Lymphogranuloma venereum

Lymphogranuloma venereum is a sexually transmitted infection caused by Chlamydia trachomatis.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by the organism Chlamydia trachomatis.

C. trachomatis causes urogenital chlamydia, the common STI. Urogenital chlamydia is usually the result of serovars D-K, whereas LGV is caused by the serovars L1, L2 and L3. Serovars are a way to group organisms into species or subspecies based on the surface antigens.

LGV is one of several genital ulcer conditions, which classically causes one or more painless shallow ulcers in the genital region.

Genital ulcers

The major causes of genital ulcers include:

• Syphilis: characterised by a single painless ulcer (chancre)
• Herpes simplex virus (HSV): multiple painful vesicles that ulcerate
• Granuloma inguinale: one or more nodules that eventually ulcerate. Usually painless
• Lymphogranuloma venereum (LGV): one or more painless papules that develop into shallow ulcers
• Chancroid: multiple deep painful ulcers with a purulent base.

In the UK, LGV is now considered hyperendemic among men who have sex with men.

LGV is predominantly seen in men who have sex with men (MSM) with up to 99% of cases in the UK seen in this group. The condition is most commonly seen among patients who are co-infected with HIV.

In the last two decades, the UK has seen the highest number of cases of LGV globally. There are ~80 cases per quarter with the highest numbers in London, Brighton and Manchester. 

Worldwide, the condition is endemic to other regions including West Africa, Southern Africa, India and South-East Asia.

LGV is caused by one of three invasive serovars (L1, L2, L3) of chlamydia trachomatis.

C. trachomatis is an obligate intracellular bacterium that can be divided into subspecies based on the antigens found on its surface. These subspecies are known as serovars and there are at least 15 known at present. 

The serovars of C. trachomatis can cause a variety of infections in humans:

• Trachoma (A-C): contagious bacterial eye infection
• Urogenital (D-K): classic chlamydia infection
• LGV (L1-L3): genital ulcer disease

The serovars L1-L3 that cause LGV are considered more virulent. The condition is acquired through sexual contact with transmission occurring through direct contact with mucous membranes. The bacteria then travels via lymphatics to regional lymph nodes and replicates within macrophages. The period from infection to clinical symptoms is between 3-30 days (Incubation period). LGV is most commonly caused by the serovar L2 and the infection has three classic stages.

LGV has three classic stages of infection.

Primary stage

This stage is characterised by development of a painless papule, pustule or shallow ulcer. If patients develop the infection through rectal intercourse they can present with a haemorrhagic proctitis, which is most commonly seen. Rarely, due to oral sex, LGV pharyngitis can occur.

Secondary stage

The secondary stage is characterised by regional lymphadenopathy (femoral/inguinal) days to weeks after the primary lesion. It can cause a marked lymphadenitis (infected nodes) that become matted together or suppurative, which is termed a buboe. 

Lymphadenopathy is painful and typically unilateral (two thirds of cases). In women, inguinal lymphadenopathy is less common (only seen in 20-30%) because it more commonly affects the deep pelvic nodes. 

Tertiary stage

The majority of patients will recover from the secondary stage. Rarely, patients may develop a chronic anogenital infection that is associated with chronic inflammation that can cause proctocolitis, fistulae, strictures or disfiguring fibrotic areas. 

This type of reaction may mimic inflammatory bowel disease.

LGV is characterised by one or more painless ulcers that develops into painful, regional lymphadenopathy.

Primary stage

Characterised by genital lesions or proctitis depending on the route of infection. Some patients may have asymptomatic carriage. 

Genital lesions

Typically identified on the coronal sulcus of the glans penis in men or posterior vaginal wall and/or vulva in women.

• Painless papule
• Painless pustule
• Painless shallow ulcer

Proctitis

• Rectal pain
• Rectal bleeding
• Rectal discharge
• Tenesmus: feeling of incomplete emptying

Secondary stage

• Lymphadenopathy: inguinal/femoral, typically unilateral and painful
• Lymphadenitis: infected lymph nodes
• Buboes: marked lymphadenitis that becomes suppurative. At risk of chronic fistulae formation
• Groove sign (15-20%): femoral and inguinal lymphadenopathy are separated by the inguinal ligament
• Systemic upset: rarely fever, pneumonitis, hepatitis, aseptic meningitis or arthritis can occur

Tertiary stage

• Proctitis/proctocolitis: bleeding, pain, tenesmus
• Fistulae
• Strictures
• Chronic lymphoedema 

In the UK, diagnosis of LGV is based on nucleic acid amplification testing (NAATs).

The diagnosis of LGV is usually based on NAAT testing of genital or rectal swabs. In resource poor settings, the diagnosis may be made clinically based on characteristic clinical features.

Recommended specimens

• Genital swab: ideally taken from base of an ulcer
• Rectal swabs
• Urethral swab
• First-catch urine
• Aspiration from lymph nodes: often utilised in presence of buboes

Diagnostic testing

• NAAT testing: identification and amplification of C. trachomatis genetic material from swabs or lymph node aspirates
• Culture: used on tissue or swab samples. Very labour intensive and expensive. Not commonly used. 
• Serology: blood test to assess for immune response with antibody generation against C. trachomatis. Variable sensitivity and specificity. Difficult to distinguish between current and past infection. 
• Histology: can be completed on tissue samples (i.e. lymph nodes). 

Laboratory techniques are available to distinguish between LGV and non-LGV serovars. 

Other investigations

Patients with suspected LGV require referral and assessment at a genitourinary medicine (GUM) clinic. This enables a full sexual health screen including testing for other STIs such as urogenital chlamydia, gonorrhoea, syphilis and HIV. 

The treatment of choice for LGV is a three week course of doxycycline.

General advice

All patients with LGV should be advised to avoid sexual contact until treatment with antibiotics is completed and they have undergone appropriate follow-up. All sexual contacts within 4 weeks of symptomatic LGV or 3 months of asymptomatic carriage of LGV will need to be contacted, screened and receive empirical treatment. 

Pharmacological management

Doxycycline is considered the first line treatment for LGV.

• First line: 
  • Doxycycline 100 mg twice daily for 21 days, OR
  • Tetracycline 2 g once daily for 21 days
• Second line:
  • Erythromycin 500 mg four times a day for 21 days, OR
  • Azithromycin 1 g weekly for 3 weeks

Without treatment, LGV can lead to a persistent infection with chronic complications.

• Lymphoedema
• Fistulae
• Strictures
• Disfiguring fibrotic scarring