Nonodontogenic bacterial infections of the oral cavity are not a common finding in the United States. Nevertheless, there has been an increase in prevalence of certain bacterial sexually transmitted diseases, such as syphilis and gonorrhea, and conditions such as tuberculosis still pose a serious threat to certain segments of the population. Finally, given the uncommon nature and pathophysiology of these diseases, diagnosis is often delayed, resulting in more clinically significant disease and potential contamination of individuals. Thus, it is prudent that clinicians be familiar with these uncommon but potentially serious infectious diseases, so treatment can be instituted promptly.
Key points
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Most nonodontogenic bacterial lesions are highly infectious; therefore, early diagnosis and treatment are of the utmost importance.
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These lesions may clinically and microscopically mimic other oral diseases, which complicate early diagnosis.
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Syphilis and gonorrhea cases are increasing in the United States; hence, it is prudent that clinicians be familiar with their potential oral manifestations.
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Although most of the oral bacterial diseases are easily treatable, delay in the diagnosis can lead to life-threatening complications.
Introduction
Nonodontogenic bacterial infections of the oral cavity are not a common finding in the United States. Nevertheless, there has been an increase in the prevalence of certain bacterial sexually transmitted diseases, such as syphilis and gonorrhea, and conditions such as tuberculosis (TB) still pose a serious threat to certain segments of the population. Finally, given the uncommon nature and the widespread clinical presentation and pathophysiology of these diseases, diagnosis is often delayed, resulting in more clinically significant disease and potential contamination of individuals. Thus, it is prudent that clinicians be familiar with these uncommon but potentially serious infectious diseases, so treatment can be instituted promptly.
Actinomycosis
Actinomycosis is a suppurative infection of filamentous, anaerobic bacterial species of the genus Actinomyces . Actinomycetes are gram-positive, pigment-producing bacilli that are considered normal saprophytic components of the oral flora, mainly from tonsillar crypts (forming concretions plugs), dental plaque, carious dentin, bone sequestra, salivary calculi, gingival sulci, and periodontal pockets. These bacteria are often isolated with other normal commensals (polymicrobial infection), reinforcing the hypothesis that other organisms may create favorable conditions (oxygen tension reduction and host defenses inhibition) to support their continued growth.
Actinomycosis is often underreported and misdiagnosed. The low potential of invasiveness and virulence contributes to the lack of incidence data. Cervicofacial actinomycosis may mimic other conditions, making diagnosis very difficult. Culture is usually negative due to the anaerobic nature of the organism, the prolonged incubation period, and the empirical use of many antibiotics, to which Actinomyces are highly sensitive. 1-4 The invasion of oral tissues by actinomycetes is attributed to loss of integrity and chronic inflammation not only from previous trauma but also from fractures, surgery, tooth extraction, endodontic treatment, sinusitis, periodontal disease, or periapical infection.
Clinical Findings
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Cervicofacial actinomycosis accounts for more than half of the cases
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Actinomyces israelii and Actinomyces gerencseriae are responsible for 70% of cases
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Chronic hard swelling in the mandible and/or the neck
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“Wooden” indurated fibrosis (lumpy jaw) in 60% of cases
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Associated soft tissue abscess with minimal pain and mild fever
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Sinus tracts draining pus containing sulfur granules
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Dark red to purple overlying skin of nonhealing sinus tracts
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Young healthy adults: men > women
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Jaw involvement
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Mandible > maxilla (4:1)
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Association with osteomyelitis, and persistent periapical inflammatory lesions ( Fig. 1 )
Fig. 1 ( A ) A persistent periapical lesion after endodontic treatment of upper incisors of an adult patient. ( B ) The gross appearance of the sample biopsied included a round grayish-colored soft fragment, measuring 5 mm, which consisted of colonies of Actinomyces (lower right).
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Other sites may be involved
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Larynx, hypopharynx, lacrimal and salivary glands, oral mucosa (tongue)
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Systemic manifestations: Fever, chills, and weight loss
Differential Diagnosis
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Other bacterial infections, TB, nocardiosis, cyst, and malignancy
Diagnostic Modalities
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Gram staining of pus and/or microscopic evaluation
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Molecular techniques have improved organism identification
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16S ribosomal RNA (rRNA) sequencing and polymerase chain reaction (PCR)
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Imaging
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Evaluation of bone involvement, disease extent, and treatment
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Computed tomography, MRI, and ultrasonography ,
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Pathology
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The sulfur granules are round gritty colonies of Actinomyces observed in vivo
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Whitish gray, yellow, brownish green, or green in color
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There is no evidence that the granules contain sulfur
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They are not pathognomonic (also produced by other types of bacteria)
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It offers bacteria protection against immune cells
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Identified histologically but frequently lost during tissue handling and processing
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Masses of club-shaped filaments arranged in radiating rosette pattern ( Fig. 2 )
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Surrounded by neutrophils
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Mineralized and cemented by host calcium phosphate
Fig. 2 Typical radiating architecture of partially mineralized, club-shaped filaments of Actinomyces surrounded by neutrophils (hematoxylin and eosin, A , 100× and B , 400×). - ○
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Granulomatous inflammation with central necrosis may be present
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Lymphocytes, plasma cells, epithelioid cells, histiocytes, and giant cells
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The periphery of the lesion can be fibrotic and avascular , ,
Therapeutic Options
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Surgical removal of infected tissue and appropriate antibiotic therapy
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Abscess drainage, removal of necrotic bone, dental extraction, and/or excision of sinus tracts
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Penicillin G or amoxicillin
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Severe (deep and chronic) cases—intravenous amoxicillin (up to 200 mg/kg/d) or penicillin G (up to 24 MIU/d) followed by oral treatment
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Prolonged treatment of up to 6 to 12 months is questionable
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Several investigators advocate that localized acute actinomycotic infections (eg, periapical and pericoronal actinomycosis) be treated more conservatively (surgical removal of infected tissue) and that antibiotics be reserved for cases in which invasion of surrounding structures and spread through the soft tissues is seen
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Long-term follow-up recommended
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Good prognosis for early treated patients ,
Tuberculosis
TB is a chronic communicable disease caused by Mycobacterium tuberculosis. The disease remains one of the most serious infectious diseases in the world and until before the coronavirus (COVID-19) pandemic, it represented the leading cause of death from a single infectious agent.
According to the WHO, an estimated 9.9 million people became ill with TB worldwide in 2020, with approximately 1.5 million deaths reported. In contrast, for the year of 2020, the United States reported only 7174 cases of TB and an incidence rate of only 2.2 cases per 100,000 persons. Although US rates are low and have been declining for the past several years, the disease still disproportionately affects certain segments of the population such as racial and ethnic minorities, foreign-born persons, those living in crowded living situations, and suffering from underlying medical conditions (eg, diabetes mellitus and infection with human immunodeficiency virus [HIV]). ,
M tuberculosis is contracted by inhalation of airborne microorganisms that are generated by individuals with active TB . Primary TB occurs in previously unexposed people, almost always involves the lungs, produces only mild symptoms, and generally goes undiagnosed. Most patients exposed to the bacterium develop a strong cell-mediated immune response that stops the progression of the infection. When this happens, the initial lung and nodal lesions of primary TB, undergo progressive inspissation, hardening, encapsulation, often followed by radiologically detectable calcification. , Although the lesion “heals,” some bacteria may remain dormant in these fibrocalcific nodules. Latent tuberculosis infection (LTBI) is the term used when the host defenses can contain M tuberculosis microorganisms but the organisms still maintain the capacity to replicate and cause disease in the future ( Box 1 ). ,
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Latent tuberculosis infection: It is characterized by the presence of immunologic sensitivity to mycobacterial antigen (as determined by a tuberculin skin test or an interferon-γ release assay) in the absence of the clinical symptoms of disease.
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Active tuberculosis or tuberculosis disease : It is diagnosed in patients who have clinical signs and symptoms of TB and show microbiological evidence of M tuberculosis infection.
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Miliary tuberculosis: It occurs when tubercle bacilli enter the bloodstream and disseminate to all parts of the body, where they grow and cause disease in multiple sites. This condition is rare but serious.
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Oral tuberculosis: It is a rare form of extrapulmonary TB, which affects only 0.1% to 5% of individuals with the disease. It may or may not coexist with pulmonary TB.
Only in a very small proportion of patients, usually young children and the immunocompromised, the initial infection is not controlled by the immune response and the patient progresses rapidly to active TB. Dissemination of bacilli may occur through the lung parenchyma, resulting in extensive pulmonary lesions and lymphohematogenous spread. Widespread infection with multiple organ involvement is called miliary TB. , , More commonly, however, TB disease develops months to years after the initial infection, due to a reactivation of LTBI. This reactivation is usually the result of a weakened immune system, and some individuals are at an increased risk of disease reactivation ( Box 2 ). ,
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a Persons infected with HIV
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Children aged younger than 5 years
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Persons recently infected with M tuberculosis (within the past 2 years)
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Persons who are receiving immunosuppressive therapy such as tumor necrosis factor-alpha antagonists, corticosteroids, or immunosuppressive drug therapy following organ transplantation
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Persons with diabetes mellitus
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Cigarette smokers and persons who abuse drugs and/or alcohol
Although TB primarily affects the lungs, it can be seen in other sites such as lymph nodes, pleura, genitourinary tract, and the oral cavity. Oral lesions can occur either in the primary or secondary forms of TB. The lesions are believed to be the result of autoinoculation by M tuberculosis bacilli in the sputum, or through hematogenous or lymphatic spread.
Clinical Findings
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Unexplained weight loss, low grade fever, night sweats, anorexia, and fatigue ,
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Pulmonary TB: chronic cough, pleuritic pain, and hemoptysis
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Oral TB
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Men > women ,
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Fourth and fifth decades of life , ,
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Typically presents as soft tissue lesions but one-fourth of cases are intraosseous
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Soft tissue lesions
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Predilection for tongue, followed by buccal mucosa, gingiva, palate, and lips ,
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Ulceration, typically described as indurated, with ill-defined margins and a hard necrotic base , ( Fig. 3 )
Fig. 3 A 40-year-old man with history of weight loss (22 lbs) and persistent cough for the last 4 months. (A) The patient presented a painful ulcer involving the left border of the tongue of 1-month duration as an oral manifestation of tuberculosis.( Courtesy of Rafaela França, DDS, Rio de Janeiro, BR.) - ▪
Swelling, nodules, fissures, and granulation tissue-like or granular lesions have been reported ,
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Intraosseous lesions:
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Mandible far more often affected than maxilla ,
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Radiolucent, destructive bony swellings ,
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Symptoms of tenderness, pain or burning, may be present
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Secondary oral TB is more common than primary oral TB and tends to affect middle-aged and elderly patients
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Primary oral TB typically occurs in children and adolescents and presents as an asymptomatic ulcer with concomitant enlargement of cervical lymph nodes
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Although persons with extrapulmonary TB are usually not infectious, lesions of oral cavity or larynx should be considered infectious
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Neck TB
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Cervical lymph nodes are more commonly affected by TB than the oral cavity with the submental and submandibular lymph nodes affected most often , ,
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Involvement of major salivary glands is also possible
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Lymph node involvement most commonly presents as a localized mass, resulting from infection of intracapsular or pericapsular lymph nodes
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May present as parenchymatous fistula/sinus tracts or an abscess ( Fig. 4 )
Fig. 4 A 47-year-old woman presents with neck fistulas secondary to TB involvement of cervical lymph nodes.( Courtesy of Fernando Lima, DDS, Rio de Janeiro, BR.)
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Differential diagnosis
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Most cases of oral TB have been clinically mistaken for a malignant process, especially squamous cell carcinoma ,
Diagnostic Modalities
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Two methods available in the United States for the detection of M tuberculosis infection:
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TB blood tests (interferon-gamma release assays [IGRAs])
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QuantiFERON-TB Gold Plus (QFT-Plus)
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T-SPOT.TB test (T-Spot)
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Mantoux tuberculin skin test
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These tests cannot distinguish LTBI from active TB disease
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Acid-fast stains and culture of infected sputum or tissue must be used to confirm the diagnosis of active disease
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Nuclei acid amplification (NAA) tests can be used to rapidly identify the microorganisms in the specimen. It can detect M tuberculosis DNA in just hours, compared with a week or more for the detection of the organism in culture
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Allows earlier detection of drug resistance when certain NAAs are used (eg, Gene Xpert)
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A posterior-anterior radiograph of the chest is mandatory for all cases suspicious for TB ,
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Oral TB:
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A biopsy of the oral ulcer is of utmost importance to confirm oral TB and rule out other important lesions in the differential diagnosis such as a carcinoma
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The microscopic presence of caseous granulomas in an oral biopsy is not diagnostic of TB but will prompt the pathologist to order Ziehl-Neelsen (ZN) or other acid-fast stains to aid in the identification of the mycobacteria
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The ZN sensitivity can be low, thus a negative result does not rule out the possibility of TB
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Molecular tests are more sensitive and may enhance the diagnosis
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Even if the microorganism is detected in the biopsy specimen, identification of the organism by culture is recommended
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Pathology
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Microscopically, TB is characterized by the presence of granulomas which are collections of giant cells and epithelioid histiocytes and which may show central caseous necrosis
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Tiny, rod-shaped, acid-fast bacilli may be identified with ZN or Kinyoun stain ( Fig. 5 )
Fig. 5 ( A, B ) Granulomas containing central necrosis affecting a lymph node of a patient with tuberculosis. ( C ) Acid-fast stain revealed numerous mycobacterial organisms presenting as red, rod-shaped bacilli (hematoxylin and eosin, A , 50× and B , 100×; Ziehl-Neelsen, C , 400×).
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