BASHH Guidelines

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Aetiology

Lymphogranuloma venereum (LGV) is caused by one of three invasive serovars (L1, L2 or L3) of Chlamydia trachomatis, though L2 is the most common strain involved.

L2 is the main serovar causing the current outbreaks in Europe and North America.

Since 2003 there have been increasing LGV outbreaks across Europe mainly amongst HIV-positive MSM

Most UK cases are among MSM involved in dense sexual networks/party scene not linked to LGV-endemic countries

LGV remains endemic in tropical areas including Southern Africa, West Africa, Madagascar, India, South-East Asia and the Caribbean.

Clinical Features

Primary Lesion

  • Incubation period 3-30 days
  • May be transient and imperceptible in the form of a painless papule or pustule or shallow erosion or ulcer
  • Often found on coronal sulcus of men and posterior vaginal wall, fourchette, vulva or cervix of women
  • Some ulcers in recent MSM outbreak have been indurated and of variable tenderness, lasting as long as several weeks
  • Extra-genital lesions reported eg perianal ulcers and fissures in MSM, lip, oral cavity, extra-genital lymph nodes.

 

LGV proctitis in MSM

  • Haemorrhagic proctitis is the primary manifestation of infection seen in MSM; a similar picture might present in the case of rectal exposure in women.
  • Symptoms include rectal pain, anorectal bleeding, mucoid and/or haemopurulent rectal discharge, tenesmus, constipation and other symptoms of lower gastro-intestinal inflammation.
  • Systemic symptoms such as fever and malaise.

 

Pharyngeal LGV infection

  • LGV can cause symptomatic ulceration and pharyngitis as well as asymptomatic carriage at this site.

 

Asymptomatic LGV infection

  • Asymptomatic rectal C. trachomatis infection in the UK is usually non-LGV Chlamydia and treatment with doxycycline 100mg BD for 7 days has been shown to be efficacious in this setting without routine testing for LGV DNA.

 

Secondary lesions, lymphadenitis or lymphadenopathy or bubo

  • The most common clinical manifestation of genital LGV in heterosexuals is tender inguinal and/or femoral lymphadenopathy, typically unilateral (two-thirds of cases). The disease process may involve one lymph node or the entire chain, which can become matted with considerable periadenitis and bubo formation. Buboes may ulcerate and discharge pus from multiple points creating chronic fistulae.
  • When both inguinal and femoral lymph nodes are involved, they may be separated by the so-called ‘‘groove sign,’’ which consists of the separation of these two lymph node systems by the inguinal ligament. Though considered pathognomonic of LGV, the ‘‘groove sign’’ only occurs in 15–20% of cases.
  • Lymphadenopathy commonly follows the primary lesion by a period of a few days to weeks (10–30 days, rarely months).
  • Systemic spread may be associated with fever, arthritis, pneumonitis and more rarely abnormal hepatic enzymes and perihepatitis.
  • Reactive arthritis in MSM following LGV proctitis has been reported in several cases in recent years.

 

Tertiary stage or the genito-anorectal syndrome

  • Chronic inflammation and destruction of tissue may lead to proctitis, proctocolitis mimicking Crohn’s disease, fistulae, strictures and chronic granulomatous disfiguring fibrosis and scarring of the vulva with esthiomene (Greek word meaning ‘‘eating away’’).
  • These conditions occur most frequently in women, reflecting the involvement of retroperitoneal lymphatics.

 

Long-term complications

  • Destruction of lymph nodes may result in genital lymphoedema (elephantiasis) with persistent suppuration and pyoderma.
  • An association with rectal cancer has been reported. The two conditions can be confused and histopatho-logical confirmation may be necessary

Diagnosis

Historically LGV was a diagnosis of exclusion. Anorectal syndrome, particularly in MSM, is diagnosed based on clinical suspicion (e.g. proctocolitis, inguinal lymphadenopathy, genital ulcer) after the exclusion of other causes.

Microscopy: Rectal polymorphonuclear leucocytes (PMNLs) from rectal swabs is predictive of LGV proctitis, especially in HIV-positive MSM, with levels of >10 and >20 PMNLs per high-power field both shown to be significant.

Nucleic acid amplification tests (NAATs) have high sensitivity and specificity and if positive for C.trachomatis DNA may then be tested for LGV specific DNA from genital, rectal and throat swabs, urine, bubo pus, lymph node aspirates and biopsy specimens.

Other tests: Culture has sensitivity of 75-85%, less for buboes and is labour intensive and rarely available. Chlamydia serology cannot necessarily distinguish past from current LGV infection, does not have high sensitivity/specificity and is only available in specialised laboratories.

 

Collection of specimens

Chlamydiae are intracellular organisms so samples should aim to contain cellular material, which can be obtained from:

  • Ulcer base exudate or from rectal mucosa
  • Aspiration of lymph node or bubo using 21-gauge needle
  • Rectal and pharyngeal swabs from MSM and women exposed at those sites
  • Urethral swab or first-catch urine specimen when urethritis and/or inguinal lymph- adenopathy is present and LGV is suspected.

Management

General advice

  • Explanation of diagnosis and sequelae with written information.
  • Screening for other STIs
  • High rates of incident HIV/HCV infections have been observed in LGV infected MSM and risk reduction advice should be offered.

Patient information leaflet 

Recommended regimens

  • 1st choice: doxycycline 100 mg twice daily orally for 21 days (or tetracycline 2 g daily or minocycline 300 mg loading dose followed by 200 mg twice daily) (IIb, III or IV, B).
  • 2nd choice: erythromycin 500mg four times daily orally for 21 days (IV, B). Azithromycin 1g weekly for 3 weeks should also be considered.

 Alternative regimens

  • Azithromycin 1g stat and 1g weekly for 3 weeks have shown clearance in rectal LGV in MSM (IV, C).
  • Ofloxacin and moxifloxacin are expected to be effective; a course of at least 2 weeks would be advisable if clinically necessary (IV, C) and test of cure should be performed.

Allergy

  • Tetracycline allergy should be treated with erythromycin or extended azithromycin regimen with test of cure (TOC).

Pregnancy/Breastfeeding

  • Should use erythromycin regimen. Extended azithromycin might be considered. TOC advised.

 

Fluctuant buboes

  • Should be aspirated through healthy adjacent skin. Surgical incision contraindicated. Provide analgesia if necessary.

Sexual contacts

  • Sexual contacts within the 4 weeks prior to the patient’s symptoms, or the last 3 months if asymptomatic LGV is detected, should be examined and tested for chlamydial infection and receive presumptive treatment with 21 days of doxycycline 100 mg twice daily or alternative regimen for the same duration (IV, C).

Follow-up

  • Patients should be followed up until symptoms resolve. Routine TOC not necessary if recommended regimen has been completed. If TOC is required it should be performed 2 weeks after completion of therapy.

 

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