Epidemiology

Of the three nationally reported notifiable STDs (chlamydia, gonorrhea, and syphilis), gonorrhea is the second most common behind chlamydia with an incidence of 350,062 new cases reported in the United States to the CDC in 2014 (i.e., 110.7 cases per 100,000 persons). This represents an increase in 10 cases per 100,000 over the previous 5-year interval. Marginally more new cases were reported in men than women; more than 50% of cases are in 15- to 24-year old individuals; and the incidence among non-Hispanic blacks are more than 10 times the rates among whites, although the rates in blacks show a decreasing trend.

Etiopathogenesis

N. gonorrhoeae, an aerobic gram-negative β-proteobacteria, typically exists as diplococci with pili (hairlike surface structures) and a marked tropism for human mucosae. It replicates easily in warm, moist areas and preferentially requires high humidity and a specific temperature and pH for optimum growth. It is a fragile bacterium that is readily killed by drying, so it is not easily transmitted by fomites. N. gonorrhoeae displays differential invasiveness based on the type of host epithelium with which it interacts. Columnar epithelium (as found in the mucosal lining of the urethra and cervix) and transitional epithelium (as in the pharynx and rectum) are highly susceptible to infection, but stratified squamous epithelium (skin and mucosal lining of the oral cavity) is generally resistant to infection. Fig. 13.1 depicts the areas of relative epithelial susceptibility to N. gonorrhoeae infection in the oral cavity and oropharynx.

Areas of relative epithelial susceptibility to infection by Neisseria gonorrhoeae within the oral cavity or oropharynx.

N. gonorrhoeae demonstrates a propensity for antibiotic resistance, which has become a major global issue.

Clinical Presentation

Infection in men usually begins in the anterior urethra after sexual exposure and a 2- to 5-day incubation period. Typically, the acute infection is symptomatic and leads to urethritis, a purulent urethral discharge, and dysuria. Asymptomatic infection can occur in a minority of men. The infection may remain localized or may extend posteriorly to involve the epididymis, prostate, seminal vesicles, or bladder. Epididymitis can lead to infertility.

In contrast to men, infection in the majority of women is asymptomatic, which is problematic because patients may not seek medical care for their problem and as a result constitute a reservoir of infection. The incubation takes 5 to 10 days. Most symptomatic infections lead to a cervicitis with resultant purulent drainage and dyspareunia and less commonly urethritis. Bartholin glands and Skene ducts may also be affected. An ascending infection may involve the endometrium, fallopian tubes, ovaries, and pelvic peritoneum, and gonorrhea is a common cause of pelvic inflammatory disease (PID), which affects about 1 million women each year in the United States. PID can be symptomatic (backache and abdominal pain may be present) and may contribute to tubal scarring, leading to infertility or ectopic pregnancy. Perinatal transmission accounts for a small percentage of cases of gonorrhea in the United States, causing gonococcal conjunctivitis and arthritis of the newborn, which if untreated can cause blindness or joint infection.

In both genders, anorectal gonorrhea may occur after anal–genital intercourse. It is commonly less intense than genital infection, but similar symptoms, including a copious purulent discharge, soreness, and pain, may be noted. Pharyngeal infection is detected in 3% to 7% of heterosexual men, 10% to 20% of heterosexual women, and 10% to 25% of homosexual men, and the lower rates in heterosexual men support that it is more likely to occur after fellatio compared with cunnilingus or oral–oral contact. Oropharyngeal infection is typically asymptomatic or manifests as a mild sore throat and clinically is associated with diffuse, nonspecific inflammation. In symptomatic cases, the oropharynx may appear erythematous, with tiny pustules ( Fig. 13.2 ), and can involve the palatine tonsils, which become enlarged with or without a yellowish exudate, and may be associated with cervical lymphadenopathy. The likelihood of transmission of pharyngeal gonorrhea to the genitalia is less common than that of genital–pharynx or genital–genital transmission. Disseminated gonorrhea also can occur infrequently (1%–2% of cases) and may result in a variety of disorders, including migratory arthritis, skin and mucous membrane lesions, endocarditis, meningitis, PID, and pericarditis.

Gonococcal infection of the oropharynx.

Laboratory and Diagnostic Findings

In symptomatic patients with a purulent discharge, Gram stain (or methylene blue/gentian violet) demonstrating gram-negative diplococci within neutrophils is the best point-of-care diagnostic for N. gonorrhoeae infection ( Fig. 13.3 ). In an asymptomatic patient or a patient without purulent discharge (as may be the case in endocervical, rectal, or pharyngeal infections), Gram staining has poor accuracy and is not indicated.

Smear demonstrating gram-negative diplococci within neutrophils.

(Source: http://www.public-domain-image.com/free-images/science/microscopy-images/gonorrhea-neisseria-gonorrhoeae/histopathology-in-an-acute-case-of-gonococcal-urethritis-using-gram-stain-technique/attachment/histopathology-in-an-acute-case-of-gonococcal-urethritis-using-gram-stain-technique .)

Culture and nucleic acid amplification testing (NAAT) are both widely available for gonorrhea testing. The CDC recommends NAAT as the first-line diagnostic for N. gonorrhoeae, for both symptomatic and asymptomatic genital tract and for extragenital site infections, although the U.S. Food and Drug Administration (FDA) has only approved NAAT platforms in genital tract infections. Given the strong likelihood for co-infection with C. trachomatis, these platforms are typically bundled to test for both organisms. Culture for N. gonorrhoeae is indicated in patients who have received a CDC-recommended antimicrobial regimen and yet have a persistent NAAT-positive result. Culture can be coupled with antimicrobial sensitivity testing, which is important given the propensity of N. gonorrhoeae for antimicrobial resistance.

Medical Management

Because of antimicrobial sensitivity, the CDC has updated treatment recommendations and now recommends dual therapy of a single dose of ceftriaxone 250 mg intramuscularly (IM) plus a single dose of azithromycin 1 g orally for the treatment of uncomplicated gonococcal infection of the cervix, urethra, pharynx, or rectum in adults (regimens for other sites, children, or during pregnancy are different). An alternative regimen, when ceftriaxone is unavailable, is a single dose of cefixime 400 mg orally plus the azithromycin 1 g orally. For patients with a cephalosporin allergy, the CDC recommends a single dose of gemifloxacin 320 mg orally plus a single dose of azithromycin 2 g orally or a single dose of gentamicin 240 mg IM plus a single dose of azithromycin 2 g orally. All sexual partners should be tested and treated, and patients who have been treated yet who have persistent signs or symptoms should undergo culture and antibiotic sensitivity testing.

Dental Considerations

A patient with a known recent gonorrhea infection that has been administered appropriate antibiotic therapy poses little threat of disease transmission to the dental team. Patients in this category can receive dental care within days of beginning antibiotic treatment. Patients with an active pharyngitis and other oral signs or symptoms suggestive of an active infection of unclear etiology should be promptly referred to a physician for further evaluation.

Oral Manifestations

Reports of gonorrhea involving the oral cavity (i.e., sites other than the oropharynx) are rare and summarized in two reviews. Encountering patients with a symptomatic pharyngitis warrants referral for further evaluation.

Epidemiology

Of the three nationally reported notifiable STDs, syphilis is the least common with an incidence of 19,999 new primary and secondary syphilis cases reported in the United States to the CDC in 2014 (i.e., 6.3 cases per 100,000 persons), a rate that has almost doubled over the past decade. The estimated number of new and existing infections (i.e., including all stages of syphilis prevalence) in 2014 was 63,450. More than 10 men are infected for every woman, with the highest incidence in black men, although the greatest increases have been reported in men who have sex with men (MSM), which is concerning because of the increased risk for the transmission of HIV infection.

Congenital syphilis occurs when a fetus is infected in utero by an infected mother. In 2014, a rate of 11.6 per 100,000 live births was reported, demonstrating an increasing trend since 2012.

Etiopathogenesis

Treponema pallidum is a slender, fragile microaerophilic spirochete. It is transmitted predominantly sexually, by genital–genital, oral–genital, or rectal–genital contact with contaminated sores. However, transmission also may occur through kissing or as a bloodborne infection and may be transmitted to fetuses, leading to congenital syphilis. T. pallidum is easily killed by heating, drying, disinfecting, and using soap and water; as such, transmission by fomites is unlikely. It is believed that T. pallidum does not invade completely intact skin; however, it can invade intact mucosal epithelium and gain entry via minute abrasions or hair follicles. Within a few hours after invasion, spread to the lymphatics and the bloodstream occurs, resulting in early widespread dissemination of the disease. The risk of transmission occurs during the primary, secondary, and early latent stages of disease but not in late syphilis.

Clinical Presentation

The clinical manifestations of syphilis are classically divided according to stages of disease, with each stage having its own unique signs and symptoms. These stages are primary, secondary, latent, tertiary, and congenital. Patients are most infectious during the first 2 years of the disease. It is important to note that many infected persons do not develop symptoms for years, yet they remain at risk for late complications if not treated.

Primary Syphilis

This stage is characterized by the chancre, a solitary (although multiple chancres are possible) round, often painless, somewhat firm lesion that develops at the site of contact with the infectious organism. The chancre usually occurs within 2 to 3 weeks (range, 10–90 days) after exposure ( Figs. 13.4 and 13.5 ), and patients are infectious before it appears. The lesion begins as a small papule and enlarges to form a surface erosion or ulceration that commonly is covered by a yellowish hemorrhagic crust that is teeming with T. pallidum. Enlarged, painless, and firm regional lymphadenopathy is typically present. The chancre usually subsides in 3 to 6 weeks without treatment, leaving variable scarring in the form of a healed papule. More than 80% of chancres occur on the genitalia, and the most common extragenital site is the oral cavity or oropharynx (others include the fingers, nipples, perineum, anus, and rectum). If adequate treatment is not provided, the infection progresses to secondary syphilis.

Primary syphilis: chancre of the penis.

(From Habif TP, Campbell JI Jr, Chapman MS, et al: Skin disease: diagnosis and treatment, ed 2, St. Louis, Mosby, 2005.)

Chancre on the tongue seen in primary syphilis.

(From Ibsen DAC, Phelan JA: Oral pathology for the hygienist, ed 4, St. Louis, Saunders, 2003.)

Secondary Syphilis

The manifestations of secondary syphilis appear 6 to 8 weeks after initial exposure and are associated with the hematogenous spread and associated systemic immunologic response to T. pallidum. The chancre may or may not have completely resolved by this time. There is a wide spectrum of systemic signs and symptoms, including fever, malaise, headache, arthralgias, generalized lymphadenopathy, and patchy hair loss and a generalized eruption of the skin and mucous membranes, including the oral cavity (see Oral Manifestations section). In some cases, secondary syphilis can be asymptomatic. The skin rash is maculopapular ( Fig. 13.6, A ) with well-demarcated and reddish brown areas involving the trunk and with a predilection for the palms and soles; they are typically not itchy. Warty lesions, known as condyloma lata, may involve the genitalia, the oral cavity, or both. Lues maligna is a rare and severe manifestation of secondary syphilis in immunocompromised patients, such as those with HIV infection. The lesions of skin and mucous membranes are highly infectious. Without treatment, secondary syphilis ultimately resolves; however, infection progresses to latent or late stages.

Lesions of secondary syphilis. A, Profuse papular rash. B, Multiple oral lesions, including mucous patches, and nonwipeable white plaques.

(A, From Habif TP, Campbell JI Jr, Chapman MS, et al: Skin disease: diagnosis and treatment, ed 2, St. Louis, Mosby, 2005. B, From Dr. Stefania Leuci, Federico II University of Naples, Italy.)

Latent Syphilis

Latent syphilis is defined as the third stage of the untreated infection. Patients are seroreactive but are asymptomatic and do not show clinical evidence of disease. Latent syphilis is divided into early latent syphilis (i.e., disease acquired within the preceding year) and late latent syphilis (>1 year). During the first 4 years of latent syphilis, patients may have mucocutaneous relapses and are considered infectious. After 4 years, relapses typically do not occur, and patients are considered noninfectious. The latent stage may last for many years or even for the remainder of the person’s life. In some untreated patients, however, progression to tertiary syphilis occurs.

Tertiary Syphilis

The tertiary (late) stage occurs in 10% to 40% of untreated persons, generally several years after disease onset. It is the destructive stage of the disease, although patients are considered noninfectious. Any organ of the body may become involved, and some have classified tertiary disease into three subtypes: neurosyphilis, cardiovascular, and gummatous disease. Neurosyphilis can result in a meningitis-like syndrome, Argyll Robertson pupils (which react to accommodation but not to light), altered tendon reflexes, general paresis, tabes dorsalis (degeneration of dorsal columns of the spinal cord and sensory nerve trunks), difficulty in coordinating muscle movements, or insanity. Cardiovascular syphilis is essentially vascular in nature and the end product of an obliterative endarteritis. This can lead to carotid and aortic stenosis and may ultimately manifest as an aneurysm of the ascending aorta. The gumma, which is the classic localized lesion of tertiary syphilis, may involve the skin, mucous membranes (including the oral cavity), bone, or within any organ. It is believed to be the end result of a hypersensitivity reaction and is basically a noninfectious inflammatory granulomatous lesion with a central zone of necrosis.

Congenital Syphilis

Syphilis may occur congenitally if the mother is infected while pregnant (i.e., secondary to treponemal bacteremia), and transplacental infection can occur as early as 9 to 10 weeks in utero. Approximately 25% of pregnancies result in stillbirth, and 12% result in neonatal death. The majority of newborns (>80%) are asymptomatic. The disease persists worldwide because a substantial number of women do not receive antenatal syphilis testing. There are early and late clinical manifestations. Early signs, manifesting at birth or up to 2 years after birth, may include hepatomegaly and associated liver dysfunction, hematologic abnormalities, mucocutaneous findings (i.e., maculopapular rash, a rhinitis secondary to nasal inflammation, perioral and perineural condylomata lata), and bone changes (osteochondritis and periostitis causing pseudoparalysis) and, less commonly, neurologic manifestations. Late stage congenital syphilis is rare, and there is a classic triad of congenital syphilis known as Hutchinson’s triad that includes interstitial keratitis of the cornea, eighth nerve deafness, and dental abnormalities (see Oral Manifestations ). In addition, rhinitis can lead to a saddle nose caused by cartilage destruction, rhagades, neurologic sequelae (including mental retardation), and bony abnormalities such as frontal bossing.

Laboratory and Diagnostic Findings

T. pallidum has never been cultured successfully on any type of medium and is difficult to stain for microscopic examination. Historically, the definitive diagnosis of syphilis has been made from microscopic examination of fresh lesion exudates during the primary and early secondary stages using positive dark-field microscopic examination. Other direct testing includes direct fluorescence antibody (DFA) tests or polymerase chain reaction (PCR). However, such testing is no longer widely available, not indicated to detect all stages of syphilis, and cannot be used to monitor the disease after treatment. With the advent of serologic tests, the traditional diagnosis of syphilis is based on clinical findings in conjunction with a two-step testing algorithm using a nontreponemal “screening” test followed by a confirmatory specific treponemal test.

Nontreponemal Testing

The nontreponemal tests include the Venereal Disease Research Laboratory (VDRL) slide test and the rapid plasma reagin (RPR) test. These tests, both equally valid but noncomparable, detect an antibody-like substance called reagin, which is a surrogate for the immunologic response to a syphilis infection. They are less specific but can better assess current disease activity. The initial test is qualitative, and if positive, a quantitative step is performed that generates “titers” values reported as serologic dilutions (e.g., 1 : 2, 1 : 4, 1 : 8). They are consistently positive and yield the highest titers between 3 and 8 weeks after the appearance of the primary chancre. A fourfold change in titers (e.g., 1 : 4 to 1 : 16 or 1 : 32 to 1 : 8) is the threshold signifying a clinically meaningful change in serial test results. In primary syphilis, nontreponemal test results usually revert to negative within 12 months after successful treatment. In secondary syphilis, up to 24 months may be required for the patient to become seronegative. Occasionally, a patient will remain seropositive for the rest of his or her life or will test positive with an associated infection or condition (false positive). With tertiary syphilis, many patients remain seropositive for life.

Treponemal Testing

These include the fluorescent treponemal antibody absorption test (FTA-ABS), T. pallidum particle agglutination assay (TPPA), T. pallidum hemagglutination assay (TPHA), and various immunoassays (i.e., enzyme immunoassays [EIAs], chemiluminescent immunoassays [CIAs], and microbead immunoassays [MIAs]). These are highly specific, but a positive test result cannot differentiate between current and past infection because antibodies remain positive in most patients.

A newer three-step “reverse” algorithm has been adopted with the intent to better capture those with a past history of infection and early stage disease. A treponemal immunoassay is performed first and if reactive is followed by a qualitative nontreponemal test. If this second test result is negative, a final quantitative nontreponemal test is performed. Recently, the FDA has approved a rapid point-of-care treponemal screening test known as the Syphilis Health Check. These point-of-care tests have similar performance to the laboratory treponemal tests and may facilitate screening in resource limited settings.

Medical Management

Testing for concomitant HIV infection and the diagnosis and management of infection in the patient’s sexual partners are recommended. Parenteral injection of long-acting benzathine penicillin G, 2.4 million IU IM in a single dose, remains the recommended and predictable treatment for primary, secondary, or early latent syphilis in adults; 50,000 IU/kg of penicillin G should be used for children or infants. As with gonorrhea, infectiousness is reversed rapidly, probably within a matter of hours after injection. A more intensive regimen is indicated for those with late latent or tertiary syphilis: injections of 2.4 million IU IM once a week for 3 weeks (i.e., total of 7.2 million IU). Neurosyphilis or ocular syphilis is managed more effectively with either 18 to 24 million IU of aqueous crystalline penicillin G delivered intravenously (IV) or 2.4 million IU procaine penicillin G given IM daily plus probenecid 500 mg four times a day, with both regimens given over a 10- to 14-day period. Neonates with possible congenital syphilis should be assessed by means of clinical, radiographic, and laboratory tests of blood and cerebrospinal fluid (CSF) for VDRL. If results prove presence of the disease or suggest that syphilis is highly probable, then the infant should be treated with IV penicillin G for at least 10 days. The first-line drug for patients allergic to penicillin (except for pregnant patients) is oral doxycycline (100 mg orally twice a day for 2 weeks) or tetracycline 500 mg four times a day for 2 weeks. Desensitization to penicillin is recommended for pregnant patients allergic to penicillin. Patients with primary or secondary syphilis who are otherwise immunocompetent should be retested at 6 and 12 months to monitor for seroconversion. HIV-infected patients and those with late latent or tertiary syphilis require more intensive or longer surveillance, respectively. The Jarisch-Herxheimer reaction is an acute febrile reaction that is frequently accompanied by chills, myalgias, and headache that occur within 24 hours after initiation of antibiotic therapy for syphilis. It occurs most often (i.e., in 50% patients) after treatment for early syphilis.

Dental Considerations

Lesions of untreated primary and secondary syphilis are infectious, as are the patient’s blood and saliva. Even after treatment has begun, its absolute effectiveness cannot be determined except through conversion of the positive serologic test to negative; however, early reversal of infectiousness is to be expected after antibiotic treatment has been initiated. The time required for this conversion varies from a few months to longer than 1 year. Therefore, patients who are currently under treatment or who remain seropositive for syphilis after receiving treatment should be viewed as potentially infectious. Still, any necessary dental care may be provided with adherence to standard precautions unless oral lesions are present. Dental treatment can commence after oral lesions have been successfully treated.

Oral Manifestations

Oral syphilitic chancres and mucous patches are usually painless unless they become secondarily infected. Both lesions are highly infectious. Oral chancres (see Fig. 13.4 ) are typically solitary lesions that may involve the lips, tongue, oropharynx, or other oral sites and may be associated with lymphadenopathy. They begin as a round papule that erodes into a painless ulcer with a smooth surface. Size can vary from a few millimeters to more than 2 cm. Sometimes chancres may demonstrate induration. The oral manifestations of secondary syphilis (present in >30% of patients) ( Fig. 13.6, B ) are highly variable and include single or multiple lesions such as mucous patches, maculopapular lesions (i.e., the likely counterpart to the skin rash), erosions, ulcerations including a peculiar “snail-track” variety, white plaques resembling leukoplakia, and papulonodular lesions. The intraoral mucous patch is often asymptomatic and appears as a slightly raised grayish plaque and may involve multiple oral sites. The oral gumma of tertiary syphilis is rare. It typically presents as a solitary lesion that most commonly involves the tongue and palate, which may be exophytic, indurated, and with surface ulceration. Palatal gummas may erode bone and perforate into the nasal cavity or maxillary sinus, creating an oronasal or oral-antral fistula. An atrophic or interstitial glossitis has also been reported in tertiary syphilis. Oral manifestations of congenital syphilis include peg-shaped permanent central incisors with notching of the incisal edge (Hutchinson’s incisors) ( Fig. 13.7 ), defective molars with multiple supernumerary cusps (mulberry molars), a high narrow palate, and perioral rhagades (skin fissures).

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