Essentials of Diagnosis
- • Diagnosis is based on the finding of one or more mucocutaneous ulcers involving the genitalia, perineum, or anus.
- • Careful inspection of all genital mucosa is important, as lesions may be inside the foreskin, labia, vagina, or rectum, and may be painless.
- • Genital herpes is the most common cause, followed by syphilis.
- • A specific pathogen often cannot be identified based on clinical findings alone; laboratory testing should include culture or polymerase chain reaction (PCR) amplification for herpes simplex virus (HSV), and serologic testing for syphilis.
- • Despite appropriate testing, no pathogen is identified in up to 50% of patients.
General Considerations
Genital ulcer disease (GUD) is a syndrome characterized by ulcerating lesions on the penis, scrotum, vulva, vagina, perineum, or perianal skin. In general usage the term refers to genital ulcerations from a sexually transmitted disease (STD), which is the most common etiology; however, nonsexually acquired illnesses, including infectious (bacterial skin infections, fungi) or noninfectious etiologies (fixed drug eruption, Behçet syndrome, sexual trauma), can present with similar ulcers. The clinician should bear in mind that nonvenereal dermatoses (eg, psoriasis) resulting from a variety of causes also can present with anogenital lesions.
The annual global incidence of GUD probably exceeds 20 million cases. The most commonly identified pathogens are HSV types 1 and 2 (HSV-1, HSV-2), syphilis, and chancroid. As recently as 20 years ago, the predominant causes of GUD in much the developing world were bacterial pathogens, especially Haemophilus ducreyi, the etiologic agent of chancroid. However, since the early 1990s the prevalence of chancroid in sub-Saharan Africa has decreased dramatically, while HSV-2 infection has increased. Although this change may be related to more widespread use of antibiotics and syndromic treatment of STDs, the HIV epidemic and behavioral changes in response may have played an equally important role. As a result, genital herpes now constitutes the most common infectious cause of GUD worldwide.
Regardless of the cause, GUD has assumed increased importance in view of its well-recognized role in facilitating HIV transmission. Surveys of HIV prevalence among patients seeking treatment for STDs have found a higher prevalence of coexisting HIV infection in those with genital ulcers than in those without, both in the United States and in the developing world. The presence of GUD in an individual not infected with HIV makes that person more susceptible to HIV infection by breaching the integumentary barrier and by recruiting macrophages and T-helper cells to the genital tract, where they may more readily be infected. Conversely, GUD in an HIV-infected individual increases his or her likelihood of transmitting HIV to a sex partner. HIV-infected patients with GUD who present for care at STD clinics actually have a higher plasma HIV viral load than similar patients without GUD. In a 2001 study of 174 HIV-serodiscordant couples in Uganda, the presence of GUD was associated with an almost fourfold increase in the probability of HIV transmission. A similar magnitude of increased risk of HIV acquisition (hazard ratio of 3.8) was associated with new onset of HSV-2 infection in the prior 6 months in a cohort of over 2700 patients in Pune, India.
Prevention
The mainstay of prevention of GUD, as for prevention of STDs in general, is risk reduction counseling. Topics of counseling include limiting the number of sex partners, use of condoms (either male or female), and regular testing for asymptomatic disease. However, there are some ways in which GUD differs from other STDs. For example, condom use is somewhat less efficacious in preventing GUD. Because causative pathogens may be transmitted by skin-to-skin contact, contact with skin that is not covered by a condom may transmit infection. Furthermore, patients may only put on a condom preparatory to penetrative sex, whereas transmission may occur via nonpenetrative contact. Finally, despite counseling messages, few patients routinely use condoms for oral sex. Some patients engage more frequently in oral sex than in anal or vaginal penetrative sex, perceiving oral sex as a lower risk activity. However, the three most common pathogens implicated in GUD (HSV-2, HSV-1, and Treponema pallidum) can be transmitted efficiently by oral sex, a fact that may be underappreciated by patients.
Among other potential prevention strategies, chemoprophylaxis is available for genital herpes in the form of daily suppressive medication such as acyclovir. Daily suppressive therapy not only reduces the frequency and severity of herpes outbreaks, but also reduces asymptomatic viral shedding and transmission. This strategy may be appropriate for many patients and is discussed in more detail in Chapter 14. In many parts of the developing world where bacterial pathogens are prevalent, mass anti-infective treatment of populations has been attempted as a prevention strategy.
Interest has recently been raised in circumcision as a possible strategy for prevention of HIV infection, and large, well-controlled studies in Africa have demonstrated significant reductions in infection rates among circumcised versus uncircumcised adults. Because some ulcerative diseases (eg, chancroid) are more common in uncircumcised men and tend to occur in the preputial sulcus and inside surface of the prepuce, circumcision may also provide some protection against these diseases; however, this hypothesis has not been studied, and the magnitude of any protective effect is unknown.
Clinical Findings
In the diagnosis of GUD, the first consideration is whether or not the condition is sexually acquired; that is, whether a potential sexual exposure has occurred. Thus, an accurate sexual history is essential to diagnosis and management. Many clinicians may not readily elicit a sexual history in busy clinical practices, and many patients are unwilling to broach the subject of their sexual practices if they are not fully comfortable with their health care provider. Nevertheless, because accurate information about potential sexual exposures is essential to a diagnosis, it is incumbent on any health care provider who sees sexually active patients to become proficient in this area of history taking. Details about obtaining an accurate sexual history are found in Chapter 31.
Once a potential sexual route of infection has been established, the history can sometimes help differentiate between different pathogens. The interval between a high-risk sexual exposure and the onset of symptoms may suggest the diagnosis. A primary genital herpes infection most often produces symptoms within a week of exposure. Symptoms of primary syphilis generally appear after 2–3 weeks, and more uncommon pathogens may have a longer incubation period. The patient’s description of the initial stages of the lesion (eg, as small blisters [vesicles]) may be helpful; however, these earlier stages may not have been noticed by the patient, particularly if the lesions are in an area that is difficult for the patient to inspect, such as the perineum, labia majora or minora, or perianal region. In addition, patients may not reliably distinguish an initial lesion as papular, vesicular, or pustular; thus, the patient’s description is frequently not contributory. A history of travel to an endemic area may increase the likelihood of a more exotic pathogen, such as chancroid or donovanosis.
If sexually acquired GUD has been ruled out, a more detailed history may be helpful in pointing toward certain less common diagnoses. An appropriate exposure history in an endemic area, for example, may suggest tularemia; likewise, a history of oral ulcers can suggest Behçet syndrome, an uncommon disease of unknown etiology whose hallmarks are recurrent oral and genital ulcers. However, most of the nonvenereal causes of genital ulceration are less common than sexually transmitted GUD. As a general rule, whenever there is doubt as to the etiology, it is safest to assume that genital ulcers are sexually acquired. Even a highly experienced provider with expertise at obtaining an accurate sexual history will frequently be given unreliable information about sexual risk.
Classic textbook descriptions would have the clinician believe that herpes, syphilis, and chancroid can be easily distinguished on the basis of physical presentation and symptoms. In fact, diagnosis of specific etiologies of GUD on the basis of clinical presentation alone is often impossible. Nevertheless, it is helpful to be familiar with the “textbook” distinguishing characteristics, which are summarized in Table 4–1. Important findings to note include whether the ulcer is single or multiple, painless or painful, tender or nontender, and indurated or soft. The base of the ulcer may be necrotic (as in chancroid) or clean (as in a syphilitic chancre); it may appear shallow or have raised or rolled margins. The location of the ulcers also should be noted, because conditions such as chancroid are most often confined to the prepuce and glans in men and the labia majora and minora in women. Ulcers seen on the scrotum in men or the cervix in women should raise suspicion for herpes or syphilis.
| Disease | Incubation Period | Pain and Tenderness | Lymphadenopathy | Description |
|---|---|---|---|---|
| Genital herpes | 2–7 d for primary infection, not applicable for recurrence | Present, along with tingling and itching | Bilateral and tender in primary infection | Clusters of small shallow ulcers that may coalesce; vesicles are often not seen in women |
| Syphilis | 10–90 d; usually 2–3 wk | Painless, nontender | Bilateral, firm, nontender | Firm, cartilaginous induration; heaped-up margins; clean base with serous exudate |
| Chancroid | 3–10 d | Painful in men; may be painless in women | Painful, tender, usually unilateral | “Soft chancre” (no induration); may be multiple, especially in women; ragged border; necrotic base that bleeds easily |
| Lymphogranuloma venereum | 3–30 d | Varies, usually painless | Very tender, usually unilateral; most often the predominant finding in male penile disease; usually absent in vaginal or anal disease | Exquisitely tender adenopathy is predominant; ulcer is small (≤1 cm) and transient |
| Donovanosis (granuloma inguinale) | 8–80 d | Painless | Absent; firm, subcutaneous granulomas (pseudobuboes) | Hypertrophic, beefy red, or verrucous; may resemble squamous cell carcinoma or condylomata lata may be present |
The presence of inguinal lymphadenopathy can provide a clue to the etiology of GUD. Enlarged inguinal lymph nodes are a common finding in many ulcerating conditions. In primary genital herpes the enlarged lymph nodes are frequently tender, whereas the classic adenopathy of syphilis is firm and nontender. Less common diseases such as chancroid and lymphogranuloma venereum usually present with tender, fluctuant inguinal lymph nodes (buboes). In lymphogranuloma venereum the primary ulcer may be transient, and lymphadenopathy, most often unilateral, is the predominant finding. The lymph nodes in patients with lymphogranuloma venereum become large and matted, and may erode through the skin to produce draining sinus tracts. Donovanosis, described in more detail below (see Differential Diagnosis), is one of the few causes of genital ulcer disease that does not characteristically include inguinal lymphadenopathy, although it can produce firm subcutaneous swellings called pseudobuboes.
Physical examination should include a thorough inspection of the oral cavity and a general skin examination. The presence of fever, malaise, headaches, or other constitutional findings in conjunction with a genital ulcer strongly suggests either primary genital herpes or a nonvenereal systemic disease such as Behçet syndrome or tularemia. In general, primary syphilis, chancroid, donovanosis, and the ulcerative stage of lymphogranuloma venereum are not associated with systemic symptoms. Rarely, a chancre will persist until the onset of secondary syphilis.
