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Lymphogranuloma Venereum (LGV)
LGV is caused by C. trachomatis serovars L1, L2, or L3 (539,540). LGV can cause severe inflammation and invasive infection, in contrast with C. trachomatis serovars A—K that cause mild or asymptomatic infection. Clinical manifestations of LGV can include GUD, lymphadenopathy, or proctocolitis. Rectal exposure among MSM or women can result in proctocolitis, which is the most common presentation of LGV infection (541), and can mimic inflammatory bowel disease with clinical findings of mucoid or hemorrhagic rectal discharge, anal pain, constipation, fever, or tenesmus (542,543). Outbreaks of LGV proctocolitis have been reported among MSM with high rates of HIV infection (544–547). LGV proctocolitis can be an invasive, systemic infection and, if it is not treated early, can lead to chronic colorectal fistulas and strictures; reactive arthropathy has also been reported. However, reports indicate that rectal LGV can also be asymptomatic (548). A common clinical manifestation of LGV among heterosexuals is tender inguinal or femoral lymphadenopathy that is typically unilateral. A self-limited genital ulcer or papule sometimes occurs at the site of inoculation. However, by the time persons seek care, the lesions have often disappeared. LGV-associated lymphadenopathy can be severe, with bubo formation from fluctuant or suppurative inguinal or femoral lymphadenopathy. Oral ulceration can occur and might be associated with cervical adenopathy (549–551). Persons with genital or colorectal LGV lesions can also experience secondary bacterial infection or can be infected with other sexually and nonsexually transmitted pathogens.
Diagnostic Considerations
A definitive LGV diagnosis can be made only with LGV-specific molecular testing (e.g., PCR-based genotyping). These tests can differentiate LGV from non–LGV C. trachomatis in rectal specimens. However, these tests are not widely available, and results are not typically available in a time frame that would influence clinical management. Therefore, diagnosis is based on clinical suspicion, epidemiologic information, and a C. trachomatis NAAT at the symptomatic anatomic site, along with exclusion of other etiologies for proctocolitis, inguinal lymphadenopathy, or genital, oral, or rectal ulcers (551,552). Genital or oral lesions, rectal specimens, and lymph node specimens (i.e., lesion swab or bubo aspirate) can be tested for C. trachomatis by NAAT or culture. NAAT is the preferred approach for testing because it can detect both LGV strains and non–LGV C. trachomatis strains (553). Therefore, all persons presenting with proctocolitis should be tested for chlamydia with a NAAT performed on rectal specimens. Severe symptoms of proctocolitis (e.g., bloody discharge, tenesmus, and rectal ulcers) indicate LGV. A rectal Gram stain with >10 white blood cells (WBCs) has also been associated with rectal LGV (545,554,555).
Chlamydia serology (complement fixation or microimmunofluorescence) should not be used routinely as a diagnostic tool for LGV because the utility of these serologic methods has not been established, interpretation has not been standardized, and validation for clinical proctitis presentation has not been done. It might support an LGV diagnosis in cases of isolated inguinal or femoral lymphadenopathy for which diagnostic material for C. trachomatis NAAT cannot be obtained.
Treatment
At the time of the initial visit (before diagnostic NAATs for chlamydia are available), persons with a clinical syndrome consistent with LGV should be presumptively treated. Presumptive treatment for LGV is indicated among patients with symptoms or signs of proctocolitis (e.g., bloody discharge, tenesmus, or ulceration); in cases of severe inguinal lymphadenopathy with bubo formation, particularly if the patient has a recent history of a genital ulcer; or in the presence of a genital ulcer if other etiologies have been ruled out. The goal of treatment is to cure infection and prevent ongoing tissue damage, although tissue reaction to the infection can result in scarring. Buboes might require aspiration through intact skin or incision and drainage to prevent formation of inguinal or femoral ulcerations.
Doxycycline 100 mg orally 2 times/day for 21 days
Azithromycin 1 gm orally once weekly for 3 weeks*
OR
Erythromycin base 500 mg orally 4 times/day for 21 days
* Because this regimen has not been validated, a test of cure with C. trachomatis NAAT 4 weeks after completion of treatment can be considered.
The optimal treatment duration for symptomatic LGV has not been studied in clinical trials. The recommended 21-day course of doxycycline is based on long-standing clinical practice and is highly effective, with an estimated cure rate of >98.5% (555,556). Shorter courses of doxycycline might be effective on the basis of a small retrospective study of MSM with rectal LGV, 50% of whom were symptomatic, who received a 7- to 14-day course of doxycycline and had a 97% cure rate (558). Randomized prospective studies of shorter-course doxycycline for treating LGV are needed. Longer courses of therapy might be required in the setting of fistulas, buboes, and other forms of severe disease (559).
A small nonrandomized study from Spain involving patients with rectal LGV demonstrated cure rates of 97% with a regimen of azithromycin 1 g once weekly for 3 weeks (560). Pharmacokinetic data support this dosing strategy (561); however, this regimen has not been validated. Fluoroquinolone-based treatments also might be effective; however, the optimal duration of treatment has not been evaluated. The clinical significance of asymptomatic LGV is unknown, and it is effectively treated with a 7-day course of doxycycline (562).
Other Management Considerations
Patients should be followed clinically until signs and symptoms have resolved. Persons who receive an LGV diagnosis should be tested for other STIs, especially HIV, gonorrhea, and syphilis. Those whose HIV test results are negative should be offered HIV PrEP.
Follow-Up
All persons who have been treated for LGV should be retested for chlamydia approximately 3 months after treatment. If retesting at 3 months is not possible, providers should retest at the patient’s next visit for medical care within the 12-month period after initial treatment.
Management of Sex Partners
Persons who have had sexual contact with a patient who has LGV within the 60 days before onset of the patient’s symptoms should be evaluated, examined, and tested for chlamydial infection, depending on anatomic site of exposure. Asymptomatic partners should be presumptively treated with a chlamydia regimen (doxycycline 100 mg orally 2 times/day for 7 days).
Special Considerations
Pregnancy
Use of doxycycline in pregnancy might be associated with discoloration of teeth; however, the risk is not well defined (563). Doxycycline is compatible with breastfeeding (431). Azithromycin might prove useful for LGV treatment during pregnancy, at a presumptive dose of 1 g weekly for 3 weeks; no published data are available regarding an effective dose and duration of treatment. Pregnant and lactating women with LGV can be treated with erythromycin, although this regimen is associated with frequent gastrointestinal side effects. Pregnant women treated for LGV should have a test of cure performed 4 weeks after the initial C. trachomatis NAAT-positive test.
HIV Infection
Persons with LGV and HIV infection should receive the same regimens as those who do not have HIV. Prolonged therapy might be required because a delay in resolution of symptoms might occur.