Bacterial Infections of the Oral Mucosa

Etiology

Syphilis   

Syphilis is caused by a spirochete known as Treponema pallidum that can be sexually transmitted (vaginal, anal, or oral contact) or passed through the placenta, causing congenital syphilis. It has an incubation period of approximately 20 to 40 days. The host for T. pallidum is humans, and it has no animal reservoir.[5]

Gonorrhea

Gonorrhea is a sexually transmitted disease caused by gram-negative cocci called Neisseria gonorrhoeae. N. gonorrhoeae mainly affects mucous membranes causing urethritis in men and cervicitis in women.

Oral or pharyngeal gonorrhea, although uncommon, is more prevalent in females or in men who have sex with men (MSM). Oropharyngeal gonorrhea is known to be rare because the saliva is a hostile environment for N. gonorrhoeae. The disease may be transmitted through oral sex and kissing, even in an asymptomatic infected person.[6]

Tuberculosis (TB) 

Tuberculosis is a granulomatous disease caused by aerobic acid-fast bacilli, Mycobacterium tuberculosis, triggering a primary pulmonary infection.

Oral tuberculosis results from a secondary infection via blood dissemination.[4] The spread of M. tuberculosis occurs through aerosols generated by coughing, sneezing, or speaking. The bacteria can remain airborne within tiny droplets for hours and infect susceptible individuals. The risk of TB transmission in a dental practice appears low, however possible, primarily through patients from high-risk areas of the world or with reactivated TB infection.[2]

Scarlet Fever 

Scarlet fever is a bacterial infection that develops in patients suffering from bacterial pharyngitis - strep throat - and occasionally from streptococcal skin or wound infections. The causative agent is Streptococcus pyogenes, which belongs to the gram-positive A beta-hemolytic streptococci group (GABHS). Humans are the primary reservoir for this bacterium, with approximately 2 to 5 days of incubation.

Scarlet fever, also known as scarlatina, can spread directly from person to person via infected saliva or nasal secretions. There is a higher risk of transmission in crowded conditions such as daycare centers and schools.[7]

Epidemiology

Approximately 4 to 12% of syphilis patients will present with oral manifestations and are usually diagnosed in the secondary phase of the disease. The mean age of syphilis diagnosis is around 34 years old, of which 51% are men.[8]

Most reported gonorrhea cases are based on urogenital testing. The epidemiology of oropharyngeal gonorrhea is limited because most clinics do not offer oropharynx screenings. The prevalence of oropharyngeal gonorrhea in MSM is 2% to 11%, in heterosexuals 3% to 7% for men, and between 2% to 10% for women.[9] Routine screening of at-risk asymptomatic patients with gonorrhea has demonstrated that pharyngeal and rectal gonococcal infections are common manifestations.[6]

Tuberculosis is more common in developing countries. In 2019, more than 80% of tuberculosis cases occurred in Indonesia, India, China, the Philippines, Pakistan, Bangladesh, Nigeria, and South Africa. Most oral manifestations of tuberculosis are secondary to the primary pulmonary infection; however, in younger patients, primary oral tuberculosis may occur from direct inoculation of the organism in the oral mucosa.[10] Around 1 to 5% of patients have oral manifestations, and 1.33% of those cases are associated with immunocompromising infections such as HIV.[10][11]

Scarlet fever can occur in all age groups, but it is more prevalent amongst children between 5 to 15 years old. Strep throat is responsible for 15 to 30% of all pharyngitis in children and 5 to 15% in adults, making the prevalence of scarlet fever higher in children. Scarlet fever is seen more in underdeveloped countries due to crowded living circumstances.[7]

Histopathology

Syphilis

Although there may be no specific microscopic feature for the diagnosis of syphilis, it should be considered where there is unusual dense lymphoplasmacytic inflammation with inflammatory exocytosis, epithelial hyperplasia, granulomatous or ulceration at the surface, and perivascular inflammation.[12][13]

Gonorrhea

Methylene blue-stained smears of N.gonorrhoeae or light microscopy of gram-negative will reveal neutrophils with intracellular diplococci. High sensitivity and specificity are reported with light microscopy for symptomatic males with urethral discharge; however, light microscopy has a lower sensitivity for diagnosing pharyngeal gonorrhea.[6]

Tuberculosis

Biopsy commonly shows caseating granulomas typically with central necrosis surrounded by epithelioid histiocytic cells, Langerhans giant cells, and lymphocytic infiltration, characteristic of TB.[14][15]

Scarlet fever

There are no specific histological changes in scarlet fever; however, neutrophilic infiltrate with spongiosis, and parakeratosis in the epidermis may be seen.[7]

History and Physical

Syphilis 

The oral manifestation of syphilis is usually the first sign of the disease. The initial oral lesion characteristic of primary syphilis, known as a chancre, appears at the site of inoculation around two weeks after the exposure. The most common locations are the buccal mucosa, tongue, and lips.

The chancre usually presents as a solitary, painless, round, and indurated nodule, with firm margins accompanied by regional lymphadenopathy. The chancre begins as a macule that evolves into a papule. The papule may erode and transform into an ulcer of around 0.5 to 1.5 cm in diameter.[16] There may also be evidence of petechial hemorrhage on the soft palate with or without a chancre.[5][1][17] Lack of pain characterizes the syphilitic lesion and prompts to differentiate it from a squamous cell carcinoma.[18]

Secondary syphilis is a highly contagious stage that appears 2 to 8 weeks after the primary chancre emerges. In this period, oral lesions can be maculopapular or mucosal patches. The mucosal patches are more common, appearing as slightly raised or shallow oval ulcers surrounded by an erythematous border with a gray pseudomembrane. Lesions on the tongue may appear as irregular fissures or pronounced ulcerations.[19] Unlike primary syphilis, oral lesions in the secondary stage of the disease are multiple and painful. Patients also report sore throats.

Systemic symptoms include fever and lymphadenopathy. In the skin, a maculopapular rash involving the palms and soles and alopecia may be found. Condylomata lata, a painless, smooth wart-like lesion, can be observed on the genitals during this period.[5]

Tertiary syphilis is a destructive stage that manifests months or years after the initial infection in patients who have not received effective treatment during the primary or secondary stages of the disease. Oral manifestations of this phase include a chronic granulomatous gumma usually located on the hard palate, which may perforate into the nasal septum. The tongue may present with leukoplakia dorsally or appear atrophic and fissured.[5][19] 

Tertiary syphilis symptoms result from complications of previous stages. They include Argyll Robertson pupil that constricts with accommodation but is not reactive to light, aortitis due to the vasa vasorum destruction, and neurosyphilis, such as tabes dorsalis.

Congenital syphilis is transferred from an infected mother to the fetus, usually after 16 weeks of pregnancy. Before this period, Langerhans cells prevent the transmission of the spirochete to the fetus. As the fetus develops, Langerhans cells' number decreases, allowing the passage of the spirochetes.

When pregnant women transmit syphilis to their children, various developmental defects commonly arise, including dental abnormalities. Hutchinson's incisors are characteristic of congenital syphilis patients, small, widely spaced, and peg-shaped incisors; semitranslucent rather than ivory, with a screwdriver-shaped incisal edge. Another dental abnormality that may be seen is Moon molars or mulberry molars, where molar anatomy is replaced by small, dome-shaped teeth, with dental cusps set closer together. Mulberry molars have also been associated with enamel hypoplasia.[20]

Gonorrhea

Transmission of gonorrhea to the oral cavity and pharynx is more common via oral-penile contact than oral-vaginal contact.[9] Oral gonorrhea presents symptomless in many cases, but a persistent sore throat is the most predominant kind when symptomatic. Other possible signs include acute ulceration, diffuse oropharyngeal erythema, edematous tissues that bleed easily, and flu-like symptoms.

Untreated oral gonorrhea may lead to disseminated gonococcal infection, causing fever, chills, skin sores, joint inflammation, and joint pain.[21] Disseminated gonorrhea is rare, occurring in approximately 0.5 to 3% of cases.[22]

Tuberculosis

Oral tuberculosis lesions are more commonly located in the posterior aspect of the dorsum of the tongue, followed by the buccal mucosa, gingiva, lips, and the floor of the mouth.[14] 

Primary oral tuberculosis manifests as a single painful, necrotic ulcer that can expand from the sulcular epithelium and the epithelium of the oral cavity to the base of the bordering vestibule.[1][17] The ulcer can last more than 2 to 3 weeks. Primary lesions are also associated with the spread of the disease to cervical lymph nodes that present as enlarged and painful. Tuberculosis osteomyelitis may also appear as lesions within the jaw.

Secondary tuberculosis presents as slowly growing, irregular, and painful oral ulcers that exhibit a thick white mucus at the base and do not self resolve. Like primary lesions, secondary lesions are usually exposed to mechanical trauma.[4][14][23] Some other systemic symptoms that may accompany a patient with tuberculosis are fever, chronic cough, sputum production, hemoptysis, night sweats, weight loss, and appetite loss.

Scarlet Fever 

Scarlet fever is typically associated with acute pharyngitis with accompanying symptoms such as sore throat, fever, odynophagia, cervical adenopathy. The skin presents with a papular-blanching rash, covering most of the body. This rash is described as a "sandpaper rash" because of the lesions' lack of confluence. It develops on the face, trunk, underarms, and groin first, spreading to the extremities later, sparing the palms and soles. 

Scarlet fever has a common oral manifestation known as "strawberry tongue" because of the hyperplastic fungiform papillae and white coating; as the white coating resolves, the remaining papules give the tongue a red, bumpy appearance. The throat may also appear erythematous along with white or yellowish patches making swallowing painful.[7][2]

Evaluation

Any non-healing oral lesion of more than two weeks old requires obtaining an excellent medical history and examining the oral cavity, its contiguous structures, and associated lymph nodes. Obtaining radiographs searching for possible hard tissue abnormalities is also required.[1]

Syphilis 

Syphilis can be screened via nontreponemal serological tests, such as the venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) tests. If these are positive, then further testing is mandatory.[19] Additional specific treponemal tests are required to rule out or confirm the diagnosis of syphilis, like the fluorescent treponemal antibody absorption (FTA-ABS) test or treponema pallidum microhemagglutination assay (TP-MHA).[5][19][24] 

Spirochetes can be detected in chancres in primary syphilis or condylomata lata in secondary syphilis using dark-field microscopy. However, dark-field microscopy should be avoided for oral lesions because the treponemal organism is part of the normal oral flora and could lead to false-positive results.[19] 

The FTA-ABS test is more reliable during the tertiary phase because the nontreponemal tests may give false negatives. The FTA-ABS test may persist as positive even after adequate therapy.

Everyone presenting with signs and symptoms of syphilis should also be tested for other sexually transmitted diseases. Additionally, to prevent congenital syphilis, pregnant women should be screened during their first trimester.[5][19][24]

Gonorrhea 

Laboratory assays directly detect the gonococcal pathogen in urogenital, anorectal, or oropharyngeal swabs and should be considered in patients presenting with symptoms and history that point towards gonorrhea.

Nucleic acid amplification tests (NAATs) can detect N. gonorrhoeae in genitals or extragenital samples such as the pharynx. The development of multiplex NAATs now allows for the simultaneous screening of extensive sexually transmitted diseases.[6]

Tuberculosis 

If tuberculosis is suspected, different tests are available, including tissue histology, tuberculin skin test, acid-fast bacillus microbial staining, and culture or polymerase chain reaction.

A biopsy of any unresolved ulcer is mandatory to confirm the diagnosis of tuberculosis and rule out carcinoma. If the tuberculin skin test returns positive, a confirming chest X-ray is required because patients who received the BCG vaccine (tuberculosis vaccine) can have a false positive tuberculin skin test.[14]

Scarlet Fever 

Scarlet fever is sometimes clinically diagnosed through history and physical examination, although this may be challenging because of its earlier stages' wide variety in severity. Throat cultures and rapid strep tests can be performed to identify group A strep (GAS). A rapid strep test is fast but less specific; if this test is positive for GAS, treatment is initiated immediately. However, if the test is negative and the suspicion of scarlet fever still exists, a throat culture is the following step. A rapid strep test is usually not recommended in older patients (above 45 years of age) because of the low prevalence in this age group.[7]

A throat culture, although time-consuming, is more specific and can detect the bacteria that the rapid strep test may miss; the latter is recommended in young patients with a CENTOR score of 2 and above. The CENTOR score estimates the possibility that the pharyngitis is streptococcal and includes parameters such as range of age groups, tonsillar exudate and inflammation, tenderness of cervical lymph nodes, fever, and the presence or absence of cough.

Treatment / Management

Syphilis 

The chancre and oral lesions in primary syphilis are self-limiting and heal without scar in three to six weeks. A single dose of long-acting benzathine penicillin G (2.4 million units) intramuscular is the drug of choice if primary lesions persist and for secondary syphilis. Tertiary syphilis is also treated with intramuscular benzathine penicillin G once weekly for three to four weeks. The duration of treatment depends on the stage of the disease and its manifestations. Patients who are allergic to penicillin are alternatively treated with doxycycline, tetracycline, or ceftriaxone. Patients diagnosed with syphilis, even if receiving treatment, should abstain from any sexual activity to prevent the spread of the disease. In addition, the sexual partners of a syphilis patient should be notified, tested, and treated accordingly. Post-treatment follow-up is required once every three months for a year using nontreponemal serological tests to ensure the effectiveness of treatment.[5][19][24](B3)

Gonorrhea 

Oropharyngeal gonorrhea can be treated with a single oral dose of 400 mg of cefixime. Increased doses of ceftriaxone and cefixime may be considered due to the growing resistance of N. gonorrhoeae to cephalosporins. The Public Health Agency of Canada recommends an oral cefixime dose of 800 mg or intramuscular ceftriaxone, the latter especially recommended for pharyngeal infections. Aztreonam administered intravenously may also be used to treat pharyngeal and rectal gonococcal infections.[6][25] Patients with sexually transmitted diseases should be referred to a genitourinary medicine specialist.(B2)

Tuberculosis 

A combination of isoniazid, rifampin, pyrazinamide, and ethambutol is used to treat tuberculosis. These drugs are given daily for the initial two months and then another four months of just isoniazid, rifampin, and ethambutol. A chest physician must provide and supervise this therapy to ensure adherence and reduce the chances of drug resistance.

Patients should also be isolated during their treatment course to prevent the further spread of disease. Some second-line agents include injectable drugs (aminoglycosides, amikacin) and fluoroquinolones.[14] BCG vaccine against TB is provided in developing countries to prevent the spread of disease.

Scarlet Fever 

The first-line treatment for GAS infections is beta-lactam antibiotics due to their clinical efficacy and low cost. Penicillins usually outperform cephalosporins and macrolides. If the patient is allergic to penicillin, the first-generation cephalosporin is effective in reducing morbidity and mortality. Penicillin (V) is typically prescribed four times a day for ten days, and other systemic symptoms may be treated with acetaminophen or ibuprofen and fluid replenishment.[7][26] The oral manifestations tend to resolve within two weeks.

Differential Diagnosis

• Squamous cell carcinoma
• Herpetic or fungal infections
• Chlamydia
• Histoplasmosis
• Kawasaki disease[17]

Prognosis

The prognosis of oral lesions is reasonably good for patients who seek care immediately. Without the proper treatment, such oral lesions could become recurrent, take longer to heal, or even progress to precancerous or cancerous lesions. The discussed diseases can present with oral manifestations as either initial symptoms or in later stages of the disease. Dentists and other health care professionals must be capable of recognizing these lesions since early diagnosis and treatment can minimize the risks of transmission and further complications.[8] The prognosis depends on the stage of the disease: syphilis; if caught in the earlier stages, morbidity and mortality decrease.[7][6][5]

Complications

Syphilis 

Untreated syphilis can lead to cardiovascular and neurological syphilis. These complications are irreversible, as the treatment of syphilis can prevent further damage but not repair the one that is already done. Patients with a high titer of secondary syphilis, who are being treated with penicillin, can develop a Jarisch-Herxheimer reaction. The reaction occurs within 24 hours of treatment when the dying organisms release inflammatory cytokines and cause headaches, muscle pain, fatigue, fever, and tachycardia.[5][19]

Gonorrhea 

Undiagnosed or untreated urogenital gonorrheal infections can ascend, causing severe reproductive complications such as pelvic inflammatory disease, endometritis, ectopic pregnancy, and infertility.[6]

Tuberculosis 

Immunocompromised patients, such as those with HIV, have weaker immune systems, making it harder for the body to control the tubercular bacteria. Drug-resistant bacteria can spread infections throughout the body and further complications, including spinal pain, meningitis, and miliary tuberculosis.[27]

Scarlet Fever 

Untreated scarlet fever can lead to rheumatic fever, which affects the heart, joints, skin, and brain. The risk of having these complications is higher in children, and they usually develop 2 to 3 weeks after the initial infection. Scarlet fever can also lead to renal complications, such as post-streptococcal glomerulonephritis; this is also more common in children than adults and can occur within a few weeks of throat infection or 3 to 6 weeks after GAS skin infection.[7]