Incidence and Prevalence

Gonorrhea is the second most commonly reported infectious disease and STD in the United States, behind chlamydial infection. An estimated 700,000 new cases are reported each year in the United States, and about half of these are reported to the Centers for Disease Control and Prevention (CDC).^1,5 The reported incidence of gonorrhea in 2009 (i.e., 111 cases per 100,000 persons) was the lowest ever reported in the United States and was significantly lower than the incidence in the mid-1970s, when more than 1 million cases were reported.^5,6

Humans are the only natural hosts for this disease, and its occurrence is worldwide. Gonorrhea is transmitted almost exclusively by sexual contact, whether genital–genital, oral–genital, or rectal–genital. The primary sites of infection are the genitalia, the anal canal, and the pharynx.

Gonorrhea can occur at any age, although it is seen most commonly in sexually active teenagers and young adults (8.5 per 1000 in the 15- to 29-year-old age group) and in the South. Rates of infection are similar in men and women, but differ by racial background. African Americans and Hispanics have 20.5 times higher rates of gonorrhea than whites.⁵ Risk factors other than age include young age at first sexual experience, multiple sexual partners, low level of education, low socioeconomic status, and living in an urban setting.^1,5 At the current rate of infection, an average dental practice of 2000 adult patients can expect to provide care for 2 patients with gonorrhea.

Etiology

Gonorrhea is caused by N. gonorrhoeae, a gram-negative intracellular diplococcus. N. gonorrhoeae is an aerobic microbe that replicates easily in warm, moist areas and preferentially requires high humidity and 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. It develops resistance to antibiotics rather easily, and many strains have become resistant to penicillin, tetracycline, and quinolones.

Signs and Symptoms

In men, symptoms usually occur after an incubation period of 2 to 5 days, although they may take as long as 30 days to appear. The most common findings include a mucopurulent (white, yellow, or green) urethral discharge, burning pain on urination, urgency, and frequency. Tenderness and swelling of the meatus may occur.

In women, a significant percentage of cases may be asymptomatic or only minimally symptomatic. Symptomatic infection may demonstrate vaginal or urethral discharge, dysuria with frequency and urgency, and burning pain when urinating. Backache and abdominal pain also may be present.

Approximately 50% of women and 1% to 3% of men are asymptomatic or only mildly symptomatic. This is unfortunate because patients may not seek medical care for their problem and as a result constitute a large reservoir of infection.

Gonococcal infection of the anal canal commonly is less intense than genital infection, but similar signs and symptoms, including a copious purulent discharge, soreness, and pain, may be noted.

Within the oral cavity, the pharynx is most commonly affected.⁸ Pharyngeal infection is reported to occur in 3% to 7% of heterosexual men, 10% to 20% of heterosexual women, and 10% to 25% of homosexual men.⁹ It usually is seen as an asymptomatic infection with diffuse, nonspecific inflammation or as a mild sore throat. The likelihood of transmission of pharyngeal gonorrhea to the genitalia seems much less than that of genital–genital transmission.^10,11 Of significance, however, is the fact that N. gonorrhoeae has been cultured in expectorated saliva from two thirds of patients with oropharyngeal gonorrhea.¹⁰

Gonococcal stomatitis or oral gonorrhea is uncommon; case reports in the literature are limited.^9,12–15 Acute temporomandibular joint arthritis caused by disseminated gonococcal infection from a genital site has been described.¹⁶

Laboratory Findings

Laboratory diagnosis of a genital N. gonorrhoeae infection can be made based on the finding of gram-negative diplococci within polymorphonuclear leukocytes in a smear of urine or of purulent discharge in symptomatic mean (Figure 13-2). In women and asymptomatic men, nucleic acid amplification testing (NAAT) of urine is recommended because of its high sensitivity and specificity, and it can be used to simultaneously test for C. trachomatis.^1,17 Culture is also available for diagnosis of N. gonorrhoeae from rectal and pharyngeal specimens. In suspected cases of oropharyngeal gonorrhea, because other species of Neisseria are normal inhabitants of the oral cavity, NAAT is more specific than a gram stain.

FIGURE 13-2 Smear demonstrates gram-negative diplococci within a leukocyte.

(Courtesy University of Iowa, Iowa City, Iowa, and Gary E. Kaiser, PhD, The Community College of Baltimore County, Baltimore, Maryland)

Incidence and Prevalence

Syphilis is the fifth most frequently reported STD in the United States today, surpassed only by chlamydial infection, gonorrhea, salmonellosis, and AIDS. In 1990, the incidence of primary and secondary syphilis reached 50,223 cases.⁵ The number of cases of primary and secondary syphilis dropped to 6,000 in 2000. Since then, the rate has been steadily climbing. In 2009, almost 13,997 cases were reported, a rate of decline of 4.6 cases per 100,000 population.^4,5,19 A disproportionately high number of cases continue to occur in the South and among Hispanic and non-Hispanic African American men and women. Syphilis occurs more commonly in persons aged 25 to 39 years. Its incidence in males is greater than in females, with a ratio of almost 6 : 1.¹⁹

Congenital syphilis occurs when the fetus is infected in utero by an infected mother. In 2008, a total of 431 cases of congenital syphilis were reported to the CDC. This represents a rate of 10.1 per 100,000 live births—higher than the 8.2 cases per 100,000 live births in 2005—but still a dramatic decline from the peak of 107.3 cases per 100,000 live births in 1991.¹⁹

Etiology

The etiologic agent of syphilis is Treponema pallidum, which is a slender, fragile anaerobic spirochete. It is transmitted predominantly sexually, including by oral–genital and rectal–genital contact with contaminated sores. However, transmission also can occur through nonsexual means such as kissing, blood transfusion, or accidental inoculation with a contaminated needle. Indirect transmission by fomites is possible but uncommon, because the organism survives for only a short time outside the body.^1,20 T. pallidum is easily killed by heating, drying, disinfecting, and using soap and water. The organism is difficult to stain, except with use of certain silver impregnation methods. Demonstration is best done with darkfield microscopy on a fresh specimen.

Pathophysiology

Available evidence suggests that T. pallidum does not invade completely intact skin; however, it can invade intact mucosal epithelium and gain entry through minute abrasions or at the hair follicles. Within a few hours after invasion, bacterial spread to the lymphatics and the bloodstream occurs, resulting in early widespread dissemination of the disease. The early response to bacterial invasion consists of endarteritis and periarteritis.²⁰ The risk of transmission is during the primary, secondary, and early latent stages of disease, but not in late syphilis.²¹ Overall, patients are most infectious during the first 2 years of the disease.

Signs and Symptoms

Manifestations and descriptions of syphilis are classically divided according to stages of the disease, with each stage having its own specific signs and symptoms related to disease duration and antigen-antibody responses. The stages are primary, secondary, latent, tertiary, and congenital. Of note, many infected persons do not develop symptoms for years, yet remain at risk for late complications if the infection is not treated.

Primary Syphilis

The classic manifestation of primary syphilis is the chancre, a solitary firm, round, granulomatous lesion that develops at the site of inoculation with the infectious organism. The chancre usually occurs within 2 to 3 weeks (range, 10 to 90 days) after exposure (Figure 13-3). Patients are infectious, however, 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 and teems with T. pallidum. It typically is painless. Associated with the chancre are enlarged, painless, hard regional lymph nodes. The chancre usually subsides in 3 to 6 weeks without treatment, leaving variable scarring in the form of a healed papule.^20,22 The genitalia, oral cavity (lips, tongue), fingers, nipples, and anus are common sites for chancres. Figure 13-4 shows examples of extragenital syphilitic chancres (lip and tongue). If adequate treatment is not provided, the infection progresses to secondary syphilis.

FIGURE 13-3 Primary syphilis: Chancre of the penis.

(From Swartz MH: Textbook of physical diagnosis, ed 6, Philadelphia, Saunders, 2010.)

FIGURE 13-4 Primary Syphilis.

A, Chancre on tongue seen in primary syphilis. B, Extragenital chancre of the lip.

(A, From Ibsen DAC, Phelan JA: Oral pathology for the hygienist, ed 5, St. Louis, Saunders, 2009.)

Secondary Syphilis

The manifestations of secondary syphilis appear 6 to 8 weeks after initial exposure. The chancre may or may not have completely resolved by this time. The symptoms and signs of secondary syphilis include fever, arthralgia and malaise, generalized lymphadenopathy, and patchy hair loss and develop in 80% of patients. Generalized eruptions of the skin and mucous membranes also occur (Figure 13-5, A) and include condyloma lata or wart-like growths on the genitalia. The papules of the rash are well demarcated and reddish brown and have a predilection for the palms and soles; they typically are not itchy. Oral manifestations of secondary syphilis include pharyngitis, papular lesions, erythematous or grayish-white erosions (mucous patches) (see Figure 13-5, B), irregular linear erosions, and, rarely, parotid gland enlargement. The lesions of skin and mucous membranes are highly infectious.^20,22 Without treatment, clinical manifestations of secondary syphilis ultimately resolve; however, infection progresses to latent or the tertiary stages.

FIGURE 13-5 Lesions of Secondary Syphilis.

A, Profuse papular rash. B, Mucous patch of the lower lip

(A, From Habif TP, et al: Skin disease: diagnosis and treatment, ed 3, St. Louis, 2011, Mosby.)

Congenital Syphilis

Syphilis or its sequelae occur in the newborn if the mother is infected while carrying the child. The disease is transmitted to the fetus in utero, usually after the 16th week, because before this time, the placenta prevents transmission of bacteria. The disease persists worldwide because a substantial number of women do not receive serologic testing for syphilis during pregnancy, or they may undergo testing too late in pregnancy to receive prenatal care.²⁴ Physical manifestations vary according to the time of infection. The sequelae of early infection include osteochondritis, periostitis (frontal bossing of Parrot), rhinitis, rash, and ectodermal changes. Syphilis contracted during late pregnancy may involve bones, teeth (see “Oral Manifestations”), eyes, cranial nerves, viscera, skin, and mucous membranes. A classic triad of congenital syphilis known as Hutchinson’s triad includes interstitial keratitis of the cornea, eighth nerve deafness, and dental abnormalities, including Hutchinson’s incisors (Figure 13-6) and mulberry molars.

FIGURE 13-6 Congenital syphilis: Hutchinson’s teeth.

Laboratory Findings

T. pallidum has never been cultured successfully on any type of medium; therefore, the definitive diagnosis of syphilis is made from a positive darkfield microscopic examination or on the basis of direct immunofluorescent antibody tests on fresh lesion exudates. Darkfield examination yields consistently positive findings only during primary and early secondary stages. Definitive diagnosis of oral lesions by this method is difficult, because other species of Treponema are indigenous to the oral cavity.

Syphilis typically is diagnosed by a two-step process involving a nonspecific (screening) antibody test, followed by a treponeme-specific test. Screening antibody tests of blood also are known as serologic tests for syphilis (STS). These tests are of two basic types, indirect and direct, and are differentiated by the types of antibodies they measure.

Incidence and Prevalence

Genital herpes is an important STD worldwide. Its exact incidence in the United States is unknown because it is not a reportable disease, and most persons have not been diagnosed because their disease is mild or asymptomatic. An estimated 50 million people, or more than 25% of persons 12 years of age and older, in the United States are infected.^1,25 An estimated 1.6 million new cases of HSV-2 occur annually in the United States.^26,27 The prevalence in developing countries is between 40% and 60%.²⁷ About 70% to 95% of first-episode cases of genital herpes are caused by HSV-2, whereas up to 30% in some series are caused by HSV-1.¹ Prevalence rates in women (25%) and in African Americans (46%) are reportedly higher than those in men (20%) and in whites (18%).²⁵ Most persons infected with HSV-2 have not been diagnosed with genital herpes thus enhancing its transmission.

Etiology

HSV belongs to a family of eight human herpesviruses that includes cytomegalovirus, Epstein-Barr virus (EBV), varicella-zoster virus (VZV), human herpesvirus type 6 (HHV-6), human herpesvirus type 7 (HHV-7), and Kaposi sarcoma–associated herpesvirus (HHV-8). HSV-1 is the causative agent of most herpetic infections that occur above the waist, especially on the mucosa of the mouth (herpetic gingivostomatitis, herpes labialis), nose, eyes, brain, and skin. Infection with HSV-1 is extremely common; most adults demonstrate antibodies to this virus. It is thought that many primary infections with HSV-1 are subclinical and thus are never known to the infected person. Transmission usually occurs through close contact, such as touching or kissing, and transfer of infective saliva. HSV-1 also is transmitted by sexual contact. Airborne droplet infection has not been well demonstrated, although it is possible.²⁸ Autoinoculation from contact with face, fingers, eyes, and genitalia is a persistent clinical problem.

HSV-2 is the causative agent of most herpes infections that occur below the waist, such as in or around the genitalia (genital herpes). HSV-2 is transmitted predominantly by sexual contact but also may be passed nonsexually. Its primary mode of transmission is through an asymptomatic viral shedder. HSV-2 can be transmitted to a newborn from an infected mother.

Although the primary site of occurrence of HSV-1 is above the waist and of HSV-2 below the waist, each infection may occur at either site and in fact can be inoculated from one site to the other (Figure 13-7). Furthermore, the two types cannot be differentiated on basis of skin lesions and other clinical manifestations.

FIGURE 13-7 Primary herpes simplex type 2 occurring in the oral cavity documented by laboratory testing.

(From Sapp JP, et al: Contemporary oral and maxillofacial pathology, ed 2, St. Louis, 2004, Mosby.)

Pathophysiology and Complications

The pathologic processes of herpesvirus infections HSV-1 and HSV-2 are essentially identical; thus, the lesions of skin and mucous membranes are identical. Infection arises from intimate contact with a lesion or infective fluid (e.g., saliva). Epithelial cells are invaded, and viral replication occurs. Characteristic cellular changes include ballooning degeneration, intranuclear inclusion bodies, and the formation of multinucleated giant cells. With cellular destruction come inflammation and increasing edema, which result in formation of a papule that progresses to a fluid-filled vesicle. These vesicles rupture, leaving an ulcerated or crusted surface.

Lymphadenopathy and viremia are prominent features. In normal persons, the primary infection is contained by usual host defenses and runs its course within 10 to 20 days. However, spread to other epidermal sites (e.g., herpetic whitlow [infection of the fingers], keratoconjunctivitis [eyes]) and in neonates during childbirth has been documented. In rare cases, infants and immunosuppressed persons can develop systemic (meningitis) and widespread infection that may result in significant morbidity and death.

During the epithelial infection, progeny enter the ends of local peripheral neurons and migrate up the axon to the regional ganglion (HSV-1 primarily in the trigeminal, and HSV-2 primarily in the sacral), where they reside for the life of the host. After stimulation such as trauma, sunlight, menses, or intercourse, the virus can reactivate, migrate down the axon, and produce recurrent infection. Of the two HSV serotypes that can infect the sacral ganglia, HSV-2 is more efficient in reactivating and producing recurrent genital lesions, whereas HSV-1 may pose a greater risk for neonatal herpes.²⁹ Also, immune suppression increases the risk for more frequent and severe recurrences.

Signs and Symptoms

Most (about 60%) new cases of HSV-2 infection are asymptomatic²⁷; newly acquired cases are asymptomatic more frequently in men than in women. After an incubation period of 2 to 7 days, lesions (i.e., papules, vesicles, ulcers, crusts, and fissures) of primary genital herpes may appear. In women, both internal and external genitalia may be involved, as well as the perineal region and the skin of the thighs and buttocks. In men, the external genitalia is typically involved, as may the skin of the inguinal area. Lesions in moist areas tend to ulcerate early, are painful, and may be associated with dysuria. Lesions on exposed dry areas tend to remain pustular or vesicular and then crust over. Painful regional lymphadenopathy accompanies the primary infection, along with headache, malaise, myalgia, and fever. Clinical manifestations subside in about 2 weeks, and healing occurs in 3 to 5 weeks.

Outbreaks of recurrent genital herpes typically occur 2 to 6 times per year and generally are less severe and more localized than the primary infection. Recurrences frequently are precipitated by menstruation, intercourse, or immunosuppression. A prodrome of localized itching, tingling, paresthesia, pain, and burning may be noted and is variably followed by a vesicular eruption (Figure 13-8). Healing occurs in 10 to 14 days. Constitutional symptoms generally are absent. Between recurrences, infected persons shed virus intermittently and asymptomatically from the genital tract.

FIGURE 13-8 Recurrent herpes simplex virus infection of the foreskin.

(From Habif TP, et al: Skin disease: diagnosis and treatment, ed 3, St. Louis, 2011, Mosby.)

HSV-1 and HSV-2 lesions are highly infectious, promoting transmission to other people, or to other sites on the body. Orogenital contact may result in spread from the source to the oral cavity or genitals of the sexual partner. The infectious period of herpetic lesions is considered to extend until the crusting stage. Therefore, all herpetic lesions (i.e., papular, vesicular, pustular, and ulcerative) before completion of crusting should be assumed to be infectious.

Laboratory Findings

Cytologic examination of a smear (Tzanck preparation) taken from the base of a herpetic lesion reveals typical features, including ballooning degeneration of cells, intranuclear inclusion bodies, and multinucleated (fused) giant cells. However, cytologic evaluation is nonspecific and less sensitive than viral culture. Diagnosis is best established by swabbing an infected secretion or ulcer and isolating the virus by cell culture or amplifying its sequences by PCR. Cultured virus is identified by staining the infected cells for HSV antigen with the use of immunofluorescence or immunoperoxidase. PCR is particularly helpful when neurologic symptoms develop and cerebrospinal fluid is sampled. Serologic detection of antibodies to HSV-1 glycoprotein G1 or HSV-2 glycoprotein G2 aids in diagnosis and management (e.g., counseling the patient about the potential for recurrences and transmission).¹

Incidence, Prevalence, and Etiology

More than 90% of adults worldwide have been infected with EBV. In the United States, about 50% of 5-year-old children and 70% of college freshmen have evidence of previous EBV infection.^33,34 The peak age of acquisition in the United States is reportedly 15 to 19 years.³⁵ The annual incidence in this adolescent age group is 3.4 to 6.7 cases per 1000 persons. Incidence has been reported as 30 times higher in whites than in blacks in the United States.³³ No gender predilection has been noted. Having numerous sexual partners increases the risk for acquisition of EBV.

Pathophysiology

EBV is a lymphotropic herpesvirus that is transmitted primarily through close personal contact (i.e., intimate kissing) and exposure to infected saliva and oropharyngeal secretions. Infrequently, it is transmitted through shared infected drinks, eating utensils, or infected blood products. Incubation time is 30 to 50 days. A prodromal period of 3 to 5 days precedes the clinical phase, which lasts 7 to 20 days. During the prodromal phase, the virus infects oropharyngeal epithelial cells and spreads to B lymphocytes in the tonsillar crypts. Infected B lymphocytes circulate through the reticuloendothelial system, triggering a marked lymphocytic response. In infectious mononucleosis, large, reactive lymphocytes expand from 1% to 2% to 10% to 40% of the circulating white blood cells. These expanded T lymphocytes are reactive to the EBV-infected B lymphocytes (Figure 13-9).³⁴ The combination of reactive lymphocytes, the cytokines they produce, and the B cell–produced (heterophile) antibodies directed against EBV antigens contributes to the clinical manifestation of the acute infection. Hepatosplenomegaly develops in about 40% to 50% of patients, self-limiting hepatitis develops in about 10%, splenic rupture occurs in 0.1% to 0.2% of all cases, and death is a rare outcome.^34,36 After the acute infection, the EBV remains latent in B lymphocytes for the life of the host and is shed in the saliva. EBV is an effective transforming agent and is associated with the development of lymphomas and nasopharyngeal.

FIGURE 13-9 Atypical lymphocytes in infectious mononucleosis.

(From Kumar V, Abbas A, Fausto N, editors: Robbins & Cotran’s pathologic basis of disease, ed 8, Philadelphia, 2010, Saunders.)

Signs and Symptoms

Infectious mononucleosis usually is asymptomatic when found in children; however, about 50% of infected young adults develop symptoms. Fever, sore throat, tonsillar enlargement, lymphadenopathy, malaise, and fatigue are the predominant features. About a third of patients demonstrate palatal petechiae during the first week of the illness, and about 30% of patients develop an exudative pharyngitis.^34,37,38 Generalized skin rash and petechiae of the lips are seen in about 10% of cases, and in sexually active persons genital ulcers may be present. The liver and spleen can enlarge, and become tender and inflamed. Symptoms tend to dissipate within 3 weeks of onset, and the majority recovers without apparent sequelae.

Laboratory Findings

The diagnosis is made on the basis of signs and symptoms and a laboratory profile characterized by marked lymphocytosis (e.g., 50% lymphocytes [primarily T lymphocytes]) with at least 10% atypical lymphocytes on a peripheral blood smear (see Figure 13-9) and a positive heterophile antibody test. Heterophile antibodies are immunoglobulin M (IgM) antibodies that bind (agglutinate) to antigens different from the antigen that induced them, such as erythrocytes from nonhuman (sheep, horses) species.⁴² This process forms the basis for the Monospot (Meridian Bioscience, Inc., Cincinnati, Ohio) rapid latex agglutination test. Symptomatic patients in whom a heterophile antibody test is negative should be retested in 7 to 10 days, because this test can be insensitive during the first week. If the second test is negative, tests for viral capsid antigen (VCA) IgG and VCA IgM antibody and EBV nuclear antigen (EBNA) should be performed.³⁸ These tests are more specific but costly. If test results are positive, the patient has heterophile-negative infectious mononucleosis. A few patients with the classic disease description may be heterophile antibody-negative and EBV IgM-negative. In these patients, tests for cytomegalovirus (CMV), Toxoplasma gondii, HHV-6, HIV, and adenovirus should be performed.^33,38 Once EBV-associated mononucleosis has been diagnosed, EBV copy numbers in the blood can be used to monitor the severity and progression of the infection.³⁹

Incidence and Prevalence

HPV infections are one of the three most common STDs in the United States. An estimated 20 million people in the United States have genital HPV infection,¹ which can be transmitted through sexual contact.⁴⁵ Although the exact incidence of HPV infection remains unknown, because HPV-induced diseases is not a reportable STD and most cases are asymptomatic or subclinical, it is estimated that more than 6 million new infections occur every year in the United States,¹ and up to 40% of sexually active persons are infected with the virus.^43,44 The infection is more common among African American women than white women. The highest rates of infection are in persons between 19 and 26 years of age.⁴⁴ Approximately 1% of sexually active adults in the United States have visible genital warts.⁴⁵ The lifetime number of sexual partners is the most important risk factor that has been identified for the development of genital warts.^46,47

Etiology

Genital HPV can be transmitted by direct contact during sexual intercourse or passage of a fetus through an infected birth canal, or by autoinoculation. Genital lesions usually appear after an incubation period of 3 weeks to 8 months. The most common manifestation of HPV replication is the venereal wart, or condyloma acuminatum. HPV types 6 and 11 are the subtypes most frequently associated with condyloma acuminatum.⁴⁸ Less commonly, HPV type 2 has been identified in condylomata.

Pathophysiology

HPV is transmitted through mucosa, skin-to-skin, or sexual contact. The virus replicates in the nuclei of epithelial cells and increases the turnover of infected cells, or it remains episomally in a latent state. Benign types such as HPV-6 and -11 have a strong tendency to induce epithelial hyperplasia and wart-like growths. High-risk HPV types (HPV-16 and -18) have a propensity to induce dysplasia and malignant transformation. HPV types 31, 33, 35, 39, 45, 51, 52, 54, 56, and 58 are considered intermediate for inducing carcinoma. Persistent oncogenic HPV infection is the strongest risk factor for the development of precancer and cancer, with HPV DNA detected in 99.7% of cervical cancers. Smoking is also a contributory cofactor.

Signs and Symptoms

Most persons infected with HPV are asymptomatic, and the infection clears on its own. Visible genital warts caused by HPV-6 or -11 typically are diagnosed as condyloma acuminatum. These growths are seen in sexually active persons and arise in warm, moist, intertriginous areas such as the anogenital skin and mouth, where friction and microabrasion allow entrance of the pathogen. Condylomata appear as small, soft, exophytic papillomatous growths (Figure 13-10, A). The irregular-appearing surface has been described to resemble a head of cauliflower; the base is sessile. The borders are raised and rounded. The color varies, ranging from pink to dusky gray. Lesions often are multiple and recurrent and can coalesce to form large, pebbly warts. Most condylomata are asymptomatic; however, patients may report itching, irritation, pain, or bleeding as a result of manipulation or trauma. During pregnancy, condylomata may enlarge as the result of increased vascularity. Condylomata can occur on the vagina, anus, mouth (see Figure 13-10, B), pharynx, or larynx and may appear weeks or months after the onset of infection.

FIGURE 13-10 Human Papillomavirus (HPV) Infections.

A, Large, cauliflower-like wart of the vagina. B, Dome-shaped HPV-induced lesions of the soft palate and retromolar trigone. C, In situ hybridization showing HPV DNA as indicated by dark purple stains in the epithelium of a condyloma acuminatum.

(A, From Habif TP, et al: Skin disease: diagnosis and treatment, ed 3., St. Louis, 2011, Mosby.)

HPV types 16, 18, 31, 33, and 35 have an infrequent association with genital warts and a more common association with dysplasia and carcinoma of the cervix. These intermediate and high-risk HPV types also contribute to the development of squamous intraepithelial neoplasia (Bowen’s disease) of the genitalia.

Laboratory Findings

HPV does not grow in cell culture, and serologic tests are not routinely performed, in part because 90% of infected persons become HPV-seronegative within 2 years. Therefore, lesions of condyloma acuminatum should be biopsied and examined microscopically, if the clinical diagnosis is uncertain. The microscopic appearance consists of a sessile base, with raised epithelial borders, a thick spinous spinosum layer (acanthosis), and hyperkeratosis. Identification of HPV within the lesion confirms the diagnosis. This is achieved with the use of FDA-approved tests that use RNA probes to detect viral DNA specific to HPV genotypes (see Figure 13-10, C). Viral subtyping can be important for determining risk for carcinogenesis when cervical tissue and an abnormal Papanicolaou smear are involved (see Chapter 26 under “ Cervical Cancer”).

Medical Considerations

The dental management of patients with an STD begins with identification. The obvious goal is to identify all people who have active disease in order to limit the spread of the infection and the adverse outcomes of disease progression. Unfortunately, this is not possible in every case, because some persons will not provide a history or may not demonstrate significant signs or symptoms suggestive of their disease. The inability of clinicians to identify potentially infectious patients applies to other diseases as well, such as HIV infection and viral hepatitis. Therefore, it is necessary for all patients to be managed as though they were infectious. The U.S. Public Health Service, through the CDC, has published recommendations for standard precautions to be followed in controlling infection in dentistry that have become the standard for preventing cross-infection⁵¹ (see Appendix B). Strict adherence to these recommendations will, for all practical purposes, eliminate the danger of disease transmission between dentist and patient.

Even though these procedures are followed, several aspects of disease transmission specific to particular STDs warrant consideration. Box 13-2 presents a summary of such dental considerations.

Patients with a History of Sexually Transmitted Disease

Patients who have had an STD should be assessed carefully. They are at increased risk for additional STDs and recurrent infection. The clinician should ensure that adequate treatment was provided for any previous infection and that new infections have not developed. Special attention should be given to unexplained lesions of the oral, pharyngeal, or perioral tissues. Also, a review of systems may reveal urogenital symptoms. Patients with a history of gonorrhea or syphilis should report a history of antibiotic therapy. Patients treated for syphilis should receive a periodic STS for 1 year to monitor conversion of results from positive to negative. Adequate medical follow-up care should have been provided; if it was not, consultation and referral to a physician should be considered.

Patients with Signs, Symptoms, or Oral Lesions Suggestive of a Sexually Transmitted Disease

In patients who have signs or symptoms that suggest an STD, or who have unexplained oral or pharyngeal lesions, further assessment is indicated. The index of suspicion should be higher if the patient is between 15 and 29 years of age and has risk factors such as being an urban dweller, being single, and belonging to a lower socioeconomic group. Any patient who has unexplained lesions should be questioned about possible relationship of the lesions to past sexual activity and should be advised to seek medical care. Herpetic lesions in or around the oral cavity should be recognizable. Patients with oral herpes lesions should not receive routine dental care but should be given palliative treatment only. For a severe primary oral infection or for infectious mononucleosis, the patient may require specific therapy and referral to a physician.

Treatment Planning Modifications

No modifications in the technical treatment plan are required for a patient with an STD. No adverse interactions have been reported between the usual antibiotics or drugs used to treat STDs and drugs commonly used in dentistry. No drugs are contraindicated. Patients with Hutchinson’s incisors due to congenital syphilis may request aesthetic repair of affected anterior teeth.

Reporting to State Health Officials

Dentists should be aware of local statutory requirements regarding reporting STDs to state health officials. Syphilis, gonorrhea, and AIDS are diseases that must be reported in every state. Local health departments and state STD programs are sources of information regarding this issue.

Oral Manifestations

Gonorrhea

The presentation of oral gonorrhea is infrequent, nonspecific, and varied—that is, it may range from acute and severe ulceration with a pseudomembranous coating to slight or diffuse erythema of the oropharynx. Lesions of oral gonorrhea may closely resemble the lesions of erythema multiforme, bullous or erosive lichen planus, or herpetic gingivostomatitis, and have been reported to cause necrosis of the interdental papillae, lingual edema, edematous tissues that bleed easily, vesiculations, and a pseudomembrane that is nonadherent and leaves a bleeding surface on removal. Lesions may be solitary or widely disseminated. Lesions usually develop within 1 week of contact with an infected person; often, a history of fellatio is reported.^8,52 With involvement of the oropharynx, patients report a sore throat, and the mucosa becomes fiery red, with tiny pustules and an itching and burning sensation (Figure 13-11). Symptoms also include an increased salivation, bad taste, fetid breath, fever, and submandibular lymphadenopathy. When the tonsils become involved, they are invariably enlarged and inflamed, with or without a yellowish exudate. The patient may be asymptomatic or incapacitated, with limited oral function (eating, drinking, talking), depending on the degree of inflammation. Diagnosis of oral lesions should be attempted with a smear and Gram stain, followed by confirmatory tests.

FIGURE 13-11 Gonococcal infection of the oral pharynx.

The initial step in treatment is to ensure that the patient is under the care of a physician and is receiving proper antimicrobial therapy. Thereafter, treatment of oral lesions is symptomatic (see Appendix C). The patient should be assured that oral infection will resolve with the use of appropriate antibiotics.

Genital Herpes

HSV-1–induced ulcers are more common in the oral cavity than are those caused by HSV-2; however, these lesions cannot be differentiated clinically, and both should be treated similarly with antiviral agents (see Box 13-1 and Appendix C). Oral and perioral herpetic lesions are infectious during the papular, vesicular, and ulcerative stages, and elective dental treatment should be delayed until the herpetic lesion has completely healed. Dental manipulation during these infectious stages poses risks of (1) inoculation to a new site on the patient, (2) development of infection in the dental care worker, and (3) aerosol or droplet inoculation of the conjunctivae of the patient or of dental personnel. Once the lesion has crusted, it can be considered to be relatively noninfectious.

A problem of particular concern to dentists is herpetic infection of the fingers or nail beds contracted by dermal contact with a herpetic lesion of the lip or oral cavity of a patient. The infection is called a herpetic whitlow, or a herpetic paronychia (Figure 13-12). It is serious, debilitating, and recurrent. Herpetic whitlow can be triggered to recur by trauma or vibration from operating dental handpieces. Also, asymptomatic HSV shedding at oral or nonoral sites can trigger erythema multiforme, a mucocutaneous eruption characterized by “target” papules and ulcers that results from an immune response to the virus.

FIGURE 13-12 Herpetic whitlow.

(From Ibsen DAC, Phelan JA: Oral pathology for the hygienist, ed 5, St. Louis, 2009, Saunders. Courtesy Susan Rod Graham.)

Incidence and Prevalence

Gonorrhea is the second most commonly reported infectious disease and STD in the United States, behind chlamydial infection. An estimated 700,000 new cases are reported each year in the United States, and about half of these are reported to the Centers for Disease Control and Prevention (CDC).^1,5 The reported incidence of gonorrhea in 2009 (i.e., 111 cases per 100,000 persons) was the lowest ever reported in the United States and was significantly lower than the incidence in the mid-1970s, when more than 1 million cases were reported.^5,6

Humans are the only natural hosts for this disease, and its occurrence is worldwide. Gonorrhea is transmitted almost exclusively by sexual contact, whether genital–genital, oral–genital, or rectal–genital. The primary sites of infection are the genitalia, the anal canal, and the pharynx.

Gonorrhea can occur at any age, although it is seen most commonly in sexually active teenagers and young adults (8.5 per 1000 in the 15- to 29-year-old age group) and in the South. Rates of infection are similar in men and women, but differ by racial background. African Americans and Hispanics have 20.5 times higher rates of gonorrhea than whites.⁵ Risk factors other than age include young age at first sexual experience, multiple sexual partners, low level of education, low socioeconomic status, and living in an urban setting.^1,5 At the current rate of infection, an average dental practice of 2000 adult patients can expect to provide care for 2 patients with gonorrhea.

Etiology

Gonorrhea is caused by N. gonorrhoeae, a gram-negative intracellular diplococcus. N. gonorrhoeae is an aerobic microbe that replicates easily in warm, moist areas and preferentially requires high humidity and 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. It develops resistance to antibiotics rather easily, and many strains have become resistant to penicillin, tetracycline, and quinolones.

Signs and Symptoms

In men, symptoms usually occur after an incubation period of 2 to 5 days, although they may take as long as 30 days to appear. The most common findings include a mucopurulent (white, yellow, or green) urethral discharge, burning pain on urination, urgency, and frequency. Tenderness and swelling of the meatus may occur.

In women, a significant percentage of cases may be asymptomatic or only minimally symptomatic. Symptomatic infection may demonstrate vaginal or urethral discharge, dysuria with frequency and urgency, and burning pain when urinating. Backache and abdominal pain also may be present.

Approximately 50% of women and 1% to 3% of men are asymptomatic or only mildly symptomatic. This is unfortunate because patients may not seek medical care for their problem and as a result constitute a large reservoir of infection.

Gonococcal infection of the anal canal commonly is less intense than genital infection, but similar signs and symptoms, including a copious purulent discharge, soreness, and pain, may be noted.

Within the oral cavity, the pharynx is most commonly affected.⁸ Pharyngeal infection is reported to occur in 3% to 7% of heterosexual men, 10% to 20% of heterosexual women, and 10% to 25% of homosexual men.⁹ It usually is seen as an asymptomatic infection with diffuse, nonspecific inflammation or as a mild sore throat. The likelihood of transmission of pharyngeal gonorrhea to the genitalia seems much less than that of genital–genital transmission.^10,11 Of significance, however, is the fact that N. gonorrhoeae has been cultured in expectorated saliva from two thirds of patients with oropharyngeal gonorrhea.¹⁰

Gonococcal stomatitis or oral gonorrhea is uncommon; case reports in the literature are limited.^9,12–15 Acute temporomandibular joint arthritis caused by disseminated gonococcal infection from a genital site has been described.¹⁶

Laboratory Findings

Laboratory diagnosis of a genital N. gonorrhoeae infection can be made based on the finding of gram-negative diplococci within polymorphonuclear leukocytes in a smear of urine or of purulent discharge in symptomatic mean (Figure 13-2). In women and asymptomatic men, nucleic acid amplification testing (NAAT) of urine is recommended because of its high sensitivity and specificity, and it can be used to simultaneously test for C. trachomatis.^1,17 Culture is also available for diagnosis of N. gonorrhoeae from rectal and pharyngeal specimens. In suspected cases of oropharyngeal gonorrhea, because other species of Neisseria are normal inhabitants of the oral cavity, NAAT is more specific than a gram stain.

FIGURE 13-2 Smear demonstrates gram-negative diplococci within a leukocyte.

(Courtesy University of Iowa, Iowa City, Iowa, and Gary E. Kaiser, PhD, The Community College of Baltimore County, Baltimore, Maryland)

Incidence and Prevalence

Syphilis is the fifth most frequently reported STD in the United States today, surpassed only by chlamydial infection, gonorrhea, salmonellosis, and AIDS. In 1990, the incidence of primary and secondary syphilis reached 50,223 cases.⁵ The number of cases of primary and secondary syphilis dropped to 6,000 in 2000. Since then, the rate has been steadily climbing. In 2009, almost 13,997 cases were reported, a rate of decline of 4.6 cases per 100,000 population.^4,5,19 A disproportionately high number of cases continue to occur in the South and among Hispanic and non-Hispanic African American men and women. Syphilis occurs more commonly in persons aged 25 to 39 years. Its incidence in males is greater than in females, with a ratio of almost 6 : 1.¹⁹

Congenital syphilis occurs when the fetus is infected in utero by an infected mother. In 2008, a total of 431 cases of congenital syphilis were reported to the CDC. This represents a rate of 10.1 per 100,000 live births—higher than the 8.2 cases per 100,000 live births in 2005—but still a dramatic decline from the peak of 107.3 cases per 100,000 live births in 1991.¹⁹

Etiology

The etiologic agent of syphilis is Treponema pallidum, which is a slender, fragile anaerobic spirochete. It is transmitted predominantly sexually, including by oral–genital and rectal–genital contact with contaminated sores. However, transmission also can occur through nonsexual means such as kissing, blood transfusion, or accidental inoculation with a contaminated needle. Indirect transmission by fomites is possible but uncommon, because the organism survives for only a short time outside the body.^1,20 T. pallidum is easily killed by heating, drying, disinfecting, and using soap and water. The organism is difficult to stain, except with use of certain silver impregnation methods. Demonstration is best done with darkfield microscopy on a fresh specimen.

Pathophysiology

Available evidence suggests that T. pallidum does not invade completely intact skin; however, it can invade intact mucosal epithelium and gain entry through minute abrasions or at the hair follicles. Within a few hours after invasion, bacterial spread to the lymphatics and the bloodstream occurs, resulting in early widespread dissemination of the disease. The early response to bacterial invasion consists of endarteritis and periarteritis.²⁰ The risk of transmission is during the primary, secondary, and early latent stages of disease, but not in late syphilis.²¹ Overall, patients are most infectious during the first 2 years of the disease.

Signs and Symptoms

Manifestations and descriptions of syphilis are classically divided according to stages of the disease, with each stage having its own specific signs and symptoms related to disease duration and antigen-antibody responses. The stages are primary, secondary, latent, tertiary, and congenital. Of note, many infected persons do not develop symptoms for years, yet remain at risk for late complications if the infection is not treated.

Primary Syphilis

The classic manifestation of primary syphilis is the chancre, a solitary firm, round, granulomatous lesion that develops at the site of inoculation with the infectious organism. The chancre usually occurs within 2 to 3 weeks (range, 10 to 90 days) after exposure (Figure 13-3). Patients are infectious, however, 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 and teems with T. pallidum. It typically is painless. Associated with the chancre are enlarged, painless, hard regional lymph nodes. The chancre usually subsides in 3 to 6 weeks without treatment, leaving variable scarring in the form of a healed papule.^20,22 The genitalia, oral cavity (lips, tongue), fingers, nipples, and anus are common sites for chancres. Figure 13-4 shows examples of extragenital syphilitic chancres (lip and tongue). If adequate treatment is not provided, the infection progresses to secondary syphilis.

FIGURE 13-3 Primary syphilis: Chancre of the penis.

(From Swartz MH: Textbook of physical diagnosis, ed 6, Philadelphia, Saunders, 2010.)

FIGURE 13-4 Primary Syphilis.

A, Chancre on tongue seen in primary syphilis. B, Extragenital chancre of the lip.

(A, From Ibsen DAC, Phelan JA: Oral pathology for the hygienist, ed 5, St. Louis, Saunders, 2009.)

Secondary Syphilis

The manifestations of secondary syphilis appear 6 to 8 weeks after initial exposure. The chancre may or may not have completely resolved by this time. The symptoms and signs of secondary syphilis include fever, arthralgia and malaise, generalized lymphadenopathy, and patchy hair loss and develop in 80% of patients. Generalized eruptions of the skin and mucous membranes also occur (Figure 13-5, A) and include condyloma lata or wart-like growths on the genitalia. The papules of the rash are well demarcated and reddish brown and have a predilection for the palms and soles; they typically are not itchy. Oral manifestations of secondary syphilis include pharyngitis, papular lesions, erythematous or grayish-white erosions (mucous patches) (see Figure 13-5, B), irregular linear erosions, and, rarely, parotid gland enlargement. The lesions of skin and mucous membranes are highly infectious.^20,22 Without treatment, clinical manifestations of secondary syphilis ultimately resolve; however, infection progresses to latent or the tertiary stages.

FIGURE 13-5 Lesions of Secondary Syphilis.

A, Profuse papular rash. B, Mucous patch of the lower lip

(A, From Habif TP, et al: Skin disease: diagnosis and treatment, ed 3, St. Louis, 2011, Mosby.)

Congenital Syphilis

Syphilis or its sequelae occur in the newborn if the mother is infected while carrying the child. The disease is transmitted to the fetus in utero, usually after the 16th week, because before this time, the placenta prevents transmission of bacteria. The disease persists worldwide because a substantial number of women do not receive serologic testing for syphilis during pregnancy, or they may undergo testing too late in pregnancy to receive prenatal care.²⁴ Physical manifestations vary according to the time of infection. The sequelae of early infection include osteochondritis, periostitis (frontal bossing of Parrot), rhinitis, rash, and ectodermal changes. Syphilis contracted during late pregnancy may involve bones, teeth (see “Oral Manifestations”), eyes, cranial nerves, viscera, skin, and mucous membranes. A classic triad of congenital syphilis known as Hutchinson’s triad includes interstitial keratitis of the cornea, eighth nerve deafness, and dental abnormalities, including Hutchinson’s incisors (Figure 13-6) and mulberry molars.

FIGURE 13-6 Congenital syphilis: Hutchinson’s teeth.

Laboratory Findings

T. pallidum has never been cultured successfully on any type of medium; therefore, the definitive diagnosis of syphilis is made from a positive darkfield microscopic examination or on the basis of direct immunofluorescent antibody tests on fresh lesion exudates. Darkfield examination yields consistently positive findings only during primary and early secondary stages. Definitive diagnosis of oral lesions by this method is difficult, because other species of Treponema are indigenous to the oral cavity.

Syphilis typically is diagnosed by a two-step process involving a nonspecific (screening) antibody test, followed by a treponeme-specific test. Screening antibody tests of blood also are known as serologic tests for syphilis (STS). These tests are of two basic types, indirect and direct, and are differentiated by the types of antibodies they measure.