Essentials of Diagnosis
- • In North America, lymphogranuloma venereum typically presents as a proctitis syndrome; elsewhere, genital ulcer disease followed by inguinal lymphadenopathy with or without bubo formation may predominate.
- • Diagnostic tests include culture and typing for Chlamydia trachomatis and molecular assays.
- • Patients should be asked about gender of sex partners and travel to areas of endemic disease or outbreaks, and behavioral risk assessment should be performed to elicit risks for transmission.
- • In patients with suspected infection, screening for other STDs, including HIV, is warranted.
General Considerations
Lymphogranuloma venereum (LGV) is a systemic sexually transmitted disease (STD) caused by L1, L2, and L3 serovars (subtypes) of Chlamydia trachomatis. LGV occurs worldwide as several clinical syndromes, the most common of which are characterized by papules or ulcers with inguinal lymphadenopathy, followed by proctitis (see Table 17–1). Although LGV is classically an invasive, inflammatory infection, patients may present without significant lymphadenopathy or with mild symptoms. Asymptomatic infection also has been observed.
| Syndrome | Pertinent History | Symptoms |
|---|---|---|
| Lymphadenopathy syndrome | ||
| Primary stage | Incubation 3–30 d | • Typically small, painless genital papule with or without urethritis or cervicitis that may ulcerate |
| • Usually unrecognized by patient and resolves without treatment | ||
| Secondary stage | Occurs 2–6 wk after primary stage | • One or more regional lymph nodes that may ulcerate (ie, bubo); inguinal or femoral nodes may cause “groove” sign |
| • One third of buboes may rupture | ||
| • Genital ulcers may be manifest concurrently with lymphadenitis | ||
| Proctitis and proctocolitis | Risk factors include anal intercourse or other anal penetration | • Rectal discharge, bleeding, pain on defecation (tenesmus), and later, frank colitis; inguinal lymph node involvement is unusual |
| • Fever or other constitutional symptoms (ie, weight loss, fatigue) may be present |
LGV is endemic in some regions (Africa, Southeast Asia, Central and South America, and Caribbean countries) while occurring sporadically in others. It remains infrequent in the United States. However, case clusters have been reported in the northern hemisphere since 2002. Notably, an outbreak of 92 cases of proctitis caused by LGV was described among men who have sex with men (MSM) in the Netherlands in 2003–2004. Since then, case clusters have been reported in Belgium, France, Sweden, and Canada, with fewer than two dozen confirmed cases reported throughout the United States by 2005.
Recent outbreaks and case clusters demonstrate the need for heightened awareness of this STD in the United States. LGV should be considered in those at risk for STDs, especially MSM and others reporting unprotected receptive anal intercourse who present with rectal complaints or lymphadenopathy. Such patients, along with any patient with a compatible clinical presentation, should be asked about travel to areas of endemic disease or outbreaks. Given the ulcerative nature of this more invasive chlamydial infection, the risk of facilitating HIV acquisition and transmission is thought to be higher.
In the United States, poorly standardized serologic tests lacking specificity and limited availability of tissue culture and molecular tests for rectal evaluation complicate both diagnosis and measurement of the true incidence of LGV. Although the incidence of fulminant LGV has dramatically decreased in industrialized countries since the advent of antibiotics, at least one researcher has suggested a low but persistent endemicity of LGV among those at risk for rectal chlamydial infection, particularly MSM.
Pathogenesis
C trachomatis is an obligate intracellular microorganism that is dependent on the host cell for ATP production and replication. The organism is surrounded by an outer membrane mainly composed of a major outer membrane protein (MOMP). Eighteen serovars of C trachomatis are classified according to the Omp 1 gene encoding MOMP. The trachoma biovar includes serovars A through K and is responsible for infections involving mucosa of the genital tract and the eye. Serovars L1, L2 (L2a/L2b), and L3 comprise the LGV biovar, which is more invasive, involving proliferation in lymphoid tissues.
Prevention
Prevention of LGV requires a multipronged strategy of promoting risk reduction among those likeliest to contract the infection, treating those diagnosed as well as those at high risk with a compatible clinical syndrome, and identifying and presumptively treating exposed sex partners who may have been infected.
Providers should assess sexual risk behaviors of patients by asking about number and gender of partners, sexual behaviors engaged in, and use of condoms. The primary risk factor identified for transmission of LGV is unprotected receptive anal intercourse or other penetration (eg, “fisting”), highlighting the importance of providers asking about such practices in routine, periodic sexual risk assessments. Tools to assist providers with risk assessment are available from the California STD/HIV Prevention Training Center (http://www.stdhivtraining.org/clinical_resources.html).
HIV-infected MSM have been most often affected in recent outbreaks of LGV proctitis in Europe. For instance, in the well-characterized Netherlands outbreak in 2003–2004, 92 confirmed cases were observed, following a prior average of 5 LGV cases per year. All patients were MSM, and among those whose HIV status was known, 77% were HIV-positive. Most patients presented with lower gastrointestinal symptoms, including mucopurulent—sometimes bloody—anal discharge and other symptoms of proctitis. Only one patient had a genital ulcer or bubo. Six of 13 patients with concurrent STDs had gonorrhea, herpes simplex virus (HSV), syphilis, or chronic hepatitis B. In all cases, LGV was associated with serum antibodies to C trachomatis and rectal C trachomatis isolates of the L1–L3 serovar subtype, but chlamydial DNA was not found in urethral specimens, such that this common diagnostic approach would not have led to recognition of chlamydial LGV in these patients. Among the 62 cases reported in 2004, LGV was temporally associated with HIV seroconversion in 2 patients, and with recent acquisition of hepatitis C infection in 5 others.
Other European case clusters in 2004–2005 were observed in Paris, Antwerp, Hamburg, and elsewhere, including the United Kingdom. Similarly, all patients were MSM, and more than half were HIV-positive.
These case clusters and reports have demonstrated the significance of local sexual networks in transmission of this STD while highlighting the barriers to accurate diagnosis of rectal infections, including LGV. The potential facilitation of HIV acquisition and transmission in the setting of an inflammatory rectal infection has heightened concerns about possible increases in LGV incidence, while surveillance challenges—including the lack of a standard case definition—make sentinel detection of incipient LGV clusters difficult.
Following the northern hemisphere cases of LGV, the US Centers for Disease Control and Prevention (CDC) established a targeted surveillance effort to identify incident cases in the United States and to advise clinicians on appropriate diagnosis and treatment of LGV (http://www.cdc.gov/std/lgv). By 2005, fewer than two dozen cases had been identified in the United States, and case clusters driven by sexual networks and international travel had not been identified.
Notwithstanding the limited recognition of LGV in the United States in recent years, it should be emphasized that diagnosis of any sexually transmitted rectal infection in an HIV-uninfected individual should be considered a sentinel event with respect to elevated risk of HIV acquisition. Such a diagnosis necessitates education, ongoing risk assessment and risk reduction counseling, and screening for other STDs and HIV, with follow-up screening 3 months after diagnosis.
In the United States, C trachomatis infection is a reportable disease, and LGV cases should be reported according to standard local regulations. In general, given the still rare incidence of LGV in the United States, providers should contact their local health departments to advise them of suspected cases.
Once the diagnosis is confirmed in infected individuals, sex partners within the prior 30 days should be clinically evaluated and, if symptomatic, managed as if potentially infected with LGV. If asymptomatic, sex partners should be treated with either oral doxycycline, 100 mg twice daily for 7 days, or a single 1-g oral dose of azithromycin.
