Lymphogranuloma venereum

INTRODUCTION — Lymphogranuloma venereum (LGV) has traditionally been described as genital ulcer disease caused by the L1, L2, and L3 biovars of Chlamydia trachomatis [1], which are found most frequently in resource-limited tropical and subtropical areas of the world [2]. More recently, LGV has been increasingly reported as a cause of proctitis in high-income settings with temperate climates among men who have sex with men (MSM) [3-8].

This topic will review the epidemiology, clinical manifestations, diagnosis, and treatment of LGV. Other manifestations of C. trachomatis infection are discussed separately. (See "Trachoma" and "Clinical manifestations and diagnosis of Chlamydia trachomatis infections".)

EPIDEMIOLOGY

●Geographic distribution – Although previously rare in temperate climates, LGV infection has been increasingly reported in high-income countries since 2003. Large outbreaks have been reported in Western Europe and North America, primarily in men who have sex with men (MSM) [3-10]. Two of the largest outbreaks in MSM occurred in New York City [9] and the United Kingdom [10]. A close epidemiologic link between outbreaks in New York City and the Netherlands was suggested through molecular typing of the serovars. In a more recent study that evaluated 5581 rectal specimens from MSM in Austria, Croatia, and Slovakia, 9 percent were positive for chlamydia, of which 2.3 percent were positive for LGV [11]. Most LGV cases in MSM present as proctitis. (See 'Secondary infection' below.)

Prior to the outbreaks in MSM, LGV was primarily endemic in heterosexual persons in areas of East and West Africa, India, parts of Southeast Asia, and the Caribbean, where it manifested as the classic form of disease with genital ulcers and lymphadenopathy (without proctitis) [2]. However, LGV is not the predominant cause of genital ulcer disease in a number of these regions despite a high frequency of exposure, as evidenced by C. trachomatis antibodies [12,13]. This was illustrated in a survey of 196 patients with genital ulcers from Madagascar, of whom 79 percent had chlamydial antibodies [12]. In this report, LGV was confirmed by multiplex polymerase chain reaction (PCR) in only 16 (8 percent); by contrast, there were much higher rates of infection with chancroid, syphilis, and herpes simplex virus (33, 29, and 10 percent, respectively). In a subsequent study of 422 patients from Malawi, LGV accounted for 6 percent of ulcers; this was the same rate as syphilis but less than the rate of herpes simplex virus 2 and chancroid, which accounted for 67 and 15 percent of ulcers, respectively [14]. (See "Chancroid" and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection" and "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Epidemiology'.)

●Association with HIV infection and other sexually transmitted infections (STIs) – The majority of MSM who have acquired LGV are also living with HIV [15]. In the New York City and United Kingdom outbreaks noted above, HIV coinfection was found in 84 and 76 percent of patients with LGV, respectively [9,10]. In a case control study of 87 MSM who had C. trachomatis serovar L2 compared with 377 MSM who had serovars D through K (the typical genital serovars), HIV seropositivity was the strongest risk factor for LGV infection [6]. The association between HIV and LGV is a major public health concern, since enhanced shedding of HIV during clinical proctitis could increase the risk of HIV transmission to uninfected sex partners [10]. (See "HIV infection: Risk factors and prevention strategies", section on 'Risk factors for infection'.)

LGV is associated with newly diagnosed HIV as well as other STIs. In the United Kingdom outbreak of 327 cases of LGV, 4 percent of the patients had a new diagnosis of HIV infection, 39 percent had a diagnosis of another STI, and approximately 19 percent were infected with hepatitis C virus [10]. Similarly, in an outbreak of LGV that occurred in Michigan between 2015 and 2016, in which 38 confirmed, probable, and suspected cases were identified, all of the cases occurred in MSM with HIV, and six (16 percent) patients had newly diagnosed HIV infection [16]. In that outbreak, syphilis and asymptomatic oropharyngeal and rectal gonorrhea were diagnosed in 16, 8, and 13 percent, respectively. Proctitis was present in half the patients.

Other independent risk factors for LGV have included concurrent genital ulcerative disease, a previously diagnosed STI, unprotected anal sex, recent travel abroad, and meeting sex partners on the internet [7,8,10].

PATHOPHYSIOLOGY — LGV is predominantly a disease of lymphatic tissue [17]. In contrast to mucosal chlamydial infections, in which inflammation is largely limited to the initial site of infection, the LGV serovars induce a lymphoproliferative reaction. This is usually accomplished through direct extension from the primary infection site to the draining lymph nodes. Both LGV serovars and other strains of C. trachomatis appear to bind to epithelial cells via heparan sulfate receptors [18].

When LGV spreads to produce a lymphangitis, areas of necrosis occur within the nodes, followed by abscess formation [17]. In one study of 12 patients, lymph node macrophages contained organisms that stained black with Warthin-Starry stain [19]. The organisms clustered within vacuoles, and by electron microscopy, both reticulate and elementary bodies were visible. Polymerase chain reaction (PCR) testing of the lymph nodes for LGV serovars of C. trachomatis was positive in 9 of the 12 cases. The pathologic findings are compatible with LGV or Bartonella (ie, "cat scratch" disease), but are not diagnostic of either entity [20]. One report describes a case of cat scratch disease that appeared to be LGV [21]. The lymph node reaction may take several weeks to develop and can result in substantial inflammation and subsequent fibrosis [17]. In a small number of cases, dissemination and systemic disease can occur.

CLINICAL MANIFESTATIONS — Three stages of LGV have been identified [17].

Primary infection — Primary infection is characterized by a genital ulcer or a mucosal inflammatory reaction at the site of inoculation. The incubation period is 3 to 12 days [17]. These lesions spontaneously heal within a few days. This stage of disease is often missed due to the small size of the ulcer, its location, and the lack of accompanying symptoms.

Secondary infection — The secondary stage appears two to six weeks later and is related to local direct extension of the infection to regional lymph nodes (ie, inguinal and/or femoral nodes) [17]. In contrast to the urogenital infections due to C. trachomatis (serovars D through K) that are often mild, LGV can cause severe inflammation and invasive infection, often with systemic symptoms [6]. Clinical manifestations include:

●Inguinal syndrome – The inguinal syndrome occurs more commonly in men and is an inflammatory reaction in the superficial and deep inguinal nodes, causing the characteristic "groove" sign (picture 1). These may form buboes (unilateral painful inguinal lymph nodes) and rupture. The vagina and cervical lymph nodes drain predominantly to retroperitoneal nodes, which may explain the relative rarity of the inguinal syndrome in women.

●Anorectal symptoms – An anorectal syndrome can occur, which may result in an inflammatory mass present in the rectum and retroperitoneum, mimicking carcinoma [17]. Patients may present with symptoms of proctocolitis with rectal discharge, anal pain, constipation, fever, and/or tenesmus. There may be hemorrhagic proctocolitis and hyperplasia of intestinal and perirectal lymphatic tissue. This can be mistaken for inflammatory bowel disease [4,5,22,23]. Complications include chronic colorectal fistulas and strictures. In the large United Kingdom outbreak, the major symptoms included rectal discharge (79 percent), pain (69 percent), rectal bleeding (58 percent), tenesmus (29 percent), and constipation (25 percent); 4 percent of patients had concomitant urogenital LGV [23].

Although most patients with anorectal disease present with proctocolitis, asymptomatic rectal infection has been increasingly recognized [24-27]. As an example, in a 2016 study from the United Kingdom, 15 of 55 patients (27 percent) with clinical data available were asymptomatic [25].

●Other manifestations – Rare cases of oropharyngeal LGV affecting cervical lymph nodes have been reported [28]. Most cases have occurred in men who have sex with men (MSM). Other rare reactive and septic complications have also been described (eg, reactive arthritis, cardiac involvement, perihepatitis) [29].

Late LGV — Fibrosis and strictures in the anogenital tract characterize late LGV, which can arise if earlier stages of infection are untreated or undertreated. Late complications include genital elephantiasis, anal fistulae and strictures, frozen pelvis, and infertility [30,31]. One of the most severe late manifestations is esthiomene, a widespread destruction of the external genitalia, typically seen in women [17].

DIAGNOSIS

General approach — The diagnosis of LGV has traditionally been difficult because of the diversity of clinical manifestations and the relative rarity of the more pathognomonic presentation (fluctuant inguinal lymphadenopathy in the setting of genital ulcer disease). In addition, laboratory procedures for diagnosing this pathogen are not well standardized, and serologic assessment has low specificity [17,20,32]. (See 'Clinical manifestations' above and 'Types of tests' below.)

In most patients, a presumptive diagnosis of LGV is made in a patient with consistent clinical findings and epidemiologic risk factors in the setting of a positive C. trachomatis nucleic acid amplification test (NAAT). A definitive diagnosis can only be made with LGV-specific molecular testing (eg, polymerase chain reaction [PCR]-based genotyping); however, these tests are not widely available. (See 'Site-specific considerations' below and 'Nucleic acid amplification testing' below.)

Although the diagnosis of LGV is best made through NAAT, serologic testing may be helpful in certain settings. As an example, in patients with late disease who present with either strictures or fistulas, there may not be material to send for NAAT. Serologic testing can also be used to support the diagnosis if the patient was treated empirically for chlamydia and there is a need to identify a pathogen retrospectively [28]. However, serologic testing is not definitive, and cannot reliably distinguish current from prior LGV infection. It may also be less useful in those with rectal infection because tests have not been validated in those who present with proctitis/proctocolitis [29]. (See 'Serology' below.)

Site-specific considerations — Additional considerations for diagnosis depend upon the site of infection.

Genital/inguinal disease — For patients with suspected genital ulcer or inguinal disease due to LGV, a swab of the lesion or aspirate of the bubo should be tested for C. trachomatis using NAAT. Other methods for detecting the organism include direct immunofluorescence or culture, although these are less commonly used. In patients with genital ulcer disease, rates of pathogen recovery are higher in those with inguinal adenopathy or buboes [33,34]. (See 'Clinical manifestations' above and 'Types of tests' below.)

Anorectal disease (eg, proctitis) — The clinical diagnosis of LGV proctitis should be suspected in men who have sex with men (MSM) and transgender women who present with any combination of proctitis, enlarged inguinal lymph nodes, and anorectal ulcers [6]. Rectal inflammation and/or bleeding is almost always present in symptomatic proctitis due to LGV. Taking an accurate sexual history and thinking of the possibility of LGV are key to making the diagnosis. (See 'Epidemiology' above.)

●Use of NAAT – For patients with suspected LGV proctitis (eg, bloody discharge, tenesmus, perianal or mucosal ulcers, severe inguinal lymphadenopathy), the best way to make the diagnosis is to test for C. trachomatis using NAAT of rectal specimens. Studies have demonstrated a high sensitivity and specificity using nucleic acid detection [35]. (See 'Nucleic acid amplification testing' below.)

•If NAAT for chlamydia is positive, we make a presumptive diagnosis of LGV proctitis and initiate therapy. (See 'Medical therapy for LGV' below.)

Patients with presumed LGV should also be evaluated for other sexually transmitted infections, (STIs) such as Neisseria gonorrhoeae, herpes simplex virus, and syphilis, as discussed in a separate topic review. (See 'HIV and other sexually transmitted diseases' below.)

•Additional testing to differentiate LGV from non-LGV biovars should be performed, if available, since it can help guide duration of therapy (21 versus 7 days, respectively). The treatment of non-LGV chlamydia infections is presented elsewhere. (See "Treatment of Chlamydia trachomatis infection", section on 'Proctitis and rectal infection'.)

However, differentiating LGV from non-LGV serotypes of Chlamydia can be challenging since PCR-based methods developed for this specific purpose are not routinely available in many countries [32,36,37]. In addition, when LGV-specific testing is performed, it may take several weeks for the results to return.

If LGV serovar typing cannot be performed or if results are not available after seven days, we typically continue treatment for LGV rather than assume the proctitis is due to a non-LGV serovar. (See 'Treatment of LGV' below.)

On rare occasion, NAAT may not be available or was not performed. In this setting, MSM with proctitis should be treated for LGV unless another etiology has been identified. This is particularly important in patients with severe rectal symptoms and signs (eg, bloody discharge, perianal ulcers, or mucosal ulcers) and/or HIV infection [1].

●Other findings – In patients with LGV proctitis, other findings that may support the diagnosis of LGV include microscopic examination of a gram-stained anorectal smear specimens with greater than 10 white blood cells per high power field (WBC/hpf) [6]. In addition, findings on anoscopy typically demonstrate perianal or mucosal ulcers and/or a bloody rectal discharge. If a biopsy is performed, pathologic findings consistent with LGV include microscopic disease with inflammation in the lamina propria and neutrophilic infiltration of crypts. (See 'Pathophysiology' above.)

Types of tests

Nucleic acid amplification testing — Genital lesions, pharyngeal and rectal specimens, and lymph node specimens can be tested for C. trachomatis using nucleic acid detection techniques (NAATs). Additional testing is needed to differentiate LGV from non-LGV biovars. NAAT has greater sensitivity and specificity compared with culture [38], including specimens from extragenital sites [35,39,40]. One assay correctly identified 53 of 55 LGV specimens, 34 of 34 non-LGV chlamydial specimens, and 30 of 30 specimens with no chlamydial infection [6,41].

The use of NAAT can vary by country. As examples:

●United States – NAAT of rectal and pharyngeal specimens was approved by the US Food and Drug Administration (FDA) in May 2019. Prior to this, many laboratories had performed the Clinical Laboratory Improvement Amendments (CLIA) validation studies needed to provide results from extragenital specimens. In the United States, a positive chlamydia NAAT does not usually result in additional testing for LGV serovars. Thus, providers must typically request LGV-specific NAAT.

If commercial tests are not available and LGV is suspected (eg, in a high-risk MSM), clinicians can send rectal swabs to either their local or state laboratory. Public health authorities should be notified to assure appropriate management of the specimen. Decisions on whether the specimen should go to the United States Centers for Disease Control and Prevention (CDC) for additional testing are made in conjunction with local public health officials. At the CDC, specimens will be tested for C. trachomatis and, if positive, will be genotyped for the identification of LGV [42]. The Sexually Transmitted Disease (STD) Laboratory Branch of the CDC Division of STD Prevention is able to provide AssayAssure transport medium for LGV testing. Information can be found on the CDC website.

●United Kingdom – In the United Kingdom, NAATs have been widely used to diagnose non-LGV and LGV chlamydia from rectal specimens. Guidelines recommend LGV typing of all chlamydial rectal isolates in individuals presenting with proctitis, and in all MSM with HIV who have a positive chlamydia test at any site, regardless of symptoms [43].

●Other countries – In Europe and Australia, guidelines also suggest a two-step approach that includes using a commercially available NAAT to detect C. trachomatis DNA/RNA. If C. trachomatis DNA/RNA is detected in an anorectal specimen, LGV genovar-specific DNA should be tested from the same specimen [29,44]. European guidelines suggest LGV testing of all chlamydia-positive anorectal samples in MSM, regardless of symptoms.

An additional discussion of NAAT for chlamydia is presented elsewhere. (See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections", section on 'Nucleic acid amplification testing (test of choice)'.)

Serology — Serologic tests can be used to support the diagnosis of LGV in the presence of a compatible clinical syndrome [1]. However, given the limitations of serologic testing, the results must be correlated with the clinical manifestations. Furthermore, a low titer serologic result does not exclude LGV, nor does a high titer confirm LGV in a patient without symptoms [45]. (See 'General approach' above.)

There are four Chlamydia genus-specific serologic assay techniques available: the complement fixation test, the single L-type immunofluorescence test, the microimmunofluorescence test, and the anti-major outer membrane protein (MOMP) immunoglobulin A (IgA) assay (in the United Kingdom) [45].

●Most authorities suggest that a complement fixation titer ≥1:64 or a microimmunofluorescence titer >1:256 supports the diagnosis. A titer of <1:32 makes the diagnosis unlikely, although such titers may be seen in the early stages of disease [1,17]. Serial titers demonstrating a titer rise are confirmatory. Microimmunofluorescence is more sensitive and specific than complement fixation, but neither test can distinguish recent from past infection.

●When clinical features are compatible with LGV, high Ig anti-MOMP antibody titers further support the diagnosis [45]. Data from the Netherlands demonstrated the anti-MOMP IgA serologic assay to be the most useful for rectal LGV infection [46]. The test had 73.9 percent sensitivity and 93.3 percent specificity even in asymptomatic MSM with rectal LGV. However, all serologic tests have limitations since they do not distinguish the serotypes and are insensitive for diagnosis of isolated proctitis [12,17].

Data comparing the different serologic tests are lacking.

Culture — Culture is not routinely used to diagnose LGV, since Chlamydia cultures are not generally available outside of referral centers, and there are a multitude of problems associated with attempts to culture the organism. As an example, culture is not typically performed during the primary stage, since the lesion is typically missed and the yield is low from ulcers or lymph node aspirates (organisms are recovered only 30 percent of the time in the secondary phase of illness) [17].

Other tests — Other types of tests have also been used to detect chlamydia, but because they are not species specific, they are not able to distinguish specific biovars. These tests include immunoassays, antigen detection, and genetic probe methods and are discussed elsewhere. (See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections", section on 'Nucleic acid amplification testing (test of choice)'.)

Occasionally, the histopathologic appearance of a biopsy specimen may support a diagnosis of LGV. (See 'Pathophysiology' above.)

TREATMENT OF LGV

Medical therapy for LGV — All patients with LGV should be treated. This includes patients with asymptomatic rectal infection if LGV is identified. (See 'Nucleic acid amplification testing' above.)

Patients should have close clinical follow-up to ensure resolution of signs and symptoms and adherence to treatment. The approach to monitoring is discussed below [1]. (See 'Monitoring response to therapy' below.)

Symptomatic disease — For patients with suspected or confirmed symptomatic LGV the duration of treatment is 21 days. This is in contrast to the seven-day course of treatment required for non-LGV chlamydia. (See "Treatment of Chlamydia trachomatis infection", section on 'Proctitis and rectal infection'.)

●Preferred treatment – For nonpregnant patients, doxycycline (100 mg orally twice daily for 21 days) is the preferred treatment for LGV. This approach is supported by guidelines from several countries, including the United States [1,10,29,43,47-49]. In those with persistent symptoms or severe disease, more than 21 days of therapy may be required [1].

Patients with HIV infection should receive the same regimen as those who are seronegative. Special considerations in pregnant women are discussed below. (See 'Treatment during pregnancy' below.)

Antimicrobial therapy both cures the infection and helps prevent further damage to tissues [50,51], although scarring can ensue in areas of tissue reaction, particularly if diagnosis and treatment are delayed. Early case series supported the use of a 21-day course of doxycycline for treatment of inguinal/genital LGV [50,52,53]. Data have also supported the use of a 21-day course of doxycycline for treatment of anorectal disease [51,54]. In a meta-analysis that included 282 men who have sex with men (MSM) with rectal LGV, the efficacy of doxycycline (as measured by microbiologic cure) was 98.5 percent (95% CI 96-100 percent) [51].

Successful treatment of LGV with fewer than 21 days of doxycycline has been described, but there are insufficient data to recommend the use of this approach. The potential efficacy of a shortened course of therapy for LGV was described in a retrospective review of 60 MSM who received fewer than 21 days of doxycycline for rectal LGV [26]; about half of the men reported rectal or other symptoms associated with LGV, while the other half were asymptomatic. In this report, 83 percent received a seven-day course of therapy. In the subset treated with seven days of doxycycline without azithromycin, 38 of 39 patients were cured; however, time to test of cure and use of other antimicrobials may have biased these results.

●Alternative regimen – For patients who cannot take doxycycline, azithromycin (1 g orally once weekly for three weeks) is an alternative. Erythromycin 500 mg four times daily for 21 days can also be used as second-line therapy, but erythromycin is associated with an increased risk of side effects [1,29].

For patients with LGV proctitis, limited data suggest once-weekly azithromycin for three weeks has similar efficacy compared with daily doxycycline for 21 days. In an open-label, nonrandomized study of 125 MSM with LGV proctitis (96 percent with HIV) patients were treated empirically for proctitis with ceftriaxone plus either once-weekly azithromycin for three weeks or doxycycline for 21 days, based on provider preference. Resolution of symptoms at week 6 and a negative rectal PCR at week 4 (if available) were seen in 98 and 95 percent of those who received azithromycin or doxycycline, respectively (treatment difference 2.2%, 95% CI -3.2 to 13.2) [55].

However, pending additional data, azithromycin should still be considered an alternative regimen since there are no controlled clinical trials supporting the efficacy of this agent for the treatment of LGV. In addition, several studies have found that doxycycline is superior to azithromycin for treatment of non-LGV rectal chlamydia [56-58]. (See "Treatment of Chlamydia trachomatis infection", section on 'Proctitis and rectal infection'.)

Asymptomatic rectal infection — In some countries (eg, the United Kingdom and other parts of Europe), type-specific testing is performed on all rectal samples that test positive for C. trachomatis. Thus, some asymptomatic patients may be diagnosed with LGV by nucleic acid amplification testing (NAAT). Although the clinical significance of asymptomatic LGV is unknown, treatment may reduce the risk of developing symptoms and transmitting infection to others.

The approach to treating asymptomatic infection varies since data are limited. We suggest a seven-day course, assuming the patient does not subsequently develop symptoms. In the study evaluating a shortened course of treatment for LGV, described above, almost half the patients were asymptomatic [26]. In addition, seven days of treatment appear sufficient for treating other types of asymptomatic rectal chlamydia [59]. However, some experts prefer a 21-day course or to do a test of cure if a seven day course is used [29,60].

Treatment during pregnancy — There are limited data on the preferred treatment for LGV in pregnant and lactating mothers. Antimicrobial regimens typically include azithromycin (1 g weekly for three weeks) or erythromycin (500 mg orally four times a day for 21 days) [1]. For most patients, we prefer azithromycin. Although there are no published data to support the efficacy of this agent for LGV during pregnancy, it is easier to take and has fewer side effects than erythromycin.

Monitoring response to therapy — Patients with LGV should be followed closely to monitor their response to therapy. In general, we expect patients with the inguinal syndrome to have marked improvement in buboes by the time treatment is completed. Patients with proctitis generally have complete resolution of symptoms after 21 days of treatment.

Our approach to repeat testing in patients treated for anorectal LGV is as follows:

●Persistent symptoms – In patients with rectal LGV who have persistent symptoms, we repeat NAAT at a minimum of two weeks after the end of therapy to exclude new infection or treatment failure. Repeat NAAT earlier than this can be considered but may result in a false positive, leading to unnecessary additional treatment. Patients with persistent or recurrent anorectal symptoms should also be evaluated for other causes of proctitis. (See "Evaluation of anorectal symptoms in men who have sex with men".)

●Symptoms resolved – For patients with LGV proctitis whose symptoms have resolved, we do a test of cure in the following patients:

•Patients treated with azithromycin – For patients treated with azithromycin, we perform NAAT four weeks after completion of treatment since the efficacy of this regimen is less clear.

•Pregnant persons- For pregnant persons, we perform NAAT four weeks after the initial positive test since treatment during pregnancy may be less effective. This differs from nonpregnant patients who received azithromycin, who should have repeat testing four weeks after completion of therapy.

Patients who test positive on a test of cure should be retreated with a second course of antibiotics. (See 'Medical therapy for LGV' above.)

For patients who were treated with doxycycline, repeat NAAT for chlamydia should also be performed approximately three months after treatment to detect new infection or reinfection from an untreated partner. If retesting at three months is not possible, providers should retest at the patient’s next visit for medical care within the 12-month period after initial treatment.

Aspiration of buboes — Buboes may require needle aspiration or incision and drainage to avoid rupture or sinus tract formation. This is primarily carried out for symptomatic relief but may aid in diagnosis when pus is sent for NAAT; repeated aspiration approached via adjacent healthy skin is sometimes required. Aspiration is safer than incision and drainage, which are associated with a greater risk of postoperative sinus formation.

HIV AND OTHER SEXUALLY TRANSMITTED DISEASES — All patients diagnosed with LGV should be tested for HIV infection and other sexually transmitted diseases. Men who have sex with men (MSM) and transgender women with LGV should also be tested for hepatitis B and C because of high rates of coinfection. If initial testing is negative, HIV, hepatitis, and syphilis serologies can be repeated at follow-up to diagnose those with early infection. (See "Screening for sexually transmitted infections" and "Hepatitis B virus: Screening and diagnosis in adults" and "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Introduction' and "Acute and early HIV infection: Clinical manifestations and diagnosis".)

Those currently without HIV who test positive for LGV should be counselled about the benefits of HIV pre-exposure prophylaxis (PrEP). In addition, persons diagnosed with HIV and those living with HIV who have detectable viremia should be urgently linked to treatment services. (See "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy" and "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "HIV pre-exposure prophylaxis".)

PREVENTION

Reducing risk of transmission to others — To minimize transmission of chlamydia to sex partners, patients should abstain from sexual intercourse until symptoms have resolved and the treatment regimen has been completed. This would be at the end of the course of doxycycline therapy or seven days after the last dose of azithromycin.

To minimize risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all of their sex partners are treated. Sex toys and other fomites should be adequately cleaned prior to reuse. (See "Lesbian, gay, bisexual, and other sexual minoritized youth: Primary care".)

Management of sex partners — Sexual contacts of a source patient with LGV should be evaluated for signs and symptoms of infection and, if possible, be tested for urethral, rectal, pharyngeal, and/or cervical chlamydia, depending on their exposure history.

●Symptomatic patients should be treated for LGV with a three-week treatment regimen, regardless of the test results. (See 'Treatment of LGV' above.)

●Asymptomatic sexual contacts of a source patient diagnosed with LGV should receive preventive therapy if the contact occurred within the 60 days prior to the source patient’s infection or if the contact occurred prior to the patient being adequately treated. Treatment should not be delayed pending test results.

Contacts should be treated with doxycycline 100 mg orally twice per day for seven days [1]. Azithromycin (1 g orally for a single dose) is an alternative regimen. Some experts extend treatment if nucleic acid amplification testing (NAAT) is positive for chlamydia (doxycycline for 21 days or azithromycin 1 g weekly for three weeks) to presumptively treat LGV, unless LGV infection can be excluded by specific typing [60]. (See 'Nucleic acid amplification testing' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sexually transmitted infections".)

SUMMARY AND RECOMMENDATIONS

●Microbiology and epidemiology – Lymphogranuloma venereum (LGV) is a genital ulcer disease caused by the L1, L2, and L3 biovars of Chlamydia trachomatis. This infection has traditionally been seen in tropical and subtropical resource-limited areas of the world. More recently, LGV has been increasingly reported as a cause of proctitis among men who have sex with men (MSM) in high-income settings with temperate climates. (See 'Introduction' above and 'Epidemiology' above.)

●Clinical manifestations – For patients with LGV, primary infection is characterized by a genital ulcer at the site of inoculation. The secondary stage appears two to six weeks later and can present as an inflammatory reaction in the superficial and deep inguinal nodes (buboes). An anorectal syndrome can also occur, and patients with proctocolitis may present with bloody rectal discharge, anal pain, perianal or mucosal ulcers, fever, and/or tenesmus. (See 'Primary infection' above and 'Secondary infection' above.)

If LGV is not recognized and treated, fibrosis and strictures can form in the anogenital tract, leading to genital elephantiasis, anal fistulae and strictures, frozen pelvis, and infertility. (See 'Late LGV' above.)

●Diagnosis – A presumptive diagnosis of LGV is made in a patient with consistent symptoms, clinical findings, epidemiologic risk factors, and a positive C. trachomatis nucleic acid amplification test (NAAT). NAAT for chlamydia can be performed on genital lesions, as well as rectal, pharyngeal, and lymph node specimens. (See 'General approach' above and 'Site-specific considerations' above.)

A definitive diagnosis can only be made with LGV-specific molecular testing; however, these tests are not widely available. (See 'Types of tests' above.)

●Treatment of symptomatic patients – All patients with symptomatic LGV require antimicrobial therapy. Treatment cures the infection and helps prevent further damage to tissues. (See 'Medical therapy for LGV' above.)

•For nonpregnant patients with confirmed or suspected symptomatic LGV, we suggest doxycycline (100 mg orally twice daily) for 21 days (Grade 2C). (See 'Symptomatic disease' above.)

•For symptomatic patients who cannot tolerate doxycycline and for pregnant women, azithromycin (1 g orally once weekly for three weeks) or erythromycin (500 mg four times daily for 21 days) can be used. We prefer azithromycin to improve adherence and reduce side effects. (See 'Symptomatic disease' above and 'Treatment during pregnancy' above.)

In patients with buboes, needle aspiration or incision and drainage may be required to avoid rupture or sinus tract formation. (See 'Aspiration of buboes' above.)

●Treatment of asymptomatic patients- In asymptomatic patients diagnosed with LGV (eg, if type-specific testing is performed on positive rectal chlamydia samples), we suggest a seven-day course of treatment (Grade 2C). Although the clinical significance of asymptomatic LGV is unknown, treatment may reduce the risk of developing symptoms and/or transmitting to others. (See 'Asymptomatic rectal infection' above.)

●Patient monitoring – Patients treated for LGV should be followed closely after treatment to monitor their response to therapy and ensure that partners have been notified. (See 'Monitoring response to therapy' above.)

In patients with rectal LGV, we perform a test of cure in pregnant persons, those with persistent symptoms, and those who were treated with an alternative agent (eg, azithromycin). The timing of NAAT depends upon the patient population. We also repeat NAAT in patients who were successfully treated with doxycycline to detect new infection or reinfection from an untreated partner approximately three months after the end of treatment.

●Testing for other sexually transmitted diseases – All patients diagnosed with LGV should be tested for HIV and other sexually transmitted diseases. If negative at baseline, HIV, hepatitis B and C, and syphilis serologies can be repeated to diagnose those with early infection. (See 'HIV and other sexually transmitted diseases' above.)

●Management of sexual partners – Sexual partners of a source patient with LGV should be treated if the contact occurred within the 60 days prior to the source patient’s infection or if the contact occurred prior to the patient being adequately treated. (See 'Prevention' above.)

For those who are asymptomatic, we suggest a seven-day course of doxycycline treatment (Grade 2C). Azithromycin (1 g orally for a single dose) is an alternative regimen. This differs from the longer course of treatment used for those with symptoms. The rationale for using a shortened duration of treatment in contacts is the same as that used for treating asymptomatic infection. However, some clinicians extend the duration of treatment if the results of NAAT are positive for C. trachomatis unless LGV infection can be excluded by type-specific testing.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jonathan Zenilman, MD, who contributed to an earlier version of this topic review.