© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Periodontology 2000, Vol. 65, 2014, 178–189 Printed in Singapore. All rights reserved
PERIODONTOLOGY 2000
Acute focal infections of dental origin I N G A R O L S E N & A R I E J.
VAN
WINKELHOFF
‘Dental focal infections are back with a bang’. This was the title of an editorial in the Journal of American Dental Association in January 1998 (21). Actually, dental focal infections have never been absent, but our attention is now being refocused on these infections. Egyptian physicians knew, already in 1500 BC, that tooth infections had to be treated carefully to prevent life-threatening complications. In 1891, Miller (44) published his theory on focal infection suggesting that oral microorganisms and their products are able to affect parts of the body adjacent to or distant from the mouth. Hunter (25) reprimanded dentists who allowed development of chronic abscesses in the oral cavity, and he believed that necrotic teeth could represent foci of infection causing arthritis, heart disease and other unexplained diseases. Billings (9) also speculated that infected teeth and tonsils could be responsible for a number of focal infections such as arthritis, rheumatism, nephritis, endocarditis and other diseases. The bacteria and their products were assumed to reach these sites through bone cavities, blood or lymph vessels, and even along nerves. Thoden van Velzen et al. (61) suggested three different ways by which oral bacteria can cause nonoral disease: (i) metastatic inflammation as a result of immune injury; (ii) metastatic injury from microbial toxins; and (iii) metastatic infection as a result of the translocation of bacteria. The focal infection theory was prevalent in the 19th century and at the start of the 20th century, particularly in the USA. It resulted in an orgy of tooth extractions, even in patients with the simplest forms of gingivitis. The practitioners performing this ‘treatment’ were called ‘hundred percenters’ because they tended to extract all teeth without considering the extent of the disease (55). The theory fell into mistrust and was gradually dismissed. Currently it is back, allegedly with a bang, although in a new perspective (23). The main reason for this is that a number of epidemiological
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studies have demonstrated the association between chronic oral infections (particularly marginal periodontitis) and systemic diseases, such as cardiovascular diseases, stroke, diabetes, low birthweight of babies born prematurely, respiratory infections and rheumatoid arthritis (15, 33, 35). These issues are the realm of periodontal medicine and will not be dealt with in the current review which is focused on acute dental focal infections. Thus, the association of dental infections with systemic health is broad and is not covered to its full extent in this article. The oral cavity contains a wide variety of organisms, including viruses, fungi and protozoa, but bacteria are the most abundant. This article will focus only on bacteria. However, bacteria may occasionally cause systemic disease in concert with viruses and yeasts, particularly in the compromised host. These organisms may also cause focal infection on their own. Oral infections are among the most prevalent infectious diseases of mankind. Being mostly chronic in nature, they relatively rarely lead to acute or dramatic consequences for the patient. However, medically compromised subjects may be at risk even for chronic oral conditions particularly if their immune system is weak. In fact, translocation of oral bacteria to nonoral sites may lead to an infectious process, even in immunocompetent subjects.
Acute oral infections Acute oral infections are diseases that have a rapid onset, severe symptoms and a short course as opposed to chronic oral infections.
Pulpitis The pathogenesis of oral focal diseases has been classically attributed to dental-pulp pathologies and
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peri-apical infections (10). The main causes for inflammation of the dental pulp (pulpitis) are bacteria and their metabolites, which reach the connective tissue of the pulp via small canals in the dentine. The bacteria are located in caries lesions, in cracks along tooth restorations or in tooth crowns. Pulp inflammation can also develop as a result of trauma, such as following crown or bridge preparation. Toxic effects from filling materials can also cause pulp inflammation. Acute pulpitis may induce almost intolerable pain. At the onset, the pain is induced by external influences such as sweets and acid food or cold. Later, the pain can be provoked by heat. Acute intervention involves excavation of carious lesions and removal of the coronal part of the inflamed pulp tissue. Subsequently, extirpation of the remaining pulp and widening of the root canal are performed, resulting in filling of the root canal and a coronal restoration. The root canal is sealed off to prevent invasion of oral bacteria and release of their products into the surrounding tissues.
Apical periodontitis Untreated pulpitis will sooner or later lead to pulp necrosis. The necrotic tissues of the crown and root pulp serve as a locus minoris resistentiae and allow oral obligate anaerobic and facultative anaerobic bacteria to cause infection. Pulp necrosis will result in inflammation of the tissue around the root apex. Inflammatory mediators, produced by macrophages and lymphocytes, will recruit and activate osteoclasts, resulting in peri-apical bone loss. This process may develop over years without overt clinical symptoms. Histologically, the tissue around the apex can be characterized as granuloma, abscess or cyst. The balance between organisms and the immune defense can be altered by overgrowth of more virulent bacteria, resulting in aggravation and acute pain. The pain can, similarly to pulpitis, become severe, particularly if pus from the apical focus accumulates below the periostium. The succeeding sequence can be abscess formation, perforation to the maxillary sinus and, in serious cases, the infection can spread as a gravity abscess or phlegmon with infiltration of neighboring regions. In some cases a fistula will develop, which may allow accumulated pus to drain and therefore a decrease in symptoms will occur. Acute pain can also develop during root-canal treatment if infected and necrotic pulp/root-canal material is forced into the peri-apical area. Maxillary sinusitis can cause otitis and temporomandibular joint symptoms that may resemble the pain from pulpitis and apical periodon-
titis. However, in sinusitis several teeth will be sensitive to percussion and the pain is aggravated when the patient bends forward.
Pericoronitis A frequent acute condition in the mouth is pericoronitis. Pericoronitis occurs around a partially erupted third molar and frequently occurs in the mandible of young individuals. As a result of the lack of local dental hygiene, a biofilm containing predominantly gram-negative anaerobic rods, spirochetes and cocci develops in the pericoronary space. The acute condition is characterized by severe pain, rubor, swelling, suppuration and problems with swallowing. Trismus may also occur.
Phlegmon and abscess formation Phlegmon (a spreading diffuse infectious process in the connective tissue with formation of suppurative/ purulent exudate or pus) and abscess formation usually result from apical periodontitis but can also be initiated by severe chronic periodontitis and pericoronitis. The symptoms can vary from local swelling and rubor to more pronounced swelling with risk of infection spreading to neighboring regions. Most of these infections are drained through fistulas into the oral cavity. However, infection may spread to neighboring regions such as the maxillary sinus, the sublingual, submandibular and infraorbital regions, orbit and brain, and to the parapharyngeal space, ending up in mediastinitis. In rare cases, so-called cervical necrotizing fasciitis can develop.
Necrotizing ulcerative gingivitis and periodontitis Necrotizing ulcerative gingivitis is a form of necrotizing periodontal disease that affects the gingiva without involving other tissues of the periodontium (4). The infection is also known as ‘trench mouth’ and Vincent’s angina or Vincent’s stomatitis (named after the French physician, Henri Vincent). Another, older, synonym is fusospirochetal gingivitis, referring to the high numbers of fusiform bacteria and spirochetes seen in the dental plaque using dark-field microscopy. Invasion of these organisms into the gingival tissue explains the acute, necrotizing and ulcerative nature of the infection. When other periodontal tissues are involved in the infection and alveolar bone loss occurs, the condition is called necrotizing ulcerative periodontitis. A major risk factor for acute
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periodontal infections is a compromised host defense. These infections can occur in patients with HIV infection and AIDS. Also, smoking and stress have been identified as risk factors for necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis. Acute periodontal infections are discussed in detail by Herrera et al. (24) in this volume of Periodontology 2000.
Bacteremia Microorganisms in the mouth are located on the teeth and on dental restorations, in root apices, mucosa, gingival epithelium, tongue and other oral tissues and in saliva. Dental treatment, injuries and infections cause bacteremia through breaches (50). Even in healthy individuals, microbes of dental plaque (biofilm) can cause ulceration of the gingival crevicular epithelium (13). Patients with mucositis are particularly prone to dissemination of bacteria through their oral ulcers. Even toothbrushing can cause bacteremia, which may be serious in individuals at risk for infective endocarditis (36). The type of dental treatment also affects €ma €la €inen (43) the risk of bacteremia. Meurman & Ha listed dental procedures and diseases associated with bacteremia and reported that the incidence of bacteremia ranged from 100% after tooth extraction to 10% in gingivitis. The intensity of bacteremia is related to the magnitude of trauma, the density of the local microbial deposits and the presence of inflammation or infection at the site of mucosal injury (43). Phenotypic and genetic methods were used to trace microorganisms released into the blood during and after endodontic treatment back to their presumed source – the root canal (16). Microbiological samples were taken from the root canals of 28 patients with asymptomatic apical periodontitis of single-rooted teeth. Blood was drawn during, and 10 min after, endodontic therapy. Microorganisms in the blood were collected after anaerobic lysis filtration and anaerobic culture. Biochemical and antimicrobial susceptibility tests, sodium dodecyl sulfate–polyacrylamide gel electrophoresis of whole-cell soluble proteins, gas chromatography of cellular fatty acids, DNA restriction patterns and ribotyping showed identical phenotypic and genetic characteristics of the root canal and blood isolates, demonstrating that endodontic treatment can be the cause of anaerobic bacteremia and fungemia. Oral bacteria in the blood can deposit directly in coronary vessels or in atherosclerotic plaques. These bacteria are more diverse than previously thought
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and include a number of anaerobes. BahraniMougeot et al. (5) identified oral bacterial species in blood cultures following single-tooth extraction and toothbrushing. Sequence analysis of 16S rRNA genes detected 98 different bacterial species recovered from 151 bacteremic subjects. Forty-eight of the isolates represented 19 novel species of Prevotella, Fusobacterium, Streptococcus, Actinomyces, Capnocytophaga, Selenomonas and Veillonella. This was not supported in a review on oral organisms found in nonoral diseases where most translocating oral species constituted commensals of low pathogenicity (64). However, this may have resulted from problems with the culture and identification of the organisms. Probably, bacteremias also contain not-yet-cultivated bacteria from oral biofilms from which only half of the bacteria can currently be cultured. Usually, bacteremia has no consequences in healthy subjects because bacteria are quickly eliminated from the bloodstream by the reticuloendothelial system of the host. Patients with artificial devices, such as prosthetic heart valves, artificial joints and other types of implants, and patients with a history of infective endocarditis, may run a greater risk for complications from bacteremia (52, 65). van Winkelhoff et al. (65) described a long-standing symptomatic bacteremia caused by Aggregatibacter actinomycetemcomitans in a patient with a pacemaker. Attacks of fever occurred for at least 1 year. The patient also had mild periodontitis. Multiple isolates of A. actinomycetemcomitans from the oral cavity and the blood were compared using DNA fingerprinting. The isolates from the blood and the oral cavity were identical and it was concluded that the oral cavity was the probable source of the infection. Successful treatment included systemic metronidazole and amoxicillin. Invasive dental procedures can be associated with a temporary increase in risk for stroke and myocardial infarction, although the absolute risks are minimal and the long-term benefits on vascular health would probably outweigh the short-lived adverse effects. This was recently shown in a study, carried out from 2002 to 2006, based on persons exposed to invasive dental treatment with a primary hospital diagnosis of ischemic stroke (n = 650) or myocardial infarction (n = 525). The rate of vascular events significantly increased after dental treatment (incidence ratio = 1.50; 95% confidence interval: 1.09–2.06) and gradually returned to baseline levels within 6 months. The positive association persisted, even after exclusion of persons with diabetes, hypertension or coronary artery disease, or persons with prescriptions for antiplatelet or salicylate drugs (45).
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Other types of dissemination of oral bacteria Dissemination of oral bacteria to extra-oral body sites may not necessarily occur through the blood. van Winkelhoff et al. (63) described a case of conjunctivitis with dacryopyorrhea in a patient with aggressive periodontitis. The conjunctivitis had existed for 3.5 years on one eye only after the patient had suffered from ocular trauma. The patient had used multiple medications, including topical antibiotics and hydrocortisone, but without resolution of the infection. Anaerobic cultivation of pus exudate from the conjunctival sac revealed multiple anaerobes, including Prevotella intermedia and Parvimonas (formerly Peptostreptoccoccus) micra. Restriction enzyme analysis of the P. intermedia isolates from the conjunctival sac and the oral cavity revealed the same clonal type, suggesting translocation of the pathogen from the oral cavity to the eye (Fig. 1). Systemically administered metronidazole plus amoxicillin supported the mechanical periodontal treatment and resolved the conjunctivitis without recurrence of the disease. Oral bacteria can also enter the immune system through the gut and become processed in Peyer’s patches. This may result in stimulation or suppression of the immune system (13). Direct spread of dentoalveolar abscesses (e.g. to the maxillary sinus, orbit and parapharyngeal spaces) can also occur (discussed later).
Dissemination of bacterial toxins The two most important toxins of oral bacteria that can be disseminated are lipopolysaccharide (endotoxin) and exotoxin. Lipopolysaccharide is released
Fig. 1. DNA fingerprints (PstI digest) of eight Prevotella intermedia isolates. Identical profiles are seen for isolates from the conjunctive sac (lanes 4 and 5), the tongue (lanes 6 and 7) and the tonsils (lanes 8 and 9). Different profiles are seen for the Prevotella intermedia isolates from the periodontal pockets (lanes 2 and 3). Lanes 1 and 10 contain a molecular weight DNA ladder.
from disintegrating, dead gram-negative bacteria, but can also be released from the outer-membrane vesicles of viable oral bacteria. Exotoxins are proteinaceous in nature and can be released from viable gram-positive bacteria. An example of the harmful effects of oral bacterial toxins involves orofacial gangrene (noma/cancrum oris) in which Fusobacterium necrophorum displays a classic endotoxin, a dermonecrotic toxin, a cytoplasmic toxin and a hemolysin affecting hard and soft tissues of the oral and para-oral structures (18). Aggregatibacter actinomycetemcomitans, the microorganism associated with aggressive periodontitis, secretes a leukotoxin (LtxA) that helps the bacterium evade the host immune response during infection (26). LtxA is a membraneactive toxin that specifically targets white blood cells. The Streptococcus milleri group (Streptococcus constellatus, Streptococcus intermedius and Streptococcus anginosus) are important pathogens in deep neck and brain abscesses. A massive release of cytokines through a T-cell response to exotoxins produced by the S. milleri group, as reported from the toxic shocklike syndrome, has been suggested in the pathogenesis of abscess formation together with the production of tissue-destroying enzymes such as collagenase and hyaluronidase (22).
Dissemination of oral bacteria owing to incompetence in immune defense An example of dissemination of oral bacteria as a result of immune incompetence is the immunologic changes caused by anticancer drugs. The antineoplastic therapy interferes with the turnover of epithelial cells; this is followed by mucosal injury and later by infection as a result of invasion with gram-negative bacteria and fungal species. Up to 37.2% of all patients receiving cancer chemotherapy develop acute oral complications, and up to 31.1% of all patients receiving cancer radiotherapy experience acute oral manifestations, which may result in significant morbidity, treatment delays and dose reductions, affecting the prognosis of the primary disease (49). In infective endocarditis the colonizing bacteria of morbid luxurious outgrowths on denuded areas of the endocardium covering the valves of the heart evade the actions of the adaptive immune system and antibiotic therapy. This may lead to valvular insufficiency. In immunocompromised individuals, alpha-hemolytic oral streptococci cause disseminated intravascular coagulation. Similarly to infective
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endocarditis, the organisms here gain access to the systemic compartment, most often through erosive lesions of the oral and oropharyngeal mucosa, which are known as mucositis (13). After translocation, the organisms initiate disseminated activation of the coagulation cascade. In both endocarditis and disseminated intravascular coagulation, oral commensals with low pathogenicity can cause life-threatening disease. During bacteremia, with, for example, Streptococcus sanguinis, the concentration of bacterial heat shock protein increases in the blood. Antibodies to oral microbial heat shock proteins can cross-react with antigens from host heat shock proteins. As a result, immune complexes can form that activate the complement system (13). This enables a role for heat shock protein in some systemic diseases, such as immune-mediated ulcers and eruptions of the mucous membrane of the oral cavity, the eyes and the genitals (Behcßet’s disease) through heat shock protein mimicry. Mention should also be made of bacterial mimicry of host peptides (e.g. collagen fragments from the platelet aggregation-associated protein epitope of S. sanguinis). This may cause autorecognition and autoimmune arthritis (13).
Orbit Buccal space Canine space
Submasseteric space
Sublingual space Submandibular space Submental space
Lateral pharyngeal space
Retropharyngeal space
Danger space
Mediastinum
Fig. 2. Drawing showing possible pathways for dental infection to spread. Courtesy of Wiley-Blackwell. From reference (30).
logic and surgical intervention, delayed diagnosis is still responsible for a high mortality rate (about 40– 50%).
Sublingual space infection
Sequelae of acute oral infections Facial space infections Orofacial infection can, in principle, spread to the skull base or to the diaphragm. The route is largely dependent on the location of infection in relation to fasciae. A general rule is that infection spreads along the route of least resistance in subcutaneous connective tissues (phlegmon) and along fascial planes with separation of the fascial layers (30). Purulent exudates collect at locations forming a space (the fascial space). Fascial spaces communicate with each other (Fig. 2), and spread of the infection can therefore progress extensively and rapidly. Affection of vital structures in the head and neck can cause airway obstruction and mediastinitis. Despite modern therapy, fascial space infection remains a significant health problem and can potentially be fatal. Dental infection is the most common cause, but also infections in the mouth, pharynx, tonsils and salivary glands can be involved as well as trauma and surgical infections. Biasotto et al. (8) and Cirino et al. (14), reviewing the literature of descending necrotizing mediastinitis, found that, despite prompt pharmaco-
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Dental infection is most frequently the cause of sublingual space infection, but also sialolith and sublingual gland infection can be involved (30). Usually sublingual space infections originate from the roots of the mandibular anterior teeth and first molars. They often expand bilaterally. A swollen tongue is a significant clinical feature. There is communication with the submandibular space posteriorly. In 240 patients treated for mouth-floor cellulitis from 2002 to 2006, 93.7% of the infections were of dental origin (68). At the first examination the patients had extension of inflammation into the parapharyngeal and pterygomandibular spaces and the neck. In 1.7% of the patients, infection progressed to neck and parapharyngeal spaces (Fig. 3) despite treatment, and in 2% of the patients, infection resulted in mediastinitis.
Submandibular space infection The submandibular space is frequently infected (Fig. 4) through the second and third mandibular molars because of the location of the mylohyoid muscle. The boundary between the mandibular angle and the neck can then become hard to distinguish as a result of swelling (30). The masticatory muscles are
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Fig. 4. Large submandibular abscess. Courtesy of Hans Reidar Haanaes.
Fig. 3. Abscess in the neck with erysipelas reaction of the skin. Courtesy of Geir Støre.
often affected. Infection can also include the masticator and lateral pharyngeal spaces.
Submental space infection Submental space infection often involves an infected mandibular incisor. As a result of the swelling the chin may seem to protrude anteriorly. In addition, the submandibular space is often affected (Fig. 5).
Ludwig’s angina Ludwig’s angina involves infection in the sublingual, submandibular and submental spaces. There is easy communication from these spaces to the contralateral side. Most cases of infection are of dental origin. There is a firm swelling of the mouth floor and the tongue is elevated. A cellulitis is present with no tendency to abscess formation. Submandibular and sublingual spaces become involved bilaterally. An endodontic infection of a mandibular molar is often the primary infection. The patient may develop signs of toxicity, with high fever, tachycardia and malaise.
Fig. 5. Large submandibular abscess with spontaneous drainage of pus. Severe caries is present in all tooth quadrants. Courtesy of Geir Støre.
It takes only 12–24 h from the start of the swelling to the onset of symptoms of respiratory infection. Baqain et al. (6) reported a case of Ludwig’s angina caused by a dental infection that progressed to mediastinitis and pericarditis. The importance of early recognition and diagnosis of the source of deep cervical infections must be emphasized (19, 37, 38). Staphylococcus aureus and black-pigmented gram-negative anaerobic rods may indicate a high risk for developing Ludwig’s angina (53). In one patient, facial cellulitis resulted from a painless dental abscess (37).
Other facial space infections These may involve the buccal, canine, masticatory, submasseteric (Fig. 6), pterygomandibular, temporal, cervical fascial, lateral pharyngeal and retropharyngeal spaces (29). Bacterial infection of the mouth occasionally spreads to these contiguous spaces. These infections may also affect the orbital cavity (57) (Fig. 7) and the brain (Fig. 8).
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Fig. 6. Abscess in the masseter region with fistula. Courtesy of Geir Støre.
Gas gangrene and necrotizing fasciitis Dental infection is a common cause of gas gangrene and necrotizing fasciitis. These infections may spread downwards to the mediastinum, leading to mediastinitis (8, 14), pericarditis, lung infection and sepsis. They may also spread upwards to the skull base and to the meninges, or through blood vessels to give suppurative thrombophlebitis, sepsis or disseminated intravascular coagulation (30). Immunosuppressive conditions and alcohol abuse may predispose but these types of infections can also occur in healthy individuals. Factors affecting mortality are diabetes, alcohol abuse, delay of surgery and complicating mediastinitis (62).
Fig. 7. Abscess from previously traumatized tooth incised in the labial fold. Courtesy of Geir Støre.
Osteomyelitis of the jaw Both suppurative and nonsuppurative forms of jaw osteomyelitis occur. The former are the most dominant. They can be acute or chronic. Dental infections are the most common cause of osteomyelitis in the jaw, and the body of the mandible is the most common site. When there is chronically impaired blood flow and when the bone contains fibrous marrow, the jaw becomes sensitive to bacterial infection. Cranial osteomyelitis was described, by Adams & Bryant (2), to develop as a late complication of dental infection that extended subtemporally.
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Fig. 8. Computed tomography (CAT) scan of a patient with multiple brain abscesses associated with Aggregatibacter actinomycetemcomitans organisms and a poor periodontal condition.
Osteoradionecrosis of the jaw Osteoradionecrosis affects bone, particularly the mandible that has been irradiated as part of cancer treatment (Fig. 9). The radiation harms normal tissue cells and affects the blood supply in bone, cartilage
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tis and found that dental infections can cause acute maxillary sinusitis, particularly if the radiographic findings of sinusitis are severe. Many cases of recurrent acute sinusitis are caused by secondary rhinogenous bacterial colonization of the antral mucosa that has been weakened and degenerated by chronic dental infection/inflammation (31).
Peritonsillar abscess
Fig. 9. Irradiated mandible with osteoradionecrosis and superinfection. Courtesy of Geir Støre.
and soft tissue. Such tissue is susceptible to infection with oral bacteria. Until recently, a common view was that the infection of the bone was superficial and secondary (40). Several studies, using scanning and transmission electron microscopy (59), DNA–DNA hybridization (60) and 16S ribosomal DNA sequencing (1), have shown independently that the medullary parts of bone in osteoradionecrosis are heavily infected with a wide variety of facultative anaerobic and strict anaerobic bacteria, some of which are not yet cultivable.
Acute maxillary sinusitis Maxillary sinusitis usually appears unilaterally and constitutes approximately 10–12% of all cases of maxillary sinusitis (12). The etiology includes most often peri-apical dental abscesses, severe periodontitis, peri-implantitis and postextraction infection. A number of other dentally related etiologies can occur (30). Maxillary sinusitis may become chronic following the acute phase or can manifest itself as a chronic inflammation without acute episodes. Acute maxillary sinusitis is caused by bacteria invading the sinus from a focus of dental infection. Infection from maxillary premolars and molars, peri-apical abscesses, severe peri-implantitis, postextraction infection and cysts are the most common causes (7). Signs and symptoms include dull or intense pressure, erythema, swelling of cheek and anterior maxilla and the drainage of foul-smelling material. Acute maxillary sinusitis can cause orbital abscess/cellulitis (41, 42), cavernous sinus thrombosis, meningitis and intracranial abscess. In cases where the origin is a peri-apical abscess, there is toothache and swelling of the gingiva and buccal vestibule. Bomeli et al. (11) examined the frequency of a dental cause for acute maxillary sinusi-
Extension of infection around the third molar may result in peritonsillar abscess. It is usually seen unilaterally, with extreme soreness of the throat, odynophagia, persistent pain in the peritonsillar area and trismus (30). The uvula may be forced to the opposite site. Fever, malaise and headache can follow. Of 311 abscesses of dental origin, the parapharyngeal and peritonsillar abscesses were the rarest and the perimandibular abscess the most common (58).
Suppurative arthritis of the temporomandibular joint Direct extension of an adjacent infection, such as osteomyelitis of the jaw, traumatic and surgical wound infection of the temporomandibular joint or hematogenous spread of bacteria from a distal site secondary to a systemic process may cause suppurative arthritis of the temporomandibular joint (32). Moses et al. (46) reported a case of septic arthritis of the temporomandibular joint after removal of third molars.
Orbital cellulitis/abscess Dental infections, maxillary osteomyelitis and dental extractions may cause orbital cellulitis (30). Complications can be loss of sight and fatal cerebral complications. Orbital cellulitis starts with a painful and erythematous swelling of the eyelid. The patients may have severe orbital pain, fever, propoptosis, conjunctivitis, chemosis, impaired movements of ~ oz-Guerra the eye and optic nerve damage. Mun et al. (47) reported a subperiosteal abscess of the orbit that was an unusual complication of an uneventful extraction of the left third maxillary molar. It was probably caused by extension of the infection to the pterygopalatine and temporal regions progressing to the inferior orbital fissure. Also, Sakkas et al. (57) and Kim et al. (28) reported an orbital abscess after extraction of a maxillary wisdom tooth. Direct spread of a dentoalveolar abscess of the maxillary first molar via the maxillary sinus
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caused eye loss in a 42-year-old HIV-seropositive woman (41). Allan et al. (3) reported a patient with orbital cellulitis and a postseptal abscess secondary to infection from a maxillary molar tooth. In this patient the infection spread to the maxillary sinus and then to the orbit via a defect in the orbital floor.
Brain and liver abscess Brain abscesses are rare but can be life-threatening. They are sometimes caused by oral infection and dental treatment (34). Oral infection with recurrent bacteremia should always be considered in the pathogenesis of the so-called ‘cryptic’ intracerebral and intraspinal infections (20). Ewald et al. (20) reported six patients with intracerebral (n = 4) and intraspinal (n = 2) infections. All patients had dental pathologies. Clinical improvement was achieved in all patients after decompression, evacuation of pus and targeted antibiotics. Wagner et al. (66) described a patient with brain and liver abscesses caused by oral infection with S. intermedius. A patient with generalized periodontal disease, dental caries and peri-apical pathology developed a cerebral abscess with right hemiparesis and epileptic fits (48). The patient made an uneventful recovery 29 months postoperatively after immediate administration of intravenous antibiotics, craniotomy, resection of the abscess cavity and removal of periodontally decayed and peri-apically involved teeth. Another patient, with deep facial space infection, developed a brain abscess (56). Although a number of reports have suggested a dental etiology for brain abscesses, few efforts have been made to compare brain-abscess isolates with isolates from the oral cavity using highly discriminative methods. Marques da Silva et al. (39) compared brainabscess isolates and oral isolates using phenotypic and three genetic (restriction fragment length polymorphism, ribotyping and random amplification of polymorphic DNA) fingerprinting techniques. The phenotypic method and restriction fragment length polymorphism showed identical profiles between brain and periodontal isolates, while ribotyping and random amplification of polymorphic DNA showed very close similarity. It was suggested that gene transfer by genetic recombination in the periodontal pocket might have been responsible for the emergence of a strain variant (of S. constellatus) that had caused an abscess at a distant site. Aggregatibacter actinomycetemcomitans in combination with Actinomyces meyeri were isolated from the pus of multiple intracerebral lesions that were ini-
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tially diagnosed as cerebral metastases of a suggested lung carcinoma. Both species were also isolated from multiple relapsing purulent skin lesions. The patient had a poor dentition (29). This combination of oral pathogens has been found more often in brain abscesses (69), and both species may represent a synergistic pathogenic combination (65). It has been suggested that a patent foramen ovale in patients with severe periodontitis may be a risk factor for intracranial infection caused by oral pathogens (27). Brain abscesses have been confused with metastatic lesions of a tumor of unknown origin. Rahamat-Langendoen et al. (54) described a patient with a very poor dentition, stomatitis and alcohol abuse; stereotactic biopsy detected the presence of brain abscess, and pus was collected from one of three lesions. Aggregatibacter actinomycetemcomitans was detected in this patient (Fig. 8).
Management of acute oral focal infections Some acute soft-tissue infections are potentially lethal. Therefore, prompt diagnosis and treatment are important. In patients where the infection has spread to neighboring regions, surgical treatment under general anesthesia and treatment with intravenous antibiotics may be necessary. Usually, abscesses are drained by incision and antibiotics are given if the general health condition is affected or if the host is immunocompromised. C-reactive protein levels have been shown to correlate well with the severity and the resolution of acute dental infections and can thus be used as a reliable parameter for monitoring the effectiveness of therapy (17).
Fig. 10. Intra-orally incised dental abscess. Courtesy of Hans Reidar Haanaes.
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Surgery Suppurative oral infections should mostly be surgically treated. This includes pulpectomy, tooth extraction and incision of abscesses in the oral cavity (Fig. 10), the head and the neck (30). Surgery helps to remove the cause of infection and promotes access of antibiotics to the infected site. Even if antibiotics are used, failure of pus drainage may cause further progression of disease and delay resolution. Fluctuation is a clear indication of an abscess that should always be drained, even if tooth extraction or endodontic treatment is carried out. If cellulitis is present, limited amounts of pus may be available by incision, unless the cellulitis spreads widely. Irrigation of the abscess cavity with saline can be useful for large abscesses. In large abscesses, a drain may prevent early closure of the incision. Drains should be removed when drainage has ceased or is minimal.
Root-canal opening Drainage of root canals can be effective, but not if the peri-apical area is unaffected. Opening of the root canal can be convenient, even in cases of cellulitis when the pus has not yet formed peri-apically. Endodontic drainage may be difficult in cases of a restricted root canal. The question of whether a root canal should be left open for evacuation of pus has not been resolved (67).
Tooth extraction Mild infections do not usually require tooth extraction. In the case of a hopeless tooth, extraction will remove the infectious source and provide drainage of pus. If the tooth cannot be spared, early extraction is preferable, even if this may aggravate the swelling.
Antibiotics Systemic antimicrobial therapy should be considered as an adjunct therapy to surgical intervention. Systemic antibiotics are often necessary in acute orofacial suppurative infections, osteomyelitis, acute maxillary sinusitis, suspected actinomycosis, acute necrotizing ulcerative periodontal infections, acute bacterial infection in an immunocompromised patient, facial space infections, acute peritonsillar abscess and acute traumatic and surgical wound infections (30). Systemic antibiotics may be indicated in immunocompromised patients, even in mild infections. Antibiotic treatment should preferably be based on microbial diagnosis and
bacterial sensitivity testing; however, as culture of anaerobic bacteria may take a long time, empirical antimicrobial therapy must be initiated based on the knowledge and experience of the clinician (51). Usually, the most suitable antibiotic will be a penicillin, which is generally considered as safe, even for pregnant women and for children with developing teeth and skeleton. Broad-spectrum antibiotics should be reserved for special occasions (e.g. serious cases with multiple agents). Multidrug regimens are recommended for severe infections, particularly when the drugs have a synergistic effect. The possibility of interaction with other medicines used by the patient should always be taken into account. For acute infections in immunocompromised patients bactericidal antibiotics are preferred over bacteriostatic antibiotics.
Supportive care Usually dental infections do not require hospitalization. Exceptions are when there is a need for urgent life-saving care; a high risk of a fatal condition or suspected serious complications; considerable fever, malaise, trismus, dysphagia or dyspnea; severe, rapid, progressive and extensively spreading infection; a need for intravenous drug administration; significant dehydration or malnutrition; reduced infection resistance; and a need for surgery under general anesthesia (30).
Acknowledgments Professor Geir Støre (Section for Maxillo-Facial Surgery, ENT Department, Rikshospitalet University Hospital, Oslo) and Professor Hans Reidar Haanaes (Section of Oral Surgery and Oral Medicine, Institute of Clinical Dentistry, Faculty of Dentistry, University of Oslo, Oslo) are acknowledged for generously supplying clinical photographs.
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25. Hunter W. Role of sepsis and antisepsis in medicine. Lancet 1910: 1: 79–86. 26. Kachlany SC. Aggregatibacter actinomycetemcomitans leukotoxin: from threat to therapy. J Dent Res 2010: 89: 561– 570. 27. Kawamata T, Takeshita M, Ishizuka N, Hori T. Patent foramen ovale as a possible risk factor for cryptogenic brain abscess: report of two cases. Neurosurgery 2001: 49: 204– 206; discussion 206–207. 28. Kim IK, Kim JR, Jang KS, Moon YS, Park SW. Orbital abscess from odontogenic infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007: 103: e1–e6. 29. Kuijper EJ, Wiggerts HO, Jonker GJ, Schaal KP, de Gans J. Disseminated actinomycosis due to Actinomyces meyeri and Actinobacillus actinomycetemcomitans. Scand J Infect Dis 1992: 24: 667–672. 30. Kuriyama T, Lewis MAO, Williams DW. Infections of the oral and maxillofacial region. In: Andersson L, Kahnberg KE, Pogrel MA, editors. Oral and maxillofacial surgery, Chapter 29. Chichester, UK: Wiley-Blackwell, 2010: 467–582. 31. Legert KG, Zimmerman M, Stierna P. Sinusitis of odontogenic origin: pathophysiological implications of early treatment. Acta Otolaryngol 2004: 124: 655–663. 32. Leighty SM, Spach DH, Myall RW, Burns JL. Septic arthritis of the temporomandibular joint: review of the literature and report of two cases in children. Int J Oral Maxillofac Surg 1993: 22: 292–297. 33. Leishman SJ, Do HL, Ford PJ. Cardiovascular disease and the role of oral bacteria. J Oral Microbiol 2010: 2: 5781. 34. Li X, Tronstad L, Olsen I. Brain abscess caused by oral infection. Endod Dent Traumatol 1999: 15: 95–101. 35. Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev 2000: 13: 547– 558. 36. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, Bahrani-Mougeot FK. Bacteremia associated with toothbrushing and dental extraction. Circulation 2008: 117: 3118–3125. pez JP, Camacho AF. Facial cellulitis resulting from a 37. Lo painless dental abscess. Pediatr Dermatol 2007: 24: 588–589. 38. Marcus BJ, Kaplan J, Collins KA. A case of Ludwig angina: a case report and review of the literature. Am J Forensic Med Pathol 2008: 29: 255–259. 39. Marques da Silva R, Caugant DA, Josefsen R, Tronstad L, Olsen I. Characterization of Streptococcus constellatus strains recovered from a brain abscess and periodontal pockets in an immunocompromised patient. J Periodontol 2004: 75: 1720–1723. 40. Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 1983: 48: 283–289. 41. Masipa JN, Bouckaert M, Masureik C, Lemmer J, Meyerov R, Feller L. Orbital abscess as a complication of odontogenic infection. A case report and review of the literature. SADJ 2007: 62: 318–319. 42. Mehra P, Caiazzo A, Bestgen S. Odontogenic sinusitis causing orbital cellulitis. J Am Dent Assoc 1999: 130: 1086–1092. €ma €la €inen P. Oral health and morbidity – 43. Meurman JH, Ha implications of oral infections on the elderly. Gerodontology 2006: 23: 3–16. 44. Miller W. The human mouth as a focus of infection. Dental Cosmos 1891: 33: 689–713.
Dental focal infections 45. Minassian C, D’Aiuto F, Hingorani AD, Smeeth L. Invasive dental treatment and risk for vascular events. A self-controlled case series. Ann Intern Med 2010: 153: 499–506. 46. Moses JJ, Lange CR, Arredondo A. Septic arthritis of the temporomandibular joint after the removal of third molars. J Oral Maxillofac Surg 1998: 56: 510–512. oz-Guerra MF, Gonza lez-Garcia R, Capote AL, Escorial 47. Mun LN. Subperiostal abscess of the orbit: an unusual V, Gõas complication of the third molar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006: 102: e9–e13. 48. Mylonas AI, Tzerbos FH, Mihalaki M, Rologis D, Boutsikakis I. Cerebral abscess of odontogenic origin. J Craniomaxillofac Surg 2007: 35: 63–67. 49. Neagu I, Tabarcea IC, Vataman R. Associated risk factors in developing oral manifestations in patients with blood dyscrasia [Article in Romanian; English summary]. Rev Med Chir Soc Med Nat Iasi 2010: 114: 555–561. 50. Olsen I. Update on bacteraemia related to dental procedures. Transfus Apher Sci 2008: 39: 173–178. 51. Olsen I, Solberg CO, Finegold SM. A primer on anaerobic bacteria and anaerobic infections for the uninitiated. Infection 1999: 27: 159–165. 52. Pallasch TJ, Slots J. Antibiotic prophylaxis and the medically compromised patient. Periodontol 2000 1996: 10: 107–138. 53. Patel M, Chettiar TP, Wadee AA. Isolation of Staphylococus aureus and black-pigmented bacteroides indicate a high risk for the development of Ludwig’s angina. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009: 108: 667–672. € m LJ, 54. Rahamat-Langendoen JC, van Vonderen MG, Engstro Manson WL, van Winkelhoff AJ, Mooi-Kokenberg EA. Brain abscess associated with Aggregatibacter actinomycetemcomitans: case report and review of literature. J Clin Periodontol 2011: 38: 702–706. 55. Rosan B, Rossman L. Endodontic microbiology. In: Lamont RJ, Burne RA, Lantz MS, LeBlanc DJ, editors. Oral microbiology and immunology, Chapter 15. Washington, D.C.: ASM Press, 2006: 349–360. 56. Sakamoto H, Karakida K, Otsuru M, Arai M, Shimoda M. A case of brain abscess extended from deep fascial space infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009: 108: e21–e25. 57. Sakkas N, Schoen R, Schmeizeisen R. Orbital abscess after extraction of a maxillary wisdom tooth. Br J Oral Maxillofac Surg 2007: 45: 245–246.
58. Schmieg E, Schmelzle R. Treatment of odontogenic abscesses [Article in German]. Dtsch Zahnarztl Z 1975: 30: 54–57. 59. Støre G, Olsen I. Scanning and transmission electron microscopy demonstrates bacteria in osteoradionecrosis. Int J Oral Maxillofac Surg 2005: 34: 777–781. 60. Støre G, Eribe ERK, Olsen I. DNA-DNA hybridization demonstrates multiple bacteria in osteoradionecrosis. Int J Oral Maxillofac Surg 2005: 34: 193–196. 61. Thoden van Velzen SK, Abraham-Inpijn L, Moorer WR. Plaque and systemic disease: a reappraisal of the focal infection concept. J Clin Periodontol 1984: 11: 209–220. 62. Umeda M, Minamikawa T, Komatsubara H, Shibuya Y, Yokoo S, Komori T. Necrotizing fasciitis caused by dental infection: a retrospective analysis of 9 cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003: 95: 283–290. 63. van Winkelhoff AJ, Abbas F, Pavicic MJ, de Graaff J. Chronic conjunctivitis caused by oral anaerobes and effectively treated with systemic metronidazole and amoxicillin. J Clin Microbiol 1991: 29: 723–725. 64. van Winkelhoff AJ, Slots J. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in nonoral infections. Periodontol 2000 1999: 20: 122–135. 65. van Winkelhoff AJ, Overbeek BP, Pavicic MJ, van den Bergh JP, Ernst JP, de Graaff J. Long- standing bacteremia caused by oral Actinobacillus actinomycetemcomitans in a patient with a pacemaker. Clin Infect Dis 1993: 16: 216–218. €n R, Schumacher M, Schumeizeisen R, 66. Wagner KW, Scho Schultze D. Case report: brain and liver abscesses caused by oral infection with Streptococcus intermedius. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006: 102: e21– e23. 67. Weine FS, Buchanan LS. Controversies in clinical endodontics: part 3. Filling from the open position. Compend Contin Educ Dent 1997;18:906–910, 912, 914, 916–918. 68. Zaleckas L, Rasteniene R, Rimkuviene J, Seselgyte R. Retrospective analysis of cellulitis of the floor of the mouth. Stomatologija 2010: 12: 23–27. 69. Zijlstra EE, Swart GR, Godfroy FJ, Degener JE. Pericarditis, pneumonia and brain abscess due to a combined Actinomyces–Actinobacillus actinomycetemcomitans infection. J Infect 1992: 25: 83–87.
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Periodontology 2000, Vol. 65, 2014, 178–189 Printed in Singapore. All rights reserved
PERIODONTOLOGY 2000
Acute focal infections of dental origin I N G A R O L S E N & A R I E J.
VAN
WINKELHOFF
‘Dental focal infections are back with a bang’. This was the title of an editorial in the Journal of American Dental Association in January 1998 (21). Actually, dental focal infections have never been absent, but our attention is now being refocused on these infections. Egyptian physicians knew, already in 1500 BC, that tooth infections had to be treated carefully to prevent life-threatening complications. In 1891, Miller (44) published his theory on focal infection suggesting that oral microorganisms and their products are able to affect parts of the body adjacent to or distant from the mouth. Hunter (25) reprimanded dentists who allowed development of chronic abscesses in the oral cavity, and he believed that necrotic teeth could represent foci of infection causing arthritis, heart disease and other unexplained diseases. Billings (9) also speculated that infected teeth and tonsils could be responsible for a number of focal infections such as arthritis, rheumatism, nephritis, endocarditis and other diseases. The bacteria and their products were assumed to reach these sites through bone cavities, blood or lymph vessels, and even along nerves. Thoden van Velzen et al. (61) suggested three different ways by which oral bacteria can cause nonoral disease: (i) metastatic inflammation as a result of immune injury; (ii) metastatic injury from microbial toxins; and (iii) metastatic infection as a result of the translocation of bacteria. The focal infection theory was prevalent in the 19th century and at the start of the 20th century, particularly in the USA. It resulted in an orgy of tooth extractions, even in patients with the simplest forms of gingivitis. The practitioners performing this ‘treatment’ were called ‘hundred percenters’ because they tended to extract all teeth without considering the extent of the disease (55). The theory fell into mistrust and was gradually dismissed. Currently it is back, allegedly with a bang, although in a new perspective (23). The main reason for this is that a number of epidemiological
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studies have demonstrated the association between chronic oral infections (particularly marginal periodontitis) and systemic diseases, such as cardiovascular diseases, stroke, diabetes, low birthweight of babies born prematurely, respiratory infections and rheumatoid arthritis (15, 33, 35). These issues are the realm of periodontal medicine and will not be dealt with in the current review which is focused on acute dental focal infections. Thus, the association of dental infections with systemic health is broad and is not covered to its full extent in this article. The oral cavity contains a wide variety of organisms, including viruses, fungi and protozoa, but bacteria are the most abundant. This article will focus only on bacteria. However, bacteria may occasionally cause systemic disease in concert with viruses and yeasts, particularly in the compromised host. These organisms may also cause focal infection on their own. Oral infections are among the most prevalent infectious diseases of mankind. Being mostly chronic in nature, they relatively rarely lead to acute or dramatic consequences for the patient. However, medically compromised subjects may be at risk even for chronic oral conditions particularly if their immune system is weak. In fact, translocation of oral bacteria to nonoral sites may lead to an infectious process, even in immunocompetent subjects.
Acute oral infections Acute oral infections are diseases that have a rapid onset, severe symptoms and a short course as opposed to chronic oral infections.
Pulpitis The pathogenesis of oral focal diseases has been classically attributed to dental-pulp pathologies and
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peri-apical infections (10). The main causes for inflammation of the dental pulp (pulpitis) are bacteria and their metabolites, which reach the connective tissue of the pulp via small canals in the dentine. The bacteria are located in caries lesions, in cracks along tooth restorations or in tooth crowns. Pulp inflammation can also develop as a result of trauma, such as following crown or bridge preparation. Toxic effects from filling materials can also cause pulp inflammation. Acute pulpitis may induce almost intolerable pain. At the onset, the pain is induced by external influences such as sweets and acid food or cold. Later, the pain can be provoked by heat. Acute intervention involves excavation of carious lesions and removal of the coronal part of the inflamed pulp tissue. Subsequently, extirpation of the remaining pulp and widening of the root canal are performed, resulting in filling of the root canal and a coronal restoration. The root canal is sealed off to prevent invasion of oral bacteria and release of their products into the surrounding tissues.
Apical periodontitis Untreated pulpitis will sooner or later lead to pulp necrosis. The necrotic tissues of the crown and root pulp serve as a locus minoris resistentiae and allow oral obligate anaerobic and facultative anaerobic bacteria to cause infection. Pulp necrosis will result in inflammation of the tissue around the root apex. Inflammatory mediators, produced by macrophages and lymphocytes, will recruit and activate osteoclasts, resulting in peri-apical bone loss. This process may develop over years without overt clinical symptoms. Histologically, the tissue around the apex can be characterized as granuloma, abscess or cyst. The balance between organisms and the immune defense can be altered by overgrowth of more virulent bacteria, resulting in aggravation and acute pain. The pain can, similarly to pulpitis, become severe, particularly if pus from the apical focus accumulates below the periostium. The succeeding sequence can be abscess formation, perforation to the maxillary sinus and, in serious cases, the infection can spread as a gravity abscess or phlegmon with infiltration of neighboring regions. In some cases a fistula will develop, which may allow accumulated pus to drain and therefore a decrease in symptoms will occur. Acute pain can also develop during root-canal treatment if infected and necrotic pulp/root-canal material is forced into the peri-apical area. Maxillary sinusitis can cause otitis and temporomandibular joint symptoms that may resemble the pain from pulpitis and apical periodon-
titis. However, in sinusitis several teeth will be sensitive to percussion and the pain is aggravated when the patient bends forward.
Pericoronitis A frequent acute condition in the mouth is pericoronitis. Pericoronitis occurs around a partially erupted third molar and frequently occurs in the mandible of young individuals. As a result of the lack of local dental hygiene, a biofilm containing predominantly gram-negative anaerobic rods, spirochetes and cocci develops in the pericoronary space. The acute condition is characterized by severe pain, rubor, swelling, suppuration and problems with swallowing. Trismus may also occur.
Phlegmon and abscess formation Phlegmon (a spreading diffuse infectious process in the connective tissue with formation of suppurative/ purulent exudate or pus) and abscess formation usually result from apical periodontitis but can also be initiated by severe chronic periodontitis and pericoronitis. The symptoms can vary from local swelling and rubor to more pronounced swelling with risk of infection spreading to neighboring regions. Most of these infections are drained through fistulas into the oral cavity. However, infection may spread to neighboring regions such as the maxillary sinus, the sublingual, submandibular and infraorbital regions, orbit and brain, and to the parapharyngeal space, ending up in mediastinitis. In rare cases, so-called cervical necrotizing fasciitis can develop.
Necrotizing ulcerative gingivitis and periodontitis Necrotizing ulcerative gingivitis is a form of necrotizing periodontal disease that affects the gingiva without involving other tissues of the periodontium (4). The infection is also known as ‘trench mouth’ and Vincent’s angina or Vincent’s stomatitis (named after the French physician, Henri Vincent). Another, older, synonym is fusospirochetal gingivitis, referring to the high numbers of fusiform bacteria and spirochetes seen in the dental plaque using dark-field microscopy. Invasion of these organisms into the gingival tissue explains the acute, necrotizing and ulcerative nature of the infection. When other periodontal tissues are involved in the infection and alveolar bone loss occurs, the condition is called necrotizing ulcerative periodontitis. A major risk factor for acute
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periodontal infections is a compromised host defense. These infections can occur in patients with HIV infection and AIDS. Also, smoking and stress have been identified as risk factors for necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis. Acute periodontal infections are discussed in detail by Herrera et al. (24) in this volume of Periodontology 2000.
Bacteremia Microorganisms in the mouth are located on the teeth and on dental restorations, in root apices, mucosa, gingival epithelium, tongue and other oral tissues and in saliva. Dental treatment, injuries and infections cause bacteremia through breaches (50). Even in healthy individuals, microbes of dental plaque (biofilm) can cause ulceration of the gingival crevicular epithelium (13). Patients with mucositis are particularly prone to dissemination of bacteria through their oral ulcers. Even toothbrushing can cause bacteremia, which may be serious in individuals at risk for infective endocarditis (36). The type of dental treatment also affects €ma €la €inen (43) the risk of bacteremia. Meurman & Ha listed dental procedures and diseases associated with bacteremia and reported that the incidence of bacteremia ranged from 100% after tooth extraction to 10% in gingivitis. The intensity of bacteremia is related to the magnitude of trauma, the density of the local microbial deposits and the presence of inflammation or infection at the site of mucosal injury (43). Phenotypic and genetic methods were used to trace microorganisms released into the blood during and after endodontic treatment back to their presumed source – the root canal (16). Microbiological samples were taken from the root canals of 28 patients with asymptomatic apical periodontitis of single-rooted teeth. Blood was drawn during, and 10 min after, endodontic therapy. Microorganisms in the blood were collected after anaerobic lysis filtration and anaerobic culture. Biochemical and antimicrobial susceptibility tests, sodium dodecyl sulfate–polyacrylamide gel electrophoresis of whole-cell soluble proteins, gas chromatography of cellular fatty acids, DNA restriction patterns and ribotyping showed identical phenotypic and genetic characteristics of the root canal and blood isolates, demonstrating that endodontic treatment can be the cause of anaerobic bacteremia and fungemia. Oral bacteria in the blood can deposit directly in coronary vessels or in atherosclerotic plaques. These bacteria are more diverse than previously thought
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and include a number of anaerobes. BahraniMougeot et al. (5) identified oral bacterial species in blood cultures following single-tooth extraction and toothbrushing. Sequence analysis of 16S rRNA genes detected 98 different bacterial species recovered from 151 bacteremic subjects. Forty-eight of the isolates represented 19 novel species of Prevotella, Fusobacterium, Streptococcus, Actinomyces, Capnocytophaga, Selenomonas and Veillonella. This was not supported in a review on oral organisms found in nonoral diseases where most translocating oral species constituted commensals of low pathogenicity (64). However, this may have resulted from problems with the culture and identification of the organisms. Probably, bacteremias also contain not-yet-cultivated bacteria from oral biofilms from which only half of the bacteria can currently be cultured. Usually, bacteremia has no consequences in healthy subjects because bacteria are quickly eliminated from the bloodstream by the reticuloendothelial system of the host. Patients with artificial devices, such as prosthetic heart valves, artificial joints and other types of implants, and patients with a history of infective endocarditis, may run a greater risk for complications from bacteremia (52, 65). van Winkelhoff et al. (65) described a long-standing symptomatic bacteremia caused by Aggregatibacter actinomycetemcomitans in a patient with a pacemaker. Attacks of fever occurred for at least 1 year. The patient also had mild periodontitis. Multiple isolates of A. actinomycetemcomitans from the oral cavity and the blood were compared using DNA fingerprinting. The isolates from the blood and the oral cavity were identical and it was concluded that the oral cavity was the probable source of the infection. Successful treatment included systemic metronidazole and amoxicillin. Invasive dental procedures can be associated with a temporary increase in risk for stroke and myocardial infarction, although the absolute risks are minimal and the long-term benefits on vascular health would probably outweigh the short-lived adverse effects. This was recently shown in a study, carried out from 2002 to 2006, based on persons exposed to invasive dental treatment with a primary hospital diagnosis of ischemic stroke (n = 650) or myocardial infarction (n = 525). The rate of vascular events significantly increased after dental treatment (incidence ratio = 1.50; 95% confidence interval: 1.09–2.06) and gradually returned to baseline levels within 6 months. The positive association persisted, even after exclusion of persons with diabetes, hypertension or coronary artery disease, or persons with prescriptions for antiplatelet or salicylate drugs (45).
Dental focal infections
Other types of dissemination of oral bacteria Dissemination of oral bacteria to extra-oral body sites may not necessarily occur through the blood. van Winkelhoff et al. (63) described a case of conjunctivitis with dacryopyorrhea in a patient with aggressive periodontitis. The conjunctivitis had existed for 3.5 years on one eye only after the patient had suffered from ocular trauma. The patient had used multiple medications, including topical antibiotics and hydrocortisone, but without resolution of the infection. Anaerobic cultivation of pus exudate from the conjunctival sac revealed multiple anaerobes, including Prevotella intermedia and Parvimonas (formerly Peptostreptoccoccus) micra. Restriction enzyme analysis of the P. intermedia isolates from the conjunctival sac and the oral cavity revealed the same clonal type, suggesting translocation of the pathogen from the oral cavity to the eye (Fig. 1). Systemically administered metronidazole plus amoxicillin supported the mechanical periodontal treatment and resolved the conjunctivitis without recurrence of the disease. Oral bacteria can also enter the immune system through the gut and become processed in Peyer’s patches. This may result in stimulation or suppression of the immune system (13). Direct spread of dentoalveolar abscesses (e.g. to the maxillary sinus, orbit and parapharyngeal spaces) can also occur (discussed later).
Dissemination of bacterial toxins The two most important toxins of oral bacteria that can be disseminated are lipopolysaccharide (endotoxin) and exotoxin. Lipopolysaccharide is released
Fig. 1. DNA fingerprints (PstI digest) of eight Prevotella intermedia isolates. Identical profiles are seen for isolates from the conjunctive sac (lanes 4 and 5), the tongue (lanes 6 and 7) and the tonsils (lanes 8 and 9). Different profiles are seen for the Prevotella intermedia isolates from the periodontal pockets (lanes 2 and 3). Lanes 1 and 10 contain a molecular weight DNA ladder.
from disintegrating, dead gram-negative bacteria, but can also be released from the outer-membrane vesicles of viable oral bacteria. Exotoxins are proteinaceous in nature and can be released from viable gram-positive bacteria. An example of the harmful effects of oral bacterial toxins involves orofacial gangrene (noma/cancrum oris) in which Fusobacterium necrophorum displays a classic endotoxin, a dermonecrotic toxin, a cytoplasmic toxin and a hemolysin affecting hard and soft tissues of the oral and para-oral structures (18). Aggregatibacter actinomycetemcomitans, the microorganism associated with aggressive periodontitis, secretes a leukotoxin (LtxA) that helps the bacterium evade the host immune response during infection (26). LtxA is a membraneactive toxin that specifically targets white blood cells. The Streptococcus milleri group (Streptococcus constellatus, Streptococcus intermedius and Streptococcus anginosus) are important pathogens in deep neck and brain abscesses. A massive release of cytokines through a T-cell response to exotoxins produced by the S. milleri group, as reported from the toxic shocklike syndrome, has been suggested in the pathogenesis of abscess formation together with the production of tissue-destroying enzymes such as collagenase and hyaluronidase (22).
Dissemination of oral bacteria owing to incompetence in immune defense An example of dissemination of oral bacteria as a result of immune incompetence is the immunologic changes caused by anticancer drugs. The antineoplastic therapy interferes with the turnover of epithelial cells; this is followed by mucosal injury and later by infection as a result of invasion with gram-negative bacteria and fungal species. Up to 37.2% of all patients receiving cancer chemotherapy develop acute oral complications, and up to 31.1% of all patients receiving cancer radiotherapy experience acute oral manifestations, which may result in significant morbidity, treatment delays and dose reductions, affecting the prognosis of the primary disease (49). In infective endocarditis the colonizing bacteria of morbid luxurious outgrowths on denuded areas of the endocardium covering the valves of the heart evade the actions of the adaptive immune system and antibiotic therapy. This may lead to valvular insufficiency. In immunocompromised individuals, alpha-hemolytic oral streptococci cause disseminated intravascular coagulation. Similarly to infective
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endocarditis, the organisms here gain access to the systemic compartment, most often through erosive lesions of the oral and oropharyngeal mucosa, which are known as mucositis (13). After translocation, the organisms initiate disseminated activation of the coagulation cascade. In both endocarditis and disseminated intravascular coagulation, oral commensals with low pathogenicity can cause life-threatening disease. During bacteremia, with, for example, Streptococcus sanguinis, the concentration of bacterial heat shock protein increases in the blood. Antibodies to oral microbial heat shock proteins can cross-react with antigens from host heat shock proteins. As a result, immune complexes can form that activate the complement system (13). This enables a role for heat shock protein in some systemic diseases, such as immune-mediated ulcers and eruptions of the mucous membrane of the oral cavity, the eyes and the genitals (Behcßet’s disease) through heat shock protein mimicry. Mention should also be made of bacterial mimicry of host peptides (e.g. collagen fragments from the platelet aggregation-associated protein epitope of S. sanguinis). This may cause autorecognition and autoimmune arthritis (13).
Orbit Buccal space Canine space
Submasseteric space
Sublingual space Submandibular space Submental space
Lateral pharyngeal space
Retropharyngeal space
Danger space
Mediastinum
Fig. 2. Drawing showing possible pathways for dental infection to spread. Courtesy of Wiley-Blackwell. From reference (30).
logic and surgical intervention, delayed diagnosis is still responsible for a high mortality rate (about 40– 50%).
Sublingual space infection
Sequelae of acute oral infections Facial space infections Orofacial infection can, in principle, spread to the skull base or to the diaphragm. The route is largely dependent on the location of infection in relation to fasciae. A general rule is that infection spreads along the route of least resistance in subcutaneous connective tissues (phlegmon) and along fascial planes with separation of the fascial layers (30). Purulent exudates collect at locations forming a space (the fascial space). Fascial spaces communicate with each other (Fig. 2), and spread of the infection can therefore progress extensively and rapidly. Affection of vital structures in the head and neck can cause airway obstruction and mediastinitis. Despite modern therapy, fascial space infection remains a significant health problem and can potentially be fatal. Dental infection is the most common cause, but also infections in the mouth, pharynx, tonsils and salivary glands can be involved as well as trauma and surgical infections. Biasotto et al. (8) and Cirino et al. (14), reviewing the literature of descending necrotizing mediastinitis, found that, despite prompt pharmaco-
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Dental infection is most frequently the cause of sublingual space infection, but also sialolith and sublingual gland infection can be involved (30). Usually sublingual space infections originate from the roots of the mandibular anterior teeth and first molars. They often expand bilaterally. A swollen tongue is a significant clinical feature. There is communication with the submandibular space posteriorly. In 240 patients treated for mouth-floor cellulitis from 2002 to 2006, 93.7% of the infections were of dental origin (68). At the first examination the patients had extension of inflammation into the parapharyngeal and pterygomandibular spaces and the neck. In 1.7% of the patients, infection progressed to neck and parapharyngeal spaces (Fig. 3) despite treatment, and in 2% of the patients, infection resulted in mediastinitis.
Submandibular space infection The submandibular space is frequently infected (Fig. 4) through the second and third mandibular molars because of the location of the mylohyoid muscle. The boundary between the mandibular angle and the neck can then become hard to distinguish as a result of swelling (30). The masticatory muscles are
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Fig. 4. Large submandibular abscess. Courtesy of Hans Reidar Haanaes.
Fig. 3. Abscess in the neck with erysipelas reaction of the skin. Courtesy of Geir Støre.
often affected. Infection can also include the masticator and lateral pharyngeal spaces.
Submental space infection Submental space infection often involves an infected mandibular incisor. As a result of the swelling the chin may seem to protrude anteriorly. In addition, the submandibular space is often affected (Fig. 5).
Ludwig’s angina Ludwig’s angina involves infection in the sublingual, submandibular and submental spaces. There is easy communication from these spaces to the contralateral side. Most cases of infection are of dental origin. There is a firm swelling of the mouth floor and the tongue is elevated. A cellulitis is present with no tendency to abscess formation. Submandibular and sublingual spaces become involved bilaterally. An endodontic infection of a mandibular molar is often the primary infection. The patient may develop signs of toxicity, with high fever, tachycardia and malaise.
Fig. 5. Large submandibular abscess with spontaneous drainage of pus. Severe caries is present in all tooth quadrants. Courtesy of Geir Støre.
It takes only 12–24 h from the start of the swelling to the onset of symptoms of respiratory infection. Baqain et al. (6) reported a case of Ludwig’s angina caused by a dental infection that progressed to mediastinitis and pericarditis. The importance of early recognition and diagnosis of the source of deep cervical infections must be emphasized (19, 37, 38). Staphylococcus aureus and black-pigmented gram-negative anaerobic rods may indicate a high risk for developing Ludwig’s angina (53). In one patient, facial cellulitis resulted from a painless dental abscess (37).
Other facial space infections These may involve the buccal, canine, masticatory, submasseteric (Fig. 6), pterygomandibular, temporal, cervical fascial, lateral pharyngeal and retropharyngeal spaces (29). Bacterial infection of the mouth occasionally spreads to these contiguous spaces. These infections may also affect the orbital cavity (57) (Fig. 7) and the brain (Fig. 8).
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Fig. 6. Abscess in the masseter region with fistula. Courtesy of Geir Støre.
Gas gangrene and necrotizing fasciitis Dental infection is a common cause of gas gangrene and necrotizing fasciitis. These infections may spread downwards to the mediastinum, leading to mediastinitis (8, 14), pericarditis, lung infection and sepsis. They may also spread upwards to the skull base and to the meninges, or through blood vessels to give suppurative thrombophlebitis, sepsis or disseminated intravascular coagulation (30). Immunosuppressive conditions and alcohol abuse may predispose but these types of infections can also occur in healthy individuals. Factors affecting mortality are diabetes, alcohol abuse, delay of surgery and complicating mediastinitis (62).
Fig. 7. Abscess from previously traumatized tooth incised in the labial fold. Courtesy of Geir Støre.
Osteomyelitis of the jaw Both suppurative and nonsuppurative forms of jaw osteomyelitis occur. The former are the most dominant. They can be acute or chronic. Dental infections are the most common cause of osteomyelitis in the jaw, and the body of the mandible is the most common site. When there is chronically impaired blood flow and when the bone contains fibrous marrow, the jaw becomes sensitive to bacterial infection. Cranial osteomyelitis was described, by Adams & Bryant (2), to develop as a late complication of dental infection that extended subtemporally.
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Fig. 8. Computed tomography (CAT) scan of a patient with multiple brain abscesses associated with Aggregatibacter actinomycetemcomitans organisms and a poor periodontal condition.
Osteoradionecrosis of the jaw Osteoradionecrosis affects bone, particularly the mandible that has been irradiated as part of cancer treatment (Fig. 9). The radiation harms normal tissue cells and affects the blood supply in bone, cartilage
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tis and found that dental infections can cause acute maxillary sinusitis, particularly if the radiographic findings of sinusitis are severe. Many cases of recurrent acute sinusitis are caused by secondary rhinogenous bacterial colonization of the antral mucosa that has been weakened and degenerated by chronic dental infection/inflammation (31).
Peritonsillar abscess
Fig. 9. Irradiated mandible with osteoradionecrosis and superinfection. Courtesy of Geir Støre.
and soft tissue. Such tissue is susceptible to infection with oral bacteria. Until recently, a common view was that the infection of the bone was superficial and secondary (40). Several studies, using scanning and transmission electron microscopy (59), DNA–DNA hybridization (60) and 16S ribosomal DNA sequencing (1), have shown independently that the medullary parts of bone in osteoradionecrosis are heavily infected with a wide variety of facultative anaerobic and strict anaerobic bacteria, some of which are not yet cultivable.
Acute maxillary sinusitis Maxillary sinusitis usually appears unilaterally and constitutes approximately 10–12% of all cases of maxillary sinusitis (12). The etiology includes most often peri-apical dental abscesses, severe periodontitis, peri-implantitis and postextraction infection. A number of other dentally related etiologies can occur (30). Maxillary sinusitis may become chronic following the acute phase or can manifest itself as a chronic inflammation without acute episodes. Acute maxillary sinusitis is caused by bacteria invading the sinus from a focus of dental infection. Infection from maxillary premolars and molars, peri-apical abscesses, severe peri-implantitis, postextraction infection and cysts are the most common causes (7). Signs and symptoms include dull or intense pressure, erythema, swelling of cheek and anterior maxilla and the drainage of foul-smelling material. Acute maxillary sinusitis can cause orbital abscess/cellulitis (41, 42), cavernous sinus thrombosis, meningitis and intracranial abscess. In cases where the origin is a peri-apical abscess, there is toothache and swelling of the gingiva and buccal vestibule. Bomeli et al. (11) examined the frequency of a dental cause for acute maxillary sinusi-
Extension of infection around the third molar may result in peritonsillar abscess. It is usually seen unilaterally, with extreme soreness of the throat, odynophagia, persistent pain in the peritonsillar area and trismus (30). The uvula may be forced to the opposite site. Fever, malaise and headache can follow. Of 311 abscesses of dental origin, the parapharyngeal and peritonsillar abscesses were the rarest and the perimandibular abscess the most common (58).
Suppurative arthritis of the temporomandibular joint Direct extension of an adjacent infection, such as osteomyelitis of the jaw, traumatic and surgical wound infection of the temporomandibular joint or hematogenous spread of bacteria from a distal site secondary to a systemic process may cause suppurative arthritis of the temporomandibular joint (32). Moses et al. (46) reported a case of septic arthritis of the temporomandibular joint after removal of third molars.
Orbital cellulitis/abscess Dental infections, maxillary osteomyelitis and dental extractions may cause orbital cellulitis (30). Complications can be loss of sight and fatal cerebral complications. Orbital cellulitis starts with a painful and erythematous swelling of the eyelid. The patients may have severe orbital pain, fever, propoptosis, conjunctivitis, chemosis, impaired movements of ~ oz-Guerra the eye and optic nerve damage. Mun et al. (47) reported a subperiosteal abscess of the orbit that was an unusual complication of an uneventful extraction of the left third maxillary molar. It was probably caused by extension of the infection to the pterygopalatine and temporal regions progressing to the inferior orbital fissure. Also, Sakkas et al. (57) and Kim et al. (28) reported an orbital abscess after extraction of a maxillary wisdom tooth. Direct spread of a dentoalveolar abscess of the maxillary first molar via the maxillary sinus
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caused eye loss in a 42-year-old HIV-seropositive woman (41). Allan et al. (3) reported a patient with orbital cellulitis and a postseptal abscess secondary to infection from a maxillary molar tooth. In this patient the infection spread to the maxillary sinus and then to the orbit via a defect in the orbital floor.
Brain and liver abscess Brain abscesses are rare but can be life-threatening. They are sometimes caused by oral infection and dental treatment (34). Oral infection with recurrent bacteremia should always be considered in the pathogenesis of the so-called ‘cryptic’ intracerebral and intraspinal infections (20). Ewald et al. (20) reported six patients with intracerebral (n = 4) and intraspinal (n = 2) infections. All patients had dental pathologies. Clinical improvement was achieved in all patients after decompression, evacuation of pus and targeted antibiotics. Wagner et al. (66) described a patient with brain and liver abscesses caused by oral infection with S. intermedius. A patient with generalized periodontal disease, dental caries and peri-apical pathology developed a cerebral abscess with right hemiparesis and epileptic fits (48). The patient made an uneventful recovery 29 months postoperatively after immediate administration of intravenous antibiotics, craniotomy, resection of the abscess cavity and removal of periodontally decayed and peri-apically involved teeth. Another patient, with deep facial space infection, developed a brain abscess (56). Although a number of reports have suggested a dental etiology for brain abscesses, few efforts have been made to compare brain-abscess isolates with isolates from the oral cavity using highly discriminative methods. Marques da Silva et al. (39) compared brainabscess isolates and oral isolates using phenotypic and three genetic (restriction fragment length polymorphism, ribotyping and random amplification of polymorphic DNA) fingerprinting techniques. The phenotypic method and restriction fragment length polymorphism showed identical profiles between brain and periodontal isolates, while ribotyping and random amplification of polymorphic DNA showed very close similarity. It was suggested that gene transfer by genetic recombination in the periodontal pocket might have been responsible for the emergence of a strain variant (of S. constellatus) that had caused an abscess at a distant site. Aggregatibacter actinomycetemcomitans in combination with Actinomyces meyeri were isolated from the pus of multiple intracerebral lesions that were ini-
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tially diagnosed as cerebral metastases of a suggested lung carcinoma. Both species were also isolated from multiple relapsing purulent skin lesions. The patient had a poor dentition (29). This combination of oral pathogens has been found more often in brain abscesses (69), and both species may represent a synergistic pathogenic combination (65). It has been suggested that a patent foramen ovale in patients with severe periodontitis may be a risk factor for intracranial infection caused by oral pathogens (27). Brain abscesses have been confused with metastatic lesions of a tumor of unknown origin. Rahamat-Langendoen et al. (54) described a patient with a very poor dentition, stomatitis and alcohol abuse; stereotactic biopsy detected the presence of brain abscess, and pus was collected from one of three lesions. Aggregatibacter actinomycetemcomitans was detected in this patient (Fig. 8).
Management of acute oral focal infections Some acute soft-tissue infections are potentially lethal. Therefore, prompt diagnosis and treatment are important. In patients where the infection has spread to neighboring regions, surgical treatment under general anesthesia and treatment with intravenous antibiotics may be necessary. Usually, abscesses are drained by incision and antibiotics are given if the general health condition is affected or if the host is immunocompromised. C-reactive protein levels have been shown to correlate well with the severity and the resolution of acute dental infections and can thus be used as a reliable parameter for monitoring the effectiveness of therapy (17).
Fig. 10. Intra-orally incised dental abscess. Courtesy of Hans Reidar Haanaes.
Dental focal infections
Surgery Suppurative oral infections should mostly be surgically treated. This includes pulpectomy, tooth extraction and incision of abscesses in the oral cavity (Fig. 10), the head and the neck (30). Surgery helps to remove the cause of infection and promotes access of antibiotics to the infected site. Even if antibiotics are used, failure of pus drainage may cause further progression of disease and delay resolution. Fluctuation is a clear indication of an abscess that should always be drained, even if tooth extraction or endodontic treatment is carried out. If cellulitis is present, limited amounts of pus may be available by incision, unless the cellulitis spreads widely. Irrigation of the abscess cavity with saline can be useful for large abscesses. In large abscesses, a drain may prevent early closure of the incision. Drains should be removed when drainage has ceased or is minimal.
Root-canal opening Drainage of root canals can be effective, but not if the peri-apical area is unaffected. Opening of the root canal can be convenient, even in cases of cellulitis when the pus has not yet formed peri-apically. Endodontic drainage may be difficult in cases of a restricted root canal. The question of whether a root canal should be left open for evacuation of pus has not been resolved (67).
Tooth extraction Mild infections do not usually require tooth extraction. In the case of a hopeless tooth, extraction will remove the infectious source and provide drainage of pus. If the tooth cannot be spared, early extraction is preferable, even if this may aggravate the swelling.
Antibiotics Systemic antimicrobial therapy should be considered as an adjunct therapy to surgical intervention. Systemic antibiotics are often necessary in acute orofacial suppurative infections, osteomyelitis, acute maxillary sinusitis, suspected actinomycosis, acute necrotizing ulcerative periodontal infections, acute bacterial infection in an immunocompromised patient, facial space infections, acute peritonsillar abscess and acute traumatic and surgical wound infections (30). Systemic antibiotics may be indicated in immunocompromised patients, even in mild infections. Antibiotic treatment should preferably be based on microbial diagnosis and
bacterial sensitivity testing; however, as culture of anaerobic bacteria may take a long time, empirical antimicrobial therapy must be initiated based on the knowledge and experience of the clinician (51). Usually, the most suitable antibiotic will be a penicillin, which is generally considered as safe, even for pregnant women and for children with developing teeth and skeleton. Broad-spectrum antibiotics should be reserved for special occasions (e.g. serious cases with multiple agents). Multidrug regimens are recommended for severe infections, particularly when the drugs have a synergistic effect. The possibility of interaction with other medicines used by the patient should always be taken into account. For acute infections in immunocompromised patients bactericidal antibiotics are preferred over bacteriostatic antibiotics.
Supportive care Usually dental infections do not require hospitalization. Exceptions are when there is a need for urgent life-saving care; a high risk of a fatal condition or suspected serious complications; considerable fever, malaise, trismus, dysphagia or dyspnea; severe, rapid, progressive and extensively spreading infection; a need for intravenous drug administration; significant dehydration or malnutrition; reduced infection resistance; and a need for surgery under general anesthesia (30).
Acknowledgments Professor Geir Støre (Section for Maxillo-Facial Surgery, ENT Department, Rikshospitalet University Hospital, Oslo) and Professor Hans Reidar Haanaes (Section of Oral Surgery and Oral Medicine, Institute of Clinical Dentistry, Faculty of Dentistry, University of Oslo, Oslo) are acknowledged for generously supplying clinical photographs.
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