as the major (or only) etiologicalagent of this disease although there has been con-siderable debate over the last 120 years regardinghow specific the aetiology of the disease reallyis and a polymicrobial nature of disease is nowwidely accepted. Currently, the consensus is

Fig. 7 Orthopantomograph demonstrating severe hori-zontal and vertical bone loss and abundant calculusdeposits in a patient with advanced aggressive periodontaldisease. There is chronic apical periodontitis involving themaxillary right molars and reactive mucosal thickening at

the floor of the right maxillary sinus. Note some cariesand displaced teeth, excluding other radiographic featuresnot described (Image courtesy of Dr Marie Anne Matias,Dento-maxillofacial Radiologist, Qscan RadiologyClinics, Brisbane QLD, Australia)

Fig. 8 Orthopantomograph demonstrating severe boneloss particularly in quadrant 1, on a background of gener-alized horizontal bone loss in a 31-year-old male. There isminimal calculus present, excluding other radiographic

features not described (Image courtesy of Dr Marie AnneMatias, Dento-maxillofacial Radiologist, Qscan RadiologyClinics, Brisbane QLD, Australia)


that there is a subgroup of oral bacteria in supra-gingival plaque that is acidogenic as well asaciduric and, as such, is able to produce sufficientorganic acids as the end products of sugar fermen-tation to lower the plaque pH below that is neces-sary for enamel (hydroxyapatite) dissolution andmaintain it at a substantially acidic pH forextended periods of time. These species are also

found at healthy sites but in numbers too low tohave a pathological impact. A change in environ-mental conditions such as an increase in the fre-quency of sugar consumption, decreased salivaryflow rate or function or exposure of previouslyhidden surfaces results in an increase in the abun-dance of these cariogenic species in plaque. Thisincrease leads to caries initiation. This is referredto as the ecological plaque hypothesis (Marsh2010) and with the advent of DNA sequencingtechnologies, the major species involved in thisshift are now being identified.

S. mutans remains a model cariogenic bacte-rium due to its long and uncontested associa-tion with human dental caries. Recent genomesequencing of S. mutans strains from around theworld has shown that the S. mutans populationstarted expanding exponentially around10,000 years ago, which coincides with the onsetof human agriculture (Cornejo et al. 2013). Thisshows how a formerly commensal species canrapidly adapt to environmental pressure, in thiscase the provision of free sugars – in particularsucrose. The bacterium adapted to the availabilityof free sugars by genetically acquiring bettertransport systems for free sugars, faster enzymesto catabolize the sugars, and more efficient waysof dealing with the consequences of rapid sugarfermentation – that is, low pH. Undoubtedly, otherbacterial species in the oral cavity will have sim-ilarly modified their genomes through naturalselection and evolved to make use of the relatively

Fig. 9 Periodontal bonedestruction and loss ofattachment seen in chronicperiodontal disease.a: periodontal soft tissues,b: alveolar bone, d: dentine,e: enamel space (Imagecourtesy of ProfessorCamile Farah, UWA DentalSchool, University ofWestern Australia, PerthWA, Australia)

Fig. 10 Caries in primary dentition affecting maxillaryand mandibular teeth (Image courtesy of Associate Profes-sor Robert Anthonappa, UWA Dental School, Universityof Western Australia, Perth WA, Australia)


abundant free sugar in an agricultural-based dietas opposed to hunter-gatherer style diets. It hasbeen shown that by extracting bacterial DNAfrom the calculus of ancient skeletons that thetransition from hunter-gatherer to farming shiftedthe oral microbial community compositiontowards a disease-associated consortium (Adleret al. 2013). During the Industrial Revolution,the cariogenic bacteria became dominant, leavingthe modern oral microbiota significantly lessdiverse, which may contribute to chronic oraldisease.

Caries is usually associated with the more shel-tered sites on the tooth with low salivary flowincluding interproximal sites and fissures on theocclusal surfaces. These sites enable the establish-ment of dense, cariogenic species-containingpolymicrobial biofilms. A low salivary flow rateallows the buildup of organic acids and the main-tenance of low pH for extended periods. Thisresults in a subsurface demineralization of theenamel commonly known as a white spot lesion.At this stage, the enamel surface remains intactand the lesion can be remineralized under the rightconditions. These include the removal of the car-iogenic bacteria, provision of supersaturated cal-cium and phosphate, and limitation of free sugars.Once the surface of the enamel cavitates, the tis-sue damage becomes irreversible and restorativemeasures are needed. In addition, cavitation

enables bacteria to penetrate the enamel surfaceinto the lesion providing a highly sheltered envi-ronment. This favors the proliferation of evenmore acidogenic and aciduric bacterial speciessuch as Lactobacillus casei (Fejerskov and Kidd2003). This can result in a rapid expansion of thecarious lesion towards the dentine, eventuallyresulting in pulp involvement (Fig. 12) (seebelow). The large variety of bacterial species andhigh numbers of bacterial cells in the advancinglesion provides an inoculum for infection of thepulp.

Caries is controlled at a human populationlevel mainly through the use of fluorides tostrengthen the enamel. With early diagnosis priorto cavitation, remineralizing agents and varnishescan be utilized following a minimal interventionapproach. This can be coupled with dietary adviceto reduce the frequency and amount of free sugarintake. Due to the complex aetiology of caries,antibacterial therapies are restricted mainly tophysical removal of supragingival plaque andthe application of broad spectrum antibacterialagents such as chlorhexidine when required.

Significant Bacterial Species

A detailed description of all the bacterial speciescausing infections of the oral cavity is well

Fig. 11 Orthopantomograph of a patient in the mixeddentition demonstrating large carious lesions involvingthe lower first permanent molars affecting the pulpal cham-bers. Some caries is also evident on several of the primary

teeth, excluding other radiographic features not described(Image courtesy of Dr Marie Anne Matias, Dento-maxillofacial Radiologist, Qscan Radiology Clinics, Bris-bane QLD, Australia)


beyond the scope of this chapter. So here we shallonly deal with some of the more significant spe-cies. Acute oral infections usually have a poly-microbial aetiology and often result in abscessformation. The source of infection is mainlyodontogenic and may be triggered by inoculationof bacteria during dental extraction or root canaltherapy. The use of non-culture-dependent tech-niques, namely DNA sequencing technologiesand computational biology, has greatly improvedour understanding of the bacterial diversity of themicrobiota associated with acute apical abscesses(dentoalveolar infections). Abscesses from whichsix or more bacterial species are isolated tend to belarger and more painful than those that have fewerspecies present which may be due to synergisticpathogenicity (Marsh and Martin 1999). Thediversity and variety of species and consortiaassociated with disease emphasizes the rolesof symbioses and other interactions amongspecies in the development of acute infections.These DNA-sequencing technologies have alsoimplicated a range of previously unidentified spe-cies such as treponemes and anaerobic Gram-positive rods including Bulleidia extructa,Cryptobacterium curtum, and Mogibacteriumtimidum in disease (Robertson and Smith 2009).The combination of culture and molecular studieshas conclusively demonstrated that the apicalabscess microbiota is polymicrobial and domi-nated by anaerobic bacteria. The Firmicutes phy-lum (Streptococcus, Dialister, Filifactor, andPseudoramibacter) and the Bacteroidetes phylum(Prevotella, Porphyromonas, and Tannerella)

contribute to more than 70% of the speciesfound in abscesses. However, species fromanother five bacterial phyla can routinely bedetected from apical abscesses, comprisingFusobacteria, Actinobacteria, Spirochaetes,Synergistetes, and Proteobacteria (Siqueira andRocas 2013).

Our understanding of the taxonomy of oralbacteria is evolving rapidly, and many speciesare lumped together for convenience into “speciesgroups” that emphasize their high degree of sim-ilarity, our inability to separate them, and/or thevery fluid nature of the species concept as itapplies to bacteria. The pigmented Prevotellaintermedia group (comprising Prevotellaintermedia, Prevotella nigrescens, and Prevotellapallens), Porphyromonas endodontalis, andP. gingivalis (see above) are anaerobic Gram-negative bacilli often associated with periapicalabscesses (Jacinto et al. 2006). Until relativelyrecently, these species were lumped together as“black-pigmented Bacteroides” and they sharemany common features including extracellularproteolytic activity that enables them to breakdown host tissues and thwart host responses, theability to acquire and store iron usually in the formof heme from host molecules such as hemoglobin,and the production of outer membrane vesiclesthat extend their sphere of influence (Gui et al.2016). F. nucleatum (see above) is frequentlyrecovered from the acute dental abscess as areclosely related species such as Fusobacteriumperiodonticum.

Fig. 12 Dentine caries (�)with associated reversiblepulpitis. d: dentine, p: pulp(Image courtesy ofProfessor Camile Farah,UWA Dental School,University of WesternAustralia, Perth WA,Australia)


Avariety of oral streptococci are reported fromacute infections which is unsurprising given theirabundance in supragingival plaque and the rolesthey play in the caries process. Most oral strepto-cocci anaerobically ferment simple sugars andsugar alcohols to organic acids, are tenacious bio-film formers, adhere to a wide variety of hostmolecules, can invade epithelial cells, and havebeen shown to interact synergistically with arange of other oral bacterial species. In particular,the α-hemolytic “viridans streptococci group” thatis made up of the S. mitis, S. oralis, S. salivarius,S. sanguinis, and S. mutans groups is associatedwith periapical abscesses (Facklam 2002). TheS. anginosus group (comprising Streptococcusmilleri or Streptococcus anginosus) is alsoreported to be involved.

Enterococcus faecalis, a close relative of theoral streptococci, is the bacterium most oftenassociated with endodontic infections. However,the role of E. faecalis as an endodontic pathogen isstill disputed (Spangberg 2006). Its associationwith disease is in part due to its abilities to formbiofilms inside dentinal tubules, to tolerate thealkaline pH used as a medicament for root canaltherapy and to remain in a persister (vegetative)state for extended time periods. Peptostreptococciare frequently isolated from apical abscesses,being detected in nearly 80% of cases. Thegenus Peptostreptococcus has recently beendivided into Parvimonas and Anaerococcus andthe asaccharolytic, anaerobic, small coccusParvimonas micra (formerly Peptostreptococcusmicros) is one of the most commonly identifiedspecies. It has been shown to be pathogenic inanimal studies, especially in polymicrobial infec-tions (Siqueira and Rocas 2013).

Treponemes play a role in the aetiology of anumber of human chronic diseases includingsyphilis and yaws (Treponema pallidum), peri-odontal diseases including chronic periodontitisand acute necrotizing ulcerative gingivitis (Trep-onema denticola, Treponema lecithinolyticum,Treponema pectinovorum, Treponema socranskii,and others) and endodontic infections and someacute dental abscesses. Treponemes are membersof the Spirochaetes phylum, a clade that is distinctfrom both Gram-positive and Gram-negative

bacteria, as such they have evolved unusual andunique virulence characteristics (Dashper et al.2011). Treponemes are all strictly anaerobic,motile, helically shaped bacteria. They areextremely difficult to culture, and their small slen-der morphology often makes them difficult todetect; however, their characteristic corkscrewshape is diagnostic. Treponemes have a high prev-alence within acute dental abscesses, which maybe due in part to their motile and chemotacticnatures coupled with their biofilm forming ability(Dashper et al. 2011). Using molecular basedtechniques T. denticola has been detected inup to 79% of dental abscesses (Siqueira andRocas 2004), while other treponemes includingT. socranskii, T. pectinovorum, T. amylovorum,and T. medium are found at lower but significantprevalence (Robertson and Smith 2009).

The Dental Pulp

The dental pulp is a soft tissue consisting mainlyof connective tissue with many cells (such asfibroblasts, odontoblasts, undifferentiated mesen-chymal cells) and a rich network of blood vesselsand nerves. It is surrounded by the hard dentaltissues (dentine, enamel, and cementum) (Yu andAbbott 2007). Hence, it is protected from externalinfluences as long as the hard tissues remainintact. The most important protective tissue forthe pulp is the enamel, since this tissue is exposedto the oral cavity and, more importantly, to thebacteria contained within the oral cavity. Once thestructural integrity of the enamel is interrupted,then potential pathways can exist for oral bacteriato invade the tooth (Fig. 13) which, in turn, canlead to pulp disease (Yu and Abbott 2007;Siquiera 2011). The typical ways in which theintegrity of the enamel is destroyed are throughthe action of bacteria, the effects of chemicals(such as acids), and mechanical events (such ascracks and fractures) (Siquiera 2011). If a restora-tion is present, then the interface between therestoration and the tooth structure is also criticalas any opening or space between them is an areathrough which bacteria may enter the tooth and


this can lead to pulp disease (Abbott 2004a;Kwang and Abbott 2012).

Dental caries is one of the most common dis-eases that occurs in humans. It is essential tounderstand that caries is a bacterial processwhich results in loss of the mineralized substanceof teeth. Dental caries can have serious conse-quences if not treated as the bacteria will progressthrough the tooth to involve the pulp and eventu-ally the periapical tissues (Yu and Abbott 2007).

Once a cavity develops in a tooth, the cariouslesion tends to develop more readily as the

bacterial plaque is protected to some extent fromcleaning and the cavity becomes deeper. Once thecavity reaches dentine, which consists of tens ofthousands of dentinal tubules per square millime-ter (Garberoglio and Brannstrom 1976), there aredirect pathways for the bacteria and theirby-products to reach the dental pulp via thesetubules (Fig. 14). Hence, pulp irritation occursonce the caries reaches the dentine. This irritationinitially leads to the formation of reactionary den-tine (also known as reparative or tertiary dentine)as the pulp attempts to wall itself off from

Fig. 13 Schematic diagram showing the common pathways of entry of bacteria into teeth to cause an infected root canalsystem and the resultant periapical response


the irritant bacteria and/or their by-products(Fig. 15). However, if the caries is left untreated,the pulp will eventually become inflamed(pulpitis) and then it will necrose as the bacteriaand the caries spread closer to the pulp chamber(Siquiera 2011).

Chemicals applied to the tooth enamel can alsolead to demineralization. Acids may be producedby bacteria (as above for caries) or they may bepresent in foods and drinks consumed by thepatient. Loss of enamel may occur through directdissolution or by softening the enamel which isthen easily abraded by the normal actions ofchewing, grinding, clenching, brushing, etc.Once the dentine is exposed via this process,bacteria can invade the tubules and subsequentlyaffect the pulp in the same manner as outlinedabove for caries (Yu and Abbott 2007).

Cracks in teeth are defects through which bac-teria can enter the tooth (Abbott 2004b; Abbottand Leow 2009; Ricucci et al. 2015). If the crack

is confined to enamel, then there is usually noconsequence as far as the pulp is concerned butthe crack may lead to a fracture which can exposethe dentine tubules. Alternately, the crackmay “grow” and extend into the dentine, thusproviding a direct pathway for bacteria to enterthe tooth and cause pulp disease (Ricucciet al. 2015).

As mentioned above, a gap between the toothand a restoration provides a pathway for potentialbacterial invasion. Likewise, breakdown of a res-toration leads to the development of a similargap where bacteria may invade (Abbott 2004a;Kwang and Abbott 2012). They may be cario-genic bacteria and cause caries (and subsequentpulp disease), or they may be other bacteria thatdo not cause caries but they lead to pulp diseasevia the dentinal tubules.

The dental pulp will undergo inflammatorychanges long before the bacteria actually reachthe pulp itself as a result of the dentine tubule

Fig. 15 Reactionarydentine (�) and associatedpulpal inflammation.d: dentine, p: pulp (Imagecourtesy of ProfessorCamile Farah, UWA DentalSchool, University ofWestern Australia, PerthWA, Australia)

Fig. 14 Caries (�)extending into the dentinaltubules. (Image courtesy ofProfessor Camile Farah,UWA Dental School,University of WesternAustralia, Perth WA,Australia)


pathways. The pulp will progress through variousstages of inflammation, known as pulpitis, with aconsequent range of different symptoms and signs(Abbott and Yu 2007; Ricucci et al. 2014; Abbott2016). In the early stages of the disease process,the inflammation will be mild and therefore thesymptoms are also relatively mild (Fig. 16). Thepain associated with this condition is usually stim-ulated by extreme temperature changes – that is,very hot or very cold foods/drinks – and the pain isusually only momentary or disappears once thestimulus has been removed from the tooth. Thisfirst stage of pulpitis is called reversible pulpitis asit is believed by clinicians that the inflammationcan resolve once the cause of the problem hasbeen removed – that is, by removing the caries(and especially the bacteria causing the caries),the irritant is removed and the pulp can recoverprovided an adequate dental restoration can beplaced in the tooth (Fig. 17). Reversible pulpitiscan be an acute or a chronic condition, depending

on the severity of symptoms and how long theyhave been present (Abbott and Yu 2007; Abbottand Leow 2009; Abbott 2016).

If a tooth with reversible pulpitis is not treated,then the pulpitis will progress to become irrevers-ible pulpitis (Fig. 18). The symptoms associatedwith this condition are generally quite severe andthe tooth is usually reactive to mild temperaturechanges – such as tap water, or warm food/drink.Often the patient will have spontaneous pain andthe pain may wake them up at night. The painusually lingers for a long period after the stimulushas been removed from the tooth. When thesesevere symptoms are present, the condition willbe acute irreversible pulpitis (Figs. 19 and 20),but some patients have less severe symptoms thatpersist for many months and hence they will havechronic irreversible pulpitis (Fig. 21) (Abbott andYu 2007; Ricucci et al. 2014; Abbott 2016).

As the inflammation spreads throughout thepulp in teeth with untreated irreversible pulpitis,

Fig. 16 Pulp hyperemia(�). d: dentine, p: pulp(Image courtesy ofProfessor Camile Farah,UWA Dental School,University of WesternAustralia, Perth WA,Australia)

Fig. 17 Reversible pulpitiswith caries (�) at the upperleft aspect of the image.d: dentine, p: pulp (Imagecourtesy of ProfessorCamile Farah, UWA DentalSchool, University ofWestern Australia, PerthWA, Australia)


+ TRAUMA(e.g. Luxation, avulsion, etc.)

Chronic Reversible Pulpitis Acute Reversible Pulpitis

Chronic Irreversible Pulpitis Acute Irreversible Pulpitis

Clinically Normal Pulp

Necrobiosis

Necrotic and Infected Pulp

Pulpless and Infected Root Canal System

Pulp Necrosis

Fig. 18 The progression of pulp disease through differentstages. There are two main pathways of progression –either (A) via the “trauma pathway” as a result of thepulp’s blood supply being severed at the apex during a

displacement injury or (B) via the “coronal pathway” as aresult of invasion of microorganisms through caries,cracks, restoration margins, or fractures of the coronalpart of the tooth (Adapted from (Abbott and Yu 2007))

Fig. 19 Caries (�)extending into the pulpshowing signs ofirreversible pulpitis. d:dentine, p: pulp (Imagecourtesy of ProfessorCamile Farah, UWA DentalSchool, University ofWestern Australia, PerthWA, Australia)


the bacteria will also continue to progress throughthe carious defect, crack, or marginal gap and willsoon invade the pulp space itself. The pulp thentypically begins to necrose with the necrosis com-mencing in the region of the pulp adjacent to thecaries, crack, or gap – that is, the pulp at the baseof the involved dentine tubules. The necrosis willthen spread throughout the entire pulp space (i.e.,into the radicular pulp and root canal system) asthe bacteria have no hindrances to their

progression since the pulp can no longer providethe usual defense mechanisms as it necroses.

Necrotic pulps are fairly rapidly digested bythe bacteria so the tooth becomes pulpless andinfected within 1–2 months, depending on theavailability of oxygen and the type of bacteriathat have invaded the root canal system (Janssonet al. 1993). When the environment is more anaer-obic, there will be more pathogenic bacteria pre-sent and the progression of the disease processwill be faster. This is typical of a tooth that has acrack, a restoration breaking down, or a cariouslesion without a frank pulp exposure. Teeth withlarge carious lesions that have exposed the pulptend to have a more aerobic environment, at leastin the coronal part of the root canal, and hence thedisease progresses at a slower rate. However, overtime, all untreated teeth will have a pulpless,infected root canal system that leads to periapicaldiseases (Jansson et al. 1993).

Infections of the root canal system may alsodevelop as a result of trauma to the tooth. Inparticular, if the apical blood supply has beensevered and the pulp does not revascularize, thenthe pulp effectively becomes instantly necrotic. Ifbacteria have contaminated the damaged tooth orif they are able to penetrate into the tooth subse-quently, then the tooth will become pulpless andinfected (Fig. 22), thus causing periapical inflam-mation, as outlined below.

Fig. 21 Chronic irreversible pulpitis. d: dentine, p: pulp(Image courtesy of Professor Camile Farah, UWA DentalSchool, University of Western Australia, Perth WA,Australia)

Fig. 20 Irreversiblepulpitis. d: dentine, p: pulp(Image courtesy ofProfessor Camile Farah,UWA Dental School,University of WesternAustralia, Perth WA,Australia)


Pulp, Root Canal, and PeriapicalInfections

The classic studies of Kakehashi and coworkers(1965, 1969) clearly demonstrated that pulp dis-ease is a direct result of the presence of bacteria inthe tooth. In those studies, the pulps of teeth ingerm-free rats and normal rats (rats with normaloral microbiota) were exposed when cavities werecut in the teeth. The cavities were left unrestoredso the pulps were open to the oral environmentuntil the animals were killed for histological eval-uation. In the germ-free animals, the pulps recov-ered whereas the pulps in the normal ratsdegenerated, necrosed, and became infected.Hence, it was clearly demonstrated that bacteriacause pulp disease.

Further classic studies by Möller (1966),Korzen et al. (1974), Sundqvist (1976), Fabriciuset al. (1982a, b), and Möller et al. (1981) subse-quently demonstrated that periapical disease isalso a direct result of the presence of bacteria inthe tooth – that is, once the root canal systembecomes infected, the periapical tissues respondinitially with inflammation and this can then pro-gress to other conditions such as extraradicularinfections, apical abscesses, facial cellulitis, or

cysts (Nair et al. 1996; Nair 1997; Abbott 2002,2004a, b, 2016; Siquiera 2011). The above studiesalso showed that the presence of necrotic pulptissue does not in itself induce a periapicalresponse as long as there are no bacteria present.A converse way of viewing this is that once aperiapical radiolucency is evident radiographi-cally, the root canal should be considered to bepulpless and infected.

Infection of the root canal system is a poly-microbial infection (Sundqvist 1990) that exists asa complex biofilm (Siquiera 2011). There is nosingle species that typically dominates theseinfections. An important aspect of root canalinfections is the coexistence of various specieswhereby most species provide essential nutrientsfor other species to survive. Hence, the bacteriaexist as a “community” in what is essentially ananaerobic environment (Siquiera 2011; Siquieraand Rôças 2011). As the pulp becomes necroticand then the root canal becomes pulpless (Janssonet al. 1993), there is no blood supply to the rootcanal system once it is infected. Hence the bodyhas no mechanism by which to fight or resist theinfection that develops. This results in a “stand-off” between the bacteria and the host with a“battle zone” at the apical foramen or at other

1° Acute Apical Periodon��s

Chronic Apical Periodon��s

2° Acute Apical Periodon��s

1° Acute Apical Abscess · Intensifica�on of Inflamma�on + symptoms

· Facial Celluli�s · Periapical Cyst (pocket/true), OR · Chronic Apical Abscess (i.e. draining sinus)

2° Acute Apical Abscess

Infected Root Canal SystemFig. 22 The interactionsbetween the differentperiapical conditions thatare a result of an infectedroot canal system. Thisillustrates the dynamicnature of these periapicalconditions (Adapted from(Abbott 2004a))


accessory foramina, if present in the tooth(Fig. 13).

Infections within the root canal system persistas long as no treatment is provided to the tooth toremove or destroy the bacteria. As time pro-gresses, bacterial numbers increase since the path-way(s) for bacterial penetration into the tooth arestill present (Fig. 13). These pathways not onlyallow new bacteria to continue to enter the tooth,but they also allow nutrients from the oral cavityto enter the tooth to help the bacteria survive.Typically, such nutrients come from foods anddrinks consumed by the patient. In addition,inflammatory exudate from the inflamed peri-radicular tissues may enter the root canal systemthrough the apical or lateral foramina and thisfluid may also provide some nutrients. Hence,bacteria that are present in an established infectionwithin a pulpless root canal system have an idealenvironment in which to survive and flourish –one that is rich in nutrients, low in oxygen, andinaccessible to the host defense system, andallows continual replenishment with new bacteriafrom the oral cavity (Sundqvist 1976).

Once there are bacteria present within the rootcanal system, the periapical tissues becomeinflamed, as outlined above. This is a response tothe bacteria and subsequent infection that

develops. The inflammatory response will usuallybe an acute response initially (known as primaryacute apical periodontitis) (Nair 1997) but gener-ally becomes chronic fairly rapidly (i.e., chronicapical periodontitis) (Figs. 23, 24 and 25). Asit becomes chronic, clastic cells (osteoclasts,cementoclasts, and dentinoclasts) are activatedand remove bone and tooth structure to createspace for the inflammatory response in the peri-apical region. Many patients do not experienceany symptoms, or perhaps only mild symptomsfor a short period of time, when periapical inflam-mation commences (Abbott 2016). This inflam-mation is the body’s defense system’s attempt atfighting the infection, but all it is able to do iscontain the infection – usually only succeeding instopping the bacteria from exiting the root canaland causing a local or a systemic infection (Nairet al. 1996). The body’s ability to continue toprevent the bacteria from spreading is limited bylocal conditions, the type and virulence of thebacteria, and the overall general health of thepatient (i.e., the effectiveness of the immune sys-tem). At times, patients experience symptomsassociated with the infected tooth – these symp-toms could be due to secondary acute apical peri-odontitis, a secondary acute apical abscess, orfacial cellulitis (Nair et al. 1996; Abbott 2004b,

Fig. 23 Orthopantomograph demonstrating radiographicevidence of chronic apical periodontitis associated with theupper left first and secondmolar teeth. There is elevation ofthe floor of the left maxillary sinus and associated reactive

mucosal changes. Other radiographic features notdescribed (Image courtesy of Dr Marie Anne Matias,Dento-maxillofacial Radiologist, Qscan RadiologyClinics, Brisbane QLD, Australia)


2016). Other conditions can also develop butwithout symptoms or with only occasional symp-toms – such as a chronic apical abscess (Fig. 26),chronic periapical granuloma (Figs. 27 and 28), an

extraradicular infection, a periapical pocket cyst(Fig. 29), or a periapical true cyst (Figs. 30, 31 and32) as specifically described by Nair (Nair 1997;Abbott 2004b, 2016). While the latter two

Fig. 24 CT demonstrating features of chronic apical peri-odontitis. There is reactive mucosal thickening in the infe-rior aspect of the left maxillary sinus related to subtleinflammatory (arrows) radiolucency around the apices of

the pulpless, infected upper left first molar (26) (Imagescourtesy of Clinical Associate Professor Andy Whyte,Perth Radiological Clinic, Perth WA, Australia)

Fig. 25 Chronic apicalperiodontitis with root tothe left of the image (Imagescourtesy Professor CamileFarah, UWADental School,University of WesternAustralia, Perth WA,Australia)


Fig. 26 Periapical abscess. Slightly irregular radiolu-cency (white dashed oval in a and b) is associated withthe distal apex of the lower right first molar (46) withwidening of the periodontal ligament space around themesial root and adjacent sclerosing osteitis. The abscess

perforates the buccal cortex (white dashed arrow in b + c)resulting in a buccal abscess (white arrows in c + d)(Images courtesy of Clinical Associate Professor AndyWhyte, Perth Radiological Clinic, Perth WA, Australia)

Fig. 27 Chronic periapical granuloma. A cropped OPG (a)shows a well-defined 7 mm periapical inflammatory radio-lucency associated with the apices of 47 (white arrows).Image (b) is an oblique sagittal CT scan reconstructionshowing small, well-defined radiolucencies associated with

37 and the mesial root of 36 (black arrows) with adjacentsclerosing osteitis of medullary bone. All lesions wereasymptomatic and likely to represent periapical granulomas(Images courtesy of Clinical Associate Professor AndyWhyte, Perth Radiological Clinic, Perth WA, Australia)


conditions are not defined as infections, it isimportant to understand that they are sequelae toan infected root canal system and they can becomeinfected at times (Nair 1997).

While the pulp progresses through severalstages of increasing severity of inflammation tothen become necrotic and infected (and then theroot canal system becomes pulpless) (Fig. 18), theperiapical tissues can alternate between the vari-ous conditions in a dynamic manner (Fig. 22)(Nair 1997; Abbott 2002, 2004a). As an example,the most typical sequence for a tooth with aninfected root canal system is to initially developprimary acute apical periodontitis which can thenbecome chronic apical periodontitis as the body’simmune system responds to the situation. Epi-sodes of secondary acute apical periodontitis

may develop when conditions suit and some bac-teria exit through the apical foramen to reach theperiapical tissues. When the body’s immune sys-tem regains control, the tissues return to havingchronic apical periodontitis. This may occur sev-eral times and the patient may ignore it if thesymptoms are not too severe or do not last forlong. However, at some stage the symptoms ofsecondary acute apical periodontitis may be moresevere and the patient seeks treatment or a sec-ondary acute apical abscess may develop withlocalized swelling and this may stimulate thepatient to seek treatment. Alternatively, a drainingsinus may develop leading to a chronic apicalabscess. This could persist for some time beforethe patient seeks treatment or until a secondaryacute apical abscess forms and causes significant

Fig. 28 Periapicalgranuloma with tooth rootto the left of the imagedemonstrating externalapical inflammatory rootresorption (Image courtesyof Professor Camile Farah,UWA Dental School,University of WesternAustralia, Perth WA,Australia)

Fig. 29 Periapical pocketcyst with tooth root to theleft of the image (Imagecourtesy of ProfessorCamile Farah, UWA DentalSchool, University ofWestern Australia, PerthWA, Australia)


discomfort. Other conditions such as periapicalpocket cysts, periapical true cysts, and facial cel-lulitis can all occur at this dynamic interface thatexists in the periapical region (Fig. 22).

Management of Pulp, Root Canal,and Periapical Conditions

Assessment/Diagnosis

The first, and most important, stage in managingpulp, root canal, and periapical conditions is toformulate an accurate diagnosis since the treat-ment provided will vary for each condition(Abbott 2016). The important aspects of diagnosisare to understand the conditions that may be pre-sent and to know the pathogenesis of the condi-tions. Each condition will have some typicalsymptoms and/or clinical and radiographic signsso the clinician must be familiar with these(Table 2). In most cases, specific – but simple –clinical tests can be performed to provide thenecessary information to make the diagnosis(Abbott 2016). The tests that should always beperformed when assessing these conditions arepulp sensibility tests (especially cold and electrictests), percussion, palpation, mobility, periodontalprobing, transillumination (Fig. 33), and biting

tests. All teeth with suspected pulp, root canal,and periapical conditions must have at least oneperiapical radiograph but sometimes furtherimages may be required – such as a tube shiftperiapical radiograph, a bitewing radiograph, ora CT scan. The typical clinical examination find-ings and responses to tests for the most commonpulp and root canal conditions are summarized inTable 3.

When a patient presents with pain suggesting apulp, root canal, or periapical condition, the firststep is to take a very detailed history since this willenable the clinician to formulate a provisionaldiagnosis before examining the patient. Havingsuch a provisional diagnosis will enable the clini-cian to target the specific region with pain and toperform the appropriate tests. The clinician shouldseek information from the patient through appro-priate questions to determine whether the pain isrelated to some form of pulpitis or some form ofapical periodontitis (Abbott 2016).

If the patient reports pain with temperaturechanges (i.e., cold, hot foods/drinks), then someform of pulpitis should be suspected (Abbott andYu 2007; Abbott 2016). Further questions regard-ing specific stimuli for the pain (e.g., very coldwater from the fridge, tap water), the nature of thepain, its severity, and how long it lasts will enablethe clinician to distinguish between reversible and

Fig. 30 Orthopantomograph showing well-circumscribedperiapical radiolucency associated with the endodonticallytreated upper right lateral incisor and canine teeth consis-tent with a radicular cyst (periapical true cyst). The patient

also presents with chronic periodontal bone loss. Otherradiographic features not described (Image courtesy of DrMarie Anne Matias, Dento-maxillofacial Radiologist,Qscan Radiology Clinics, Brisbane QLD, Australia)


irreversible pulpitis as well as whether the condi-tion is acute or chronic.

If the patient complains of a dull ache or painon biting/chewing without thermal symptoms,then some form of apical periodontitis should besuspected along with an infected root canalsystem. Further questions, clinical tests, andradiographs will enable the clinician to be morespecific with the diagnosis – for example, lackof responses to pulp sensibility tests in conjunc-tion with a periapical radiolucency will indicatea pulpless, infected root canal system with

secondary acute apical periodontitis (if no swell-ing or pus present) or a secondary acuteapical abscess (if there is swelling and pus)(Abbott 2004a, 2016).

An essential part of the diagnostic process is toalso determine the cause of the problem. This isessential as removal of the cause should be thefirst stage of treatment for any condition in orderto avoid continuation or recurrence of the diseaseprocess (Abbott and Yu 2007). Pulp, root canal,and periapical conditions are generally caused bybacteria, as discussed above – however, the

Fig. 31 Apical radicular cyst (periapical true cyst). In theright mandibular body, associated with a carious lowerright first premolar (44) root remnant, there is an 18 mmapical radicular cyst (white arrows in a + b) that extendsdistally to the apex of the carious and pulpless lower rightsecond premolar (45) and mesially to the apex of the lowerright canine (43). There is a further periapical inflamma-tory radiolucency associated with the pulpless, infectedlower right lateral incisors (42) (white dotted arrows) likelyto represent a granuloma. The patient was asymptomatic.Apical radicular cysts, even when large, can be difficult tosee on panoramic radiographs in the posterior maxilla (c)

being obscured by superimposition of the “ghost opacity”of the palate and air above the tongue. A 24 mm cystextends from the apex of upper left second premolar(25) to the apices of the upper left third molar (28) (whitedashed arrows). The lesion is more clearly shown on acoronal CT reconstruction (d); it elevates the sinus floor,typical of a lesion of odontogenic origin and protrudes intothe inferior half of the left maxillary sinus (white dashedarrows). There is an additional small retention cyst (RC) inthe zygomatic recess of the left maxillary sinus (Imagescourtesy of Clinical Associate Professor Andy Whyte,Perth Radiological Clinic, Perth WA, Australia)


important issue is to determine how the bacteriaentered the tooth. Typically, the pathway of entrywill be via caries, cracks in the tooth structure orbetween the restoration and the tooth structure as aresult of marginal breakdown of the restoration(Kwang and Abbott 2012). Other potential path-ways are via a fracture of the tooth or the restora-tion if dentine is exposed, or via a periodontalpocket if it reaches a lateral canal foramen or theapical foramen (Fig. 34).

Managing Pulpitis

Reversible pulpitis should be managed conserva-tively by removing the cause of the problem (e.g.,caries, cracks, restoration), placing a sedative lin-ing and a temporary restoration. The tooth shouldthen be monitored for 3–4 months to determinewhether the pulp recovers and returns to a clini-cally normal state. This can be determined via aclinical examination including pulp sensibilitytesting to assess whether the pulp responds nor-mally. If the symptoms continue after the initialmanagement, then this likely indicates that thepulpitis was irreversible or has progressed to anirreversible state and therefore root canal treat-ment will be necessary. However, if the symptomsresolve and the tooth responds normally to pulpsensibility testing after 3–4 months, then the

pulpitis has resolved and the tooth can be restoredin a more definitive manner. Alternatively, ifthe symptoms resolve and the tooth does notrespond to pulp sensibility tests after 3–4 months,then the pulp has likely necrosed in which case,root canal treatment will be necessary (Abbott andLeow 2009).

Teeth presenting with irreversible pulpitis willrequire either extraction or root canal treatment(Fig. 35), with the latter being the preferred man-agement as it retains the tooth. However, theprognosis and the feasibility of undertaking thistreatment will be dependent on the tooth havingsufficient coronal tooth structure to enable it tobe restored adequately and with a restorationthat will prevent bacteria reentering the tooth formany years. Hence, an integral part of the rootcanal treatment is to remove all existing restora-tions, caries, and cracks prior to commencingroot canal treatment in order to investigate thesuitability of the tooth for further restoration(Abbott 2004a).

The main aims of root canal treatment whentreating irreversible pulpitis are to remove thecause of the disease (as above) and to removethe inflamed pulp tissue. The latter is achievedthrough a combination of the mechanical pro-cesses (such as filling and enlarging the rootcanal) and the chemical processes such as irriga-tion with sodium hypochlorite (NaOCl). This

Fig. 32 Periapical true cyst(radicular cyst)demonstrating simpleepithelial lining (�) andcholesterol crystals (c) incystic lumen. (Imagecourtesy of ProfessorCamile Farah, UWA DentalSchool, University ofWestern Australia, PerthWA, Australia)


solution is a powerful antibacterial agent as wellas an excellent solvent of organic tissue, even atrelatively low concentrations such as 1%. Hence,in irreversible pulpitis cases, its major function isto dissolve the inflamed pulp. Other irrigants arealso recommended (such as 17% ethylenediaminetetra-acetic acid with cetrimide – EDTAC) toremove inorganic matter from the canals as wellas the smear layer that forms during root canalinstrumentation (Baumgartner and Mader 1987).

Anti-inflammatory and antibacterial intracanalmedicaments are usually recommended to helpresolve the periapical inflammation that will alsobe present and to help ensure there are no bacteriain the root canal system, respectively (Abbott

1990). Once all symptoms have resolved and ini-tial healing is evident, the root canal filling can becompleted and the coronal part of the tooth can berestored.

Systemic antibiotics are not indicated and theyare not necessary for irreversible pulpitis since it isan inflammatory condition. While it is caused bythe presence of bacteria in the tooth, this shouldnot be considered as an “infection.” Any adjunc-tive systemic medication following treatmentshould only be nonsteroidal anti-inflammatorydrugs (NSAID) or analgesics to control inflamma-tion and pain, if present (Hargreaves and Abbott2005; Therapeutic Guidelines 2012a).

Table 2 Typical symptoms reported by patients that are associated with the most common pulp and root canalconditions. Refer to Abbott (2016) for further detailsa

Symptoms/signs

Acutereversiblepulpitis

Acuteirreversiblepulpitis

Necrotic andinfected pulp

Pulpless andinfected root canalsystem

Root-filled andinfected root canalsystem

Stimuli thatcause pain

Thermalchanges

Thermalchanges

Usually Nil – butmay be pain onchewing or biting ifacute apicalperiodontitis orabscess present



Thermalsensitivity

Extremeheat orcold

Mild heat orcold

No No No

Nature ofpain

Short,sharp

Short, sharppain whichbecomes adull ache

Dull ache Dull ache Dull ache

Duration ofpain

Very brief(a fewseconds upto1–2 min)

Lingers(>5–10 min)

Short – usually onlywhile biting orchewing



Spontaneouspain

No May bepresent

No No No

Pain worsewith lyingdown

No May bepresent

No No No

Pain wakespatient atnight

No May bepresent

No No No

Pain onbiting and/orchewing

May bepresent

May bepresent

No – unless acuteapical periodontitisor abscess present



aChronic reversible pulpitis will have similar symptoms and signs but they will be less severe and will have been presentfor longer periods of time than acute reversible pulpitis. Likewise, chronic irreversible pulpitis will have similar symptomsand signs but they will be less severe and will have been present for longer periods of time than acute irreversible pulpitis


Managing Infected Root Canal Systems

When a tooth has an infected root canal systemthat is causing any of the periapical conditionsoutlined above, the treatment options are eitherroot canal treatment or extraction. If there is suf-ficient tooth structure remaining to enable thetooth to be restored adequately and with a resto-ration that will prevent bacteria re-entering thetooth for many years, then root canal treatment isthe preferred option. The main aims of root canaltreatment for infected teeth are to remove thebacteria and all debris from the root canals andto destroy any bacteria that remain within the restof the root canal system. This treatment shouldalso remove all sources of nutrition for the bacte-ria. Once the canal has been disinfected, the apicalperiodontitis or apical abscess should resolve(Figs. 36 and 37).

If the tooth has an infected root canal systemthen irrigation with sodium hypochlorite has twofunctions – one is to dissolve any organic tissueand the other is to disinfect the root canal system(Baumgartner and Mader 1987). EDTAC shouldalso be used as it has some antibacterial action inaddition to its ability to prevent and remove the

inorganic smear layer that forms during treatment(Baumgartner and Mader 1987).

Intracanal medicaments play an important, andessential, role in treating infected root canal sys-tems as they are able to diffuse through the dentinetubules and reach bacteria that are not accessibleto mechanical instrumentation or the irrigatingsolutions. Medicaments are typically in the formof a corticosteroid/antibiotic paste or calciumhydroxide. The corticosteroid/antibiotic pastesare indicated for severe pain of an inflammatorynature (Abbott 1990). Calcium hydroxide is themost effective, predictable, and commonly usedexample of an antibacterial medicament. It largelyworks as a result of its high pH of 12.2. It is usedin a paste form which should be left in the rootcanal for at least 3–4 weeks to allow time for thehydroxyl ions to diffuse through the dentine andthe entire root canal system and to reach its max-imum pH level of about 8.5–9.5 in the outerdentine (i.e., adjacent to the cementum) (Nerwichet al. 1993).

Once the root canal system has been ade-quately disinfected and initial signs of healingare evident, the root canal filling can be placedalong with a definitive coronal restoration. Thetooth should then be reviewed clinically andradiographically on a regular basis to ensure thatthe periapical healing continues. Completehealing can take varying time periods rangingfrom a few months up to 5 years (Bystrom et al.1987). Healing is quite predictable following rootcanal treatment (Figs. 36 and 37) unless there is anextraradicular infection, a foreign body reaction,or a periapical true cyst (Nair 1997).

Periapical Surgery

Some teeth with infected root canal systems mayrequire periapical surgery to remove the diseasedtissue from the periapical region. However, this isuncommon with modern endodontic proceduresand materials. The cases that will require peri-apical surgery are those with:

• A persistent intracanal infection that has notresponded to root canal treatment

Fig. 33 Transillumination of a molar tooth reveals a crack(red arrow) on the distal surface. Another likely crack(green arrow) is also visible. Note that the tooth structureon the buccal side of the crack is illuminated by the stronglight source, while the lingual side is not illuminatedbecause the light rays have been deflected by the crack


Table

3Typ

icalclinicalexam

inationfind

ings

andrespon

sesto

testsforthemostcom

mon

pulp

androot

canalcon

ditio

ns.R

efer

toAbb

ott(20

16)forfurtherdetails

a

Clin

icalfind

ings/

respon

sesto

tests

Clin

ically

norm

alpu

lpAcutereversible

pulpitis

Acuteirreversible

pulpitis

Necrotic

andinfected

pulp

Pulplessandinfected

root

canalsystem

Roo

t-filledandinfected

root

canalsystem

Coldpulp

sensibility

test

Respo

nds

with

outp

ain

Painful

respon

se–

similarto

presentin

gcomplaint

Verypainful

respon

se–similar

topresentin

gcomplaint

Norespon

seNorespon

seNorespon

se

Electricpulp

sensibility

test

Respo

nds

with

outp

ain

Respo

ndswith

out

pain

Respo

ndswith

out

pain

–may

respon

dto

lower

levelo

fcurrent

Norespon

seNorespon

seNorespon

se

Hot

pulp

sensibility

test

Norespon

seMay

beapainful

respon

se–similar

topresentin

gcomplaint

May

beavery

painfulrespo

nse–

similarto

presentin

gcomplaint

Norespon

seNorespon

seNorespon

se

Swellin

gNo

No

No

Ifaprim

aryacuteapical

abscessispresent

Ifaprim

aryor

second

ary

acuteapicalabscessis

present

Ifaprim

aryor

second

ary

acuteapicalabscessis

present

Percussion

No

No(unlessacrack

underm

ininga

cusp)

No(unlessacrack

underm

ininga

cusp)

Too

thmay

feel“different”

ifchronicapical

period

ontitisor

may

betend

erifacuteapical

period

ontitisor

abscess

present

Too

thmay

feel“different”

ifchronicapical

period

ontitisor

may

betend

erifacuteapical

period

ontitisor

abscess

present

Toothmay

feel“different”

ifchronicapical

period

ontitisor

may

betend

erifacuteapical

period

ontitisor

abscess

present

Palpation

No

No

No

Not

ifchronicapical

period

ontitisbu

tmay

betend

erifacuteapical

period

ontitisor

abscess

present

Not

ifchronicapical

period

ontitisbu

tmay

betend

erifacuteapical

period

ontitisor

abscess

present

Not

ifchronicapical

period

ontitisbu

tmay

betend

erifacuteapical

period

ontitisor

abscess

present


Drainingsinus

present

No

No

No

No

Onlyifchronicapical

abscess

Onlyifchronicapical

abscess

Mob

ility

Normal

(unless

concurrent

period

ontal

disease)

Normal(unless

concurrent

period

ontald

isease)

Normal(unless

concurrent

period

ontald

isease)

Normal(unless

concurrent

period

ontal

disease)

Normal(unless

concurrent

period

ontal

disease)

Normal(unless

concurrent

period

ontal

disease)

Periodon

tal

probing

Normal

(unless

concurrent

period

ontal

disease)

Normal(unless

concurrent

period

ontald

isease)

Normal(unless

concurrent

period

ontald

isease)

Normal(unless

concurrent

period

ontal

disease)

Normal(unless

concurrent

period

ontal

disease)

Normal(unless

concurrent

period

ontal

disease)

Transillu

mination

May

reveal

cracks

ifpresent

May

revealcracks

ifpresent

May

revealcracks

ifpresent

May

revealcracks

ifpresent

May

revealcracks

ifpresent

May

revealcracks

ifpresent

Rad

iograp

hic

findings

Normal

periapical

tissues

Normal,o

rmay

beslightly

widened

PDLspace,or

cond

ensing

osteitis

Normal,o

rmay

beslightly

widened

PDLspace,or

cond

ensing

osteitis

Normal,o

rmay

beslightly

widened

PDL

space

Radiolucencypresent

Radiolucencypresent

Caries,crack,o

rrestoration

break

dow

npresent

No

Yes

Yes

Yes

Yes

Yes

a Chron

icreversible

pulpitiswill

have

similarfind

ings

tothoseof

acutereversible

pulpitis.Likew

ise,

chronicirreversible

pulpitiswill

have

similarfind

ings

tothoseof

acute

irreversiblepu

lpitis.In

caseswith

infected

rootcanals,the

periapicalfind

ings

will

depend

onwhetherthetoothhasacuteor

chronicapicalperiod

ontitis,anacuteor

chronicabscess,

oranyof

theotherperiapicalcond

ition

smentio

nedin

thetext


Fig. 34 Endodontic-periodontic lesion. Heavily restoredlower left first molar showing location of 5 mm periodontalpocket (a). Radiograph showing separate distal apicalradiolucency and mesial periradicular radiolucency in thelocation of the periodontal pocket (b). The tooth had apulpless, infected root canal system and secondary acuteapical periodontitis. Radiograph at 6 month review after

instrumentation and dressing with calcium hydroxideshowing healing of apical and periradicular radiolucencies(c). Radiograph at 12 month recall after root canal fillingand core placement with continued periradicular health(Images courtesy of Dr Oliver Pope, Endodontist, End-odontists on Collins, Melbourne VIC, Australia)

Fig. 35 The mandibular first molar tooth (tooth 36) hadacute irreversible pulpitis and primary acute apical peri-odontitis following placement of a crown. This problemmost likely developed as a result of irritation from theoperative procedure of the crown preparation. Root canal

treatment was done which relieved the symptoms. (a)Preoperative periapical radiograph. (b) Postoperativeradiograph after placing the root canal filling. (c)Eighteen-year review showing a stable tooth and normalperiapical tissues


• An extraradicular infection• A foreign body reaction• A periapical true radicular cyst

The differential diagnosis of these conditions isdifficult, and it is usually not possible to distin-guish between them based on clinical and radio-graphic (including CT scans) findings (Bornsteinet al. 2015). These conditions are not common andlikely constitute only less than 1% of all cases of

periapical radiolucencies, although there are nodata available to determine this. Biopsy studiesthat have been reported in the past merely provideinformation about the relative frequency of eachcondition within the biopsy cohort, and they donot indicate how often these problems occuramong all periapical radiolucencies (Franklinand Jones 2006; Jones and Franklin 2006; Haet al. 2014; Kelloway et al. 2014). It is impossibleto estimate this because the vast majority of

Fig. 36 The maxillary right central incisor had an uncom-plicated crown fracture which was restored with compositeresin 5 years prior to the patient presenting with a pulpless,infected root canal system and a secondary acute apicalperiodontitis with external apical inflammatory resorptionafter the restoration had broken down. The tooth had rootcanal treatment using a series of intracanal medicaments to

arrest the resorptive process, to encourage apexification ofthe open apical foramen, and to encourage periapicalrepair. (a) Preoperative periapical radiograph. (b) “Work-ing length” determination radiograph. (c) Postoperativeradiograph showing apical closure with a hard tissue bar-rier and periapical bone repair

Fig. 37 The mandibular left first molar tooth had apulpless, infected root canal system with secondary acuteapical periodontitis as a result of breakdown of an oldrestoration and the presence of a crack under the distalaspect of the restoration. Routine root canal treatment

was provided and the periapical tissues healed unevent-fully. (a) Preoperative periapical radiograph. (b) Postoper-ative radiograph showing periapical bone repair,reestablishment of a normal periodontal ligament spaceand lamina dura


radiolucencies heal with routine root canal treat-ment. Hence, these conditions are usually onlyconsidered when a periapical radiolucency per-sists within the first 4–5 years following rootcanal treatment (Abbott 2011) or symptoms donot resolve during the root canal treatment(Fig. 38). Radiolucencies that appear(or reappear) many years after root canal treat-ment has been completed may be an indicationof a new disease process within the tooth – that is,the restoration has broken down (or there is acrack or caries) and the root canal system hasbecome infected again. This will particularly bethe case if the periapical tissues had radiographicevidence of healing following the initial root canaltreatment.

A persistent periapical radiolucency may ormay not be associated with symptoms or clinicalsigns other than the radiolucency. Hence, it isessential that all teeth be followed up and moni-tored by the clinician until there is radiographicevidence of healing. If the patient has symptoms

or there are clinical signs such as a draining sinus,then further investigation is warranted. If the rootcanal treatment has been adequately performedand there have been no lost or fractured restora-tions, then the clinician might assume thatthe ongoing problem is a “periapical problem”(Abbott 2011). However, it must be noted thatmost cases of persistent radiolucency have beenreported to be due to an intracanal infection, andtherefore root canal retreatment is usually thetreatment of choice initially (Abbott 2011).Then, if the radiolucency still persists, one canassume it is truly a “periapical problem” such asan extraradicular infection, a foreign body reac-tion, or a periapical true cyst. These conditionswill require periapical surgery to remove theaffected tissue from the periapical region – usuallyonly a periapical curettage (Fig. 38) is required butin some teeth, retrograde root canal cleaning andfilling may be performed (Abbott 2011).

Fig. 38 The maxillary right central incisor (tooth 11) had apulpless, infected root canal system with pulp canal calcifi-cation and secondary acute apical periodontitis following alateral luxation injury 15 years prior to presentation. Thetooth had several infractions within the crown. The patientalso reported having occasional episodes of secondary acuteapical abscesses. Root canal treatment was instigated but theabscesses continued to occur every fewmonths and the largeperiapical radiolucency showed no signs of reduction insize. Hence, the root canal filling was completed in

conjunction with a periapical curettage to remove theaffected tissue. Histological examination of the biopsiedtissuewas suggestive of a radicular cyst. The adjacent lateralincisor (tooth 12) responded normally to pulp sensibilitytesting with cold and electric tests before, during, and aftertreatment of the central incisor. (a) Preoperative periapicalradiograph. (b) Postoperative radiograph following rootcanal filling and periapical surgery. (c) Two-year reviewradiograph shows periapical bone repair, reestablishmentof a normal periodontal ligament space and lamina dura


Antibiotics: When and When Notto Use

Systemic antibiotics are not required when thepatient has inflammatory conditions such asreversible or irreversible pulpitis. In fact, systemicantibiotics are contraindicated in these cases asthere are potential disadvantages of bacterialresistance and patient sensitization.

Systemic antibiotics are not often requiredwhen treating an infected root canal system, andthey are contraindicated unless the patient isshowing systemic signs of an infection. Mostteeth that develop symptoms associated with aninfected root canal system will have secondaryacute apical periodontitis (i.e., an inflammatoryreaction in the periapical region) or a secondaryacute apical abscess (i.e., a localized infection inthe periapical conditions) (Nair 1997; Abbott2004b, 2016). These conditions should be man-aged with root canal treatment or extraction. Theydo not require systemic antibiotics, and adminis-tration of such agents should be avoided in orderto reduce the potential problems of bacterial resis-tance and patient sensitization to antibiotics. Sys-temic antibiotics will not help to resolve thedisease since the antibiotic will not be distributedto the site of infection as there is no blood supplyto the root canal once the pulp has necrosed, andespecially once the tooth has become pulpless, orif it has had previous root canal treatment.

Systemic antibiotics are occasionally neededfor some patients with infected root canal systems– such as when the bacteria have spread from theroot canal system to the adjacent jaw and beyond– that is, a spreading infection (TherapeuticGuidelines 2012a). However, in most cases of aninfected root canal system, systemic antibioticsshould only be used when the patient has definitesigns of systemic infection – that is, malaise,fever, increased body temperature, or lymphnode involvement. Systemic antibiotics may alsobe considered when the patient is immunocom-promised. In any patient where systemic antibi-otics are indicated, it is also essential to providethe appropriate dental treatment (commence rootcanal treatment or extract the tooth) as suchinterceptive treatment is the most predictable

means of reducing the number of bacteria presentand thus leads to far more rapid resolution ofsymptoms. Removing as many bacteria as possi-ble via dental treatment also reduces the numberof bacteria that could develop resistance, thusreducing the chances of potential complications(Therapeutic Guidelines 2012a).

If the patient has developed severe swellingand/or a spreading infection as a result ofan infected root canal system, then prompt andthorough treatment is required. These cases typi-cally require aggressive therapy in the form ofextraction or root canal treatment in conjunctionwith systemic antibiotics given intramuscularly orintravenously in a hospital setting, particularly ifthe airway has become involved. Further discus-sion of such conditions is presented later in thischapter.

If a patient does require antibiotics, then theantibiotics should only be considered as anadjunct to the treatment provided to the tooth.The antibiotics should only be required for ashort term – typically 4–5 days in most cases – ifadequate dental treatment has been provided. Theantibiotic chosen should be one with a narrow, butappropriate, spectrum of activity. Its dose needs tobe high enough to be effective since higher dosesare more likely to rapidly kill or inhibit bacteriabefore they can develop resistance and survive(Therapeutic Guidelines 2012a). The principlesof “selective pressure” apply whereby the stronger(i.e., more resistant) species survive while theweaker (i.e., less resistant) species die. If thestronger species survive, then resistance becomesmore common, the antibiotic is less effective andthe infection continues.

When patients display systemic symptoms butthere is no sign of a spreading infection – that is, alocalized abscess – then oral administration ofantibiotics is indicated. The typical bacteria asso-ciated with infected root canal systems and thathave been isolated from periapical abscesses arequite susceptible to phenoxymethyl penicillin(commonly known as penicillin V). They arealso susceptible to amoxicillin, but this is abroader spectrum drug that is commonly usedfor many infections in humans (Baumgartnerand Xia 2003; Skucaite et al. 2010). Hence,


phenoxymethyl penicillin is considered to be thebest “first choice” drug to use as long as thepatient is not hypersensitive to penicillin. If thepatient is hypersensitive to penicillin, thenclindamycin is recommended. See Table 4 forrecommended dosing regimens.

Treatment and Preventionof Odontogenic MaxillofacialInfections

Several causes exist in the development of maxil-lofacial fascial space infections; however,odontogenic issues, mostly untreated periapicalinfection and pericoronitis, account for the greatmajority of clinical presentations (Figs. 39 and40). Socioeconomic factors and inappropriatefirst-line medical and surgical management epi-sodes underlie many preventable and seriousmaxillofacial infections.

Principles of Management

The key to effective management of fascial spaceinfections is to recognize the severity of the infec-tion and the potential for patient decompensation.In doing so, the patient’s treatment should betailored to ensure that medical and surgical treat-ment is adequate, and it is located and timedappropriately. Attempts have been made to quan-tify severity (Flynn 2000) in order to assistin treatment planning, but this is not practical,as the patient’s condition is changeable andinfluenced by multiple factors. The factorsinfluencing severity are summarized in Table 5.In terms of the infection itself, the rate of progres-sion, location, and state of the airway are the most

Table 4 Recommended antibiotics for a localized odontogenic infection where the patient displays systemic symptomsand/or signs. Refer to (Therapeutic Guidelines 2012b) for further details and alternative antibiotics

If there is NO history of allergy/hypersensitivity to penicillin

Recommended antibiotic Adult dose regimen Child dose regimen

Firstchoice

Phenoxymethylpenicillin (alsoknown as penicillinV)

500 mg to be taken orally every 6 h on anempty stomach (i.e., 1 h before meals) for5 days (an initial loading dose of 1000 mgcan be considered)

12.5 mg/kg up to 500 mg, to betaken orally every 6 h on an emptystomach (i.e., 1 h before meals) for5 days

Secondchoice

Amoxicillin 500 mg to be taken orally every 8 h for5 days (an initial loading dose of 1000 mgcan be considered)

12.5 mg/kg up to 500 mg, to betaken orally every 8 h for 5 days

If there IS a history of allergy/hypersensitivity to penicillin

Recommended antibiotic Adult dose regimen Child dose regimen

Clindamycin 300 mg to be taken orally every 8 h for5 days (an initial loading dose of 600mg canbe considered)

7.5 mg/kg up to 300 mg, to be takenorally every 8 h for 5 days

Fig. 39 Buccal and submandibular space involvementand abscess progression


important factors. Patient-specific factors includ-ing age and medical-comorbidities are taken intoconsideration because of the importance of thehost response in the presence of potentially life-threatening infection. If in doubt, the decisionregarding management should be made by anoral and maxillofacial surgeon.

Medical Management

In some situations, where infection is localized inthe buccal or canine space and the patient is not

unwell or in systemic inflammatory response syn-drome (SIRS), it may be treated with a conserva-tive approach, on an out-patient basis, withregular follow-up and definitive management.This might include a localized infection resultingfrom a recently restored or endodontically treatedtooth. In such a situation, it may be appropriate torefer the patient for a single dose of intravenousantibiotics for loading before commencing oralantibiotics. In more serious infections, or incases where there is no improvement despiteattempts to manage conservatively, intravenousaccess should be obtained to facilitate fluid resus-citation and intravenous antibiotic therapy. Empir-ical antibiotics should be used initially, and thenthey can be tailored according to the results ofmicrobiological testing.

It is essential to recognize reduced patientreserve in even seemingly minimally complicatedinfections because of the risk of rapid progressionand host compromise. It is the balance betweenmicrobial virulence and host immunity that deter-mines the extent of spread and ultimately the riskof morbidity and death. The host response tosevere infection can cause physiologic disruptionto the patient, increasing insensible fluid losses,and caloric requirements. Blood sugar levels mustbe monitored and controlled, and all patients withdiabetes should be managed collaboratively withan endocrinologist. Not only do these patientshave increased susceptibility to odontogenicinfections, requiring prolonged hospital admis-sion, but they have reduced resistance to themore severe sequelae such as necrotizing fasciitisand Ludwig’s angina (Figs. 41 and 42). Othermedical team members may include the generaland infectious disease physicians, and intensive

Table 5 Multifactorial influence on the patient condition in determining the severity of infection and decision making bypractitioners

Patient/host factorsInfection/pathology factors Practitioner factors

AgeImmune compromisePoly-pharmacyPrevious/preceding infectionLifestyle factors including smoking tobacco, alcoholconsumption, and other drug use

Source ofinfectionNeck spaceinvolvementAirwaycompromiseRate ofprogression

Level of experienceConfidence in diagnosing andmanaging infectionAbility to manage complicationsAirway skillsAccess to hospital facilities anddiagnostic imaging

Fig. 40 Buccal space collection 12 weeks post lower rightthird molar surgery following repeated course of antibi-otics. Extension into subcutaneous tissues


care doctors, depending on the requirements ofthe patient. Input by allied health care profes-sionals such as dieticians and speech pathologistsis also an essential part of management. Nutritionshould be optimized to ensure wound healingand to avoid excessive catabolism. Speech pathol-ogists may be particularly helpful in the manage-ment of a tracheostomy or oropharyngealdysfunction.

Antibiotic Therapy

Neck space infections are usually polymicrobialin nature, and the bacteria are part of the normaloral microbiota. When local and systemic hostdefenses are overcome, these commensalsbecome pathologic. Local host defenses includeanatomical boundaries, and these may bebreached as a result of inflammation or injury,causing direct bacterial contamination of tissues,hematogenous or lymphatic spread.

Empirical therapy is commenced ideally afterpus, blood, or tissue samples are obtained formicroscopy, culture, and sensitivity testing.These cover the β-hemolytic streptococcus and

associated anaerobic bacteria such as Peptostrep-tococcus, pigmented Bacteroides, Prevotella, andPorphyromonas, all of which have been describedas causative agents in odontogenic infections.Other isolates include viridans streptococciand S. milleri (part of the S. anginosus group)S. aureus, and S. epidermis, and Actinomycesspecies. A penicillin derivative in addition to met-ronidazole is usually recommended. Penicillinscombined with a beta-lactamase inhibitor such asclavulanic acid are an alternative to dual therapyand have been shown to be effective againstanaerobic infection. In cases of penicillin allergy,clindamycin is the drug of choice. In severe infec-tions gentamycin may be recommended in addi-tion to tazocin (pipercillin/tazobactam) andvancomycin (Har-El et al. 1994).

Surgery and Drainage

While cellulitis alone may be treated with antibi-otic therapy, surgical treatment by way of incisionand drainage has the advantage of decompressingneck spaces for airway protection in addition tofacilitating removal of pus. The presence of pus isoften underestimated on clinical and radiologicalassessment, so the threshold for intervention

Fig. 42 Ludwig’s angina. Bilateral involvement of sub-lingual and submandibular spaces (arrows)

Fig. 41 Ludwig’s angina. Overlying cellulitis marked tomonitor clinical progression


should be low, particularly in infections that fail torespond to medical management. Surgery alsoallows a thorough examination under anesthesia,for the source of infection to be removed (usuallyby tooth extraction) and for tissue samples of anyassociated pathology to be taken. The principlesof surgical drainage have been well documentedby other authors. In particular, the incision shouldbe placed in healthy skin and mucosa when pos-sible, in a natural skin fold and in a dependentposition (Fig. 43); dissection should be blunt; anddrains should be placed initially and removedwhen the discharge is minimal (Topazian et al.2002). Incisions may be intra- or extraoraldepending on these principles and the severity ofinfection and location, but the process of makingsuch decisions is beyond the scope of this chapter.In general, an extraoral approach is preferred formoderate-to-severe infections, with placement ofextraoral drains, because of the dependenceof drainage (Bottin et al. 2003). A combinedintra- and extraoral approach is not uncommonin multilevel deep neck space involvement.Through-and-through drainage has the advantageof two portals of pus drainage, but it is not realisticto expect to be able to irrigate the neck withdependent flow from the oral cavity out of theneck incision. Common drains include Penrose,which is similar to the cut finger of a glove and thecorrugated or Yeates drains. They assist in drain-age of pus by capillary action. Drains have thedisadvantages of being a portal of infection in to

the wound, and they are uncomfortable and con-tribute to scarring.

Some patients may require multiple drainageand wash-out operations, particularly if they failto respond to treatment or re-collect pus in thesame or other previously uninvolved neck spaces.These patients usually have identifiable host fac-tors causing reduced immunity or a particularlyvirulent organism or both. Thus, in the postoper-ative phase, regular clinical and biochemicalassessment is necessary, and further radiologicalassessment may also assist in the decision toreturn to theater. Other causes of treatment failureinclude incorrect diagnosis or inadequate primarysurgical intervention or medical management.

Airway Considerations

Unrecognized impending airway loss due to pro-gression of infection/swelling and patient fatiguecauses asphyxiation and death (Fig. 44). Closeliaison with anesthetic staff should facilitate safeand timely general anesthetic for patients with anemergent airway or if access to the airway hasbeen significantly impeded by trismus or swell-ing. Safe options for such patients include awakefiber-optic intubation and urgent elective trache-ostomy under local anesthetic. Tracheostomyallows the upper airway obstruction to be

Fig. 44 Axial CT (level of mid ramus) showing abscessformation within left parapharyngeal space (arrows) andshift of the airway to contralateral side

Fig. 43 Access to left pterygoid space via submandibularapproach for dependent drainage


bypassed to facilitate intraoperative patient venti-lation and resolution of the obstruction in thepostoperative phase. It has been suggested thatelective tracheostomy should be the airway ofchoice in Ludwig’s angina (Parhiscar and Har-El2001) in order to avoid failed intubation andfacilitate patient weaning. It is, however, rarelyperformed in developed countries, due toadvanced anesthetic techniques and equipment.It may be appropriate to keep some patientssedated and ventilated postoperatively to allowresolution of swelling prior to extubation.

Prevention of Infection

Prevention of oral disease, most notably caries,periodontitis, and pericoronitis, is a complex andmultifaceted. A significant proportion of patientsusually seek treatment from their general dental ormedical practitioner before presenting to hospital(Bridgeman et al. 1995), and so it falls on thesepractitioners to make potentially life-saving deci-sions. From a surgeon’s perspective, the key ele-ments of preventing life-threatening neck spaceinfections are to:

1. Recognize and diagnose early.2. Treat localized infection the first time it occurs

and not allow it to progress to a chronic(or acute-on-chronic) problem.

3. Remove the source of infection, which mayrequire extraction of one or multiple teeth.

4. Drain pus on presentation.5. Refer the patient early and do not hesitate to

speak directly with the admitting team toobtain advice and/or keep them abreastof recent events. Good communication canpotentially be life-saving.

Osteomyelitis, Osteoradionecrosis(ORN), and Antiresorptive Agent-Induced Osteonecrosis of the Jaws(ARONJ)

Osteomyelitis, osteoradionecrosis (ORN), andanti-resorptive-induced osteonecrosis of the jaws(ARONJ) are potentially devastating chronic

pathologic conditions of the jaws. Accurate diag-nosis and differentiation between them is essen-tial, and in particular, underlying bony pathologyor malignancy needs to be ruled out. While oste-omyelitis may occur in isolation, patients withORN and ARONJ may develop osteomyelitissecondarily. Combined surgical and medical man-agement is often required, and they are difficult totreat.

Osteomyelitis of the Jaws

Osteomyelitis is inflammatory destruction of thebone marrow. The condition is summarized inTable 6. The aetiology of osteomyelitis of thejaws is usually, but not always, microbial. Con-ventionally, secondary osteomyelitis is identifiedas a microbe-induced progressive inflammation ofthe bone marrow of the jaws that may or may notresult in suppuration (pus formation). The sourceof infection is usually odontogenic and may betriggered by inoculation of bacteria during dentalextraction or root canal therapy. Infection, inflam-mation, and pus spreads via haversian andVolkmann’s canals through the marrow and thento the cortices and periosteum towards oralmucosa or skin. When advanced, the skin mayrarely be involved, resulting in oro-cutaneousfistulation.

Staphylococcus aureus, Staphylococcus epi-dermis, and Pseudomonas aeruginosa are some-times reported from chronic abscesses andosteomyelitis, especially in immunocompromisedsubjects. These exogenous opportunistic patho-gens can cause infection during operative proce-dures or by gaining access through sinuses (Marshand Martin 1999). A more recent microbiomicstudy of chronic osteomyelitis of the jaws demon-strated the highly polymicrobial nature ofthis disease, with an average of 80 bacterial spe-cies detected in each sample. F. nucleatum,P. gingivalis, and T. denticola were among thecore microbiome associated with disease althoughfurther work is needed to elucidate the bacterialaetiology of disease (Goda et al. 2014). Osteomy-elitis can be extremely difficult to eradicate with-out extensive and often repetitive surgicaldebridement (see above). The major virulence


factors or characteristics of bacteria associatedwith osteomyelitis include biofilm formation thatlimits the efficacy of antibiotics and the innate

host defense, invasion of and replication withinhost cells including osteoblasts and genomicdiversity and horizontal gene transfer that enablethe emergence of phenotypic variants includingpersistent cells that have limited antibiotic suscep-tibility (Loughran et al. 2016).

The radiological characterization of osteomy-elitis is varied and assists in the diagnosis.Plain radiographic appearances include boneresorption and osteolysis, osteosclerosis, mixedradiolucency/radio-opacity with a moth-eatenappearance, onion-peeling, periosteitis, sequestra-tion, and cortical discontinuity indicative of path-ological fracture. Some examples of these easilyrecognizable abnormalities are given in Fig. 45.Useful summaries of the options for diagnosticimaging have been published (Underhill et al.2003; Pineda et al. 2009), and a more detaileddescription outlined in the chapter on diagnosticimaging in this textbook.

For completeness, it should be noted that thereare other forms of marrow inflammation that donot present or progress in this conventional man-ner and that may not be associated with a (detect-able) bacterial pathogen. These conditions arelabeled as primary osteomyelitis by some authors(Bevin et al. 2008) and they occur in specificsituations and may be age dependent. They areincluded in the classification of osteomyelitis in

Fig. 45 Plain film radiographic bony changes inosteomyelitis

Table 6 Summary of key features of osteomyelitis

Definition Inflammation of bone marrow

Aetiology Usually infectious-bacterial infection

Pathogenesis Contiguous spread from odontogenicinfection or traumaHematogenous spreadLymphatic spread

Natural history Progressive in nature with potentialfor extension in to thetemporomandibular joints (septicarthritis), periosteum (peri osteitis), orcollection of pus (abscess)

Risk factors –local

Reduced vascularity of tissuesMobile fractureUnderlying bony pathology – benignor malignant

Risk factors –systemic

Immune compromiseSteroid therapyAntiresorptive agentsSmokers

Symptoms AsymptomaticPainSwellingReduced mouth openingNumb lip and chin (Vincent’s sign)Systemic symptoms of infection

Clinical signs TrismusErythema and cellulitisFever and malaiseLymphadenopathy

Keyinvestigations

Blood tests: FBE, CRP, ESR, renaland liver function testsOPGCTMRINuclear medicine techniquesMicroscopy, culture, and sensitivitiesHistopathologyTetracycline and Woods (UV) lamp todetect necrotic bone

Treatment Surgical – Removal of source ofinfection, debridement,sequestrectomy, saucerization,decortication, drainage of pus,resection, fracture immobilization,reconstruction, and dentalrehabilitationMedical – Infectious disease teaminput with long-term antibioticcoverageAdjunctive – Hyperbaric oxygentherapy


Table 7, with references listed for additional read-ing, but further discussion is beyond the scopeof this chapter. There are multiple classificationsfor osteomyelitis, as suggested by Lew andWaldovgel (1997), Topazian et al. (2002), andHudson (1993). However clinically, it is usefulto consider whether the disease is focal or diffuse,acute (up to 4 weeks) or chronic (>1 month),and suppurative versus nonsuppurative (Sueiet al. 2005).

Osteomyelitis is more common in the mandi-ble due to poorer blood supply and denser corti-ces, as compared to the maxilla (Fig. 46). Factorsthat affect vascularity also include increasingage, smoking, and other pathology that adverselyaffects local blood supply such as radiotherapy,osteopetrosis, Paget’s disease of bone, and fibro-osseous diseases. Blood supply is further reducedby increased medullary pressure, pus formation,and periosteal stripping, exacerbating the patho-logical process. The aim of surgical treatment (seeTable 5) is to reduce bacterial load, increase vas-cularity of the site, and enable primary closure atthe affected site.

Osteoradionecrosis

Osteoradionecrosis (ORN) is progressive devital-ization over time of bone that has been exposed toionizing radiation, usually following the primaryor adjunctive treatment of head and neck cancer.The condition is summarized in Table 8. Clinicalstaging represents the spectrum of severity, from asmall stable intraoral area(s) of bone exposure

(stage I) to progressive pain, chronic infection,pathological fracture, and oro-cutaneous fistula(stages II and III) (Schwartz and Kagan 2002).Table 9 delineates the treatment options accordingto stage of disease. There are multiple stagingsystems, including Marx’s initial system thatwas based on response to hyperbaric oxygen ther-apy (HBO) (Marx 1983). Schwartz and Kagan(2002) have suggested a more contemporary stag-ing based on clinical features that can be used toguide treatment.

The pathophysiology of ORN is not fullyunderstood but has been well covered byother authors (Lyons and Ghazali 2008; O’Delland Sinha 2011). There are multiple theoriesattempting to explain ORN but the main onesinclude radiation, trauma, and infection resultingin radiation osteomyelitis (Meyer 1970); hypo-vascularity, hypocellularity, and hypoxia, withaberrant wound healing due to reduced oxygensupply to the tissues (Marx 1983); andfibroatrophy due to deregulation of fibroblasticactivity in the jaws (Delanian and Lefaix 2004).Adjunctive therapies available reflect these theo-ries, and include HBO to increase tissue oxygentension (Marx et al. 1985) or pentoxifylline,tocopherol, and clodronate, a controversial newregimen suggested by some authors for the pre-vention and/or treatment of ORN by preventingfree radical damage and fibrosis (Lyons andGhazali 2008; Delanian et al. 2011).

Diagnosis of ORN relies on ensuring that thereis no underlying primary or recurrent malignancy.For this, radiography and biopsy are essential(Figs. 47 and 48).

Table 7 Classification of osteomyelitis

Diffuse Localized

Acute Acute diffuse suppurative Acute localized suppurative

Chronic > 1 month Chronic diffuse suppurativeChronic diffuse sclerosing with proliferative periositis(Garré’s osteomyelitis) (Bevin et al. 2008)Chronic diffuse sclerosing (Montonen and Lindqvist2003)May be part of SAPHO syndrome (synovitis, acne,

pustulosis, hyperostosis, osteitis) (Suei et al. 1996;Eyrich et al. 1999)Juvenile chronic mandibular osteomyelitis (Heggieet al. 2003)

Chronic localized suppurativeChronic focal sclerosing(condensing osteitis) (MacDonald-Jankowski 1999)


Surgery is indicated for the treatment of ORNin stage III disease and in failed conservativemanagement (Alam et al. 2009). Resection,extended back to bleeding, seemingly healthybone, and vascularized reconstruction may bethe only viable treatment option. An osseo-cutaneous free flap such as the fibula has beenshown to be reliable and successful in the recon-struction of resultant segmental mandibulardefects (Chaine et al. 2009).

Antiresorptive Agent-InducedOsteonecrosis of the Jaws (ARONJ)

This condition, a form of osteonecrosis of the jaws(ONJ), was first recognized in patients beingtreated with long-term bisphosphonate therapy(Ruggiero et al. 2014). More recently, it hasbeen recognized as a rare complication of anti-resorptive therapy, of which bisphosphonates areone group of agents (Fig. 49). Table 10 summa-rizes the key features of this condition.

The pathophysiology if ARONJ is still notunderstood. There are multiple theories described,and it is likely that the disease aetiology is

Fig. 46 Osteomyelitis of the left mandibular body. Therehas been previous open reduction and internal fixation ofright parasymphyseal and left mandibular fractures. Theright parasymphyseal fracture has healed (a) and there isextensive periosteal new bone formation on the buccal andto a lesser extent lingual cortices on the left mandibularbody (white arrows) in a and b. Radiolucency is present

around two of the screws in the buccal fixation plate(dotted white arrows in b and c) with irregular corticallysis (b). A gallium isotope scan with low-dose CTcoregistration shows intense uptake in the left mandibularbody consistent with osteomyelitis (black arrows in d)(Images courtesy of Clinical Associate Professor AndyWhyte, Perth Radiological Clinic, Perth WA, Australia)


multifactorial. Osteoclastic bone resorption andremodeling is inhibited by multiple agents includ-ing some bisphosphonates and denosumab,resulting in interferences in the natural (rapid)bony turnover in the jaws. It is suggested thatthis reduction in remodeling results in reducedcapacity to heal and ultimately bone necrosis

(Baron et al. 2011). A second theory is thatthe inhibition of angiogenesis may result in inter-ruption of vascular supply to bone, causingosteonecrosis (Allen and Burr 2009). Zoledronicacid is a bisphosphonate with antiangiogenicproperties (Wood et al. 2002). Other hypotheses,or more likely contributing factors, include the

Table 8 Summary of key features of osteoradionecrosis

Definition Radiation-induced devitalization and necrosis of boneIrradiated bone is exposed without healing for>3 months in absence of antiresorptive medicationor malignancy (Schwartz and Kagan 2002)

Aetiology Ionizing radiation of the jaws, usually �60Gy. The greater the absorbed radiation dose, thegreater the risk (Morrish et al. 1981)

Pathogenesis Multiple theories have been proposed but still not fully understood

Incidence 2.6–15% of people exposed to ionizing radiation (O’Dell and Sinha 2011)

Natural history ORN is a late complication of radiation exposureMay remain stable for years or progress to severe disease requiring surgical interventionNecrotic bone may become secondarily infected


High mineral content of bone, in particular posterior mandibleHigher radiation dose, higher the riskPrevious surgery to treat malignancyBulky tumors (T3/T4 stage)Usually triggered by local trauma – e.g., dental extraction or implant or dental infection – but maybe spontaneous


ImmunocompromisedConcurrent chemotherapy with radiotherapySteroid therapySmokersPoor nutritional status

Symptoms AsymptomaticBad taste (dysgeusia)HalitosisPainDysesthesiaLocal and systemic symptoms of infection including swelling, trismus, dysphagia

Clinical signs Bone exposureJaw mobilitySequestration of boneFistulationLocal and systemic symptoms of infection including erythema, cellulitis, lymphadenopathy,fever, and malaise

Key investigations Blood tests: FBE, CRP, ESR, renal and liver function testsDental panoramic tomographyComputerized tomography (CT)Magnetic resonance imaging (MRI)Nuclear medicine techniquesHistopathologyMicroscopy, culture, and sensitivities

Prevention Dental prophylaxis and treatment as required, particularly to manage radiation-inducedxerostomia and high caries riskExtraction of teeth with dubious prognosis 2–3 weeks prior to commencement of radiotherapyOral hygieneAvoidance of tobacco, alcohol, ill-fitting denturesIntensity-modulated radiation therapy (IMRT)


presence of inflammation or infection or complexpolymicrobial biofilms in the oral cavitythat make the jaws specifically susceptibleto osteonecrosis (Sedghizadeh et al. 2008), poten-tial soft tissue toxicity of bisphosphonates(Landesberg et al. 2008), the presence of innateor acquired immune dysfunction (Sonis et al.2009), and microtrauma of tissues due to oralfunction (Figs. 50 and 51).

Treatment of ARONJ is dependent on thestage of disease and the oncological status of thepatient. The decision to treat a patient with or atrisk of ARONJ should be made in full consulta-tion with the patient’s physician or oncologist andan oral and maxillofacial surgeon. A positionpaper of the American Association of Oral andMaxillofacial Surgeons (AAOMS; (Ruggiero

et al. 2014)) outlines the complexities in decisionmaking and the risk of developing ARONJaccording to type and duration of therapy.Table 11 is a summary of treatment according tothe stage of the disease. The aim of treatment is toeliminate pain, control infection, and minimizeprogression of necrosis. Unproven adjunctivetherapies include HBO, platelet rich plasma,bone morphogenic protein, and parathyroidhormone.

Conclusion and Future Directions

The jaw bones have a predisposition to develop-ing varying forms of infection and osteonecrosis.The mandible is more predisposed to necrosis,when compared to the remaining skeleton,because of its high bone turnover and ingress ofbacteria through minor breakdown portals in theoral mucosa or the dentition. Radiotherapy andbisphosphonate medication have been discussedas important contributors.

Advances in imaging, and the ability to replaceand reconstruct diseased hard and soft tissues,have been numerous in the last two decades.Microvascular and tissue transfer techniques com-bined with dental implantology are currently themainstay for rehabilitation. Tissue engineering,the use of biological scaffolds, and the emergingsuccess of targeted stem cell use combined withthese technologies may have a place in maxillaryand mandibular reconstruction. It remains to be

Table 9 Treatment of osteoradionecrosis by stage (Schwartz and Kagan 2002)

Stage Clinical features Treatment

I Exposure of boneSuperficial with minimal ulcerationAsymptomatic

Antibiotic therapy if infectionTopical antiseptic, e.g., chlorhexidine

II Localized mandibular involvement; cortical andmedullary necrosis; possible oro-cutaneous fistula

Consideration of conservativedebridement, sequestectomy,saucerization

A – Minimal softtissue involvement

B – Extensive softtissue involvement

III Diffuse mandibular involvement to lower borderPathological fractureOro-cutaneous fistula

Surgery with possible resection andvascularized reconstructionA – Minimal soft

tissue involvement

B – Extensive softtissue involvement

Fig. 47 Panoramic tomograph of stage III osteoradio-necrosis (ORN) with full-thickness moth-eaten appearanceand pathological fracture


seen whether these can be used during the activephases of infection or varying forms ofosteonecrosis, to curb or inhibit the progress ofthese pathologies.

At present mandibular osteonecrosis is a rela-tively uncommon condition, but its relevance liesin the fact that no cure is forthcoming. Those who

are at risk require a lifetime of extreme prophy-lactic dental care. There are clear consequencesand relevance of this topic to the dental and med-ical professions. Several new cancer drugs arereported to induce osteonecrosis. As oncologicaloutcomes improve, the number of patients pre-senting with ARONJ will increase.

Fig. 48 Osteoradionecrosis (ORN) of the left mandibularbody. Eighteen months post radiotherapy for an oropha-ryngeal carcinoma, an oblique sagittal CT reconstructionshows extensive irregular radiolucency and sclerosiswithin alveolar and basal bone in the molar region of theleft mandibular body with involvement of the IAC. Thereis a nonhealed 38 socket, destruction of the crown of37 and distal caries in 36 (dotted black oval in a). Thereis similar but less marked changes of ORN in the left

posterior maxillary alveolus (white dashed oval in a) withextensive distal caries in 27 and mucosal thickening in theleft maxillary sinus. Following a left hemi-mandibulectomy, reconstruction with a fibula flap andextraction of the left posterior maxillary teeth (b), ORNhas progressed in the left maxilla (white dotted oval in b)and also the left ramus. (Images courtesy of Clinical Asso-ciate Professor Andy Whyte, Perth Radiological Clinic,Perth WA, Australia)

Fig. 49 Radiographic evidence of bisphosphonate-relatedosteonecrosis of the jaw involving the posterior left man-dible, angle and extending into the ramus. Other

radiographic features not described (Image courtesy of DrMarie Anne Matias, Dento-maxillofacial Radiologist,Qscan Radiology Clinics, Brisbane QLD, Australia)


Table 10 Summary of key features of antiresorptive agent-induced osteonecrosis of the jaws (ARONJ)

Definition Antiresorptive agent-induced osteonecrosis of the jawsPeople exposed to systemic antiresorptive therapy in absence of radiation therapy or malignancyresulting in nonhealing lesions lasting greater than 8 weeks (Ruggiero et al. 2014)

Aetiology Bisphosphonates – intravenous or oralRANK ligand inhibitors – e.g., denosumabAntiangiogenic medication – e.g., VEGF inhibitors, tyrosine kinase inhibitors

Pathogenesis Multiple theories have been proposed but still not fully understood

Incidence 0.7–7% in patients being treated for malignancy (3% best estimate after tooth extraction)0–0.2% in patients being treated for osteoporosis (0.5% best estimate after tooth extraction)10% patients on antiresorptive therapy for renal cell carcinoma

Natural history May remain stable for years or progress to severe disease requiring surgical interventionNecrotic bone may become secondarily infected


Operative treatment – dentoalveolar surgeryOral diseaseTraumatic denturesMandible (vs. maxilla)


Increased risk in:Dose – higher dose and intravenous administrationCumulative dose – longer duration of therapyDrug typeIndication – therapeutic indications, particularly malignancy (bony metastases and multiple

myeloma)Immune-deficiency, particularly simultaneous administration of steroids and diabetesComorbidities including anemiaSmokersPotential genetic susceptibility

Symptoms AsymptomaticBad taste (dysgeusia)HalitosisPainDysesthesiaLocal and systemic symptoms of infection including swelling, trismus, dysphagia

Clinical signs Bone exposureJaw mobilitySequestration of boneFisulationLocal and systemic symptoms of infection including erythema, cellulitis, lymphadenopathy,fever, and malaise

Key investigations Blood tests: FBE, CRP, ESR, renal and liver function tests; CTX (C-telepeptide) as a measure ofbone turnoverDental panoramic tomographyComputerized tomography (CT)Magnetic resonance imaging (MRI)Nuclear medicine techniquesHistopathologyMicroscopy, culture, and sensitivities

Prevention Dental screening, prophylaxis, and treatment of patients about to commence antiresorptivetherapyExtraction of teeth with dubious prognosis and healing prior to commencement of drug therapyOral hygieneAvoidance of tobacco, alcohol, ill-fitting dentures, or other risk factorsDrug holiday (if indicated) (Ruggiero et al. 2014)


Fig. 50 Medication-induced osteonecrosis of the jawright mandible. Current treatment with antiresorptiveagents with exposed bone in the 47 region for over8 weeks. Sagittal (a) and axial (b) reconstructions from aCT scan demonstrate a nonhealed 47 socket, ill-definedlysis, and sclerosis in adjacent alveolar bone. Periodontitis

is present around the anterior mandibular teeth. Defects inthe buccal and lingual cortices (white arrows in b) suggestincipient sequestrum formation (Images courtesy ClinicalAssociate Professor Andy Whyte, Perth RadiologicalClinic, Perth WA, Australia)

Fig. 51 Medication induced osteonecrosis of the jaw.Cone Beam CT shows focal areas of necrosis involvingthe lingual tori on the right side (arrows). This patientpresented with pain in the anterior right mandible was onActonel (risedronate) but also had a history of breast cancer(Image courtesy of Dr Marie Anne Matias, Dento-maxillofacial Radiologist, Perth Radiological Clinic,Perth WA, Australia)


Cross-References

▶Classification of Orofacial Pain▶Clinical Evaluation of Oral Disease▶Diagnostic Imaging Principles and Applica-tions in Head and Neck Pathology

▶Gingival Pathology▶LaboratoryMedicine and Diagnostic Pathology▶Non-Odontogenic Bacterial Infections▶Non-Odontogenic Bone Pathology▶Odontogenic Pathology▶Orofacial Pain in Patients with Cancer andMucosal Diseases

▶Orofacial Pain in the Medically ComplexPatient

▶ Pharmacotherapeutic Approaches in OralMedicine

▶ Soft and Hard Tissue Operative Investigationsin the Diagnosis of Oral Disease

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Adler CJ, Dobney K,Weyrich LS, Kaidonis J, Walker AW,Haak W, Bradshaw CJA, Townsend G, Soltysiak A,Alt KW, Parkhill J, Cooper A. Sequencing ancientcalcified dental plaque shows changes in oral micro-biota with dietary shifts of the Neolithic and Industrialrevolutions. Nat Genet. 2013;45(4):450–5.

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Table 11 Treatment of established antiresorptive agent-induced osteonecrosis of the jaws (ARONJ) by stage, modifiedfrom the AAOMS position paper 2014 (Ruggiero et al. 2014)

Stage Clinical features Treatment

Atrisk

None Prevention measures

0 Nonspecific symptoms andradiological changes

Analgesia and antibiotics as required

I Exposure of boneIntraoral fistulationNo evidence of infection

Antiseptic rinsesReview of antiresorptive therapyRegular follow-up

II Stage I but with infection +/�pus

Stage I with addition of antibiotic therapyConservative debridement to relieve soft tissue irritation andsequestrectomy as required with primary closure if possible

III Stage II but with one or moreof:Involvement of basal bonePathological fractureOro-cutaneous fistulaOro-nasal communicationborderPathological fractureOro-cutaneous fistula

Stage II but with more extensive surgical debridement or resection andmicrovascular reconstructionPalliation for patients with poor prognosis


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http://link.springer.com/Orofacial Pain in Patients with Cancer and Mucosal Diseases

http://link.springer.com/Orofacial Pain in Patients with Cancer and Mucosal Diseases

http://link.springer.com/Orofacial Pain in the Medically Complex Patient

http://link.springer.com/Orofacial Pain in the Medically Complex Patient

http://link.springer.com/Pharmacotherapeutic Approaches in Oral Medicine

http://link.springer.com/Pharmacotherapeutic Approaches in Oral Medicine

http://link.springer.com/Soft and Hard Tissue Operative Investigations in the Diagnosis of Oral Disease

http://link.springer.com/Soft and Hard Tissue Operative Investigations in the Diagnosis of Oral Disease

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