2.5.3 Lymphogranuloma venereum (LGV)

In India and Africa LGV is estimated to account for less than 10% of genital ulcer disease (GUD). In Europe the current LGV epidemic has been detected among MSM and causing mainly proctitis. Some cases of heterosexual LGV have been seen in Europe, most of them were imported from endemic countries. In 2023, a total of 3075 cases were reported in 22 European countries, almost all among men who have sex with men (MSM) and most of the cases (77%) reported in Spain and the Netherlands. In many parts of Europe, surveillance for LGV is not well developed due to limited diagnostic capacity. Most of these patients are HIV-infected.

Lymphogranuloma venereum is an uro- and anogenital infection caused by C. trachomatis, serovars L1-3.

Chlamydia trachomatis is an intracellular Gram-negative bacterium which can cause ocular infections, trachoma, genital infections and the sexually transmitted lymphogranuloma venereum (LGV).

C. trachomatis isolates are classified serologically with 15 serovariants, based on the major outer membrane protein. LGV is caused by the invasive L1-3 strains (serovars) of C. trachomatis that disseminate via underlying connective tissue and spread to regional lymph nodes. In Europe, the majority of LGV cases are caused by the C. trachomatis biovar L2b, thought to be imported from the United States by the end of the previous century. Most cases have been detected among MSM. C. trachomatis serovars D–K cause cervicitis in women and urogenital infections in men.

The clinical picture of LGV depends on the site of transmission. Transmission to the genital area can cause inguinal disease while to the rectal canal an anorectal syndrome. LGV is divided to three stages.

• The first stage of LGV develops after an incubation period of one to four weeks. In the current LGV epidemic among MSM, proctitis is the primary manifestation of infection. Patients complain severe anorectal pain, purulent discharge and bleeding from the rectum, tenesmus and constipation. In proctoscopy oedema, a distal haemorrhagic proctitis with purulent exudate, ulceration and tumorous masses can be detected. LGV proctitis mimics chronic inflammatory bowel diseases like Crohn’s disease. Radiological imaging may demonstrate pelvic node involvement. LGV proctitis can be asymptomatic, too. In traditional LGV the primary lesion is often an unnoticed small painless papule or pustule that erodes to an ulcer and heals within one week. Mucopurulent discharge can occur in the urethra, the cervix or the rectum depending on the inoculation site.

• The second or inguinal stage begins 2 to 6 weeks after the onset of primary lesion. There is painful inflammation of the inguinal and/or femoral lymph nodes causing unilateral enlargement, inflammation, and abscesses (buboes) that may rupture. Inguinofemoral lymphadenopathy is mainly seen when the inoculation site is located on the external genitals, often in males. Women often have primary involvement of the rectum, vagina or cervix. These regions drain to the deep iliac or perirectal nodes, causing intra-abdominal or retroperitoneal lymphadenopathy with lower abdominal or back pain. Constitutional symptoms like low-grade fever, chills, malaise, myalgia and arthralgias may occur.

• The third stage of LGV is called anogenitorectal syndrome and is more often present in women and MSM. Patients develop proctocolitis followed by perirectal abscesses, fistulas, strictures and stenosis of the rectum.

Lymphogranuloma venereum is usually classified by recognized stages of the infections. See signs and symptoms.

Microbiological diagnosis is usually two-step. The commercially available C. trachomatis NAAT test is used for screening and if positive, the diagnosis is confirmed by the detection of LGV biovar-specific C. trachomatis DNA from the same specimen. The material for testing can be from ulcers of the primary lesions, anorectal specimens or aspirates of inguinal nodes.

As most LGV cases are detected among MSM, it is recommended to screen all men with anorectal samples positive for C. trachomatis also for LGV, irrespective of symptoms. Also those who are eligible for HIV pre-exposure prophylaxis (PrEP) should be considered for testing. Those who are positive are then screened for LGV proctitis. Many LGV positive men are also HIV-positive, so screening for other STIs including HIV, hepatitis B and hepatitis C should be offered.

Most complications are preventable if treatment is initiated in the early stages.

• Anogenitorectal syndrome with chronic progressive lymphangitis can lead to chronic oedema and sclerosing fibrosis, resulting in strictures and fistulas of the involved region, which can ultimately lead to elephantiasis, esthiomene (the chronic ulcerative disease of the external female genitalia) and the frozen pelvis syndrome.

• LGV proctitis can lead to rectal stricture, with subsequent sequelae of soiling, pain, constipation and the possible development of mega colon, proctocolitis followed by perirectal abscess, fistulas, strictures and stenosis of the rectum, possibly leading to haemorrhoid-like swellings of obstructed rectal lymphatic tissue.

• Systemic spread of C. trachomatis occasionally results in arthritis, pneumonitis or (peri) hepatitis. Rare systemic complications include cardiac involvement, aseptic meningitis and ocular inflammatory disease.

First line treatment is doxycycline 100 mg twice a day orally for 21 days and second line erythromycin 500 mg four times a day orally for 21 days. Doxycycline is contraindicated in pregnancy and breastfeeding. Fluctuant buboes should be aspirated promptly through healthy adjacent skin.

Patients should be informed that LGV is an invasive bacterial infection that is sexually transmitted but curable with antibiotics. Symptoms should resolve within 1-2 weeks of commencing antibiotic therapy. Patients should abstain from any sexual contact until they have completed therapy. Patients with LGV should be followed up at the end of treatment to ensure resolution of symptoms and signs of infection, to check that adequate partner notification has been complete and to re-screen for syphilis, hepatitis B, C and HIV 3 months after the LGV diagnosis. A test of cure for LGV is not considered necessary if the recommended 21-day course of doxycycline is completed.