Lymphogranuloma Venereum

Synonyms: LGV, Durand-Nicholas-Favre's disease, lymphopatia venereum, lymphogranuloma inguinale, tropical bubo, poradenitis inguinales

• This disease is due to infection with the L1, L2 or L3 serovars of Chlamydia trachomatis.
• Unlike genitourinary chlamydial infection which infects squamocolumnar epithelial cells, these serovars cause infection of mononuclear phagocytes in the lymphatic system.
• The disease was largely confined to tropical regions of the world, but there are now outbreaks arising locally in Europe (particularly The Netherlands) and America, predominantly affecting men who have sex with men. This was largely rectal infection presenting with proctitis.¹
• Cases in the developed world are largely due to the L2 serovar.

• The disease is endemic in East and West Africa, India, The Caribbean, South America and South-East Asia.²
• There are no reliable figures for population prevalence.
• In India and Africa it accounts for 2–10% of genital ulcer disease.
• The Health Protection Agency recently launched a case ascertainment and awareness initiative and >100 cases occurred in the UK during the first half of 2005. Subsequent studies have revealed that the number of cases have now reduced to 12 per month (32 per month back in 2005).^3,4
• These were largely confined to the metropolitan London area and Brighton, but smaller clusters have occurred in other areas.

Risk factors

• Unprotected sexual intercourse²
• Receptive anal intercourse
• Sexual contacts in endemic areas
• Prostitution
• Multiple sexual partners⁵
• Male gender
• Anal enema use⁶

The clinical presentation is divided into primary, secondary and tertiary patterns.

Primary LGV

• Primary LGV presentation is seen in about one third of infected men, but rarely in women.
• Occurs 3 days to 3 weeks after exposure.²
• Usually present with painless papule or shallow ulcer/erosion.
• May be groups of lesions resembling herpes infection.
• Symptoms of urethritis may occur.
• In men it is usually the coronal sulcus, frenulum, penile shaft, foreskin, glans, scrotum, urethra or anus that are affected.
• Men may develop a penile lymphangitis of the dorsal penile shaft, with cord-like thickening.
• A tender nodule may form in the regional lymph glands which can undergo rupture or sinus formation.
• When women do display symptoms of primary LGV, it affects the posterior vaginal wall, posterior lip of cervix, vulva and fourchette.
• Oral cases may occur in men and women following oral sexual intercourse.

Secondary LGV

• Usually occurs 10–30 days after exposure but may take several months to develop.
• Buboes (grossly enlarged tender nodes) form in the regional lymph drainage.
• There may be symptoms of systemic illness such as fever, headache, nausea, vomiting, lethargy and arthralgia.
• Buboes affect either the inguinal, pelvic or perirectal lymph nodes, depending on the original site of genital infection and may be unilateral or bilateral.
• If oral infection occurs then the submaxillary and cervical lymph glands are affected.
• The groove sign may occur, particularly in men, due to separation of the enlarged inguinal and femoral lymph nodes by the inguinal ligament. This sign is present in about a fifth of male cases. However, it has also been associated with non-Hodgkin's lymphoma.⁷
• There is usually erythema and induration of skin overlying the enlarged nodes and there may be rupture of the buboes with sinus or fistula formation.
• The skin may be affected by erythema multiforme, urticaria, erythema nodosum or scarlatiniform rash.
• Rarely there may be signs of conjunctivitis, hepatomegaly, meningoencephalitis, pericarditis, pneumonia and arthritis.

Tertiary LGV

• This late presentation can occur up to 20 years after infection.
• There is usually proctocolitis, which can be confused with other causes of distal colonic inflammation.
• Patients may complain of anal itching, bloody mucopurulent anal discharge, rectal pain and tenesmus, passage of very thin stools with constipation or weight loss.
• Swollen haemorrhoid-like structures, due to lymphatic obstruction, may be seen at the rectal margin.
• Digital rectal examination or proctoscopy may reveal a granular mucosa and enlarged nodes beneath it.
• There may be rectal fibrosis and stricture in advanced cases (reversible with treatment)⁸ and elephantiasis of the genitals in men.
• Esthiomene - an 'eating away' of the genitalia may affect women. There is chronic hypertrophy and granulomatous enlargement of the vulva with ulceration and erosion.

Depends on the stage of disease.

Primary and secondary disease resembles

• Syphilis
• Genital herpes
• Cat scratch disease (Bartonella henselae infection)
• Chancroid (Haemophilus ducreyi – another tropical STI)
• Donovanosis, aka granuloma inguinale (Calymmatobacterium granulomatis – another tropical STI)
• Bubonic plague
• Mycobacterial infections
• Tularaemia
• Malignant causes of lymphadenopathy, e.g. Hodgkin's disease

Anogenital syndrome

• Anal/rectal carcinoma
• Actinomycosis
• Schistosomiasis
• Lymphatic filariasis
• Mycosis

• Other causes of inguinal lymphadenopathy and genital ulceration must be considered and ruled out.
• Full screening for sexually transmitted infections should be carried out if possible, preferably via genitourinary medicine clinic.²
• Samples for culture or analysis may be collected from percutaneous drainage of buboes, or from exudate of ulcer base or rectal tissue.
• Complement fixation (CF) test has sensitivity of 80%, with cross-reactivity with other chlamydial species and serovars.
• A microimmunofluorescence test for the L serovars of C. trachomatis has higher sensitivity and specificity than CF test.
• Polymerase chain reaction assays have highest specificity and sensitivity and are increasingly being used to reach a definitive diagnosis.⁹
• CT imaging may be used to assess extent of lymphadenopathy and look for alternative causes.
• Sigmoidoscopy/colonoscopy with tissue biopsy may be needed to diagnose the cause of anorectal symptoms. Tissue histology can be non-specific.

Medical therapy

• First-line treatment is usually with doxycycline 100 mg twice daily for 21 days, or erythromycin 500 mg 4 times daily for the same period.¹⁰ Protocols using doxycycline are successful both in those who are and are not co-infected with HIV.¹¹
• Tetracycline or minocycline may also be used. Azithromycin may be given 1g weekly for 3 weeks and appears to be effective.
• This regimen has recently been reviewed and there is no current evidence for it to be altered.¹¹

Surgical therapy

• Buboes may be drained percutaneously to relieve symptoms.
• Surgical excision is best avoided due to risk of sinus or fistula formation.

Other therapy

• Patient should refrain from unprotected sexual intercourse until they and any contacts have completed treatment and follow-up.

Monitoring

• Follow-up after 3 weeks with testing to look for evidence of cure may be needed.
• Patients with rectal stricture or other advanced complications may require surgical intervention.

• If diagnosed in primary/secondary stage, full cure is expected with appropriate antibiotic therapy.²
• Tertiary cases may have long-term complications despite bacteriological cure.
• Infection provides no significant immunity to future re-infection, and relapse of infection after treatment may occur in some cases.

• Bubo rupture with sinus or fistula formation
• Fibrosis/deformation of penis
• Cervicitis or salpingitis in women
• Colonic obstruction due to rectal stricture
• Conjunctivitis
• Arthritis
• Pericarditis
• Pneumonia
• Meningoencephalitis
• Hepatomegaly

• Awareness of disease in developed world
• Surveillance and testing in GUM clinics/opportunistically in primary care
• Practice of safe sex
• Contact tracing of confirmed cases, where possible